Oxycontin: The Politics, Science, and Sensationalization of an Abusable Pharmaceutical

THE SCIENCE OF OPIOIDS

Opioids Background Information

Scientific Basic

Modern Use

Oxycodone

Abuse Liability

OxyContin

OXYCONTIN AND THE MEDIA

The Media

OXYCONTIN ABUSE

Drug Abuse

Emergency Room Visits

OxyContin Related Deaths

THE DEA AND DIVERSION

The DEA

Illicit OxyContin

FEDERAL HEARINGS AND LAW ENFORCEMENT

Congressional and Public Hearings

Enforcement and Prevention Efforts

Opioid Policy and Practice

THE OXYCONTIN BUSINESS

The Pharmaceutical Industry

The Marketing of OxyContin

Purdue Response and Public Relations

Prescription Monitoring Programs

LEGAL AND SOCIAL ISSUES

Legal Cases

The Fallout

CONCLUSION

- INTRODUCTION –

This is the story of OxyContin, a schedule II opioid pain reliever introduced in 1996 which was more widely abused after its introduction that any prescription drug in the past 20 years. Sales of the drug, marketed by Purdue Pharma, rose to over $1 billion in less than five years, making it one of the fastest growing and highest grossing pharmaceuticals in recent times. Along with its popularity and rapid growth came widespread abuse, attracting attention from the media, the Food and Drug Administration, the Drug Enforcement Administration, Congress, law enforcement officials, and the medical community. Heralded as a highly effective groundbreaking new medication, OxyContin brought relief to millions of chronic pain patients, but also brought suffering and death to drug abusers. The backlash from this was felt by the manufacturer, the medical community, and legitimate pain patients who suddenly found themselves labeled as addicts and unable to obtain medication. The appropriateness of long-term opioid use was brought to the forefront of debate among medical professionals, and the progress which had been made during the past decade in the aggressive treatment of chronic pain conditions appeared to take a step backwards.

To understand OxyContin, one must first know something of the history of opioids, which derive from the opium poppy known botanically as Papaver somniferum first cultivated by humans circa 3400 B.C. From the opium poppy morphine was created, and then in 1898 Bayer released the most famous drug brand of all time, Heroin. A wide variety of opioids were created over the next century, including oxycodone, the active ingredient in OxyContin.

All opioids have in common an unrivaled pain relieving efficacy without toxicity to the body, allowing their use in large quantities over long duration. Unfortunately, opioids also bring euphoria and pleasure to many of their users, leading to widespread use and abuse. Modern science is still unable to separate the euphoric and pain-relieving qualities of opioids, making their use controversial and requiring restrictions on their availability. Longer term opioid use leads to tolerance as well, requiring users to take larger quantities over time to achieve the same initial effects.

OxyContin was unique in that it was available in slow-release 12 hour high-dose formulations, giving physicians to ability to indefinitely increase patient dosage and maintain continued pain relief. Oxycodone seemed to have a lower number of side effects compared to other opioids, but also seemed to produce a uniquely enjoyable euphoric quality and was easily abused because of the high potency of the pills.

The story of OxyContin was in a large part created by the media, which brought national attention to the drug with a wave of sensationalized news stories which began in early 2001. OxyContin was proclaimed a national epidemic and called the ‘New Crack’ with a ‘heroin-like’ high, supposedly claiming hundreds of lives yearly. These claims were not borne out by fact, but the news media was undeterred, and devoted a startling amount of attention to the drug in a 6 month period. This gave the DEA, Congress, the FDA, and the medical community no choice but to respond to these claims.

In truth, abuse of prescription drugs had been occurring for decades. An analysis of prescription drug abuse data showed that OxyContin was responsible for less than 1.0 percent of total drug abuse emergency department mentions. It had also contributed to less than 20 percent of all opioid abuse mentions, and was in fact overshadowed by established opioids such as Vicodin, Morphine, and Percocet. A review of the coroner’s toxicology reports also suggested that the death numbers reported by the media may have been dramatically overstated, and that many of the OxyContin overdose victims had consumed alcohol, anti-anxiety drugs such as Valium, and other opioids.

The Drug Enforcement Administration had already begun to investigate OxyContin diversion and abuse on a small scale in 1999 and 2000, but as the media coverage hit in 2001 and congressional hearing appeared imminent, the DEA drastically stepped up its rhetoric and its investigation of physicians. Before a congressional subcommittee in August 2001, the director of the DEA made it clear that OxyContin was the agency’s number one priority, characterized as a societal threat unlike any which had been seen for decades. Within six months, the DEA requested a budget allocation of $25 million to combat OxyContin diversion and abuse on top of the $114 million it was already requesting for its Diversion Control department.

The diversion of OxyContin was due to its high street price; approximately $1 per milligram, nearly 10 times the pharmacy price. Stories were frequently reported about corrupt doctors making thousands of dollars through liberal prescription practices. Legitimate patients were sometimes selling their medication to supplement their income, and people were importing the drug from Mexico and Canada. Originally only popular in certain rural areas, the drug seemed to spread to urban areas as the intense media coverage brought it to attention, and the DEA predicted that the plague was heading west.

Congressional subcommittees were convened to discuss the issue and the company was called on to address the problem. The DEA announced a National Action Plan to combat diversion and abuse through coordination of law enforcement agencies, cooperation with the manufacturer, public education campaigns, and discussions with physician and patient groups. Unsurprisingly, these groups were largely unreceptive because they had been hard at work throughout the decade passing legislation and changing medical opinion to support the increased use of opioids in treating a wider variety of chronic pain conditions. They knew that with increased scrutiny would come a constriction of legitimate use from doctors who feared the threat of DEA investigations. No matter how often the DEA stated that it gave full support to doctors who used opioids appropriately, it was never exactly clear what the DEA’s interpretation of ‘appropriate use’ meant, so physicians were left to look out for their own interests.

It began to appear that partial responsibility for the problem lay with Purdue’s aggressive marketing of the drug. Sales grew from $300 million in 1996 to $1.49 billion in 2001 in part because of Purdue’s targeting of physicians who were already liberal prescribers. Some began to suggest the Purdue had downplayed the risks of the drug by claiming that it had reduced addiction liability due its slow-release mechanism. In also may have been marketed for a wider range of conditions than was appropriate. In 2001 Purdue began to make some effort to combat the problem by withdrawing the highest dose formulation and conducting anti-prescription drug abuse advertising campaigns. Under DEA pressure, the warning label and indications were changed in 2001 to convey the risks of the drug and the appropriate patient populations.

In the face of rising criticism of its practices and calls to withdraw the drug, Purdue remained defiant, claiming innocence and placing the blame fully on those who chose to manipulate doctors and abuse the drug. While publicly proclaiming support for prescription monitoring programs and giving the state of Florida $2.1 million to establish its own monitoring program in exchange for halting an investigation, Purdue quietly opposed other attempts to create or strengthen monitoring programs. A rising tide of legal cases also began to occupy Purdue as patients filed suit against the company for inappropriate labeling and misleading marketing.

As media attention began to subside, OxyContin was still on the radar of the DEA and Congress. After having caught the few corrupt doctors, the DEA settled for frightening the rest into changing their prescribing practices. The doors of clinics began to close and physicians became reluctant to prescribe the drug. It was this change in the medical community’s comfort with opioid use which was perhaps OxyContin’s most tragic legacy. While many doctors simply switched to other possibly less effective opioids, some stopped prescribing altogether. Patients’ advocacy groups found their cause had been set back dramatically, and legitimate chronic pain patients often found themselves unable to obtain treatment.

- THE SCIENCE OF OPIOIDS -

Opioid Background Information

The opium poppy, known botanically as Papaver somniferum, was first cultivated circa 3400 B.C. in lower Mesopotamia. Opium is an extract of the exudates derived from the seedpods of the flower. Ancient Sumerians, Assyrians, Babylonians, and Egyptians learned that smoking the extract would bring on pleasurable effects. The Sumerians referred to the poppy plant as Hul Gil or ‘joy plant’. Use of the plant later spread to Arabia, India, and China.

In the sixteenth century, Philippus von Hohenheim, better known as Paracelsus, invented laudanum by extracting opium into brandy. The alkaloids found in opium are significantly more soluble in alcohol than in water, so this new alcohol opium drink, essentially a tincture of morphine, easily drinkable and highly potent, became very popular. By the nineteenth century, vials of laudanum and raw opium were freely available at any English pharmacy or grocery store.

Progress continued in 1805 when morphine was first isolated from opium by the German pharmacist Wilhelm Sertürner. He called it morphium, after Morpheus, the Greek god of dreams. Morphine proved far more useful than opium for the medical field, as opium taken orally has unpleasant gastric side-effects. With the invention of the hypodermic syringe later in the century, pure morphine could be injected without these unpleasant side-effects. In Europe and America, morphine injection became very popular with high society and middle-class professionals. At the time, people believed that injecting morphine wasn’t addictive, and was a safe substitute for opium addiction, which when discontinued caused malaise, flu-like symptoms, and depression.

People soon realized that morphine was indeed addictive, and began looking for a non-addictive alternative. In 1874 the English pharmacist C.R. Alder Wright boiled morphine and acetic acid to produce diacetylmorphine. This new compound was soon synthesized by the German pharmaceutical company, Bayer, and put on the market in 1898 under the brand name Heroin.

Heroin was advertised as a “sedative for coughs” and became widely popular. Physicians handed out free samples. It was sold in dozens of countries, but doctors soon noticed that patients were consuming inordinately high quantities. Bayer halted production in 1913 and in 1914, the United States passed the Harrison Narcotic Act, a comprehensive set of opiate laws. In 1924, federal law was amended which made heroin use illegal for any reason, including medical. Within a decade, the Bureau of Narcotics had arrested over 50,000 users and 25,000 physicians for Heroin use.

Scientific Basics of Opioids

Pure opium contains sugars, proteins, fats, water, meconic acid, plant wax, latex, gums, ammonia, sulphuric and lactic acids, and numerous alkaloids, most notably morphine (10%-15%), codeine (1%-3%), noscapine (4%-8%), papaverine (1%-3%), and thebaine (1%-2%). Of these components, modern medicine uses morphine, codeine, and a number of derivatives of thebaine. It is thebaine from which the majority of today’s opioids are made. Thebaine has no analgesic effect itself, but can be used to synthesize hydrocodone (Vicodin), dihydromorphenone (Dilaudid), oxycodone (Percocet), and a number of other more obscure opioids. Completely synthetic morphine analogues include classes of drugs called the diphenylpropylamines (e.g. methadone), the 4-phenylpiperidines (e.g. meperidine), the morphinans (e.g. levorphanol) and 6,7-benzomorphans (e.g. metazocine). All contain a piperidine ring or part of its ring structure.

The entire pharmacologically active class of drugs inspired by the opium poppy are called ‘opioids’. This term includes compounds which occur naturally in the plant, such as codeine and morphine, semi-synthetics, which are compounds made from the combination of an opium product and another chemical, such as diacetylmorphine (made from morphine) and oxycodone (made from thebaine), and pure synthetics, compounds which are made with chemicals from other sources, such as methadone and fentanyl. The term ‘opiate’ refers only to natural and semi-synthetic compounds. Although ‘opiate’ and ‘opioid’ are often used interchangeably, use of the term ‘opiate’ is incorrect when referring to two very popular modern drugs, methadone, used in pain management and opioid maintenance therapy, and fentanyl, used in the Duragesic™ patch for long-term pain management. Additionally, the term ‘narcotic’, which originally meant, ‘agents which cause somnolence or induce sleep’, is today a legal rather than scientific term. Under the Single Convention on Narcotic Drugs Act of 1961 and the U.S. Controlled Substances Act (CSA), substances classified as narcotics include opioids, marijuana, and cocaine.

Opioids affect the body because their structure closely resembles a type of molecule called endorphins which are naturally produced by the body. Endorphins are small-chain peptides that activate our endogenous opioid receptors, a type of receptor site on specific neurons in the body. Endorphins are involved in controlling respiration, nausea, vomiting, pain modulation, hormonal regulation and itching. The analgesic effect of opioids is due to their influence on the way the brain receives messages of painful stimuli from the spinal cord. The patient in pain is still aware of the source of the pain, but it does not bother him anymore. Other physiological effects include the slowing of respiration and heartbeat, suppression of the cough reflex, and relaxation of the smooth muscles of the gastrointestinal tract. In fact, long before opioids were used as painkillers, opium was used to control diarrhea. They also cause miosis, or contraction of the pupils, a very reliable signal of opioid use. The release of histamine resulting from opioids can cause itching and perspiration, another telltale sign of use.

Owing to their resemblance to the body’s natural molecules, one of the most unique aspects of opioids is that their analgesic effect causes virtually no effect on the other sensory perceptions, consciousness, or motor function. All other substances with a painkilling effect, such as laughing gas, alcohol, ether and barbiturates also have, at their effective dose, an impairing effect on consciousness, motor coordination, intellect, and emotional control.“Individuals may take morphine or some other opiate for 20 years or more without showing intellectual or moral deterioration according to the common experience of physicians.”[1] The drowsiness which can be caused by opioids is generally experienced only at higher ‘recreational’ doses. Of course, while opioids do not impair consciousness, they can certainly have an effect on a user’s mental state.

The widely spread belief that morphine brings about an uncanny mental condition, accompanied by fantastic ideas, dreams, and what-not, is wrong, notwithstanding certain popular literature on the subject. The most striking thing about morphine, taken in ordinary doses by one who is not an addict, is that it dulls general sensibility, allays or suppresses pain or discomfort, physical or mental, whatever its origin, and that disagreeable sensations of any kind, including unpleasurable states of mind, are done away with. In fact, the suppression of pain is the only outstanding effect of morphine when given for that purpose.[2]

The emotional and mental effects of opioids are due to their action on the large cell complex known as the limbic system and nucleus accumbens. The lessening of painful and distressing stimuli can often induce a euphoric state in users. This state is described as having aprofound sense of control and well-being, a warmth felt throughout the entire body, sometimes as a dreamy and relaxed state of contentment.

The initial effects were pleasant. Then, for a brief moment I noticed a feeling of unusual well-being; my bed was more pliable, the object in my room seemed more familiar, my body seemed lighter. It is true I noticed nothing extraordinary; I had no illusion or hallucinations. My breathing was easier and freer. I though about my personal affairs, my work and my dislikes. Things that had seemed difficult now seemed easy. Some of the problems of real life appeared to me in a new guise, with their solutions perfectly obvious.[3]

The Modern Use of Opioids

For historic and scientific reasons, there are a number of different opioids currently in clinical use. Morphine is considered by many to be the gold standard because it has been in use the longest. Howeverin comparison to other opioids, morphine generally causes more nausea and pruritus[4]. All opioids are not the same, because the endogenous opioid system of the body is in fact quite complicated, with three main receptor type classifications known as mu, delta, and kappa, along with dozens of receptor subtypes which are still being identified. Because of the high degree of complexity of the body’s receptor systems and the variability of people’s metabolism, different opioids illicit different effects and have varied pharmacological profiles.

The use of opioids today is generally restricted to analgesic uses only, and even then, only for specific types of pain. Traditionally, opioids were restricted to situations where their use was only for a short duration, such as in post-operative pain, or elderly patients in late-term hospital care. Their use has liberalized somewhat in past decades to include other pain conditions, such as lower back pain, cancer, severe burns, migraine headaches, arthritis, myocardial ischemia, renal colic, and gout. Restrictions on opioid use are necessary in part because of the desire of people to abuse them for their mental effects, and in part because of the phenomenon of tolerance, dependence, and addiction.

While opioids may seem an ideal drug due to the absence of toxicity which accompanies so many modern drugs, they are not without their problems. Aside from the side effects which are due to the crude, non-receptor specific agonists used by modern science, the body begins to adapt to the presence of exogenous opioids by growing new opioid receptors. This causes a need to increase dosage to achieve the same effect. When the exogenous opioids are no longer administered, the body undergoes withdrawal symptoms due to the receptor adaptations. Symptoms of withdrawal can include restlessness, muscle and bone pain, insomnia, diarrhea, vomiting, cold flashes with goose bumps, yawning, tearing, nasal discharge, tremors, anxiety, and involuntary leg movements. These withdrawal symptoms are unpleasant for pain patients and recreational drug users alike, and can lead to drug seeking behavior, crime, and various social ills. While research continues to be done to eliminate the euphoric effect of opioids, prevent their abuse, refine their precision, and limit the onset of tolerance, the medical community of today is forced to work with opioids currently available, and does its best to work around their limitations.

About the Opioid Oxycodone

The chemical formula is 4, 5-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride. Oxycodone is a semi-synthetic opioid derived from the opium alkaloid thebaine. It is typically made into the salt form, oxycodone hydrochloride, a white, odorless crystalline powder that is highly soluble in water and slightly soluble in alcohol. It’s chemically known as 4, 5a-epoxy-14-hydroxy-3-methoxy-17– methylmorphinan-6-one hydrochloride. It has a high oral bioavailability relative to other opioids, between 60 and 87 percent, making it ideal for oral administration. Oral bioavailability is the percentage of active drug which reaches systemic circulation through oral administration relative to direct injection into the bloodstream. High oral bioavailability is desirable because it reduced the physical size of tablets, and gives the physician greater precision when titrating doses because of predictable pharmacokinetics. Oxycodone also has a high nasal bioavailability[5], between 50 and 65 percent, which makes it a good candidate for a nasally administered formulation, but also for nasal abuse. It can also be given intramuscularly, intravenously, subcutaneously, and rectally, although these routes of administration are less desirable and generally unnecessary.

The serum half-life following oral administration is 3.5 to 4 hours. Its effective duration of analgesic action is 3 to 4 hours. As with all pure opioid agonists, there is no ‘ceiling effect’ to the analgesia, so patients can continue to increase their dosages indefinitely as tolerance builds and maintain analgesic effect. Like other opioids, its most dangerous potential side effect is the respiratory depression by direct action on the brain stem respiratory centers. It depresses the cough reflex by action on the cough center in the medulla, can produce some degree of nausea and vomiting, causes miosis even in total darkness, and slows digestion of food in the small intestine. Headache, dry mouth, constipation, somnolence, pruritus, sweating, dizziness, and asthenia are also reported by a small percentage of users[6].

Abuse Liability

During a congressional hearing on August 28, 2001, Dr. Michael Levy, Director of Supportive Oncology and Director of the Pain Management Center at the Fox Chase Cancer Center, stated, “I could find no data in my review of the literature, or our clinical experience, that there was anything to say that oxycodone had any greater risk for addiction than morphine, hydromorphone, or fentanyl.” The label on certain oxycodone products states, “Roxicodone™ can produce drug dependence of the morphine type, and therefore, has the potential for being abused.”[7] Another states, “OxyContin™ is an opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine.”[8]

The reality is however a fair bit more complicated. When studying the addictive properties of a drug, there are many variables involved. Environmental setting and stimuli play a significant part, as does the route of administration. Generally speaking, the time to peak plasma concentration of a substance decreases as one moves from oral administration, to nasal, to intravenous injection, to smoking. This time to onset of effects is a critical factor in the addictive potential of a drug, as a substance which gives a quick and immediate high is more addictive to the brain than one which comes on gradually. For instance, cocaine can be smoked, injected, ‘snorted’, or taken orally. In its smokable ‘freebase’ form, referred to as ‘crack cocaine’, its habit forming potential is significantly higher than when it is taken nasally, generally in the powder form cocaine hydrochloride. Cocaine can also be taken orally, or the original leaf of the plant can be chewed, giving a much subtler, longer lasting and less addictive effect, though most modern users do not use these routes. With any given opioid, users who inject the substance become dependent and tolerant more quickly than those who use it orally.

There is also variability among the opioids themselves. When administered by the same route, opioids are metabolized by the body differently, causing different times to peak plasma concentration and different half-lives. The molecular structure also effects the times it takes for a substance to cross the blood-brain barrier. Diacetylmorphine (Heroin) reaches the brain in 15-30 seconds when injected, and when smoked, reaches the brain in around 7 seconds. Once in the brain, it is converted into morphine, but the ‘rush’ of its quick onset and volume of distribution make it inherently more addictive and give it a different subjective high compared to morphine. In terms of duration of plasma concentration, Methadone has a half-life of 15-30 hours, while hydromorphone has a half-life of 2-3 hours. This partially accounts for the reason methadone is used a maintenance agent, because is does not provide as intense a ‘high’, and only requires daily administration. However half-life alone is not the only predictor of abuse potential, because individual opioids effect different receptor subtypes and produce different subjective effects.

Subjective effects can vary from person to person, so while there are general trends in preference, one individual may have different preferences compared to another. When factoring in the variable of administration routes, the task of determining the exact abuse liability of a given opioid is then nearly impossible. Controlled clinical studies cannot attempt to replicate the real world setting of opioid users, nor consider price and availability. Manufacturers instead make reference to a substance ‘having an abuse liability similar to morphine’ in order to provide the most impact, because for historical and social reasons, perception is that morphine is a more dangerous or addictive drug compared to modern opioids. The truth is that certain opioids may indeed have higher inherent abuse liability than morphine. Based on the higher rates of side effects from morphine, and subjective user comments, it appears that oxycodone may indeed be somewhat more enjoyable for many, and therefore more addictive.

Subjective comments from users[9] [‘Oxy’ refers to OxyContin tablets whose active ingredient is oxycodone]:

“I’ve had some almost 99% pure Heroin and I have to say it’s definitely better than Oxy[10], especially when considering the high price of Oxy.”

“Heroin has a very ‘narcotic’ feel to it, but oxy has a seriously ‘medical’ feel to it. It’s a very ‘clean’ high.”

“When you intravenously inject Oxy, the rush doesn’t last very long at all. The major part of it is over in about 20 minutes. Heroin lasts a lot longer.”

“Oxy is over quicker. Much cleaner [compared to heroin] though. Not as sleep and not so much of the itch. Oxy doesn’t make me as nauseated. Oxy makes everything beautiful.”

“All I can say is that I get a very giddy happy high from oxycodone while I get a knockout loaded feeling from heroin.”

“Morphine Sulfate is useless to me orally. It is extremely not well absorbed by this route. Morphine is not quickly absorbed even by injection compared to some others, and tends to cause more histemic and emetic reactions, not to mention more respiratory depression. It has a nice dreamlike quality though. Not at the top, but still very nice to have.”

“You get a lot more ‘nod[11]’ with Heroin than with Oxy.”

