UNITED STATES OF AMERICA
FOOD AND DRUG ADMINISTRATION
CENTER FOR DRUG EVALUATION AND RESEARCH
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ANESTHETIC AND LIFE SUPPORT DRUGS ADVISORY COMMITTEE
MEETING
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THURSDAY
JANUARY 31, 2002
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The Advisory Committee met at 8:00 a.m. in the Grand Ballroom of the Holiday Inn, Two Montgomery Village Avenue, Gaithersburg, Maryland, Dr. Nathaniel P. Katz, Acting Chair, presiding.
PRESENT:
NATHANIEL P. KATZ, M.D. M Acting Chair
JIM ANTHONY, PhD Guest
MICHAEL A. ASHBURN, M.D., MPH Consultant
JANICE BITETTI, M.D. Member
JEFF BLOOM Patient Rep.
AMANDA S. CARLISLE, PhD, M.D. Consultant
HOWARD D. CHILCOAT, M.D. Guest
MARIA K. CONNOLLY, D.N.Sc Consumer Rep.
KATHLEEN M. FOLEY, M.D. Guest
ERIC S. HOLMBOE, M.D. Consultant
TERESE T. HORLOCKER, M.D. Consultant
BRUCE ALLEN LEVY, M.D., J.D. Guest
LYNN A. LLOYD, R.Ph Consultant
MITCHELL B. MAX, N.D. Consultant
CHARLES H. McLESKEY, M.D. Industry Rep.
LAURA F. McNICHOLAS, M.D. Consultant
WINSTON C.V. PARRIS, M.D., FAcPM Member
STEVEN PASSIK, M.D. Guest
RUSSELL PORTENOY, M.D. Guest
MARCUS M. REIDENBURG, M.D. Consultant
RICHARD G. ROBERTS, M.D. Guest
PRESENT: (continued)
MARK SCHREINER, M.D. Guest
CHARLES SCHUSTER, M.D. Guest
RICHARD M. SMILEY, M.D., PhD Member
JOSEPH R. TOBIN, M.D. Member
KIMBERLY TOPPER Executive Secretary
I-N-D-E-X
PAGE
Call to Order and Introductions 4
Conflict of Interest Statement 8
Welcome to Second Day and Comments 13
Open Public Hearing 17
Industry Presentation 80
J. David Haddox, M.D., DDS
Introduction to Session III: 123
Prescription Drug Abuse
Bob Rappaport, M.D.
Current Data on Abuse and Diversion 132
Judy Ball, Ph.D.
FDA Assessment of Abuse Liability 157
Deborah Leiderman, M.D.
Criminal Drug Diversion 176
Howard Davis, DEA
Epidemiology of Prescription Drug Abuse: 192
Implications for the Clinical Setting
Howard Chilcoat, M.D.
Prescription Drug Abuse in Pain Patients 210
Steven Passik, M.D.
Regulatory Approaches to Risk Management 240
of Prescription Opioid Drug Abuse
Sharon Hertz
Questions and Discussion 257
Adjourn 366
P-R-O-C-E-E-D-I-N-G-S
(8:06 a.m.)
ACTING CHAIRMAN KATZ: Good morning. For those of you who were not here yesterday, my name is Nathaniel Katz. This is the Anesthetic and Life Support Drugs Advisory Committee meeting, Day Number Two. The topic is Opioids, and today we will be focusing primarily on addiction and related matters.
What I'd like to begin with is introductions. Most of the folks from the Advisory Committee introduced themselves yesterday. However, we have some new faces sitting around the table, some of whom are still getting coffee, I suppose. I think those folks were here yesterday.
So if we could perhaps go around the U-shaped table and, if anybody was not here yesterday, if they could briefly introduce themselves for the group. Why don't we start again at that end of the table.
DR. KWEDER: I'm Sandy Kweder from FDA.
DR. RAPPAPORT: Bob Rappaport, the Deputy Division Director for the Division of Anesthetics, Critical Care and Addiction Drug Products at the FDA.
DR. HERTZ: I'm Sharon Hertz, Medical Officer with the Division of Anesthetics, Critical Care and Addiction Drug Products.
ACTING CHAIRMAN KATZ: Why don't we go ahead and do everyone again, because there are a number of people, I hear, especially from the public who were not here yesterday. So we can do it quickly, I think.
DR. MAX: I'm Mitchell Max. I'm a neurologist at the National Institute of Dental and Craniofacial Research.
DR. LLOYD: And I'm Lynn Lloyd, the Executive Director of the Arizona Board of Pharmacy.
DR. REIDENBURG: I'm Marcus Reidenburg, an internist and pharmacologist at Cornell.
DR. HOLMBOE: I'm Eric Holmboe. I'm a general internist from Yale University.
DR. ASHBURN: Michael Ashburn, an anesthesiologist. I'm the Medical Director of Pain Programs, the University of Utah and at Primary Children's Medical Center.
DR. McNICHOLAS: Laura McNicholas from the University of Pennsylvania and the Philadelphia VA. I am a psychiatrist in substance abuse.
DR. HORLOCKER: I'm Terese Horlocker. I'm an anesthesiologist at the Mayo Clinic.
DR. CONNOLLY: I'm Maria Connolly, and I am Associate Professor at Loyola University, Chicago, and I am the Consumer Representative to this panel.
DR. SMILEY: Rich Smiley, anesthesiologist at Columbia University in New York.
DR. TOBIN: I'm Joe Tobin, pediatric anesthesia and intensive care, Wake Forest, University.
ACTING CHAIRMAN KATZ: I'm Nathaniel Katz again. I'm a neurologist. I am affiliated with Brigham and Women's Hospital and the Dana Farber Cancer Institute in Boston, Massachusetts.
DR. CARLISLE: I'm Sue Carlisle. I'm an anesthesiologist and intensivist from the University of California, San Francisco, and Chief of Anesthesia at San Francisco General Hospital.
DR. PARRIS: I'm Winston Parris, Tampa Pain Relief Center and Professor of Anesthesiology at University of South Florida in Tampa.
DR. LEVY: I'm Bruce Levy. I'm the former Director at the Texas State Board of Medical Examiners and the former Executive Vice President of the Federation of State Medical Boards.
DR. McLESKEY: Charlie McLeskey, an anesthesiologist. I work for Abbott Labs, and I'm representing industry today.
MR. BLOOM: Hi. I'm Jeff Bloom. I'm a retired AIDS volunteer patient advocate, and I'm from Washington D.C.
DR. PORTENOY: I'm Russ Portenoy. I'm a neurologist and Chairman of the Department of Pain Medicine and Palliative Care at the Beth Israel Medical Center in New York.
DR. ROBERTS: Rich Roberts, family physician, University of Wisconsin.
DR. SCHREINER: Mark Schreiner. I'm a pediatric anesthesiologist at Children's Hospital, Philadelphia.
DR. ANTHONY: Jim Anthony, epidemiologist from Johns Hopkins School of Public Health.
DR. SCHUSTER: Charles Schuster, psychopharmacologist, Professor of Psychiatry and Behavioral Neurosciences and the Director of the Addiction Research Institute at Wayne State University.
DR. FOLEY: I'm Kathy Foley. I'm a neuroncologist and attending neurologist at Memorial Sloan Kettering Cancer Center, and I direct a project called the Project on Death in America to improve the care of the dying which has an international perspective to make drugs available to developing countries, particularly analgesic drugs for the treatment of pain in patients with cancer and AIDS.
DR. PASSIK: I'm Steve Passik. I'm a psychologist from Community Cancer Care in Indianapolis and the University of Indiana School of Medicine.
DR. CHILCOAT: I'm Howard Chilcoat. I'm an epidemiologist at the Johns Hopkins Bloomberg School of Public Health.
ACTING CHAIRMAN KATZ: I thank everybody for going through that. I want to remind you, the speakers, there is a technical issue with the microphone. So when you speak, you need to hit your button and turn your microphone on, and when you are finished speaking, you need to hit it and turn it off; because it creates some sort of technical problem.
Let me make one more introduction which is not made yet. This is Kimberly Topper sitting to my left. You will hear me whispering back and forth to her during the meeting when she tells me what I'm doing wrong and what I'm doing right. Without her, I can assure you that there would be no meeting today. Nothing would happen correctly, and she will be reading the conflict of interest disclosure.
MS. TOPPER: The following special government employees have been granted general matters waivers which permits their participation in today's discussion: Michael Ashburn, Janice Bitetti, Richard Gorman, Eric Holmboe, Terese Horlocker, Mitchell Max, Laura McNicholas, Winston Parris, Marcus Reidenburg, Richard Smiley, Joseph Tobin, Nathaniel Katz, Llyn Lloyd, Maria Connolly, Amanda Carlisle.
The Committee will discuss the medical use of opiate analgesics in various patient populations, including pediatric patients and patients with chronic pain of nonmalignant etiology, as well as to the risk and benefit ratio of extending opiate treatment into these populations.
The Committee will also address concerns regarding the abuse potential, diversion and increasing incidence of addiction to opiate analgesics, especially to the modified release opiate analgesics.
The FDA is in the process of amending its policy concerning disclosure of financial interests that give rise to waivers for participation in meetings at which particular products are not at issue. Unlike issues before Committee in which the particular product is discussed, issues of broader applicability such as the topic of today's meeting involve many industrial sponsors and academic institutions.
The committee members have been screened for their financial interests as they may apply to the general topic at hand. However, because general topics impact on so many institutions, it is not prudent to recite all the potential conflicts as they apply to each member.
FDA acknowledges that there may be potential conflicts of interest but, because of the general nature of the discussion before the Committee, these potential conflicts are mitigated. Should the discussion turn to issues related to a specific party matter, the Chair of the Committee will either terminate the proceedings or redirect the discussion to only matters of general interest.
With respect to FDA's invited guests, the following are reported interests which we believe should be made public to allow the participants to objectively evaluate their comments.
Dr. James Anthony serves as a researcher and has contracts and grants from NIDA, NIMH, NIA, CSAT, CSAP and NIJ. In addition, in the past Dr. Anthony has given a talk for Purdue Pharma and has served as a scientific advisor for Star Scientific.
Dr. Steven Passik is a researcher on contracts and grants from Eli Lilly, Janssen, Ortho Biotech, Organon, and Pfizer. He also consults for Eli Lilly, Janssen and Ortho Biotech. Additionally, he is a scientific advisor to Eli Lilly, Janssen, Adolor, and he receives speaker fees from Eli Lilly, Janssen, Ortho Biotech, Organon, Pfizer, Purdue Pharma, Roxanne and Knoll.
Dr. Richard Roberts is a scientific advisor to Pharmacia's Detrol Global Advisory Board and the Pfizer/ Pharmacia Bextra Primary Care Advisory Board.
Dr. Charles Schuster has consulted for Alza Corporation in the past.
Dr. Neil Schechter serves on Astra-Zeneca's Speaker Bureau.
Dr. Mark Schreiner is a Medical Director of the Children's Clinical Research Institute. As such, he is involved in clinical trials sponsored by Baxter Pharmaceutical, Sanofi Synthelabo, Novartis, Purdue Pharma, L.P., King Pharmaceuticals, Abbott, and GlaxoSmithKline. He receives no direct compensation from the pharmaceutical sponsors.
