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Report to Congressional Requesters:

United States General Accounting Office:

GAO:

December 2003:

Prescription Drugs:

OxyContin Abuse and Diversion and Efforts to Address the Problem:

OxyContin Abuse and Diversion:

GAO-04-110:

GAO Highlights:

Highlights of GAO-04-110, a report to congressional requesters 

Why GAO Did This Study:

Amid heightened awareness that many patients with cancer and other 
chronic diseases suffer from undertreated pain, the Food and Drug 
Administration (FDA) approved Purdue Pharma’s controlled-release pain 
reliever OxyContin in 1995. Sales grew rapidly, and by 2001 OxyContin 
had become the most prescribed brand-name narcotic medication for 
treating moderate-to-severe pain. In early 2000, reports began to 
surface about abuse and diversion for illicit use of OxyContin, which 
contains the opioid oxycodone. 

GAO was asked to examine concerns about these issues. Specifically, 
GAO reviewed (1) how OxyContin was marketed and promoted, (2) what 
factors contributed to the abuse and diversion of OxyContin, and 
(3) what actions have been taken to address OxyContin abuse and 
diversion.

What GAO Found:

Purdue conducted an extensive campaign to market and promote OxyContin 
using an expanded sales force to encourage physicians, including 
primary care specialists, to prescribe OxyContin not only for cancer 
pain but also as an initial opioid treatment for moderate-to-severe 
noncancer pain. OxyContin prescriptions, particularly those for 
noncancer pain, grew rapidly, and by 2003 nearly half of all OxyContin 
prescribers were primary care physicians. The Drug Enforcement 
Administration (DEA) has expressed concern that Purdue’s aggressive 
marketing of OxyContin focused on promoting the drug to treat a wide 
range of conditions to physicians who may not have been adequately 
trained in pain management. FDA has taken two actions against Purdue 
for OxyContin advertising violations. Further, Purdue did not submit 
an OxyContin promotional video for FDA review upon its initial use in 
1998, as required by FDA regulations. 

Several factors may have contributed to the abuse and diversion of 
OxyContin. OxyContin’s availability in doses that were twice as potent 
as morphine may have made it an attractive target for misuse. Further, 
the original label’s safety warning advising patients not to crush the 
tablets because of the possible rapid release of a potentially toxic 
amount of oxycodone may have inadvertently alerted abusers to methods 
for abuse. Moreover, the significant increase in OxyContin’s 
availability in the marketplace may have increased opportunities to 
obtain the drug illicitly in some states. Finally, the history of 
abuse and diversion of prescription drugs, including opioids, in some 
states may have predisposed certain areas to problems with OxyContin. 
However, GAO could not assess the relationship between the increased 
availability of OxyContin and locations of abuse and diversion because 
the data on abuse and diversion are not reliable, comprehensive, or 
timely.

Federal and state agencies and Purdue have taken actions to address 
the abuse and diversion of OxyContin. FDA approved a stronger safety 
warning on OxyContin’s label. In addition, FDA and Purdue collaborated 
on a risk management plan to help detect and prevent OxyContin abuse 
and diversion, an approach that was not used at the time OxyContin was 
approved. FDA plans to provide guidance to the pharmaceutical industry 
by September 2004 on risk management plans, which are an optional 
feature of new drug applications. DEA has established a national 
action plan to prevent abuse and diversion of OxyContin. State 
agencies have investigated reports of abuse and diversion. In addition 
to developing a risk management plan, Purdue has initiated several 
OxyContin-related educational programs, taken disciplinary action 
against sales representatives who improperly promoted OxyContin, and 
referred physicians suspected of improper prescribing practices to the 
authorities. 

What GAO Recommends:

To improve efforts to prevent or identify abuse and diversion of 
controlled substances such as OxyContin, FDA’s risk management plan 
guidance should encourage pharmaceutical manufacturers with new drug 
applications to submit plans that contain a strategy for identifying 
potential problems with abuse and diversion. FDA concurred with GAO’s 
recommendation. DEA agreed that such risk management plans are 
important, and Purdue stated that the report appeared to be fair and 
balanced.

www.gao.gov/cgi-bin/getrpt?GAO-04-110.

To view the full product, including the scope and methodology, click 
on the link above. For more information, contact Marcia Crosse at 
(202) 512-7119.

[End of section]

Contents:

Letter:

Results in Brief:

Background:

Purdue Conducted an Extensive Campaign to Market and Promote 
OxyContin:

Several Factors May Have Contributed to OxyContin Abuse and Diversion, 
but Relationship to Availability Cannot Be Assessed:

Federal and State Agencies and Purdue Have Taken Actions to Prevent 
Abuse and Diversion of OxyContin:

Conclusions:

Recommendation for Executive Action:

Agency and Purdue Comments and Our Evaluation:

Appendix I: Scope and Methodology:

Appendix II: Summary of FDA Changes to the Original Approved OxyContin 
Label:

Appendix III: Databases Used to Monitor Abuse and Diversion of 
OxyContin and Its Active Ingredient Oxycodone:

DAWN Data:

NFLIS Data:

STRIDE Data:

National Survey on Drug Use and Health Data:

Monitoring the Future Survey Data:

Appendix IV: Comments from the Food and Drug Administration:

Appendix V: Comments from the Drug Enforcement Administration:

Tables:

Table 1: Sales Representative Positions Available for OxyContin 
Promotion, 1996 through 2002:

Table 2: Total OxyContin Sales and Prescriptions for 1996 through 2002 
with Percentage Increases from Year to Year:

Table 3: Selected Language Approved by FDA in Warning Sections of 
OxyContin Labels, 1995 and 2001:

Table 4: Selected Language Approved by FDA in the Indication Sections 
of OxyContin Labels, 1995 and 2001:

Table 5: FDA Changes to the Original OxyContin Label Made from June 
1996 through July 2001:

Figure:

Figure 1: Promotional Spending for Three Opioid Analgesics in First 6 
Years of Sales:

Abbreviations:

DAWN: Drug Abuse Warning Network: 
DEA: Drug Enforcement Administration: 
FDA: Food and Drug Administration: 
FD&C Act: Federal Food, Drug and Cosmetic Act: 
HHS: Department of Health and Human Services: 
HIDTA: High Intensity Drug Trafficking Area: 
JCAHO: Joint Commission on Accreditation of Healthcare Organizations: 
NFLIS: National Forensic Laboratory Information System: 
ONDCP: Office of National Drug Control Policy: 
PDUFA Prescription Drug User Fee Act of 1992: 
PhRMA: Pharmaceutical Research and Manufacturers of America: 
RADARS: Researched Abuse, Diversion, and Addiction-Related 
Surveillance: 
SAMHSA: Substance Abuse and Mental Health Services Administration: 
STRIDE: System to Retrieve Information from Drug Evidence: 
WHO: World Health Organization:

United States General Accounting Office:

Washington, DC 20548:

December 19, 2003:

The Honorable Frank R. Wolf: 
Chairman: 
Subcommittee on Commerce, Justice, State, and the Judiciary, and 
Related Agencies: 
Committee on Appropriations: 
House of Representatives:

The Honorable James C. Greenwood: 
Chairman: 
Subcommittee on Oversight and Investigations: 
Committee on Energy and Commerce: 
House of Representatives:

The Honorable Harold Rogers: 
House of Representatives:

Patients with cancer may suffer from fairly constant pain for months or 
years. Patients with other diseases or conditions, such as rheumatoid 
arthritis, osteoarthritis, chronic back pain, or sickle cell anemia, 
may also suffer from pain that lasts for extended periods of time. 
Since 1986, the World Health Organization (WHO) and others have 
reported that the inadequate treatment of cancer and noncancer pain is 
a serious public health concern. To address this concern, efforts have 
been made to better educate health care professionals on the need to 
improve the treatment of both cancer and noncancer pain, including the 
appropriate role of prescription drugs.

Amid the heightened awareness that many people were suffering from 
undertreated pain, in 1995 the Food and Drug Administration (FDA) 
approved the new drug OxyContin, a controlled-release semisynthetic 
opioid analgesic manufactured by Purdue Pharma L.P.,[Footnote 1] for 
the treatment of moderate-to-severe pain lasting more than a few 
days.[Footnote 2] According to Purdue, OxyContin provides patients with 
continuous relief from pain over a 12-hour period, reduces pain 
fluctuations, requires fewer daily doses to help patients adhere to 
their prescribed regimen more easily, allows them to sleep through the 
night, and allows a physician to increase the OxyContin dose for a 
patient as needed to relieve pain.[Footnote 3] Sales of the drug 
increased rapidly following its introduction to the marketplace in 
1996. By 2001, sales had exceeded $1 billion annually, and OxyContin 
had become the most frequently prescribed brand-name narcotic 
medication for treating moderate-to-severe pain in the United States.

In early 2000, media reports began to surface in several states that 
OxyContin was being abused--that is, used for nontherapeutic purposes 
or for purposes other than those for which it was prescribed--and 
illegally diverted.[Footnote 4] According to FDA and the Drug 
Enforcement Administration (DEA), the abuse of OxyContin is associated 
with serious consequences, including addiction, overdose, and 
death.[Footnote 5] When OxyContin was approved, the federal government 
classified it as a schedule II controlled substance under the 
Controlled Substances Act because it has a high potential for abuse and 
may lead to severe psychological or physical dependence.[Footnote 6] 
DEA has characterized the pharmacological effects of OxyContin, and its 
active ingredient oxycodone, as similar to those of heroin. Media 
reports indicated that abusers were crushing OxyContin tablets and 
snorting the powder or dissolving it in water and injecting it to 
defeat the intended controlled-release effect of the drug and attain a 
"rush" or "high" through the body's rapid absorption of oxycodone. 
During a December 2001 congressional hearing, witnesses from DEA and 
other law enforcement officials from Kentucky, Virginia, and West 
Virginia described the growing problem of abuse and diversion of 
OxyContin.[Footnote 7] Questions were raised about what factors may 
have caused the abuse and diversion, including whether Purdue's efforts 
to market the drug may have contributed to the problem. In February 
2002, another congressional hearing was conducted on federal, state, 
and local efforts to decrease the abuse and diversion of 
OxyContin.[Footnote 8]

Because of your concerns about these issues, you asked us to examine 
the marketing and promotion of OxyContin and its abuse and diversion. 
Specifically, we addressed the following questions:

1. How has Purdue marketed and promoted OxyContin?

2. What factors contributed to the abuse and diversion of OxyContin?

3. What actions have been taken to address OxyContin abuse and 
diversion?

To identify how Purdue marketed and promoted OxyContin, we interviewed 
Purdue officials and analyzed company documents and data. We also 
interviewed selected Purdue sales representatives who were high and 
midrange sales performers during 2001 and physicians who were among the 
highest prescribers of OxyContin. To determine how Purdue's marketing 
and promotion of OxyContin compared to that of other drugs, we examined 
the promotional materials and information related to FDA actions and 
interviewed officials from companies that manufacture and market three 
other opioid drugs, Avinza, Kadian, and Oramorph SR, that like 
OxyContin are classified as schedule II controlled substances.[Footnote 
9] Because of their concern about the proprietary nature of the 
information, the three companies that market these drugs did not 
provide us with the same level of detail about the marketing and 
promotion of their drugs as did Purdue. We also examined data from DEA 
on promotional expenditures for OxyContin and two other schedule II 
controlled substances. To examine what factors may have contributed to 
the abuse and diversion of OxyContin, we interviewed officials from 
DEA, FDA, and Purdue and physicians who prescribe OxyContin. We also 
analyzed IMS Health data on sales of OxyContin nationwide and Purdue's 
distribution of sales representatives, as part of an effort to compare 
the areas with large sales growth and more sales representatives per 
capita with the areas where abuse and diversion problems were 
identified. However, limitations on the abuse and diversion data 
prevented an assessment of the relationship between the availability of 
OxyContin and areas where the drug was abused or diverted. To determine 
what actions have been taken to address OxyContin abuse and diversion, 
we interviewed FDA officials and examined FDA information regarding the 
drug's approval and marketing and promotion. We also interviewed DEA 
officials and examined how DEA determined the prevalence of OxyContin 
abuse and diversion nationally. In addition, we examined state efforts 
to identify those involved in the abuse and diversion of OxyContin. We 
also reviewed actions taken by Purdue to address this problem. (See 
app. I for a detailed discussion of our methodology.):

We performed our work from August 2002 through October 2003, in 
accordance with generally accepted government auditing standards.

Results in Brief:

Purdue conducted an extensive campaign to market and promote OxyContin 
using an expanded sales force and multiple promotional approaches to 
encourage physicians, including primary care specialists, to prescribe 
OxyContin as an initial opioid treatment for noncancer pain. OxyContin 
sales and prescriptions grew rapidly following its market introduction 
in 1996, with the growth in prescriptions for noncancer pain outpacing 
the growth in prescriptions for cancer pain from 1997 through 2002. By 
2003, nearly half of all OxyContin prescribers were primary care 
physicians. DEA has expressed concern that Purdue's aggressive 
marketing of OxyContin focused on promoting the drug to treat a wide 
range of conditions to physicians who may not have been adequately 
trained in pain management. Purdue has been cited twice by FDA for 
using potentially false or misleading medical journal advertisements 
for OxyContin that violated the Federal Food, Drug and Cosmetic Act 
(FD&C Act), including one advertisement that failed to include warnings 
about the potentially fatal risks associated with OxyContin use. 
Further, Purdue did not submit an OxyContin promotional video for FDA 
review at the time of its initial distribution in 1998, as required by 
FDA regulations. Therefore, FDA did not have the opportunity to review 
the video at the time of its distribution to ensure that the 
information it contained was truthful, balanced, and accurately 
communicated. FDA reviewed a similar video in 2002 and told us that the 
video appeared to have made unsubstantiated claims about OxyContin and 
minimized its risks.

Several factors may have contributed to OxyContin's abuse and 
diversion. OxyContin's controlled-release formulation, which made the 
drug beneficial for the relief of moderate-to-severe pain over an 
extended period of time, enabled the drug to contain more of the active 
ingredient oxycodone than other, non-controlled-release oxycodone-
containing drugs. This feature may have made OxyContin an attractive 
target for abuse and diversion, according to DEA. OxyContin's 
controlled-release formulation, which delayed the drug's absorption, 
also led FDA to include language in the original label stating that 
OxyContin had a lower potential for abuse than other oxycodone 
products. FDA officials thought that the controlled-release feature 
would make the drug less attractive to abusers. However, FDA did not 
recognize that the drug could be dissolved in water and injected, which 
disrupted the controlled-release characteristics and created an 
immediate rush or high, thereby increasing the potential for abuse. In 
addition, the safety warning on the label that advised patients not to 
crush the tablets because a rapid release of a potentially toxic amount 
of the drug could result--a customary precaution for controlled-release 
medications--may have inadvertently alerted abusers to a possible 
method for misusing the drug. The rapid growth in OxyContin sales, 
which increased the drug's availability in the marketplace, may have 
made it easier for abusers to obtain the drug for illicit purposes. 
Further, some geographic areas have been shown to have a history of 
prescription drug abuse and diversion that may have predisposed some 
states to the abuse and diversion of OxyContin. However, we could not 
assess the relationship between the increased availability of OxyContin 
and locations where it is being abused and diverted because the data on 
abuse and diversion are not reliable, comprehensive, or timely.

Since 2000, federal and state agencies and Purdue have taken several 
actions to try to address abuse and diversion of OxyContin. In July 
2001, FDA approved a revised OxyContin label adding the highest level 
of safety warning that FDA can place on an approved drug product. The 
agency also collaborated with Purdue to develop and implement a risk 
management plan to help detect and prevent abuse and diversion of 
OxyContin. Risk management plans were not used at the time OxyContin 
was approved. The plans are an optional feature of new drug 
applications that are intended to decrease product risks by using one 
or more interventions or tools beyond the approved product labeling. 
FDA plans to provide guidance on risk management plans to the 
pharmaceutical industry by September 2004. Also at the federal level, 
DEA initiated 257 OxyContin-related abuse and diversion cases in fiscal 
years 2001 and 2002, which resulted in 302 arrests and about $1 million 
in fines. At the state level, Medicaid fraud control units have 
investigated OxyContin abuse and diversion; however, they do not 
maintain precise data on the number of investigations and enforcement 
actions completed. Similarly, state medical licensure boards have 
investigated complaints about physicians who were suspected of abuse 
and diversion of controlled substances, but they could not provide data 
on the number of investigations involving OxyContin. Purdue has 
initiated education programs and other activities for physicians, 
pharmacists, and the public to address OxyContin abuse and diversion. 
Purdue has also taken disciplinary action against its sales 
representatives who improperly promoted OxyContin and has referred 
physicians who were suspected of misprescribing OxyContin to the 
appropriate authorities. Although Purdue has used very specific 
information on physician prescribing practices to market and promote 
OxyContin since its approval, it was not until October 2002 that Purdue 
began to use this information and other indicators to identify patterns 
of prescribing that could point to possible improper sales 
representative promotion or physician abuse and diversion of OxyContin.

