HEALTH POLICY AND ETHICS
`
`6. Mamlin J, Kimaiyo S, Nyandiko W,
`Tierney W, Einterz R. Academic Institu-
`tions Linking Access to Treatment and
`Prevention: Case Study. Geneva, Switzer-
`land: World Health Organization; 2004.
`7. Einterz R, Kimaiyo S, Mengech H, et al.
`Responding to the HIV pandemic: the
`
`power of an academic medical partner-
`ship. Acad Med. 2007;82:812–818.
`8. Coates J, Swindale A, Bilinsky P.
`Household Food Insecurity Access Scale
`(HFIAS) for Measurement of Household
`Food Access: Indicator Guide. Washington,
`DC: Food and Nutrition Technical Assis-
`
`tance Project, Academy for Educational
`Development; 2006.
`
`9. Marston B, De Cock K. Multivitamins,
`nutrition, and antiretroviral therapy for
`HIV disease in Africa. N Engl J Med.
`2004;351:78–80.
`
`The Promotion and Marketing of OxyContin: Commercial
`Triumph, Public Health Tragedy
`
`Art Van Zee, MD
`
`I focus on issues surround-
`ing the promotion and market-
`ing of controlled drugs and
`their
`regulatory oversight.
`Compared with noncontrolled
`drugs, controlled drugs, with
`their potential for abuse and
`diversion, pose different pub-
`lic health risks when they are
`overpromoted and highly pre-
`scribed. An in-depth analysis
`of the promotion and market-
`ing of OxyContin illustrates
`some of the associated issues.
`Modifications of the promo-
`tion and marketing of controlled
`drugs by the pharmaceutical
`industry and an enhanced ca-
`pacity of the Food and Drug
`Administration to regulate and
`monitor such promotion can
`have a positive impact on the
`(Am J Public
`public health.
`Health. 2009;99:221–227. doi:
`10.2105/AJPH.2007.131714)
`
`CONTROLLED DRUGS, WITH
`their potential for abuse and di-
`version, can pose public health
`risks that are different from—and
`more problematic than—those of
`uncontrolled drugs when they
`are overpromoted and highly
`
`prescribed. An in-depth analysis of
`the promotion and marketing of
`OxyContin (Purdue Pharma,
`Stamford, CT), a sustained-release
`oxycodone preparation, illustrates
`some of the key issues. When
`Purdue Pharma introduced Oxy-
`Contin in 1996, it was aggressively
`marketed and highly promoted.
`Sales grew from $48 million in
`1996 to almost $1.1 billion in
`2000.1 The high availability of
`OxyContin correlated with in-
`creased abuse, diversion, and ad-
`diction, and by 2004 OxyContin
`had become a leading drug of abuse
`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. However, fun-
`damental changes in the promo-
`tion and marketing of controlled
`drugs by the pharmaceutical in-
`dustry, and an enhanced capacity
`of the FDA to regulate and mon-
`itor such promotion, can positively
`affect public health.
`OxyContin’s commercial suc-
`cess did not depend on the merits
`
`of the drug compared with other
`available opioid preparations. The
`Medical Letter on Drugs and Ther-
`apeutics concluded in 2001 that
`oxycodone offered no advantage
`over appropriate doses of other
`potent opioids.3 Randomized dou-
`ble-blind studies comparing Oxy-
`Contin given every 12 hours with
`immediate-release oxycodone given
`4 times daily showed comparable
`efficacy and safety for use with
`chronic back pain4 and cancer-
`related pain.5,6 Randomized
`double-blind studies that compared
`OxyContin with controlled-release
`morphine for cancer-related pain
`also found comparable efficacy
`and safety.7–9 The FDA’s medical
`review officer, in evaluating the
`efficacy of OxyContin in Purdue’s
`1995 new drug application, con-
`cluded that OxyContin had not
`been shown to have a significant
`advantage over conventional,
`immediate-release oxycodone
`taken 4 times daily other than a
`reduction in frequency of dosing.10
`In a review of the medical literature,
`Chou et al. made similar conclu-
`sions.11
`
`The promotion and marketing
`of OxyContin occurred during a
`recent trend in the liberalization of
`the use of opioids in the treatment
`of pain, particularly for chronic
`non–cancer-related pain. Purdue
`pursued an ‘‘aggressive’’ campaign
`to promote the use of opioids in
`general and OxyContin in partic-
`ular.1,12–17 In 2001 alone, the com-
`pany spent $200 million18 in an
`array of approaches to market and
`promote OxyContin.