“When you get that oxy buzz,” she says, “it’s a great feeling. You’re happy. Your body don’t hurt. Nothing can bring you down. It’s a high to where you don’t have to think about nothing. All your troubles go away. You just feel like everything is lifted off your shoulders.”[12]

The mental effects of oxycodone appear to be well liked by users, but distinctly different from heroin. Most intravenous users note that the oxycodone ‘high’ from injection is of a much shorter duration than from heroin. The effects of heroin generally seem to be more popular. On addiction and withdrawal:

“The addiction that comes with Oxy is nothing compared to the nightmare of being addicted to Heroin.”

“It takes a while to develop a significant habit with Oxy, but with Heroin, you can develop a large habit very quickly. Heroin seems to be much more addictive.”

“Oxy withdrawal is much more painful physically that Heroin withdrawal. The bone and muscle aches are much more severe than what occurs with Heroin withdrawal. However the anxiety involved with Heroin withdrawal is extremely intense. Much more so than with Oxy withdrawal.”

“I recently tried to stop taking them [OxyContin™ pills] for a day and I visited what I believed to be the bowels of hell! I got extremely nauseous, with heavy sweating, hot and cold flashes, uncontrollable coughing, diarrhea, insomnia, rapid heartbeat, watery eyes, excessive yawning, and depression - the worst feelings I've ever felt. It got so bad that I seriously contemplated ending it just so I wouldn't feel this way anymore.”

There does appear to be a high degree of consensus that heroin has a higher addiction potential. This may be due partially to the higher frequency of injection for heroin administration, though pharmacological factors are likely the main reason. Oxycodone users typically take the drug orally or nasally because extra purification steps are necessary to prepare it for injection [this applies to both aspirin and acetaminophen containing products as well as wax-matrix OxyContin, though the procedures are different]. The user comment about oxycodone withdrawal being more physically painful could indicate that it acts more effectively as a pain reliever, while the comment that heroin withdrawal causes greater anxiety may mean that heroin provides a more intense sense of relaxation and euphoria.

Oxycodone was originally synthesized in a German laboratory in 1916. It has been used in Europe by injection and orally since 1917. Oral 5mg oxycodone formulations have been available in the U.S. since the 1950's, typically combined with a co-analgesic agent such as aspirin or acetaminophen, which is referred to as a ‘‘combination analgesic product”. Common brand names have been Percodan, an aspirin formulation, and Percocet, Tylox, and Roxicet, acetaminophen formulations. In large doses, aspirin and acetaminophen can be toxic to the liver, stomach and kidneys. Therefore, drugs containing aspirin or acetaminophen are limited in their usefulness because a patient can only take up to a set amount per day to avoid toxicity. Because the pills were only available in 5mg formulations, patients who were using them for longer durations who began to develop tolerance were also forced to take high numbers of pills per day.

In the past decade, single-entity oxycodone products became available in the U.S., as 5mg immediate-release tablet formulations with common brand names Roxicodone, Percolone, and OxyIR. A liquid formulation named OxyFast also became available. According to the FDA, there are 59 oxycodone containing products currently available in the United States as of 2002. These single-entity oxycodone formulations removed the potential for aspirin or acetaminophen toxicity, but the problem of dosing frequency and pill numbers still remained because the effective duration of oxycodone is only 4 hours.

OxyContin™

Image - OxyContin Chart explained in text. OxyContin™ is the brand name of a 12 hour slow-release wax matrix formulation of oxycodone. It was developed by Purdue Pharma L.P. and approved by the FDA December 12, 1995 in 10mg, 20mg, and 40mg dosage forms. An 80mg dosage form was approved January 6, 1997, and a 160mg dosage form was approved March 15, 2000, though the company later suspended shipment of the product on May 11, 2001. The product label states, “OxyContin Tablets are a controlled-release oral formulation of oxycodone hydrochloride indicated for the management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time.” The unique traits of this product were that it was available in dosage strengths two, four, eight, and sixteen times greater that previous oxycodone formulations, and that the oxycodone was released slowly, providing a duration of effect between 9 and 12 hours.

Commercial sale and marketing of OxyContin began in January of 1996. At the time, competing products on the market for time-release high dose opioid formulations were 8, 12, and 24 hour oral formulations of morphine, and a 72 hour formulation of the opioid fentanyl in a skin patch. In part because of the aggressiveness of Purdue’s marketing campaign, and in part because of the unique and superior qualities of the drug, prescriptions for the drug increased dramatically, rising from approximately 300,00 in 1996, to 6,814,000[13] in 2001.

The current retail price for OxyContin tablets is $1.38 for 10mg tablets, $2.48 for 20mg tablets, $4.30 for 40mg tablets, and $8.16 for 80mg tablets. A generic 5mg capsule of oxycodone retails for 28¢[14], roughly half the cost of an equivalent OxyContin formulation. The majority of prescriptions filled are covered by some form of health insurance, so these numbers are not indicative of what the typical patient pays out of pocket, however OxyContin is clearly an expensive medication relative to its direct substitutes.

At issue is whether OxyContin provides superior pain relief compared to other oxycodone products and other time-release opioid formulations. There is no clear answer to this question, as medical professionals have differing opinions, and patient subjective feedback is not quantifiable.

There is no evidence that oxycodone offers any advantage over appropriate doses of other opioids, and it appears to have the same potential for addiction as morphine.[15]

“I am now a chronic pain patient who relies on OxyContin to be able to hold a job and be a productive member of society despite the constant pain I am in. I have tried many different pain medications, but only OxyContin has the prolonged pain control necessary for around the clock functioning. It does not make me high or drowsy and I am using the same dose I started on 6 months ago; there has been no need for an increase in dosage and I have no desire to take any more than I currently do.”[16]

There seems to be some degree of clinical consensus that oxycodone is superior to morphine in terms of side effects and other pharmacological parameters. Controlled-release oxycodone (CRO) has the characteristics of an 'ideal' opioid analgesic drug: short half-life, long duration of action, predictable pharmacokinetics, absence of clinically active metabolites, rapid onset of action, easy titration, no ceiling dose, minimal adverse effects, and minimal associated stigma. CRO has been shown to be effective in the control of pain caused by cancer, osteoarthritis, post-herpetic neuralgia, major surgery, and degenerative spine disease.[17]

It does appear that clinical studies have proven that oxycodone is a superior opioid to morphine in terms of incidence of nausea and hallucinations, and possibly more effective in certain types of pain control. More questionable, however, is whether there is any superiority of a controlled-release formulation of oxycodone over a regular formulation other than in terms of dosing frequency. One study seemed to confirm that controlled-release oxycodone provides additional benefits, however as is common with clinical studies in this field, the work was funded by the manufacturer Purdue Pharma, which causes some question as to its validity. Conclusions of scientific studies stated:

In comparison to other opioids, morphine generally causes more nausea and pruritus. It also has the disadvantage of being relatively hydrophilic, which delays its transport across the blood-brain barrier. In addition, morphine has several active metabolites whose levels can vary with renal or hepatic function. The drug apparently induces its own metabolism, which makes it difficult to maintain a steady serum level.[18]

…the two opioids [morphine and oxycodone] provided comparable analgesia. The total incidence of adverse experiences reported by the patients was similar, but significantly more vomiting occurred with morphine, whereas constipation was more common with oxycodone.[19]

There have been sporadic reports of agitation, sleeplessness, and dysphoria in patients taking high doses of oxycodone, which suggests that, in addition to µ-opioid effects, the drug also has kappa-opioid effects. It may thus have some added advantage for treatment of visceral pain, which appears to respond to kappa-receptor agonists.[20]

controlled-release oxycodone given every 12 hours was comparable with immediate-release oxycodone given four times daily in efficacy and safety....[21]

CR and IR oxycodone were equally effective in the management of cancer-related pain. The adverse event profiles of CR and IR oxycodone were similar. Overall, however, significantly fewer adverse events were reported for CR oxycodone compared with IR oxycodone...[22]

OxyContin has certain other unique aspects relatives to available single-entity oxycodone formulations. The physical product is very small relative to its potency. An OxyContin tablet weighs approximately 3 times the milligrams of active content oxycodone. For comparison, the common brand name oxycodone combination analgesic product Percocet contains 5mg of oxycodone hydrochloride and 325mg acetaminophen, along with cellulose, starch, and other inactive ingredients, bringing the product weight to over 400mg.

The high concentration of active opioid product in OxyContin creates two major issues of concern. First is the possibly of a drug overdose, which can result if the wax-matrix slow-release mechanism is defeated, leading to an immediate release of the drug. Since its introduction, the product label for OxyContin has stated:

”OxyContin TABLETS ARE TO BE SWALLOWED WHOLE AND ARE NOT TO BE BROKEN, CHEWED, OR CRUSHED. TAKING BROKEN, CHEWED, OR CRUSHED OxyContin TABLETS LEADS TO RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF OXYCODONE.”[23]

So if one simply chews the tablet, breaking the wax-matrix, all of the oxycodone is released at once. For a 40mg tablet, that means instead of taking the equivalent of 2.6 Percocets every 4 hours, a user is consuming the equivalent of 8 Percocet tablets at one time. As the indicated dosage in non-opioid tolerant individuals is typically 1-2 Percocet tablets at a time, this is 4 times the recommended dose, and can in certain cases lead to fatal respiratory depression. In the typical adult, this dose would likely only lead to nausea and a period of immobility, however in susceptible individuals or when combined with another depressant drug, such as alcohol, the consequences can be more severe.

Of even greater interests to addicts and abusers is the possibility of nasal administration of the drug, which leads to an onset of peak effect in 25 minutes[24], compared to 60-90 minutes from oral administration (this includes if the tablet is chewed, which causes a greater peak but the same rate of onset). The outer coating of the OxyContin tablet is easily scraped off or wiped off with a wet paper towel, and with moderate force the wax-matrix core can be crushed into a fine power. This powder has active oxycodone concentrated at approximately 300mg/g, compared to the roughly 12 mg/g resulting from a crushed Percocet tablet, a 25 fold greater concentration. When a user attempts to snort a Percocet tablet, the mucous membrane becomes saturated with powder, causing sub-optimal absorption of the drug, while with OxyContin powder, the mucous membrane allows complete absorption. Coupled with oxycodone’s approximately 60 percent[25] nasal bioavailability, relatively high compared to other opioids, such as morphine at approximately 10 percent[26], the phenomenon of nasal abuse of OxyContin has become popular.

- -

The Media

According the LexisNexis academic search engine there were 573 stories in major U.S. papers between March 11, 2000, and March 31, 2003 which mentioned OxyContin in their title or lead paragraph. Yet despite the fact that the drug was introduced in January of 1996, there were no mentions of it in the four years and two months before The Columbus Dispatch, a local newspaper in Ohio, ran a story on March 11 about a doctor named John F. Lilly who had been arrested for illegally prescribing prescription drugs, including the drug OxyContin.

The story, written by staff reporter Bob Dreitlzer, said that Dr. John Lilly had been arrested as he tried to buy an automatic weapon from an undercover police officer. When searching his home, authorities found six automatic weapons and $400,000 cash. The arrest had followed an investigation in which authorities said Dr. Lilly had been illegally prescribing the drugs Valium, Vicodin, and OxyContin, among others. The article stated that, “[OxyContin] is a drug related to morphine that comes in a time-release capsule.” It also quoted a local prosecutor who said, “"For whatever reason, [OxyContin] is the drug of choice among users on the street here.'' The article headline ran, “Officials Hope Doctor's Arrest Will Stem Flow of Illegal Drugs Scioto County Man Charged.”[27]

Two months later on May 21, The Boston Globe ran a story on page 22 of section D titled, “A Prescription for Crime: Abuse of 2 Painkillers Blamed for Rise in Violence in Maine's Poorest County.”[28] The article began with a comment from the Washington County sheriff saying his 40-bed jail had been filled to capacity since December with people caught during break-ins and armed robberies while in pursuit of “heroin-like narcotics”. The story stated that drug agency statistics show that the remote county's per-capita use of OxyContin was more than twice the state average. It also mentioned that the previous year, “…the Maine Drug Enforcement Agency nearly doubled its arrests for pharmaceutical narcotics.”

A month later on June 27, the Times-Picayune, a New Orleans newspaper, ran the headline on its front page, “Potent New Painkiller on the Street, Cops Say; Task Force Investigating Street Sales of 'New Vicodin'.”[29] The first line stated, “A potent and addictive painkiller called Oxycontin may soon replace Vicodin as the most heavily abused prescription drug, according to federal and local authorities.” A local representative from the Drug Enforcement Administration was quoted as saying, “We're just starting to see Oxycontin abused and have started active investigations.”

However the major newspapers had yet to pick up on the OxyContin story. Small local papers in Maine and Kentucky began running stories with increasing frequency, but during the next six months, there were only 3 back-page stories in national newspapers which mentioned OxyContin, usually in reference to drugstore robberies. Finally, on February 8, 2001[30], The New York Times picked up on an announcement made the previous day that state and federal authorities in Kentucky had arrested 201 accused drug dealers for distributing the prescription drug OxyContin in a series of coordinated raids dubbed ‘Operation OxyFest’. The local U.S. attorney Joseph Famularo was quoted as saying that at least 59 people had died from OxyContin overdoses in eastern Kentucky during the prior year.

The New York Times ran the Associated Press feed on page 20, but the next day, February 9, ran their own story on the front page. The headline read, “Cancer Painkillers Pose New Abuse Threat.”[31] That night, the ABC television show 20/20 had an episode called “Painkiller ‘Epidemic’” based on the Kentucky drug raids. Following suit, The Washington Post ran, “Virginia Police Fear Rise of New Drug,”[32] on the front page of its metro section the next morning.

The major national newspapers had in fact been beaten to the punch by Time Magazine, which had run a story titled, “The Potent Perils of a Miracle Drug,”[33] on January 8. The line, “OxyContin is a leading treatment for chronic pain, but officials fear it may succeed crack cocaine on the street,” was run below the title. U.S. News & World Report featured an article titled, “The ‘Poor Man’s Heroin’,”[34] on February 3, based on the arrest of Dr. Lilly in Ohio from the previous March. After a two month pause, on April 9, Newsweek’s cover read “Painkillers”, and inside had the story titled, “How One Town Got Hooked,”[35] about the rampant abuse of ‘oxy’, as it was popularly referred to, in the rural town of Hazard, Kentucky. Another story in the same issue was titled, “Playing with Pain Killers.”[36]

There seemed to be common themes in the stories and to the media’s behavior. They generally portrayed OxyContin as a uniquely addictive, ultra-powerful narcotic with a ‘heroin-like’ high. They also suggested that the death toll from this drug was rising rapidly and eclipsing the deaths from abuse of other prescription drugs. Lastly, they gave little attention to the patients who were being helped by the drug, instead searching for the most sensational sound bites available. John Burke, Command of the Warren County Ohio Drug Task Force had this to say:

Most of my peers that I spoke to, and myself, were frustrated with the media when we were interviewed. They were anxious to hear stories of OxyContin® abuse, but were largely disinterested in comments that the drug had a very legitimate function with the vast majority of its users.

I recently invited a local television station to spotlight a pharmaceutical diversion investigator that I hired to address the overall problem of prescription drug abuse in our county. They photographed him meeting pharmacists in our county and allowed him a brief statement about drug diversion. They had asked about OxyContin®, and I told them I did not know how much of a problem the drug was in our area until I got feedback from my new investigator; until he had some time to gain experience in our area.

The story aired two nights later and I knew there was a problem when I saw the promotional piece. The story strongly insinuated that I hired the investigator because of the OxyContin abuse issue! This, of course, was totally untrue, but rebuttal opportunities are few and far between.[37]

At the time the stories were run, a thorough examination of the toxicological data of the supposed OxyContin deaths had not been done, so the press chose use the number given by the local U.S. attorney, or whoever was willing to provide them with a number. According to the February 9^th New York Times story, U.S. attorney for the east district of Kentucky Joseph Famularo had stated, “I personally counted 59 deaths since January of last year that local police attributed to addicts using the drug, and I suspect that's pretty conservative.”[38] In addition, without any hard numbers as to the extent of the abuse or information about the exact nature of OxyContin’s addiction potential, they began comparing it to crack cocaine and heroin.

The Associated Press quoted Harlan County Kentucky sheriff's department detective Roger Hall, as saying, “They'll [an OxyContin abuser] kick a bag of cocaine out of the way to get to 'Oxy',”[39] for their story about Operation OxyFest. The Port St. Lucie News in Florida ran with “The New Crack” in its headline. U.S. News & World Report gets credit for popularizing the phrase ‘poor man’s heroin’ with their February 3 article title. Though if they had done any hard research, they would have realized that the street price of OxyContin was greater than that of Heroin nearly as soon as it reached the black market. Perhaps the term was meant to refer to the fact that OxyContin was first popular in rural areas which don’t have as easy access to heroin markets.

‘Hillbilly heroin’ also become a popular term, as rural Appalachia was one area were abuse stories were first reported. Disregarding the fact that ‘hillbilly’ is considered a derogatory term, it was used in the headline of articles by The Houston Chronicle on August 7, 2001[40], and by The Atlanta Journal and Constitution on August 19, 2001[41], aside from numerous uses in the main text of various articles. General misinformation about the drug and its users was commonplace in the glut of stories in the mainstream media that all ran between January 8 and April 9 of 2001. In reality, they had very little information to work with, aside from a few quotes about death statistics, law enforcement arrest numbers, and company sales figures, so the press painted their own picture and began making comparisons to crack and heroin, as well as running sensationalized human interest stories about individual cases.

While perhaps they did not realize it at the time, the media was following a classic pattern of drug coverage, creating a new drug scare and playing on the public’s fear of the term ‘synthetic’.

Since the mid-1980s, the worst condemnations have been reserved for cocaine in its crack form. Remarkably often, too, popular anxiety has focus on less celebrated drugs, namely synthetic or manufactured chemicals, which have enjoyed a rhetorical importance far greater than might be suggested by their meager treatment in the vast literature on drugs and drug policy. At times of crisis, these drugs have been seen, however briefly, as national menaces at least as daunting as heroin or cocaine…

Reasonably or otherwise, synthetic chemicals arouse deep-seated fears concerning the power of science and technology to reshape human nature and subvert or corrupt humanity in a well-intentioned quest for social betterment.

The idea that drugs can reduce users to primitive savagery is inextricably bound up with the racial fears that have always been so critical an element of America’s drug scares. Synthetics are more closely associated with white dealers and users than with minorities, and they are as likely to be found in rural or suburban contexts as in inner cities: thus they defy the conventional stereotypes of the American drug problem.[42]

The fact was that the majority of OxyContin’s initial abusers were white and lived in poor rural areas. Something sinister existed as the media and administrators from wealthy white areas talked about this drug as if it were heroin, a drug associated with inner city minorities. They painted the picture that its popularity was growing exponentially and that after it took hold in rural areas it would head for the suburbs.

Ironically, the attention given to the drug by the press may have increased both the number of abusers and the number of crimes associated with it. Stories of drug robberies for OxyContin were among the most popular stories to run initially. On February 10, 2001 the Plain Dealer, a Cleveland, Ohio newspaper ran the story, “Abuse of Prescription Painkiller Spreading: Overdoses are Believed to Have Killed Dozens,” which began with the story of a masked man wielding a gun who broke into a pharmacy and demanded the store’s supply of OxyContin. Only 6 days later, another Cleveland suburb pharmacy was robbed and the perpetrator demanded the store’s supply of OxyContin. Considering the Cleveland area statistics at the time for pharmacy robberies and OxyContin related cases, the timing seemed more than a coincidence[43]. Nationally, statistics on pharmacy robberies followed the same pattern, as a dramatic increase in OxyContin related robberies only occurred in the Spring and Summer of 2001, following the intense media coverage of the January through April period.

In terms of abuse numbers, the source of the drug’s popularity is difficult to isolate, however it seems only logical that the intense media coverage of the drug increased its popularity.

However unwittingly, the media ensure that a new drug gains a popularity it might never have acquired if it had simply been ignored. Instead, the substance is described in the most exaggerated terms, stressing its extremely powerful, pleasurable and enduring effects in a way that in other contexts would be seen as unabashed advertising. The act of defining a new drug of choice, an ultimate high, a hot drug, may lead potential users to ask themselves why they are not sufficiently fashionable to have experienced it.[44]

A Cleveland heroin dealer was quoted in mid April as saying, “I never heard of the stuff until about a month ago when one of my customers asked me about it. He showed me an article in the paper that talked about how everyone wanted to get hold of this shit, so I did a little checking and found some available.”[45] The media’s glamorous portrayal of the drug’s effects may likely have encouraged people to experiment with the supposedly unique new heroin like drug. For a teenager without access to an urban drug dealer, this may have seemed liked an excellent alternative.

After the initial media flurry, stories continued to run about robberies and small-time arrests, but attention began to turn somewhat towards the manufacturer and its marketing practices, as well as the lawsuits which were beginning to crop up. May 14, 2001, Newsweek ran, “Painkiller Crackdown,” with the highlight, “Did the makers of OxyContin push too hard?”[46] On July 2, U.S. News & World Report ran “’Not An Appropriate Use’,”[47] a short article about the class action lawsuit against Purdue, and the same day, Newsweek ran, “Drugs: Profits vs. Pain Relief” with more vague references to lawsuits. The entire six month episode of OxyContin media attention was effectively and tastefully capped off by the New York Times Magazine on July 29^th with its cover story, “The Alchemy of OxyContin: From Pain Relief to Drug Addiction,”[48] about a rural town in West Virginia named Man.

The writer, Paul Tough, went to Man and spent time with locals in order to write a piece about the lives of those effected.

I came to Man to try to understand how America's latest drug problem started, to see its roots and trace how it has spread.

In Man, Paula said, it was like OxyContin came out of nowhere. One day no one had heard of oxys, and a month later, the pills had become a way of life for hundreds of locals. It became so easy to buy OxyContin in and around Man, Paula said, that until recently, she never really thought about the fact that everyone involved was breaking the law.

The piece was written in typical New York Times Magazine literary style and ran over 7000 words. It was the longest and most comprehensive article written on OxyContin to date. Though it was intended more as an accessible human interest piece about the lives of people effected, it included statements from doctors and Purdue Pharma representatives and generally did a good job of providing quality background information.

After the New York Times Magazine piece OxyContin coverage dropped dramatically. Newspaper attention shifted to stories of doctors’ arrests and more pharmacy robberies, as well as the occasional lawsuit. The weekly news magazine forgot about the drug, though nine months later, in April of 2002, Newsweek and U.S. News & World Report simultaneously remembered it long enough to run to short articles. April 22, Newsweek ran, “Oxy’s Offspring,”[49] about the babies of young OxyContin addicted mothers, and April 29 U.S. News and World Report published the 210 word article, “More Blame and Praise for a Pain Drug,”[50] which centered around a DEA statement that 464 drug overdose deaths had been pinned to OxyContin.

