July 31, 2007
STATEMENT OF DR. JAMES N. CAMPBELL
Professor of Neurosurgery
School of Medicine, Johns Hopkins University
Director of the Blaustein Pain Treatment Center of the
Johns Hopkins Hospital
Chairman of the Board of the American Pain Foundation
FOR THE HEARING ON
"Evaluating the Propriety and Adequacy of the OxyContin Criminal Settlement"
COMMITTEE ON THE JUDICIARY
UNITED STATES SENATE
JULY 31, 2007
Chairman Leahy and Members of the Committee, thank you for the invitation to testify today. I am Professor of Neurosurgery at the School of Medicine at the Johns Hopkins University. I am also the Director the Blaustein Pain Treatment Program at the Johns Hopkins Hospital, as well as Chairman of the Board at the American Pain Foundation and past president of the American Pain Society. I have dedicated my career, spanning 30 years, to the mission of decreasing the suffering associated with pain. I do research on pain funded by the NIH, see patients, and engage in a number of pro bono activities pursuant to this mission. I come before this hearing because of my concern for patients who have pain and their access to care.
I have a perspective on the problem of pain in America because I am in the trenches battling with the issue of how to help individual patients who are devastated by the problem of chronic pain. My perspective also arises from my work with the American Pain Foundation. The APF is the nation's leading nonprofit organization devoted exclusively to serving the needs of people with pain. The APF works toward its mission by providing information, education, and advocacy. I founded the APF with the help of several colleagues including Dr. Kathleen Foley, who served for fifteen years as head of the Pain and Palliative Care Services at Memorial Sloan Kettering Hospital, and Dr. Charles Cleeland, Director of the Pain Research Group at M.D. Anderson Cancer Center. We recognized that there was a need for a national grassroots organization that was dedicated to furthering research, providing education, and raising awareness about the problem of chronic and acute pain in America. Purdue Pharma has contributed generously during the ten years that the APF has been in existence.
I am testifying before you today because I believe the adverse publicity and the prosecution of several Purdue Pharma executives in relation to OxyContin risk the welfare of patients in pain. Access to treatment is a major problem affecting millions of patients who suffer with pain. This hearing has the potential to clarify many misunderstood facts about OxyContin and it is in this spirit that I appear before you today.
Chronic Pain is Under-treated in the United States
Let me begin by pointing out that chronic pain is a serious public health problem and numerous surveys report that more than 50 million Americans live with chronic pain. The National Center for Health Statistics of the Centers for Disease Control and Prevention estimate that, including all types and duration of pain, there are 76.2 million persons afflicted, more than the total number suffering from diabetes mellitus (20.8 million), coronary heart disease and stroke (18.7 million) and cancer (1.4 million) combined. Yet, pain is arguably the most untreated, under-treated, and mistreated serious health problem in the United States. For instance, a recent study in the Journal of the American Medical Association of nursing home patients with cancer found that 24% of patients with significant pain received nothing stronger than aspirin. Another study showed that an estimated 70% of those with cancer experience significant pain, yet fewer than half of these individuals received adequate treatment for their pain.
Pain Exacts A Heavy Toll
People who endure chronic, unrelieved pain are more likely to suffer depression and anxiety. They have trouble sleeping, have other physical ailments, and take longer to recover from these ailments. They lose time at work, lose their jobs, and have other financial problems. They have more difficulty caring for children and other dependents, and suffer deteriorated relationships with family and friends. There is evidence that chronic pain adversely affects the immune system. Patients with back pain may even suffer brain damage. Pain is a serious problem and treatment has to be considered an essential function of medical care.
Furthermore, the Drug Enforcement Administration, together with two independent groups, issued a document in 2004 stating that uncontrolled pain accounts for "many tens of billions of dollars of needed health care and lost productivity" and the National Institutes of Health have stated that pain costs "the American public more than $100 billion each year."
I have treated thousands of patients who suffer with severe significant pain. I have treated patients who contemplated suicide - and know of patients who have committed suicide - some of this is due simply to the problem of under treatment. OxyContin, and other powerful opioids, are the smart, safe and sometimes the only effective choice for many of these patients.