`
`PROMOTION OF
`OXYCONTIN
`
`From 1996 to 2001, Purdue
`conducted more than 40 national
`pain-management 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 phar-
`maceutical company symposium
`influences physicians’ prescribing,
`
`February 2009, Vol 99, No. 2 | American Journal of Public Health
`
`Van Zee | Peer Reviewed | Health Policy and Ethics | 221
`
`1
`
`

`

`HEALTH POLICY AND ETHICS
`
`6. Mamlin J, Kimaiyo S, Nyandiko W,
`Tierney W, Einterz R. Academic Institu-
`tions Linking Access to Treatment and
`Prevention: Case Study. Geneva, Switzer-
`land: World Health Organization; 2004.
`7. Einterz R, Kimaiyo S, Mengech H, et al.
`Responding to the HIV pandemic: the
`
`power of an academic medical partner-
`ship. Acad Med. 2007;82:812–818.
`8. Coates J, Swindale A, Bilinsky P.
`Household Food Insecurity Access Scale
`(HFIAS) for Measurement of Household
`Food Access: Indicator Guide. Washington,
`DC: Food and Nutrition Technical Assis-
`
`tance Project, Academy for Educational
`Development; 2006.
`
`9. Marston B, De Cock K. Multivitamins,
`nutrition, and antiretroviral therapy for
`HIV disease in Africa. N Engl J Med.
`2004;351:78–80.
`
`The Promotion and Marketing of OxyContin: Commercial
`Triumph, Public Health Tragedy
`
`Art Van Zee, MD
`
`I focus on issues surround-
`ing the promotion and market-
`ing of controlled drugs and
`their
`regulatory oversight.
`Compared with noncontrolled
`drugs, controlled drugs, with
`their potential for abuse and
`diversion, pose different pub-
`lic health risks when they are
`overpromoted and highly pre-
`scribed. An in-depth analysis
`of the promotion and market-
`ing of OxyContin illustrates
`some of the associated issues.
`Modifications of the promo-
`tion and marketing of controlled
`drugs by the pharmaceutical
`industry and an enhanced ca-
`pacity of the Food and Drug
`Administration to regulate and
`monitor such promotion can
`have a positive impact on the
`public health.
`(Am J Public
`Health. 2009;99:221–227. doi:
`10.2105/AJPH.2007.131714)
`
`CONTROLLED DRUGS, WITH
`their potential for abuse and di-
`version, can pose public health
`risks that are different from—and
`more problematic than—those of
`uncontrolled drugs when they
`are overpromoted and highly
`
`prescribed. An in-depth analysis of
`the promotion and marketing of
`OxyContin (Purdue Pharma,
`Stamford, CT), a sustained-release
`oxycodone preparation, illustrates
`some of the key issues. When
`Purdue Pharma introduced Oxy-
`Contin in 1996, it was aggressively
`marketed and highly promoted.
`Sales grew from $48 million in
`1996 to almost $1.1 billion in
`2000.1 The high availability of
`OxyContin correlated with in-
`creased abuse, diversion, and ad-
`diction, and by 2004 OxyContin
`had become a leading drug of abuse
`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. However, fun-
`damental changes in the promo-
`tion and marketing of controlled
`drugs by the pharmaceutical in-
`dustry, and an enhanced capacity
`of the FDA to regulate and mon-
`itor such promotion, can positively
`affect public health.
