Art Van Zee the Promotion and Marketing of Oxycontin Commercial Triumph Public Health Tragedy
CONTROLLED DRUGS, WITH their potential for corruption and diversion, can pose public wellness risks that are dissimilar from—and more problematic than—those of uncontrolled drugs when they are overpromoted and highly prescribed. An in-depth assay of the promotion and marketing of OxyContin (Purdue Pharma, Stamford, CT), a sustained-release oxycodone grooming, illustrates some of the central bug. When Purdue Pharma introduced OxyContin in 1996, it was aggressively marketed and highly promoted. Sales grew from $48 meg in 1996 to almost $1.1 billion in 2000.ane The high availability of OxyContin correlated with increased abuse, diversion, and addiction, and by 2004 OxyContin had become a leading drug of corruption in the United States.2
Under current regulations, the Food and Drug Administration (FDA) is limited in its oversight of the marketing and promotion of controlled drugs. Nevertheless, key changes in the promotion and marketing of controlled drugs by the pharmaceutical industry, and an enhanced capacity of the FDA to regulate and monitor such promotion, can positively affect public wellness.
OxyContin'south commercial success did not depend on the merits of the drug compared with other available opioid preparations. The Medical Alphabetic character on Drugs and Therapeutics concluded in 2001 that oxycodone offered no advantage over appropriate doses of other strong opioids.iii Randomized double-blind studies comparing OxyContin given every 12 hours with immediate-release oxycodone given 4 times daily showed comparable efficacy and safety for use with chronic back painiv and cancer-related pain.5,6 Randomized double-blind studies that compared OxyContin with controlled-release morphine for cancer-related hurting also establish comparable efficacy and safety.7–nine The FDA's medical review officer, in evaluating the efficacy of OxyContin in Purdue'due south 1995 new drug awarding, concluded that OxyContin had not been shown to have a meaning advantage over conventional, immediate-release oxycodone taken four times daily other than a reduction in frequency of dosing.10 In a review of the medical literature, Chou et al. fabricated similar conclusions.xi
The promotion and marketing of OxyContin occurred during a recent trend in the liberalization of the apply of opioids in the treatment of pain, particularly for chronic non–cancer-related pain. Purdue pursued an "aggressive" entrada to promote the use of opioids in general and OxyContin in item.1,12–17 In 2001 alone, the company spent $200 100000018 in an assortment of approaches to market and promote OxyContin.
PROMOTION OF OXYCONTIN
Department:
From 1996 to 2001, Purdue conducted more than 40 national pain-direction and speaker-training conferences at resorts in Florida, Arizona, and California. More than 5000 physicians, pharmacists, and nurses attended these all-expenses-paid symposia, where they were recruited and trained for Purdue's national speaker bureau.19(p22) It is well documented that this type of pharmaceutical visitor symposium influences physicians' prescribing, even though the physicians who nourish such symposia believe that such enticements practise not alter their prescribing patterns.xx
I of the cornerstones of Purdue's marketing program was the use of sophisticated marketing data to influence physicians' prescribing. Drug companies compile prescriber profiles on private physicians—detailing the prescribing patterns of physicians nationwide—in an effort to influence doctors' prescribing habits. Through these profiles, a drug company tin place the highest and lowest prescribers of particular drugs in a unmarried zero code, canton, state, or the entire state.21 I of the critical foundations of Purdue's marketing program for OxyContin was to target the physicians who were the highest prescribers for opioids across the country.1,12–17,22 The resulting database would aid identify physicians with large numbers of chronic-pain patients. Unfortunately, this aforementioned database would also identify which physicians were only the most frequent prescribers of opioids and, in some cases, the least discriminate prescribers.