Though it’s somewhat difficult to fault the U.S. News writer for unquestioningly reprinting the DEA’s statements, Newsweek’s writer based her story about the OxyContin addicted babied on the statements of a local nurse. According to the “certified nurse midwife in the remote Maine town of Calais, “ who, “has now become a drug counselor and a reluctant expert on Maine's epidemic of narcotic abuse…many babies suffered withdrawal in the nursery, crying inconsolably, shaking with tremors and fighting diarrhea.” The nurse estimated that of the 40 babies she delivered the previous year, “10 were born to women hooked on opiates, and OxyContin was their drug of choice.” Despite the lack of any records, exact statistics, or outside analysis, the writer seemed to suggest that OxyContin addicted babies were becoming a national phenomenon. The similarities to the coverage of the ‘crack babies’ epidemic in the mid 1980s was a frightening and likely natural connection for readers to make.

Philip Jenkins provided an insight which applies very well to the case of OxyContin. He wrote, “It is tempting for the mass media to illustrate a looming drug crisis by taking one area in which a drug is indeed very popular and suggesting that these conditions will soon become generalized.”[51] The fact is, at least initially, OxyContin abuse was confined to fairly specific rural areas. Dr. Phil Fisher of the Appalachian Pain Foundation commented, “This is an isolated area where it’s hard for people to get real street drugs. By and large, OxyContin is not a street drug in most places.”[52] The demographic and economic conditions of Appalachia, low income, 20 percent unemployment, an older population, and a number of laborers with chronic pain issues from work in mines all made it a fertile area for OxyContin to take hold.

Yet it is really not surprising that the media portrayed OxyContin as it did. Indeed, mainstream media is known for its sensationalistic, sound-bite style news coverage, and has a history of dealing with drug issues in a way completely disconnected or disproportionate to actual events. In the late 1970s and early 1980s, the press covered PCP, or ‘angel dust’, referring to it as the “number one teen killer”. In the mid 1980s, crack cocaine was the demon drug of the country. In the late 1980s, the opioid fentanyl was called the “serial killer of designer drugs”. In 1990, the media ran stories about a dangerous new form of smokable methamphetamine nicknamed ‘ice’, but soon shifted their attention to a new drug called methcathinone, or CAT, which was supposedly “more addictive than crack”. The phrase was already becoming a cliché as U.S. News & World Report called it the “new drug of choice”, a “scourge that federal officials now say could threaten the entire nation.” In 1996, attention returned again to methamphetamine in its powder form, and then to the ‘date rape’ drugs GHB and Rohypnol. The statistics on use and abuse of these drugs never correlated with the attention they received.

Indicative of the media’s influence on public perception of drugs, on January 23, 2002, a man accused of distributing OxyContin on trial in Tazewell, Virginia, filed a motion requesting a change of venue for his trial. Steve Shelton of Raven, Virginia, requested that his trial be moved to a county or city located outside of Southwest Virginia. The motion read:

The widespread publicity concerning the nature of the alleged offenses and the defendant's alleged involvement in the offenses presents a reasonable certainty that the defendant will be denied his constitutional right to a fair and impartial jury. The articles and stories concerning OxyContin, including the editorials, have created a negative public perception of those accused of possessing or selling OxyContin illegally.

The motion included over 40 pages of clipped newspaper articles about OxyContin. The ubiquitous media coverage of OxyContin would likely have provided jurors with an inaccurate and biased view of both the drug and its social relevance. This is only one example of the media’s influence on legal proceedings, public policy, and legislation, yet there is no one to hold accountable for this spread of misinformation. The effects of the media would soon be seen by pain patients trying to get access to proper medication and make the right choices regarding their health, and the doctors who were in the position of balancing the medical needs of their patients with the rising threat of DEA investigations and public condemnation.

In an ironic and telling turn, on February 9, 2003, the New York Times ran an 1800 word story on their front page titled, “Methadone, Once the Way Out, Suddenly Grows as a Killer Drug.”[53] The article began:

Methadone, a drug long valued for treating heroin addiction and for soothing chronic pain, is increasingly being abused by recreational drug users and is causing an alarming rise in overdoses and deaths, federal and state officials say.

"Out of noplace came methadone," said James McDonough, director of the Florida Office of Drug Control. "It now is the fastest rising killer drug."

This new attention to methadone seems to follow in the traditional of pattern of finding new drugs to sensationalize based on the comments of a few government official and some conveniently interpreted statistics. However, the article also spoke of a problem which the media itself bore some responsibility in creating.

Physicians are increasingly prescribing [methadone] for pain relief, in part because law enforcement officials have been cracking down on OxyContin… "The availability of methadone for treatment and pain has put people who would not normally be in a position to divert drugs in that position," said Sgt. Scott J. Pelletier. In most states with increased methadone deaths, the methadone being abused appears to be tablets prescribed for pain.

As physicians were forced to prescribe methadone instead of OxyContin because of public perception and the DEA’s decision to single out OxyContin from other pain medications, abuse of the drug grew. It seems that a certain minority of people prescribed pain pills are going to give them away or distribute them no matter what type or brand they are.

As is apparent from the pattern and content of the media’s coverage of OxyContin, there is little connection or correlation with science or social impact. OxyContin did not appear and disappear in a 6 month period, nor did the number of crimes and deaths correspond to the number of media articles.

The seriousness attached to a given problem rarely reflects an objective assessment of the social threat posed by the issue in question. A situation can last for many years without being viewed as a problem, and the fact that it is suddenly seen as a crisis or an epidemic does not necessarily mean that it has become dramatically worse.[54]

This statement is a very appropriate insight for the OxyContin phenomenon, as an objective review of national drug abuse statistics, toxicology reports, prescription drugs trends, and emergency room data will reveal.

- OXYCONTIN ABUSE -

Drug Abuse

Hard numbers on drug abuse are in one sense impossible to obtain because there is no national database of citizens and their substance use habits. The available numbers are based on government surveys, police estimates, emergency room admittance information, and toxicology reports. The main source for drug use is a self-reported survey called the National Household Survey on Drug Abuse (NHSDA), conducted by Substance Abuse and Mental Health Services Administration (SAMSA). The NHSDA interviews approximately 70,000 people age 12 years or older, in every State, over a 12-month period. In the government’s eyes, the NHDSA is, “the primary source of information on the prevalence, patterns, and consequences of alcohol, tobacco, and illegal drug use and abuse in the general U.S. civilian non institutionalized population, age 12 and older.”

Unfortunately for our analysis, the NHDSA report does not contain detailed information about current pain medication use, only a category in the ‘Psychotherapeutics’ section labeled ‘Pain Relievers’. Fortunately, there is data from the ‘Initiation of New Substance Use’ section which has obtained information about OxyContin use since 1999. This section, which determines the number of new users of a substance, can be used to observe trends of new users in contrast to the current number of regular (in the past month) users.

In terms of current ‘non-medical’ use of prescription pain relievers, in 1999 there were an estimated 2.6 million users, in 2000, there were 2.8 million users, and in 2001, the number rose to 3.5 million users[55]. It is clear from an analysis of both the ‘new initiate’ data and ED admittance trends that only a small portion of this is attributable to OxyContin.

According to the 1999 National Household Survey on Drug Abuse, in 1998, an estimated 1.6 million Americans used prescription pain relievers ‘non-medically’ for the first time. This was a significant increase over the level of the 1980s, when there were generally fewer than 500,000 first-time users per year. Between 1990 and 1998, the number of new users of pain relievers each year increased by 181 percent[56]. The rising trend in the number of yearly new pain reliever users is visible in the accompanying chart.

This data, which was collected before OxyContin prescriptions had reached their current numbers, and before there were reports of diversion, street use, and abuse of OxyContin, speak to a greater trend in the use and abuse of pain medications. This is likely due both to the greater use of opioid pain medications which was occurring throughout the 1990s, before OxyContin’s introduction, and changes in public and medical perception of opioid pain relievers which had begun in the late 1980s[57].

The trend of new pain reliever initiates continued to grow through 1999, 2000, and 2001. In 1999, 1.7 million people use pain relievers non-medically for the first time. In 2000, the number reached 2.0 million[58], and between 2000 and 2001, the number of people who had used a pain reliever ‘non-medically’ at least once in their lifetime rose from 19.2 million to 22.1 million, a 2.9 million person increase[59]. While these numbers are alarming, a comparison to the responses for OxyContin shows that OxyContin was not contributing an increasing percentage of these new initiates.

In 1999, the NHDSA added OxyContin to the section of its survey which asks about first time use of a drug. This is separate from the section on regular use, in which it was not included. According to the NHDSA data, by 1999, 221,000 people had used OxyContin non-medically at least once in their lifetime. Between 1999 and 2000, there were 178,000 new first-time non-medical users (This number is smaller than the 1999 number because the question was first added to the survey in 1999 and OxyContin had been introduced in 1996). Between 2000 and 2001, there were 558,000 new first-time users[60]. While this is a significant increase in OxyContin percentage terms, relative to the total increase of 2.9 million first-time pain reliever users, the number is not so dramatic.

Considering that in 2000, there were 2.0 million first-time non-medical users of pain relievers and only 178,000 of them were OxyContin, it seems reasonable to attribute the percentage gains within the OxyContin category to the obvious factors; shifting preferences of users due to the recent introduction of the product; intense media coverage; and the increasing acceptance and prescription of the product. Not to something inherent in OxyContin which is inducing a new trend in the abuse of prescription pain medications.

Furthering this conclusion is the more detailed data from the ‘number of lifetime users’ section, which breaks pain relievers down into more specific opioid categories. While between 2000 and 2001, when the number of people who has used OxyContin once in their life increased by 558,000, to 957,000, the number of people who had tried Vicodin ‘non-medically’ at least once in their lives increased by 2.8 million, to 9.5 million. The fact that 2.8 million new people tried Vicodin while only 558,000 new people tried OxyContin seemed to escape the press as they sensationalized OxyContin’s rise. Apparently the press headline, “Potent New Painkiller on the Street, Cops Say; Task Force Investigating Street Sales of 'New Vicodin',”[61] was a bit off the mark. Indeed, Vicodin and other older opioids continued to attract new initiates in far larger number than OxyContin.

Between 2000 and 2001 the number of ‘at least once in their lifetime’ users of Darvocet and Codeine increased by 1.4 million, to 14.9 million. Percocet initiates increased by 1.4 million, to 7.8 million. Generic hydrocodone initiates increased by 1.0 million to 2.8 million, while morphine only increased by 100,000, to 1.64 million[62] during a period in which its total prescription numbers were declining. It is apparent that in relation to the million-plus increase in initiates of other opioids, OxyContin’s usage numbers are not that significant.

To put the ‘non-medical’ use of pain relievers in perspective, according to the NHDSA, in 2001, an estimated 15.9 million Americans age 12 years or older used an ‘illicit’ drug during the month prior to the survey interview. Of these users, an estimated 1.7 million were current cocaine users, 1.4 million used tranquilizers, 1.3 million used hallucinogens, 0.8 used Ecstasy, and 12.1 million used marijuana or hashish[63]. Also during the 2001 survey, an estimated 66.5 million Americans reported current use of a tobacco product, and an estimated 109 million people, 48.3 percent of the age 12 or older population, reported being current drinkers of alcohol[64]. This was an increase of 5 million people from the 2000 survey numbers of 104 million current drinkers. In contrast, the 3.5 million current ‘non-medical’ users of pain relievers represent 1.6 percent of the over age 12 population and showed an increase of 0.7 million people.

Emergency Room Visits

The other major source of data which provides trends in drug abuse is the Drug Abuse Warning Network (DAWN). DAWN is a national public health surveillance system that monitors trends in drug-related emergency department visits and deaths.

The Drug Abuse Warning Network relies on a sample of hospitals operating 24-hour emergency departments (EDs) to capture data on ED visits induced by or related to substance abuse. DAWN data do not measure prevalence of drug use in the population, but the probability sample of hospitals is designed to produce representative estimates of ED drug episodes and drug mentions for the coterminous United States and for 21 metropolitan areas. The Substance Abuse and Mental Health Services Administration (SAMHSA), the agency responsible for DAWN, is required under Section 505 of the Public Health Service Act to collect such data.[65]

It should be noted that the method they use to determine exactly which drugs are involved in incidents is open to a certain degree of interpretation bias. As they explain:

DAWN collects data by reviewing medical records. Patients are never interviewed. In each participating facility, a designated DAWN Reporter reviews all available medical records to identify ED visits that were caused by or related to drug use. For each reportable case, limited information — including patient demographics, reason for ED visit, and the drug(s) involved — is abstracted from those records and submitted to DAWN. Because the quality and completeness of information documented in medical records vary, data from DAWN should be interpreted with these limitations in mind.[66]

As patients are often unconscious and unable to report drug use during admittance, doctors often make their own judgment in determining which drugs are involved. Considering that the symptoms of opioid overdose are nearly identical, it is questionable as to rather a doctor would be able to determine exactly which opioid was involved. Toxicological information is also available in only a limited number of cases.

Not all drugs are confirmed by toxicology tests. Cases are reportable to DAWN if the medical record or death investigation case file indicates that the ED visit / death was caused by or related to drug use. A positive toxicology test is neither necessary nor sufficient to make the case reportable. EDs and medical examiners have widely varying protocols for how often they run toxicology tests, under what circumstances, and for which drugs. This variability limits the extent to which DAWN can rely on toxicology alone.

While the DAWN report does its best to correct for these data gaps by extrapolating from known brand name drug references and equalizing between unknown drugs from a given family, there is certain room for error and bias. If greater publicity of oxycodone abuse existed, more opioid overdose cases might be interpreted as being the result of oxycodone.

The number of total oxycodone ED drug mentions recorded by DAWN were 3,190 in 1996, 5,012 in 1997, 5,211 in 1998, 6,429 in 1999, 10,825 in 2000, and 18,409 in 2001.[67] DAWN also provides data distinguishing between pure oxycodone mentions and oxycodone combination product mentions. Combination oxycodone products include either aspirin or acetaminophen, so if the examiner determines that these drugs are not present, the episode is classified as a pure oxycodone mention. Between 1996 and 2001, combination product mentions increased from 3,090 to 7,309, while pure oxycodone classified mentions increased from 100 to 11,100.

It is this dramatic increase in pure oxycodone mention which proves so damning for OxyContin, as OxyContin account for 81.4 percent of the single-entity oxycodone product market in 2000[68]. Therefore one could conclude that approximately 9,000 ED oxycodone mentions in 2001 were attributable to OxyContin. Assuming the methodology of medical examiners did not change during the period, the rise in single-entity ED mentions is substantial. Even if the determination of the presence of a single-entity oxycodone product is sound this does not conclusively prove the use of OxyContin. As the DAWN report states:

DAWN can measure ED visits or deaths associated with drugs containing oxycodone, but not for OxyContin® alone. DAWN publishes information about particular drugs at the generic level, not at the brand level. Drug data submitted to DAWN contain the terms used in the source record at whatever level of detail was available. After receipt of the data, drugs are recoded into generic categories and duplicate entries are eliminated. Because of the variation in the raw drug data from source records, DAWN data on individual brands are deemed unreliable and are not published. Individuals using the DAWN data must not assume that all generic drug mentions are attributable to a specific brand name.[69]

This lack of brand data, coupled with the scientific impossibility of differentiating between single-entity oxycodone products, allows Purdue a certain amount of freedom in contesting these numbers. The analysis of medical examiner reports later in this section demonstrates just how dramatic the difference in interpretation can be if one is willing to play with the numbers. Even assuming that OxyContin was responsible for 9,000 of the oxycodone ED mentions in 2001, a comparison with the ED mentions for other opioids, recent trends in opioid analgesic use, and the ED mentions for other drugs make this number seem fairly reasonable.

First of all, it is important to note that while OxyContin prescriptions exhibited a dramatic rise after their introduction, from 300,000 in 1996 to 6.8 million in 2001, prescriptions for other opioid analgesics also rose dramatically during the same period. Not so much in percentage terms, but in real number terms, from 155 million prescriptions in 1996, to approximately 190 million prescriptions in 2000[70], an increase of 35 million including OxyContin. While the OxyContin prescriptions may have contributed more than others in terms of milligrams due to their higher per-pill potency, the rise in prescriptions was still only approximately 17 percent total number of opioid prescriptions.

In contrast to the seemingly dramatic 9000 oxycodone ED mention episodes that may have been due to OxyContin, during the same period, total ‘narcotic analgesic’ mentions increased from 46,941 in 1996 to 99,317[71] in 2001, a rise of 52,376. Even in comparison to the largest increase in oxycodone mentions, from 3,792 in 2000 to 11,100 in 2001, total ‘narcotic analgesic’ mentions increased from 82,373 to 99,317 during the same period.

Though no other opioid experienced a percentage rise in mentions as dramatic as single-entity oxycodone, from 100 in 1996 to 11,100 in 2001, a number of other opioids rivaled it or came close in numbers terms; hydrocodone product mentions increased by 10,148, to 21,567; methadone mentions increased by 6,596 to 10,725; and morphine mentions increased by 2,539 to 3,403. Fentanyl, a potent opioid analgesic used in slow-release skin patches considered highly abuse-resistant, and commonly used as an OxyContin substitute, experienced a rise nearly as dramatic in percentage terms, from 34 mentions in 1996, to 710 mentions in 2001.

In perspective, the DAWN ‘psychotherapeutic agents’ category, which includes all prescription pharmaceutical, had a total of 495,808 ED mentions. Of this, single-entity oxycodone contributed 11,100 mentions, which is 2.2 percent of total pharmaceutical mentions, and 1.0 percent of the 1,165,367 total substance abuse mentions[72]. The benzodiazepines, a class of drugs which includes Valium, Xanax, Ativan, Klonopin, and others, received 103,972 ED mentions in 2001, up 25,333 mentions since 1996. DAWN’s ‘Major Substances of Abuse’ category, which includes cocaine, heroin, marijuana, amphetamine, methamphetamine, MDMA, ketamine, LSD, PCP, miscellaneous hallucinogens, GHB, Rohypnol, and inhalants, rose by 190,883 mentions between 1996 and 2001, to 669,559[73]. Cocaine ED mentions alone rose by 40,614, almost 4 times the number attributable to oxycodone, to 193,034 mentions, nearly twice the number of mentions for the entire family of opioids under ‘narcotic analgesics’.

Heroin, itself an opioid very similar to those available by prescription, rose by 20,084 mentions, to 93,064 mentions in 2001. The increase in number of heroin mentions alone is greater than the total number of oxycodone mentions, and twice that of the mentions resulting from oxycodone. The total number of heroin mentions is nearly equal to the number of mentions resulting from the entire class of opioids currently in medical use, and nine times the number of ED mentions resulting from oxycodone abuse.

OxyContin Related Deaths

From the beginning, the number of OxyContin related deaths received a great deal of attention from the press. The most often quoted initial statistic was the one given by U.S. Attorney for the Eastern District of Kentucky, Joseph Famularo, when the completion of Operation OxyFest was announced on February of 2001. In the Associated Press report, he was quoted as saying that OxyContin had been responsible for 59 deaths[74] in eastern Kentucky during the past year. Attorney General for Virginia, Mark Earley, soon stated that OxyContin had been responsible for 32 deaths in southwestern Virginia since 1997, and later increased the number to 39 on information provided by Assistant Medical Examiner William Massello.

A wide range of numbers began to appear in press stories, often with no citation, or with vague references to local law enforcement officials. The truth was, a systematic examination of the toxicology reports had not yet been done, and nobody really knew the exact numbers. Reporter Sandeep Kaushik contacted Attorney Famularo’s office in regards to the 59 deaths figure given by Famularo, and was told by his spokeswoman, Wanda Roberts, “That figure was given to us by local law enforcement.”[75] Kaushik noted that the fact the number was generated by local police seemed troubling as they had used it to justify their investigation. Ms. Roberts declined to confirm that the figure was accurate. Mr. Kaushik then contacted David W. Jones, executive director of the Kentucky State Medical Examiner's Office. Dr. Jones stated, “As far as deaths go, I've heard different numbers in different places at different times. I have no idea where these people are getting their facts and figures.” According to Jones, there were 27 oxycodone related deaths in the state of Kentucky in 2000. Of these deaths, 2 of the victims had traces of alcohol in their systems, and 23 had traces of other opioids, including hydromorphone and heroin. Only 2 of the victims were shown to have had only oxycodone in their systems.

In a hearing before the House Subcommittee on Oversight and Investigations August 28, 2001, Representative James Greenwood of Pennsylvania stated in the hearing’s introduction:

In its testimony today, Purdue Pharma will argue that the death figures heralded by newspapers nationwide are inaccurate and are the prime mover of the negative hype surrounding OxyContin.

The company claims that the death reports do not take into account the fact that in the vast majority of these cases, oxycodone was detected, not OxyContin, per se. In addition, the company asserts that even in deaths where OxyContin was found, there were additional drugs present that contributed to or even caused the death of the individuals.

Law enforcement officials are skeptical of the company’s claims. The chief toxicologist in the Philadelphia Medical Examiner’s Office of Health care states, ‘‘Oxycodone has been in use for 80 years. The controlled release has not been. It is that elevated dose that is killing them.’’

The Delaware County coroner also argues that, ‘‘When you see 2 deaths, 3 deaths, 5 deaths, and then 17 deaths, it doesn’t take a rocket scientist to realize it is the OxyContin.’’[76]

The statements of this representative seem to suggest that law enforcement officials and toxicologists are all at odds with Purdue’s interpretation of the data. Considering that none of the House members at the hearing were trained toxicologists, it seems likely that they would have been inclined to believe the position of the public officials as opposed to the claims of the company.

The Purdue representative at the hearing, Michael Friedman, the Executive Vice President and Chief Operating Officer, delivered this statement:

The press has reported and repeated over two hundred times that in Kentucky, OxyContin caused the deaths of 59 people. Our contacts with the State Medical Examiner and local coroners establish that a number of deaths resulted from combinations of illegal and legal drugs, which occasionally included oxycodone, the active ingredient in OxyContin. Thus far, these local authorities have not asserted that a single death was attributable to the abuse of OxyContin alone.

The press has also reported 35 deaths from OxyContin use in Maine. Similar information from the Office of the Chief Medical Examiner showed that there were two cases where abuse of OxyContin was the sole cause of death, one of these a suicide.

It was in Purdue interest to influence the perception of these legislators with the authority to suspend or revoke OxyContin’s FDA approval. However they remained unable to directly influence the media’s coverage of the deaths, and of course the media had an incentive to continue using the more sensational numbers from the remarks of public officials rather than the company’s analysis.