To improve efforts to prevent or identify the abuse and diversion of 
schedule II controlled substances such as oxycodone, we recommend that 
FDA's risk management plan guidance encourage the pharmaceutical 
manufacturers that submit new drug applications for these substances to 
include plans that contain a strategy for monitoring the use of these 
drugs and identifying potential abuse and diversion problems.

We received comments on a draft of this report from FDA, DEA, and 
Purdue. FDA agreed with our recommendation that risk management plans 
for schedule II controlled substances contain a strategy for monitoring 
and identifying potential abuse and diversion problems. DEA reiterated 
its statement that Purdue's aggressive marketing of OxyContin 
exacerbated the abuse and diversion problems and noted that it is 
essential that risk management plans be put in place prior to the 
introduction of controlled substances into the marketplace. Purdue said 
the report appeared to be fair and balanced, but that we should add the 
media as one of the factors contributing to abuse and diversion 
problems with OxyContin. We incorporated their technical comments where 
appropriate.

Background:

Ensuring that pharmaceuticals are available for those with legitimate 
medical need while combating the abuse and diversion of prescription 
drugs involves the efforts of both federal and state government 
agencies. Under the FD&C Act, FDA is responsible for ensuring that 
drugs are safe and effective before they are available in the 
marketplace. The Controlled Substances Act,[Footnote 10] which is 
administered by DEA, provides the legal framework for the federal 
government's oversight of the manufacture and wholesale distribution of 
controlled substances, that is, drugs and other chemicals that have a 
potential for abuse. The states address certain issues involving 
controlled substances through their own controlled substances acts and 
their regulation of the practice of medicine and pharmacy. In response 
to concerns about the influence of pharmaceutical marketing and 
promotional activities on physician prescribing practices, both the 
pharmaceutical industry and the Department of Health and Human 
Services's (HHS) Office of Inspector General have issued voluntary 
guidelines on appropriate marketing and promotion of prescription 
drugs.

Medical Treatment of Pain:

As the incidence and prevalence of painful diseases have grown along 
with the aging of the population, there has been a growing 
acknowledgment of the importance of providing effective pain relief. 
Pain can be characterized in terms of intensity--mild to severe--and 
duration--acute (sudden onset) or chronic (long term). The appropriate 
medical treatment varies according to these two dimensions.

In 1986, WHO determined that cancer pain could be relieved in most if 
not all patients, and it encouraged physicians to prescribe opioid 
analgesics. WHO developed a three-step analgesic ladder as a practice 
guideline to provide a sequential use of different drugs for cancer 
pain management. For the first pain step, treatment with nonopioid 
analgesics, such as aspirin or ibuprofen, is recommended. If pain is 
not relieved, then an opioid such as codeine should be used for mild-
to-moderate pain as the second step. For the third step--moderate-to-
severe pain--opioids such as morphine should be used.

Beginning in the mid-1990s, various national pain-related organizations 
issued pain treatment and management guidelines, which included the use 
of opioid analgesics in treating both cancer and noncancer pain. In 
1995, the American Pain Society recommended that pain should be treated 
as the fifth vital sign[Footnote 11] to ensure that it would become 
common practice for health care providers to ask about pain when 
conducting patient evaluations. The practice guidelines issued by the 
Agency for Health Care Policy and Research provided physicians and 
other health care professionals with information on the management of 
acute pain in 1992 and cancer pain in 1994, respectively.[Footnote 12] 
Health care providers and hospitals were further required to ensure 
that their patients received appropriate pain treatment when the Joint 
Commission on Accreditation of Healthcare Organizations (JCAHO), a 
national health care facility standards-setting and accrediting body, 
implemented its pain standards for hospital accreditation in 2001.

OxyContin:

OxyContin, a schedule II drug manufactured by Purdue Pharma L.P., was 
approved by FDA in 1995 for the treatment of moderate-to-severe pain 
lasting more than a few days, as indicated in the original 
label.[Footnote 13] OxyContin followed Purdue's older product, MS 
Contin, a morphine-based product that was approved in 1984 for a 
similar intensity and duration of pain and during its early years of 
marketing was promoted for the treatment of cancer pain. The active 
ingredient in OxyContin tablets is oxycodone, a compound that is 
similar to morphine and is also found in oxycodone-combination pain 
relief drugs such as Percocet, Percodan, and Tylox. Because of its 
controlled-release property, OxyContin contains more active ingredient 
and needs to be taken less often (twice a day) than these other 
oxycodone-containing drugs.[Footnote 14] The OxyContin label 
originally approved by FDA indicated that the controlled-release 
characteristics of OxyContin were believed to reduce its potential for 
abuse. The label also contained a warning that OxyContin tablets were 
to be swallowed whole, and were not to be broken, chewed, or crushed 
because this could lead to the rapid release and absorption of a 
potentially toxic dose of oxycodone. Such a safety warning is customary 
for schedule II controlled-release medications. FDA first approved the 
marketing and use of OxyContin in 10-, 20-, and 40-milligram 
controlled-release tablets. FDA later approved 80-and 160-milligram 
controlled-release tablets for use by patients who were already taking 
opioids.[Footnote 15] In July 2001, FDA approved the revised label to 
state that the drug is approved for the treatment of moderate-to-severe 
pain in patients who require "a continuous around-the-clock analgesic 
for an extended period of time." (See app. II for a summary of the 
changes that were made by FDA to the original OxyContin label.):

OxyContin sales and prescriptions grew rapidly following its market 
introduction in 1996. Fortuitous timing may have contributed to this 
growth, as the launching of the drug occurred during the national focus 
on the inadequacy of patient pain treatment and management. In 1997, 
OxyContin's sales and prescriptions began increasing significantly, and 
they continued to increase through 2002. In both 2001 and 2002, 
OxyContin's sales exceeded $1 billion, and prescriptions were over 7 
million. The drug became Purdue's main product, accounting for 90 
percent of the company's total prescription sales by 2001.

Media reports of OxyContin abuse and diversion began to surface in 
2000. These reports first appeared in rural areas of some states, 
generally in the Appalachian region, and continued to spread to other 
rural areas and larger cities in several states. Rural communities in 
Maine, Kentucky, Ohio, Pennsylvania, Virginia, and West Virginia were 
reportedly being devastated by the abuse and diversion of OxyContin. 
For example, media reports told of persons and communities that had 
been adversely affected by the rise of addiction and deaths related to 
OxyContin. One report noted that drug treatment centers and emergency 
rooms in a particular area were receiving new patients who were 
addicted to OxyContin as early as 1999. Pain patients, teens, and 
recreational drug users who had abused OxyContin reportedly entered 
drug treatment centers sweating and vomiting from withdrawal. In West 
Virginia, as many as one-half of the approximately 300 patients 
admitted to a drug treatment clinic in 2000 were treated for OxyContin 
addiction. The media also reported on deaths due to OxyContin. For 
example, a newspaper's investigation of autopsy reports involving 
oxycodone-related deaths found that OxyContin had been involved in over 
200 overdose deaths in Florida since 2000.[Footnote 16] In another 
case, a forensic toxicologist commented that he had reviewed a number 
of fatal overdose cases in which individuals took a large dose of 
OxyContin, in combination with alcohol or other drugs.

After learning about the initial reports of abuse and diversion of 
OxyContin in Maine in 2000, Purdue formed a response team made up of 
its top executives and physicians to initiate meetings with federal and 
state officials in Maine to gain an understanding of the scope of the 
problem and to devise strategies for preventing abuse and diversion. 
After these meetings, Purdue distributed brochures to health care 
professionals that described several steps that could be taken to 
prevent prescription drug abuse and diversion. In response to the abuse 
and diversion reports, DEA analyzed data collected from medical 
examiner autopsy reports and crime scene investigation reports. The 
most recent data available from DEA show that as of February 2002, the 
agency had verified 146 deaths nationally involving OxyContin in 2000 
and 2001.

According to Purdue, as of early October 2003, over 300 lawsuits 
concerning OxyContin were pending against Purdue, and 50 additional 
lawsuits had been dismissed. The cases involve many allegations, 
including, for example, that Purdue used improper sales tactics and 
overpromoted OxyContin causing the drug to be inappropriately 
prescribed by physicians, and that Purdue took inadequate actions to 
prevent addiction, abuse, and diversion of the drug. The lawsuits have 
been brought in 25 states and the District of Columbia in both federal 
and state courts.

Controlled Substances Act:

The Controlled Substances Act established a classification structure 
for drugs and chemicals used in the manufacture of drugs that are 
designated as controlled substances.[Footnote 17] Controlled 
substances are classified by DEA into five schedules on the basis of 
their medicinal value, potential for abuse, and safety or dependence 
liability. Schedule I drugs--including heroin, marijuana, and LSD--have 
a high potential for abuse and no currently accepted medical use. 
Schedule II drugs--which include opioids such as morphine and 
oxycodone, the primary ingredient in OxyContin--have a high potential 
for abuse among drugs with an accepted medical use and may lead to 
severe psychological or physical dependence. Drugs on schedules III 
through V have medical uses and successively lower potentials for abuse 
and dependence. Schedule III drugs include anabolic steroids, codeine, 
hydrocodone in combination with aspirin or acetaminophen, and some 
barbiturates. Schedule IV contains such drugs as the antianxiety drugs 
diazepam (Valium) and alprazolam (Xanax). Schedule V includes 
preparations such as cough syrups with codeine. All scheduled drugs 
except those in schedule I are legally available to the public with a 
prescription.[Footnote 18]

FDA's Regulation of Prescription Drugs:

Under the FD&C Act and implementing regulations, FDA is responsible for 
ensuring that all new drugs are safe and effective. FDA reviews 
scientific and clinical data to decide whether to approve drugs based 
on their intended use, effectiveness, and the risks and benefits for 
the intended population, and also monitors drugs for continued safety 
after they are in use.

FDA also regulates the advertising and promotion of prescription drugs 
under the FD&C Act. FDA carries out this responsibility by ensuring 
that prescription drug advertising and promotion is truthful, balanced, 
and accurately communicated.[Footnote 19] The FD&C Act makes no 
distinction between controlled substances and other prescription drugs 
in the oversight of promotional activities. FDA told us that the agency 
takes a risk-based approach to enforcement, whereby drugs with more 
serious risks, such as opioids, are given closer scrutiny in monitoring 
promotional messages and activities, but the agency has no specific 
guidance or policy on this approach. The FD&C Act and its implementing 
regulations require that all promotional materials for prescription 
drugs be submitted to FDA at the time the materials are first 
disseminated or used, but it generally is not required that these 
materials be approved by FDA before their use. As a result, FDA's 
actions to address violations occur after the materials have already 
appeared in public. In fiscal year 2002, FDA had 39 staff positions 
dedicated to oversight of drug advertising and promotion of all 
pharmaceuticals distributed in the United States. According to FDA, 
most of the staff focuses on the oversight of promotional 
communications to physicians. FDA officials told us that in 2001 it 
received approximately 34,000 pieces of promotional material, including 
consumer advertisements and promotions to physicians, and received and 
reviewed 230 complaints about allegedly misleading advertisements, 
including materials directed at health professionals.[Footnote 20]

FDA issues two types of letters to address violations of the FD&C Act: 
untitled letters and warning letters. Untitled letters are issued for 
violations such as overstating the effectiveness of the drug, 
suggesting a broader range of indicated uses than the drug has been 
approved for, and making misleading claims because of inadequate 
context or lack of balanced information. Warning letters are issued for 
more serious violations, such as those involving safety or health 
risks, or for continued violations of the act. Warning letters 
generally advise a pharmaceutical manufacturer that FDA may take 
further enforcement actions, such as seeking judicial remediation, 
without notifying the company and may ask the manufacturer to conduct a 
new advertising campaign to correct inaccurate impressions left by the 
advertisements.

Under the Controlled Substances Act, FDA notifies DEA if FDA is 
reviewing a new drug application for a drug that has a stimulant, 
depressant, or hallucinogenic effect on the central nervous system and 
has abuse potential. FDA performs a medical and scientific assessment 
as required by the Controlled Substances Act, and recommends to DEA an 
initial schedule level to be assigned to a new controlled substance.

FDA plans to provide guidance to the pharmaceutical industry on the 
development, implementation, and evaluation of risk management plans as 
a result of the reauthorization of the Prescription Drug User Fee Act 
of 1992 (PDUFA).[Footnote 21] FDA expects to issue this guidance by 
September 30, 2004. FDA defines a risk management program as a 
strategic safety program that is designed to decrease product risks by 
using one or more interventions or tools beyond the approved product 
labeling. Interventions used in risk management plans may include 
postmarketing surveillance, education and outreach programs to health 
professionals or consumers, informed consent agreements for patients, 
limitations on the supply or refills of products, and restrictions on 
individuals who may prescribe and dispense drug products. All drug 
manufacturers have the option to develop and submit risk management 
plans to FDA as part of their new drug applications.

DEA's Regulation of Controlled Substances:

DEA is the primary federal agency responsible for enforcing the 
Controlled Substances Act. DEA has the authority to regulate 
transactions involving the sale and distribution of controlled 
substances at the manufacturer and wholesale distributor levels. DEA 
registers legitimate handlers of controlled substances--including 
manufacturers, distributors, hospitals, pharmacies, practitioners, and 
researchers--who must comply with regulations relating to drug security 
and accountability through the maintenance of inventories and records. 
All registrants, including pharmacies, are required to maintain records 
of controlled substances that have been manufactured, purchased, and 
sold. Manufacturers and distributors are also required to report their 
annual inventories of controlled substances to DEA. The data provided 
to DEA are available for use in monitoring the distribution of 
controlled substances throughout the United States and identifying 
retail-level registrants that received unusual quantities of controlled 
substances. DEA regulations for schedule II prescription drugs, unlike 
those for other prescription drugs, require that each prescription must 
be written and signed by the physician and may not be telephoned in to 
the pharmacy except in an emergency. Also, a prescription for a 
schedule II drug may not be refilled. A physician is required to 
provide a new prescription each time a patient obtains more of the 
drug. DEA also sets limits on the quantity of schedule II controlled 
substances that may be produced in the United States in any given year. 
Specifically, DEA sets aggregate production quotas that limit the 
production of bulk raw materials used in the manufacture of controlled 
substances. DEA determines these quotas based on a variety of data 
including sales, production, inventories, and exports. Individual 
companies must apply to DEA for manufacturing or procurement quotas for 
specific pharmaceutical products. For example, Purdue has a procurement 
quota for oxycodone, the principle ingredient in OxyContin, that allows 
the company to purchase specified quantities of oxycodone from bulk 
manufacturers.

States' Regulation of the Practice of Medicine and Pharmacy and Role in 
Monitoring Illegal Use and Diversion of Prescription Drugs:

State laws govern the prescribing and dispensing of prescription drugs 
by licensed health care professionals. Each state requires that 
physicians practicing in the state be licensed, and state medical 
practice laws generally outline standards for the practice of medicine 
and delegate the responsibility of regulating physicians to state 
medical boards. States also require pharmacists and pharmacies to be 
licensed. The regulation of the practice of pharmacy is based on state 
pharmacy practice acts and regulations enforced by the state boards of 
pharmacy. According to the National Association of Boards of Pharmacy, 
all state pharmacy laws require that records of prescription drugs 
dispensed to patients be maintained and that state pharmacy boards have 
access to the prescription records. State regulatory boards face new 
challenges with the advent of Internet pharmacies, because they enable 
pharmacies and physicians to anonymously reach across state borders to 
prescribe, sell, and dispense prescription drugs without complying with 
state requirements.[Footnote 22] In some cases, consumers can purchase 
prescription drugs, including controlled substances, such as OxyContin, 
from Internet pharmacies without a valid prescription.