A lucrative bonus system encouraged sales representatives to increase sales of OxyContin in their territories, resulting in a large number of visits to physicians with loftier rates of opioid prescriptions, equally well every bit a multifaceted data entrada aimed at them. In 2001, in addition to the average sales representative's almanac salary of $55 000, almanac bonuses averaged $71 500, with a range of $fifteen 000 to nearly $240 000. Purdue paid $40 million in sales incentive bonuses to its sales representatives that year.nineteen
From 1996 to 2000, Purdue increased its internal sales force from 318 sales representatives to 671, and its total physician call list from approximately 33 400 to 44 500 to approximately 70 500 to 94 000 physicians.19 Through the sales representatives, Purdue used a patient starter coupon programme for OxyContin that provided patients with a free limited-time prescription for a vii- to 30-day supply. By 2001, when the program was ended, approximately 34 000 coupons had been redeemed nationally.19
The distribution to wellness care professionals of branded promotional items such as OxyContin angling hats, stuffed plush toys, and music meaty discs ("Arrive the Swing With OxyContin") was unprecedented for a schedule II opioid, co-ordinate to the Drug Enforcement Administration.19
Purdue promoted among primary intendance physicians a more than liberal apply of opioids, particularly sustained-release opioids. Main care physicians began to use more of the increasingly popular OxyContin; by 2003, nearly half of all physicians prescribing OxyContin were main intendance physicians.xix Some experts were concerned that primary care physicians were not sufficiently trained in pain management or addiction issues.23 Primary intendance physicians, particularly in a managed care environment of time constraints, likewise had the to the lowest degree amount of time for evaluation and follow-up of patients with complicated chronic pain.
Purdue "aggressively" promoted the utilize of opioids for use in the "non-malignant pain marketplace."15(p187) A much larger market than that for cancer-related pain, the non–cancer-related pain market constituted 86% of the full opioid market in 1999.17 Purdue's promotion of OxyContin for the treatment of non–cancer-related pain contributed to a nearly tenfold increase in OxyContin prescriptions for this type of pain, from nearly 670 000 in 1997 to about 6.two million in 2002, whereas prescriptions for cancer-related pain increased virtually fourfold during that same flow.xix Although the science and consensus for the apply of opioids in the treatment of acute hurting or pain associated with cancer are robust, there is still much controversy in medicine about the use of opioids for chronic non–cancer-related pain, where their risks and benefits are much less clear. Prospective, randomized, controlled trials lasting at least 4 weeks that evaluated the utilise of opioids for chronic, non–cancer-related pain showed statistically significant but small to modest improvement in pain relief, with no consequent improvement in physical functioning.24–38 A recent review of the apply of opioids in chronic back pain concluded that opioids may exist efficacious for brusque-term hurting relief, but longer-term efficacy ( > xvi weeks) is unclear.39
In the long-term utilize of opioids for chronic non–cancer-related pain, the proven analgesic efficacy must be weighed confronting the following potential problems and risks: well-known opioid side effects, including respiratory depression, sedation, constipation, and nausea; inconsistent improvement in functioning; opioid-induced hyperalgesia; adverse hormonal and allowed effects of long-term opioid treatment; a loftier incidence of prescription opioid abuse behaviors; and an ill-defined and unclarified risk of iatrogenic addiction.forty
MISREPRESENTING THE RISK OF ADDICTION
Section:
A consistent feature in the promotion and marketing of OxyContin was a systematic endeavour to minimize the take chances of addiction in the use of opioids for the treatment of chronic not–cancer-related pain. One of the most critical issues regarding the use of opioids in the treatment of chronic non–cancer-related pain is the potential of iatrogenic addiction. The lifetime prevalence of addictive disorders has been estimated at 3% to 16% of the general population.41 However, we lack any big, methodically rigorous prospective study addressing the event of iatrogenic addiction during long-term opioid employ for chronic nonmalignant pain.42
In much of its promotional entrada—in literature and audiotapes for physicians, brochures and videotapes for patients, and its "Partners Confronting Pain" Web site—Purdue claimed that the risk of habit from OxyContin was extremely pocket-size.43–49