Dr. Kathleen Foley in the past ten years has consulted with many of the companies that make analgesic drugs. In the past year she has worked with Purdue Pharma, Janssen, Knoll and Abbott. She is also on the Speakers Bureau for Purdue Pharma, Knoll and Janssen. Additionally, she is a scientific advisor to the American Pain Foundation.
Dr. Russell Portenoy has constituencies with Merck, Ligand, and Akros. He is also on the Speakers Bureau for Purdue Pharma and Janssen. Dr. Portenoy also serves as scientific advisor for Cima Pharmaceuticals, Durect, Chrysalis. Additionally, he reports involvement on contracts and grants with Parke-Davis, Boehringer Ingelheim, Elan, Ortho Bio, Endo, Ametek, Medtronic, Purdue Pharma, Pfizer, Janssen, Abbott, Curatech, Ortho-McNeil, Elan, Pfizer and Searle.
In addition, we would like to disclose that Charles McLeskey is participating in this meeting as an industry representative and acting on behalf of regulated industry. As such, he has not been screened for conflict of interest. Thank you.
ACTING CHAIRMAN KATZ: Thank you, Kimberly. What I'd like to do now is to reintroduce Dr. Bob Rappaport, who is Deputy Division Director of the Division of Anesthetic Critical Care and Addiction Drug Products at the FDA, and he will be giving us introductory comments this morning.
DR. RAPPAPORT: Dr. Katz, members of the Committee, ladies and gentlemen, I would like to thank you for returning for the second day of this Advisory Committee meeting on opiate analgesic use and abuse.
I would also like to thank the Committee for their discussion and commentary at yesterday's session. I am confident that your input will prove invaluable in our deliberations with our colleagues in industry regarding their development programs for opiate analgesics.
I would also like to thank the many individuals who have taken their time from their busy lives to present at the open public hearings. Your voices, too, will impact on the decisions we make in the future.
Yesterday we addressed the many practical issues related to the interface between clinical practice and clinical trial design. Today we will address the difficult topic of risk management.
Opiate analgesics are a two-edged sword in the medical armamentarium. They provide precious pain relief, relief of discomfort and relief of fear for many patients in pain, and yet their use can also have devastating effects when they are improperly prescribed, when they are diverted for illicit use or when children are accidentally exposed to these potent drugs.
Our purpose today is to find the right balance between the benefits and risks associated with opiate analgesics. We at the agency are well aware of the concerns of the people who speak passionately for both the enormous value as well as the significant risks associated with these products.
To help us to continue to provide safe and effective opiate analgesics to patients in need while avoiding the inherent risks of these products, we ask that you focus your comments on the discussion points that we have provided to you in your background packages. We also ask that you open your minds to both sides of what is clearly an emotional and complex topic for all of us.
Today you will first hear an industry perspective on the development of opiate analgesics. Following that, Dr. Judy Ball from the Substance Abuse and Mental Health Services Administration will present data on abuse and diversion of these products.
Dr. Deborah Leiderman will inform you about the process by which the FDA assesses the abuse liability of new drug products, and Mr. Howard Davis will present the DEA's perspective on criminal drug diversion in our communities.
You will also be informed about the epidemiology of prescription drug abuse by Dr. Howard Chilcoat, and about the problems associated with drug abuse in pain patients by Dr. Steven Passik.
Finally, Dr. Sharon Hertz will present to you some of the regulatory approaches that the agency has employed thus far to mitigate the problems associated with the abuse of opioid analgesics.
Armed with this invaluable information, we are asking that you incorporate it into your deliberations on a series of discussion points. First, we are asking you to address the adequacy of the available data to determine the prevalence of addiction among patients treated with opiates for chronic pain.
Second, we want you to address the available methods for assessing and monitoring addiction in the clinical setting and how those methods might be extended to clinical trials.
Finally, we are asking you to comment on what measures we should consider when we are assessing the development of an overall risk management strategy designed to reduce the abuse and diversion of opiate analgesics while avoiding restriction of access to these drug products by patients in need of treatment.
Once again, as I did yesterday, I would like to read briefly from Dr. McCormick's cover memo. While she has been unable to participate in this meeting due to a medical condition, her words speak eloquently to the conflicting concerns we face when assessing opiate drug development plans.
"This meeting is about the patient suffering from pain who requires opiate therapy for adequate management. It is about the patient who is an addict who also experiences chronic pain. It is about the individual who may have a propensity for substance abuse, who seeks opiate medication under false pretenses.
"It is about the youth who tries prescription drugs for the first time and dies from an overdose. It is about the infant or child suffering from a painful condition who may benefit from what once were adult medications."
Thank you.
ACTING CHAIRMAN KATZ: Thank you, Dr. Rappaport, for introducing some of the difficult challenges that we will be facing today in making some progress on these issues.
What we will do now is proceed to the open public hearing. I see some of our speakers are ready. What I would like to do is just make a few comments to the speakers, which are identical to the ones that I made yesterday.
The purpose of these comments is to make sure that everybody from our rather full list gets a chance to speak their mind. The main theme here is that I am going to be the nasty guy that makes everybody stick to their required time. So you've got three minutes. If you use less than three minutes, there's a special place in heaven reserved for you, I know.
There will be a green light on for two minutes. Then it will turn yellow for your last minute, and then at the very end there will be a red light, and then there will be a horrible buzzer, and then there will be unspeakable punishments.
Everybody should have a list of the order of speakers and, if you see that you are next, you should sit up by one of those "speaker ready" chairs, and the FDA technical people will help you find the right place.
So with that, why don't we have our first speaker, please.
MS. UNDERWOOD: Good morning. It's a pleasure to have this opportunity to speak with you. I'm Catherine Underwood, and I'm the Executive Director of the American Pain Society.
The APS is an interdisciplinary professional society of over 3500 members. The Society is a public, not for profit organization and has received support from pharmaceutical companies in the form of unrestricted educational grants in support of its mission.
Pain is one of the most common reasons people consult a physician. Yet it frequently is inadequately treated, leading to enormous social cost in the form of needless suffering, lost productivity, and excessive health care expenditures.
Patients with chronic pain and related disability are best treated by an interdisciplinary team. Since chronic pain is not a single entity but may have myriad causes and perpetuating factors, treatment strategies and options include behavioral therapies, rehabilitation, interventional therapies, and the sustained use of a number of different medications, including opioids.
Barriers to the use of opioids include often exaggerated concerns about addiction, respiratory depression and other side effects, including tolerance. In addition, fears of diversion and regulatory scrutiny weigh heavily on the physician's mind when he or she is considering prescribing these medications.
The APS shares society's concerns about addressing the diversion and potent opioids and other controlled substances for illicit use. Substance abuse, including alcohol, tobacco, opioids and other substances, lead to individual, family, and societal harm. However, we must not allow diversion and abuse of opioids by some to deny deserving suffering patients access to medications that relieve their suffering, lessen their disability, and improve their quality of life.
When considering options to address opioid diversion, policy makers should carefully consider the following: Opioids are important in the treatment of chronic pain, and benefits far outweigh risks in carefully selected patients. Opioids should be administered within the context of established patient care guidelines.
Physician and other health care provider education and training regarding the diagnosis and treatment of pain is poor. Patient care and outcomes could be improved with better education.
Tension exists between efforts to decrease abuse and diversion of opioids versus access to these medications for legitimate use. Policy makers, regulators and those in law enforcement should carefully consider the potential for harm to patients caused by efforts to control abuse and diversion.
Finally, policy makers should also strongly support increased funding for chronic pain research so that we can better understand the role opioids play in the treatment of these complex diseases.
Thank you for your time.
ACTING CHAIRMAN KATZ: Thank you. Next speaker, please. Before you begin, let me just remind all the speakers as well that it is important to begin after you say your name and who you are with your potential disclosure. So who do you work for, if there is anybody that sponsored your trip down here, if you work for an organization that is funded by a pharmaceutical company, please lay all that out right up front. Next speaker, please. Anybody there? Next speaker?
DR. CORK: Good morning. My name is Randall Cork. I'm the Chair of Anesthesiology at Louisiana State University, and I'm the Director of the Pain Management Clinic there. We serve an area of mainly northern Louisiana, eastern Texas, southern Arkansas.
In terms of disclosures, I've been in academic medicine for about 20 years. I've done a number of research studies in the name of the various institutions, and these institutions include University of Arizona and Louisiana State University, both of which have gotten funds from Merck, Roche, Pfizer, Alza and other companies.
I have also given some talks in northern Louisiana and souther Arkansas that have been funded by some of these companies.
I'm going to briefly comment on the written comments that I have submitted to the Committee, and then kind of take the opportunity of using whatever time might be left to address some of the things that were raised yesterday during the meeting.
In terms of my written comments, they are very brief. They specifically address the issue of opioids compare to nonsteroidal anti-inflammatory agents. It's always impressed me that we spend all of this time and energy attempting to regulate opioids, but we kill many more patient with nonsteroidals than we do opioids, and yet the regulatory efforts in that direction are minimal. Those drugs are available over-the-counter. We kill 17,000 people a year with nonsteroidals.
With regard to some of the comments that were made yesterday, specifically in my context I was not paid to come here by a drug company. The Department of Anesthesiology funded my trip because of the concern that our patients have expressed that the government is getting ready to help them again.
They were previously helped by the government of Louisiana when they instituted some of the rules that the Texas Board instituted in terms of regulation of physicians. What happened at that time was that suddenly the physicians in Louisiana were afraid to prescribe opioids again, and their patients all suddenly ended up on the doorstep of LSU. We now have about 500 patients on our waiting list.
Some questions for Dr. Levy that I have regarding these board regulations: It seems that the regulations do tend to effectively punish those physicians who prescribe opioids too much, but there has never been an instance as I know where Texas has disciplined a physician for not treating pain adequately enough, and yet as we found out from previous speakers, that seems to be the main problem.
ACTING CHAIRMAN KATZ: Dr. Cork, I'm afraid I'm going to have to ask you to bring your comments to a close.
DR. CORK: Thank you very much.
ACTING CHAIRMAN KATZ: The next speaker, please.
DR. BATTISTA: Hi. I'm Dr. Ellen Battista. I'm going to read off my paper here. I have over 15 years of experience in chronic pain treatment, both in cancer pain, nonmalignant pain. I have treated also children with pain and have established several programs in this area.
Currently I'm in a chronic pain practice. On the personal side, I am the mother of two, one teenager and a wanna-be teenager. As every parent, I have concerns whether my children will make good choices in life, and I am concerned with whether my children will engage in risky adolescent behavior that provides them with encounters with tobacco, alcohol and illicit drug use.
My multiple roles in life as a pain treatment provider and mother have caused me to look closely at the issues at hand today regarding the medical use of opiates versus its effect in drug abuse in this country. After close evaluation of the facts and my experience, I have come to today's meeting for the purpose of supporting legitimate medical use of opiates in the treatment of pain.
As you all know, over 100 million North Americans suffer from chronic pain. They are either partially or totally disabled by pain. The toll of unrelieved pain is high.
It leaves the individual with loss of function of daily activities, loss of financial stability, alters the individual's relationship with significant others, causes severe depression where suicide may be contemplated to escape its suffering.
It costs industry over $60 million annually -- billions, excuse me, not millions. There has been much research over the past 35 years, and we have improved our ability to treat pain. It still is not perfect.
More specifically, the advent of opiate drugs that are long lasting, sustained release or controlled release have provided patients an opportunity to experience more continuous relief than their predecessor drugs that afforded only several hours of relief.
