expertise is in somewhat other areas than Dr. Crout. But I would remind you that, you know, the problem is that I am not sure that Dr. Warren and I would disagree if we sat down and went through the issues as were outlined by Dr. Crout. Dr. GOLDBERG. Was any member of that advisory committee as qualified as Dr. Crout to evaluate the quality of the 33 studies? Dr. SCHMIDT. Well, I do not know all of the committee members well, although one of them was the dean Dr. GOLDBERG. No names necessarily, I am just asking generally. Dr. SCHMIDT. I believe that Dr. Crout is probably the most qualified person in the country to be heading the Bureau of Drugs and I would believe that of that group he is the most qualified to make the kind of judgment that was made in this instance of propranolol. Dr. GOLDBERG. Then, in other words, you had the in-house capability for judging those 33 studies without using outside consultation? Dr. SCHMIDT. Well, if we were limited to this one decision in the year, I would say, yes. But that conjures up everything we talked to yesterday regarding the massive decisions we made and the quality of those decisions and so on. Mr. BROWN of Ohio. Could I just ask one question? Have those decisions ever been quantified? I am sorry I missed the testimony yesterday. How many NDA's are resolved within a year! Dr. CROUT. We approve about 60, turn down about 100, but part of that 100 is a recycling. Mr. BROWN of Ohio. So that over a 5-year span, it wouldn't neces sarily be 160 times 5. It would be some of those 100 back again. Dr. CROUT. Yes, but, also, there are 2,000 or 3.000 supplementals and there are several thousand IND's in-house. We get about 1,000 IND's coming in per year and have a pool of about 4,000. Of course, some of them are repetitive. and decisionmaking is not very hard: but some of those are terribly difficult. So the quantity of agonizing decisions is quite different from the quantity of applications coming through. We do not have a list of agonizing decisions and that would be an interesting list-I suspect for you, also. Mr. BROWN of Ohio. I must say I was mentally making the picture of which ones are the agonizing and which ones are the ones that you wrote on where the vote is 330 to 4, vou know. Dr. CROUT. Our life is a little like that and you cannot always tell from reading the newspapers or the controversy surrounding it, or what have you, which are the tough ones and which aren't. Mr. FOUNTAIN. I know we have a record of all of our agonizing decisions. Mr. BROWN of Ohio. Unfortunately, we have a record of all of them and some of them are more agonizing the second time around. If you could quantify that for the record, I think that would be helpful. Dr. CROUT. Let me say that I have been verv active in academie medicine for a number of years, before I came here, which involved teaching, conducting studies, being a principal investigator on several grants, making rounds with residents, seeing patients, running a hypertension clinic. And life at the Food and Drug Administration from the standpoint of decisionmaking, is substantially more active than that. It is more active in my experience than any other job I have ever had and more active than any job in academic medicine except perhaps being a department chairman or dean, which is roughly comparable. It is that kind of a decisionmaking environment. Mr. BROWN of Ohio. Well, the experience in the hypertension clinic that you had might come in handy. Mr. FOUNTAIN. Dr. Crout, let me ask you this, and I ask it in no way to reflect upon you, but to enable us to get the total picture. As I understand it, you were an investigator for propranolol, for the company, were you not, before you came to FDA. Dr. CROUT. NO. I worked with the drug and was on an IND, and I solicited the drug from the company, and didn't receive any money for it and did not have a grant in my laboratory. This was back in about 1966, or 1967. Mr. FOUNTAIN. Was that as a clinical investigator? Dr. CROUT. As a clinical investigator, yes. So you have to decide what "working for the company" means. At that time, propranolol was not marketed at all. And in the hypertension area, I have a particular interest in a rare sort of disease called pheochromocytoma, for which this drug is useful. And we used to see an occasional patient with this condition at the University of Texas Southwestern Medical School at Dallas where I was. Mr. Brown of Ohio. With how many such drugs did you have a contact with at that time, that you had an IND? Dr. CROUT. Oh, three or four, and