Purdue trained its sales representatives to conduct the message that the risk of addiction was "less than i percentage."50(p99) The company cited studies past Porter and Jick,51 who plant iatrogenic addiction in just four of 11 882 patients using opioids and by Perry and Heidrich,52 who institute no addiction amid 10 000 burn patients treated with opioids. Both of these studies, although shedding some low-cal on the risk of addiction for acute pain, exercise non help institute the risk of iatrogenic addiction when opioids are used daily for a prolonged time in treating chronic hurting. There are a number of studies, notwithstanding, that demonstrate that in the treatment of chronic not–cancer-related pain with opioids, there is a loftier incidence of prescription drug abuse. Prescription drug corruption in a substantial minority of chronic-pain patients has been demonstrated in studies by Fishbain et al. (3%–eighteen% of patients),53 Hoffman et al. (23%),54 Kouyanou et al. (12%),55 Chabal et al. (34%),56 Katz et al. (43%),57 Reid et al. (24%–31%),58 and Michna et al. (45%).59 A contempo literature review showed that the prevalence of addiction in patients with long-term opioid treatment for chronic not–cancer-related pain varied from 0% to 50%, depending on the criteria used and the subpopulation studied.60
Misrepresenting the run a risk of addiction proved plush for Purdue. On May 10, 2007, Purdue Frederick Company Inc, an affiliate of Purdue Pharma, along with iii company executives, pled guilty to criminal charges of misbranding OxyContin by claiming that it was less addictive and less bailiwick to abuse and diversion than other opioids, and will pay $634 million in fines.61
Although enquiry demonstrated that OxyContin was comparable in efficacy and safety to other available opioids,11,63 marketing catapulted OxyContin to blockbuster drug condition. Sales escalated from $44 million (316 000 prescriptions dispensed) in 1996 to a 2001 and 2002 combined sales of well-nigh $3 billion (over 14 meg prescriptions).19
The remarkable commercial success of OxyContin, nonetheless, was stained by increasing rates of abuse and addiction. Drug abusers learned how to simply crush the controlled-release tablet and swallow, inhale, or inject the high-authorisation opioid for an intense morphinelike high.64 There had been some precedence for the diversion and corruption of controlled-release opioid preparations. Purdue's own MS Contin had been abused in the late 1980s in a mode similar to how OxyContin was afterwards to be; by 1990, MS Contin had get the most abused prescription opioid in one major metropolitan surface area.65 Purdue's own testing in 1995 had demonstrated that 68% of the oxycodone could be extracted from an OxyContin tablet when crushed.66
Opioid prescribing has had meaning geographical variations. In some areas, such as Maine, W Virginia, eastern Kentucky, southwestern Virginia, and Alabama, from 1998 through 2000, hydrocodone and (non-OxyContin) oxycodone were being prescribed two.five to v.0 times more than than the national average. By 2000, these same areas had become high OxyContin-prescribing areas—up to five to six times higher than the national average in some counties (Table 1).67 These areas, in which OxyContin was highly available, were the first in the nation to witness increasing OxyContin abuse and diversion, which began surfacing in 1999 and 2000.23 From 1995 to 2001, the number of patients treated for opioid abuse in Maine increased 460%, and from 1997 to 1999 the state had a 400% increase in the number of chronic hepatitis C cases reported.68 In eastern Kentucky from 1995 to 2001, at that place was a 500% increment in the number of patients entering methadone maintenance treatment programs, about 75% of whom were OxyContin dependent (Mac Bell, ambassador, Narcotics Handling Programs, Kentucky Sectionalization of Substance Abuse, written communication, March 2002). In West Virginia, the first methadone maintenance handling plan opened in August 2000, largely in response to the increasing number of people with OxyContin dependence. Past October 2003, W Virginia had 7 methadone maintenance treatment clinics with 3040 patients in handling (1000. Moore, Role of Behavioral Health Services, Office of Alcoholism and Drug Abuse, West Virginia, written communication, March 16, 2004). In southwestern Virginia, the first methadone maintenance treatment program opened in March 2000, and within 3 years it had 1400 admissions (Due east. Jennings, Life Center of Galax, Galax, Virginia, written communication, March 12, 2004).