In addition to these regulatory boards, 15 states operate prescription 
drug monitoring programs as a means to control the illegal diversion of 
prescription drugs that are controlled substances. Prescription drug 
monitoring programs are designed to facilitate the collection, 
analysis, and reporting of information on the prescribing, dispensing, 
and use of controlled substances within a state. They provide data and 
analysis to state law enforcement and regulatory agencies to assist in 
identifying and investigating activities potentially related to the 
illegal prescribing, dispensing, and procuring of controlled 
substances. For example, physicians in Kentucky can use the program to 
check a patient's prescription drug history to determine if the 
individual may be "doctor shopping" to seek multiple controlled 
substance prescriptions. An overriding goal of prescription drug 
monitoring programs is to support both the state laws ensuring access 
to appropriate pharmaceutical care by citizens and the state laws 
deterring diversion. As we have reported, state prescription drug 
monitoring programs offer state regulators an efficient means of 
detecting and deterring illegal diversion. However, few states 
proactively analyze prescription data to identify individuals, 
physicians, or pharmacies that have unusual use, prescribing, or 
dispensing patterns that may suggest potential drug diversion or abuse. 
Although three states can respond to requests for information within 3 
to 4 hours, providing information on suspected illegal prescribing, 
dispensing, or doctor shopping at the time a prescription is written or 
sold would require states to improve computer capabilities. In 
addition, state prescription drug monitoring programs may require 
additional legal authority to analyze data proactively.[Footnote 23]

Guidelines for Marketing Drugs to Health Care Professionals:

At the time that OxyContin was first marketed, there were no industry 
or federal guidelines for the promotion of prescription drugs. 
Voluntary guidelines regarding how drug companies should market and 
promote their drugs to health care professionals were issued in July 
2002 by the Pharmaceutical Research and Manufacturers of America 
(PhRMA). In April 2003, HHS's Office of Inspector General issued 
voluntary guidelines for how drug companies should market and promote 
their products to federal health care programs. Neither set of 
guidelines distinguishes between controlled and noncontrolled 
substances.

PhRMA's voluntary code of conduct for sales representatives states that 
interactions with health care professionals should be to inform these 
professionals about products, to provide scientific and educational 
information, and to support medical research and education.[Footnote 
24] The question-and-answer section of the code addresses companies' 
use of branded promotional items, stating, for example, that golf balls 
and sports bags should not be distributed because they are not 
primarily for the benefit of patients, but that speaker training 
programs held at golf resorts may be acceptable if participants are 
receiving extensive training. Purdue adopted the code.

In April 2003, HHS's Office of Inspector General issued final voluntary 
guidance for drug companies' interactions with health care 
professionals in connection with federal health care programs, 
including Medicare and Medicaid. Among the guidelines were cautions for 
companies against offering inappropriate travel, meals, and gifts to 
influence the prescribing of drugs; making excessive payments to 
physicians for consulting and research services; and paying physicians 
to switch their patients from competitors' drugs.

Purdue Conducted an Extensive Campaign to Market and Promote OxyContin:

Purdue conducted an extensive campaign to market and promote OxyContin 
that focused on encouraging physicians, including those in primary care 
specialties, to prescribe the drug for noncancer as well as cancer 
pain. To implement its OxyContin campaign, Purdue significantly 
increased its sales force and used multiple promotional approaches. 
OxyContin sales and prescriptions grew rapidly following its market 
introduction, with the growth in prescriptions for noncancer pain 
outpacing the growth in prescriptions for cancer pain. DEA has 
expressed concern that Purdue marketed OxyContin for a wide variety of 
conditions to physicians who may not have been adequately trained in 
pain management. Purdue has been cited twice by FDA for OxyContin 
advertisements in medical journals that violated the FD&C Act. FDA has 
also taken similar actions against manufacturers of two of the three 
comparable schedule II controlled substances we examined, to ensure 
that their marketing and promotion were truthful, balanced, and 
accurately communicated. In addition, Purdue provided two promotional 
videos to physicians that, according to FDA appear to have made 
unsubstantiated claims and minimized the risks of OxyContin. The first 
video was available for about 3 years without being submitted to FDA 
for review.

Purdue Focused on Promoting OxyContin for Treatment of Noncancer Pain:

From the outset of the OxyContin marketing campaign, Purdue promoted 
the drug to physicians for noncancer pain conditions that can be caused 
by arthritis, injuries, and chronic diseases, in addition to cancer 
pain. Purdue directed its sales representatives to focus on the 
physicians in their sales territories who were high opioid prescribers. 
This group included cancer and pain specialists, primary care 
physicians, and physicians who were high prescribers of Purdue's older 
product, MS Contin. One of Purdue's goals was to identify primary care 
physicians who would expand the company's OxyContin prescribing base. 
Sales representatives were also directed to call on oncology nurses, 
consultant pharmacists, hospices, hospitals, and nursing homes.

From OxyContin's launch until its July 2001 label change, Purdue used 
two key promotional messages for primary care physicians and other high 
prescribers. The first was that physicians should prescribe OxyContin 
for their pain patients both as the drug "to start with and to stay 
with." The second contrasted dosing with other opioid pain relievers 
with OxyContin dosing as "the hard way versus the easy way" to dose 
because OxyContin's twice-a-day dosing was more convenient for 
patients.[Footnote 25] Purdue's sales representatives promoted 
OxyContin to physicians as an initial opioid treatment for moderate-to-
severe pain lasting more than a few days, to be prescribed instead of 
other single-entity opioid analgesics or short-acting combination 
opioid pain relievers. Purdue has stated that by 2003 primary care 
physicians had grown to constitute nearly half of all OxyContin 
prescribers, based on data from IMS Health, an information service 
providing pharmaceutical market research. DEA's analysis of physicians 
prescribing OxyContin found that the scope of medical specialties was 
wider for OxyContin than five other controlled-release, schedule II 
narcotic analgesics. DEA expressed concern that this resulted in 
OxyContin's being promoted to physicians who were not adequately 
trained in pain management.

Purdue's promotion of OxyContin for the treatment of noncancer pain 
contributed to a greater increase in prescriptions for noncancer pain 
than for cancer pain from 1997 through 2002.[Footnote 26] According to 
IMS Health data, the annual number of OxyContin prescriptions for 
noncancer pain increased nearly tenfold, from about 670,000 in 1997 to 
about 6.2 million in 2002.[Footnote 27] In contrast, during the same 6 
years, the annual number of OxyContin prescriptions for cancer pain 
increased about fourfold, from about 250,000 in 1997 to just over 1 
million in 2002. The noncancer prescriptions therefore increased from 
about 73 percent of total OxyContin prescriptions to about 85 percent 
during that period, while the cancer prescriptions decreased from about 
27 percent of the total to about 15 percent. IMS Health data indicated 
that prescriptions for other schedule II opioid drugs, such as 
Duragesic[Footnote 28] and morphine products, for noncancer pain also 
increased during this period. Duragesic prescriptions for noncancer 
pain were about 46 percent of its total prescriptions in 1997, and 
increased to about 72 percent of its total in 2002. Morphine products, 
including, for example, Purdue's MS Contin, also experienced an 
increase in their noncancer prescriptions during the same period. Their 
noncancer prescriptions were about 42 percent of total prescriptions in 
1997, and increased to about 65 percent in 2002. DEA has cited Purdue's 
focus on promoting OxyContin for treating a wide range of conditions as 
one of the reasons the agency considered Purdue's marketing of 
OxyContin to be overly aggressive.

Purdue Significantly Increased Its Sales Force to Market and Promote 
OxyContin:

Purdue significantly increased its sales force to market and promote 
OxyContin to physicians and other health care practitioners. In 1996, 
Purdue began promoting OxyContin with a sales force of approximately 
300 representatives in its Prescription Sales Division.[Footnote 29] 
Through a 1996 copromotion agreement, Abbott Laboratories provided at 
least another 300 representatives, doubling the total OxyContin sales 
force.[Footnote 30] By 2000, Purdue had more than doubled its own 
internal sales force to 671. The expanded sales force included sales 
representatives from the Hospital Specialty Division, which was created 
in 2000 to increase promotional visits on physicians located in 
hospitals. (See table 1.):

Table 1: Sales Representative Positions Available for OxyContin 
Promotion, 1996 through 2002:

Positions available[A]: Purdue Prescription Sales Division; 
1996: 318; 
1997: 319; 
1998: 377; 
1999: 471; 
2000: 562; 
2001: 641; 
2002: 641.

Positions available[A]: Purdue Hospital Specialty Division; 
1996: 0; 
1997: 0; 
1998: 0; 
1999: 0; 
2000: 109; 
2001: 125; 
2002: 126.

Positions available[A]: Subtotal--All Purdue sales representatives; 
1996: 318; 
1997: 319; 
1998: 377; 
1999: 471; 
2000: 671; 
2001: 766; 
2002: 767.

Positions available[A]: Abbott Laboratories sales representatives[B]; 
1996: 300; 
1997: 300; 
1998: 300; 
1999: 300; 
2000: 300; 
2001: 300; 
2002: 300.

Positions available[A]: Total; 
1996: 618; 
1997: 619; 
1998: 677; 
1999: 771; 
2000: 971; 
2001: 1,066; 
2002: 1,067.

Source: GAO analysis of Purdue data.

[A] All positions were not necessarily filled in a given year.

[B] Under the OxyContin copromotion agreement, Abbott Laboratories 
provided at least 300 sales representatives each year.

[End of table]

The manufacturers of two of the three comparable schedule II drugs have 
smaller sales forces than Purdue. Currently, the manufacturer of Kadian 
has about 100 sales representatives and is considering entering into a 
copromotion agreement. Elan, the current owner of Oramorph SR, has 
approximately 300 representatives, but told us that it is not currently 
marketing Oramorph SR. The manufacturer of Avinza had approximately 50 
representatives at its product launch. In early 2003, Avinza's 
manufacturer announced that more than 700 additional sales 
representatives would be promoting the drug under its copromotion 
agreement with the pharmaceutical manufacturer Organon--for a total of 
more than 800 representatives.

By more than doubling its total sales representatives, Purdue 
significantly increased the number of physicians to whom it was 
promoting OxyContin. Each Purdue sales representative has a specific 
sales territory and is responsible for developing a list of about 105 
to 140 physicians to call on who already prescribe opioids or who are 
candidates for prescribing opioids. In 1996, the 300-plus Purdue sales 
representatives had a total physician call list of approximately 33,400 
to 44,500. By 2000, the nearly 700 representatives had a total call 
list of approximately 70,500 to 94,000 physicians. Each Purdue sales 
representative is expected to make about 35 physician calls per week 
and typically calls on each physician every 3 to 4 weeks. Each hospital 
sales representative is expected to make about 50 calls per week and 
typically calls on each facility every 4 weeks.

Purdue stated it offered a "better than industry average" salary and 
sales bonuses to attract top sales representatives and provide 
incentives to boost OxyContin sales as it had done for MS Contin. 
Although the sales representatives were primarily focused on OxyContin 
promotion, the amount of the bonus depended on whether a representative 
met the sales quotas in his or her sales territory for all company 
products. As OxyContin's sales increased, Purdue's growth-based portion 
of the bonus formula increased the OxyContin sales quotas necessary to 
earn the same base sales bonus amounts. The amount of total bonuses 
that Purdue estimated were tied to OxyContin sales increased 
significantly from about $1 million in 1996, when OxyContin was first 
marketed, to about $40 million in 2001. Beginning in 2000, when the 
newly created hospital specialty representatives began promoting 
OxyContin, their estimated total bonuses were approximately $6 million 
annually. In 2001, the average annual salary for a Purdue sales 
representative was $55,000, and the average annual bonus was $71,500. 
During the same year, the highest annual sales bonus was nearly 
$240,000, and the lowest was nearly $15,000. In 2001, Purdue decided to 
limit the sales bonus a representative could earn based on the growth 
in prescribing of a single physician after a meeting with the U.S. 
Attorney for the Western District of Virginia at which the company was 
informed of the possibility that a bonus could be based on the 
prescribing of one physician.

Purdue Employed Multiple Approaches to Market and Promote OxyContin:

In addition to expanding its sales force, Purdue used multiple 
approaches to market and promote OxyContin. These approaches included 
expanding its physician speaker bureau and conducting speaker training 
conferences, sponsoring pain-related educational programs, issuing 
OxyContin starter coupons for patients' initial prescriptions, 
sponsoring pain-related Web sites, advertising OxyContin in medical 
journals, and distributing OxyContin marketing items to health care 
professionals.

In our report on direct-to-consumer advertising, we found that most 
promotional spending is targeted to physicians.[Footnote 31] For 
example, in 2001, 29 percent of spending on pharmaceutical promotional 
activities was related to activities of pharmaceutical sales 
representatives directed to physicians, and 2 percent was for journal 
advertising--both activities Purdue uses for its OxyContin promotion. 
The remaining 69 percent of pharmaceutical promotional spending 
involved sampling (55 percent), which is the practice of providing drug 
samples during sales visits to physician offices, and direct-to-
consumer advertising (14 percent)--both activities that Purdue has 
stated it does not use for OxyContin.

According to DEA's analysis of IMS Health data, Purdue spent 
approximately 6 to 12 times more on promotional efforts during 
OxyContin's first 6 years on the market than it had spent on its older 
product, MS Contin, during its first 6 years, or than had been spent by 
Janssen Pharmaceutical Products, L.P., for one of OxyContin's drug 
competitors, Duragesic. (See fig. 1.):

Figure 1: Promotional Spending for Three Opioid Analgesics in First 6 
Years of Sales:

[See PDF for image]

Note: Dollars are 2002 adjusted.

[End of figure]

During the first 5 years that OxyContin was marketed, Purdue conducted 
over 40 national pain management and speaker training conferences, 
usually in resort locations such as Boca Raton, Florida, and 
Scottsdale, Arizona, to recruit and train health care practitioners for 
its national speaker bureau. The trained speakers were then made 
available to speak about the appropriate use of opioids, including 
oxycodone, the active ingredient in OxyContin, to their colleagues in 
various settings, such as local medical conferences and grand round 
presentations in hospitals involving physicians, residents, and 
interns. Over the 5 years, these conferences were attended by more than 
5,000 physicians, pharmacists, and nurses, whose travel, lodging, and 
meal costs were paid by the company. Purdue told us that less than 1 
percent annually of the physicians called on by Purdue sales 
representatives attended these conferences. Purdue told us it 
discontinued conducting these conferences in fall 2000. Purdue's 
speaker bureau list from 1996 through mid-2002 included nearly 2,500 
physicians, of whom over 1,000 were active participants. Purdue has 
paid participants a fee for speaking based on the physician's 
qualifications; the type of program and time commitment involved; and 
expenses such as airfare, hotel, and food. The company currently 
marketing the comparable drug Avinza has a physician speaker bureau, 
but does not sponsor speaker training and conferences at resort 
locations. Kadian's current company does not have a physician speaker 
bureau and has not held any conferences.

From 1996, when OxyContin was introduced to the market, to July 2002, 
Purdue has funded over 20,000 pain-related educational programs through 
direct sponsorship or financial grants. These grants included support 
for programs to provide physicians with opportunities to earn required 
continuing medical education credits, such as grand round presentations 
at hospitals and medical education seminars at state and local medical 
conferences. During 2001 and 2002, Purdue funded a series of nine 
programs throughout the country to educate hospital physicians and 
staff on how to comply with JCAHO's pain standards for hospitals and to 
discuss postoperative pain treatment. Purdue was one of only two drug 
companies that provided funding for JCAHO's pain management educational 
programs.[Footnote 32] Under an agreement with JCAHO, Purdue was the 
only drug company allowed to distribute certain educational videos and 
a book about pain management; these materials were also available for 
purchase from JCAHO's Web site. Purdue's participation in these 
activities with JCAHO may have facilitated its access to hospitals to 
promote OxyContin.

For the first time in marketing any of its products, Purdue used a 
patient starter coupon program for OxyContin to provide patients with a 
free limited-time prescription. Unlike patient assistance programs, 
which provide free prescriptions to patients in financial need, a 
coupon program is intended to enable a patient to try a new drug 
through a one-time free prescription. A sales representative 
distributes coupons to a physician, who decides whether to offer one to 
a patient, and then the patient redeems it for a free prescription 
through a participating pharmacy. The program began in 1998 and ran 
intermittently for 4 years. In 1998 and 1999, each sales representative 
had 25 coupons that were redeemable for a free 30-day supply. In 2000 
each representative had 90 coupons for a 7-day supply, and in 2001 each 
had 10 coupons for a 7-day supply. Approximately 34,000 coupons had 
been redeemed nationally when the program was terminated following the 
July 2001 OxyContin label change. The manufacturers of two of the 
comparable drugs we examined--Avinza and Kadian--used coupon programs 
to introduce patients to their products. Avinza's coupon program 
requires patients to make a copayment to cover part of the drug's cost.