amongst them was propranolol. Propranolol is a major advance in the treatment of cardiac arrhythmias that occur in the course of this disease. So I wrote to the firm, got the drug, and treated three or four patients with it and sent those data back to the firm in the form of case reports. I think they were probably among the uncontrolled supporting evidence for the use of propranolol in cardiac arrhythmia, when that drug was approved for this indication in 1967, I believe, or 1968. I believe it was first approved in 1967. Other than that, I was not an investigator and did not have a grant to study. Mr. FOUNTAIN. You got no compensation? Dr. CROUT. No. Mr. FOUNTAIN. Would you say that you were in that capacity working for the company as a clinical investigator. Dr. CROUT. No, absolutely not. Most investigators of drugs in an academic environment take offense at being thought of as working for the company. That is one of the problems with doing drug research. Their own ethic is usually that "I am an independent investigator.” And they are quite insulted to be treated by the law sometimes as working for the firm. So I clearly had the ethic of being an independent investigator at that time, and would have been insulted to have been thought of as working for the firm. Dr. GOLDBERG. Dr. Crout, when you came to the Food and Drug Administration is it not a fact that you requested, with respect to two drugs for which you had been a clinical investigator, that Dr. Walters or somebody else rather than yourself, handle all of the decisionmaking on them, and that you be excluded from any consideration of regulatory action? Dr. CROUT. Yes, for the first year I was there. That is true. Dr. GOLDBERG. A memorandum has been provided to me by FDA, which says that the Director of the Bureau of Drugs, who I believe was Dr. Simmons at the time, had subsequently decided to waive that restriction in your case; is that correct? Dr. CROUT. Yes. Dr. GOLDBERG. We could put that memorandum in the record with your permission, Mr. Chairman. Mr. FOUNTAIN. Yes. [The document referred to follows:] DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLIC HEALTH SERVICE, Memorandum to: Acting Director, Division of Cardiopulmonary-Renal Drug From: Acting Director, Office of Scientific Evaluation. Shortly after joining the Agency, I signed a memorandum on October 19. 1971 stating that I did not wish to be involved in those drugs with which I had previously been associated as an investigator. Among these drugs were Propranolol and Bethanidine. For this reason I have previously indicated that Dr. Philip Walters would represent OSE in any regulatory matters concerned with these drugs. As of November 29, 1972, Dr. Simmons has determined on the advice of Miss McEniry that I have no conflict of interest with regard to Propranolol and Bethanidine and should feel free to participate in regulatory matters on these drugs. Accordingly, I will in the future join Dr. Walters in representing OSE regarding these drugs. J. RICHARD CROUT, M.D. Dr. CROUT. In neither of those circumstances, did I receive any money from the firm, nor did my lab have a grant. It was merely I was an investigator on them and got the drugs on my own initiative. Dr. GOLDBERG. Now what are the ground rules for consultants to the agency with respect to participating in any decisionmaking for a drug if they have been investigators for that drug, with or without compensation? Dr. CROUT. All right. We are now on the general issue of conflict of interest regulations. I would like Mr. Hutt to speak to that, in principle, because the principles of that he can establish. Mr. FOUNTAIN. If you can do it in about 30 seconds, fine, because we have 2 or 3 minutes in which to answer a rollcall. Mr. HUTT. Well, I don't think getting into this entire area in 30 seconds would be worthwhile. Mr. FOUNTAIN. I don't think so either. I think you should have time to go into detail. We will resume this particular subject on Tuesday morning. Tomorrow we have some outside witnesses. As I understand it, you do not need to be here tomorrow. Dr. SCHMIDT. Right. Mr. FOUNTAIN. The subcommittee stands adjourned until tomorrow morning at 9:30. [Whereupon, at 12:20 p.m., the subcommittee adjourned, to reconvene at 9:30 a.m., Friday, March 8, 1974.] USE OF ADVISORY COMMITTEES BY THE FOOD AND DRUG ADMINISTRATION FRIDAY, MARCH 8, 1974 HOUSE OF REPRESENTATIVES, INTERGOVERNMENTAL RELATIONS SUBCOMMITTEE OF THE COMMITTEE ON GOVERNMENT OPERATIONS, Washington, D.C. The subcommittee met, pursuant to notice, at 9:40 a.m., in