Opiate analgesics can be therapeutic in a percentage of patients with pain problems. Their use should depend on intended outcome, and they should be monitored.
The issue at today's meeting is whether legitimate use of these opiates provide a risk to society at large, and we know that the adolescents are at highest risk. But despite this fact that we know that, we have no clearcut guidelines as to why drug abuse is a problem in certain individuals and why moment decisions have long term consequences.
It would appear that addiction behaviors are not only facilitated by environment but may also be influenced by heredity, cognitive development. In short, the addiction issue is complicated and multi-faceted.
Herein may lay the problem with the issues. We are taking a complicated issue of addiction, trying to place responsibility on one category of drug, and superimposing the issue of legitimate medical use for the treatment of pain, when the problems need to be analyzed and dealt with separately.
In a desperate attempt to curtail drug addiction in our society, we have tried to impose a cause and effect model where it is not appropriate. Simplistic solutions for curtailing or limiting a drug category will not alter appropriate -- not alter abuse for other drugs.
The issue of addition needs to be --
ACTING CHAIRMAN KATZ: I'm sorry. I have to ask you bring your comments to a close.
DR. BATTISTA: I am. Any action that limits or curtails legitimate medical use for opiates will harm millions of Americans who need these medications for the treatment of their pain. These drugs are vital. The use of opiate --
ACTING CHAIRMAN KATZ: I'm sorry. You have to stop speaking. Your time is finished.
DR. BATTISTA: I'm sorry. Okay.
ACTING CHAIRMAN KATZ: Could we have the next speaker, please.
MS. BALUSS: Good morning. My name is Mary Baluss. I am from the Palliative Care Law Project. I have nothing to declare.
I submitted a written statement to the Committee, and I hope that you will review it. In the interest of time and not being repetitive, I'd like to make three major points that were in the brief, but I wanted to highlight them somewhat.
The first is that pain is an epidemic, and it is untreated, as you've heard. I think one of the factors there that doesn't get much talked about is the fact that opioids are the first line of defense against pain in the poor, that there is a great deal of talk about opioids being appropriate only after other modalities have failed. However, in underserved, low economic status populations, it is not possible to refer the patient for extensive MRIs, and they are not available to the anesthesiologies and the procedural efforts to cure pain.
These folks are often limited, because they are on Medicaid. Medicaid often limits the number of prescriptions, and very few specialists will take Medicaid.
So if you restrict Oxycontin to specialists and if the state medical boards continue to harp on -- and I don't mean to be disrespectful -- all other modalities, then the people who work all their lives at jobs that are intensely physical, who have no medical insurance, and who live in a community where the first line of analgesia is alcohol will be seriously disserved.
Secondly, I want to tell you about -- and this is partly in response to Dr. Levy's presentation yesterday. After I left here yesterday, I got three communications. One was from a man in Missouri whose uncle was dying of massively metastasized cancer, who had had no pain medicine beyond over-the-counters, and his doctor, knowing full well he was in pain, had said to them I am not going to lose my license.
This is a doctor who chose gross malpractice over treating pain, because of fear of losing his license. Dr. Levy was very, I think, appropriately clear yesterday about the number of sanctions by state medical boards. However, that understates the problem very dramatically, because it doesn't take into account letters from state medical boards that quite reasonably scare people off the market. It --
ACTING CHAIRMAN KATZ: Could you wrap up, please?
MS. BALUSS: Yes. So there are -- The other two pieces of news that I got yesterday was that one doctor's DEA license was being pulled. Thank you.
ACTING CHAIRMAN KATZ: Thank you very much for your comments, in particular those about the role of opioids in the poor. You can go ahead and have a seat, please.
I just want to reemphasize the purpose of the timer for the subsequent speakers. The purpose of the timer is so that today in a very difficult and challenging area where there is a wide diversity of opinions and a wide spectrum of individuals to be represented, we want to make sure that everybody is heard. So I have to be the rude one to enforce the timer, but I hope that you will forgive me in advance and do your best to stick within your allotted time.
Yes, the next speaker, please.
DR. GALLAGHER: Good morning. My name is Rollin Gallagher. I am representing the American Academy of Pain Medicine and its Board of Directors. The American Academy of Pain Medicine does receive funds from a variety of industry sources for continuing education in pain medicine.
The American Academy of Pain Medicine recognizes and is concerned about reports of potential actions by the DEA and the FDA about the -- to restrict the availability of Oxycontin, and the recent media coverage sensationalizing opioid diversion and abuse is causing several states to consider the ban of some opioid preparations.
This action will adversely affect the care and the lives of many millions of patients who legitimately require these medications and opioids in general for management of their pain disorders in order to function in their lives.
Media publicity, when biased and nonscientifically based, further promotes a believe in the general public that proper treatment of pain disorders with opioids will invariably result in addiction.
Physicians fearing undue discrimination, persecution, investigation and possible prosecution will avoid prescribing opioids to the detriment of their patients, and even when they are the safest and the most effective treatments.
The AAPM, the American Academy of Pain Medicine, and the AMA are on record as strongly opposing medication diversion and abuse and supporting the DEA and state medical boards' efforts to curtail diversion. We support and sponsor continuing education of all physicians on the appropriate use of opioids as part of pain treatment.
We recognize, however, that addiction is an important neurobiological brain disorder affecting many aspects of a person's life, and the root cause of drug abuse is not any one drug but rather untreated addiction and the lack of access to good addiction treatments.
In June the AAPM sponsored a resolution to the AMA which was passed to established policy to (1) support the prevention and treatment of pain disorders, including the continued education of doctors in the use of opioids and other treatments for pain; (2) to support education of all medical students and physicians in pain and addictions; (3) to serve as educational resources to the media by providing objective information regarding the management of pain.
In the interest of time, I will wrap it up for you guys. I support the other statements that have been made about the importance of opioids in pain treatment. The AAMA and the APM remain committed to promoting appropriate pain treatment, and we will be available to you and your distinguished panelists to explore acceptable and available methods to prevent and eliminate diversion and abuse of controlled substances. Thank you very much.
ACTING CHAIRMAN KATZ: Thank you, Dr. Gallagher. May we have the next speaker, please.
MR. LIEB: Good morning. My name is Rick Lieb, and I am here to speak with you not only as a Board member of the National Pain Foundation but also as a person who lives with chronic pain.
Consequently, let me be presumptuous and say that I feel as though I am talking for the millions of people in the U.S. who live daily with pain. I am here because I am concerned at the recent publicity surrounding the misuse and abuse of pain medications, particularly Oxycontin, because of backlash in this country that will set back pain treatment years, if not decades.
Both as a Board member of the NPF and as an individual with chronic pain, I am concerned that this resulting backlash from these tragic incidents will have even more severe repercussions for people like me who rely on these kinds of pain medications to live more normal lives.
I would like to share with you in a very brief manner my personal experience with chronic pain. In 1995 and 1996 I had two low back fusions in an effort to fix degenerative disk disease. As a result, I was left with arachnoiditis which, as you know, is a condition that is progressive and is really disabling and generally leaves people unable to work.
From 1996 to 1998 I lived with this problem. I continued to work, but the pain was clearly beginning to interfere with my personal and professional life.
In my search for pain relief, I visited multiple doctors. Every single -- Every visit was incredibly frustrating. Just five years ago, many physicians viewed pain either as a character flaw or as untreatable because of their own reluctance to prescribe pain medication stronger than nonsteroidals.
In addition, many doctors strongly suggested to me that the use of any medications more potent than nonsteroidals was an admission of character weakness and could lead to addiction. This personal indictment occurred despite any analysis of my own personal background, including a tour in Vietnam as a Marine infantry officer, a flourishing family and demonstrated success in the business world and being on various -- in a publicly held firm and on multiple public and private boards.
In 1998 I met my current pain management doctor. He taught me an entire program, and I manage my pain, including the appropriate use of opioids. He taught me that pain is real and that the appropriate use of narcotic medications will reduce pain, improve an individual's quality of life, and enable someone to continue on with their personal and professional goals.
He taught me that opioid use is not a result of a character flaw, but an appropriate part of pain management treatment.
I strongly urge the Committee to consider the needs of the many rather than the failings of the few when the time comes to draft public policy for the safe and effective use of these medications.
I speak on behalf of the Board of Directors of the National Pain Foundation to offer our assistance in addressing the serious problem of diversion and access to good medical care and successful pain treatment. Thank you.
ACTING CHAIRMAN KATZ: Thank you, sir. May we have the next speaker.
MR. LIEB: Seven seconds.
MR. CINQUE: I have a brief disclosure. The organization I represent does receive unrestricted educational grants from the pharmaceutical industry.
I'm Michael Cinque, pharmacist, Chief Pharmaceutical Care Officer for Excelerex. Excelerex provides pain management support services for hospice patients across the nation.
I'm here today on behalf of the American Pharmaceutical Association, the national professional society of pharmacists. Prescription medications are safe and effective when used appropriately, but they can be deadly when used incorrectly.
Pharmacists are the health care providers who work most closely with patients to make the best use of medications. We also work with prescribers and other providers to prevent medication misuse such as diversion and abuse.
We look for such abuse markers to visit -- as visiting multiple prescribers and unusually large quantities. However, it's not always easy to determine if a prescription is fraudulent. No simple algorithm determines appropriate use, and pharmacists cannot view every patient as a potential drug abuser without compromising their responsibilities as a health provider.
The APhA applauds the FDA and DEA efforts to ensure the legitimate users of opiate analgesics maintain the ability to continue using these products. We caution, however, against efforts to restrict distribution or create administrative processes like triplicate prescriptions that limit a provider's ability to prescribe or dispense appropriate therapy.
With every barrier erected to limit diversion, the potential for those barriers to diminish appropriate prescribing increases exponentially. Restrictions in the drug distribution process will disturb patient care by delaying access to medication therapy and disrupt existing patient/pharmacist/prescriber relationships.
Any additional stigma attached to these drugs will have a chilling effect on a provider's willingness to prescribe and dispense the appropriate pain medication and patients' interest in using it.
APhA believes that measures to curb abuse and addiction should be considered, but discourages using any administrative barriers like triplicate prescriptions as a risk management solution.
A survey conducted by New York State's Public Health Council found 71 percent of physicians surveyed reported that they do not prescribe the most effective pain medication for cancer patients if the prescription requires a special state monitored prescription form for controlled substances, even when the medication is legal and medically indicated for the patient.
We were pleased that during the December House subcommittee hearing on Oxycontin, both DEA Administrator Hutchinson and Subcommittee Chairman Wolf stated that they do not want or intend to restrict legitimate use of Oxycontin. According to Hutchinson, the DEA recognizes that the best means of preventing the diversion of controlled substances, including Oxycontin, is to increase awareness of the proper use and potential dangers of products. We agree, and not that pharmacists can be an excellent communicator of that information.
In conclusion, it's important that patients do not lose timely access to a valuable class of effective pain medication because of a failure to prevent medication misuse. Again, I emphasize that restricted distribution and administrative barriers are not the answer.
The solution requires the education of health professionals, law enforcement personnel, and the public on the use and abuse of pain medication.
Thank you for your consideration of the views of the nation's pharmacists.
ACTING CHAIRMAN KATZ: Thank you very much. Next, please.