Perhaps somewhat inappropriately, material was also included in the hearing from Mr. Edward Bisch, of Philadelphia, PA, whose son had died the previous February from abusing a combination of alcohol, the benzodiazepine Xanax, and OxyContin. The introduction to his prepared statement read:

I would like to thank the members of the committee for allowing my voice to be heard. My name is Edward Bisch from Philadelphia PA., On Presidents day of this year. February 19, 2001 I received a call that all parents DREAD and pray they NEVER receive. Christi my 15 year old daughter could not wake her brother ‘‘Eddie’’ up. That was the first day I ever heard the word OXYCONTIN. I was shocked when a police officer came in the house and said Oxycontin, ‘‘kids are dying left and right from this’’? I could NOT believe what I was hearing and angrily yelled? WHY DID I NEVER HEAR OR WAS WARNED ABOUT THIS DRUG?

From that moment on I started to educate myself on Oxycontin and started warning as many people as I could about the devastation of abusing it. My family and I quickly decided to publicly AIR our dirty laundry about Eddie’s death to get the word out to as many people as possible about OXYCONTIN ABUSE. We notified the MEDIA and were more appalled when the Philadelphia Daily News reported OXYCONTIN was also involved in 20 Philadelphia deaths within a three month period, but no warning was given about this rising epidemic?

Mr. Bisch went on to say that he spends much of his time learning about OxyContin and trying to increase public awareness through chain emails, talks, and a website he created called OxyABUSEkills.com. At no point in his letter did he mention that his son had been abusing Xanax and alcohol at the same time as OxyContin, nor that his son had been using OxyContin on weekends for months. To Mr. Bisch’s credit, he does state on the front page of his website:

My 18 year old son died 2/19/01 after chewing a Central Nervous System (CNS) depressant and powerful painkiller drug called OXYCONTIN which mixed with other substances that were already in his system, including alcohol.

It's been months since Eddie's death and I have learned a lot and spoken with many people thru my website. Most deaths -- I would estimate 90% -- that OXY was involved in actually were due to POLYPHARMACY (abusing more than one drug including alcohol). Yes, Eddie is one of these cases. Later I found out he abused Xanax earlier in the day.[77]

Yet the legislators at the hearing were not made aware of this, and it was perhaps misleading for them to be exposed to an emotional plea from a parent saying his son died from an OxyContin overdose.

Terrance W. Woodworth, Deputy Director of the Office of Diversion Control for the Drug Enforcement Administration explained at the August 28, 2001 hearing that, “The DEA has written letters to each member of the National Association of Medical Examiners requesting medical examiner/autopsy, toxicology, and crime scene investigator reports on all deaths related to oxycodone in the years 2000 and 2001.” As of the writing of this paper, the most up to date information on that study is available on the DEA website in a report titled, “Summary of Medical Examiner Reports on Oxycodone-Related Deaths,” dated May 16, 2002.

As part of the ongoing study being conduced by the DEA, the DEA wrote letters to 775 medical examiners from the National Association of Medical Examiners requesting their reports on all deaths “induced by, associated with, or related to oxycodone and/or, specifically, the oxycodone product, OxyContin” for the years 2000 and 2001. They then classified the reports into four categories: OxyContin verified deaths; OxyContin likely deaths; undetermined deaths; and incomplete reports.

The classification ‘OxyContin verified deaths’ was assigned when tablet contents in the gastrointestinal tract could be identified as OxyContin, or when there was evidence in the medical examiner’s report that the victim had an OxyContin prescription, an OxyContin tablet was found at the crime scene, on the person, or reported by any credible witness present at death. The classification ‘OxyContin likely deaths’ was used when there was oxycodone positive toxicology without the presence of acetaminophen or aspirin. This was due to the earlier explanation that of the 7.2 million single-entity oxycodone prescriptions in 2000, 81.4 percent were for OxyContin, and the only other two high dose oxycodone formulations, Intensol 20mg and generic oxycodone 30mg, had each been for only 24,000 and 1,000 prescriptions, representing 0.3 percent of the market.

As of February 14, 2002, the DEA had received 949 complete medical examiner reports from 32 states. They classified 464 deaths, 49 percent of the total reports, ‘OxyContin likely’. Of these, 146 were classified as ‘OxyContin verified’. The report stated:

Contrary to some reports, the documented evidence clearly shows that only 19% of the OxyContin deaths can be verified to be the result of a alcohol-drug interaction. Important also is the fact that only nine deaths were associated with the presence of a "recent injection site", and only one death associated with snorting the drug; the vast majority of deaths have been associated with oral consumption of the drug.[78]

The finding that of the 464 ‘OxyContin’ verified deaths, only 88 had quantifiable levels of blood alcohol at the time of death, was significant, as Purdue’s campaign to counter the OxyContin death reports had focused considerably on the prevalence of alcohol abuse among the victims. The data on injection sites and oral consumption was also highly important, since attention had been devoted in the press and in congressional hearings to the nature of the drug’s abusers. The image of the OxyContin abuser as a needle wielding heroin-type junkie had been common, as had that cocaine-user type substance ‘snorter’. These images prove to be false, but the report also contradicted the company’s stance that abusers are hardcore drug addicts and administering the medication in an unorthodox manner. If the majority of the people who overdosed were in fact taking the drug orally and intact, the company’s plans to create an abuse-resistant replacement pill would then have little impact on abuse and death numbers.

Most controversial were the polydrug toxicologies and the DEA’s stance regarding them.

Of the 949 complete medical examiner reports received, the majority were associated with polydrug toxicologies. More than 40% contained a benzodiazepine (Valium-like drugs); approximately 40% contained an opiate in addition to oxycodone; about 30% contained an antidepressant; about 14% contained over-the-counter antihistamines or cold medications; about 15% contained cocaine or its metabolites. These drugs reflect the typical drug combination patterns described in the published scientific literature associated with opiate addiction/dependence and show up as common "drug mentions" in the Drug Abuse Warning Network (DAWN) emergency department mentions of heroin/morphine episodes. Limiting the comparison to just the 464 OxyContin likely and OxyContin verified toxicologies showed a similar pattern of polydrug use.[79]

Purdue had taken the stance that any polydrug verified death should not be classified as an OxyContin death. As depressant drugs interact, they can dramatically increase each others’ potency. Therefore Purdue could reasonably claim that OxyContin was not the main cause of death and merely a contributor. The DEA had a somewhat different position however.

An additional caveat must be made regarding standard OxyContin treatment regimens as they apply to poly-drug use. According to the manufacturer’s product information, most of these patients receiving around the clock opiate therapy will need to have immediate release medications available for "rescue" from breakthrough pain or to prevent pain that occurs predictably during certain patient activities. Rescue medications are suggested to be immediate-release opiate formulations either alone or in combination with acetaminophen, aspirin, or other non-steroidal anti-inflammatory drugs (NSAID’s). The manufacturer’s product information clearly states, "Food has no significant effect on the extent of absorption from OxyContin". There is no adverse reaction notification for the co-administration of OxyContin and nicotine from cigarette smoking or with caffeine – a psychoactive drug found in many food products, including coffee. By these treatment designs a "normal" patient receiving a standard OxyContin prescription regimen approved by the Food and Drug Administration may be a poly-drug user. One treatment strategy recommended for "chronic pain" patients is the co-administration of opioids with anti-depressants – again, a treatment strategy, by its design, results in polydrug usage. With these facts in mind it was not surprising to find that many of the OxyContin deaths were associated with polydrug toxicologies. This does not minimize the significance of the role of OxyContin® in these deaths.

The DEA had a valid and relevant point in mentioning how the typical OxyContin user would likely also be prescribed a combination-type opioid formulation for breakthrough pain. In certain scenarios, following a doctor’s order, it might theoretically be possible for a patient to take their breakthrough medication and simultaneously overdose on OxyContin and the combination product, which would leave acetaminophen or aspirin to be found in the toxicology report. Assuming the patient is taking the medication as directed, however, this is extremely unlikely. The DEA was also correct in mentioning that chronic pain patients are also often prescribed an anti-depressant, which would explain the presence of anti-depressants in the toxicology reports.

It seemed, however, that the DEA was attempting to suggest that a patient could overdose on OxyContin when following a typical treatment regime. They had little evidence to support this assertion. As previously mentioned, if a patient is already taking 40mg, 80mg, or 160mg of OxyContin a day, they are likely tolerant to opioids, and a 5mg formulation breakthrough opioid would do little to induce respiratory depression. Additionally, anti-depressants are not actually systemic depressants, and would have no impact on the risk of respiratory depression. In fact, people who are susceptible to drug abuse are often chronic depressives, and may take an anti-depressant medication while simultaneously abusing drugs. Most surprisingly, however, the DEA seemed to go out of its way to suggest the polydrug toxicologies are a normal part of an OxyContin treatment regime by mentioning the “co-administration” of OxyContin with nicotine or caffeine. This is hardly what is meant by a polydrug toxicology. Most polydrug overdose victims have a benzodiazepine or another type of opioid in their systems. Neither of these would be common in a typical OxyContin regime, as the benzodiazepines are also depressants, and in any case would likely be unnecessary since opioids generally have a calming effect. Another opioid would also be uncommon as the breakthrough medication would likely be of the same type as the regular medication, merely in a smaller dose.

As Purdue would like to make clear, the DEA toxicology reports seemed to prove the OxyContin overdoses follow the typical pattern of polydrug abusers, not that of a typical OxyContin patient on a treatment regime. Indeed, according to the DEA’s numbers, which they do not aggregate in their report, stating only “the majority”, less than half of 464 ‘OxyContin likely’ classified deaths were due to OxyContin alone.

As part of their pubic relations and damage control campaign, in February of 2003, Purdue funded an analysis of the oxycodone death data which was published in the Journal of Analytical Toxicology. The report was titled, “Oxycodone Involvement in Drug Abuse Deaths: A DAWN-Based Classification Scheme Applied to an Oxycodone Postmortem Database Containing Over 1000 Cases.”[80] Purdue’s influence was noted in the methodology section of the report, which stated, “The study was funded by Purdue Pharma L.P. The principal investigators, who are not employed by Purdue Pharma, served as consultants and received compensation for their participation in this work.”

It was disseminated through PR Newswire, a company which, “provides electronic distribution, targeting and measurement services on behalf of companies, agencies and organizations who seek to reach the news media, the investment community and the general public with their up to the minute, full-text news developments.”[81] The title of the PR Newswire release on February 26, 2003 read, “New Study Finds Oxycodone Rarely the Sole Cause of Drug Abuse Deaths; Landmark Analysis Sets Standard for Interpretation of Deaths Involving Drug Abuse.” Though the title is somewhat misleading, and Purdue’s influence is buried behind the journal article and behind the news release, the attempt at drawing attention to the polydrug nature of the OxyContin deaths is legitimate.

The Journal of Analytical Toxicology study created an oxycodone postmortem database of 1014 complete records which they obtained from the medical examiner and coroner’s offices in 23 states between August 27, 1999 and January 17, 2002. Of these, they determined that 919 of the cases involved drug abuse, and of those 30, or 3.3 percent, were the result of single-entity oxycodone products alone. The report also notes that according to their methods, only 12 of the 30 oxycodone single-entity cases identified OxyContin as the source of the oxycodone, though going by oxycodone product prescriptions, it is likely that all 30 were due to OxyContin. The study found that of the 919 drug abuse cases, 889, or 96.7 percent of the cases were the result of multiple drugs, with oxycodone in combination with benzodiazepines, alcohol, cocaine, marijuana, or antidepressants.

There were a few questionable aspects to this study. First, they attempted to gain legitimacy by associating themselves with DAWN, the government drug reporting system, by stating, “A system of case categorization was developed for this study based on the Drug Abuse Warning Network (DAWN) system for reporting drug abuse mortality data in the United States, using the same standardized, well-understood terminology.” The authors were suggesting that their analysis was somehow more precise because of their new labeling system. This is misleading, as they used the same standard methods for analyzing the toxicology data. As mentioned earlier, also they drew attention to the fact that only 12 cases had OxyContin tablet identified. But most misleadingly, they suggested that the presence of another drug meant that OxyContin was not the sole contributing factor in the death. The reality of these polydrug toxicology analyses is that many of the combination drugs are neutral or even beneficial when used with OxyContin. While alcohol and benzodiazepines are depressants, cocaine is a stimulant, and would counteract the respiratory depression induced by oxycodone. Marijuana and anti-depressants would likely be neutral in their effect, though high doses of anti-depressant medication can actually be stimulating.

While the government study did not state how many of the 464 single-entity oxycodone cases were polydrug, the Purdue study did not state how many of the 919 cases were single-entity oxycodone with other drugs. Considering the DAWN ratio of single-entity oxycodone to combination oxycodone ED mentions, roughly 1:1, it is likely that the government’s number of cases is accurate. Of these 464 cases in a two year period, a portion resulted from combination with another depressant drug, but a larger portion were probably the result of oxycodone alone.

- THE DEA AND DIVERSION -

By definition, agencies whose primary mission is the control or suppression of illegal drugs have a vested interest in portraying those substances as threatening and ubiquitous. This is true for the DEA especially; its raison d’etre depends on finding and combating drug abuse, preferably with a regular infusion of issues that are sufficiently new and distinctive to grab the attention of media and political leaders, who face many rival demands for resources.[82]

-Philip Jenkins

The DEA

Oxycodone, the active ingredient in OxyContin, is a controlled substance in Schedule II of the Controlled Substances Act (CSA), 21 U.S.C. Sec. 801 et seq., which is administered by the DEA. The CSA mandates that the DEA prevent, detect, and investigate the diversion of legally manufactured controlled substances while, at the same time, ensuring that there are adequate supplies to meet the legitimate medical needs in the United States.[83] The DEA controls schedule II substances at the manufacturing level with quotas, and monitors their distribution to pharmacy wholesalers. All doctors who write prescriptions for scheduled substances are required to register with the DEA and are issued a unique license number. Certain states also maintain prescription monitoring programs, which the DEA helps administer and can access to observe distribution trends and to investigate questionable prescribing practices.

The DEA was created in 1973 by President Nixon who declared “an all-out global war on the drug menace”. In that year, the administration had 2,898 agents and an operating budget of $74.9 million. In 2003, the fiscal year budget proposal for the DEA was for $1.7 billion and 8,497 positions, of which $114 million and 793 positions were under the Diversion Control Fee Account (DCFA), used to monitor the diversion of controlled substances. DEA Administrator Asa Hutchinson explained before the House Committee on Appropriations:

The illegal use and sale of OxyContin^® is a growing problem throughout the nation. It is particularly widespread in the eastern United States although it is quickly spreading to the West. The growing popularity of OxyContin^® as a drug of abuse has given rise to an increase of associated criminal activity. Individuals demanding OxyContin® by name have targeted pharmacies nationwide for robberies, bypassing cash and other controlled substances.[84]

With this justification, the DEA requested an additionally $24.6 million and 133 positions including 75 Diversion Investigators to “strengthen its enforcement capabilities to prevent, detect, and investigate the diversion of controlled substances, particularly OxyContin.” $12.5 million of this was to support the DEA’s E-Commerce and Internet Online Project, which would “allow for the rapid and effective detection of diversion”.

Throughout the OxyContin episode, the DEA had a difficult line to walk. On one side, it had to show that it was taking a strong stance and direct action against the OxyContin ‘epidemic’ which was being created by the press. At the same time it had to balance the needs of patients and doctors. The DEA chose to play up the significance of the OxyContin problem to Congress and use the opportunity to request increased funding, while maintaining a constant stream of rhetoric about balance for patient and doctors at the same time that it was frightening them into altering their prescribing practices with the threat of investigations.

In the initial congressional hearing on August 28, 2001, Administrator Hutchinson stated:

The DEA does not intend to restrict the legitimate use of OxyContin, nor to prevent practitioners acting in the usual course of their medical practice from prescribing OxyContin for patients with legitimate medical needs. The Controlled Substance Act and DEA regulations do not attempt to define legitimate medical purpose, nor do they set standards as to what constitutes the usual course of professional practice. DEA relies upon the medical community to make these determinations.[85]

Administrator Hutchinson was clear to point out that the DEA regulations do not define legitimate medical purpose. Yet the reference to the ‘standards which constitute the usual course of professional practice’ was essentially carte blanche for the DEA to set whatever parameters it wanted to initiate an investigation. Before the Appropriations Committee, Mr. Hutchinson again attempted to stress how the DEA was taking a ‘measured, reasonable approach’.

The DEA recognizes that the best means of preventing the diversion of controlled substances, including OxyContin® and all other drugs, is to increase awareness of the proper use and potential dangers of the products. DEA is taking a measured, reasonable approach to dealing with OxyContin® and other drugs of abuse, and is committed to ensuring that there are adequate supplies of pain medications for those with legitimate needs while we strive to protect the public from the consequences of abuse.[86]

As he was explaining the importance of increased awareness, however, he was requesting money only for the purpose of diversion investigations. He did not explain that the DEA is not in the position to distribute information to pain patients, nor that being ‘committed to ensuring that there are adequate supplies of pain medications’ is a highly misleading statement.

There was never an issue of inadequate product supply of OxyContin, and the only threat that ever existed to adequate supplies was one created by the DEA itself. On May 17, 2001, during testimony before a Congressional subcommittee, DEA director Donnie Marshall told members of Congress that he was considering rolling back the annual quota the DEA sets on production of OxyContin. Marshall stated that he was “thinking of reducing the quota to the 1996 level unless Purdue did more to help reduce abuse of the drug. That's a drastic step and it would be a very controversial step, because there is the need for this drug out there, but I am seriously considering that.''[87] Though not factually correct in that the DEA cannot set OxyContin production quotas, it can limit the oxycodone quota of a specific company, which would have directly effected Purdue’s production of OxyContin.

In response to this threat, Richard S. Weiner, executive director of the American Academy of Pain Management in Sonora, Calif., sent a letter to Marshall the following week saying “it would be unethical” to cut the amount of OxyContin available. Weiner wrote, “That would be a very dangerous and wrong-headed policy, and would make it more difficult for people in pain to get [OxyContin], leaving thousands of people with less adequate remedies and hurting their quality of life.” Despite the predictable reaction of doctors, the DEA continued to emphasize that it was encouraging the use of controlled substances “where appropriate”.

It its 2001 OxyContin Special Industry Communicator, Larry Houck of the DEA Office of Diversion Control wrote:

A common misperception among medical professionals is the belief that the DEA’s regulations and policies impede effective pain management. For those of you unfamiliar with the DEA’s pain position, the reality is that practitioner fear of the DEA is unwarranted where controlled substances are used appropriately. In fact, far from prohibiting controlled substance use, the Controlled Substances Act, which Congress enacted and which the DEA enforces, its implementing regulations and the DEA all encourage their use where appropriate. The operative word, however, is "appropriate."[88]

Mr. Houck was attempting to somehow convince doctors that they should not feel threatened by the DEA because it desired ‘appropriate’ use. The obvious logic that doctors will prescribe controlled substances less if they believe there is the risk of scrutiny seemed to escape him. The fact is that the threat of DEA investigations is likely to make a doctor under-prescribe controlled medications because the DEA investigations, even if they lead to an innocent verdict, would put an economic burden on a doctor in the form of lawyer’s fees, lost business, and damaged reputation.

Regarding the DEA’s doctor inquires, Mr. Houck wrote:

There has been a misperception that the DEA investigates all doctors who prescribe significant quantities of narcotic drugs. Contrary to popular belief, dosage quantities and duration of treatment do not alone trigger DEA investigations because there are numerous legitimate reasons for such prescribing or administration patterns. Quantities and types of drugs involved are frequently components of an investigation but alone cannot trigger anything more than a closer look at the activity in question.[89]

The DEA seemed to be missing the point about the fears of doctors, and instead of suggesting that it make its investigative procedures more transparent or less burdensome for doctors, merely continued to emphasize that it knew what patterns to look for in uncovering illegal activities.

In a public relations move, aimed at convincing doctors, patients, and the public that the DEA had their best interests in mind, on October 23, 2001 a press conference was held in Washington, D.C. The news release was titled, “Drug Enforcement Administration, 21 Health Groups Call for Balanced Policy on Prescription Pain Medications Like OxyContin: Goal is to Protect Legitimate Use of Prescription Drugs for Patients in Pain”. It began:

In an unprecedented collaboration, the U.S. Drug Enforcement Administration today joined 21 of the nation’s leading pain and health organizations to call for a balanced policy governing prescription pain medications such as OxyContin. DEA Administrator Asa Hutchinson urged a policy that protects the appropriate use of opioid pain relievers for patients who need them, while also preventing abuse and diversion of the drugs.[90]

With little other recourse to influence the DEA, physicians, nurses, pharmacists and patient advocates participated in the press conference. Together, they released a joint statement titled, “Promoting Pain Relief and Preventing Abuse of Pain Medications: A Critical Balancing Act.” Selections from the beginning read:

As representatives of the health care community and law enforcement, we are working together to prevent abuse of prescription pain medications while ensuring that they remain available for patients in need.

Both health care professionals, and law enforcement and regulatory personnel, share a responsibility for ensuring that prescription pain medications are available to the patients who need them, and for preventing these drugs from becoming a source of harm or abuse.

Preventing drug abuse is an important societal goal, but there is consensus, by law enforcement agencies, health care practitioners, and patient advocates alike, that it should not hinder patients' ability to receive the care they need and deserve.[91]

Patients rights advocates did a good job of ensuring there was language in the joint statement focusing on the needs of people with chronic pain. According to the statement, the DEA supported the idea that while preventing drug abuse is an important societal goal, “it should not hinder patients' ability to receive the care they need.”

Only a week before the DEA requested an additional $24.6 million to “prevent, detect, and investigate the diversion of controlled substances”, DEA Administrator Hutchinson addressed the American Pain Society in Baltimore, Maryland on March 14, 2002. In his speech, he touted the joint statement of the press conference.

The last time I was with some members of your organization was in the fall at our press conference releasing our joint statement on promoting pain relief and preventing abuse of pain medications. It was a historic moment for the DEA, the American Pain Society, and the 20 other health organizations that joined together in that consensus statement.

We have a shared goal of making sure that controlled substances are used only for the health and welfare of the American public. We made a commitment at that press conference to achieving a balanced approach to the prescribing and regulating of opioids. My message to you tonight is that we stand by that commitment.[92]

Yet there were ominous undertones to his message. In his next statement:

While OxyContin has probably received more publicity than any other abused legal drug, it is not of course the first time we've seen this kind of problem. If we go back a century and look at the beginning of our drug abuse problems in this country, we learn that, by 1900, about one American in 200 was either a cocaine or opium addict. A great number of those had become addicted inadvertently through legal medicines. These were legal drugs then because science and experience had not yet taught us how dangerous those drugs are.