`OxyContin’s commercial suc-
`cess did not depend on the merits
`
`of the drug compared with other
`available opioid preparations. The
`Medical Letter on Drugs and Ther-
`apeutics concluded in 2001 that
`oxycodone offered no advantage
`over appropriate doses of other
`potent opioids.3 Randomized dou-
`ble-blind studies comparing Oxy-
`Contin given every 12 hours with
`immediate-release oxycodone given
`4 times daily showed comparable
`efficacy and safety for use with
`chronic back pain4 and cancer-
`related pain.5,6 Randomized
`double-blind studies that compared
`OxyContin with controlled-release
`morphine for cancer-related pain
`also found comparable efficacy
`and safety.7–9 The FDA’s medical
`review officer, in evaluating the
`efficacy of OxyContin in Purdue’s
`1995 new drug application, con-
`cluded that OxyContin had not
`been shown to have a significant
`advantage over conventional,
`immediate-release oxycodone
`taken 4 times daily other than a
`reduction in frequency of dosing.10
`In a review of the medical literature,
`Chou et al. made similar conclu-
`sions.11
`
`The promotion and marketing
`of OxyContin occurred during a
`recent trend in the liberalization of
`the use of opioids in the treatment
`of pain, particularly for chronic
`non–cancer-related pain. Purdue
`pursued an ‘‘aggressive’’ campaign
`to promote the use of opioids in
`general and OxyContin in partic-
`ular.1,12–17 In 2001 alone, the com-
`pany spent $200 million18 in an
`array of approaches to market and
`promote OxyContin.
`
`PROMOTION OF
`OXYCONTIN
`
`From 1996 to 2001, Purdue
`conducted more than 40 national
`pain-management 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 phar-
`maceutical company symposium
`influences physicians’ prescribing,
`
`February 2009, Vol 99, No. 2 | American Journal of Public Health
`
`Van Zee | Peer Reviewed | Health Policy and Ethics | 221
`
`2
`
`

`

`HEALTH POLICY AND ETHICS
`
`TABLE 1—Distribution of OxyContin, Oxycodone (Excluding
`OxyContin), and Hydrocodone per 100 000 Population:
`Virginia, West Virginia, and Kentucky, 2000
`
`Distribution in Grams per 100 000 Population
`
`State and County
`
`OxyContin
`
`Oxycodone
`(Excluding OxyContin)
`
`Hydrocodone
`
`Virginia
`
`Dickenson
`
`Lee
`
`Buchanan
`
`Scott
`
`Roanoke City
`
`Tazewell
`
`Winchester City
`
`Manassas City
`
`Fauquier
`
`Wythe
`
`Kentucky
`
`Cumberland
`
`Perry
`
`Harlan
`
`Leslie
`
`Whitley
`
`25 801
`
`23 398
`
`19 138
`
`18 328
`
`17 856
`
`17 135
`
`15 242
`
`14 735
`
`14 396
`
`14 236
`
`22 113
`
`20 996
`
`19 359
`
`18 221
`
`13 438
`
`2 777
`
`6 232
`
`3 235
`
`4 946
`
`2 808
`
`3 482
`
`6 764
`
`5 920
`
`6 935
`
`3 165
`
`1 486
`
`6 145
`
`3 121
`
`4 017
`
`3 410
`
`16 692
`
`8 445
`
`15 996
`
`12 274
`
`7 201
`
`27 714
`
`14 057
`
`5 511
`
`4 434
`
`8 812
`
`8 148
`
`27 413
`
`10 141
`
`16 925
`
`19 532
`
`44 872
`
`even though the physicians who
`attend such symposia believe that
`such enticements do not alter their
`prescribing patterns.20
`One of the cornerstones of
`Purdue’s marketing plan was the
`use of sophisticated marketing
`data to influence physicians’ pre-
`scribing. Drug companies compile
`prescriber profiles on individual
`physicians—detailing the prescrib-
`ing patterns of physicians nation-
`wide—in an effort to influence
`doctors’ prescribing habits.