Opioids Are Effective Medications
Drug abuse and addiction are major problems in America. Prescription drug abuse is part of that problem, though tobacco and alcohol use remain the biggest abuse problems. Regardless of this, still in this year, 2007, I think remarkably, opioids remain the most effective class of drugs for treatment of moderate and severe pain. In every study I know where opioids have been compared to other medications, opioids have proven to be the more effective drug. Unlike other pain medications, such as aspirin and Tylenol, opioids are not associated with enduring drug toxicities. Opioids such as OxyContin do not cause liver damage, kidney damage, or hemorrhage from the stomach. While addiction and abuse are concerns, in my experience, these problems are rare events in patients with serious chronic pain and no history of substance abuse. This is not to say opioids are a panacea for pain. Patients are often inadequately relieved of pain and they complain of other side effects of opioids including the problem of constipation. While all patients on opioids have a physical dependence, meaning that they will have a physiological withdrawal problem if they stop the medication abruptly, few develop addiction. This is worth restating: addiction is a rare problem in patients who take opioid medications as prescribed for serious pain.
Development of OxyContin
OxyContin is an extended release preparation of oxycodone, one of the most commonly used opioids in the world. Two benefits of OxyContin are:
? Abuse is related to the kinetics of drug delivery to the brain. Rapid delivery is correlated with a higher abuse potential. OxyContin was developed to have slower drug delivery kinetics. The fact is that the more gradual rise in oxycodone blood levels with an extended release formulation, such as OxyContin, is very likely to have less abuse potential when taken as instructed, than the same medication provided in an immediate release preparation such as what is present in medications such as Tylox, Vicodin, and Percocet.
? A second advantage of OxyContin is that it provided a medication that provides more steady blood levels of oxycodone with less frequent dosing. This strategy is likely to improve the so-called therapeutic window, which refers to the ratio of benefit to adverse effects.
When taken as instructed, OxyContin almost certainly achieves both objectives. Thus, OxyContin when introduced in 1995 was considered a major advance in pain treatment. The only other extended release opioids at the time were controlled release morphine products, which many patients did not tolerate well.
Why is OxyContin Abused?
Frequently overlooked in the media hype about OxyContin is an understanding of the pharmacological facts about this drug. OxyContin is nothing more than an extended release form of the common pain reliever, oxycodone. What was not clear to anyone when OxyContin was first introduced, was that the larger amounts of oxycodone provided in the OxyContin pills would become an attraction to drug abusers. Drug abusers learned that the pills could be modified (for example, crushed) such that oxycodone could be extracted in relatively large amounts. The typical oxycodone pills contain 5 to 10 mg of oxycodone. OxyContin pills vary in dose and may contain anywhere from 10 to 80 mg of oxycodone. OxyContin is a very effective medication for patients with pain. The success and popularity of the drug meant that the medication became widely available. Thus, abuse became an increasing issue in particular, for reasons still not understood, in rural areas of the country. No one I know in 1995 in the drug industry, at the FDA, or in the academic community foresaw what would later become a major problem with regard to OxyContin abuse. What I saw in my practice were patients who often got effective pain relief with OxyContin where nothing else would work.
What I believe is often lost in the discussion of OxyContin is that the abuse problem itself arises almost entirely from intentional abuse rather than from use according to proper prescribing. Taking the medication as directed with all of the precautions outlined in the packaging insert approved by the FDA and used by Purdue Pharma simply does not lead to abuse problems. As with a wide variety of chemicals available freely in our society, there are ways to misuse OxyContin, but this abuse problem arises because the abuser deliberately subverts the slow delivery mechanism in order to use the drug for non-medical purposes.
Role of Purdue Pharma in the Promotion of OxyContin
It is a fact that when OxyContin was launched, its package insert was recognized to include even more information about the risks and benefits of opioids and their potential for abuse than did the package inserts for other comparable opioid drugs. And when it became apparent that there was a problem with the abuse and diversion of the drug in 2000 - 2001, Purdue and its executives took what I consider to be Herculean steps to combat this abuse.
I cannot attest one way or the other as to the alleged hyperbolic promotion of OxyContin by certain employees of Purdue Pharma. My understanding of the facts is that upper management did not in fact promote any illegal sales practices by their employees. The criminal prosecution of senior executives at Purdue Pharma may play to certain popular sentiments, but sends a chilling message to those who dare to develop high-risk drugs for important diseases.
The use of opioids, any opioid, for treatment of pain is a serious undertaking and all physicians know this. We have learned more about drug abuse in recent years, but identifying the abuser and preventing diversion of prescription medications remains a very challenging task for physicians, concerned with the compassionate care of patients and the protection of their welfare. I in no way condone the misbranding of any drug. In this case I understand that some employees made statements to some doctors either overstating the benefits, or understating the risks of OxyContin. That is wrong. But I also must state that I believe all physicians understand what a schedule II narcotic is. This is how OxyContin was labeled and every physician recognizes that every narcotic is the potential target of diversion, abuse, and misuse.
