FEDERAL DRUG ADMINISTRATION HEARING APRIL 23, 2002 STATEMENT 1. PERSONAL INTRODUCTION I am William W. Brown, currently 69 years of age, from Columbus, Ohio. My address is 2999 East Dublin-Granville Road, Suite 217, Columbus, Ohio 43231. I have been a practicing attorney in Columbus for forty-two years and a licensed pilot for 35 years and have suffered with Irritable Bowel Syndrome for nearly forty years. Other than IBS my health is very food: low cholesterol levels, and no prior genetic or personal history of cancer, hear problems, diabetes or stroke. I was first diagnosed with irritable bowel syndrome in approximately 1963 by a Columbus gastroenterologist so at that time call it a "dumping syndrome" later called spastic colon. His statement was that this was all caused by stress and if you get over the stress you will eliminate the problem. In the late 1960s a family physician prescribed Lomotil which worked for a while. The dosage had to be increased gradually since the body apparently adapts to it. By the elate 1990s it only had moderate effects and only if you were taking four pills at a time. It is well known that the maximum dosage is eight pills per day, and as a pilot I am not allowed to take its medication while flying. Since I used my airplane in business, flying to client conference in Michigan, Ohio, Washington D.C., Chicago, etc., the non-use of this medication restricted the use of my aircraft. After a physical examination in the summer of 1999 with a Columbus gastroenterologist he said "Well, you have the same problem you have always had which we now call irritable bowel syndrome. Maybe in ten years we will find a cure and laugh about it." In October of 1999 I went to Mayo Clinic in Rochester, Minnesota for a complete physical examination which included a colonoscopy. Prior to that time I had every possible test made to determine what the nature of the disease was and what could be done to transform it including dermatological examinations for food sensitivity, H pylori, gall bladder scans and complete blood work-up. In November 1999 Mayo Clinic in Rochester did colon motility testing and determined that motility was far too rapid. Upon using Alosetron beginning in November of 1999 for six weeks the subsequent colon motility testing was much improved at a reduced rate. During that period that I was taking Alosetron I was able to eat practically anything. Subsequent to this open label study I was on at Mayo Clinic and after the Alosetron trial was over I was given a prescription for Zofran which was moderately effective until Lotronex was approved in March of 2000. I began taking two tablets per day of Lotronex as soon as it was available on the market and continued until December of 2000, approximately a month after it was recalled. I remained on Zofran from time to time as needed until November 2001 when I began participation in a Solvency Cilasetron double blind study in Columbus, Ohio. Since that time I have been unable to take any medication for IBS except the study medication which apparently is a placebo since the IBS symptoms are back with a vengeance. 2. EFFECTS OF IBS-D A. SOCIAL Since suffering with irritable bowel syndrome, may events have been eliminated from our calendar including such things as the symphony, opera, stage and even movies due to the fact that frequently explosive IBS occurs at an unpredictable time and with no warning. B. TRAVEL Short travel is mandated with IBS, however with Lotronex anything is possible. One has to be aware where all bathrooms are at all times when traveling and consider the frequent need to travel with a complete new set of underwear, medication, etc., travel is too difficult. C. WORK When I am trying cases I most often take two briefcases to the court room. One contains underwear, medication, wash cloths and other things necessary in the event an explosive diarrhea situation occurs. In addition over the last forty years I have frequently had to cancel or interrupt client conferences due to explosive diarrhea or just being too exhausted after a serious bout of diarrhea for several days. D. EATING HABITS I must avoid many food including the following: Herbs, salads, sauces, ethnic foods, wine, blue cheese, bearnaise sauce, bacon, lettuce, tomatoes, cabbages, rare beef, and many other foods. Even foods cooked with wine are an automatic problem. I might add that his gets worse as you get older. On two occasions, business golf outings were interrupted with episodes of explosive diarrhea. No bathrooms wee available, only bushes and woods. Needless to say this was extremely embarrassing for both me and the clients. 3. AFTER LOTRONEX Lotronex is almost a "miracle cure" for me. I was able to travel anywhere as long as I had my supply of Lotronex with me. In fact my wife and I were able to make an around the world trip to places not normally visited such as Easter Island, Papua New Guinea, Cambodia, India, Oman, and even Tanzania without third world countries which have very little medicine available or clean bathrooms. In addition I have been able to eat almost anything including the worst offenses to me which are wine, hers, tomatoes and blue cheese. I have never experienced any side effects with the use of Lotronex including constipation. This has also been true with my use of Lotronex. Nothing works for me except Lotronex. In the past and over the years I have tried Metamucil, Immodium, Levbid, Calcium and Lonotil. None of these have ever worked for me at all with the exception of Lomita to some extent. IMAGE Ever since man discovered fire he realized the risk of getting burned. The risk was acceptable however in order that he might have heat, light, and be able to cook his meals, and he accepted that risk. Until nearly one hundred years ago our government maintains that attitude-that man must accept certain risks, and the government' s job was not ensure man against all risks. Until nearly one hundred years ago, our government has told us, first, that fire must be licensed. Next we were told there wee only certain people who could light fires, and then only in certain places could fire be made. There were also laws passed which created fines and imprisonment for violating fire laws. At the turn of the 21st century our government is now saying the risk of using fire is too great to live