`Through these profiles, a drug
`company can identify the highest
`and lowest prescribers of particu-
`lar drugs in a single zip code,
`county, state, or the entire coun-
`try.21One of the critical foundations
`of Purdue’s marketing plan for
`OxyContin was to target the physi-
`cians who were the highest pre-
`scribers for opioids across the
`country.1,12–17,22 The resulting da-
`tabase would help identify physi-
`cians with large numbers of
`chronic-pain patients. Unfortu-
`nately, this same database would
`also identify which physicians were
`simply the most frequent pre-
`scribers of opioids and, in some
`cases, the least discriminate pre-
`scribers.
`A lucrative bonus system en-
`couraged sales representatives to
`increase sales of OxyContin in
`their territories, resulting in a large
`number of visits to physicians with
`high rates of opioid prescriptions,
`as well as a multifaceted informa-
`tion campaign aimed at them. In
`2001, in addition to the average
`sales representative’s annual sal-
`ary of $55 000, annual bonuses
`averaged $71500, with a range of
`$15000 to nearly $240 000.
`Purdue paid $40 million in sales
`
`incentive bonuses to its sales rep-
`resentatives that year.19
`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 pro-
`gram for OxyContin that provided
`patients with a free limited-time
`prescription for a 7- to 30-day
`supply. By 2001, when the pro-
`gram was ended, approximately
`34 000 coupons had been
`redeemed nationally.19
`The distribution to health care
`professionals of branded promo-
`tional items such as OxyContin
`fishing hats, stuffed plush toys, and
`music compact discs (‘‘Get in the
`Swing With OxyContin’’) was un-
`precedented for a schedule II opi-
`oid, according to the Drug En-
`forcement Administration.19
`Purdue promoted among pri-
`mary care physicians a more lib-
`eral use of opioids, particularly
`sustained-release opioids. Primary
`care physicians began to use more
`of the increasingly popular Oxy-
`Contin; by 2003, nearly half of all
`physicians prescribing OxyContin
`were primary care physicians.19
`Some experts were concerned that
`primary care physicians were not
`sufficiently trained in pain manage-
`ment or addiction issues.23 Primary
`care physicians, particularly in a
`managed care environment of time
`constraints, also had the least
`amount of time for evaluation and
`follow-up of patients with compli-
`cated chronic pain.
`Purdue ‘‘aggressively’’ pro-
`moted the use of opioids for use in
`
`Greenup
`
`McCreary
`
`Clinton
`
`Bell
`
`Clay
`
`West Virginia
`
`Pocahontas
`
`Raleigh
`
`Berkeley
`
`Logan
`
`McDowell
`
`Greenbrier
`
`Mercer
`
`Hancock
`
`Harrison
`
`Cabell
`
`US average
`
`13 222
`
`12 573
`
`12 517
`
`11 739
`
`11 563
`
`17 318
`
`16 813
`
`16 299
`
`16 153
`
`15 770
`
`15 752
`
`15 040
`
`13 465
`
`12 409
`
`11 665
`
`3 750
`
`5 151
`
`3 026
`
`2 911
`
`3 118
`
`3 260
`
`3 605
`
`5 959
`
`5 254
`
`2 224
`
`3 200
`
`2 539
`
`3 306
`
`4 327
`
`3 407
`
`3 608
`
`1 761
`
`12 996
`
`14 892
`
`26 037
`
`21 093
`
`17 651
`
`8 718
`
`5 009
`
`22 950
`
`24 235
`
`12 380
`
`21 175
`
`8 831
`
`12 658
`
`13 018
`
`5 083
`
`Source. Office of Diversion Control, Drug Enforcement Administration.67
`Note. Data are for the counties or independent cities with the highest quantities of
`opioids (in grams) prescribed in each of the 3 states.