The same bias which was apparent in the DEA’s review of the oxycodone toxicology reports was apparent here. Mr. Hutchinson is simultaneously associating OxyContin with cocaine and opium, and suggesting that OxyContin is like other previously legal drugs which lead a great number of people to become addicted. He seems to imply that science and experience will also lead us to make OxyContin illegal. The same attempt to show that OxyContin was addictive and dangerous, even when used correctly, was also seen in the wording of the DEA’s oxycodone review and interpretation of the concept of polydrug use.

Speaking as if the physicians in attendance were in agreement with him, Mr. Hutchinson continued:

In light of all this, I know the medical community has become somewhat wary about the use of OxyContin and other opioids. I know Dr. Ashburn told Congress that "Fears of diversion and regulatory scrutiny weigh heavily on the physician's mind when prescribing these medications." Other medical groups have expressed similar concerns to me.

I'm here to tell you that we trust your judgment. You know your patients. The DEA does not intend to play the role of doctor. Only a physician has the information and knowledge necessary to decide what is appropriate for the management of pain in a particular situation. The DEA is not here to dictate that to you. We do not intend to restrict legitimate use of OxyContin or other similar drugs. We will not prevent practitioners acting in the usual course of their medical practice from prescribing OxyContin for patients with legitimate medical needs. We never want to deny deserving patients access to drugs that relieve suffering and improve the quality of life.

This was quite idealistic talk from Administrator Hutchinson. Unfortunately, this rhetoric was in stark contrast to the reality of the situation. The fact was that hundreds of doctors were already being investigated specifically for prescribing OxyContin.

In testimony before House Subcommittee on Oversight and Investigations August 28, 2001, when explaining the gravity of the OxyContin situation to Congressman Rogers, Mr. Hutchinson had stated:

In 1999 we had a half a dozen OxyContin cases; in 2000 we had 37 cases; and in 2001, up to August, we had 168 cases. So over a year’s time—really in 2001, we have over five times as many cases as in the entire year of 2000. And so you can see that it is dramatically eating up our investigative resources. [93]

So in the eight months of 2001, the DEA had undertaken 168 OxyContin investigations. Attempting to comfort the physicians to whom he was delivering his speech, Mr. Hutchinson noted:

The vast majority of doctors will never even see the DEA during their careers. In 2001, more than 900,000 physicians were registered with the DEA to handle controlled substances. During that year, we initiated only 861 investigations of physicians. [94]

Yet that means that in 2001, over a quarter of the DEA’s physician investigations were regarding the prescription of OxyContin. For a doctor deciding which pain medication to prescribe, it seems likely that this would have significant weight in his decision, and could cause him to utilize an alternative which may not be optimal for his patient.

Of course, aside from anecdotal evidence, this is difficult to prove empirically. The total OxyContin prescription numbers for 2002 are not yet available, so whether OxyContin use has declined or the growth in prescriptions had declined is unknown. Even assuming that the trend in prescription growth was due in large part to the medical superiority of OxyContin rather than to diversion and abuse, the DEA’s actions have likely had a significant dampening effect on the behavior of physicians. Dr. Steven Passik of the Markey Cancer Center in Lexington, Kentucky wrote a letter regarding this dampening effect to the Journal of Pain and Symptom Management. Titled, “Same As It Ever Was? Life After the OxyContin Media Frenzy,” Dr. Passik concluded:

The regulatory environment seems to have taken a step backwards as well, or at least the perception of it has. Once again, doctors routinely tell me that they are afraid to prescribe adequate doses because of fear of sanction. Once again, the idea that investigations will be triggered by numbers of prescriptions and milligrams is rampant. Is it true? I think it is hard to say, but I am afraid that there may be a widening gap between the philosophy espoused by top members of the law enforcement community and what is happening on the ground.[95]

Illicit OxyContin

"We had a 92-year-old lady that legitimately needed these drugs, but there was none in her system because she was selling them."

-Fred Evans, board member of the American Pain Society

OxyContin is a schedule II controlled substance, which means that a doctor’s prescription is required to obtain it at a pharmacy, and it is subject to the strictest regulation practices and scrutiny of any available controlled substance. Illegal techniques to obtain it include pharmacy diversion, over-prescribing by corrupt physicians, ‘doctor shopping’ by patients, fraudulent prescriptions, pharmacy theft, and international smuggling.

According to the DEA, diversion by physicians and pharmacists are the primary sources of diverted pharmaceuticals available on the illicit market[96]. Typically, a physician writes a prescription for a fictitious patient and has it filled by an accomplice, or a pharmacist will forge prescriptions and order directly from the distributor. ‘Doctor shopping’ is also popular - a practice where an individual with a legitimate or fabricated illness visits a high number of doctors and attempts to get medication prescribed for the same condition. In certain areas, a physician may be known for easily dispensing prescriptions or an individual may cross into a neighboring state to obtain the prescription.

It seems that the states hardest hit by robberies were the ones where the original outbreaks occurred. Massachusetts was a bit of an anomaly as it had not been part of the original abuse wave, but the intense coverage by the Boston Globe may have increased the awareness of criminals in the area. According to the DEA Office of Diversion Control, 700 pharmacy thefts involving OxyContin were reported between January 2000 and June 2001. The distribution pattern was somewhat erratic; 82 thefts were reported in Florida; 90 in Pennsylvania; 69 in Kentucky; 74 in Ohio; 12 in Maine; 60 in Massachusetts; and 34 in California. Information published by the Massachusetts Board of Pharmacy showed that there were 7 robberies involving OxyContin in 1998, 27 in 1999, and 25 in 2000. Robberies then jumped to 105 in 2001, 87 of them armed.[97] Officials in Kentucky said that 5.5 percent of their pharmacies had experienced OxyContin related robberies, and in Maine 4 percent experienced OxyContin related robberies.

At the February 12, 2002 Senate hearing on OxyContin, The National Association of Chain Drug Stores issues this statement:

NACDS represents nearly 190 chain pharmacy companies that operate about 34,000 retail pharmacies all across the United States. We filled about 70 percent of the 3 billion prescriptions provided across the nation last year.

Our members’ pharmacies have been targeted by OxyContin abusers for armed robberies. We are concerned for the safety of our pharmacists, technicians, clerks, cashiers, and our customers. We support an all-out effort on the part of the manufacturer to reformulate the product to produce one that is equally effective for legitimate patients with chronic pain but, at the same time, resistant to potential diversion and abuse of the drug. Any pressure that can be exerted on the manufacturer, the Food and Drug Administration and the Drug Enforcement Administration to expedite the development of such a product will be instrumental in eliminating this public health crisis.[98]

Despite the number of robberies, however, the reality of the situation was that pharmacies were benefiting from OxyContin sales, and NACDS made no move to remove the drug from its shelves. Indeed, pharmacy lobbying groups had long opposed electronic prescription monitoring programs and other measures which would reduce total sales of pharmaceuticals[99]. In Massachusetts, one of the states harder hit by robberies, the two supermarket chains Shaw’s and Stop & Shop attracted some attention for their change in OxyContin handling procedures, though they merely added a 3 day wait period to fill the prescriptions.

Along with legitimate armed robberies and numerous of people walking into pharmacies and claiming to have a gun, there were a few more bizarre stories. On December 17, 2002 in Chester, Virginia a man with long white hair and a beard, a red suit and hat, black boots, and a large belly resembling Santa Claus walked into a pharmacy and asked for OxyContin while brandishing a firearm. January 21, 2003 in Oil City, Pennsylvania a man took a pharmacy employee hostage but later released her unharmed after a 2 ½ hour standoff. And on February 6, 2003 in Natick, Massachusetts, a state trooper on medical leave was arrested in a hospital for allegedly robbing a pharmacy at gunpoint the day after Christmas.

On December 4, 2002 U.S. Customs seized a shipment of 7,000 counterfeit OxyContin tablets at Boston’s Logan airport and 20,000 counterfeit tablets at New York’s JFK airport with a combined street value of over $1 million. Analysis of the tablets showed that they did not contain oxycodone, but suggested that an organized crime ring of some type was likely distributing them.

Importation from Mexico and Canada is also another potential source of illicit OxyContin. The number of dosage units exported by Purdue to Mexico had been increasing dramatically, from 5,000g in 1998, to 26,500g in 1999, to 89,000g in 2000[100]. Purdue had already begun restricting higher strength dosage units and been labeling the tablets with “EX” on one side instead of “OC” like the U.S. versions, but on December 9, 2001 nine armed individuals wearing masks stole 30,000 20mg 30-tablet bottles of OxyContin from a pharmaceutical distributor in Mexico City with a street value of $1.8 million, so Purdue decided to suspend all shipments to Mexico indefinitely. In Canada, Purdue began marketing tablets with “CON” and switched distribution from its Totowa, New Jersey facility to one of its facilities in England to combat diversion. While it is possible for American citizens to obtain OxyContin in Mexico and Canada and import them back to the United States, this threat is not great. 89,000g sounds significant, yet Nevada alone consumed 92,000g of OxyContin in 2000, and Florida with its large elderly population consumed over 1.1 million grams in 2000.[101]

photo - Oxycodone Controlled-Release Tablets for Mexico and Canada explained in text. Much of the crime and resourcefulness of people trying to obtain OxyContin illegally has been due to the high street price of the drug. OxyContin generally has a black market value of $1 per milligram, so tablets which cost between $1.30 and $7.60 retail typically sell for $10 to $80 each on the street. For an addict trying to obtain his next dose, or a drug dealer trying to make a profit, this creates a powerful incentive to obtain the drug for free or at retail price. Unfortunately DEA and police constriction of street supply serves only to maintain the incentive and high black market price.

The Office of National Drug Control Policy (ONDCP) publishes a biannual report called Pulse Check which provides up to date information about “hardcore drug-abusing populations, emerging drugs, new routes of administration, varying use patterns, changing demand for treatment, drug-related criminal activity, and shifts in supply and distribution patterns.” It regularly covers cocaine, marijuana, heroin, methamphetamine, and club drugs. In the November 2001 issue, a new section was added labeled ‘Special Topic: Synthetic Opioids’ specifically to address issues relating to OxyContin. The information contained in the November 2001, April 2002, and November 2002 issues of Pulse Check is the most up to date information about current street level OxyContin use.

During the April 2001 Pulse check report, for which the data was collected before the initial media attention, only Portland, Maine reported it as an emerging drug, but by the November 2001 report it was seen as emerging across the country. According to the November 2001 report, initial reports of diversion and abuse were in rural areas of Kentucky, Maine, Maryland, Pennsylvania, Virginia, and West Virginia, when in 2001 it began to emerge in metropolitan areas such as Baltimore, Boston, Denver, Detroit, Miami, Philadelphia, St. Louis, and Washington D.C.[102] This patterned seemed to confirm what many had said, that rural areas with existing prescription drug abuse issues and little access to typical street drugs were originally the most vulnerable, and only after the intense media attention did the drug move into urban areas where heroin was the established illicit opioid of choice. The states in which it was reported as emerging also seemed to correlate with the states in which OxyContin per capita consumption was highest.

Condemning remarks for the media came in a section labeled ‘Pulse Check sources reflect mixed views on the accuracy of media attention’. The report stated, “Although most responding Pulse Check sources believe that the media has portrayed the diversion of OxyContin accurately in their communities, several sources believe that the media has overemphasized the problem.” It continued:

…many sources (the law enforcement source in Birmingham and Washington, DC; the epidemiologic sources in Boston, New Orleans, Philadelphia, Seattle, and Sioux Falls; and the non-methadone source in Sioux Falls) believe that the media has overemphasized the problem. The opinion of several sources is that not only has the media overplayed the problem of diverted synthetic opiates like OxyContin® in their communities, but also they have helped encourage abuse. For example, the Boston epidemiologic source states, "Large amounts of media coverage have probably led to increased use by alerting opiate addicts to a possible market….it has probably increased illicit (OxyContin®) sales." The Portland (ME) epidemiologic source reports that the intense press coverage is accurate for the area, but that media attention "may have increased the value of illicit OxyContin®; it may have increased the desire to obtain it."[103]

A number of public officials were aware of and made comments about the effect of the media on the popularity of OxyContin. While there is no conclusive way to prove this, when law enforcement officials are concerned about a drug receiving too much press attention it seems certain that significant problems are being created by the coverage.

In terms of perception of the seriousness of the problem, in 2001, the period which received the most media coverage, 32 of the 83 Pulse Check sources perceived OxyContin diversion or abuse as a somewhat serious or very serious problem in their communities. The Northeast had the highest number of responders saying that is was a very serious problem, approximately 35 percent, while only 10 percent of western sources felt this way and none of the Midwestern sources. In response to, “How has the perceived problem changed between fall 2000 and spring 2001?”, 37 of the 83 sources perceived OxyContin diversion and abuse as escalating in their communities, while none felt that it was declining.[104]

A year later, however, after the media attention had died down, Pulse Check noted in the introduction to the November 2002 report that, “Some signs indicate that diversion and abuse of [OxyContin] might have peaked during the last reporting period.”[105] In response to the question, “How serious is abuse and diversion of synthetic opioids?”, only 1 source, Miami law enforcement, felt that it was a very serious problem, in contrast to the 32 serious responses during the report from the previous year. In terms of availability, it seemed that either the DEA’s efforts were being successful, or the decrease in media attention was changing public perceptions, because the November 2002 report showed very limited availability. In November 2001, 18 of 26 sources had said that it was somewhat or widely available, while by 2002 only 1 state listed it as widely available.

In the November 2002 report, nearly all sources were reporting that sellers were predominantly independent. Only Miami and New Orleans reported the existence of organized sales structures. This was in stark contrast to the DEA’s attempts to suggest that OxyContin was being diverted and distributed by organized crime rings. In the March 2002 DEA diversion report, they had stated:

Illicit OxyContin distribution is not limited to localized distributors as it also includes polydrug trafficking organizations.[106]

While there may have been occasional reports of this sort of activity, given to the difficultly of obtaining large quantities of OxyContin and the nature of sales, it has been highly uncommon. Organized distribution sound threatening and implies a more entrenched social problem, so it is not surprising that the DEA would emphasize this.

Sales most commonly took place in the central city and rural areas, with many of the buyers residing in the suburbs. According to law enforcement sources, OxyContin is sold hand-to-hand through acquaintance networks, although occasionally delivery services are used. Private residences were the most common location, followed by streets around methadone treatment clinics. The most common slang terms for OxyContin were “Oxy”, “OC’s”, “Oxy-cotton”, “Blues”, “Forties”, “O’s”, and “Cotton”, with the most commonly sold pill being the 40mg version followed by the 20mg and 80mg formulations. White males were the predominant demographic of OxyContin abusers, with their numbers overrepresented in comparison to the general population. Only Washington, D.C. reported Black males as being overrepresented. Most abusers were also of low or middle socioeconomic status according to all respondents. Users were generally young adults or adults, without a significant pattern to the age groups. Oral ingestion was also reported as the most common method of administration, although injection and snorting were also occasionally reported.[107]

Aside from the statistics on pharmacy robberies, it is difficult to provide any quantitative data on OxyContin related crimes. In comments to the media, a number of law enforcement officials provided some dramatic numbers, but these were unverifiable. In Charlestown, Virginia Nicholas County public defender Greg Hurley stated, "Every other person who walks into my office is involved in this stuff - selling, stealing, whatever. Half the crimes in this county are related to OxyContin." The DEA Drugs and Chemicals of Concern OxyContin diversion report stated, “Some jurisdictions report as much as a 75% increase in property and other crimes that they specifically attribute to the abuse of OxyContin. An official in Tazewell County, Virginia estimates that OxyContin® addiction is behind 80 to 95% of all crimes committed there.”[108] It seems unlikely however that these were anything other than hyperbole or isolated incidents, since crime rates in counties showed no correlation with OxyContin per capita consumption or rates of diversion.

- FEDERAL HEARINGS AND LAW ENFORCEMENT -

Congressional and Public Hearings

Members of any political organization charged with investigating social problems of any sort will attempt to attract as much publicity as possible by presenting themselves as concerned, active and well-informed guardians of the public good.[109]

-Philip Jenkins

A total of three congressional hearings were held on OxyContin, with two in the House of Representatives and one in the Senate. The first hearing was on August 28, 2001, before the House Subcommittee on Oversight and Investigation titled ‘OxyContin: Its Use and Abuse’. The subcommittee is one of six subcommittees of the Commerce and Energy Committee and is responsible for overseeing the FDA, DEA, and activities of the pharmaceutical industry as a whole. The Chairman of the subcommittee was Representative Greenwood of Pennsylvania, who explained,

We are here in a fact-finding mode, to hear from experts from around the country and from this areas, as to recommendations, what their experiences have been, what recommendations they may have for us, so that we can take that information back to Washington and see if what legislative or administrative activities that might help to resolve this problem.[110]

The meeting was attended by a police officer, a district attorney, a representative from the FDA, a DEA director, a medical doctor, and the top officers from Purdue Pharma.

The hearing seemed to maintain a neutral tone, commensurate with its fact finding nature, though at one point Deputy Directory Terrance Woodworth of the DEA Office of Diversion Control knowingly misled Representative Greenwood during a discussion. In explaining the number of oxycodone ED mentions, Mr. Woodworth stated:

Mr. WOODWORTH: The [oxycodone] mentions from 1988 through 1996 were roughly 1,000 per quarter during that time period. And in 1996, as I mentioned, they went to 3,190. And then they increased in 1999 to 6,429. And in 2000, they are at 10,825, I believe.

Mr. GREENWOOD. So a tenfold increase in the number of times that Oxycodone is referenced in a visit to the emergency room. And obviously a lot of people abuse this drug, overdose from this drug, and that doesn’t result in their death. They are coming to the emergency room in various conditions, a tenfold increase in seeing the presence of this drug associated with emergency room visits. Is that right?

Mr. WOODWORTH. Yes, sir.[111]

In fact Mr. Woodworth was correct in saying that oxycodone mentions were roughly 1,000 per-quarter until 1996. They then actually declined that year, to 3,190 mentions for the total year, but this switch from quarter to full year ED mention numbers confused Mr. Greenwood because of the decline, so he interpreted the following numbers to also be per-quarter figures. Believing that Mr. Woodworth had said oxycodone mentions went from 1000 per quarter to 10,825 per quarter, Mr. Greenwood asked if there had been a tenfold increase, and Mr. Woodworth said “yes” knowing that in fact there had only been a threefold increase. This issue aside, the hearing was relatively objective compared to the one which followed.

The second hearing was held December 11, 2001 by a subcommittee of the House Committee on Appropriation, which controls the funding for the DEA. Representative Frank Wolf of Virginia was Chairman of the hearing on what he referred to as “the illegal use of the highly addictive painkiller OxyContin”. Testimony was heard from the DEA, law enforcement officials from Virginia and Kentucky, Purdue Pharma representatives, an individual recovering from addiction to OxyContin, the American Cancer Society, the American Pain Society, and a physician from the Johns Hopkins Pain Medicine Department.

Congressman Wolf began the meeting by referring to a number of news stories he had read in the New York Times about OxyContin related crimes and corrupt pain management clinics. He continued with a dramatic story from the Richmond Times Dispatch:

On November 30^th, the Richmond Times Dispatch reported that a doctor from southwest Virginia was sentenced to 6 years in prison for writing hundreds of unnecessary prescriptions for OxyContin and other drugs. Two days earlier, the paper reported the sentencing of two parents from Franklin County, Virginia for felony child neglect after their 16-month-old daughter overdosed on OxyContin pills she allegedly picked up off the floor of their home.[112]

These comments were hardly objective or appropriate. Though it was not possible to verify this story, it appears to be typical sensationalized journalism. Congressman Rogers, former District Attorney of Kentucky, continued:

Thank you, Mr. Chairman. More importantly, thank you for holding this hearing at a very opportune time, as our former colleague in this body has assumed these heavy responsibilities to head the DEA.

You have inherited OxyContin in my area, the worst scourge that we have had in the drug wars. There is an absolute epidemic of OxyContin misuse in eastern Kentucky. This substance is running rampant through the small rural communities of Appalachia, wreaking havoc on the adolescent population. In my 20 years of service in this spot, and 11 years before that as a D.A. in Kentucky, I have never seen this devastating an effect from one substance on people, particularly young people.

Though Pulse Check reports stated that juvenile populations were largely unaffected, Congressman Rogers determined that OxyContin was “wreaking havoc on the adolescent population”, “an absolute epidemic”, and “the worst scourge that we have had in the drug wars”. If he had only been reading newspapers, it might be understandable that he had developed this perception of the matter, but any objective review would have told him otherwise. Indeed, it appeared that his dramatization of events might have been designed in part to convince others of the necessity of the DEA funding increase which Administrator Hutchinson was about to request and Congressman Rogers planned to advocate.

In a later exchange with Mr. Hutchinson regarding the DEA’s budget, Congressman Rogers made it clear that he felt the DEA was underpowered and should step up its efforts.

Mr. ROGERS: You are severely undermanned, do you admit?

Mr. HUTCHINSON: Absolutely.

Mr. ROGERS: Shouldn’t you consider stepping up your drug diversion efforts in the local communities? I mean, there are a thousand pharmacies in Kentucky. You have seven diversion officers for the whole State, and a few special agents. Every one of those places where pharmacies are located have local police forces, local sheriff’s forces and State law enforcement, and yet we are hearing from those people that DEA is not really plugged into this. They are not getting the proper resources from DEA and the Federal agencies. And I am asking you, do you need more money for that type of thing?

Mr. HUTCHINSON: The answer is yes, Mr. Chairman.

Mr. ROGERS: How much money do you need?

Mr. HUTCHINSON: We have put in a budget request for FY 2003, and we have asked for 50 additional diversion investigators, which would be funded out of our diversion fee account. And this is absolutely essential for us in terms of our diversion investigators. Whenever you look at what we have to do to support, you know, our local counterparts, I would assure you, of those 50 diversion investigators, we will get some resources in Kentucky.

This exchange was essentially a plug for increased DEA funding, for which Congressman Rogers, being from Kentucky and a former district attorney, was a big proponent.

The Senate also held a hearing on February 12, 2002, called for by Senator Warner of Virginia. It was titled ‘OxyContin: Balancing Risks and Benefits’. Senator Kennedy of Massachusetts, Senator Gregg of New Hampshire, and Senator Collins of Maine were also present to hear the testimony from Dr. VanZee from the St. Charles Pain Clinic in Virginia, a sergeant from the Virginia State Police, the director of the FDA Office of New Drugs, Purdue’s Vice President of Research, and several others. Senator Collins made the introduction, and set the tone with these comments.

We are here today to examine the benefits and the risks of a legal but regulated narcotic pill marketed under the name of OxyContin. There are many people who have a legitimate medical need for OxyContin and we cannot forget that in some cases this drug has made a real difference in the quality of their lives.