MS. BURKHOLDER: Good morning. I am Rebecca Burkholder with the National Consumers League. I would like to inform the Committee that occasionally the League receives financial support form pharmaceutical companies for specific consumer education projects in which we maintain full editorial control. This amounts to less than one-half of one percent of our annual operating budget.
The National Consumers League is a national nonprofit consumer organization that has represented consumers and workers in the marketplace for over 100 years. The League provides information and educational materials to consumers so they can make wise health care decisions, including the safe and effective use of pharmaceuticals.
The League commends the FDA for looking at the problem of illegal and inappropriate use of opioid analgesics. A delicate balance must be struck, however, between the prevention of abuse of a powerful opioid and ensuring that individuals suffering from debilitating chronic pain have access to drugs that offer prolonged relief.
NCL believes FDA's decision to strengthen the labeling of Oxycontin is justified. The black box warning prominently reminds physicians, pharmacists and patients that Oxycontin contains a powerful opioid with potential for abuse and addiction.
The more detailed indication and usage section helps limit overprescription by identifying situations in which the drug is not indicated. These warnings should change any faulty prescription practices as well as alert physicians to the potential for abuse, misuse and diversion.
Although misuse and diversion are and will continue to be potential problems for all opioids, it would be indefensible to deny pain patients a safe and effective therapy. Today there are between 50 and 60 million Americans who suffer from chronic pain.
The under-treatment of pain affects the quality of life for millions of people, from cancer patients to those who suffer from severe osteoarthritis or back pain. Oxycontin is one of the effective treatments for pain, because it provides continuous relief from prolonged or chronic pain.
It is critical that any regulatory measures taken to reduce abuse and diversion of opioid analgesics not interfere with the legitimate use of these drugs. For those patients who find Oxycontin the most effective safe treatment for pain, the drug should continue to be available.
We encourage the FDA to continue to education health professionals and the public on the appropriate use of opioid pain medications. FDA should also continue to monitor reports of abuse, misuse and diversion of opioids and work with other Federal agencies and drug manufacturers to ensure that opioids remain available to the appropriate patients.
We believe that the stronger FDA warnings for Oxycontin will help ensure that the drug is not misused.
Finally, the League hopes the FDA will continue to take into account the entrance of millions of legitimate uses of opioid analgesics when it makes important decisions concerning these drugs. Thank you.
ACTING CHAIRMAN KATZ: Thank you. Next, please.
DR. BUEDE: Good morning, members of the Committee and audience. My name is Dennis Buede. I have a PhD in Engineering and no conflicts of any kind with pharmaceutical companies to report.
I am here today as the spouse of someone who suffers from perimenopausal exacerbated severe hormonal migraines, often three days of duration and duration disabling pain. For approximately 12 months my wife has been under the care of Dr. Statkis of the Dulles Pain Management Center.
Not only has her condition greatly improved, but the improvement in her wellbeing and ability to function has made it possible for me to accept a position at Stevens Institute of Technology. This position requires greater time away from home.
As a Professor of Systems Engineering and with a specialization in decision analysis, the description of your announcement indicating that you were undertaking the risk to benefit ratio of extending opioid treatment into the populations of pediatric patients and patients with nonmalignant etiology intrigued me.
This is very relevant to our family situation, especially since the DEA has mounted a campaign against doctors and pharmacists responsible for the Oxycontin abuse.
I would like to address some key issues involving both values and uncertainties for viewing the risk to benefit analysis that you are considering. First, let us address uncertainties. Uncertainties exist for many reasons. Three of the most important for the opioid treatment of pain are the variation among humans -- none of us is the same, and no solution fits us all; the unknowns in medicine that are still left for us to fathom; and the relative ratio of people using opioids for pain relief versus abusing the opioids for an addiction.
The first example of uncertainty presents itself to us on a daily basis. Yet we are constantly finding educators and health care providers trying to fit us all in the same pair of shoes. When one of us visits a doctor and receives any kind of medicine, there exists uncertainty about whether our body will respond the way others have.
As an example of the second reason, a limited knowledge in medicine, it was not too long ago that we discovered that infants feel pain, changing the medical recommendations of family decisions associated with such practices as circumcision.
I would like to also address the fact that -- the issue of patient complaining of pain. It is not difficult to use opioids responsibly. I know it is indeed a difficult issue faced by prescribing doctors.
I would like to offer an analogy for viewing this problem. In this nation and many others, there are a certain number of bad police persons. As a society, we do not disband the police force, because most police persons are honest, and we need them, just as we need pain relievers.
A police chief cannot tell a bad potential hiree from a good potential hiree with perfect accuracy during the interview process, just as a doctor does not have the ability to perfectly discern a new patient is a person in pain from an addict.
Just as we let the police chief hire the individuals that he/she believes are the best candidates, we should let the doctor prescribe the appropriate pain medication.
ACTING CHAIRMAN KATZ: Dr. Buede, I'll have to ask you to wrap up your comments.
DR. BUEDE; Okay. I'd like to wrap up with this statement from Albert Schweitzer in 1953: "We must all die, but that I can save a person from days of torture, that is my great and ever new privilege. Pain is a more terrible lord of mankind than even death itself."
I would suggest that this privilege be considered at the FDA as well. Thank you.
ACTING CHAIRMAN KATZ: Thank you very much. Next speaker, please.
DR. CRANMER: Yes. I'm Kerry Cranmer from Oklahoma City. I have been a geriatrician, have been involved in Speaker's Bureau for Abbott, Lilly, Falding, Janssen, Purdue, Ortho-McNeil and Novartis. We have done Phase III and IV studies for Omnicare Clinical Research involving several companies.
As a geriatrician, I have limited my practice to long term care and the treatment of the frail elderly. Our concern is to be able to provide the comfort and dignity that they do deserve.
I want to kind of spend a little bit of time discussing what some of the research has shown as far as the prevalence, the results and the treatment of pain in the frail elderly population.
First of all, in 1996 Winnie Stein showed that 45 to 80 percent of all the patients in long term care facilities had chronic daily pain, depending, of course, on the facility. In 1998 we are all aware of Joanne Lynn's support study showing that 50 percent of the patients dying in the hospitals were in moderate to severe pain in the last few days of life.
In 1998 Bernibye basically showed that cancer patients going into long term care were not treated in their daily pain, and that 40 percent of them showed chronic daily pain, and approximately 25 percent of those were not on any analgesics whatsoever.
The next year provided another study based on a chart review. The MDS, minimum data set, is required on every patient admitted to nursing homes. Based on those assessment forms, we found out that -- and reviewing 50,000 of those patients -- that the same figures were found. Thirty-three percent were in daily pain, and 25 percent of those were on no analgesics whatsoever.
We found out by that that we had to increase physical therapy. We had increased depression. We had increased loss of activities of daily living.
Even last year, Joan Tino at Brown University showed us in 110,000 charts that were viewed and MDS data that was reviewed, we found out that similar findings, and I'll just surmise to say that we had 40 percent of those that were in severe pain, were still in severe pain 60 to 180 days later.
We have a tremendous prevalence of pain in these areas. The results of that chronic pain have basically shown us that we have physical as well as psychological consequences. The depression, the increased activities of daily living are major issues that we have to be concerned about.
Opioids are the most geriatric friendly medications that we can use. Nonsteroidal anti-inflammatories can provide renal impairment in their chronic use. I think proproxyphene has been on the inappropriate list for over 20 years now for geriatric patients.
Opioids remain the preferred treatment for the elderly. Diversion is always a concern for every conscientious physician, and yet we have yet to find in the nursing home increased stolen televisions and selling of sex for increased drugs. We just haven't seen it.
I just want to surmise to say that we feel like we have to address the needs of the frail elderly in America and provide the comfort and dignity that they deserve. Thank you.
ACTING CHAIRMAN KATZ: Thank you very much. Next, please.
MR. MONAHAN: Thank you for the opportunity to be here this morning. My name is Jim Monahan. I'm the Program Administrator of Houston Hospice in Houston, Texas. I've been doing hospice work for the last 16 1/2 years.
This morning I am speaking on behalf of Houston Hospice and the Texas and New Mexico Hospice Organization on whose Board I serve as Vice President. Neither I nor Houston Hospice has been reimbursed or given any consideration by pharmaceutical companies to be here today, although both the hospice and the hospice organization have received educational grants from pharmaceutical companies to put on educational offerings to the professional community.
I'm speaking on behalf of the 14 to 1500 patients also who will be treated by Houston Hospice in this next year and by the many thousands of other patients treated by the hospices in Texas, New Mexico and the rest of the country, with the goals of eliminating pain and other symptoms and finding meaning in the last days and weeks of life.
Let me tell you about one of these families. Last summer I went to visit a patient in one of the better hospitals in Houston. He was in his mid-seventies. When I arrived at the hospital, his granddaughter was holding his hand and saying, "Grandpa, I love you."
He was moaning in pain. That was his response. His family was there, adult children and his wife of many years. After some conversation about hospice and hospice goals, they said we know he's dying; if he could die without pain, we'll be happy. The man was in extreme pain. He had been in the hospital for ten days at that point.
His son and daughters were medical personnel. They were nurses, paramedics and helicopter pilots who did emergency medicine. The son came to me and said that his father's physician had suggested morphine for his dad, but it was up to the son. It was up to the son to make that decision.
There were fears that the son expressed of addiction, of ceiling limits that we know about with patients afraid that if they start now, it won't be available later, and just stoic ideas of a very practical family about using narcotics at the end of life.
I think this is wrong. It shouldn't be left to the family. It shouldn't be left to the person. It should be up to the health care providers to make these decisions with the input of the family, and every obstacle that we put into place that limits the good pain control is a disservice.
Obstacles include physical obstacles such as limits on the manufacturing or distribution, psychological obstacles such as fear and other factors involved, and educational obstacles. We need to teach our health care providers more. We need to do less to increase and enhance the fear of distribution of medications.
Two days ago in the local paper I saw an article about the theft of Oxycontin from a pharmacy. I did not see in today's paper anything about the wonderful testimony yesterday about people's pain, people's lives being given back from eight years of pain, and others.
These are the stories that are overlooked by our media. It's up to us to get the word out about good pain control, good symptom control to the American public and to our health care providers. Thank you.
ACTING CHAIRMAN KATZ: Thank you, Mr. Monahan. Next, please.
DR. GLOTH: I'm Dr. Michael Gloth. I'm on your list for yesterday actually, and there was apparently a mix-up, and I got today as being my day.
I'm Associate Professor of Medicine at Johns Hopkins. I'm the Chief of Geriatrics at Union Memorial Hospital. I serve as President of Victory Springs Senior Health Associates, one of the few private practices in the country that consists of physicians all fellowship trained in geriatrics.
I serve on the American Geriatric Society Board that is currently revising the chronic pain guidelines for the older adult, and I also serve on the panel that is revising the Behrs criteria. I'm the immediate past President of the Hospital Network of Maryland.
Eastern Cooperative Oncology Group study, a study of cancer patients looking at pain, demonstrated that the number one risk factor in that study for inadequate pain management was simply being over the age of 70.
We often get sidetracked with side effects, and thus do not provide effective pain management. It would be unfortunate if additional regulation and restrictions on opioids were instituted and, by doing so, we limited the availability of these opioids to those folks that need them.