Tabular array 1 Distribution of OxyContin, Oxycodone (Excluding OxyContin), and Hydrocodone per 100 000 Population: Virginia, West Virginia, and Kentucky, 2000
With increasing diversion and abuse, opioid-related overdoses escalated. In southwest Virginia, the number of deaths related to opioid prescriptions increased 830%, from 23 in 1997 to 215 in 2003 (William Massello 3, MD, banana main medical examiner, Office of Chief Medical Examiner, Western Commune, Virginia Department of Wellness, written advice, January 12, 2007). The high availability of OxyContin in these 5 regions seemed to exist a simple correlate of its abuse, diversion, and addiction.
With the growing availability of OxyContin prescriptions, the one time-regional trouble began to spread nationally. By 2002, OxyContin accounted for 68% of oxycodone sales.69 Lifetime nonmedical use of OxyContin increased from one.9 million to 3.1 million people between 2002 and 2004, and in 2004 there were 615 000 new nonmedical users of OxyContin.70 By 2004, OxyContin had get the about prevalent prescription opioid driveling in the United States.2
The increasing OxyContin abuse problem was an integral office of the escalating national prescription opioid abuse problem. Liberalization of the use of opioids, particularly for the treatment of chronic non–cancer-related pain, increased the availability of all opioids as well as their abuse. Nationwide, from 1997 to 2002, at that place was a 226%, 73%, and 402% increase in fentanyl, morphine, and oxycodone prescribing, respectively (in grams per 100 000 population). During that same catamenia, the Drug Abuse Warning Network reported that hospital emergency department mentions for fentanyl, morphine, and oxycodone increased 641%, 113%, and 346%, respectively.71 Among new initiates to illicit drug apply in 2005, a total of 2.1 million reported prescription opioids as the first drug they had tried, more for marijuana and almost equal to the number of new cigarette smokers (2.three meg).72 Most abusers of prescription opioids become their diverted drugs directly from a doctor's prescription or from the prescriptions of friends and family unit.73
In terms of illicit drug abuse, prescription opioids are now alee of cocaine and heroin and second simply to marijuana.72 Mortality rates from drug overdose have climbed dramatically; by 2002, unintentional overdose deaths from prescription opioids surpassed those from heroin and cocaine nationwide.74 Nationally, as well as regionally, the high availability of OxyContin and all prescription opioids was correlated with loftier rates of abuse and diversion.
THE FOOD AND DRUG Assistants
Section:
Under the Food, Drug, and Cosmetics Act and implementing regulations, the FDA regulates the advertising and promotion of prescription drugs and is responsible for ensuring that prescription drug advertisement and promotion are truthful, balanced, and accurately communicated. There is no distinction in the act between controlled and noncontrolled drugs regarding the oversight of promotional activities. Although regulations require that all promotional materials for prescription drugs be submitted to the FDA for review when the materials are initially disseminated or used, it is mostly not required that these materials be approved by the FDA prior to their use. The FDA has a limited number of staff for overseeing the enormous amount of promotional materials. In 2002, for instance, 39 FDA staff members were responsible for reviewing roughly 34 000 pieces of promotional materials.19 This express staffing significantly diminishes the FDA's ability to ensure that the promotion is true, balanced, and accurately communicated.
In 1998, Purdue distributed 15 000 copies of an OxyContin video to physicians without submitting it to the FDA for review, an oversight afterward acknowledged by Purdue. In 2001, Purdue submitted to the FDA a second version of the video, which the FDA did non review until October 2002—after the Full general Bookkeeping Role inquired about its content. After its review, the FDA concluded that the video minimized the risks from OxyContin and made unsubstantiated claims regarding its benefits to patients.xix
When OxyContin entered the market place in 1996, the FDA canonical its original characterization, which stated that iatrogenic habit was "very rare" if opioids were legitimately used in the management of pain. In July 2001, to reflect the available scientific evidence, the label was modified to state that data were non bachelor for establishing the true incidence of addiction in chronic-pain patients. The 2001 labeling also deleted the original statement that the delayed absorption of OxyContin was believed to reduce the corruption liability of the drug.19 A more thorough review of the available scientific bear witness prior to the original labeling might take prevented some of the demand for the 2001 label revision.