`
`222 | Health Policy and Ethics | Peer Reviewed | Van Zee
`
`American Journal of Public Health | February 2009, Vol 99, No. 2
`
`3
`
`

`

`HEALTH POLICY AND ETHICS
`
`the ‘‘non-malignant pain mar-
`ket.’’15(p187) A much larger market
`than that for cancer-related pain,
`the non–cancer-related pain market
`constituted 86% of the total opioid
`market in 1999.17 Purdue’s promo-
`tion of OxyContin for the treatment
`of non–cancer-related pain con-
`tributed to a nearly tenfold increase
`in OxyContin prescriptions for this
`type of pain, from about 670000 in
`1997 to about 6.2 million in 2002,
`whereas prescriptions for cancer-
`related pain increased about four-
`fold during that same period.19 Al-
`though the science and consensus
`for the use of opioids in the treat-
`ment of acute pain or pain associ-
`ated 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 use of
`opioids for chronic, non–cancer-re-
`lated pain showed statistically sig-
`nificant but small to modest im-
`provement in pain relief, with no
`consistent improvement in physical
`functioning.24–38 A recent review
`of the use of opioids in chronic back
`pain concluded that opioids may be
`efficacious for short-term pain relief,
`but longer-term efficacy (>16
`weeks) is unclear.39
`In the long-term use of opioids
`for chronic non–cancer-related
`pain, the proven analgesic efficacy
`must be weighed against the fol-
`lowing potential problems and
`risks: well-known opioid side ef-
`fects, including respiratory de-
`pression, sedation, constipation,
`and nausea; inconsistent im-
`provement in functioning; opioid-
`induced hyperalgesia; adverse
`
`hormonal and immune effects of
`long-term opioid treatment; a high
`incidence of prescription opioid
`abuse behaviors; and an ill-
`defined and unclarified risk of
`iatrogenic addiction.40
`
`MISREPRESENTING THE
`RISK OF ADDICTION
`
`A consistent feature in the pro-
`motion and marketing of Oxy-
`Contin was a systematic effort
`to minimize the risk of addiction
`in the use of opioids for the treat-
`ment of chronic non–cancer-re-
`lated 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 life-
`time prevalence of addictive dis-
`orders has been estimated at 3%
`to 16% of the general popula-
`tion.41 However, we lack any large,
`methodically rigorous prospective
`study addressing the issue of iatro-
`genic addiction during long-term
`opioid use for chronic nonmalig-
`nant pain.42
`In much of its promotional
`campaign—in literature and au-
`diotapes for physicians, brochures
`and videotapes for patients, and its
`‘‘Partners Against Pain’’ Web
`site—Purdue claimed that the risk
`of addiction from OxyContin was
`extremely small.43–49
`Purdue trained its sales repre-
`sentatives to carry the message
`that the risk of addiction was ‘‘less
`than one percent.’’50(p99) The
`company cited studies by Porter
`and Jick,51 who found iatrogenic
`addiction in only 4 of 11882 pa-
`tients using opioids and by Perry
`and Heidrich,52 who found no ad-
`diction among10000 burn patients
`
`treated with opioids. Both of these
`studies, although shedding some
`light on the risk of addiction for
`acute pain, do not help establish the
`risk of iatrogenic addiction when
`opioids are used daily for a pro-
`longed time in treating chronic pain.
`There are a number of studies,
`however, that demonstrate that in
`the treatment of chronic non–
`cancer-related pain with opioids,
`there is a high incidence of pre-
`scription drug abuse. Prescription
`drug abuse in a substantial minority
`of chronic-pain patients has been
`demonstrated in studies by
`Fishbain et al. (3%–18% of pa-
`tients),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 recent
`literature review showed that the
`prevalence of addiction in patients
`with long-term opioid treatment for
`chronic non–cancer-related pain
`varied from 0% to 50%, depending
`on the criteria used and the sub-
`population studied.60
`Misrepresenting the risk of ad-
`diction proved costly for Purdue.