It must also be recognized that OxyContin underwent extensive study and examination before it was put on the market. At the end of 1994, Purdue submitted a New Drug Application for OxyContin to the FDA. This application included detailed information on numerous clinical trials of the drug, in which thousands of individuals participated. The FDA approved the application a year later and found that the drug was safe and effective when administered in accordance with its label. It is simply wrong to say that OxyContin is a defective product. This would be like saying that medicines containing morphine and hydrocodone are defective products. It remains not only plausible but likely that when taken as directed that OxyContin in fact does have less abuse potential than other immediate release medications.
Did Purdue Pharma Responsibly Warn of Abuse Liabilities?
I note again that abuse largely depends on the deliberate extraction of oxycodone from the pill for purposes of injecting or snorting the drug. Purdue warned of abuse issues from the beginning. The original OxyContin package insert warned the prescribing physician that:
? "OxyContin is a mu-agonist opioid with an abuse liability similar to morphine and is a Schedule II controlled substance."
? "Oxycodone products are "common targets for both drug abusers and drug addicts."
? "Drug seeking" behavior is very common to addicts.
? The top line of the package insert bore the "CII" symbol, immediately telling doctors that OxyContin is a Schedule II drug.
? The section of the package insert entitled "Information for Patients/Caregivers" also warned that OxyContin is a "potential drug of abuse" and that patients should guard their medication from theft.
The package insert then was subsequently revised as new information about abuse became available including the addition of a boxed warning in July 2001, the strongest warning the FDA issues for an approved drug product.
The abuse problem has occurred, almost exclusively, outside of the realm in which Purdue marketed the medication. Purdue never advertised OxyContin directly to consumers. Purdue markets OxyContin for the use in legitimate pain patients under the careful supervision of physicians. The OxyContin label warns in bold capital letters against crushing, breaking or chewing the tablets. That, however, is what abusers do, transforming it into a different product, and one that can be very dangerous and addictive. In stark contrast, the scientific evidence suggests that addiction to opioids by legitimate chronic pain patients without prior histories of substance abuse using the medication as directed is rare. Furthermore, no causal effect has been demonstrated between the marketing of OxyContin and the abuse and diversion of the drug. For example, in several states where formulary programs have substituted methadone for OxyContin, methadone overdoses have risen and even eclipsed OxyContin abuse, despite the fact that no pharmaceutical company actively markets methadone for the treatment of pain.
Purdue Responded to the Increased Incidence of Abuse with Initiatives Aimed at
When OxyContin abuse was identified as an unexpectedly significant problem, Purdue developed an extensive series of initiatives to combat prescription drug abuse. In fact, these initiatives have helped to build for risk management for all opioids. Examples of a few of the programs Purdue has participated in, initiated, or funded follows:
? Disseminating tamper resistant prescription pads to physicians.
? Educating physicians and pharmacists about how to protect their practice from abuse.
? Developing and funding the heralded research-based initiative ("RADARS"), which gathers quantitative and qualitative data on abuse trends.
? Researching abuse-resistant formulations of OxyContin.
? Funding community-based programs to prevent and drug abuse and addiction.
? Developing public service campaigns that educate the public about the dangers of prescription drug abuse.
These programs and initiatives have helped educate medical professionals and law enforcement about how to combat and deal with prescription abuse. These programs have also attempted to educate the public about the risks inherent in using these medications other than as prescribed and outside the supervision of a physician. These programs have worked to promote the safe use of all opioids, and represent Purdue's leadership in the area of abuse prevention. Many of them have become models in the field. I know of no pharmaceutical company that has taken the problem of abuse and diversion more seriously than Purdue and that has done more to help healthcare professionals attempt to combat the problem.
OxyContin stands as one of the effective choices to treat serious pain in patients. Despite the stigma associated with this drug, many physicians recognize that OxyContin (and I might add other competing extended release preparations of oxycodone) is an important part of the pain treatment arsenal. Purdue Pharma in my opinion is to be lauded for pioneering the use of extended release opioid preparations for treatment of pain. Many thousands if not millions of patients have benefited. Abuse is a major problem as well. We do a disservice to attack the problem of abuse by limiting the treatment choices of patients with pain. This august committee might make note that our ultimate goal is to develop better choices for patients through research conducted via the funding from the NIH, and the pharmaceutical industry. Our goal should be to encourage industry and academia to find drugs that have no abuse liability and yet relieve pain safely and effectively. While it does appear that some sales representatives at Purdue may have understated the inherent risks of using opioid therapy, it is in my view reckless to say that because of this, senior executives are criminally responsible. Purdue has helped fill a void in pain treatment. Many thousands of patients have benefited. I believe Purdue and its management deserve recognition for their contribution to the welfare of these many patients.