Purdue has also used Web sites to provide pain-related information to 
consumers and others. In addition to its corporate Web site, which 
provides product information, Purdue established the "Partners Against 
Pain" Web site in 1997 to provide consumers with information about pain 
management and pain treatment options. According to FDA, the Web site 
also contained information about OxyContin. Separate sections provide 
information for patients and caregivers, medical professionals, and 
institutions. The Web site includes a "Find a Doctor" feature to enable 
consumers to find physicians who treat pain in their geographic 
area.[Footnote 33] As of July 2002, over 33,000 physicians were 
included. Ligand, which markets Avinza, one of the comparable drugs, 
has also used a corporate Web site to provide product information. 
Purdue has also funded Web sites, such as FamilyPractice.com, that 
provide physicians with free continuing medical educational programs on 
pain management.[Footnote 34] Purdue has also provided funding for Web 
site development and support for health care groups such as the 
American Chronic Pain Association and the American Academy of Pain 
Medicine. In addition, Purdue is one of 28 corporate donors--which 
include all three comparable drug companies--listed on the Web site of 
the American Pain Society, the mission of which is to improve pain-
related education, treatment, and professional practice. Purdue also 
sponsors painfullyobvious.com, which it describes as a youth-focused 
"message campaign designed to provide information--and stimulate open 
discussions--on the dangers of abusing prescription drugs.":

Purdue also provided its sales representatives with 14,000 copies of a 
promotional video in 1999 to distribute to physicians. Entitled From 
One Pain Patient to Another: Advice from Patients Who Have Found 
Relief, the video was to encourage patients to report their pain and to 
alleviate patients' concerns about taking opioids. Purdue stated that 
the video was to be used "in physician waiting rooms, as a 'check out' 
item for an office's patient education library, or as an educational 
tool for office or hospital staff to utilize with patients and their 
families." Copies of the video were also available for ordering on the 
"Partners Against Pain" Web site from June 2000 through July 2001. The 
video did not need to be submitted to FDA for its review because it did 
not contain any information about OxyContin. However, the video 
included a statement that opioid analgesics have been shown to cause 
addiction in less than 1 percent of patients. According to FDA, this 
statement has not been substantiated.

As part of its marketing campaign, Purdue distributed several types of 
branded promotional items to health care practitioners. Among these 
items were OxyContin fishing hats, stuffed plush toys, coffee mugs with 
heat-activated messages, music compact discs, luggage tags, and pens 
containing a pullout conversion chart showing physicians how to 
calculate the dosage to convert a patient to OxyContin from other 
opioid pain relievers.[Footnote 35] In May 2002, in anticipation of 
PhRMA's voluntary guidance for sales representatives' interactions with 
health care professionals, Purdue instructed its sales force to destroy 
any remaining inventory of non-health-related promotional items, such 
as stuffed toys or golf balls. In early 2003, Purdue began distributing 
an OxyContin branded goniometer--a range and motion measurement guide. 
According to DEA, Purdue's use of branded promotional items to market 
OxyContin was unprecedented among schedule II opioids, and was an 
indicator of Purdue's aggressive and inappropriate marketing of 
OxyContin.

Another approach Purdue used to promote OxyContin was to place 
advertisements in medical journals. Purdue's annual spending for 
OxyContin advertisements increased from about $700,000 in 1996 to about 
$4.6 million in 2001. All three companies that marketed the comparable 
drugs have also used medical journal advertisements to promote their 
products.

OxyContin Advertisements Violated the FD&C Act:

Purdue has been cited twice by FDA for using advertisements in 
professional medical journals that violated the FD&C Act. In May 2000, 
FDA issued an untitled letter to Purdue regarding a professional 
medical journal advertisement for OxyContin.[Footnote 36] FDA noted 
that among other problems, the advertisement implied that OxyContin had 
been studied for all types of arthritis pain when it had been studied 
only in patients with moderate-to-severe osteoarthritis pain, the 
advertisement suggested OxyContin could be used as an initial therapy 
for the treatment of osteoarthritis pain without substantial evidence 
to support this claim, and the advertisement promoted OxyContin in a 
selected class of patients--the elderly--without presenting risk 
information applicable to that class of patients.[Footnote 37] Purdue 
agreed to stop dissemination of the advertisement. The second action 
taken by FDA was more serious. In January 2003, FDA issued a warning 
letter to Purdue regarding two professional medical journal 
advertisements for OxyContin that minimized its risks and overstated 
its efficacy, by failing to prominently present information from the 
boxed warning on the potentially fatal risks associated with OxyContin 
and its abuse liability, along with omitting important information 
about the limitations on the indicated use of OxyContin.[Footnote 38] 
The FDA requested that Purdue cease disseminating these advertisements 
and any similar violative materials and provide a plan of corrective 
action. In response, Purdue issued a corrected advertisement, which 
called attention to the warning letter and the cited violations and 
directed the reader to the prominently featured boxed warning and 
indication information for OxyContin.[Footnote 39] The FDA letter was 
one of only four warning letters issued to drug manufacturers during 
the first 8 months of 2003.[Footnote 40]

In addition, in follow-up discussions with Purdue officials on the 
January 2003 warning letter, FDA expressed concerns about some of the 
information on Purdue's "Partners Against Pain" Web site. The Web site 
appeared to suggest unapproved uses of OxyContin for postoperative pain 
that may have been inconsistent with OxyContin's labeling and lacked 
risk information about the drug. For example, one section of the Web 
site did not disclose that OxyContin is not indicated for pain in the 
immediate postoperative period--the first 12 to 24 hours following 
surgery--for patients not previously taking the drug, because its 
safety in this setting has not been established. The Web site also did 
not disclose that OxyContin is indicated for postoperative pain in 
patients already taking the drug or for use after the first 24 hours 
following surgery only if the pain is moderate to severe and expected 
to persist for an extended period of time. Purdue voluntarily removed 
all sections of the Web site that were of concern to FDA.

FDA has also sent enforcement letters to other manufacturers of 
controlled substances for marketing and promotion violations of the 
FD&C Act. For example, in 1996, FDA issued an untitled letter to Zeneca 
Pharmaceuticals, at the time the promoter of Kadian,[Footnote 41] for 
providing information about the drug to a health professional prior to 
its approval in the United States. Roxane Laboratories, the 
manufacturer of Oramorph SR, was issued four untitled letters between 
1993 and 1995 for making misleading and possibly false statements. 
Roxane used children in an advertisement even though Oramorph SR had 
not been evaluated in children, and a Roxane sales representative 
issued a promotional letter to a pharmacist that claimed, among other 
things, that Oramorph SR was superior to MS Contin in providing pain 
relief. FDA has sent no enforcement letters to Ligand Pharmaceuticals 
concerning Avinza.

Purdue Distributed an OxyContin Video without FDA's Review That Appears 
to Have Made Unsubstantiated Claims and Minimized Risks:

Beginning in 1998, Purdue, as part of its marketing and promotion of 
OxyContin, distributed 15,000 copies of an OxyContin video to 
physicians without submitting it to FDA for review. This video, 
entitled I Got My Life Back: Patients in Pain Tell Their Story, 
presented the pain relief experiences of various patients and the pain 
medications, including OxyContin, they had been prescribed. FDA 
regulations require pharmaceutical manufacturers to submit all 
promotional materials for approved prescription drug products to the 
agency at the time of their initial use. Because Purdue did not comply 
with this regulation, FDA did not have an opportunity to review the 
video to ensure that the information it contained was truthful, 
balanced, and accurately communicated. Purdue has acknowledged the 
oversight of not submitting the video to FDA for review. In February 
2001, Purdue submitted a second version of the video to FDA, which 
included information about the 160-milligram OxyContin tablet. FDA did 
not review this second version until October 2002, after we inquired 
about its content. FDA told us it found that the second version of the 
video appeared to make unsubstantiated claims regarding OxyContin's 
effect on patients' quality of life and ability to perform daily 
activities and minimized the risks associated with the drug.

The 1998 video used a physician spokesperson to describe patients with 
different pain syndromes and the limitations that each patient faced in 
his or her daily activities. Each patient's pain treatment was 
discussed, along with the dose amounts and brand names of the 
prescription drugs, including OxyContin, that either had been 
prescribed in the past or were being prescribed at that time. The 
physician in the videos also stated that opioid analgesics have been 
shown to cause addiction in less than 1 percent of patients--a fact 
that FDA has stated has not been substantiated. At the end of the 
video, the OxyContin label was scrolled for the viewer.

In 2000, Purdue submitted another promotional video to FDA entitled I 
Got My Life Back: A Two Year Follow up of Patients in Pain, and it 
submitted a second version of this video in 2001, which also included 
information on the 160-milligram OxyContin tablet. Purdue distributed 
12,000 copies of these videos to physicians. Both versions scrolled the 
OxyContin label at the end of the videos. FDA stated that it did not 
review either of these videos for enforcement purposes because of 
limited resources. Distribution of all four Purdue videos was 
discontinued by July 2001, in response to OxyContin's labeling changes, 
which required the company to modify all of its promotional materials, 
but copies of the videos that had already been distributed were not 
retrieved and destroyed.

FDA said that it receives numerous marketing and promotional materials 
for promoted prescription drugs and that while every effort is made to 
review the materials, it cannot guarantee that all materials are 
reviewed because of limited resources and competing priorities. FDA 
officials also stated that pharmaceutical companies do not always 
submit promotional materials as required by regulations and that in 
such instances FDA would not have a record of the promotional pieces.

Several Factors May Have Contributed to OxyContin Abuse and Diversion, 
but Relationship to Availability Cannot Be Assessed:

There are several factors that may have contributed to the abuse and 
diversion of OxyContin. OxyContin's formulation as a controlled-release 
opioid that is twice as potent as morphine may have made it an 
attractive target for abuse and diversion. In addition, the original 
label's safety warning advising patients not to crush the tablets 
because of the possible rapid release of a potentially toxic amount of 
oxycodone may have inadvertently alerted abusers to possible methods 
for misuse. Further, the rapid growth in OxyContin sales increased the 
drug's availability in the marketplace and may have contributed to 
opportunities to obtain the drug illicitly. The history of abuse and 
diversion of prescription drugs in some geographic areas, such as those 
within the Appalachian region, may have predisposed some states to 
problems with OxyContin. However, we could not assess the relationship 
between the growth in OxyContin prescriptions or increased availability 
with the drug's abuse and diversion because the data on abuse and 
diversion are not reliable, comprehensive, or timely.

OxyContin's Formulation May Have Made It an Inviting Drug for Abuse and 
Diversion:

While OxyContin's potency and controlled-release feature may have made 
the drug beneficial for the relief of moderate-to-severe pain over an 
extended period of time, DEA has stated that those attributes of its 
formulation have also made it an attractive target for abuse and 
diversion. According to recent studies, oxycodone, the active 
ingredient in OxyContin, is twice as potent as morphine.[Footnote 42] 
In addition, OxyContin's controlled-release feature allows a tablet to 
contain more active ingredient than other, non-controlled-release 
oxycodone-containing drugs.

One factor that may have contributed to the abuse and diversion of 
OxyContin was FDA's original decision to label the drug as having less 
abuse potential than other oxycodone products because of its 
controlled-release formulation. FDA officials said when OxyContin was 
approved the agency believed that the controlled-release formulation 
would result in less abuse potential because, when taken properly, the 
drug would be absorbed slowly, without an immediate rush or high. FDA 
officials acknowledged that the initial wording of OxyContin's label 
was "unfortunate" but was based on what was known about the product at 
that time.

FDA officials told us that abusers typically seek a drug that is 
intense and fast-acting. When OxyContin was approved, FDA did not 
recognize that if the drug is dissolved in water and injected its 
controlled-release characteristics could be disrupted, creating an 
immediate rush or high and thereby increasing the potential for misuse 
and abuse. DEA officials told us that OxyContin became a target for 
abusers and diverters because the tablet contained larger amounts of 
active ingredient and the controlled-release formulation was easy for 
abusers to compromise.

The safety warning on the OxyContin label may also have contributed to 
the drug's potential for abuse and diversion, by inadvertently 
providing abusers with information on how the drug could be misused. 
The label included the warning that the tablets should not be broken, 
chewed, or crushed because such action could result in the rapid 
release and absorption of a potentially toxic dose of oxycodone. FDA 
places similar safety warnings on other drugs to ensure that they are 
used properly. FDA officials stated that neither they nor other experts 
anticipated that crushing the controlled-release tablet and 
intravenously injecting or snorting the drug would become widespread 
and lead to a high level of abuse.

OxyContin's Wide Availability May Have Increased Opportunities for 
Illicit Use:

The large amount of OxyContin available in the marketplace may have 
increased opportunities for abuse and diversion. Both DEA and Purdue 
have stated that an increase in a drug's availability in the 
marketplace may be a factor that attracts interest by those who abuse 
and divert drugs. Following its market introduction in 1996, OxyContin 
sales and prescriptions grew rapidly through 2002. In 2001 and 2002 
combined, sales of OxyContin approached $3 billion, and over 14 million 
prescriptions for the drug were dispensed. (See table 2.) OxyContin 
also became the top-selling brand-name narcotic pain reliever in 2001 
and was ranked 15th on a list of the nation's top 50 prescription drugs 
by retail sales.[Footnote 43]

Table 2: Total OxyContin Sales and Prescriptions for 1996 through 2002 
with Percentage Increases from Year to Year:

Year: 1996; 
Sales: $44,790,000; 
Percentage increase: N/A; 
Number of prescriptions: 316,786; 
Percentage increase: N/A.

Year: 1997; 
Sales: 125,464,000; 
Percentage increase: 180; 
Number of prescriptions: 924,375; 
Percentage increase: 192.

Year: 1998; 
Sales: 286,486,000; 
Percentage increase: 128; 
Number of prescriptions: 1,910,944; 
Percentage increase: 107.

Year: 1999; 
Sales: 555,239,000; 
Percentage increase: 94; 
Number of prescriptions: 3,504,827; 
Percentage increase: 83.

Year: 2000; 
Sales: 981,643,000; 
Percentage increase: 77; 
Number of prescriptions: 5,932,981; 
Percentage increase: 69.

Year: 2001; 
Sales: 1,354,717,000; 
Percentage increase: 38; 
Number of prescriptions: 7,183,327; 
Percentage increase: 21.

Year: 2002; 
Sales: 1,536,816,000; 
Percentage increase: 13; 
Number of prescriptions: 7,234,204; 
Percentage increase: 7.

Sources: Purdue and IMS Health.

Legend: N/A = not applicable.

Note: GAO analysis of OxyContin sales and prescription data from Purdue 
and IMS Health, which includes data from all 50 states and the District 
of Columbia. Sales include combined retail and nonretail sales in 
drugstores, hospitals, and long-term-care facilities from the IMS 
Health U.S. National Sales database. Prescriptions include retail 
pharmacy, long-term-care, and mail-order prescriptions from IMS 
Health's National Prescriptions Audit.

[End of table]

History of Prescription Drug Abuse in Some States May Have Predisposed 
Them to Problems with OxyContin:

According to DEA, the abuse and diversion of OxyContin in some states 
may have reflected the geographic area's history of prescription drug 
abuse. The White House Office of National Drug Control Policy (ONDCP) 
designates geographic areas with illegal drug trade activities for 
allocation of federal resources to link local, state, and federal drug 
investigation and enforcement efforts. These areas, known as High-
Intensity Drug Trafficking Areas (HIDTA), are designated by ONDCP in 
consultation with the Attorney General, the Secretary of the Treasury, 
heads of drug control agencies, and governors in the states 
involved.[Footnote 44]

According to a 2001 HIDTA report,[Footnote 45] the Appalachian region, 
which encompasses parts of Kentucky, Tennessee, Virginia, and West 
Virginia, has been severely affected by prescription drug abuse, 
particularly pain relievers, including oxycodone, for many years. Three 
of the four states--Kentucky, Virginia, and West Virginia--were among 
the initial states to report OxyContin abuse and diversion. 
Historically, oxycodone, manufactured under brand names such as 
Percocet, Percodan, and Tylox, was among the most diverted prescription 
drugs in Appalachia. According to the report, OxyContin has become the 
drug of choice of abusers in several areas within the region. The 
report indicates that many areas of the Appalachian region are rural 
and poverty-stricken, and the profit potential resulting from the 
illicit sale of OxyContin may have contributed to its diversion and 
abuse. In some parts of Kentucky, a 20-milligram OxyContin tablet, 
which can be purchased by legitimate patients for about $2, can be sold 
illicitly for as much as $25. The potential to supplement their incomes 
can lure legitimate patients into selling some of their OxyContin to 
street dealers, according to the HIDTA report.

