Drugs Advisory Research Articles

Report From the 93rd Cardiovascular and Renal Drugs Advisory Committee Meeting, August 9–10, 2001

Report From the 93rd Cardiovascular and Renal Drugs Advisory Committee Meeting, August 9–10, 2001

Cardiovascular News

Cardiovascular News

Evaluation of antiarrhythmic drug efficacy in patients with an ICD. Unlimited potential or replete with complexity and problems?

A report from a Study group, proposed by A. J. Camm, London, of the Working Groups on Arrhythmias and Cardiac Pacing of the European Society of Cardiology; co-sponsored by the North American Society of Pacing and Electrophysiology. The Study Group was convened on 29 August 1997 at Saltsjöbaden, near Stockholm. The meeting was chaired by A. J. Camm, London, and C. M. Pratt, Houston. Based on the presentation and discussions, a first draft of the documents was prepared by C. Pratt and J. Camm which was then circulated to all members three times for their review. All members of the Study Group approved the final manuscript. This report represents the opinion of the members of this Study Group and does not necessarily reflect the official position of either society.The meeting of the Study Group was made possible by unrestricted educational grants from Medtronic, Guidant, Proctor & Gamble, Berlex and Sanofi.Also, presented, in part, at the Cardio-Renal Drugs Advisory Board meeting of the Food and Drug Administration, Bethesda, Maryland, on 30 April 1999.

Temozolomide ??? a new weapon in glioma and metastatic melanoma

Temozolomide [‘Temodal’; Schering-Plough] was recently approved in Europe and has subsequently been launched in the UK for the treatment of patients with glioblastoma multiforme showing progression or recurrence after standard therapy. * It has also been unanimously recommended for accelerated approval by the Oncologic Drugs Advisory Committee to the US FDA for the treatment of adults with anaplastic astrocytoma who have relapsed after treatment with a nitrosourea and procarbazine. ** Leading investigators at a satellite symposium sponsored by Schering-Plough at the 9th International Congress on AntiCancer Treatment [ Paris, France; February 1999 ] discussed recent clinical advances with temozolomide in these indications and also in metastatic melanoma, for which it is awaiting registration.

Carvedilol and the Food and Drug Administration (FDA) Approval Process: The FDA Paradigm and Reflections on Hypothesis Testing

Carvedilol (Coreg®), a beta- and alpha-blocker and an antioxidant drug, was evaluated for moderate to severe heart failure patients in a program containing four United States and one Australia/New Zealand study. The data were evaluated twice by the Cardiovascular and Renal Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA). These meetings resulted in opposite decisions by the advisory committee. The crux of the argumentation was the two-positive-trial FDA paradigm. Carvedilol did not meet the usual paradigm because an exercise end point was not statistically different from placebo in three U.S. trials. Most other end points were highly significant, and death, which was monitored across the U.S. program, was different with p < 0.0001. Here we argue that the usual paradigm is very useful but not an absolute principle, that the usual paradigm can sometimes miss the strength of evidence even in the primary end points, and that rational decision making requires on occasion that other evidence must lead to approval. Control of the type I error rate should be taken very seriously, should rarely be violated, and serves the biomedical community well. It is not an absolute principle, however, but rather must be considered in context.

The AIDS Net: HIV/AIDS resources on the World Wide Web.

While driving to work, a physician who specializesintreatinginfectiousdiseases hears a radio news report about a new antiviral agent for human immunodeficiency virus (HIV). He walks into his office, logs onto the Internet, and accesses one of several professionally oriented Web sites that provide frequent updates on clinical developments in HIV and acquired immunodeficiency syndrome (AIDS). There he finds that the US Food andDrugAdministration’s(FDA’s)Antiviral Drugs Advisory Committee has recommended that abacavir sulfate be slated for accelerated approval. He obtains details about the drug’s dosing, its preliminary clinical trial results, and its adverse interactions with other agents. He decides to review the records of his patients who have HIV to see if some could be candidates for this new drug, once it receives FDA approval.

From Rx to OTC: More Drugs Make the Switch

SWITCHING DRUGS from prescription to over-the-counter (OTC) status is proceeding at an ever-increasing pace. In the 10years from 1984 to 1994,9drugs were switched from prescription to OTC status—an average of about 1 a year. But in 1995 alone, 7 agents were moved to OTC status, and last year, 13 drugs were switched to OTC. Two more have been added so far in 1997 (see box). "This is a trend and it's going to continue," said Randy Juhl, PhD, speaking at a briefing for health professionals held by the Food and Drug Administration (FDA). Juhl is dean of the University of Pittsburgh School of Pharmacy and a former chair of the FDA's Nonprescription Drugs Advisory Committee. Juhl noted that only in December 1992 did the OTC advisory committee hold its first meeting. David Kessler, MD, former FDA commissioner, put the group together in response to pressure to place more drugs in

Thrombolysis for stroke.