It is important for us to make sure that we recognize that such singling out of opioids will lead to a limited use of these opioids by prescribers. Recognize that the Behrs criteria will not list Oxycontin as a drug to be avoided in the elderly. IT is one of the opioids that reaches its steady state in the most timely fashion of all oral opioids available.
In the interest of maintaining my special place in heaven, I am going to close, but I hope that you all will maintain your special place in heaven by allowing us to continue our efforts to relieve suffering for seniors. Thank you.
ACTING CHAIRMAN KATZ: You forgot your disclosures, Dr. Gloth.
DR. GLOTH: I'm sorry. I am affiliated with just about every pharmaceutical organization that is associated with oral analgesics. I'm either serving as a speaker on their speaker's bureau, a consultant, or else I have received grants from those organizations. Thank you.
ACTING CHAIRMAN KATZ: Thank you very much. You still get your place in heaven. Let me remind the subsequent speakers to begin with their disclosures. Thanks.
MR. COLEMAN: Good morning. My name is John Coleman, and I am a former Assistant Administrator of the Drug Enforcement Administration who for several years was in charge of law enforcement operations for the agency, including those carried out by the DEA Office of Diversion Control.
In 1998 I retired from the DEA after 32 years of service. Although I appear here today as a private citizen, in the interest of full disclosure, I must state that I am member of the Speaker's Bureau for Janssen Pharmaceutica. I have also been the recipient of an unrestricted educational grant from Janssen to support my academic work.
I would like to spend the next few minutes talking about something I believe is directly related to the questions posed by the Committee regarding prescription drug abuse.
Given my background, I am concerned about the quality of data being collected and published by the government on prescription drug abuse in America. Prescription drug abuse is a function of many things, including price, availability, accessibility, rate of onset and duration of effects, the effects themselves and the route and ease of administration.
Subjective factors also play an important role, but they are far more difficult to isolate and assess on a global basis. Knowing some of the key factors that influence prescription drug abuse should intuitively lead us to design survey instruments that distinguish and measure these specific characteristics.
Of all the national drug abuse surveys conducted by the Federal government, none provides enough specificity to measure these factors. Ironically, field collection procedures often harvest the data, only to have them discarded when they are aggregated and assigned to broad categories or generic chemical names for publication.
Let me give you an example of what I mean. According to figures released by the Drug Abuse Warning Network, our most important survey for estimating drug abuse, in the year 2000 hydrocodone was the nation's most frequently abused prescription opioid. This information is surely useful, but consider how much more useful it would be if we knew the specific formulations of hydrocodone that were most often abused.
This limitation in data becomes even more critical in the case of C2 opioids that are available in injectable, solid doses, sustained release and/or transdermal forms. Research shows that the form of an opioid may be an important determinant of its overall abuse potential.
As a former DEA official, I am familiar with some forensic databases that do provide product specificity for prescription drug abuse, and exhibits that are submitted to laboratories for analysis. These data provide very useful information but cannot be used as a prognostic system or one that estimates drug abuse in the general population.
I urge this Committee to support the efforts of the Substance Abuse and Mental Health Services Administration as it redesigns its survey methodologies that I believe can be improved significantly with some very reasonable and modest adjustments. What I propose is almost something unheard of in government, a no or low cost solution.
As for the potential economic consequences for those products identified as most frequently abused, I would offer that the interests of both the public and industry will be best served by more, not less, information. Indeed, it seems like an imminently proper use of government regulatory authority to encourage the development of abuse resistant drugs and/or innovative delivery systems that inhibit abuse. I believe that over time --
ACTING CHAIRMAN KATZ: Mr. Coleman --
MR. COLEMAN: -- providing product specific abuse information will have immediate benefits for the groups I have cited. Thank you very much.
ACTING CHAIRMAN KATZ: Thank you. And I'll point out for the group that Judy Ball from SAMHSA will be addressing some of these issues later on in her discussion. Next speaker, please. No next speaker?
Why don't we do this then. Are there any other speakers who are on the speaker's list for yesterday who, for some reason, could not make it and are available today? Okay.
Next then, we will go -- We have a very short waiting list of other speakers who wanted to share some comments with us. The ones that I am aware of -- Is Myron Yaster here? Okay. Dennis Fisher?
DR. FISHER: Thank you, Dr. Katz. I'm Dennis Fisher. I am a Vice President for Medical Affairs of the Durect Corporation in California. Until about two years ago, I was a professor of anesthesia at the University of California, a pediatric anesthesiologist and very involved in pharmacokinetic and pharmacodynamic studies of opioids and other anesthetic drugs.
The issue I would like to address regards some comments that were made yesterday regarding the conduct of studies in pediatric patients. The Committee could readily have come away from the meeting yesterday thinking that it's very easy to conduct chronic studies in pediatric patients.
Dr. Katz, I think, tried to elicit some comments about the difficulty of that, but unfortunately the various members of the Committee, I think, directed that it really was not difficult to conduct those studies.
I'd like to cite an example that indicates some of the difficulties of doing these chronic studies. Recently, I spoke to the Medical Director of a large pharmaceutical company that is presently evaluating a pediatric formulation of their new opioid.
This company had so far been able to conduct studies in a little over 100 patients, but it had taken 18 months to enroll these 100 patients, and they had over 100 sites that they had used to enroll these 100 patients. These 100 sites were in something like 15 countries on four continents.
One can readily imagine the quality of data from a study conducted with 50 different case report forms in different languages, etcetera, etcetera. I think the reality is that doing these chronic studies, the true chronic studies, not the acute perioperative studies, is very difficult.
I would be very concerned if the Committee would leave here with the wrong impression of that. I welcome comments from Dr. Robin and Dr. Schreiner regarding this issue. Thank you very much.
ACTING CHAIRMAN KATZ: Thank you, Dr. Fisher. I think that it would be fine to take one or two minutes while we are on the subject, if anybody from the Committee or invited guests wanted to respond to Dr. Fisher or comment about whether it is easy or difficult to do trials in pediatric populations. It would be a good time to do that. Dr. Foley?
DR. FOLEY: I want to support what Dr. Fisher said. This is exactly what we from the National Cancer Policy Board heard repeatedly, at least looking at chronic pain studies in children with cancer.
ACTING CHAIRMAN KATZ: Did anybody else want to comment about that? Dr. Schreiner, did you want to talk about that?
DR. SCHREINER: I think if you are looking at the true chronic pain population such as cancer, it is going to be very difficult to do studies that go beyond seven days. The majority of pediatric use for opioids is for much shorter periods of time.
I think that the other thing is, if the studies can be focused on the information that we really need to know and eliminate the unnecessary parts of the studies that create barriers for patients' willingness to participate, then it would be easier to do the trials.
I personally as a pediatrician want as much information as possible, but I want it to be focused on the information that we need to use the drugs.
ACTING CHAIRMAN KATZ: Thank you all for your comments on that important issue. Now is there anybody else here who did not pre-register to speak in the open forum who would like to come up to the podium and have three minutes to share comments? I can't guaranty that everybody will get time, but we can certainly start. Yes, please, name, disclosures and your thoughts.
MS. STEFFLER: Good morning. Thank you. My name is Dorothy Steffler. I have nothing to disclose. I am here in twofold purpose. I am the mother of the young gentleman aged 42 who went through the crisis.
Everyone is talking about the euphoria that comes with use of Oxycontin or opioids. The euphoria that he displays is the new life that he now has, and it's more of a happiness and a socialization return rather than the deep depression and antisocial life that he had. So that could be misleading, that term.
I am also here because I am a state inspector for the Department of Health in the state of Pennsylvania. I have been there for 11 years. I've been in health care since 1951.
I am one of the persons who, on a daily basis, visits the nursing care facilities with the elderly, and I have seen hands on the difference since pain management has been addressed by the HCFA, now CMS.
It is my responsibility in my position to write deficiencies for physicians who have not managed pain. We see -- I have seen in this year since HCFA has addressed it as the fifth vital sign -- and I do a lot of this in-servicing, too, not only the nursing staff and the professionals but the housekeepers and the nurse aides who are there to see the nonverbal pain behaviors that are exhibited.
We see a decline in dietary, in their weights, sudden, unexpected, and physicians usually immediately go to Megase or supplements. No one asks them if they are hurting, and we have been on this promotion.
So I am twofold in the use of opioid therapy. I have seen it. They are giving Darvoset n100, Tylenol 325 times two, 650, q4. I can read it in every single record that I audit, but I have seen the difference in this year of the rise in the activities of daily living when in the plan of care we are addressing pain management for the elderly and the nonverbal we have taught -- are in the process of teaching. However, it's the physicians that we need to reinvent the wheel, because they are fearful of writing anything.
As the physician before had mentioned, it is in the MDS. We scrutinize the MDS. That's the pain -- or the money, financial part, and we have residents who have nonverbal pain, and it is less than daily or excruciating, mild to moderate. But we have strictly one medication. That is Tylenol, again 325. They are fearful.
I do see the difference when they do order. Some of them are doing Duragesic patches. I do Oxycontin, not only for hospice but the other one. Thank you so much.
ACTING CHAIRMAN KATZ: Thank you. Is there anybody else from the public who would like to have three minutes to share thoughts with us about these issues?
DR. MERRICK: Mr. Chairman, Dr. Merrick from yesterday, if you would allow me to speak again. I just have -- I want to echo a few comments from some eloquent speakers this morning.
One of the factors a family physician -- I have no disclosures, self-funded. As a family physician, one of the greatest barriers I've seen to the treatment of chronic pain in the poor in my area of rural Virginia is going to be access to how to pay for all the ancillary services and complementary services that you can give patients in treatment of chronic pain. They are simply not available. Opioids are the keystone for treating rural poor as far as chronic pain.
The second issue, to address the gentleman from the pharmaceutical industry, from the pharmacist industry rather: One of the key obstacles that I have as a family doctor treating chronic pain now is the fact that pharmacists in my area will not fill my prescriptions because even I have communicated with them before as far as the patient is legitimate. They have gotten a copy of the patient-doctor contract. I've done everything I can possibly do to contact the pharmacist.
One of the problems I see is the pharmacists of this country have not been brought along with all of the physicians in the education with chronic pain, and I think that that is a major issue that we are going to have to address if we are going to really have a comprehensive national approach to chronic pain, is bringing the pharmacists with us. Thank you.
The last comment was basically, in yesterday's discussion I noticed that function was left out as a major keystone to see the effectiveness of opioid treatment. That, to me, is one of the major issues, is function is the key to whether or not successful therapy is being administered. Thank you.
ACTING CHAIRMAN KATZ: Thank you, Dr. Merrick, and we'll hear more about that from Dr. Passik today as well.
What I'd like to do now, since we still have a few extra minutes, is if there were any of the public speakers from today whom I had to rudely cut off at three minutes, if you would like an extra three minutes -- but I would just ask you to bear in mind what's already been said and, if you've got something new to add to the conversation, we would look forward to hearing it. So three minutes each, please.
DR. CORK: Well, thank you very much.
ACTING CHAIRMAN KATZ: You're welcome.
DR. CORK: Again, I'm Dr. Randall Cork from Louisiana State University.
There were some issues regarding the specific questions that I know the FDA wants answered that I wanted to take an opportunity to respond to those, the two questions from yesterday, the target population and the second question about clinical trials.
In terms of target population, I really think that it's important to have a multi-level target. I think that the FDA should be concerned that -- We know about opioids. They have been around for so many thousands of years. There is really no reason to focus on efficacy so much with opioids. You need to focus on safety with opioids, and I think Dr. Portenoy's three points on safety should be adhered to in terms of FDA plans for certification of new drugs.