It would be disingenuous, however, to dismiss the current epidemic of OxyContin abuse as simply the latest drug of choice, no different from last year’s or perhaps next year’s popular drug. The testimony this afternoon will highlight how OxyContin has insinuated itself into communities and, as one Maine law enforcement officer has described it, spread like wildfire. Washington County has a population of only about 35,000 citizens. It is estimated by law enforcement officials that 1,000 of those citizens are addicted. That is just a startling statistic. These statistics, however shocking, do not fully convey the destruction of human lives caused by the abuse of OxyContin. When talking to people on the front lines in Maine I have heard stories of lost jobs, broken families, and young people who naively thought that a legal drug available at a local pharmacy could not possibly do them any real harm but who are now in a desperate fight to reclaim their lives.[113]

The Senator’s dramatization of the OxyContin ‘epidemic of OxyContin abuse’, which she implies is somehow uniquely different from other popular drugs of abuse, is simply factually incorrect. As is seen from the ED oxycodone mentions, the extent of OxyContin abuse is undramatic relative to the abuse of other drugs, and the same horrifying tales of human destruction have been told for decades about other drugs of the moment. Despite the Senator’s accusatory tone, no action was taken against Purdue at this or any of the other hearings.

Other public OxyContin events developed as well. A hearing was held by the FDA Advisory Committee on January 30-21, 2002 regarding the appropriate use of opioid mediations in various populations, including the risk-to-benefit ratio of allowing use of opioid for patients with chronic nonmalignant pain. A balanced approach was stressed, and some members noted that restrictions on opioid use had a substantial likelihood of hurting legitimate patients. The National Consumers League also held an OxyContin related panel discussion titled ‘Second Symposium on Risk and the Media: Communicating Consumer Health and Safety Risk’ at the National Press Club on January 24, 2002.

Former Chief Medical Correspondent for ABC News George Strait moderated the discussion, which examined news reports on OxyContin and attempts make suggestions on how to improve the accuracy of media coverage. The American Enterprise Institute of Public Policy Research also held a meeting on February 7, 2002 titled ‘The OxyContin “Crisis” - Who’s To Blame?’, which was largely critical of the media’s behavior and presentation of the problem.

In an attempt to capitalize on the attention OxyContin was receiving, the National Institute on Drug Abuse launched a “campaign against misuse of legally prescribed drugs” in April of 2002. The campaign seemed to be lacking substance, however. The Journal of the Medical Association reported on the meeting in its May 2002 issue, writing:

At a press conference announcing the effort to raise awareness about the dangers of these drugs, representatives from pharmacies and drug manufacturers joined NIDA director Alan I. Leshner, PhD, at the podium. All offered obligatory support for the endeavor, which at the moment amounts to a collection of pamphlets, Web sites, and other educational materials. Lacking any fixed agenda other than drawing the attention of the Washington media the parade of spokespersons balked at questions about the true scope of the problem and how to remedy it.[114]

This criticism of NIDA’s effort can be extended to the entire drug abuse problem, in that the reality is that little can be done to prevent the abuse of prescription medications other than drastically restricting their supply. Education programs may help slightly, but there are few ways, if any, to reach the generally population other than television and magazine advertisements. The distribution of information pamphlets in doctor’s offices or health clinics by NIDA, the DEA, or any government agency attempting to influence the behavior of the populace have little impact or influence.

Philip Jenkins’ quote regarding self-perpetuations seems to aptly fit the behaviors of the government agencies involved.

The first operant concerns self-perpetuation. No matter what the original purpose was behind any human activity, as soon as it becomes institutionalized, its purpose immediately becomes self-perpetuation. Governmental bureaucracies are mainly concerned with protecting their budget and avoiding legislative demise.[115]

Perhaps this is unrealistic, but government agencies involved in the effort to reduce drug abuse should admit that despite their best efforts, a percent of the population is going to choose to abuse prescription drugs no matter what. Agencies are rarely willing to admit that there are diminishing marginal returns to their efforts, and instead make unrealistic promises and continued requests for funding.

In a move typical of federal agencies, the Substance Abuse and Mental Health Services Agency (SAMHSA) director of the Center for Drug Abuse Treatment took the opportunity at the February 12, 2002 Senate hearing to request additional funds. Dr. Westley Clark stated:

As you know, SAMHSA is the lead Federal agency for improving the quality and availability of substance abuse prevention, addiction treatment and mental health services in the United States. SAMHSA has both funding authority and certain key regulatory responsibilities that will play a central role in the national response to abuse of and addiction with OxyContin and the many other prescription analgesics which can be abused by Americans in the grip of opioid addiction. It must be recognized that the abuse of OxyContin is not primarily by those who are pain patients but by those who are opioid addicts.

This administration is committed to supporting local programs that combat the personal despair and community disintegration brought by drug addiction. Our new fiscal year 2003 budget requests an increase of $60 million for the Substance Abuse Block Grants to the States and an additional $67 million for competitive drug treatment grants, which can be specifically targeted to urgent local needs such as those we are discussing today.[116]

While increased funding for treatment and maintenance programs is critical considering the number of heroin and opioid addicts who are unable to be enrolled in clinics, the $60 million in block grants for states seems more like a case of funding for funding sake, rather than a program which could have any appreciable influence on OxyContin abuse or the improvement in the quality of life enjoyed by citizens.

As of this writing, no substantial actions had specifically been taken against Purdue Pharma or the sale of OxyContin. The hearings likely did have some influence on support for the DEA’s funding increases, however. On January 16, 2003, a press release went out which read, “The government is launching an advertising campaign aimed at educating people about the risks of abusing prescription drugs.”, however no specific information was provided. March 31, 2003, Representative Wolf of Virginia who had been an opponent of OxyContin the hearing the previous year, made a bid for some publicity by asking the Department of Health and Human Services to restrict prescriptions of the painkiller OxyContin to people with severe pain. He wrote to the agency, “The drug should not be marketed to treat moderate pain. Too many people have died, too many families have suffered and too many communities have been devastated by the improper use of this drug.”[117] As the chair of the House Appropriations Committee, his opinion has some weight, yet there did not seem to be wide support for this measure.

There did seem to be some murmurings of other congressional hearing when on March 10, 2003 House Energy and Commerce Committee Chairman Billy Tauzin and Representative John Dingell requested that Purdue provide information about its new unapproved painkiller Palladone, a slow-release formulation of hydromorphone, including as draft risk-management plan and potential drug sales forecast. They also requested any available records comparing the addictive properties or abuse potential of OxyContin to Palladone. No official hearing date had been announced.

Enforcement and Prevention Efforts

The February 2001 announcement of Operation OxyFest was the first major action by the government in OxyContin enforcement efforts. The operation was conducted by state and federal authorities over a 9 month period and resulted in the arrest of approximately 200 individuals. According to the U.S. Attorney, the raids were the largest ever made in Kentucky. Aside from efforts at the local and state level, the DEA had not yet developed a unified plan deal with the problem, nor received any direct publicity. By the Summer of 2001, however, the DEA had developed what it termed the ‘OxyContin comprehensive National Action Plan’. The action plan had four sections titled ‘Enforcement and Intelligence Tools’; ‘Regulatory and Administrative Powers’; ‘Industry Cooperation’; and ‘Awareness / Education / Outreach initiatives’.[118]

The first element involved the coordination of field offices and existing law enforcement resources to “target individuals and organizations involved in the diversion, illegal sale, pharmacy theft, fraud and abuse of OxyContin.” The agency also planned to work with NIDA and SAMSHA to improve OxyContin data collecting service. The degree of the DEA’s success in these measures is uncertain, as there were no more public announcements of large coordinated raids after Operation OxyFest, except for Operation Grinch announced on December 18, 2001 by Lee County, Kentucky’s Sheriff Harvey Pelfrey. The arrest of 40 individuals was announced, but credit for the operation was given to the local police department, without any mention of state or federal involvement.[119] The raid received no national attention.

The second element of the DEA plan was to elicit support from other regulatory agencies. This included cooperation with the FDA, and work with the Federation of State Medical Boards to educate physicians about pain treatment and addiction. The benefits of these efforts are questionable, as the FDA was already pursing its own efforts to demonstrate its commitment to correcting the problem. It had been criticized in the Congressional hearings for approving OxyContin, and was already busy pressuring Purdue to make a less abusable formulation of OxyContin and to change its product insert with a strengthened warning label. As far as the DEA’s cooperation with the State Medical boards, the DEA has always played an adversarial role since physicians view the DEA’s actions as meddling in their autonomy and reducing their ability to effectively treat patients. Attempts by the State Medical Boards to insulate themselves from DEA influence already existed in the form of pain treatment guidelines which patients advocacy groups had been pushing though state legislatures.[120]

The third element, industry cooperation, also seemed to ring hollow, as Purdue was already undertaking its own public relations efforts with pamphlets to physicians, an informational website, and a modification of the tablets it exported. Purdue had an incentive to take these initiatives on its own, and preempted whatever suggestions the DEA might have desired, such as with the withdrawal of the 160mg tablet formulation. The company also mentioned that it was working with medical organizations to “better assess the legitimate medical needs for narcotic analgesics”[121]. It is unlikely that these efforts bore any fruit, as the consensus of the medical community was that chronic pain patients were still under-treated, not over-treated as the DEA was attempting to suggest.[122] The DEA’s continued use of the term “narcotic” to refer to opioid analgesics merely served as an insult.

The last element of the action plan, designed to “recognize the importance of the appropriate use of opioids in the treatment of pain”, was to increase national awareness of the dangers of OxyContin abuse though an aggressive national outreach effort to schools, the healthcare industry, and state and local governments. No specifics were given or are currently available about the specific elements of this plan, but considering that the DEA’s conception of ‘appropriate use’ is squarely at odds of that of physicians and the healthcare industry, it seems unlikely that this initiative will have much relevance.

It appears that the DEA’s ‘National Action Plan’ was designed more as a document to be displayed for the upcoming congressional hearing and budget increase requests than as a legitimate agenda. A thorough analysis of its initiatives showed it to be hollow in content, yet Administrator Hutchinson proudly displayed it before the appropriating committee in March of 2002, and made no mention that by this point there was already evidence to suggest that the OxyContin problem was receding. As part of the original August 28, 2001 congressional hearing, an affidavit of the Lee County, Kentucky Sheriff Gary Parsons had been included which read:

In recent weeks, I have observed what appears to be a significant reduction in the abuse of OxyContin. I have seen a re-emergence of previous drugs of abuse such as Lortab, Tylox, and Xanax. The street value of OxyContin tablets has increased and contributed to this reduction in use. I also attribute the reduction in the abuse of OxyContin to the efforts of law enforcement, the arrest of corrupt doctors, heightened awareness of prescription drug abuse to educational efforts, and the assistance of Purdue Pharma in supplying our office with placebo OxyContin tablets to be used in reverse buy and bust operations.[123]

Despite this and other evidence about the reduction in the problem, the DEA still wrote in the conclusion of its March 2002 OxyContin™ Diversion report:

OxyContin abuse and diversion will continue to spread throughout the United States. OxyContin abuse and diversion will continue to pose a significant problem for law enforcement authorities.[124]

There were literally no statistics available to support these claims by the DEA other than the rise seen in the number of prescriptions and the small number of increases seen in oxycodone ED mentions.

Perhaps as another indicator of the weakness of the DEA’s evidence, by October 14, 2001, eight months after Operation OxyFest’s conclusion, fewer than half of the 150 people who were arrested on state charges had plead guilty or been convicted, and in one county, charges against seven of the fifteen people arrested had been dismissed. Though the lack of convictions was due in part to the trial deadlines and sentencing guidelines of the state court system, attorneys familiar with the cases said that weak evidence was a significant factor.[125]

The story was different in federal court, where the majority of the 52 suspected charged had pled guilty, in part because those with the strongest evidence against them had been tried in federal courts, and in part because of stricter federal sentencing guidelines. On March 6, 2002 a federal judge sentenced a Lee County, Kentucky man to 36 years in prison for two counts of trafficking OxyContin and two counts of possessing a gun during a drug trafficking crime. Federal prosecutors said that it was the stiffest known sentence to date for a crime involving OxyContin. According to the Assistant U.S. Attorney Eric Hunt, the judge’s sentence was the minimum possible, but because the crimes happened on different days, the first offense carried a mandatory five-year term and the second offence 25 years. It appeared that the government was setting an example of the man, as it admitted that the guns had been given to the man as payment for OxyContin and there was no evidence that he had intent to use them. Of the forty others which had been sentences by federal judges, the majority has been order to spend time in halfway house or in-home detention.

Of course the problem did not recede entirely on its own. Other important measures were taken to combat the problem. State Medicaid Fraud Control Units played a part in a number of convictions, detecting patterns when patients submitted claims from a number of physicians for the same illness. On June 11, 2001 Pulaski, Virginia became the first town in the country to use a fingerprint security system to track legal prescriptions of OxyContin. The police department provided the six local pharmacies with fingerprint kits so that all customers filling OxyContin prescriptions would have their prints on record in invisible ink. If a prescription turned out to be forged or stolen, police would then have a record of the print.

In certain states, Purdue began making available special tamper-resistant prescription pads to make forgery more difficult. In Massachusetts, Shaw’s supermarket chains and Stop and Shop supermarkets added a three day delay to their OxyContin fulfillment period. On March 26, 2002 the FDA fast-tracked clearance for an oxycodone assay developed by American Bio Medica Corp of New York. The assay, known as Rapid One OXY is capable of detecting very low levels of oxycodone in urine and differentiating between other opioids. It was to be used in clinics, and in certain situations, to detect if patients were using the medication which they had been prescribed. U.S. Customs was also altered to the possibility of important OxyContin shipments.

Beginning with the first OxyContin related arrest of Dr. Lilly in Ohio on March 11, 2000 the investigations of doctors rapidly increased. In 2000, the DEA conducted 37 OxyContin related investigations, and in the first seven months of 2001 conducted 168 investigations. This was a significant portion of the 861 total investigations the DEA initiated that year, of which 697 resulted in actions against violators with 535 convictions and 80 arrests.[126]

The arrests made good news stories and received substantial attention. On December 23, 2001 Dr. Lievertz of Indiana was arrested for writing over $1 million worth of OxyContin prescriptions over two years which were paid for by state Medicaid, more than six times the dollar volume of the next highest prescriber in the state. One patient was written $130,000 worth of prescriptions which at times would have had the patient consuming 31 pills per 12-hour period.[127] In Florida, Dr. Denis Deonarine was charged with racketeering, drug dealing, and first degree murder after a patient overdosed on OxyContin and a number of other opioid pain relievers, alcohol, and Xanax. After a raid on the Comprehensive Care and Pain Management Center in Myrtle Beach, South Carolina in June of 2000 the six doctors who operated the clinic were arrested. In Roanoke, Virginia Dr. Cecil Knox and two office workers were indicted by a federal grand jury for violations of the Racketeer Influenced and Corrupt Organization Act, originally designed to prosecute organized crime cases, and faced charges of life in prison and $27 million in fines. And in mid-February, in one of the highest profile cases, Dr. James Graves was found guilty of manslaughter and unlawful delivery of a controlled substance by a Florida court and sentenced to 30 years in prison. Prosecutors claimed that he had been making over $500,000 a year by writing illicit prescriptions. His conviction was the first for an OxyContin related death.

While many of the cases are still under appeal, and despite the protests of defense lawyers and doctors about manipulation by patients, it appears that the DEA had convincing evidence in the vast majority of these cases. These sensational cases and the cases of all the doctors involved in OxyContin related crimes were the exception to the rule, however, and represented the activity of less than one tenth of one percent of licensed doctors. There have always been a small number of corrupt doctors, and the number investigated by the DEA had been constant leading up to 2001, when it increased by under 5 percent. Apparently the type of corrupt doctors who had been writing prescriptions for schedule II opioids had switched to OxyContin, and but after it began to attract DEA attention, they switched away from it again, leaving the DEA with the first batch of corrupt doctors. In fact the number of investigations declined in 2002 from 861 to 681, despite the increased resources which the DEA devoted.

It was this intense OxyContin related scrutiny and threat of investigations which led doctors to choose alternatives to OxyContin. It is not hard to see the logic that despite the DEA’s best intentions of not influencing doctors who were acting in the normal course of treatment with legitimate patients, they had a significant adverse effect on the proper or optimal treatment of those patients. Suggesting that this was beneficial to a reduction in OxyContin abuse would run counter to the DEA’s argument that corrupt doctors and illegitimate patients intent on diversion and distribution were the main source of the problems.

Another option which had been discussed was the removal of OxyContin prescribing privileges from regular physicians and restricting it only to pain specialists. The problem with this is that the majority of patients who need quality chronic pain medication don’t have access to the approximately 4,000 pain specialists in the country. If a cancer patient were to obtain treatment at an urban institution and return home to a rural community to be treated by a family physician, he would be unable to obtain medication. Dr. Bruce Bagley, Chair of the American Academy of Family Physicians representing over 91,000 family physicians explained his association’s stance at the February 28, 2002 hearings:

Limiting the prescribing rights of certain physicians would create a dangerous new precedent of federal intervention into the practice of medicine. The American Academy of Family Physicians views such proposals as detrimental to the health of our patients and urges Congress to oppose such recommendations.

As of this writing this suggestion has not received any further attention from congress.

Recent Opioid Policy and Practice

This is not just about OxyContin. This is about the potential for rolling back progress made in pain management. It's been an extremely hard uphill climb to get physicians to become more comfortable prescribing opiates and overcoming the stigma among patients about potential addiction and abuse.

-Dr. John Giglio, Executive Director of the American Pain Foundation

According to the American Pain Foundation, an estimated 50 million Americans suffer from chronic pain, with a cost of approximating $100 billion attributable to lost workdays, excessive or unnecessary hospitalizations, unnecessary surgical procedures, inappropriate medication, and patient-incurred expenses from self-treatment. In 1994, the Department of Health and Human Services issued new guidelines encouraging the use of opioids in the treatment of cancer pain, and in February 1999, the Veterans Administration added pain as a fifth vital sign, along with pulse, temperature, respiration, and blood pressure. October 28, 2000, Public Law 106-386 was enacted declaring the decade commencing on January 1, 2001 to be the Decade of Pain Control and Research. When the OxyContin coverage first began, bills were currently pending in both the House and Senate called The Conquering Pain Acts of 2001, S. 1024, and H.R. 2156, which would have recognized that chronic pain is a health problem affecting at least 50 million Americans. These bills are still pending.

Professional concern for achieving balance in drug policy emerged in 1985 from a new national organization of state drug control officials. At the heart of this concern was the recognition that opioids were underused in the treatment of pain.[128] Through the 1990s, there was a rapidly growing trend for states to adopt policies which addressed the prescribing of opioid analgesics for chronic pain. Impetus for change came from state medical boards who wished to adopt guidelines which recognized the role of opioids and set acceptable parameters for there use. Physician and patient chronic pain advocates pressured legislators to adopt policies which would insulate physicians from disciplinary action when prescribing opioids.

In 2000 there was a sharp drop in the number of state pain policies adopted or amended, from 16 in 1999 to six. In 2001, six new policies were adopted, of which four were considered to have language which had the potential to enhance pain management and none which would impede it. Guidelines were published in Kentucky which contained guidance for physicians on how to prevent abuse and diversion of pain medications, making it the first state with a pain policy to address such issues. This was likely done as a response to the intense media coverage OxyContin initially received in Kentucky.

Physicians often have concerns about prescribing controlled substances because of fears of regulatory scrutiny. Increased regulation can change prescribing patterns and cause the underuse of medications as physicians use only minimal doses. Stronger regulations also communicate that controlled substances are dangerous, and reinforce fears of opioid use. Despite a clinical consensus that opioid medications should be used as first-line treatment for a number of chronic pain conditions, cancer pain studies have shown that opioid use often does not conform to published guidelines, due to fears of regulatory scrutiny, addiction, and inadequate knowledge of prescribing principles.[129] A 1998 study of 1300 New York state physicians showed that more than half were moderately to very concerned about regulatory oversight, and that more than a quarter changed their prescribing practices solely because of such concerns.

Despite these issues, there was significant increase in the medical use of opioids between 1990 and 1996. Morphine use increased by 59 percent, oxycodone use by 23 percent, hydromorphone use by 19 percent, and fentanyl use by 1,168 percent.[130] During the same period, the total number of opioid analgesic drug abuse mentions increased by only 6.6 percent, and the proportion of opioid abuse mentions relative to total drug abuse mentions decreased from 5.1 percent to 3.8 percent.[131] These statistics proved that there was no accompanying increase in abuse with the rising use of opioids.

Until the introduction of OxyContin in 1996, there were only three long acting opioid formulations available: MS Contin, a slow-release morphine formulation developed by Purdue; Duragesic, a slow-release fentanyl skin patch developed by Janssen; and methadone, which has a long duration of action due to the nature in which it is metabolized. The availability of a wide variety of opioids is critical to proper medical treatment, as patients have varying responses to different opioids. Dr. Richard Payne of the Memorial Sloan-Kettering Cancer Center of New York explained the importance of multiple pain medications before the Senate subcommittee hearing:

My clinical experience is quite consistent with the evidence-based clinical practice guidelines widely published for the management of pain, which emphasize the need for the availability of multiple pain medications for clinicians so as to enhance our ability to select the right drug for the right patients.

It is now very clear that with respect to the use of opiods to manage pain, one drug does not fit all. In my cancer center, for example, up to 15 to 20 percent of our patients require an opioid drug other than morphine to provide the best pain relief with the minimum number and intensity of side effects. In fact, a study from our center reported that 80 percent of our patients required at least one switch of opioid medications, 44 percent required two or more switches, and 20 percent required three or more switches of opioid medications to get to the right medication to manage their pain in the most optimal manner.[132]

This need for multiple opioid medications made OxyContin a valuable addition to the arsenal of pain management specialists. Dr. Payne went on to explain:

OxyContin 
has the clinical advantages of high oral bioavailability, short half-life, long 
duration of effect, predictable pharmacokinetics - all of these factors have much 
to do with the relative popularity of OxyContin for the treatment of pain, much 
more so than any marketing details by the pharmaceutical industry.

For clinical reasons, OxyContin was a 
superior medication to others on the market, and provided another option to enhance 
the care of patients.

The stigma associated with morphine and methadone was also a factor in the popularity of OxyContin. According to Dr. Payne, “Clinical practice has shown that oxycodone has less associated stigma than morphine. Many healthcare providers and patients associate morphine, but not oxycodone, with advanced illness, impending death, and high risk of addiction. Dr. Howard Heit, a pain specialist in Fairfax, Virginia explained, "If Grandma is placed on morphine it's like, 'Oh, my God,' but if Grandma comes home placed on OxyContin - that was O.K."