`On May 10, 2007, Purdue Fred-
`erick Company Inc, an affiliate of
`Purdue Pharma, along with 3
`company executives, pled guilty to
`criminal charges of misbranding
`OxyContin by claiming that it was
`less addictive and less subject to
`abuse and diversion than other
`opioids, and will pay $634 million
`in fines.61
`Although research demon-
`strated that OxyContin was com-
`parable in efficacy and safety to
`other available opioids,11,63 mar-
`keting catapulted OxyContin to
`blockbuster drug status. Sales esca-
`lated from $44 million (316000
`
`prescriptions dispensed) in 1996 to
`a 2001 and 2002 combined sales
`of nearly $3 billion (over 14 million
`prescriptions).19
`The remarkable commercial
`success of OxyContin, however,
`was stained by increasing rates
`of abuse and addiction. Drug
`abusers learned how to simply
`crush the controlled-release
`tablet and swallow, inhale, or in-
`ject the high-potency opioid for
`an intense morphinelike high.64
`There had been some precedence
`for the diversion and abuse of con-
`trolled-release opioid preparations.
`Purdue’s own MS Contin had been
`abused in the late 1980s in a fash-
`ion similar to how OxyContin was
`later to be; by 1990, MS Contin had
`become the most abused prescrip-
`tion opioid in one major metropol-
`itan area.65 Purdue’s own testing in
`1995 had demonstrated that 68%
`of the oxycodone could be ex-
`tracted from an OxyContin tablet
`when crushed.66
`Opioid prescribing has had
`significant geographical varia-
`tions. In some areas, such as
`Maine, West Virginia, eastern
`Kentucky, southwestern Vir-
`ginia, and Alabama, from 1998
`through 2000, hydrocodone and
`(non-OxyContin) oxycodone
`were being prescribed 2.5 to 5.0
`times more than the national
`average. By 2000, these same
`areas had become high Oxy-
`Contin-prescribing areas—up to
`5 to 6 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 na-
`tion to witness increasing OxyCon-
`tin abuse and diversion, which be-
`gan surfacing in 1999 and 2000.23
`
`February 2009, Vol 99, No. 2 | American Journal of Public Health
`
`Van Zee | Peer Reviewed | Health Policy and Ethics | 223
`
`4
`
`

`

`HEALTH POLICY AND ETHICS
`
`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, there was a
`500% increase in the number of
`patients entering methadone main-
`tenance treatment programs, about
`75% of whom were OxyContin
`dependent (Mac Bell, administrator,
`Narcotics Treatment Programs,
`Kentucky Division of Substance
`Abuse, written communication,
`March 2002). In West Virginia, the
`first methadone maintenance treat-
`ment program opened in August
`2000, largely in response to the
`increasing number of people with
`OxyContin dependence. By Octo-
`ber 2003, West Virginia had 7
`methadone maintenance treatment
`clinics with 3040 patients in treat-
`ment (M. Moore, Office of Behav-
`ioral Health Services, Office of Al-
`coholism and Drug Abuse, West
`Virginia, written communication,
`March 16, 2004). In southwestern
`Virginia, the first methadone main-
`tenance treatment program opened
`in March 2000, and within 3 years
`it had1400 admissions (E. Jennings,
`Life Center of Galax, Galax, Vir-
`ginia, written communication,
`March 12, 2004).
`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 III,
`MD, assistant chief medical exam-
`iner, Office of Chief Medical Ex-
`aminer, Western District, Virginia
`Department of Health, written
`
`communication, January 12,
`2007). The high availability of
`OxyContin in these 5 regions
`seemed to be a simple correlate of
`its abuse, diversion, and addiction.
`With the growing availability of
`OxyContin prescriptions, the once-
`regional problem began to spread
`nationally. By 2002, OxyContin
`accounted for 68% of oxycodone
`sales.69 Lifetime nonmedical use
`of OxyContin increased from 1.9
`million to 3.1 million people be-
`tween 2002 and 2004, and in
`2004 there were 615000 new
`nonmedical users of OxyContin.70
`By 2004, OxyContin had be-
`come the most prevalent prescrip-
`tion opioid abused in the United
`States.2
`The increasing OxyContin
`abuse problem was an integral
`part of the escalating national
`prescription opioid abuse prob-
`lem. Liberalization of the use of
`opioids, particularly for the treat-
`ment of chronic non–cancer-
`related pain, increased the avail-
`ability of all opioids as well as their
`abuse. Nationwide, from 1997 to
`2002, there was a 226%, 73%,
`and 402% increase in fentanyl,
`morphine, and oxycodone pre-
`scribing, respectively (in grams per
`100 000 population). During that
`same period, 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
`use in 2005, a total of 2.1 million
`reported prescription opioids as the
`first drug they had tried, more than
`for marijuana and almost equal to
`the number of new cigarette
`smokers (2.3 million).72 Most
`
`abusers of prescription opioids get
`their diverted drugs directly from a
`doctor’s prescription or from the
`prescriptions of friends and fam-
`ily.73
`In terms of illicit drug abuse,
`prescription opioids are now
`ahead of cocaine and heroin and
`second only to marijuana.72 Mor-
`tality 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 corre-
`lated with high rates of abuse and
`diversion.