In terms of clinical trials, the issue of chronic efficacy, I think if you dwell on that, it will only serve to delay the introduction of new drugs into the system and will increase the cost of those drugs.
So in terms of today's questions, the adequacy of available data in terms of the prevalence of addiction, I believe the FDA can help with that by indicating on the package insert, as Dr. Portenoy recommended, the risk of addiction for the drugs. I think physicians need to be educated that short acting narcotics have a higher risk of addiction than longer acting narcotics such as Oxycontin.
The methods for assessment and monitoring of addiction, I think, are a good idea. Those things should be introduced into the protocols and addressed in the package insert.
In terms of reduction of addiction or the risk of addiction, I really believe that that is more of a police issue rather than an FDA issue. I think that rehabilitation, forced rehabilitation has been shown to be effective in terms of reduction of addiction.
In terms of another comment that was made yesterday from Dr. Zedd or Zetma from Virginia -- I forget what -- it had to do with criticizing the drug company for providing education to physicians. I think that was misplaced. I think Purdue Pharmaceuticals should be commended. They have provided us with a lot of educational materials to involve the Family Practice Department and to provide education to our medical students about treatment of chronic pain.
Thank you very much for this additional three minutes.
ACTING CHAIRMAN KATZ: Thank you. May we have the next speaker, please? Mr. Coleman.
MR. COLEMAN: Thank you very much, Doctor, for this opportunity to resume.
As I was talking about the specificity of the data that I believe is seriously needed, I would like to add that, in my view, we will not be very effective in addressing prescription drug abuse until we can identify with a reasonable degree of specificity the frequency of drugs by product names and formulations that are being abused.
Presently, we do not have this information available in the field of drug abuse research, although something similar does exist in another very similar or somewhat related field. For example, the FDA is justifiably proud of its adverse event reporting system that is used to collect and disseminate post-marketing drug and therapeutic biological product safety reports.
In addition to other pertinent information, the AERS data format requests that the contributors enter a, quote, "valid trade name" for the product being reported. I am sure that every member on this Committee is familiar with the value of the AERS.
Now I ask you, how valuable would that information be for you or your patients if the, quote, "valid trade name" were dropped somewhere in the process and replaced by simply a generic chemical name?
I hope this helps you to understand my concerns about the need for better drug abuse data. by not providing what the AERS refers to as valid trade name for the most frequently abused drugs, usefulness of surveys is limited. As a result, anecdotal information often takes over and, as someone on the Committee yesterday wisely pointed out, anecdotal information may regrettably become the basis at times for public policy.
Thank you very much. That's the conclusion of my statement.
ACTING CHAIRMAN KATZ: Thank you, Mr. Coleman. Next, please.
DR. DESJARDINS: Thank you, Dr. Katz. I'm Dr. Paul Desjardins, Senior Vice President for Clinical Site Operations for a research organization named SCIREX Corporation. I am also a member of the American Society of Clinical Pharmacology and Therapeutics and I am speaking on behalf of the investigators and individuals who are actually trying to perform the clinical research to develop better drugs and better strategy for dealing with patients who have both acute and chronic pain.
I would like to suggest to the Advisory Board and to our colleagues from the Food and Drug Administration that we are in a very similar position to those of us who were investigators 30 years ago who were facing many of the same questions in terms of how best to deal with patients with moderate and severe acute pain.
The analgesic guidelines which were developed by the scientific community with the concurrence of the Food and Drug Administration and sponsors was an enormously successful project. The current guidelines which exist deal in explicit detail for drugs with acute pain, but deal very superficially on drug development issues for patients with chronic pain, and in particular developing the standards for what will be considered appropriate and well controlled clinical trials.
I would strongly urge that the Advisory Committee work with and advise the Food and Drug Administration to continue that process, to update either those guidelines or develop separate guidelines which will address the scientific issue to the satisfaction of the clinicians, the scientists and the regulators who have to make very difficult decisions. Thank you.
ACTING CHAIRMAN KATZ: Thank you. Did anybody want to address the issue of whether there are any plans in place for reexamining the analgesic guidelines or shall we leave those discussions for later?
DR. RAPPAPORT: I just want to clarify that at this time the guidelines that are out there are outdated, as far as we are concerned, and we are in the process of developing new guidelines. I can't give you an exact time course for when those will be ready, but we are working toward those coming out as soon as possible, and we are working with the other analgesic division to see that they are consistent across the agency.
ACTING CHAIRMAN KATZ: Thank you, Dr. Rappaport. Next speaker, please.
MS. BALUSS: Thank you.
ACTING CHAIRMAN KATZ: We will have time for one more after this.
MS. BALUSS: It's unusual for a lawyer to be talking about facts, but I do have to prove them.
I wanted to talk with you about how little we know that is very relevant to some of the law enforcement and diversion questions that come up.
We don't really know who the chronic pain patients are or where they are or what has failed them and what has worked. We don't know a whole lot about long term outcomes for them.
Where that becomes important to me is that I see someone testifying that a doctor has acted improperly because he has continued to prescribe opioids for someone whose function may or may not have improved enough. Well, what's enough, and how long should someone -- Is there a temporal limit on opioid therapy?
I don't think we know this, and it works as a severe detriment, because some of these little markers get translated into kind of unstructured evidence where it really isn't evidence.
I think that we need to know a whole lot more about outcomes. We have no idea -- We are requiring doctors and penalizing doctors for not having a good command and control system, but we don't know whether the patient contracts affect the diversion rate at all, and there are a lot of other things we don't know about that kind of medicine. Thank you.
ACTING CHAIRMAN KATZ: Thank you. Next, please.
DR. BUEDE: My name is Dennis Buede again. I want to address one issue I hadn't quite gotten to. That has just been raised by the last two speakers, our intrinsic failure as humans to think that we know a lot more than we do.
Oh, I see this in engineering, and I have also seen it in visiting many doctors that we've gone to over the years. My wife and I were talking to a prospective primary care physician just a few weeks ago, and he was telling my wife that he really does not prefer to treat the pain. He prefers to treat the underlying cause.
Yet in most cases today, as many of you know, the doctor has no hope of finding an underlying cause. There has been some recent research. It may or may not prove to be true, but it indicates that by treating the pain, the patient has a much better chance of recovering from whatever is ailing them if you are also able to treat the other aspects.
So while we are stuck in this situation, and I probably think that we probably know less than half of what there is to know about medicine and taking care of people, we still have to make decisions with the best information that we have and recognize this amount of uncertainty. Thank you.
ACTING CHAIRMAN KATZ: Thank you. Dr. Max, one comment.
DR. MAX: Yes. I just want to comment in regard to Paul Desjardins' call for more academic FDA consultation. Ray Dionne at the National Institute of Dental Research and Jim Witter of the Anti-Inflammatory Allergies Division of CDER are holding a symposium on the NIH campus on some issues in acute and chronic pain drug development on March 13th and 14th, and they want -- It's an open meeting, and you can contact either of them for an agenda.
It seems like it's still open for shaping. That's all I know about it.
ACTING CHAIRMAN KATZ: Thank you. That will be the end of our open public hearing for today. Thank you very much, everyone, for coming, in particular the patients and their families for taking the trouble to come visit us today.
What I would like to do now -- We do have an industry presentation that we have scheduled for 9:30. What I would like to do in the five or so minutes before we start that is to make a few introductory comments of my own for today's session, and then also to attempt to summarize for the folks who were not here yesterday what seemed to me to be the salient themes in our conversation from yesterday that, hopefully, will inform our discussion today.
Of course, it's always a risky business to summarize everything, because nobody ever really agrees on what exactly it was they heard, but I'll do my best. If I get anything completely backwards, then, hopefully, somebody will raise their hand and briefly point that out, without necessarily reopening the discussion in just the few minutes that we have before our scheduled presentation.
Let me begin by thanking the rest of the Committee and invited guests for what I think was a very productive and professional discussion yesterday. This is a very difficult topic, the issue of opioids, and people tend to get very dogmatic and excited about it, and I think that our discussion yesterday was very fruitful.
Today we have even greater challenges, I think, in our discussion. I don't know that there is any medical issue that I deal with that gets people as excited or dogmatic as the issue of addiction and opioids, and it's been that way for a long time. Medical professionals are coming at this from very much different angles. Historically, there's been fairly little communication among different subspecialties of medicine in terms of how one can understand these problems.
There are different languages that we use to describe the same phenomena, and we will often have difficulties in communication, not necessarily because of disagreement about underlying principles, but because we are using different words for the same thing. That will be a challenge for us today.
So I look forward to the -- What I want to do is reiterate what I said yesterday in my introductory comments, which is that the goal of today's meeting is not necessarily to solve the problem of addiction and opioids, which we certainly aren't going to be able to do.
It's not even to come to consensus on all these issues, which also, I think, is unrealistic, I've heard today. We will definitely end up disagreeing on some of these issues, but what I hope that we can do for the FDA today is to at least lay the issues on the table, help to define what the problems are that we are dealing with, present all the relevant points of view, even though they may be opposing, and try to understand them, and discuss what the implications are of those perspectives for development and marketing of opioid analgesics.
I think, if we can do that, that will be a tremendous accomplishment. I would ask the members of the Committee today, when they do make their comments, to try to move forward from what have been the historical problems of the past in communicating about these issues.
One problem has been that we all have biases because we tend to see very select populations and then come to conclusions about what is true about the whole world. So as you do make your comments about what you think is true, please bear in mind whether your convictions may result from seeing selected populations, and present your views to the Committee with that in mind.
Secondly, as you present your convictions and thoughts to the group, I would ask you to try to also communicate what you feel the level of evidence is for your assertions.
Is it an anecdote or a collection of anecdotes? We heard yesterday what that amounts to. Is it research? What kind of research is it? Is it randomized controlled trials? Is it long term follow-up? That way we will be able to evaluate your comments more thoughtfully in terms of what the strength is underlying them.
So that's my charge for the group for this morning.
To quickly try to summarize some of the salient themes that I heard discussed yesterday which will, hopefully, provide a platform for our discussion today before we begin our industry presentation, this is what I heard yesterday. Again, if I get anything completely wrong, without necessarily opening up the discussion right this second, I hope somebody corrects me.
Number one, it seems like we all agree or we certainly heard many times that opioids are essential for relieving pain. There has been a great -- That's point number one.
There has been a great deal of progress made over the last few decades by increasing the availability of opioids to physicians who need to prescribe them appropriately, and a great deal of progress made with demonstrations in the literature of safety and efficacy of opioids for both acute and chronic pain.
My point number three is that any restrictions on the availability of opioids to patients or prescribers have substantial potential risks of harming patients and reversing some of the progress that's been made. So there clearly is risk involved in any restrictions.
Therefore, the theme that I heard was that it's important that we all take a balanced approach in our recommendations about opioids where we simultaneously try to balance maximal availability to patients that need them, at the same time trying to stem the problems of addiction, diversion and related processes without trying to impede patient access. I heard that many times yesterday.
I also heard that taking care of patients with chronic pain, including the prescription of opioids, is appropriately within the province of the primary care physician, although there may be a need for education and further efforts to optimize therapy in that setting and any other setting. I heard that expressed many times, and the specific issue of the need for more education I heard expressed many times as well.