Though doctors were already comfortable using Percocet and Tylox, they were unable to use them long term, both because of acetaminophen and aspirin toxicity, and because a number of states had ambiguous definitions of the number of dosage units that a doctor could prescribe at a time.[133] The language in most states typically stated ‘one dosage unit’, which could be interpreted as one pill, or as the amount taken at one time. States such as Massachusetts and New York simply state ‘a 30-day supply’, while Rhode island states ‘a 30-day supply or 250 dosage units’, and New Jersey states ‘a 30-day supply or 120 dosage units, whichever is less’. This meant that physicians often required patients to return every week to obtain a prescription since schedule II prescriptions could not be phoned into pharmacies. OxyContin solved this issue, and was rapidly adopted because of this and its other benefits.

- THE OXYCONTIN BUSINESS -

The Pharmaceutical Industry

The pharmaceutical industry is one of the largest in the country, with U.S. sales of $154 billion in 2001, up $22.4 billion from 2000[134]. OxyContin was the highest grossing schedule II pharmaceutical, ranked fifteenth of the top selling drugs with sales of $1.49 billion in 2001. Two other non-scheduled NSAID prescription pain relievers, Celebrex and Vioxx, ranked higher with sales of $2.39 billion and $2.03 billion, though OxyContin’s sales increased by 41.1 percent from the previous year compared to only 18.4 percent and 33.3 percent for Celebrex and Vioxx, respectively. [135]

Worldwide, sales of opioid analgesics were $4.7 billion in 2000, and are expected to grow by $455 million a year for the next five years.[136] OxyContin, sold internationally by Mundipharma International, captured 31.5 percent of this market in 2000 with sales of $1.48 billion. The next highest market share product was the Duragesic patch by Johnson & Johnson with sales of $925 million, constituting 19.7 percent of the market. Farther behind, Mundipharma International’s product MS Contin was ranked third, with sales of $230 million, making up 4.1 percent of the market.

The sales growth of OxyContin was simply stunning for a company that only passed sales of $100 million in 1987. Introduced in 1984, another opioid analgesic product, MS Contin slow-release morphine, had been Purdue Pharma’s highest grossing product until 1996. Prescriptions for MS Contin had risen to almost 1 million by 1996, though after OxyContin’s introduction its sales declined to less than 800,00 prescriptions in 2000. It was OxyContin’s introduction and astronomical sales which made Purdue one of the fastest growing pharmaceutical companies in the world. Sales of OxyContin passed $1 billion by 2000, only 4 years after its introduction, and had reached 6.8 million prescriptions and $1.49 billion by 2001.

Purdue Pharma L.P. was not actually formed until 1991, when it was created by the Purdue Frederick Company which had existed since 1952 selling laxatives and antiseptic products. In 1983 the companies had moved to Norwalk, Connecticut just before the launch of MS Contin, its first pain management product. In 2000, both Purdue Pharma and the Purdue Frederick Company moved to a new headquarters in Stamford Connecticut. Purdue and its associated companies employ approximately 3,000 people in the U.S., and over 5,000 worldwide through its alliances with Mundipharma International in Germany and Napp Pharmaceutical Group in the United Kingdom. According to court documents filed by Purdue in connection with a patent dispute, OxyContin accounted for 83 percent of the privately held company’s revenue in 2001.

Considering Purdue’s reliance on OxyContin’s revenue, it was understandably concerned in November of 1998 when the FDA approved a 10mg and 30mg sustained release oxycodone formulation named Roxicodone SR, developed by Roxane Laboratories. Purdue immediately filed a patent dispute in a U.S. Federal Court in Manhattan claiming infringement of its three sustained-release technology patents set to expire in 2007 and 2013. Boehringer Ingelheim, the parent company of Roxane Laboratories argued that it was using a different sustained-release technology, and that the patent did not cover the use of oxycodone itself, but the Federal Court upheld Purdue’s patent position in May of 2000 and issued an injunction against the launch of Roxicodone SR.

Another lawsuit was filed by Purdue against IMPAX Laboratories in April 2002 claiming patent infringement related to IMPAX’s plan to market generic 10mg, 20mg, 40mg, and 80mg oxycodone sustained-release formulations, which had been approved by the FDA in February. IMPAX claimed that the lawsuit was a stall tactic by Purdue, and noted that are a wide variety of ways available to created extended release formulations of drugs. As of this writing, Purdue was currently engaged in litigation with Boehringer Ingelheim, Roxane Laboratories, End Pharmaceuticals, and Teva Pharmaceuticals. Endo Pharmaceuticals also received approval for immediate-release 10mg, 10mg, 40mg, and 80mg oxycodone tablets in July of 2002, though the product is not yet available. Although less vulnerable to a patent attack from Purdue, this product could pose as great a threat as OxyContin in terms of abuse and overdose.

The Marketing of OxyContin

Though OxyContin was somewhat more abusable and dangerous that previously available opioid formulations, opioids had been abused for decades, so it was Purdue’s marketing of the product which left it open to the most criticism. The foundations had been laid in the 1980s with MS Contin’s introduction. Purdue began funding patient advocacy groups, including the American Pain Foundation, the National Foundation for the Treatment of Pain, and the American Chronic Pain Association. Purdue also underwrote dozens of scientific studies on the effectiveness of opioids in the treatment of pain. Through these groups Purdue was able to pressure states to adopt various pain management and opioid use guidelines. As attitudes began to shift Purdue expanded the market for MS Contin beyond cancer pain.

In 1994 Purdue launched a public-education program called Partners Against Pain. It initially concentrated on cancer pain, and later expanded to include other forms of long-term pain. Through videos, patient pain journals and an elaborate Web site, Purdue promoted the ideas that pain was much more widespread than had previously been thought, that it was treatable, and that in many cases it could and should be treated with opioids. No specific products were advocated, and Purdue’s name was not mentioned in any of the material.

By 1995 Purdue began shifting its marketing resources away from MS Contin (as its patent had expired) and towards OxyContin. Using a marketing strategy increasingly common in the industry, Purdue paid for the transportation and hotel costs for 2000 to 3000 doctors to attend weekend meetings in Florida, California, and Arizona to discuss pain management issues. Doctors were then recruited and paid fees to speak at some of the 7,000 pain management seminars that Purdue sponsored around the country. The aggressive treatment of pain with long-acting opioid formulations was advocated.

In 1996 Purdue had assembled an initial sales force of 350 and planned to devote 70 percent of their primary sales calls to OxyContin immediately after its introduction, reducing that to 40 percent in 2000. The initial sales forecast was $350 million dollars[137] over the first five years of the product’s life, but by the end of 2000 sales totaled nearly $2 billion. Realizing that it had drastically underestimated demand, Purdue quickly expanded its sales force to 800, and increased its percentage of primary sales calls to 80 percent. Other elements of the Purdue plan included the use of a group of doctors known as the ‘Speakers Bureau’ to give lectures about the benefits of OxyContin during hospital programs. Doctors were also mailed information about the drug with a reply card which they could send back requesting more information. Purdue would then use the reply card to encourage local hospitals to stock the product.

There was apparently nothing unusual or inappropriate in Purdue’s marketing program. As OxyContin began to receive increased attention and reports of abuse and diversion began to surface, people began to look more critically at Purdue’s tactics. On August 21, 2001, a week before the first congressional hearing, Attorney General Mike Fisher publicly accused Purdue Pharma of using overly aggressive marketing practices. On November 9, 2001 the Associated Press reported that the Florida State Attorney General’s Office had announced that it was conducting an investigation into Purdue’s marketing practices. On February 12, 2002, Dr. Art Van Zee of St. Charles Virginia spoke before the Senate subcommittee in criticism of Purdue’s marketing practices:

Purdue Pharma, in the most extensive opioid promotion in the history of the industry, has used sophisticated marketing data to determine which physicians in the country prescribe opioids most liberally and, in some cases, least discriminately and coupled that data with lucrative financial incentives to their sales representatives.[138]

After explaining the company’s questionable marketing practices, he went on to explain how one Purdue sales representative in Florida made $100,000 over and above her base salary of $50,000 in 2000 for her massive success in selling the drug.

Though unsubstantiated, Dr. Van Zee’s accusation that physicians who Purdue targeted were prescribing “indiscriminately” certainly raised questions about the appropriateness of such targeted marketing practices. During later questioning Dr. Goldenheim, Vice President of Research for Purdue, reported that Purdue had spent just over $200 million, or 19 percent of OxyContin’s 2001 sales on marketing. He noted that this was a “fairly typical figure for our industry”. While in percentage terms that may be true for certain products, it does not appear to be accurate in dollar terms. According to Competitive Media Reporting, the manufacturers of Celebrex and Vioxx, Pharmacia and Merck, spent only $135 million and $130 million[139] respectively on advertising for their products with sales of over $2 billion.

Reports soon began to surface about the behavior of Purdue marketing representatives. On July 2, 2001 U.S. News and World Report ran an article titled “Did the Makers of OxyContin Push Too Hard?”[140] Dr. William Harris, a family practitioner in Charleston, West Virginia reported that a Purdue representative suggested he prescribe OxyContin for osteoarthritis. “I told him that this was not an appropriate use for the drug. He then said that I could be sued for not using the drug for pain. I had to throw him out of my office,” stated Dr. Harris. On March 6, 2003 records were released by the Florida Attorney General’s Office from an earlier interview with Purdue’s former district manager for West Virginia William Gergely. In the records, Gergely stated that he and others had used misleading marketing tactics, including telling some doctors that OxyContin was “non-habit forming.” He also stated that the company had told him that the medication was virtually non-addicting.

It appears that Purdue may have been making claims regarding OxyContin’s “less addictive” nature as early as 1995 when it first received FDA product approval. According to Dr. John Jenkins, Director of the FDA Office of New Drugs, Purdue had suggested that OxyContin would have reduced addiction liability because of the delayed absorption of the drug.[141] While this was somewhat true in that there is no significant serum peak after the drug’s absorption, the initial pharmacokinetics are the same as a regular Percocet tablet. The longer duration of action eventually proved more addictive. The FDA did not foresee the frequency with which people crushed or snorted the pills. According to John Woodworth of the DEA, a Purdue salesman was also on record stating the OxyContin had less abuse liability and should not be a schedule II substance.[142]

In its defense, Purdue provided documents which showed that in November 2001, in an effort to prevent sales staff from profiting off doctors who illegally prescribed OxyContin, sales people were told that any commissions from sales to a doctor who had been arrested or investigated for improper prescribing would be deducted from their bonuses. How much of a deterrent this was is difficult to say. Michael Friedman, Purdue’s Executive Vice President stated the company’s position at the August 28, 2001 hearing:

Purdue’s marketing efforts for OxyContin have been conservative by any standard. Purdue is scrupulous in training its field sales force to promote OxyContin only for its approved indications. Purdue managers monitor its field force for compliance with these policies. Sales representatives are told that in the event of a violation of our marketing policies, the offender will be subject to discipline, up to and including termination. Purdue does not believe that aggressive marketing played any role whatsoever in the abuse and diversion of OxyContin. The physicians who were victims of “doctorshopping” or prescription fraud were hardly in this position because of our marketing. To the contrary, our marketing has encouraged physicians to take actions that would reduce the abuse and diversion of OxyContin.

These statements appeared to be in conflict with the evidence that was continuing to surface.

Also uncovered in the investigation by the Florida Attorney General’s Office was a pamphlet published by the Partners Against Pain Group which read, “Drug addiction means using a drug to get ‘high’ rather than to relieve pain. You are taking opioid pain medication for medical purposes. The medical purposes are clear and the effects are beneficial, not harmful.” The pamphlet was clearly minimizing the risk of using an opioid medication. While defending itself during a congressional hearing, Purdue also made reference to a brochure on prevention of abuse and diversion it included in an ‘opioid therapy documentation kit’ which was distributed by marketing representatives. It did not go into detail on the 250,000 copies of ‘the model guidelines for the use of controlled substances for the treatment of pain’ brochure which it also distributed, that basically advocated the aggressive use of opioids and explained to physicians that they were ethically required to do so.

Under the Food, Drug and Cosmetic Act of 1962, the FDA has jurisdiction over the advertising of prescription drugs. The Division of Drug Marketing, Advertising, and Communications is responsible for regulating prescription drug advertising and promotions, and monitors all drug advertisements and promotional materials. All materials are submitted to the FDA at their initial time of dissemination or publication, though it does not require that material be approved prior to its use. This means that FDA censure takes place after the material has appeared in public, and the typical enforcement action is to request that the company stop using the material in violation. Corrective advertisements or letters are also sometimes requested.

According to the FDA, there were no known events of direct-to-consumer advertising of OxyContin. Under the FDC Act nothing prohibits Purdue from doing so, even with a schedule II substance, however it voluntarily chose not to and instead advertised in publications directed to health care professions. Between 1996 and 2003, Purdue received three separate notices of violation for its promotional materials. The first was for an MS Contin advertisement dated November 20, 1996 in which the company made unsubstantiated claims that MS Contin was superior to other slow-release morphine formulations. A warning letter was sent, and the company immediately pulled the advertisement. The second warning was for an OxyContin advertisement which ran in a May 4, 2000 issue of The New England Journal of Medicine claiming that OxyContin was “Proven Effective in Arthritis Pain.” The FDA determined that the advertisement was false and misleading because the advertisement suggested that OxyContin was useful in treating all types of arthritis and should be used as a first-line therapy in its treatment. This claim had not been substantiated, so the FDA sent a warning letter to Purdue May 11, 2000 informing them of their position, and Purdue immediately withdrew the advertisement.

While these first two violations were relatively benign, a third warning sent in January 11, 2003 had a more serious tone. Though this may have been due in part to the increased scrutiny the FDA was receiving, the advertisements were clearly inappropriate, with one depicting a healthy and vital older man fishing with his grandson. The two advertisements were run in the Journal of the American Medical Association on October 2, 2002 and November 13, 2002. The FDA’s warning letter stated:

Your journal advertisements omit and minimize the serious safety risks associated with OxyContin, and promote it for uses beyond which have been proven safe and effective. In addition, your journal advertisements fail to present in the body of the advertisements critical information regarding limitations on the indicated use of OxyContin, thereby promoting OxyContin for a much broader range of patients with pain than are appropriate for the drug. The combination in these advertisements of suggesting such a broad use of this drug to treat pain without disclosing the potential for abuse with the drug and the serious, potentially fatal risks associated with its use, is especially egregious and alarming in its potential impact on the public health.[143]

The FDA was clearly upset, concluding that the advertisements were “egregious and alarming in [their] potential impact on the public health.” After the warnings, Purdue immediately withdrew the advertisements, but it appeared that Purdue felt it could operate with relative impunity.

In November 2002 the Florida inquiry into Purdue’s marketing practices which had begun to turn up damaging evidence was prematurely ended when Purdue agreed to pay $2.1 million to help the state set up a computer databank to monitor prescription drug abuse. Purdue had given the state a list of over 100 current and former sales employees earlier in the investigation of which William Gergely was the only individual interviewed. This raised the question of how much more damning evidence might have turned up had the investigation continued. On January 28, 2003 however a circuit judge in Broward County, Florida ruled that Purdue marketing plans from 1999 to 2001 uncovered during the investigation would be made public within 60 days. Purdue had gone to court the year before to prevent the release of the records, arguing that they were exempt from Florida’s public record laws because they contained trade secrets. As of this writing, Purdue was still appealing the ruling.

Purdue’s success at keeping its marketing document secret began to look even more uncertain when on March 1, 2003 House Energy and Commerce Committee Chairman W.J. Tauzin asked the company to turn over by March 21 a wide range of marketing records, including court depositions of salespeople and records describing the sales bonus plan. As of this writing, Purdue’s degree of compliance is unknown.

Purdue Response and Public Relations Efforts

At the August 28, 2001 congressional hearing Congressman Greenwood asked Terrace Woodworth, Deputy Director of the DEA Office of Diversion Control, “Is there any question in your mind that [Purdue] knew that they had a problem early on, prior to the year 2000?” Mr. Woodworth replied, “There certainly was no question in my mind, and I believe that that would be the same case for Purdue Pharma.”[144]

Purdue claimed differently, and stated that they were not aware of significant problems with OxyContin abuse until April of 2000 when The Bangor Daily News of Maine ran the story with the line, “OxyContin is quickly becoming the recreational drug of choice in Maine.” The article was shown to Purdue’s senior medical director Dr. David Haddox, who explained that Purdue quickly formed a response team in the summer of 2000 composed of medical personnel, public relations specialists, and top executives as campaign managers.

To give support to their position at the August 28, 2001 hearing, Purdue asked to be allowed to include information in their defense as part of the official record. Miraculously, they returned a week later with an OpEd piece published in the Lexington, Kentucky Herald-Leader newspaper on September 3, 2001. The piece was written by former U.S. Attorney for the Eastern District of Kentucky Joseph Famularo, leader of operation OxyFest who had referred to OxyContin ‘a locust plague’, who had left his job in June of 2001 and since become a consultant to Purdue Pharma. It read:

Purdue did not have any reason in 1995 to expect or anticipate the abuse of OxyContin. The suddent rise in the drug’s abuse, some four years after it came to the prescription drug market, took everyone by surprise, including the Good and Drug Administration, law enforcement, and Purdue.

I first heard of the OxyContin problem in southeastern Kentucky in the early fall of 2000 while I was a U.S. Attorney. Likewise, the DEA supervisor for Kentucky told me that he had not heard of OxyContin until he was assigned to Kentucky in late 2000.[145]

Considering Mr. Famularo’s new occupation, the credibility of his statements are questionable. Exactly when Purdue first began to suspect issues of diversion is also uncertain, but with their detailed sales data they were certainly aware about high concentrations of per-capita consumption in 1998 and 1999.

Purdue’s first public move to show their concern was the withdrawal of the 160mg tablet formulation on June 18, 2001, only a year after it had been introduced. As sales of this formulation were only 1 percent of total OxyContin sales, it had little effect on Purdue’s bottom line and allowed them to demonstrate their concern over the dangers of abuse. They were also very to point out that it was a voluntary action on their part, and not the result of any DEA pressure. In its March 2002 OxyContin Diversion Report, the DEA was also careful to clarify that they had not influenced Purdue’s actions.[146]

The second effort was announced by the FDA and Purdue on July 25, 2001, where both stated that they were working in cooperation to strengthen the warning and precautions label on the OxyContin insert. They added what was called a “black box warning” [see insert], the strongest type of warning that the FDA uses. Purdue described this as an effort to lessen the chance that OxyContin would be prescribed inappropriately, while the FDA regarded it as clear indication that OxyContin was not to be used as ‘as needed’ medication, and was intended only for moderate to severe long-term pain. The inclusion of the statement that OxyContin had “an abuse liability similar to morphine” was considered the most powerful way to convey OxyContin’s addictive nature.

Under pressure from the FDA, Purdue also mailed a letter to healthcare professionals on July 18, 2001 informing them of the changes to the product insert and highlighting the problems of OxyContin diversion and abuse. It read:

Dear Health Care Professional,

Reports of illegal misuse, abuse, and diversion of OxyContin Tablets from various parts of the country have prompted Purdue Pharma L.P. to revise sections of the prescribing information, specifically 1) WARNINGS (including a new Box Warning) which call attention to the potential for misuse, abuse and diversion and 2) INDICATIONS which reinforces the appropriate patient population for whom this product is intended.

OxyContin is an opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine. This should be considered when prescribing or dispensing OxyContin in situations where the prescriber or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. While concerns about abuse, addiction, and diversion should not prevent the proper management of pain, healthcare professionals should be alert to the problems of misuse, abuse, and diversion.

This 
was apparently sufficient to placate the FDA, though Congressman Greenwood suggested 
during the February 12, 2002 
Senate hearing that perhaps Purdue should also send representatives directly to 
physicians with this message instead of merely mailing it.  
Purdue declined this advice, and emphasized that it had developed a mathematical 
model that attempted to identify areas where abuse potential was expected to be 
highest, and created a program where company sales representatives were trained 
to “actively participate” in stopping the abuse and diversion of OxyContin.  
They noted that the DEA was assisting them in the training sessions and 
that physicians would be provided with “additional tools for proper pain assessment.”[147]  
The prudence of allowing Purdue to conduct these physician training sessions 
is questionable considering Purdue’s track record of providing literature which 
advocates the use of opioids and underplays their risks.  
Exact details on this program were not provided.

Purdue also announced a ’10-point plan’ to address the problem, which 
included efforts to combat prescription fraud, international smuggling, and to 
raise public awareness about the issue.  Some 
were unhappy about the focus of the plan however.  
Trent Smith of Gilbert Maine commented, “I read about the tamper-proof 
prescription pads and I think, give me a break!  
That seems like such a little thing. It's almost intentionally missing 
the point. Rather than prescription pads, I would like to see something done in 
rehab, something where they're making an effort to help these folks get better.”  
Indeed, it did seem as if Purdue was intentionally missing the point.   
At no time did it take responsibility for the addicts or abusers themselves. 
Of course this would have been legal suicide for the company by making it vulnerable 
to a wider range of lawsuits.  In July of 
2001 Purdue also announced a $100,000 grant to start a “mini-MBA” program in local 
high schools.  The Boston Globe quoted a 
Maine school administrator asking why the company “wouldn’t have come up here 
and asked us what we want.  If they had, 
we would have asked for money for the treatment of addicts rather than entrepreneurial 
training.”[148]

Purdue also began a prescription drug abuse public education campaign 
through radio and print advertising and a website.  
On November 12, 2001 it began running radio advertisements in Palm Beach 
County, Florida, Cincinnati, Philadelphia, and Charleston, West Virginia as a 
pilot program for the campaign it announced February 15, 2001.  
The advertisements encouraged community leaders and concerned citizens 
to become involved in the issue and brought attention to the efforts Purdue was 
making to address the problem.  Purdue also 
created a website called Painfully Obvious as a “public service program to educate 
parents, teachers, and young teenagers about the dangers of abusing prescription 
medications.  Predictably, no specific mention 
of OxyContin was made on the website or in the advertisements.  
Purdue continued to attempt to disassociate OxyContin from the general 
problem of drug abuse.

In Massachusetts on May 28, 2002, Purdue announced 
a partnership with the Executive Office of Public Safety to increase awareness 
of the dangers of prescription drug abuse.  Elements 
of the plan included a grant for a tip line and reward program, a public education 
program targeted at teens, the provision of doctors with tamper-resistant prescription 
pads, training for law enforcement, and a “Parent’s Guide to Street Drugs”.  
None of these efforts were specifically direct at or mentioned OxyContin.  
In January 2003 Purdue also announced a ‘Product Replacement Program’ which 
would replace uninsured OxyContin tablets stolen from pharmacies in robberies 
after July 1, 2001.  Purdue’s generosity 
in this move is questionable, as it seemed just as much an effort to encourage 
the further availability of OxyContin as to recoup the loses of pharmacies.