in the cold and the dark - the risks of getting burned are too great to allow the risk to continue, plus someone might sue us. 4. RISK MANAGEMENT I have read the complete 247 page transcript of the June 27, 2000 Advisory Committee meeting and understand the FDA's concerns on postmarketing of Lotronex It would appear that Glaxo Smith Kline had already developed an aggressive and responsible postmarketing plan, as outlined by Dr. Elizabeth Anderson and J. S. Hull, which included an FDA approved observational cohort design study and communication program. The communications program itself is as thorough as possible and needs no re- explanation. Dr. Michael Camilleri of Mayo Clinic in an article written for the Gastroenterology Journal last year addressed this issue and discussed what he called the "Exquisite Dilemma" of the risk/benefit issue. "Unfortunatley, withdrawing a drug while saving some individuals from a serious adverse effect, may deprive others of the only agent able to relieve their suffering." There is currently no effective postmarketing surveillance on most drugs to enable the manufacturer or the FDA to more clearly determine drug efficacy or safety. In the case of Lotronex, I would be willing to participate in a reporting system. The problem seems to be that physicians do not make reports and patients do not always follow advice. What methods may be available to ensure the safety of Lotronex? A number of ideas have been advanced: (a) Compassionate Use: While FDA may permit a limited use for certain persons, it has been reported that most pharmaceutical companies including Glaxo SmithKline are not willing to commit to that approach. (b) Restrict dispensation of the drug to gastroenterologist. This is overly restrictive as many family physicians and general practitioners are more knowledgeable about Lotronex than specialists. In my own case, my family physician has 20% or four of his staff who are affected with IBS-D and has read all of the literature available on IBS and Lotronex. In addition many patients may live in small communities with no access to a gastroenterologist. c) Waivers: Most of us who were greatly benefited by Lotronex would be willing to sign waivers of nonliability in favor of the FDA and the pharmaceutical company. This, however does not address postmarketing concerns of the FDA. d) Warning Labels: Better warning labels probably are ineffective. The patients seldom read them, or feel they do not apply to them. e) Physician Education: Perhaps the FDA can create a class of physicians who are permitted to write these prescriptions who have, or have agreed to certain minimal requirements in Lotronex education, and who have agreed to monitor closely the patient's use of Lotronex; possibly set minimum guidelines on prescriptions, such as quarterly physician/patient visits, colonoscopy every 3-5 years, or annual physical examinations, all to be reported by the physician to the FDA. 5. GENDER AND AGE DISCRIMINATION The FDA originally approved Lotronex for women only. Several writers have indicated men were not benefited from the drug. This assertion is false, as you can see by the number of men speaking today. it would appear from the historical position that women may suffer more from IBS than men. It is also true that there are may more women undergoing studies than men for at least two reasons: The first is that a woman's physical makeup is far more complex than men. Second, probably is that men are just plain not as interested in study programs. In addition there have been a number of articles indicating that IBS generally diminishes with age. This is also not true. Certainly my IBS is ten times worse at age 69 as it was at 59. To my knowledge, there have been no studies that have quantified this position. I urge you to make Lotronex available for men, as well as women. Postmarketing surveys t be done by Glaxo Smith Kline can support this position. 6. CONCLUSION My position is that the job of the FDA is to ensure the safety and efficacy of any drug but not to ensure that no one is at risk by taking any drug which would include aspirin. All drug manufacturers including Glaxo Smith Kline are entitled to sell their products at a reasonable profit after approval of the FDA so long as there e are reasonable warning labels. No pharmaceutical company is guaranteeing in any way that nobody is at risk in taking their medication. That is why we have warning labels. It is the responsibility of the patient and the local physician to whom the patient goes to ensure the medication is being taken properly. My feeling is in many cases that patient feels that if they were prescribed one pill then two is twice is good and everybody knows that this is not the case. in addition it is the patient's responsibility to monitor their own health not run to the attorney to sue the manufacturer because they were negligent themselves in using the medication. Perhaps there needs to be more physician education regarding the prescription of Lotronex. I have a son who is a drug representative of Eli Lilly and previous to that with Upjohn Pharmaceuticals. This has been his chosen career for the last ten years and he tells me it is very difficult due to the schedules of the physicians to allow him to "detail" the individual drugs which he is representing. In his case it is a diabetes medication. therefore, I would urge that Lotronex be brought back as soon as possible and be allowed to be dispensed by any physician and that the physicians be educated in the proper use of Lotronex with their patients. This should require a closer relationship between the doctor and the patient although even the doctor is not going to be able to monitor the patient's use of the prescription. The absence of treatment is a violation of the Hippocratic oath in and of itself. Finally considering the number of physicians who have prescribe Lotronex accurately and successfully and the number of patients whose quality of life has been so dramatically improved it would appear unreasonable to eliminate this medication. The medical standard has always been "first do no harm." Since many of you on this advisory panel are physicians it would appear to me that it almost amounts to medical malpractice to deny those of us who were so benefited from Lotronex, the use of this medication.