I also heard expressed that broad labeling for mu agonist opioids is in general something that should be strived for, and that we heard clearly from Jeff Bloomer, patient representative, that broad labeling is better for patients, and we heard from Dr. McLeskey that that is also more attractive to industry.
We heard a number of times, most especially from Dr. Foley, that in terms of the patient populations that are potentially appropriate for opioid analgesics, we don't have enough data to exclude a priori any patient population for consideration of opioids for long term therapy. There's just not enough data at this point in time. More data is needed.
Therefore, we shouldn't a priori exclude any patients from consideration for both clinical treatment and clinical trials. However, we also heard that different subpopulations may have rather different considerations in terms of understanding the risk/benefit ratio.
For example, patients with a history of substance abuse, elderly as we heard today, pediatrics -- there may be a number of subpopulations where we need more specific information to really understand the risk/benefit analysis. That's what I heard yesterday.
I heard that, quote/unquote, "traditional" efficacy programs may be sufficient to define a drug as an opioid analgesic and that that may be sufficient to work toward this broad labeling, and it seemed to me that I heard that one did not need to demonstrate efficacy in every last type of pain in order to understand that an analgesic was behaving like an opioid analgesic.
I also heard that there was, however, other very important types of information that was critical to the understanding of the risk/benefit ratio of opioids, particularly for chronic pain. In particular, we need to understand safety issues to understand the risk/benefit ratio of opioids, and safety includes the risk of addiction.
It includes neuropsychological side effects. It may include, as some folks mentioned, potential endocrine side effects. These are important issues in terms of understanding the risk/benefit ratio of opioids.
We need to understand the durability of response, and perhaps we will get a chance to talk more about tolerance today. Dr. Portenoy addressed that a bit yesterday. Again, we need to understand risk/benefit for certain specific subpopulations.
We heard some creative discussions yesterday about how some of these studies might be done. Since some of these issues are not necessarily product specific but are germane to the whole class of opioid analgesics, there was some discussion about whether there could be collaboration between industry and NIH to study these risk/benefit issues across the class of opioids.
There was discussion about whether there could be a possibility of acquiring some of these studies as part of a Phase IV program, and also I heard discussion about whether these would be more appropriately part of a traditional Phase III program, and we certainly didn't resolve the issue yesterday about how these studies are most appropriately conducted.
So that's what I heard yesterday. For now, right before a presentation, if anybody thinks that I got something completely wrong or neglected to say something that was absolutely critical from yesterday on these points, please point it out now. There will certainly be ample time later to delve into the details of everything that I've said now, including the topic for today, which is addiction.
Dr. Roberts, please.
DR. ROBERTS: The only thing I would add, Dr. Katz -- that was an excellent summary. You were awake the whole day. The only thing I might add is that we discussed at several junctures the value of going to the practice setting to do the kinds of research that needs to be done, because it's really where the rubber hits the road, and the issues of diversion contrasted against effectiveness, safety -- I mean, that's really where you're going to see what's happening out there.
ACTING CHAIRMAN KATZ: Thanks. Dr. Haddox, then why don't we -- Thank you very much -- go to your presentation then, and perhaps, Dr. Haddox, you could give a more complete introduction to yourself before you begin the presentation.
DR. HADDOX: Thank you very much. I appreciate the opportunity to be here to address the Committee. I thank the PhRMA and thank the FDA for giving me this opportunity.
By way of disclosure, I am a relative newbie to the industry, and in the past five years I have either consulted for or spoken on behalf of Astra, Merck, Pfizer, Janssen, Purdue, Ortho-McNeil Pharmaceuticals, Roxanne, and I had some research funded at Emory by Wyeth-Ayerst.
For those of you who don't know me, I started out life as a dentist. I then went to medical school, and I did a residency in anesthesiology and psychiatry following that. Following the dual residency, I then went into a pain medicine fellowship.
I am certified in pain medicine, in psychiatry. I have a subspecialty certification in addiction psychiatry pain management, and I was a practicing clinician/educator up until two years ago when I joined Purdue Pharma.
I am the past President of the American Academy of Pain Medicine, the American Board of Pain Medicine, and a former Director of the American Pain society.
If we can get the slides going today, what I would like to do is share with you an industry perspective on how we can ensure the proper use and curb abuse of opioids.
One of my main functions, I forgot to admit, is to make sure that Dr. Portenoy is not alone as the only graybeard in the field of pain.
I would like to talk with you briefly about the disease burden of pain. I know there's been a lot of comments about that, but I'd like to report some data. I want to talk briefly, recap the treatment of chronic pain in particular, since that is an issue that's come up quite a bit.
I would like to talk and share with you what we have learned about -- in the past two years about prescription drug abuse, and I'm sure it's no surprise to the Committee that we've learned a lot about this in the past two years.
I would like to close with an analysis of risk management plans and where the industry sits on this and where we should sit on this.
When we talk about the disease burden from chronic pain, we are somewhat hampered, because we don't have overall national statistics. The Centers for Disease Control and Prevention, for instance, does not assay chronic pain in its annual disease and health survey.
So we really don't know from a full demographic study what is going on, but there are three surveys that I would like to highlight for you. Now these surveys are done by reputable survey organizations, typical polling organizations with demographically representative studies that can be extrapolated to represent the entire United States, and they span five years.
The first occurred in the state of Michigan. The second was about midway between, and the last was one that we paid for and had done actually just a few days ago in preparation for this presentation.
In 1997 a survey was done in the state of Michigan called "The State of Pain," and it showed that 1.2 potentially out of their 9.8 or about 12 percent of their population had a pain problem that had lasted for more than six months, either continually or intermittently.
Seventy-seven percent of the sample had experienced pain for over a year. Thirty-five percent had missed more than 20 days of work, a tremendous economic and social burden to the society and to the individual and family.
In a heavily managed care penetration state, 13 percent had been denied medications, devices or referral to a specialist. Now this can be extremely demoralizing for a patient with chronic pain. The types of patients that I saw in my clinical academic practice often had to go through enormous hoops to even get into the door.
This can be so demoralizing that, in fact, ten percent of the survey had contemplated the idea of suicide as a way of relieving their pain.
I have personal experience with this in a patient that I'd like to share with you. I was treating a woman who, fortunately, with our integrated treatment plan at Emory had done very, very well. She was very pleased with our care and, while she was not perfect, she was much better. She was sleeping better. Her quality of life had returned and, most importantly, she was able to enjoy things again.
She was doing very well. I was seeing her about every month, along with our psychologist and a physical therapist. She came in one day, and she was very distraught. I, treating chronic pain, know that we have flare-ups and things go, but I asked her what was going on.
She immediately broke down into tears, and she told me that her 26-year-old daughter who was a worker's compensation patient, who had chronic low back pain from a work related injury, and she had -- because the mother had come to a pain center and had found out that there were, in fact, pain physicians and multi-disciplinary teams, and her quality of life had improved so much, she was entreating her daughter to get the primary assigned doctor at worker's comp to refer her to a pain program, mine or someone else's.
The daughter had a lot of hope for this, and she pursued this actively with her adjuster, and what they did was denied it, and they sent her to yet another type of specialist.
This person diagnosed depression, not terribly surprising, given the fact that this woman's life was coming undone, prescribed an antidepressant, and after a few weeks she took her own life, 26-years-old, low back pain, noncancer pain. Took her own life, and she left in her suicide note to her mother that all hope had been dashed when her referral was denied, because she had seen how well her mother had done, and she was hoping she would be in that category.
I submit to you that this is an absolute travesty in a country that has the best available health care system, ostensibly, in the world.
In 1999 the American Academy of Pain Medicine and the American Pain Society did a survey funded by Janssen looking at moderate to severe, chronic, noncancer pain.
The extrapolated figure was again about ten percent of U.S. adults, but this is a slightly smaller scale, because we are not looking at any chronic pain. We are looking at moderate to severe, and you had to have a five or above on a numerical rating scale to actually get into the survey.
I have the seven and the eight through ten highlighted as 57 percent of people that had severe pain in this survey. Fifty-one percent, consistent with the things we heard yesterday, are in fact seeing a primary care physician. Another chunk were seeing some other specialist, and a very small percentage were seeing a pain specialist.
Two-thirds of the sample had lived with pain for more than five years. Seventy-eight percent reported daily pain, and ten percent reported turning to alcohol as an analgesic, which we all know is a very dangerous pastime.
I was interested in how the public felt about treatment with opioids in preparation for this presentation. So we contracted with Harris Interactive and surveyed 1439 patients who had chronic pain and who had been taking an opioid for at least four months.
Most commonly reported: Arthritis, low back pain, migraine, cancer, not terribly surprising, and some patients reported more than one pain causing condition.
The analgesics spread: About what you would expect. 638 were taking Schedule II opioids. Schedule III through V were 1125, NSAIDs about the same, and acetaminophen about 800, and many were taking more than one. In fact, the average, if you look at chemicals, it was about three to four chemicals per person, including combination analgesics.
The numerical pain rating estimates on a one to ten scale: You can see here that 22 percent were in the severe range. Now remember, these are people taking opioids. That's how you would get qualified for the study -- or for the survey.
We asked if pain was controlled. Twenty percent said no, not surprisingly. In those whose pain was well controlled, 39 percent had had to go to more than three physicians and pursue care for more than six months to get some kind of care that resulted in decent pain control, and in the ones whose pain was not controlled, 65 percent, two-thirds, had seen more than three physicians, had been trying for -- Almost all had been trying for more than nine months, and still their pain was not well controlled.
We asked some statements: Do you agree or disagree with the following statement? Patients do not have trouble obtaining needed pain medications. Fifty-four percent of the sample disagreed. These are people taking pain medications.
We asked: I have not experienced any problems getting treatment for my pain. Thirty-five percent disagreed.
As you've heard yesterday and today, a significant barrier to treatment is the fear of addiction, and in clinical practice, and many clinicians here on the panel know this quite well, there is a great deal of confusion between the entity physical dependence, which most of us recognize as a known effect of certain classes of medications, and addiction, which is a disease.
So we asked this case. We said, imagine that a patient was taking a pain medication for six months and suddenly stopped taking it. As a result of not taking the medication, they experienced nausea, sweats, had difficulty sleeping, and felt tense and jittery. Based on this information, can you conclusively state that the patient is addicted, physically dependent, both, neither, or not sure?
Now people on this panel know that the correct answer, based on this limited case information, is (b). That's the only thing that you can conclusively state. There might be other things, but that's what you can state based on what was presented.
When we looked at how the patients did, 37 percent, little over a third, got it right. Unfortunately, 16 percent said this was addiction. Thirty-five percent said it was both. Two percent said neither, and ten percent were not sure. So a little over 50 percent of the patients are confusing this on a regular basis.
When we asked the question a slightly different way: If you are taking a pain medication and you stop it and you have withdrawal, does that mean you are addicted? -- 53 percent said yes.
The Liaison Committee on Pain and Addiction composed of the American Academy of Pain Medicine, the American Pain Society, and the American Society for Addiction Medicine got together, and it promulgated definitions that they hope will become standard that will span all specialties, not just addiction or not just pain.
They stated that addiction is a primary chronic neurobiologic disease. It is a disease with genetic, psychosocial, and environmental factors influencing its development and manifestations, and it is characterized, as Dr. Portenoy said yesterday, by behaviors that include one or more of the following: impaired control over drug use; compulsive use; continued use despite harm; and craving.