room 2154, Rayburn House Office Building, Hon. L. H. Fountain (chairman of the subcommittee) presiding. Present: Representatives L. H. Fountain, Don Fuqua, James V. Stanton, and John H. Buchanan, Jr. Also present: Dr. Delphis C. Goldberg, professional staff member; Gilbert S. Goldhammer, consultant; and Richard L. Thompson, minority professional staff, Committee on Government Operations. Mr. FOUNTAIN. Our first witness this morning is Dr. Julia Apter, M.D., Ph. D., from Rush Medical College in Chicago, Ill. Dr. Apter is a physician and a biomathematician, and a member of the Cardiology and Renal Advisory Committee. Dr. Apter, we are delighted to have you with us this morning. Before you proceed with your prepared statement, I would like to ask you if you have a curriculum vitae, which we might enter into our record. If you don't have one, you can send it to us. STATEMENT OF JULIA APTER, M.D., PH. D., RUSH MEDICAL COLLEGE, CHICAGO, ILL. Dr. APTER. I do have an abbreviated curriculum vitae with me, but I will submit a more complete one for inclusion in the record. [The document referred to follows:] CURRICULUM VITAE OF JULIA T. APTER, M.D., PH. D. Born: April 7, 1918 in Philadelphia, Pa.; Married December 13, 1941 to Nathaniel S. Apter, M.D. Education: B.A. (Physics), University of Pennsylvania, 1939. M.S. (Physiology), Northwestern University, 1959. Ph. D. (Mathematical Biology), University of Chicago, 1964. Post-Doctoral trainee in Mathematical Biology, USPHS, University of Chicago, 1961-1964. Special Fellow of National Heart Institute (Mathematical Biology), 1964-1965. Internship: Rotating-Baltimore City Hospital, 1943. Residency Ophthalmology-University of Chicago Hospitals, 1949-1951. 151 Hospital Appointments: Director, Neurophysiology Research, Manteno State Hospital, 1950-1956. Attending in Ophthalmology, Mary Thompson Hospital, 1957-1961. Director of Section of Mathematical Biology, Presbyterian-St. Luke's Hospital, 1966-1971. Associate Attending Surgeon, Presbyterian-St. Luke's Hospital, 1966-1967. Attending Surgeon, Presbyterian-St. Luke's Hospital, 1967-. Director of Laboratory of Biomaterials and Biomechanics, Rush-Presbyterian-St. Luke's Medical Center, 1971-. Senior Scientist, Rush-Presbyterian-St. Luke's Medical Center, 1972–. Academic Appointments: Instructor in Ophthalmology, Johns Hopkins University, 1943–1946. Assistant Instructor, Associate in Ophthalmology, Northwestern University, 1951-1959. Research Associate in Psychiatry, University of Illinois, 1959-1961. Research Associate (Instructor), Mathematical Biology, University of Chicago, 1964-1966. Research Associate (Associate Professor) in Surgery, University of Chicago, 1966. Associate Professor of Surgery, University of Illinois, 1966-1968. Professor of Surgery, Rush Medical College, 1971-. Professor of Materials Science, Northwestern University, 1971. Board Certification: Diplomate, American Board of Ophthalmology, 1957. Children: Marion Hope, 11-28-45; BA (magna cum laude) Physical Chemistry, Cornell, 1968, Pritzker School of Medicine, M.D., 1972. Eve Terry, 2-28-48; MA (Moral Sciences) Cambridge University, 1971 (Upper second standing). Professional Societies: Institute of Electrical and Electronics Engineers (Senior Member). (Chairman, Committee on Professional Opportunities for Women, 1970-1973). (Educational Activities Board Consultant, 1971– ). (Chairman, Ad Hoc Committee on Medical Engineering Training, 1971-73). (Pre-College Guidance Committee, 1971–73). (Chairman, Committee on Medical Engineering Training, 1973- ). Technical Activities: (Chairman, Regional Council GEMB, 1971-1971). (Committee on Environmental Quality, 1970- ). (Member, National Administration Committee for Group on Engineering in Medicine and Biology, 1970-1975). (a) Goals Committee, 1971. (b) Student Prize Committee, 1971. (e) Outstanding Speaker, 1973 (f) Conference Committee, 1973. United States Activities Committee, 1973– : (Chairman, Committee on Professional Opportunities for Women, 1973- ). (Member, Government Relations Committee, 1973- ). Biophysical Society: (Director of Placement Service, 1970- ). (Member, Committee on Professional Opportunities for Women, 1972- ). (Chairman, Committee on Biophysical Sciences Training, 1971-1972). Association of Women in Science (Chairman, Résumé Subcommittee of the Registry Committee, 1971). Academy of Ophthalmology and Otolaryngology (Fellow). American Physiological Society. AAAS (Nominating Committee for Medical Sciences, 1974). American Federation for Clinical Research. American Institute of Physics. |