As mentioned earlier, Purdue recruited former U.S. Attorney from 
Kentucky Joseph Famularo as a consultant.  Another 
former government official, Larry Houck, staff coordinator for the DEA Office 
of Diversion Control soon left for employment by the D.C. law firm Hymen, McNamara, 
and Phelps, one of whose clients was Purdue.  And 
on May 28, 2002 Purdue announced that it was hiring the firm Giuliani Partners, 
LLC, the company of former New York City Mayor Rudolph Giuliani, to work as an 
external advisor.  According to the press 
release, Giuliani Partners was to help with Purdue’s public prescription drug 
abuse and diversion campaign.

Purdue also continued its tradition of giving grants for pain related 
issues with a $3 million grant to the Massachusetts General Hospital on February 
5, 2002 to help create the MGH Purdue Pharma Pain Center “dedicated to treating 
people suffering from chronic pain and educating healthcare professionals about 
the tools and techniques available for such treatment”.  
On April 24, 2002 Purdue publicly announced the award of a $50,000 Prize 
for Pain Research to Dr. William Willis of the University of Texas.

The last element of Purdue’s anti-abuse efforts and public relations campaign was the formulation of an abuse-resistant version of OxyContin. On February 18, 2001 Purdue received attention from its announcement that it was filing an international patent application for an abuse-resistant opioid pain reliever. This was somewhat misleading, in that Purdue knew both that the research needed to produce a marketable product based on this technology was not yet available, and that even after its development it would not prevent the oral abuse of the medication which the Pulse Report was reporting was most common, despite Purdue’s characterization of abusers injecting and snorting the drug.

Under fire from the congressional subcommittee, the FDA explained that it did not require Purdue to add an antagonist (a type of chemical which blocks the effects of the agonist counterpart) to its original formulation both because other pure opioid sustained release products were available, and because the technology was not mature enough to allow proper pain relieving efficacy. Frequent mention was made of the use of antagonist technology in a product called Talwain which had been widely abused by injection in the 1970s. It was explained that the antagonist added to Talwain was only effective in combating injection, and that it produced increased side effects and limited the maximum pain relief which could be achieved.

Purdue attempted to manipulate these issues and stated before the February 12, 2002 subcommittee:

And as recently as 1999, DEA wrote to us and again reminded us that this was principally a problem of oral abuse. It was not until last year, when OxyContin press became so prevalent, when we began investigating, when we had these meetings that were just described to you, that we learned that in addition to the oral abuse, that OxyContin was also, on occasion, being crushed and used intravenously. As a result of that, we have started on a very intensive program, around the first of this year, to formulate it with Naloxone.

Purdue was doing two questionable things here; first, it was suggesting that it had been informed of the problem by the DEA in 1999, contrary to its assertion that it had not known about the problem until April of 2000; second, it was attempting to focus attention on the intravenous use of OxyContin and suggest that the opioid antagonist Naloxone could be used to combat the problem, knowing that in reality a Naloxone formulation was unfeasible.

On July 22, 2002 Purdue came forward with an update on its development of the abuse-resistant formulation, stating that it would not be able to complete clinical development of the product for at least 4 to 5 years. The announcement highlighted that Purdue had spent over $100 million in the previous 2 years on the development of the abuse-resistant formulation. Purdue explained that during clinical trials, Naloxone sometimes blocked pain relief for legitimate patients who were taking the tablets correctly. No one drew attention to the fact that this outcome had already been predicted and that Purdue was clearly doing this as a public relations ploy. During the press release, the company also announced that it was investigating the use of the opioid antagonist Naltrexone which would be sequestered in special beads which would break if crushed or injected, continuing to draw attention to this subgroup of users and away from the issue of oral abuse. While in fairness the technology to block the ‘high’ of opioids is currently unavailable, Purdue took liberties with the science in a hollow attempt to show that it was taking action.

Prescription Monitoring Programs

Although the DEA monitors the distribution of pharmaceuticals directly to pharmacies, only 18 states have prescription monitoring programs that track the distribution to patients.[149] The DEA and law enforcement officials have long argued that more such programs should be put in place and the existing programs strengthened in order to identify corrupt doctors and patients who forge prescriptions, however lobbying by drug companies, doctors, pharmacies, and patient advocacy groups has prevented the rapid adoption of such programs.

These groups report that with the introduction of monitoring programs and multiple copy prescription programs, use of schedule II substances decrease dramatically. Studies showed that schedule II drug prescriptions decreased by 64 percent in Texas, 57 percent in Rhode Island, 54 percent in New York, and 50 percent in Idaho after they adopted such programs.[150] As the vast majority of these reductions are obviously not due to compliance by corrupt physicians, it appears that monitoring programs can cause doctors to prescribe suboptimal medications in response to increased scrutiny. While the position of pharmaceutical companies and pharmacies is not born out of altruism, the reality is that doctors are simply not comfortable with having their practices monitored.

As OxyContin began receiving increased national attention, there were renewed calls for more prescription monitoring programs. Despite the public attention, a bill to create a drug tracking system was defeated in North Carolina in 2001, and a system which had been operating in New Mexico for two years was shut down due to opposition from doctors and pharmacists. Purdue began to support monitoring programs publicly, but quietly opposed a bill in West Virginia which would have singled out OxyContin. Though it was passed by the state legislature, Governor Bob Wise vetoed the bill after doctors and pharmacists complained about patients’ privacy issues.

Development of prescription monitor programs appears to be intensifying. A $2 million grant from the Department of Justice was approved in 2002 to be distributed to Ohio, West Virginia, Virginia, Pennsylvania, California, Massachusetts, Nevada, and Utah. In Florida, development on a program began in November 2002 after Purdue agreed to give the state $2.1 million to create a state-of-the-art software monitoring program. Florida said that it would share the systems with other states if they requested. The Virginia General Assembly also passed legislation to create a monitoring program on March 8, 2002.

- LEGAL AND SOCIAL ISSUES -

Legal Cases

In 2001, websites began to appear created by law firms recruiting patients to sue Purdue. One such website, www.oxycontinlegalhelp.com, stated, “The total number of deaths linked directly to OxyContin abuse is still not tallied and more deaths are happening daily. It is believed that the number of deaths in the U.S. for the year 2000 that are attributable to the abuse of this drug will be over 700.”[151] Another called www.aboutoxycontin.com, run by the law firm Pikoff & Riff, L.L.P. wrote to patients, “If you or someone you know has taken OxyContin and has suffered any serious side effects, such as addiction or death, please fill out our online questionnaire to contact our law firm. Those who have been injured may be entitled to monetary compensation for their injuries.”[152]

The first lawsuits came within days of each other during June of 2001, just after the initial wave of media coverage had peaked. On June 12, 2001 the state of West Virginia announced that it was filing suit against the manufacturer Purdue Pharma and co-marketer Abbott Laboratories for failing to warn patients about the addictive nature of OxyContin. On June 19, 2001 in Washington, D.C., a group of seven former OxyContin addicts and relatives of addicts filed a $5.2 billion lawsuit, and on June 22, 2001 the first suit in Kentucky was filed by attorneys representing five living plaintiffs and the estates of deceased OxyContin abusers. The attorneys were also seeking class-action certification.

Howard Udell, Purdue Executive Vice President and General Counsel was in charge of planning Purdue’s legal defense. After interviewing ten blue-chip litigation firms, he hired New York’s Chadbourne & Park along with Atlanta’s King & Spalding, both veterans of the tobacco suits of the 1990s. These firms, along with Purdue’s 18 in-house lawyers made up Purdue’s legal defense team. Udell’s plan was to win at all costs, as a single loss would open the way for hundreds of other similar suits. Instead of allowing plaintiffs to dismiss cases voluntarily or drop class certification motions, Purdue would push to have courts rule on the merits of cases, winning dismissals with prejudice that would prevent plaintiffs from refiling suits. By the end of July, Purdue’s legal defense fees were running around $3 million a month, and by the end of 2002 it had spent over $45 million dollars in legal fees.

By October of 2002 Purdue’s efforts began to pay off. On October 17, 2002 a federal judge in Kentucky refused to grant class-action certification in Gevedon v. Purdue Pharma. In November, Burton v. Purdue Pharma became the first OxyContin lawsuit to be dismissed, brought by plaintiffs who claimed Purdue had failed to warn patients of the dangers of the medication. On December 19, 2002 in the California Superior Court for Los Angeles County, Judge Malcolm Mackey made a judgment in favor of Purdue on an unfair trade practices case brought by a California resident. The judge dismissed all the plaintiff’s claims with prejudice, and ruled that California state court should not be deciding on an issue that is the subject of federal regulation. The most recent case to be decided was on March 19, 2003 in Kentucky federal court, where a judge dismissed the pending personal injury suit Couch v Purdue Pharma. This was the twenty-second case against Purdue to be dismissed in the past year.

Despite Purdue’s success thus-far, a number of substantial threats still remain for the company. On August 30, 2002 Ohio Judge Michael Sage of Butler County Common Pleas Court decided to give class-action certification to a suit representing over 1000 people who claimed they became addicted when taking OxyContin as their doctors prescribed. The suit also accused Purdue of using misleading and inappropriate marketing practices. While the initial suits had focused on the addictive nature of the product itself, later suits devoted more attention to Purdue’s marketing tactics and the demographics it had targeted. As more material began to come to light about the practices of marketing representatives, this argument began to look increasingly viable.

As of this writing, over one hundred fifty cases are still pending against the company and lawsuits continue to be filed at the rate of roughly a dozen a month. States such as Maine have held off filing charges, waiting to see the outcome of West Virginia’s case. Some have suggested that there are signs plaintiffs are regrouping, and though Purdue has not yet lost a case, one unfavorable judgment could lead the company towards bankruptcy.

The Fallout

Aside from the deaths and emergency room visits, the presence of OxyContin addicts in methadone maintenance clinics and opioid rehabilitation centers was one of the most visible reminders of the human suffering caused by OxyContin. Within 6 months of opening in March of 2000, The Life Center of Galax, Virginia, originally created for heroin addicts, had 254 patients of whom 95 percent were reported to be entering the program with OxyContin addictions. At the East Indiana Treatment Center for opioid addicts, patient enrollment doubled from 689 in 1998 to 1,420 in 2000. More than half, 768 were from the neighboring state of Ohio, and 581 were from Kentucky, two of the states with the highest initial reports of OxyContin abuse.

People with limited economic means were also affected, as nine states, including Florida, Maine, Ohio, South Carolina, and West Virginia modified their Medicaid policies to require prior authorization on OxyContin prescriptions. Maine chose to require doctors of patients without cancer to show documented use of two alternative long-acting narcotics before an OxyContin prescription would be authorized. These barriers to OxyContin’s use meant that patients were often forced to use inferior opioids which resulted in an inferior standard of living to what was available.

In an even more dramatic move, July 21, 2001 Vermont Governor Howard Dean banned the use of state welfare funds to pay for OxyContin prescriptions. Though the decision only affected about 70 people, in October the governor extended the ban to all Vermont residents enrolled in state-funded health care programs, approximately 128,000 people. In 2002, in an effort to contain rising drug costs, Oregon decided to exclude OxyContin and MS Contin from the state’s preferred drug list for Medicaid enrollees. Though the state claimed that the move was to save money through the use of generics, Purdue filed suit on September 30, 2002 arguing that health officials were violating a state law that prohibits limits on drugs used for treating cancer.

Some of the greatest harm was to patients with chronic pain who were being successfully treated with OxyContin and then forced to switch to another medication. Legitimate patients were stigmatized and sometimes treated like addicts. Because of this stigma, patients for whom OxyContin may have been the optimal medication refused to try it. Others who were being treated were told by their doctors that their prescriptions could no longer be renewed because of increased fears of scrutiny.

Last and perhaps most important was the issue of the decreased use of opioids. Exact prescribing statistics are currently unavailable, but a significant amount of anecdotal evidence suggests that doctors have become less comfortable prescribing opioids. Though Purdue was behind much of the advocacy of opioids during the past decade, physicians and researchers beyond the scope of Purdue’s influence were also publishing studies and reaching the conclusion that the use of opioids in a wider variety of patients was appropriate and beneficial. In the face of increased DEA scrutiny and an atmosphere of general defensiveness, doctors began to shift away from the more liberal use of opioids, with some choosing to switch entirely to high potency NSAIDS such as Vioxx and Celebrex. Difficult cases were referred to pain specialists who were considered to have more legitimacy in their prescribing practices while at the same time liability issues and social stigma were causing a contraction in this specialized group of physicians.

Dr. Steven Passik of the Markey Cancer Center in Lexington, Kentucky wrote to the Journal of Pain and Symptom Management with his observation on these developments:

It is my sense that, once again, in the absence of real data, the pendulum is swinging away from the use of opioids. Even their reasonable use is being abandoned by practitioners due to societal and regulatory pressures. This effect is not always visible in the number of prescriptions written or in the sales of these products. Indeed, some 15% of pain specialists write the overwhelming percentage of opioid prescriptions. So if primary care and other doctors abandon ship, the impact of the change in their prescribing is not always obvious. But it is obvious to their patients. When uncomplicated patients are sent to pain clinics to find someone willing to prescribe opioids for them, taking up precious slots that ought to be reserved for patients who truly need specialist level care, everyone suffers. It seems to me that this is happening more frequently now. The basic principle of escalating doses to effect or toxicity has been replaced by a desire to find survival doses - at which the patient can get a reasonable amount of pain relief and the clinic doesn’t run the risk of sanction and survives.[153]

The effect on legitimate patients of the OxyContin crisis had gone largely overlooked, save for a few human interest stories. The accuracy of the American Pain Foundation’s estimate that 50 million Americans suffer from chronic pain is uncertain, as is the appropriateness of long-term opioid in certain patient populations. It is clear though that millions of people are going untreated or undertreated. While the pain treatment legislation passed during the 1990s may have reduced the barriers to future progress, it is the climate within the medical community which controls the use of opioids. And for the moment, it appears that OxyContin has darkened the forecast for the use of opioids in the near future.

- CONCLUSION -

Some important questions arise from the story of OxyContin. Some of them can be answered, and some of them cannot, either because of lack of scientific information or because there is no simple answer.

The answer to why sales of the medication grew so quickly is perhaps easiest to answer. OxyContin’s rapid growth was due to the confluence of a number of phenomenon: opioid use had already increased dramatically prior to the introduction OxyContin and the climate of opioid of opioid use was becoming more liberal; pain management guidelines and legislation were being passed and adopted by states throughout the decade, legalizing and legitimizing increased use while easing doctor’s fears of DEA persecution; OxyContin had less social stigma than the most commonly used existing slow-release opioid morphine, so patients and doctors were more comfortable using it; oxycodone was also a superior opioid relative to others available in terms of its side effects and metabolism; doctors were already familiar with existing oxycodone formulations such as Percocet and felt comfortable with oxycodone’s use; Purdue conducted an extremely aggressive, well funded, target marketing campaign already perfected through their experience with MS Contin; and the attention from the media generated increasing demand for the drug on the street and among abusers, further fueling its popularity.

The question of the degree of severity of OxyContin abuse is also possible to answer. On closer analysis, it appears that rates of abuse for OxyContin were no worse that for existing opioid products. It was merely the sudden growth of OxyContin prescriptions which created the dramatic rise in oxycodone emergency department mentions. Even at its peak of ED mentions in 2001, oxycodone still only accounted for a tenth of total opioid analgesic ED mentions. During its banner year, five-fold as many new people tried Vicodin ‘non-medically’ as OxyContin. Vicodin, Percocet, Darvocet, Codeine, Morphine, and hydrocodone had all been tried by greater numbers of people. Also during its peak ED mentions year, it accounted for only 2.2 percent of total pharmaceutical mentions, and less than 1.0 percent of total substance abuse mentions.

Though perhaps controversial to say, the total number of OxyContin confirmed deaths, even when omitting that many of them involved alcohol and other prescription drug, is relatively insignificant. NSAIDs, the main group of non-opioid pain relievers, account for 7,600 deaths a year[154], more than 20 times the rate of death for OxyContin use and abuse. In 1998, before OxyContin was widely popular, 2,337,256 people died, and of that 16,932[155] people died of drug-induced causes. OxyContin was responsible for approximately 150 deaths a year, one percent of that number. And according to the National Institute on Alcohol Abuse and Alcoholism, in 1996 an estimated 110,640 people in the US died due to alcohol, nearly a thousand times the number that died from OxyContin use.

This leads to the question of whether it is socially acceptable to allow freer use of opioids while knowing a certain rate of abuse and death will occur. The problem is that contrary to what the DEA says, very few doctors have ever freely prescribed opioids. Only one in every two thousand doctors is ever investigated, and less than that are convicted of inappropriate prescribing practices. While we are commonly exposed to stories of corrupt doctors, in reality it is very difficult to obtain quantities of opioids from physicians because the phenomenon of doctor shopping and opioid abuse has existed for decades. The pressure the DEA applies in trying to marginally increase the number of corrupt doctors they catch has a dramatic effect on the overall use of opioids. Without being able to provide exact numbers, millions of people who legitimately need opioid pain medication under today’s accepted practices are being denied access to drugs because of physicians’ fears.

The percentage of illicit OxyContin on the street obtained from foreign sources, robberies, and doctor shopping is infinitely small relative to the total amount of OxyContin which is legitimately prescribed. This means that there is very little the DEA can do to prevent the current rates of opioid abuse. Further restrictions result in the suffering of millions in exchange for a marginal reduction in the annual number of emergency department mentions and deaths. Its rhetoric aside, the DEA seems to care little for this suffering and is instead concerned with legitimizing its role in the drug war.

Purdue’s responsibility also deserves a closer examination. It is clear that they deliberately targeted doctors who were the most liberal prescribers of opioids. Yet this in itself is not a crime. It seems unlikely that they deliberately targeted doctors they knew were corrupt, but at the same time they did little to prevent the operation of such doctors. Purdue was also guilty of aggressively advocating the use of opioids through a multitude of channels: the funding of pain patient and physician advocacy groups; scientific studies proving the efficacy of opioids; pain seminars; websites; pamphlets; and advertising in all of the major professional journals. The crucial question is whether or not long-term opioid use is as from the problems of tolerance, addiction, and dependence as Purdue claims.

If their science is correct, they are heroes. They will have attempted to do a major service to the millions of Americans who suffer from chronic pain. If their science is incorrect, they are criminals, subjugating millions of members of the population through dependence on high-dose opioids.

The truth is that the opioids of today are still little different from Heroin. The mechanisms through which they act and the euphoria they create are nearly identical. Scientists have not yet found a way to prevent the tolerance which occurs to opioids as the body’s endogenous opioid system re-regulates in response to the presence of exogenous opioids. Modern slow-release formulations simply stretch out the period over which tolerance occurs. Tolerance free opioids are on the horizon, but a great deal research needs to be done until they are perfected.

The reason that OxyContin came in 10mg, 20mg, 40mg, 80mg, and 160mg dosage formulations was that because patients often have to increase their dose every six months to achieve the same analgesic effect. While some studies suggest that patients may find ‘maintenance doses’ where they achieve adequate pain relief and no longer have to increase their intake, others suggest that nearly every patient needs to continue increasing his dose indefinitely without ever defeating the body’s homeostatic mechanisms. No definitive long term study has yet been done to determine exactly what is occurring, as the answer is clouded in conflicting studies and economic interests.

Opioids are appropriate for certain patient populations, such as those suffering from cancer and terminal diseases. Whether they should be more widely used in non-terminal patients is uncertain. Should Purdue be allowed to have people become depended on their high-dose opioid formulations? Is this any different from the market Bayer created for itself in the 15 years between 1898 and 1913 before it finally halted production of Heroin? Of course in many ways it is, as the practical duration of opioid use has been stretched out a few years by slow-release formulations. Yet many parallels exist between Bayer’s product of a century ago and Purdue’s product of today. In their current state, opioids will continue to be a controversial class of drugs requiring restrictions and common sense in their use.

[1] Dr. Lawrence Kolb. US Assistant Surgeon General. 1925.

[2] Sandoz, Edouard. Report on Morphinism to the Municipal Court of Boston. Journal of Criminal Law and Criminology. XIII p13. 1922.

[3] Faucher, Louis. Contribution a l’Etude du Reve Morphinique et de Morphinomanie. These de Montpellier. No. 8 1911.

[4] Dr. Daniel Brookoff. Clinical Associate Professor, University of Tennessee College of Medicine. Associate Director, Comprehensive Pain Institute, Methodist Hospitals of Memphis. Chronic Pain: The Case for Opioids. 2000.

[5] Takala, A., Kaasalainen, V., Seppala, T., Kalso, E., Olkkola, K.T. Pharmacokinetic comparison of intravenous and intranasal administration of oxycodone. Acta Anaesthesiol Scand. Vol. 41 No.2 p309-12 1997.

[9] Posted by anonymous users to Papaver Somniferum website user discussion boards. http://www.poppies.org/

[10] ‘Oxy’ is a term which refers to OxyContin™, a brand name formulation containing pure oxycodone.

[11] ‘Nod’ is from the phrase "on the nod" which refers to the period of tranquility after an opioid injection, during which a user’s eyes may close and their head nods slightly as they sit immobile.

[12] Comments from individual named Paula in The Alchemy of OxyContin. Paul Tough. New York Times Magazine. July 29, 2001.

[13] Drug Topics. Vol. 146 No. 5 p38 March 04, 2002.

[15] The Medical Letter. Oxycodone and Oxycontin. September 17, 2001.

[16] Mr. James Signorile. Comments submitted to FDA docket 01N-0256. December 16, 2001.

[17] Levy, M. H. European Journal of Pain. Vol. 5 Sup. A p113-6 2001.

[18] Dr. Daniel Brookoff. Clinical Associate Professor, University of Tennessee, Memphis, College of Medicine, and Associate Director, Comprehensive Pain Institute, Methodist Hospitals of Memphis. Chronic Pain: The Case for Opioids. 2000.

[19] Heiskanen, T. and Kalso, E. Controlled-release Oxycodone and Morphine in Cancer Related Pain. Pain Journal of the International Association for the Study of Pain. Vol. 73 No. 1 p37-45 1997.

[20] Dr. Daniel Brookoff. Clinical Associate Professor, University of Tennessee, Memphis, College of Medicine, and Associate Director, Comprehensive Pain Institute, Methodist Hospitals of Memphis. Chronic Pain: The Case for Opioids. 2000.

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