Limitations on Abuse and Diversion Data Prevent Assessment of the 
Relationship with OxyContin's Availability:

The databases DEA uses to track the abuse and diversion of controlled 
substances all have limitations that prevent an assessment of the 
relationship between the availability of OxyContin and areas where the 
drug is being abused or diverted. Specifically, these databases, which 
generally do not provide information on specific brand-name drugs such 
as OxyContin, are based on data gathered from limited sources in 
specific geographic areas and have a significant time lag. As a result, 
they do not provide reliable, complete, or timely information that 
could be used to identify abuse and diversion of a specific drug.

DEA officials told us that it is difficult to obtain reliable data on 
what controlled substances are being abused by individuals and diverted 
from pharmacies because available drug abuse and diversion tracking 
systems do not capture data on a specific brand-name product or 
indicate where a drug product is being abused and diverted on a state 
and local level. Because of the time lags in reporting information, the 
data reflect a delayed response to any emerging drug abuse and 
diversion problem. For example, the Drug Abuse Warning Network (DAWN) 
estimates national drug-related emergency department visits or deaths 
involving abused drugs using data collected by the Substance Abuse and 
Mental Health Services Administration (SAMHSA). The data are collected 
from hospital emergency departments in 21 metropolitan areas that have 
agreed to voluntarily report drug-abuse-related information from a 
sample of patient medical records, and from medical examiners in 42 
metropolitan areas.[Footnote 46] However, DAWN cannot make estimates 
for rural areas, where initial OxyContin abuse and diversion problems 
were reported to be most prevalent, nor does it usually provide drug-
product-specific information, and its data have a lag time of about 1 
year. DEA stated that development of enhanced data collection systems 
is needed to provide "credible, legally defensible evidence concerning 
drug abuse trends in America."[Footnote 47]

DEA relies primarily on reports from its field offices to determine 
where abuse and diversion are occurring. DEA officials stated that the 
initial areas that experienced OxyContin abuse and diversion problems 
included rural areas within 8 states--Alaska, Kentucky, Maine, 
Maryland, Ohio, Pennsylvania, Virginia, and West Virginia. In July 
2002, DEA told us that it learned that OxyContin abuse and diversion 
problems had spread into larger areas of the initial 8 states, as well 
as parts of 15 other states, to involve almost half of the 50 
states.[Footnote 48] According to DEA officials, while DEA field 
offices continue to report OxyContin as a drug of choice among abusers, 
OxyContin has not been and is not now considered the most highly abused 
and diverted prescription drug nationally.[Footnote 49] OxyContin is 
the most abused single-entity prescription product according to those 
DEA state and divisional offices that report OxyContin abuse.

Federal and State Agencies and Purdue Have Taken Actions to Prevent 
Abuse and Diversion of OxyContin:

Since becoming aware of reports of abuse and diversion of OxyContin, 
federal and state agencies and Purdue have taken actions intended to 
address these problems. To protect the public health, FDA has 
strengthened OxyContin label warnings and requested that Purdue develop 
and implement an OxyContin risk management plan. In addition, DEA has 
stepped up law enforcement actions to prevent abuse and diversion of 
OxyContin. State Medicaid fraud control units have also attempted to 
identify those involved in the abuse and diversion of OxyContin. Purdue 
has initiated drug abuse and diversion education programs, taken 
disciplinary actions against sales representatives who improperly 
promote OxyContin, and referred physicians who were suspected of 
improperly prescribing OxyContin to the appropriate authorities. 
However, until fall 2002 Purdue did not analyze its comprehensive 
physician prescribing reports, which it routinely uses in marketing and 
promoting OxyContin, and other indicators to identify possible 
physician abuse and diversion.

Reports of Abuse and Diversion Led to Label Changes and Other Actions 
by FDA:

Reports of abuse and diversion of OxyContin that were associated with 
an increasing incidence of addiction, overdose, and death prompted FDA 
to revise the drug's label and take other actions to protect the public 
health. In July 2001, FDA reevaluated OxyContin's label and made 
several changes in an effort to strengthen the "Warnings" section of 
the label. FDA added a subsection--"Misuse, Abuse, and Diversion of 
Opioids"--to stress that physicians and pharmacists should be alert to 
the risk of misuse, abuse, and diversion when prescribing or dispensing 
OxyContin. FDA also added a black box warning--the highest level of 
warning FDA can place on an approved drug product. FDA highlighted the 
language from the original 1995 label--stating that OxyContin is a 
schedule II controlled substance with an abuse liability similar to 
morphine--by moving it into the black box. Also, while the original 
label suggested that taking broken, chewed, or crushed OxyContin 
tablets "could lead to the rapid release and absorption of a 
potentially toxic dose of oxycodone," a more strongly worded warning in 
the black box stated that taking the drug in this manner "leads to 
rapid release and absorption of a potentially fatal dose of oxycodone" 
(emphasis added). (See table 3.) In addition to the black box warning, 
FDA also changed the language in the original label that described the 
incidence of addiction inadvertently induced by physician prescribing 
as rare if opioids are legitimately used in the management of pain. The 
revised label stated that data are not available to "establish the true 
incidence of addiction in chronic patients.":

Table 3: Selected Language Approved by FDA in Warning Sections of 
OxyContin Labels, 1995 and 2001:

Warning label in 1995: "Warning: OxyContin Tablets are to be swallowed 
whole, and are not to be broken, chewed, or crushed. Taking broken, 
chewed, or crushed OxyContin Tablets could lead to the rapid release 
and absorption of a potentially toxic dose of oxycodone."; Black box 
warning in 2001: "Warning: OxyContin is an opioid agonist and a 
Schedule II controlled substance with an abuse liability similar to 
morphine."; "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." (emphasis added).

Source: FDA-approved label for Purdue's OxyContin.

[End of table]

As mentioned earlier, the indication described in the original label 
was also revised to clarify the appropriate time period for which 
OxyContin should be prescribed for patients experiencing moderate-to-
severe pain. The language in the 1995 label was changed from "where use 
of an opioid analgesic is appropriate for more than a few days" to 
"when a continuous, around-the-clock analgesic is needed for an 
extended period of time." (See table 4.) A summary of changes made by 
FDA to the original OxyContin label is given in appendix II.

Table 4: Selected Language Approved by FDA in the Indication Sections 
of OxyContin Labels, 1995 and 2001:

Indication in 1995: "OxyContin Tablets are a controlled-release oral 
formulation of oxycodone hydrochloride indicated for the management of 
moderate-to-severe pain where use of an opioid analgesic is appropriate 
for more than a few days."; Black box indication change in 2001: 
"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." (emphasis added).

Source: FDA-approved label for Purdue's OxyContin.

[End of table]

Beginning in early 2001, FDA collaborated with Purdue to develop and 
implement a risk management plan to help identify and prevent abuse and 
diversion of OxyContin. As a part of the risk management plan in 
connection with the labeling changes, Purdue was asked by FDA to revise 
all of its promotional materials for OxyContin to reflect the labeling 
changes. In August 2001, FDA sent a letter to Purdue stating that all 
future promotional materials for OxyContin should prominently disclose 
the information contained in the boxed warning; the new warnings that 
address misuse, abuse, diversion, and addiction; and the new 
precautions and revised indication for OxyContin. Purdue agreed to 
comply with this request.

FDA officials told us that it is standard procedure to contact a drug 
manufacturer when the agency becomes aware of reports of abuse and 
diversion of a drug product so that FDA and the drug manufacturer can 
tailor a specific response to the problem. While FDA's experience with 
risk management plans is relatively new, agency officials told us that 
OxyContin provided the opportunity to explore the use of the plans to 
help identify abuse and diversion problems. FDA is currently making 
decisions about whether risk management plans will be requested for 
selected opioid products. Also, in September 2003, FDA's Anesthetic and 
Life Support Drugs Advisory Committee held a public hearing to discuss 
its current review of proposed risk management plans for opioid 
analgesic drug products to develop strategies for providing patients 
with access to pain treatment while limiting the abuse and diversion of 
these products.

FDA has also taken other actions to address the abuse and diversion of 
OxyContin. It put information on its Web site for patients regarding 
the appropriate use of OxyContin.[Footnote 50] FDA worked with Purdue 
to develop "Dear Health Care Professional" letters, which the company 
distributed widely to health care professionals to alert them that the 
package insert had been revised to clarify the indication and 
strengthen the warnings related to misuse, abuse, and diversion. FDA 
also has worked with DEA, SAMHSA, the National Institute on Drug Abuse, 
ONDCP, and the Centers for Disease Control and Prevention to share 
information and insights on the problem of abuse and diversion of 
OxyContin.

DEA Developed an Action Plan to Deter OxyContin Abuse and Diversion:

In April 2001, DEA developed a national action plan to deter abuse and 
diversion of OxyContin. According to DEA officials, this marked the 
first time the agency had targeted a specific brand-name product for 
monitoring because of the level and frequency of abuse and diversion 
associated with the drug. Key components of the action plan include 
coordinating enforcement and intelligence operations with other law 
enforcement agencies to target people and organizations involved in 
abuse and diversion of OxyContin, pursuing regulatory and 
administrative action to limit abusers' access to OxyContin, and 
building national outreach efforts to educate the public on the dangers 
related to the abuse and diversion of OxyContin. DEA has also set 
Purdue's procurement quota for oxycodone at levels lower than the 
levels requested by Purdue.

DEA has increased enforcement efforts to prevent abuse and diversion of 
OxyContin. From fiscal year 1996 through fiscal year 2002, DEA 
initiated 313 investigations involving OxyContin, resulting in 401 
arrests. Most of the investigations and arrests occurred after the 
initiation of the action plan. Since the plan was enacted, DEA 
initiated 257 investigations and made 302 arrests in fiscal years 2001 
and 2002. Among those arrested were several physicians and pharmacists. 
Fifteen health care professionals either voluntarily surrendered their 
controlled substance registrations or were immediately suspended from 
registration by DEA. In addition, DEA reported that $1,077,500 in fines 
was assessed and $742,678 in cash was seized by law enforcement 
agencies in OxyContin-related cases in 2001 and 2002.

Among several regulatory and administrative actions taken to limit 
abusers' access to OxyContin and controlled substances, DEA's Office of 
Diversion Control, in collaboration with the Department of Justice's 
Office of Justice Programs, Bureau of Justice Assistance, provides 
grants to states for the establishment of prescription drug monitoring 
programs. The conference committee report for the fiscal year 2002 
appropriation to the Department of Justice directed the Office of 
Justice Programs to make a $2 million grant in support of the Harold 
Rogers Prescription Drug Monitoring Program, which enhances the 
capacity of regulatory and law enforcement agencies to collect and 
analyze controlled substance prescription data. The program provided 
grants to establish new monitoring programs in Ohio, Pennsylvania, 
Virginia, and West Virginia. California, Kentucky, Massachusetts, 
Nevada, and Utah also received grants to enhance existing monitoring 
programs.

DEA has also attempted to raise national awareness of the dangers 
associated with abuse and diversion of OxyContin. In October 2001 DEA 
joined 21 national pain and health organizations in issuing a consensus 
statement calling for a balanced policy on prescription medication use. 
According to the statement, such a policy would acknowledge that health 
care professionals and DEA share responsibility for ensuring that 
prescription medications, such as OxyContin, are available to patients 
who need them and for preventing these drugs from becoming a source of 
abuse and diversion. DEA and the health organizations also called for a 
renewed focus on educating health professionals, law enforcement, and 
the public about the appropriate use of opioid pain medications in 
order to promote responsible prescribing and limit instances of abuse 
and diversion. DEA is also working with FDA to encourage state medical 
boards to require, as a condition of their state licensing, that 
physicians obtain continuing medical education on pain management.

When OxyContin was first introduced to the market in 1996, DEA granted 
Purdue's initial procurement quota request for oxycodone. According to 
DEA, increases in the quota were granted for the first several years. 
Subsequently, concern over the dramatic increases in sales caused DEA 
to request additional information to support Purdue's requests to 
increase the quota. In the last several years, DEA has taken the 
additional step of lowering the procurement quota requested by Purdue 
for the manufacture of OxyContin as a means for addressing abuse and 
diversion. However, DEA has cited the difficulty of determining an 
appropriate level while ensuring that adequate quantities were 
available for legitimate medical use, as there are no direct measures 
available to establish legitimate medical need.

State Agencies Have Responded to Reports of OxyContin Abuse and 
Diversion:

State Medicaid fraud control units and medical licensure boards have 
taken action in response to reports of abuse and diversion of 
OxyContin. State Medicaid fraud control units have conducted 
investigations of abuse and diversion of OxyContin, but generally do 
not maintain precise data on the number of investigations and 
enforcement actions completed. Although complete information was not 
available from directors of state Medicaid fraud control units in 
Kentucky, Maryland, Pennsylvania, Virginia, and West Virginia with whom 
we spoke, each of those directors told us that abuse and diversion of 
OxyContin is a problem in his or her state. The directors told us that 
they had investigated cases that involved physicians or individuals who 
had either been indicted or prosecuted for writing medically 
unnecessary OxyContin prescriptions in exchange for cash or sexual 
relationships.

State medical licensure boards have also responded to complaints about 
physicians who were suspected of abuse and diversion of controlled 
substances, but like the Medicaid fraud control units, the boards 
generally do not maintain data on the number of investigations that 
involved OxyContin. Representatives of state boards of medicine in 
Kentucky, Pennsylvania, Virginia, and West Virginia told us that they 
have received complaints from various sources, such as government 
agencies, health care professionals, and anonymous tipsters, about 
physicians suspected of abuse and diversion of controlled substances. 
However, each of the four representatives stated that his or her board 
does not track the complaints by specific drug type and consequently 
cannot determine whether the complaints received allege physicians' 
misuse of OxyContin. Each of the four representatives also told us that 
his or her medical licensure board has adopted or strengthened 
guidelines or regulations for physicians on prescribing, administering, 
and dispensing controlled substances in the treatment of chronic pain. 
For example, in March 2001, the Kentucky Board of Medical Licensure 
adopted guidelines to clarify the board's position on the use of 
controlled substances for nonterminal/nonmalignant chronic 
pain.[Footnote 51] The boards of medicine in Pennsylvania, Virginia, 
and West Virginia each have guidelines for the appropriate use of 
controlled substances that are similar to those adopted by Kentucky.

Purdue Is Implementing a Risk Management Plan for OxyContin:

In response to concerns about abuse and diversion of OxyContin, in 
April 2001 FDA and Purdue began to discuss the development of a risk 
management plan to help detect and prevent abuse and diversion of 
OxyContin. Purdue submitted its risk management plan to FDA for review 
in August 2001.[Footnote 52] The plan includes some actions that Purdue 
proposed to take, as well as others that it has already taken. Purdue's 
risk management plan includes actions such as strengthening the safety 
warnings on OxyContin's label for professionals and patients, training 
Purdue's sales force on the revised label, conducting comprehensive 
education programs for health care professionals, and developing a 
database for identifying and monitoring abuse and diversion of 
OxyContin.

Under the risk management plan, OxyContin's label was strengthened, 
effective in July 2001, by revising the physician prescribing 
information and adding a black box warning to call attention to 
OxyContin's potential for misuse, abuse, and diversion. (See app. II.) 
Purdue trained its sales force on the specifics of the revised label 
and provided sales representatives with updated information on the 
appropriate use of opioid analgesics, legal guidelines associated with 
promotion of its products, and their responsibility and role in 
reporting adverse events. Purdue also reiterated to its sales 
representatives that failure to promote products according to the 
approved label, promotional materials, and applicable FDA standards 
would result in disciplinary action by the company. According to 
Purdue, from April 2001 through May 2003 at least 10 Purdue employees 
were disciplined for using unapproved materials in promoting OxyContin. 
Disciplinary actions included warning letters, suspension without pay, 
and termination.