On June6,1996, the Peripheral and Central Nervous System Drug Advisory Committee to the US Food and Drug Administration (FDA) voted 10 to 0 that tissue-type plasminogen activator (t-PA [lateplase]) is safe and effective therapy for acute ischemic stroke. 1 The focus of the committee was on part 2 of the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Study 2 as the pivotal efficacy study and on part 1 as the supportive study. Why was the panel unanimous in judging t-PA as effective? In part 2 of the NINDS t-PA Stroke Study, 2 patients treated with 0.9-mg/kg t-PA intravenously within 3 hours of symptom onset were more likely to have minimal or no disability at 3 months compared with patients treated with placebo. Efficacy was consistent over 4 assessment scales. The relative advantage of t-PA ranged from 32% to 55%. A global statistic, combining results from the

Establishment and evaluation of a statewide drug and alcohol specialist advisory service.

The New South Wales Drug and Alcohol Specialist Advisory Service aims to provide prompt, relevant and reliable advice on the clinical management of drug- and alcohol-related problems to health professionals throughout New South Wales. We gauged the performance of the Service against present indicators by interviewing 120 callers who had contacted the Service during its first two years. Accessibility and the quality of information provided were rated highly. Of the 120 respondents, 105 (90 per cent) rated the speed of response to their calls as very good or excellent, and 109 (91 per cent) considered the advice given to be very relevant to their needs. Nearly all (97 per cent) indicated their intention to reuse the Service, and 78 (65 per cent) nominated it as their preferred source of clinical advice on drug and alcohol problems. The Service has established itself as an accessible and reliable source of advice on the management of drug and alcohol problems, especially for rural health professionals. This model of a telephone-based consultancy could have application in other medical specialities.

The role of tocolysis in the prevention of preterm birth.

BirthVolume 23, Issue 1 p. 40-41 The Role of Tocolysis in the Prevention of Preterm Birth Jay D. Iams MD, Jay D. Iams MD Jay D. Iams is the Frederick P. Zuspan Professor of Obstetrics, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Fifth Floor, Means Hall, 1654 Upham Drive, Columbus, OH 43210-1228.Search for more papers by this author Jay D. Iams MD, Jay D. Iams MD Jay D. Iams is the Frederick P. Zuspan Professor of Obstetrics, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Fifth Floor, Means Hall, 1654 Upham Drive, Columbus, OH 43210-1228.Search for more papers by this author First published: March 1996 https://doi.org/10.1111/j.1523-536X.1996.tb00460.xCitations: 6 This testimony was given at a meeting of the Fertility and Maternal Health Drugs Advisory Committee, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, October 29, 1992, chaired by Ezra C. Davidson, Jr., MD. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume23, Issue1March 1996Pages 40-41 RelatedInformation

Adverse drug reaction reporting: Opinions and attitudes of medical practitioners in Ireland

AbstractDespite the critical role of adverse drug reaction (ADR) reporting in ensuring the safety of drugs in clinical practice, fewer than 10% of such reactions are reported. We analysed the views of 207 doctors in Ireland and, although well disposed towards reporting, most doctors (97%) were uncertain about the reporting criteria of the regulatory agency, the National Drugs Advisory Board (NDAB), and unclear as to the purposes of the reporting scheme. The unavailability of report forms (52%) or the address of the NDAB (28%), together with being too busy or unsure how to report were identified as major deterrents to reporting. There was general agreement about the factors important in the decision to report—seriousness of the reaction, an unusual reaction or a reaction to a new product. Almost 90% of doctors requested guidelines on reporting and regular bulletins on ADRs. Our survey indicates that doctors need ongoing education and information about this important area of drug safety if the benefits of their positive attitudes towards it are to be realized.

{BLR 1677} Breakthrough Drug Advisory Council - Health Security Act

{BLR 1677} Breakthrough Drug Advisory Council - Health Security Act

Trends Driving the over-the-Counter Drug Market

There are three reasons why the worldwide market for over-the-counter (OTC) pharmaceuticals is growing. First, consumers understand and want to be involved in caring for their health. They demand more information about all forms of health care; as a result, patients are more knowledgeable. They have a better understanding of what medicines are for and how to use them. Second, the changing health care environment, particularly in the United States, will accelerate the pace of prescription-to-nonprescription drug switches. This is an attempt by governments to control rising medical costs. Third, regulatory agencies, including the United States Food and Drug Administration (FDA), are facilitating the growth of OTC pharmaceuticals. Examples are advertising and patient information directives in the European Community that promote self-care, and the over-the-counter Drug Advisory Committee (ODAC) in the United States, with the goal of providing safe, effective OTC medicines to the public.