CONCLUSIONS
Section:
OxyContin appears to be as efficacious and safety equally other available opioids and as oxycodone taken 4 times daily.eleven,63 Its commercial success, fueled by an unprecedented promotion and marketing campaign, was stained by escalating OxyContin abuse and diversion that spread throughout the country.2,75 The regions of the land that had the earliest and highest availability of prescribed OxyContin had the greatest initial abuse and diversion.23,67 Nationally, the increasing availability of OxyContin was associated with higher rates of abuse, and it became the most prevalent driveling prescription opioid by 2004.2
Compared with noncontrolled drugs, controlled drugs, with their potential for corruption and diversion, pose different public health risks when overpromoted and highly prescribed. Several marketing practices appear to be especially questionable.
The boggling amount of money spent in promoting a sustained-release opioid was unprecedented. During OxyContin'south kickoff 6 years on the market, Purdue spent approximately half dozen to 12 times more on promoting information technology than the visitor had spent on promoting MS Contin, or than Janssen Pharmaceutical Products LP had spent on Duragesic, one of OxyContin's competitors.19 Although OxyContin has not been shown to be superior to other available potent opioid preparations,11,63 by 2001 it had become the most often prescribed brand-name opioid in the United States for treating moderate to severe pain.xix Carefully crafted limits on the marketing and promotion of controlled drugs would help to realign their actual employ with the principles of evidence-based medicine.
Physicians' interactions with pharmaceutical sales representatives have been found to influence the prescribing practices of residents and physicians in terms of decreased prescribing of generic drugs, prescribing cost, nonrational prescribing, and rapid prescribing of new drugs.76 Carefully crafted limits on the promotion of controlled drugs by the pharmaceutical sales force and enhanced FDA oversight of the grooming and operation of sales representatives would also reduce over- and misprescribing.
Although there are no available data for evaluating the promotional effect of free starter coupons for controlled drugs, it seems likely that the over- and misprescribing of a controlled drug are encouraged by such promotional programs and the public health would be well served by eliminating them.
The apply of prescriber profiling data to influence prescribing and improve sales is imbedded in pharmaceutical detailing. Very little data are publicly available for understanding to what extent this marketing practice boosts sales. One market research report indicated that profiling improved profit margins by every bit much equally iii per centum points and the initial uptake of new drugs past 30%.77 The use of prescriber profiling data to target high-opioid prescribers—coupled with very lucrative incentives for sales representatives—would seem to fuel increased prescribing by some physicians—perhaps the about liberal prescribers of opioids and, in some cases, the least discriminate. Regulations eliminating this marketing tool might decrease some potential overprescribing of controlled drugs.
The public health would exist better protected if the FDA reviewed all advertising and promotional materials as well equally associated educational materials—for their truthfulness, accuracy, residue, and scientific validity—before broadcasting. Such a change would require a considerable increase in FDA support, staffing, and funding from what is currently bachelor. Public monies spent on the front end stop of the trouble could prevent some other such tragedy.
The pharmaceutical industry's function and influence in medical education is problematic. From 1996 through July 2002, Purdue funded more than 20 000 pain-related educational programs through directly sponsorship or financial grants,19 providing a venue that had enormous influence on physicians' prescribing throughout the country. Particularly with controlled drugs, the potential for blurring marketing and pedagogy carries a much college public wellness take a chance than with uncontrolled drugs. At to the lowest degree in the expanse of controlled drugs, with their high potential for corruption and diversion, public health would best be served by severing the pharmaceutical industry'south direct role and influence in medical education.
Marketing and promotion by the pharmaceutical manufacture have considerably amplified the prescription sales and availability of opioids. A number of factors have contributed to the marked growth of opioid abuse in the Usa, just 1 cistron is certainly the much increased availability of prescription opioids.78 The public involvement and public health would be better served by a redefinition of acceptable and allowable marketing practices for opioids and other controlled drugs.
Acknowledgments
I thank Michael McNeer, Medico, for his thoughtful review of the essay and helpful suggestions.
References
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Source: https://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2007.131714
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