`
`THE FOOD AND DRUG
`ADMINISTRATION
`
`Under the Food, Drug, and
`Cosmetics Act and implementing
`regulations, the FDA regulates the
`advertising and promotion of pre-
`scription drugs and is responsible
`for ensuring that prescription drug
`advertising and promotion are
`truthful, balanced, and accurately
`communicated. There is no dis-
`tinction in the act between con-
`trolled and noncontrolled drugs
`regarding the oversight of promo-
`tional activities. Although regula-
`tions 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 gener-
`ally not required that these mate-
`rials be approved by the FDA
`prior to their use. The FDA has a
`limited number of staff for over-
`seeing the enormous amount of
`promotional materials. In 2002,
`
`for example, 39 FDA staff
`members were responsible for
`reviewing roughly 34 000 pieces
`of promotional materials.19 This
`limited staffing significantly dimin-
`ishes the FDA’s ability to ensure
`that the promotion is truthful,
`balanced, and accurately commu-
`nicated.
`In 1998, Purdue distributed
`15000 copies of an OxyContin
`video to physicians without sub-
`mitting it to the FDA for review, an
`oversight later acknowledged by
`Purdue. In 2001, Purdue submit-
`ted to the FDA a second version of
`the video, which the FDA did not
`review until October 2002—after
`the General Accounting Office in-
`quired about its content. After its
`review, the FDA concluded that
`the video minimized the risks from
`OxyContin and made unsubstan-
`tiated claims regarding its benefits
`to patients.19
`When OxyContin entered the
`market in 1996, the FDA ap-
`proved its original label, which
`stated that iatrogenic addiction
`was ‘‘very rare’’ if opioids were
`legitimately used in the man-
`agement of pain. In July 2001, to
`reflect the available scientific
`evidence, the label was modified
`to state that data were not
`available for establishing the
`true incidence of addiction in
`chronic-pain patients. The 2001
`labeling also deleted the origi-
`nal statement that the delayed
`absorption of OxyContin was
`believed to reduce the abuse
`liability of the drug.19 A more
`thorough review of the available
`scientific evidence prior to the
`original labeling might have pre-
`vented some of the need for the
`2001 label revision.
`
`224 | Health Policy and Ethics | Peer Reviewed | Van Zee
`
`American Journal of Public Health | February 2009, Vol 99, No. 2
`
`5
`
`

`

`HEALTH POLICY AND ETHICS
`
`CONCLUSIONS
`
`OxyContin appears to be as ef-
`ficacious and safe as other avail-
`able opioids and as oxycodone
`taken 4 times daily.11,63 Its com-
`mercial success, fueled by an un-
`precedented promotion and mar-
`keting campaign, was stained by
`escalating OxyContin abuse and
`diversion that spread throughout
`the country.2,75 The regions of the
`country that had the earliest and
`highest availability of prescribed
`OxyContin had the greatest initial
`abuse and diversion.23,67 Nation-
`ally, the increasing availability of
`OxyContin was associated with
`higher rates of abuse, and it became
`the most prevalent abused pre-
`scription opioid by 2004.2
`Compared with noncontrolled
`drugs, controlled drugs, with their
`potential for abuse and diversion,
`pose different public health risks
`when overpromoted and highly
`prescribed. Several marketing
`practices appear to be especially
`questionable.