Purdue also has provided education programs for health care 
professionals and the public under its risk management plan. For 
example, in 2001 Purdue supported seminars that examined ways health 
care professionals can help prevent abuse and diversion of opioids. 
Purdue worked with DEA and other law enforcement agencies to develop 
and implement antidiversion educational programs. In 2002, Purdue also 
launched the Web site painfullyobvious.com to educate teenagers, 
parents, law enforcement officers, and discussion leaders about the 
dangers of prescription drug abuse.

Because reliable data on the abuse and diversion of controlled 
substance drugs are not available, Purdue developed the Researched 
Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System, 
as part of its risk management plan, to study the nature and extent of 
abuse of OxyContin and other schedule II and III prescription 
medications and to implement interventions to reduce abuse and 
diversion.[Footnote 53] According to Purdue, RADARS collects and 
computes abuse, diversion, and addiction rates for certain drugs based 
on population and determines national and local trends.

Since the launch of OxyContin, Purdue has provided its sales force with 
considerable information to help target physicians and prioritize sales 
contacts within a sales territory. Sales representatives routinely 
receive daily, weekly, monthly, and quarterly physician prescribing 
reports based on IMS Health data that specify the physicians who have 
written prescriptions for OxyContin and other opioid analgesics, and 
the number of prescriptions written. Although this information has 
always been available for use by Purdue and its sales representatives, 
it was not until fall 2002 that Purdue directed its sales 
representatives to begin using 11 indicators to identify possible abuse 
and diversion and to report the incidents to Purdue's General Counsel's 
Office for investigation. Among the possible indicators are a sudden 
unexplained change in a physician's prescribing patterns that is not 
accounted for by changes in patient numbers, information from credible 
sources such as a pharmacist that a physician or his or her patients 
are diverting medications, or a physician who writes a large number of 
prescriptions for patients who pay with cash. As of September 2003, 
Purdue--through its own investigations--had identified 39 physicians 
and other health care professionals who were referred to legal, 
medical, or regulatory authorities for further action. Most of the 39 
referrals stemmed from reports by Purdue's sales force.

Other actions included in the plan that were taken by Purdue prior to 
submission of its risk management plan include discontinuance of the 
160-milligram tablet of OxyContin to reduce the risk of overdose from 
this dosage strength, the development of unique markings for OxyContin 
tablets intended for distribution in Mexico and Canada to assist law 
enforcement in identifying OxyContin illegally smuggled into the United 
States, and the distribution of free tamper-resistant prescription pads 
designed to prevent altering or copying of the prescription. Purdue 
also implemented a program in 2001 to attempt to predict "hot spots" 
where OxyContin abuse and diversion were likely to occur, but 
discontinued the program in 2002 when Purdue concluded that nearly two-
thirds of the counties identified had no abuse and diversion.

Conclusions:

At present, both federal agencies and the states have responsibilities 
involving prescription drugs and their abuse and diversion. FDA is 
responsible for approving new drugs and ensuring that the materials 
drug companies use to market and promote these drugs are truthful, 
balanced, and accurate. However, FDA examines these promotional 
materials only after they have been used in the marketplace because the 
FD&C Act generally does not give FDA authority to review these 
materials before the drug companies use them. Moreover, the FD&C Act 
provisions governing drug approval and promotional materials make no 
distinction between controlled substances, such as OxyContin, and other 
prescription drugs. DEA is responsible for registering handlers of 
controlled substances, approving production quotas and monitoring 
distribution of controlled substances to the retail level. It is the 
states, however, that are responsible for overseeing the practice of 
medicine and pharmacy where drugs are prescribed and dispensed. Some 
states have established prescription drug monitoring programs to help 
them detect and deter abuse and diversion. However, these programs 
exist in only 15 states and most do not proactively analyze 
prescription data to identify individuals, physicians, or pharmacies 
that have unusual use, prescribing, or dispensing patterns that may 
suggest potential drug diversion or abuse.

The significant growth in the use of OxyContin to treat patients 
suffering from chronic pain has been accompanied by widespread reports 
of abuse and diversion that have in some cases led to deaths. The 
problem of abuse and diversion has highlighted shortcomings at the time 
of approval in the labeling of schedule II controlled substances, such 
as OxyContin, and in the plans in place to detect misuse, as well as in 
the infrastructure for detecting and preventing the abuse and diversion 
of schedule II controlled substances already on the market.

Addressing abuse and diversion problems requires the collaborative 
efforts of pharmaceutical manufacturers; the federal and state agencies 
that oversee the approval and use of prescription drugs, particularly 
controlled substances; the health care providers who prescribe and 
dispense them; and law enforcement. After the problems with OxyContin 
began to surface, FDA and Purdue collaborated on a risk management plan 
to help detect and prevent abuse and diversion. Although risk 
management plans were not in use when OxyContin was approved, they are 
now an optional feature of new drug applications. FDA plans to complete 
its guidance to the pharmaceutical industry on risk management plans by 
September 30, 2004. The development of this guidance, coupled with 
FDA's current review of proposed risk management plans for modified-
release opioid analgesics, provides an opportunity to help ensure that 
manufacturers include a strategy to monitor the use of these drugs and 
to identify potential problems with abuse and diversion.

Recommendation for Executive Action:

To improve efforts to prevent or identify the abuse and diversion of 
schedule II controlled substances, we recommend that the Commissioner 
of Food and Drugs ensure that FDA's risk management plan guidance 
encourages pharmaceutical manufacturers that submit new drug 
applications for these substances to include plans that contain a 
strategy for monitoring the use of these drugs and identifying 
potential abuse and diversion problems.

Agency and Purdue Comments and Our Evaluation:

We provided a draft of this report to FDA, DEA, and Purdue, the 
manufacturer of OxyContin, for their review. FDA and DEA provided 
written comments. (See apps. IV and V.) Purdue's representatives 
provided oral comments.

FDA said that it agreed with our recommendation that its risk 
management plan guidance should encourage all pharmaceutical 
manufacturers submitting new drug applications for schedule II 
controlled substances to include strategies to address abuse and 
diversion concerns. FDA stated that the agency is working on the risk 
management plan guidance. FDA also noted that the FD&C Act makes no 
distinction between controlled substances and other prescription drugs 
in its provisions regulating promotion, but that as a matter of general 
policy, the agency more closely scrutinizes promotion of drugs with 
more serious risk profiles. However, FDA does not have written guidance 
that specifies that promotional materials for controlled substances 
receive priority or special attention over similar materials for other 
prescription drugs. Furthermore, our finding that FDA did not review 
any of the OxyContin promotional videos provided by Purdue until we 
brought them to the agency's attention raises questions about whether 
FDA provides extra attention to promotional materials for controlled 
substances that by definition have a high potential for abuse and may 
lead to severe psychological or physical dependence. FDA recommended 
that we clarify our description of the content of the warning letter 
issued to Purdue and provide additional information describing the 
extent of the corrective action taken by Purdue. FDA also recommended 
noting in the report that part of the risk management plan in 
connection with the 2001 labeling changes was a requirement that all 
OxyContin promotional materials be revised to reflect the labeling 
changes and all future materials prominently disclose this information. 
Finally, FDA noted that the promotional videos discussed in the report 
were submitted by Purdue prior to the labeling change and discontinued 
as a result of the labeling change. As we note in the report, Purdue 
acknowledged that all the promotional videos were not submitted to FDA 
at the time they were distributed. Moreover, although Purdue told us 
that these videos were no longer distributed after the label change, 
those videos that had been distributed were not collected and 
destroyed. We revised the report to reflect FDA's general comments. FDA 
also provided technical comments that we incorporated where 
appropriate.

In its written comments, DEA agreed that the data on abuse and 
diversion are not reliable, comprehensive, or timely, as we reported. 
DEA reiterated its previous statement that Purdue's aggressive 
marketing of OxyContin fueled demand for the drug and exacerbated the 
drug's abuse and diversion. DEA also stated that Purdue minimized the 
abuse risk associated with OxyContin. We agree with DEA that Purdue 
conducted an extensive campaign to market and promote OxyContin using 
an expanded sales force and multiple promotional approaches to 
encourage physicians, including primary care specialists, to prescribe 
OxyContin as an initial opioid treatment for noncancer pain, and that 
these efforts may have contributed to the problems with abuse and 
diversion by increasing the availability of the drug in the 
marketplace. However, we also noted that other factors may have 
contributed to these problems. We also agree that Purdue marketed 
OxyContin as having a low abuse liability, but we noted that this was 
based on information in the original label approved by FDA. DEA also 
acknowledged that the lack of a real measure of legitimate medical need 
for a specific product (OxyContin), substance (oxycodone), or even a 
class of substances (controlled release opioid analgesics) makes it 
difficult to limit manufacturing as a means of deterring abuse and 
diversion. DEA also noted that it is essential that risk management 
plans be put in place prior to the introduction of controlled 
substances into the marketplace, consistent with our recommendation. We 
revised the report to provide some additional detail on problems 
associated with OxyContin and Purdue's marketing efforts. DEA provided 
some technical comments on the draft report that we incorporated where 
appropriate.

Purdue representatives provided oral comments on a draft of this 
report. In general, they thought the report was fair and balanced; 
however, they offered both general and technical comments. 
Specifically, Purdue stated that the report should add the media as a 
factor contributing to the abuse and diversion of OxyContin because 
media stories provided the public with information on how to "get high" 
from using OxyContin incorrectly. Our report notes that the safety 
warning on the original label may have inadvertently alerted abusers to 
a possible method for misusing the drug. However, we note that the 
original label was publicly available from FDA once OxyContin was 
approved for marketing. Purdue also suggested that we include 
Duragesic, also a schedule II opioid analgesic, as a fourth comparable 
drug to OxyContin. The three comparable drugs we used in the report 
were chosen in consultation with FDA as comparable opioid analgesics to 
OxyContin, because they were time-released, morphine-based schedule II 
drugs formulated as tablets like OxyContin. In contrast, Duragesic, 
which contains the opioid analgesic fentanyl and provides pain relief 
over a 72-hour period, is formulated as a skin patch to be worn rather 
than as a tablet. Purdue representatives also provided technical 
comments that were incorporated where appropriate.

We also provided sections of this draft report to the manufacturers of 
three comparative drugs we examined. Two of the three companies with a 
drug product used as a comparable drug to OxyContin reviewed the 
portions of the draft report concerning their own product, and provided 
technical comments, which were incorporated where appropriate. The 
third company did not respond to our request for comments.

As agreed with your offices, unless you publicly announce this report's 
contents earlier, we plan no further distribution until 30 days after 
its issue date. At that time, we will send copies of this report to the 
Commissioner of Food and Drugs, the Administrator of the Drug 
Enforcement Administration, Purdue, and the other pharmaceutical 
companies whose drugs we examined. We will also make copies available 
to others upon request. In addition, the report will be available at no 
charge on the GAO Web site at http://www.gao.gov.

If you or your staffs have any questions about this report, please call 
me at (202) 512-7119 or John Hansen at (202) 512-7105. Major 
contributors to this report were George Bogart, Darryl Joyce, Roseanne 
Price, and Opal Winebrenner.

Marcia Crosse: 
Director, Health Care--Public Health and Military Health Care Issues:

Signed by Marcia Crosse: 

[End of section]

Appendix I: Scope and Methodology:

To identify the strategies and approaches used by Purdue Pharma L.P. 
(Purdue) to market and promote OxyContin, we interviewed Purdue 
officials and analyzed company documents and data. Specifically, we 
interviewed Purdue officials concerning its marketing and promotional 
strategies for OxyContin, including its targeting of physicians with 
specific specialties and its sales compensation plan to provide sales 
representatives with incentives for the drug's sales. We also 
interviewed selected Purdue sales representatives who had high and 
midrange sales during 2001 from Kentucky, Pennsylvania, Virginia, and 
West Virginia--four states that were initially identified by the Drug 
Enforcement Agency (DEA) as having a high incidence of OxyContin drug 
abuse and diversion--and from California, Massachusetts, and New 
Jersey--three states that DEA did not initially identify as having 
problems with OxyContin. We asked the sales representatives about their 
training, promotional strategies and activities, and targeting of 
physicians. We also interviewed physicians who were among the highest 
prescribers of OxyContin regarding their experiences with Purdue sales 
representatives, including the strategies used to promote OxyContin, as 
well as their experiences with sales representatives of manufacturers 
of other opioid analgesics. We reviewed Purdue's quarterly action plans 
for marketing and promoting OxyContin for 1996 through 2003, Purdue's 
sales representative training materials, and materials from ongoing 
OxyContin-related litigation. To obtain information on how Purdue's 
marketing and promotion of OxyContin compared to that of other 
companies, we identified, in consultation with the Food and Drug 
Administration (FDA), three opioid analgesics that were similar to 
OxyContin. The three drugs--Avinza, Kadian, and Oramorph SR--are all 
time-released, morphine-based analgesics that are classified as 
schedule II controlled substances. We examined the promotional 
materials each drug's manufacturer submitted to FDA and any actions FDA 
had taken against the manufacturers related to how the drugs were 
marketed or promoted. We also interviewed company officials about how 
they marketed and promoted their respective drugs. Because of their 
concerns about proprietary information, the three companies did not 
provide us with the same level of detail about their drugs' marketing 
and promotion as did Purdue.

To examine factors that contributed to the abuse and diversion of 
OxyContin, we reviewed DEA abuse and diversion data as part of an 
effort to compare them with DEA's OxyContin state distribution data and 
with IMS Health data on the rates of OxyContin sales and prescription 
dispensing to determine if they occurred in similar geographic areas. 
We also analyzed the distribution of Purdue sales representatives by 
state and compared them with the availability of OxyContin and abuse 
and diversion data to determine whether states with high rates of 
OxyContin sales and prescription dispensing and abuse and diversion 
problems had more sales representatives per capita than other states. 
However, limitations in the abuse and diversion data prevent an 
assessment of the relationship between the availability of OxyContin 
and areas where the drug was abused and diverted. We also reviewed the 
High Intensity Drug Trafficking Area (HIDTA) reports on states with 
histories of illegal drug activities. We interviewed DEA and FDA 
officials, physicians who prescribed OxyContin, officials from 
physician licensing boards in selected states, officials from national 
health practitioner groups, and company officials and sales 
representatives about why OxyContin abuse and diversion have occurred.

To determine the efforts federal and state agencies and Purdue have 
made to identify and prevent abuse and diversion of controlled 
substances such as OxyContin, we interviewed FDA officials and analyzed 
information from FDA regarding the marketing and promotion of 
controlled substances, specifically OxyContin; FDA's decision to 
approve the original label for OxyContin; and FDA's subsequent decision 
to revise OxyContin's labeling, as well as FDA's role in monitoring 
OxyContin's marketing and advertising activities. We also interviewed 
DEA officials about the agency's efforts to identify and prevent abuse 
and diversion, including its national action plan for OxyContin, and 
how it determines the prevalence of OxyContin abuse and diversion 
nationally. We also interviewed officials from national practitioner 
associations, Medicaid fraud control units, and physician licensing 
boards in states with initial reports of abuse and diversion--Kentucky, 
Maryland, Pennsylvania, Virginia, and West Virginia--regarding 
concerns they had about the abuse and diversion of OxyContin. We 
reviewed Purdue's OxyContin risk management plan submissions to FDA 
from 2001 through 2003 to identify actions taken by Purdue to address 
abuse and diversion of OxyContin.

[End of section]

Appendix II: Summary of FDA Changes to the Original Approved OxyContin 
Label:

Table 5 provides a description of the changes made by FDA to sections 
of the original OxyContin approved label from June 1996 through July 
2001. These changes included a black box warning, the strongest warning 
an FDA-approved drug can carry, and specifically addressed areas of 
concern related to the opioid characteristics of oxycodone and its risk 
of abuse and diversion.

Table 5: FDA Changes to the Original OxyContin Label Made from June 
1996 through July 2001:

Summary of FDA changes to original OxyContin label in 2001: Black box 
warning was added to stress the opioid nature of oxycodone and risks 
for abuse and diversion of the drug; 

Language in OxyContin label approved in 2001: 

"WARNING: OxyContin is an opioid agonist and a Schedule II controlled 
substance with an abuse liability similar to morphine; 
Oxycodone can be abused in a manner similar to other opioid agonists, 
legal or illicit. This should be considered when prescribing or 
dispensing OxyContin in situations where the physician or pharmacist 
is concerned about an increased risk of misuse, abuse, or diversion; 
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; 
OxyContin Tablets are NOT intended for use as a prn analgesic. 
OxyContin 80 mg and 160 mg Tablets ARE FOR USE IN OPIOID-TOLERANT 
PATIENTS ONLY. These tablet strengths may cause fatal respiratory 
depression when administered to patients not previously exposed to 
opioids. 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.".