Contrast this with physical dependence, which is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or the administration of an antagonist or a neutralizing or reversal drug.
Physical dependence is a known effect of certain drugs, including opioids. Addiction is a disease that sometimes involves opioids and sometimes involves other substances.
So as we go to treat chronic pain, we must integrate therapies. I found this very interesting, because this is very similar to what Dr. Portenoy showed you yesterday, and yet we developed these quite independently, I assure you.
Physical therapy can certainly have many things to offer people with chronic pain. Therapy for the comorbidities, the sleep disturbance, the anxiety disorders, etcetera. The cognitive therapies have been shown to be extremely useful, particularly in helping people cope with pain as severe as rheumatoid arthritis. Behavioral therapies are a mainstay of many programs, involving the lifestyle changes you've heard mentioned several times yesterday.
The interventions, the things that I did as an anesthesiologist, spinal cord stimulators, pumps, nerve blocks, have a role in helping certain patients. Surgery may be of use in some other patients.
The spectrum of rehabilitation services ranging from orthotics and splints and specific occupational therapy all the way to comprehensive rehabilitation programs such as run at many -- like that are run at many universities.
Of course, pharmacotherapy is going to be a part of this. What the physician does is to take each individual patient sitting before them and integrate a plan of care, drawing from each of these various spokes on the wheel to optimize the function and comfort of that individual patient.
When you talk about pharmacotherapy, of course, you are going to talk about prescription medicine. In this discussion that we've been having yesterday and will continue to have today, it's important to emphasize there are two distinct populations at the very least that we are discussing, patients with legitimate need who are appropriately using these very valuable medications and inappropriate use, the abusers, the diverters, the people suffering with addiction.
Prescription drug abuse is a longstanding, serious problem in this country. It predates the Food, Drug and Cosmetic Act. This is not new. I think what is new, and quite frankly I'm very happy that it's new, is the heightened awareness of the problem.
Clearly, that has happened, and Purdue takes this very seriously, and we are devoting enormous energy to reduce the inappropriate use of these medications. But what is the real scope?
As you've heard today from Mr. Coleman and others yesterday, and you will hear more today, there are issues with our national data sources. The surveys that are commonly used to show trend information about abuse were not designed to assess abuse of prescription medications and, therefore, they have some areas that could be improved.
In fact, this was pointed out at a NIDA press conference in April of last year, that prescription drug abuse is a largely unrecognized problem in this country and is a significant component of the overall drug abuse picture and, unfortunately, not much has happened since that press conference in heightening the understanding.
Now we've learned a lot about diversion in the past few years. We are very actively engaged with law enforcement as well as regulators and clinicians. Doctor shoppers are clearly one source of diverted drug. These may be organized rings.
I've actually heard of people conducting classes in how to dupe doctors, how to forge medical records, how to feign signs, or how to feign symptoms and create signs to lead a doctor down the wrong path, or it might be the sole proprietor, the individuals who are doing it for money or to support an abuse interest, or both.
Prescription fraud comes in many varieties: Altered prescriptions, simply changing the number or the information; forged prescriptions, stealing prescription pads from the doctor's office; or counterfeiting, just manufacturing prescription pads, fairly simple to do these days with scanners. Theft from patients and from pharmacists, and then prescribers.
The AMA has described the classic four D's: The outdated physician; the duped physician; the dishonest, criminal physician; and the physician who he or she himself is impaired and is engaged in prescription drug diversion to support their own habit.
The public health ramifications of this are substantial. There is the problem of experimentation in naive persons, and by naive I mean in both contexts here, people who are opioid naive. That is, they have had little exposure to opioids and, therefore, have not induced respiratory depression tolerance; or the naive person who is taking something they know nothing about.
There is a new wave sweeping the country where people put a bunch of pills, prescription pills, in a candy dish and pass them around, and you take one or two or a handful at a party. This is called pharming, p-h-a-r-m-i-n-g. It's a very distressing trend, and as a parent of two young daughters, that just scares me to death.
Then we have found, as has the DEA in their autopsy studies have found, that quite frequently prescription drug abuse is not abusing a single drug. It is abusing multiple drugs in combination, often with alcohol, a very deadly cocktail.
There are the problems of substance abuse which you've heard about and will hear more about today, the cost to society, the cost to the individuals and, most importantly, the cost to patients, how this is impacting access and appropriate care.
If we look then at an integrated approach to ensuring proper use and curbing abuse, as some of the questions the FDA has posed to you today, certainly statutes and regulation have a role here.
The Controlled Substances Act is designed to ensure an adequate supply for legitimate medical and scientific needs of controlled substances, while at the same time preventing diversion.
Regulation such as -- and statutes such as prescription monitoring programs, as was referenced yesterday by Dr. Levy: Electronic data capture programs can be very, very effective in curbing abuse and making sure legitimate patients have the medication available to them.
Surveillance systems and interventions: Again, going to Dr. Levy's talk yesterday. The medical board gets the prescription monitoring plan data, and then can make appropriate educational or, rarely, disciplinary interventions as needed.
Law enforcement: There are many, many jurisdictions in this country where there is not a single officer doing drug diversion work. There are many doing vice and street narcotics, but there's relatively few who are focusing on this very important problem.
Access to addiction treatment: We know the statistics are very clear that addiction treatment is more effective, resulting in fewer relapses, and is far more economical than incarceration.
Education and prevention: If we can educate our young people, give them the smarts to say no to prescription drug abuse, to not start to dabble in that area and go down this road, we will find that this is also more effective and cheaper than even treatment.
New chemical entities and new formulations: Purdue is actively pursuing these kinds of things to try to find medications or create formulations that will not be desirable to abusers and yet will still provide full benefit to patients.
Well designed, articulated, multi-pronged, living risk management programs that can adapt to new situations as information is brought forth is a very important part to this approach.
Finally, improved practice at the clinical level: Better knowledge and skills and better application of those knowledge and skills.
All of these facets together working in harmony can result in optimal public health.
The risk management plans have been talked about by the FDA for sometime, and they are to be commended for pursuing this, because it is time that we look at this in a different perspective.
As we get more and more sophisticated medications on the market, we are going to find new risks that we didn't even see before, and we have to be able to communicate those risks and manage them appropriately for optimal public health.
Scheduling, of course, when you are talking about controlled substances, is the linchpin of a risk management program. Scheduling, by its very nature, implies that the drug has abuse potential, and yet, if it's a Schedule II or lower, has legitimate medical need.
Labeling is the dominant communication, the thought from which all subsequent communication from a manufacturer to the end prescriber or dispenser derives. Labeling has to be accurate. It has to be clear, and going to the scheduling issue again, if labeling -- if the box warning you heard about today is the strongest form of labeling that the FDA can use, and scheduled drugs by their very nature have abuse liability, we support the use of box warnings appropriate to the schedule for every scheduled drug. In fact, we in conjunction with the FDA worked on the box warning for Oxycontin's package insert, and we submitted without any prompting or discussion a similar box warning for our MS Contin product.
The education of health care professionals is an imperative part of risk management. These are the people who are making the clinical decisions. This should be an industrywide commitment. Purdue, for our part, has been doing a great deal of education and prevention of diversion, stopping abuse, detecting and assessing addiction.
In the last two years, we have touched over 250,000 health care professionals with those messages. In places where Oxycontin abuse and diversion were problematic in some of the rural areas where it was difficult for people to travel long distances, we did long distance learning education through Webcasting and through teleconferences. We took the information to them, made it accessible in their backyard.
We have put together CD ROMs of important links on the Webs of diversion related and addiction related materials, monographs, and in documentation kits which we have distributed, about a quarter million kits to guide a doctor through the documentation process that the medical boards require.
Education of patients and caregivers: When we started getting into trying to understand the abuse and diversion problem of prescription drugs, we ran up on a sobering fact. All of the educational programs that currently exist to try to dissuade our young people from drug abuse mentioned nothing about prescription drugs. They tell you about street drugs, but they don't tell you what's in your medicine chest or your kitchen at home.
So we created a program called "Painfully Obvious" that is designed specifically to market the message to youth in a way that youth will get, which would be quite different than marketing to you, I assure you, that prescription drug abuse is drug abuse.
We also have created what I believe to be -- and it's been approved by the agency -- the first patient package insert for a scheduled opioid.
Surveillance activities I referred to earlier, and there is a number of different types of activities, including the post-market experience, the MedWatch program, and other types of programs which I'll highlight in a moment.
Stepped interventions: When you do surveillance and you gather experience, you must make interventions that are appropriate to the information that you find. You must continuously assess the outcome of those interventions in a constant cycle of reassessment, reemphasizing different parts of the risk management plan, and revision as situations dictate.
In balancing the need to treat chronic pain, I'd like to give you some examples of what the various players can do.
Government, clearly, can encourage education about pain care and addiction. In California there is now a legislative mandate that, as a condition of licensure, you must have pain medicine and palliative care education in medical school. West Virginia has now invoked required CME for pain for renewal of licensure.
Class labeling: The broad labeling we've talked about is appropriate, but also there is information that is appropriate to the class. We have enough knowledge now about opioids that we can put in reasonable statements in all opioid labels to talk about things that are common. Also the long term studies that are proposed would provide more information in this area.
In law enforcement: In some states, for instance, the trafficking in Schedule III opioids is a misdemeanor. It's not a felony, and busy prosecutors often will not waste time with misdemeanors.
Industry can certainly encourage, facilitate and provide education. We have distributed, for instance, the Federation of State Medical Board guidelines. Purdue has distributed well over 100,000 copies of those to physicians around the country. The APS Analgesic Guides, thousands of copies. Lawful prescribing slide kits, addiction assessment slide kits, and we have also been very actively involved in educating law enforcement.
Risk communication: Clearly communicating the risks such as the box warning.
Here's an example of some of the diversion information we put out, and we have samples that I will leave with Ms. Topper for the Advisory Committee. You can see with a simple four strokes of the pen, I was able to alter the prescription on the left to now get something that is four times as strong as the physician intended and to walk home with 60 more than the physician intended.
If, however, we get physicians to carefully write this out with the word "ten" behind the strength and the quantity, as they would write their own checks, this would be much harder to do.
There's a phenomenon called rinsing whereby someone uses a solvent to try to take away the ink that I've written and then write in what they wish. Tamper resistant prescription pads, not pre-printing your DEA registration number on prescription can help with this.
The tamper-resistant pads I mentioned, we are now distributing. These pads have six different security features included. A couple that I'll point out: You can see the word "void" appearing here when it is scanned or photocopied. In the actual sample, it's much more prominent. It doesn't project well.
It says right here "valid for controlled substances only" so that the pharmacist knows, if they get a controlled substance from a prescription pad in my office and it's not on one of these, they should be suspicious.
This background bleeds very easily if you try the rinsing or alteration technology. On the back there is a watermark, and there is also a disappearing thermochromic ink that, when you rub it, the heat from the friction of your finger makes it disappear; and while you can emulate that with a scanner, you can't duplicate that with a scanner.
We are now distributing these on a state by state basis, starting with areas where prescription abuse and diversion have been most prominent.
Government can also, as you heard today, assist with data collection and interpretation on pain, addiction, abuse and diversion, and we welcome partnerships with NIH for these long term studies that were talked about yesterday.
Government can promulgate s