`The extraordinary amount of
`money spent in promoting a sus-
`tained-release opioid was unprec-
`edented. During OxyContin’s first
`6 years on the market, Purdue
`spent approximately 6 to 12 times
`more on promoting it than the
`company had spent on promoting
`MS Contin, or than Janssen Phar-
`maceutical Products LP had spent
`on Duragesic, one of OxyContin’s
`competitors.19 Although OxyCon-
`tin has not been shown to be su-
`perior to other available potent
`opioid preparations,11,63 by 2001 it
`had become the most frequently
`prescribed brand-name opioid in
`the United States for treating mod-
`erate to severe pain.19 Carefully
`
`crafted limits on the marketing and
`promotion of controlled drugs
`would help to realign their actual
`use with the principles of evidence-
`based medicine.
`Physicians’ interactions with
`pharmaceutical sales representa-
`tives have been found to influence
`the prescribing practices of resi-
`dents and physicians in terms of
`decreased prescribing of generic
`drugs, prescribing cost, nonratio-
`nal prescribing, and rapid pre-
`scribing of new drugs.76 Carefully
`crafted limits on the promotion of
`controlled drugs by the pharma-
`ceutical sales force and enhanced
`FDA oversight of the training and
`performance of sales representa-
`tives would also reduce over- and
`misprescribing.
`Although there are no available
`data for evaluating the promo-
`tional effect of free starter coupons
`for controlled drugs, it seems
`likely that the over- and mispre-
`scribing of a controlled drug are
`encouraged by such promotional
`programs and the public health
`would be well served by eliminat-
`ing them.
`The use of prescriber profiling
`data to influence prescribing and
`improve sales is imbedded in
`pharmaceutical detailing. Very lit-
`tle data are publicly available for
`understanding to what extent this
`marketing practice boosts sales.
`One market research report indi-
`cated that profiling improved
`profit margins by as much as 3
`percentage points and the initial
`uptake of new drugs by 30%.77
`The use of prescriber profiling data
`to target high-opioid prescribers—
`coupled with very lucrative incen-
`tives for sales representatives—
`would seem to fuel increased
`
`prescribing by some physicians—
`perhaps the most 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 be
`better protected if the FDA
`reviewed all advertising and pro-
`motional materials as well as as-
`sociated educational materials—
`for their truthfulness, accuracy,
`balance, and scientific validity—
`before dissemination. Such a
`change would require a consider-
`able increase in FDA support,
`staffing, and funding from what is
`currently available. Public monies
`spent on the front end of the
`problem could prevent another
`such tragedy.
`The pharmaceutical industry’s
`role and influence in medical ed-
`ucation is problematic. From 1996
`through July 2002, Purdue
`funded more than 20 000 pain-
`related educational programs
`through direct sponsorship or fi-
`nancial grants,19 providing a venue
`that had enormous influence on
`physicians’ prescribing throughout
`the country. Particularly with con-
`trolled drugs, the potential for
`blurring marketing and education
`carries a much higher public health
`risk than with uncontrolled drugs.
`At least in the area of controlled
`drugs, with their high potential for
`abuse and diversion, public health
`would best be served by severing the
`pharmaceutical industry’s direct role
`and influence in medical education.
`Marketing and promotion by
`the pharmaceutical industry have
`considerably amplified the pre-
`scription sales and availability of
`opioids. A number of factors have
`
`contributed to the marked growth
`of opioid abuse in the United
`States, but one factor is certainly
`the much increased availability of
`prescription opioids.78 The public
`interest and public health would be
`better served by a redefinition of
`acceptable and allowable marketing
`practices for opioids and other
`controlled drugs. j
`
`About the Author
`Requests for reprints should be sent to
`Art Van Zee, MD, Stone Mountain Health
`Services, St Charles Clinic, Box S, St
`Charles, VA 24282 (e-mail: artvanzee@
`adelphia.net).
`This article was accepted May 9, 2008.
`
`Acknowledgments
`I thank Michael McNeer, MD, for his
`thoughtful review of the essay and helpful
`suggestions.
`
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