Summary of FDA changes to original OxyContin label in 2001: Clinical 
pharmacology; 
--Provides a pharmacological description of oxycodone as a pure opioid 
agonist whose principal action is analgesia; 
-- Identifies other members of the opioid agonist class, such as 
morphine, hydromorphone, fentanyl, and hydrocodone; 
--Describes the pharmacological properties of opioids in general 
(anxiolysis, euphoria, feelings of relaxation, respiratory depression, 
constipation, miosis, cough suppression, and analgesia); 
--Describes respiratory depression as one of the most serious side 
effects of opioids that could lead to overdose or death; 

Language in OxyContin label approved in 2001: 

"CLINICAL PHARMACOLOGY; 
Oxycodone is a pure agonist opioid whose principal therapeutic action 
is analgesia. Other members of the class known as opioid agonists 
include substances such as morphine, hydromorphone, fentanyl, codeine, 
and hydrocodone. Pharmacological effects of opioid agonists include 
anxiolysis, euphoria, feelings of relaxation, respiratory depression, 
constipation, miosis, and cough suppression, as well as analgesia. 
Like all pure opioid agonist analgesics, with increasing doses there 
is increasing analgesia, unlike with mixed agonist/antagonists or non-
opioid analgesics, where there is a limit to the analgesic effect with 
increasing doses. With pure opioid agonist analgesics, there is no 
defined maximum dose; 
the ceiling to analgesic effectiveness is imposed only by side 
effects, the more serious of which may include somnolence and 
respiratory depression.".

Summary of FDA changes to original OxyContin label in 2001: Misuse, 
abuse, and diversion of opioids; 
A subsection on misuse, abuse and diversion was added to the WARNINGS 
section of the label; 
-- Characterizes oxycodone as an opioid agonist of the morphine-type 
and stresses that opioid agonists are sought by drug abusers and 
people with addiction disorders and are subject to diversion; 
--Makes clear that oxycodone can be abused in a manner similar to 
other opioid agonists, legal or illicit, and that physicians and 
pharmacists should be aware of and alert to risk of misuse, abuse, and 
diversion when prescribing or dispensing oxycodone; 
--Modifies original label statement that iatrogenic addiction 
(addiction induced inadvertently by a physician or a physician's 
treatment) is rare if opioids were legitimately used in the management 
of pain to state that data are not available to establish the true 
incidence of addiction in chronic patients; 

Language in OxyContin label approved in 2001: 

"Misuse, Abuse and Diversion of Opioids; 
Oxycodone is an opioid agonist of the morphine-type. Such drugs are 
sought by drug abusers and people with addiction disorders and are 
subject to criminal diversion; 
Oxycodone can be abused in a manner similar to other opioid agonists, 
legal or illicit. This should be considered when prescribing or 
dispensing OxyContin in situations where the physician or pharmacist 
is concerned about an increased risk of misuse, abuse, or diversion; 
OxyContin has been reported as being abused by crushing, chewing, 
snorting, or injecting the dissolved product. These practices will 
result in the uncontrolled delivery of the opioid and pose a 
significant risk to the abuser that could result in overdose and death 
(see WARNINGS and DRUG ABUSE AND ADDICTION); 
Concerns about abuse, addiction, and diversion should not prevent the 
proper management of pain. The development of addiction to opioid 
analgesics in properly managed patients with pain has been reported to 
be rare. However, data are not available to establish the true 
incidence of addiction in chronic pain patients; 
Healthcare professionals should contact their State Professional 
Licensing Board, or State Controlled Substances Authority for 
information on how to prevent and detect abuse of this product.".

Summary of FDA changes to original OxyContin label in 2001: Drug abuse 
and addiction; 
--Emphasizes that the abuse potential of oxycodone is equivalent to 
that of morphine; 
--Describes the controlled status of OxyContin and emphasizes that, 
like morphine and other opioids used in analgesia, oxycodone can be 
abused and is subject to criminal diversion; 
--Stresses proper prescribing practices, dispensing, and storage; 
--Deletes statement that delayed absorption of OxyContin was believed 
to reduce the abuse liability of the drug; 
--Stresses the risks associated with parenteral injection of OxyContin 
and reiterates the original label's description of drug addiction and 
"drug-seeking" behaviors commonly in addicts and abusers; 

Language in OxyContin label approved in 2001: 

"DRUG ABUSE AND ADDICTION; 
OxyContin is a mu-agonist with an abuse liability similar to morphine 
and is a Schedule II controlled substance. Oxycodone, like morphine 
and other opioids used in analgesia, can be abused and is subject to 
criminal diversion; 
Drug addiction is characterized by compulsive use, use for non-medical 
purposes, and continued use despite harm or risk of harm. Drug 
addiction is a treatable disease, utilizing a multi-disciplinary 
approach, but relapse is common; 
"Drug-seeking" behavior is very common in addicts and drug abusers. 
Drug-seeking tactics include emergency calls or visits near the end of 
office hours, refusal to undergo appropriate examination, testing or 
referral, repeated "loss" of prescriptions, tampering with 
prescriptions, and reluctance to provide prior medical records or 
contact information for other treating physician(s). "Doctor shopping" 
to obtain additional prescriptions is common among drug abusers and
 people suffering from untreated addiction; 
Abuse and addiction are separate and distinct from physical dependence 
and tolerance. Physicians should be aware that addiction may not be 
accompanied by concurrent tolerance and symptoms of physical 
dependence in all addicts. In addition, abuse of opioids can occur in 
the absence of true addiction and is characterized by misuse for non-
medical purposes, often in combination with other psychoactive 
substances. OxyContin, like other opioids, has been diverted for non-
medical use. Careful record keeping of prescribing information, 
including quantity, frequency, and renewal requests is strongly 
advised; 
Proper assessment of the patient, proper prescribing practices, 
periodic reevaluation of therapy, and proper dispensing and storage 
are appropriate measures that help to limit abuse of opioid drugs; 
OxyContin consists of a dual-polymer matrix, intended for oral use 
only. Abuse of the crushed tablet poses a hazard of overdose and 
death. This risk is increased with concurrent abuse of alcohol and 
other substances. With parenteral abuse, the tablet excipients, 
especially talc, can be expected to result in local tissue necrosis, 
infection, pulmonary granulomas, and increased risk of enocarditis and 
valvular heart injury. Parenteral drug abuse is commonly associated 
with transmission of infectious disease such as hepatitis and HIV.".

Summary of FDA changes to original OxyContin label in 2001: Safety and 
handling; 
--Emphasizes the controlled status of OxyContin; 
--Alerts health care professionals that OxyContin could be a target 
for theft and diversion and instructs that they should contact their 
State Professional Licensing Board or State Controlled Substances 
Authority for information on how to prevent and detect abuse or 
diversion of the product; 

Language in OxyContin label approved in 2001: 

"SAFETY AND HANDLING; 
OxyContin Tablets are solid dosage forms that contain oxycodone which 
is a controlled substance. Like morphine, oxycodone is controlled 
under Schedule II of the Controlled Substances Act; 
OxyContin has been targeted for theft and diversion by criminals. 
Healthcare professionals should contact their State Professional 
Licensing Board or State Controlled Substances Authority for 
information on how to prevent and detect abuse or diversion of this 
product." 

Source: FDA-approved label for Purdue's OxyContin.

[End of table]

[End of section]

Appendix III: Databases Used to Monitor Abuse and Diversion of 
OxyContin and Its Active Ingredient Oxycodone:

DEA uses several databases to monitor abuse and diversion of controlled 
substances, including OxyContin and its active ingredient oxycodone. 
Specifically, the agency monitors three major databases--the Drug Abuse 
Warning Network (DAWN), the National Forensic Laboratory Information 
System (NFLIS), and the System to Retrieve Information from Drug 
Evidence (STRIDE).[Footnote 54] DEA also monitors other data sources to 
identify trends in OxyContin abuse and diversion, such as the Substance 
Abuse and Mental Health Services Administration's (SAMHSA) National 
Survey on Drug Use and Health, formerly the National Household Survey 
on Drug Abuse, and the Monitoring the Future Study funded by the 
National Institute on Drug Abuse.[Footnote 55]

DAWN Data:

SAMHSA operates the DAWN system, which estimates national drug-related 
emergency department visits and provides death counts involving abused 
drugs. DAWN collects data semiannually on drug abuse from hospital 
emergency department admission and medical examiner data from 21 
metropolitan areas and a limited number of metropolitan medical 
examiners who agree to voluntarily report medical record samples. The 
emergency department and medical examiner data generally do not 
differentiate oxycodone from OxyContin, unless the individual provides 
the information to the hospital or identifiable tablets are found with 
the person. Although samples from hospitals outside the 21 metropolitan 
areas are also available, DAWN is not able to make drug-related 
emergency department visit or death estimates for rural or suburban 
areas.

NFLIS Data:

NFLIS, a DEA-sponsored project initiated in 1997, collects the results 
of state and local forensic laboratories' analyses of drugs seized as 
evidence by law enforcement agencies. NFLIS is used to track drug abuse 
and trafficking involving both controlled and noncontrolled substances 
and reports results by a drug's substance, such as oxycodone, and not 
by its brand name. DEA stated that because new laboratories are being 
added, its data should not yet be used for trending purposes. As of 
March 2003, 35 state laboratories and 52 local or municipal 
laboratories participated in the project.

STRIDE Data:

STRIDE, another DEA database, reports the results of chemical evidence 
analysis done by DEA laboratories in drug diversion and trafficking 
cases. Oxycodone data are reported by combining single and combination 
oxycodone drugs and do not provide specific enough information to 
distinguish OxyContin cases and exhibits. The database's lag time, 
which varies by laboratory, depends on how quickly the findings are 
entered after the seizure of the drug substance and its analysis.

National Survey on Drug Use and Health Data:

The National Survey on Drug Use and Health, another SAMHSA database, is 
used to develop national and state estimates of trends in drug 
consumption.[Footnote 56] Prior to 2001, the self-reported survey asked 
participants if they had illicitly used any drug containing oxycodone. 
In 2001, the survey included a separate section for pain relievers, and 
asked participants if they had used OxyContin, identifying it by its 
brand name, that had not been prescribed for them. State samples from 
the survey are combined to make national-and state-level estimates of 
drug use, and because the estimated numbers derived for OxyContin are 
so small, it is not possible to project illicit OxyContin use on a 
regional, state, or county basis.

Monitoring the Future Survey Data:

The Monitoring the Future Survey, funded by the National Institute on 
Drug Abuse and conducted by the University of Michigan, annually 
monitors the illicit use of drugs by adolescent students in the 8th, 
10th, and 12th grades. The 2002 survey included new questions using the 
brand names of four drugs, including OxyContin, in its survey on the 
annual and 30-day prevalence of drug use.

[End of section]

Appendix IV: Comments from the Food and Drug Administration:

Food and Drug Administration 
Rockville MD 20857:

November 6, 2003:

Marcia Crosse:

Director, Health Care-
Public Health and Military Health Care Issues 
United States General Accounting Office 
441 G Street, NW:

Washington, DC 20548:

Dear Ms. Crosse:

Please find the enclosed comments from the Food and Drug Administration 
on the GAO draft report entitled, PRESCRIPTION DRUGS: Factors That May 
Have Contributed to OxyContin Abuse and Diversion and Efforts to 
Address the Problem, (GAO-04-110). The Agency provided technical 
comments directly to your staff.

We appreciate the opportunity to review and comment on this draft 
report before its publication as well as the opportunity to work with 
your staff in developing this report.

Sincerely,

Mark B. McClellan, M.D., Ph.D. 
Commissioner of Food and Drugs:

Signed by Mark B. McClellan

Enclosure:

General Comments by the Department of Health and Human Service's Food 
and Drug Administration (FDA) on General Accounting Office's (GAO) 
Draft Report. PRESCRIPTION DRUGS: Factors That May Have Contributed to 
OxyContin Abuse and Diversion Efforts to Address the Problem (GAO-04-
110):

FDA appreciates the opportunity to comment on GAO's draft report which 
focuses additional attention on the abuse and diversion of prescription 
drugs.

We have a few general comments regarding the overall report, as 
follows:

FDA's Regulation of Prescription Drugs:

As currently written, GAO's draft report suggests that FDA decided as a 
matter of policy not to distinguish between types of drugs in 
regulating promotion. FDA believes it is important to clarify that the 
FD&C Act makes no distinction between controlled substances and other 
prescription drugs in its provisions regulating promotion, but that as 
a matter of general policy, the Agency more closely scrutinizes 
promotion of drugs with more serious risk profiles.

OxvContin Advertisements Violated the FD&C Act:

FDA believes it is important to clarify the content of the warning 
letter issued to Purdue Pharma. In January 2003, FDA issued a warning 
letter to Purdue regarding two journal advertisements for OxyContin 
that minimized its risks and overstated its efficacy, by failing to 
present any information from the boxed warning on the potentially fatal 
risks associated with OxyContin and its abuse liability, along with 
omitting important information about the limitations on the indicated 
use of OxyContin. The FDA requested that Purdue cease disseminating 
these advertisements and any similar violative materials and provide a 
plan of corrective action.

We recommend that GAO include additional information describing the 
widespread dissemination of the corrective advertisement and the nature 
of its content, because we believe it gives important information on 
the extent to which complete and accurate information on OxyContin's 
risks and its limited indication was disseminated to healthcare 
providers this year resulting from the warning letter. This corrective 
advertisement ran for three months and appeared in approximately 30 
medical journals. The three-paged advertisement, entitled "Important 
Correction of Drug Information," contained a two-paged spread, with a 
"Dear Healthcare Practitioner" letter on one side, which called 
attention to the warning letter and the cited violations, and directed 
the reader to the boxed warning and indication information for 
OxyContin prominently featured on the opposite side of the spread.

Reports of Abuse and Diversion Led to Label Changes and_ Other Actions 
by FDA:

FDA recommends noting in the report that an important part of the risk 
management plan in connection with the 2001 labeling changes was that 
all OxyContin promotional materials be revised to reflect the labeling 
changes and all future promotional materials prominently disclose this 
information. As part of the risk management plan in connection with the 
labeling changes, Purdue was asked to revise all of its promotional 
materials for OxyContin to reflect the labeling changes. The FDA sent a 
letter to Purdue, dated August 3, 2001, stating that all future 
promotional materials for OxyContin should prominently disclose the 
information contained in the boxed warning, the new warnings that 
address misuse, abuse, diversion, and addiction, and the new 
precautions and revised indication for OxyContin. Purdue agreed to 
comply with this request in a letter dated August 7, 2001.

We also believe it is important to clarify that all three of the 
patient videos discussed in the report were submitted prior to the 
labeling change and discontinued as a result of the labeling change and 
these communications. As the discussion of these patient videos is 
currently written in the report, it could be misinterpreted that two of 
the patient videos were submitted after the labeling change as part of 
Purdue's modification of its promotional materials.

Recommendation for Executive Action:

"To improve efforts to prevent or identify the abuse and diversion of 
schedule II controlled substances, the Commissioner of Food and drugs 
should ensure that FDA's risk management plan guidance encourages 
pharmaceutical manufacturers that submit new drug applications for 
these substances to include plans that contain a strategy for 
monitoring the use of these drugs and identifying potential abuse and 
diversion problems.":

FDA agrees with GAO's recommendation and is currently working on the 
guidance.

[End of section]

Appendix V: Comments from the Drug Enforcement Administration:

U.S. Department of Justice 
Drug Enforcement Administration:

www. dea.gov:

Ms. Marcia Crosse, Director Health Care-
Public Health and Military Health Care Issues 
General Accounting Office 441 G Street, N. W. 
Washington, D.C. 20548:

NOV 05 2003:

Dear Ms. Crosse:

The Drug Enforcement Administration (DEA) submits the following 
comments on the facts and findings of the draft report, PRESCRIPTION 
DRUGS: Factors that May Have Contributed to OxyContin Abuse and 
Diversion and Efforts to Address the Problem (GAO-0A-110).

In general, the report is not as forthright as warranted on the causes/
factors relating to the diversion of OxyContin. The root of the problem 
that this GAO report addresses appears to be the unfortunate 
convergence of Purdue's marketing techniques and the public/policy 
focus on pain undertreatment. The DEA has previously stated that the 
company's aggressive methods, calculated fueling of demand and the 
grasp for major market share very much exacerbated OxyContin's 
widespread abuse and diversion. While Purdue highlights its funding of 
pain-related educational programs and websites and its partnership with 
various organizations, the fact remains that Purdue's efforts-which may 
be viewed as self-serving public relations damage control-would not 
have been necessary had Purdue not initially marketed its product 
aggressively and excessively. Contributing to the abuse and diversion 
problem (and the product's excessive availability) is the fact that in 
promoting this drug to practitioners, Purdue deliberately minimized the 
abuse risk associated with OxyContin, as the report states on pages 21 
and 35.	The claim in Purdue's `educational' video for physicians that 
opioid analgesics cause addiction in less than one percent of patients 
is not only unsubstantiated but also dangerous because it misleads 
prescribers.

In a further example of Purdue's pattern of aggressive pursuit of 
market share, the report states on page 31: "As part of its marketing 
campaign, Purdue distributed the usual types of branded promotional 
items to health care practitioners. Among these items were OxyContin 
fishing hats, stuffed plush animal toys, coffee mugs, compact discs..." 
In fact, the use of such branded promotional items for a Schedule II 
opioid is unprecedented. Distribution of promotional items such as 
hats, plush toys and coffee mugs is an indicator of Purdue's 
aggressive, excessive, and inappropriate marketing of their product, 
OxyContin. The DEA suggests the Department of Health and Human Services 
restrict promotional materials for Schedule II substances to items 
related to the practice of medicine or pharmacy.

Increased availability of controlled substances leads to increased 
opportunities for diversion. Therefore, it is essential that stringent 
risk management plans are put in place prior to the introduction of 
these products into the marketplace.

Unfortunately, there are limitations to DEA's ability to document the 
extent of diversion of specific products and DEA agrees with GAO's 
observation, on the bottom of page 36 of the draft report, that "data 
on abuse and diversion are not reliable, comprehensive, or timely." DEA 
also advocates the development of a system to provide "credible, 
legally defensible evidence concerning drug abuse trends in America," 
as stated on page 42 of the draft report. DEA included an additional 
$750,000 in its 2003 budget request for an enhanced scientific data 
collection system that would include a National Medical Examiner 
Information System; however, this request has not been funded. This 
agency welcomes a recommendation by GAO that more reliable, 
comprehensive and timely databases be developed.

In addition, there are minor inaccuracies in this report, detailed 
below:

First remark, ref page 3, 2nd full sentence of GAO draft report: DEA 
suggests the following edit to the draft report language (new/
replacement language is in bold italics): "Unlike nonopioid pain 
relievers, oxycodone, the active ingredient in OxyContin, has no known 
analgesic hits no ceiling effect, that is, the dose amount a patient 
can take can be increased by the physician as needed to relieve pain. 
However, as the dose escalates, there is always a danger ofserious side 
effects, including respiratory depression and death.":

* Page 5, line 9: refers to "...three other opioid drugs, Avinza, 
Kadian, and Oramorph SR, that like OxyContin are classified as schedule 
II controlled substances." These drugs should be further identified as 
high dose extended release opioid drugs, not simply "opioid drugs," 
here and throughout this document.

* Page 18, first paragraph: states "...a prescription for a schedule II 
drug may not be refilled, and the patient must see the practitioner 
again in order to obtain more drugs." While it is correct that schedule 
II drug prescriptions may not be refilled, a patient is not required to 
see the practitioner again but must obtain a new prescription.

Please correct the document language noted above to ensure the report's 
accuracy. The DEA appreciates the opportunity to provide comment to the 
GAO in these important matters.

Sincerely,

Rogelio Guevara: 
Chief Inspector: 

Signed by Rogelio Guevara: 

[End of section]

FOOTNOTES

[1] OxyContin is an opioid analgesic--a narcotic substance that 
relieves a person's pain without causing the loss of consciousness. 
Hereafter, we refer to the company as Purdue.

[2] As discussed later in this report, FDA approved the revised 
OxyContin label in July 2001 to describe the time frame as "when a 
continuous around-the-clock analgesic is needed for an extended period 
of time."

[3] According to FDA, there is no known limit to the amount of 
oxycodone, the active ingredient in OxyContin, that can be used to 
treat pain.

[4] Prescription drug diversion can involve such activities as "doctor 
shopping" by individuals who visit numerous physicians to obtain 
multiple prescriptions, prescription forgery, and pharmacy theft. 
Diversion can also involve illegal sales of prescription drugs by 
physicians, patients, or pharmacists, as well as obtaining controlled 
substances from Internet pharmacies without a valid prescription.

[5] According to the National Institute on Drug Abuse, addiction is a 
chronic, relapsing disease, characterized by compulsive drug seeking 
and use and by neurochemical and molecular changes in the brain, 
whereas physical dependence is an adaptive physiological state that can 
occur with regular drug use and results in withdrawal symptoms when 
drug use is discontinued.

[6] Under the Controlled Substances Act, which was enacted in 1970, 
drugs are classified as controlled substances and placed into one of 
five schedules based on their medicinal value, potential for abuse, and 
safety or dependence liability. Schedule I drugs have no medicinal 
value; have not been approved by FDA; and along with schedule II drugs, 
have the highest potential for abuse. Schedule II drugs have the 
highest potential for abuse of any approved drugs. 

[7] OxyContin, Hearings of the Subcommittee on the Departments of 
Commerce, Justice, and State, the Judiciary, and Related Agencies, 
House Committee on Appropriations, 107th Cong. Part 10 (Dec. 11, 2001).

[8] OxyContin: Balancing Risks and Benefits, Hearing of the Senate 
Committee on Health, Education, Labor, and Pensions, 107th Cong. 287 
(Feb. 12, 2002).

[9] Avinza was approved by FDA in 2002 and is marketed by Ligand 
Pharmaceuticals; Kadian was approved in 1996 and is marketed by 
Alpharma-US Human Pharmaceuticals; and Oramorph SR was approved in 1991 
and is now owned by Élan Corporation, which told us it is not currently 
marketing the drug. 

[10] Title II of the Comprehensive Drug Abuse Prevention and Control 
Act of 1970 (Pub. L. No. 91-513, §§100 et seq., 84 Stat. 1236, 1242 et 
seq.).

[11] The other four vital signs physicians use to assess patients are 
pulse, blood pressure, core temperature, and respiration.

[12] In 1999, the name of the Agency for Health Care Policy and 
Research was changed to the Agency for Healthcare Research and Quality. 
The agency, which is part of HHS, is responsible for supporting 
research designed to improve the quality of health care, reduce its 
costs, and broaden access to essential services.

[13] When we refer to OxyContin's label we are also referring to the 
drug's package insert that contains the same information about the 
product. 

[14] For example, according to Purdue's comparable dose guide a patient 
taking one Percodan 4.5-milligram tablet or one Tylox 5-milligram 
tablet every 6 hours can be converted to either a 10-or a 20-milligram 
OxyContin tablet to be taken every 12 hours. For a 12-hour dosing 
period, one OxyContin tablet replaces two Percodan or Tylox tablets, 
and one OxyContin tablet contains twice as much oxycodone as one of the 
other tablets. 

[15] In April 2001, Purdue discontinued distribution of the 160-
milligram tablets because of OxyContin abuse and diversion concerns.

[16] Doris Bloodsworth, "Pain Pill Leaves Death Trail: A Nine-Month 
Investigation Raises Many Questions about Purdue Pharma's Powerful Drug 
OxyContin," Orlando Sentinel, Oct. 19, 2003.

[17] Section 201, classified to 21 U.S.C. § 811.

[18] Some schedule V drugs that contain limited quantities of certain 
narcotic and stimulant drugs are available over the counter, without a 
prescription.

[19] FDA regulations require that promotional labeling and 
advertisements be submitted to FDA at the time of initial dissemination 
(for labeling) and initial publication (for advertisements). The FD&C 
Act defines labeling to include all labels and other written, printed, 
or graphic matter accompanying an article. For example, promotional 
materials commonly shown or given to physicians, such as sales aids and 
branded promotional items, are regulated as promotional labeling. FDA 
may also regulate promotion by sales representatives on computer 
programs, through fax machines, or on electronic bulletin boards. 

[20] For details on FDA's oversight of drug advertising see U.S. 
General Accounting Office, Prescription Drugs: FDA Oversight of Direct-
to-Consumer Advertising Has Limitations, GAO-03-177 (Washington, D.C.: 
Oct. 28, 2002).

[21] The Prescription Drug User Fee Act of 1992, Pub. L. No. 102-571, 
title I, 106 Stat. 4491, was reauthorized by the Food and Drug 
Modernization Act of 1997, Pub. L. No. 105-115, 111 Stat. 2296, and, 
most recently, by the Prescription Drug User Fee Amendments of 2002, 
Pub. L. No. 107-188, title V, subtitle A, 116 Stat. 594, 687.

[22] For more details on Internet pharmacies, see U.S. General 
Accounting Office, Internet Pharmacies: Adding Disclosure Requirements 
Would Aid State and Federal Oversight, GAO-01-69 (Washington, D.C.: 
Oct. 19, 2000).

[23] For more details on these programs, see U.S. General Accounting 
Office, Prescription Drugs: State Monitoring Programs Provide Useful 
Tool to Reduce Diversion, GAO-02-634 (Washington, D.C.: May 17, 2002).

[24] In addition, the American Medical Association, a professional 
association for physicians, issued guidelines in 1990 regarding gifts 
given to physicians by drug industry representatives. For example, 
physicians may accept individual gifts of nominal value that are 
related to their work, such as notepads and pens, and may attend 
conferences sponsored by drug companies that are educational and for 
which appropriate disclosure of financial support or conflicts of 
interest is made.

[25] Following OxyContin's July 2001 label change, Purdue modified its 
promotional messages but continued to focus on encouraging physicians 
to prescribe OxyContin for patients taking pain relievers every 4 to 6 
hours. In 2003, Purdue began using the promotional claim "there can be 
life with relief" in OxyContin promotion. 

[26] IMS Health reported noncancer prescriptions written for the 
following types of pain conditions: surgical aftercare; musculoskeletal 
disorders including back and neck disorders, arthritis conditions, and 
injuries and trauma including bone fractures; central nervous system 
disorders including headache conditions such as migraines; 
genitourinary disorders including kidney stones; and other types of 
general pain.

[27] The IMS Health data included information from the National Disease 
and Therapeutics Index and the National Prescription Audit. The 
National Disease and Therapeutics Index does not capture data from 
anesthesiologists and dental specialties. The National Prescription 
Audit data include retail pharmacy, long-term-care, and mail-order 
prescriptions.

[28] Duragesic is a skin patch used to deliver the opioid pain reliever 
fentanyl over a 72-hour period.

[29] These sales representatives were also responsible for promoting 
other Purdue products.

[30] Abbott Laboratories sales representatives' promotion of OxyContin 
is limited to hospital-based anesthesiologists and surgeons and major 
hospitals, medical centers, and freestanding pain clinics. 

[31] U.S. General Accounting Office, Prescription Drugs: FDA Oversight 
of Direct-to-Consumer Advertising Has Limitations, GAO-03-177 
(Washington, D.C.: Oct. 28, 2002).

[32] During 2000 through 2002, JCAHO sponsored a series of educational 
programs on pain management standards with various cosponsors, 
including pain-related groups such as the American Pain Society and the 
American Academy of Pain Medicine.

[33] The "Find a Doctor" feature is a physician listing service 
provided by the National Physicians DataSource, LLC. 

[34] Purdue has also helped to fund the Dannemiller Memorial Education 
Foundation and the American Academy of Physician Assistants Web sites. 

[35] It is common drug industry practice for companies to provide 
conversion tables for sales representatives to distribute to health 
care practitioners. Purdue used a similar pen for its older product, MS 
Contin.

[36] FDA indicated that in 2000, it issued 75 untitled letters to 46 
drug manufacturers, as well as 4 warning letters to 4 drug 
manufacturers, for using promotional activities that violated the FD&C 
Act. 

[37] The advertisement appeared in the New England Journal of Medicine 
in May 2000.

[38] The advertisements appeared in the Journal of the American Medical 
Association in October and November 2002.

[39] According to FDA, the corrective advertisement ran for 3 months 
and appeared in approximately 30 medical journals.

[40] FDA indicated that from January through August 2003, it issued 4 
warning letters to four manufacturers and 12 untitled letters to seven 
drug manufacturers for using promotional activities that violated the 
FD&C Act.

[41] Zeneca Pharmaceuticals promoted Kadian for Faulding Laboratories, 
the drug's manufacturer at that time.

[42] See, for example, G.B. Curtis, et al. "Relative Potency of 
Controlled-Release Oxycodone and Morphine in a Postoperative Pain 
Model," European Journal of Clinical Pharmacology, vol. 55, no. 6 
(1999): 55:425-429. 

[43] This information is from the National Institute for Health Care 
Management's Prescription Drug Expenditures reports for 2000 and 2001, 
prepared using American Institutes for Research analysis of Scott-Levin 
Prescription Audit Data. OxyContin was ranked 18th in 2000.

[44] In making a designation, ONDCP considers whether the geographic 
area is a center of drug production, manufacturing, importation, or 
distribution; whether state and local law enforcement agencies have 
committed resources to respond aggressively to the drug trafficking 
problem; whether drug activities in the area are having a harmful 
impact on other areas of the country; and whether a significant 
increase in federal resources is necessary to respond to the area's 
drug-related activities. 

[45] Appalachia High Intensity Drug Trafficking Area Task Force, The 
OxyContin Threat in Appalachia (London, Ky.: August 2001).

[46] The reliability of the data collected depends on whether the 
emergency room patient visit was reported as drug related, whether the 
patient reported taking a particular drug, and whether the emergency 
room physician indicated a drug's brand name in the patient's medical 
record.

[47] See app. III for more details on the abuse and diversion databases 
DEA uses.

[48] The 15 states are Alabama, Arizona, Colorado, Connecticut, 
Florida, Louisiana, Massachusetts, Mississippi, Missouri, New Jersey, 
North Carolina, South Carolina, Texas, Washington, and Wisconsin.

[49] Hydrocodone products, such as Anexsia, Hycodan, Lorcet, Lortab, 
and Vicodin, remain among the most abused and diverted scheduled 
prescription drugs nationally.

[50] See www.fda.gov/cder/drug/infopage/oxycontin/default.htm.

[51] The Kentucky guidelines for the use of controlled substances in 
pain treatment provide that (1) a complete medical history and 
examination be conducted and documented in patient medical records, (2) 
a written treatment plan state objectives for determining treatment 
success, (3) the risks and benefits of the use of controlled substances 
be discussed by physician and patient, (4) periodic review of the 
course of treatment be conducted, (5) consultation or referral to an 
expert in pain management be considered for patients who are at risk 
for substance abuse, (6) patient's medical record be kept accurate and 
complete, and (7) physicians be in compliance with applicable federal 
and state controlled substance laws and regulations. 

[52] Amended versions of Purdue's risk management plan for OxyContin 
were submitted to FDA for review in April 2002 and in March 2003.

[53] RADARS will collect information on brand-name and generic versions 
of buprenorphine, fentanyl, hydrocodone, hydromorphone, oxycodone, 
morphine, and methadone. Benzodiazepine is scheduled to be added to 
RADARS in late 2003. 

[54] Other databases used by DEA to assess changes in drug abuse and 
diversion include the Drug Early Warning System, the Drug and Alcohol 
Services Information System, the Treatment Episode Data Set, the 
National Survey of Substance Abuse Treatment Services, the Uniform 
Facility Data Set, the Poison Control Center Data or Toxic Exposure 
Surveillance System, the Automation of Reports and Consolidated 
Ordering System, the DEA Theft System, and the DEA Field Reports and 
Investigative Teletypes.

[55] The National Institute on Drug Abuse is part of the National 
Institutes of Health within the Department of Health and Human 
Services.

[56] Self-reporting individuals are interviewed regarding their illicit 
drug use over three periods--within the last 30 days, during the past 
year, and during their lifetime. The survey data are limited, as it is 
not possible to determine specifically which year respondents may have 
used a drug illicitly, because they are asked both whether they have 
ever used the drug illicitly in their lifetime and whether they have 
used it during the past year.

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