Estimates of the number of injecting drug users in a defined area

Three estimates of the number of injecting drug users residing within the Eastern Sydney Area Health Service (ESAHS) were obtained by applying the capture-recapture technique to data from three reliable sources, specifically, Methadone Services, the Bourke Street Drug Advisory Service and the Albion Street Clinic. The obtained estimates were 3449, 3046 and 1103 respectively. Statewide methadone statistics were also used to obtain an estimate of 15,082 injecting drug users in New South Wales. This estimate was close to the linearly projected estimates (14,274 and 14,416) from two previous studies. Estimates based upon the methadone statistics indicate that approximately 23% of injecting drug users in New South Wales reside within the ESAHS. A sensitivity analysis was performed to assess the effects on the estimates of the likely violation of the closed population assumption.

The Drug Advisory Service of England and Wales—the first 2 years

An historical account is presented of the introduction and subsequent work of the Drug Advisory Service (DAS) of England and Wales since 1986. Data are presented from an analysis of the recommendations contained within the first 11 reports. The structural and operational strengths and weaknesses of the present approach are considered, and alternative approaches which might constitute constructive modifications or supplements to the present system are discussed.

Contraceptive Development Lags in U.S.

Contraceptive development in the US has been halted by all but one company Ortho Pharmaceuticals. The reasons for this are complex and the problem is very serious. Legal and regulatory pressures have taken away the incentive to do research. There are 3 million unwanted pregnancies each year in this country. If contraceptive use were more widespread and the technology was constantly being improved by a highly competitive market, then this number would be much lower. There are several new forms of birth control being studies for use in the US, such as injectables using microspheres or microcapsules which can last for 1, 3, or 6 months, biodegradable pellets that are inserted under the skin of the hip or upper arm slowly release hormones, the vaginal ring which is saturated with time-released hormones and is worm around the opening of the uterus like a diaphragm, transdermal patches which are changed weekly for 3 weeks with a placebo patch to allow menstruation, osmotic pills which gradually release hormones on a lower and less frequent schedule, and vaccines which can immunize women against hormones in the placenta, egg or from sperm. This research is at an early stage. Luteinizing hormone-releasing hormone (LHRH) analogues suppress ovulation by affecting the pituitary gland. This method has the side effect of blocking ovarian production of estrogen and progesterone. Male methods like Inhibit inhibit the production of follicle-stimulating hormone (FSH). Gossypol has been used in China, but one side effect is that it is sometimes irreversible. Outside the US the injectables Depo-Provera and Noristerat are approved in 90 and 40 countries respectively. Norplant is a progesterone releasing implant, made in Finland, that lasts up to 5 years; it was recommended for approval in 1989 by the FDA's Fertility and Maternal Health Drug Advisory Committee RU-486 prevents the cells in the uterus from receiving progesterone, was developed in France. The Filshie clip is a titanium and silicone rubber barrier that blocks the fallopian tubes. Ovablock is a silicone plug that blocks the fallopian tubes and increase reversibility.

THEOPHYLLINE AND SCHOOL PERFORMANCE

After review of the clinical literature, FDA has concluded, in agreement with its Pulmonary-Allergy Drugs Advisory Committee, that there is insufficient data to state that theophylline produces an adverse effect on the school performance of children. However, the agency encourages further well-controlled studies on this subject. Agency Review Because of questions about the methodology used in these studies and the statistical interpretation of the results, in October 1987 FDA's Pulmonary-Allergy Drugs Advisory Committee reviewed all the studies and made recommendations to the agency. In accordance with the recommendations of this committee and after further agency review, FDA concludes that the present data do not support the conclusion of an adverse effect of theophylline on the performance of school children. However, consistent with the recommendations of the Advisory Committee, further well-controlled studies are needed. Such studies should include welldefined psychological parameters and be carried out by individuals familiar with the best psychological tests available. The goal of these studies should be to clarify whether any association exists between theophylline and learning behavior or school performance.

THEOPHYLLINE AND SCHOOL PERFORMANCE

After review of the clinical literature, FDA has concluded, in agreement with its Pulmonary-Allergy Drugs Advisory Committee, that there is insufficient data to state that theophylline produces an adverse effect on the school performance of children. However, the agency encourages further well-controlled studies on this subject. Agency Review Because of questions about the methodology used in these studies and the statistical interpretation of the results, in October 1987 FDA's Pulmonary-Allergy Drugs Advisory Committee reviewed all the studies and made recommendations to the agency.

The TPA controversy and the drug approval process. The view of the Cardiovascular and Renal Drugs Advisory Committee

The TPA controversy and the drug approval process. The view of the Cardiovascular and Renal Drugs Advisory Committee

Buprenorphine abuse among opiate addicts.

SummaryBuprenorphine has been described as a potent analgesic with low abuse potential. Sporadic reports in the world literature would seem to contradict this view. A retrospective study of all opiate addicts first presenting over a 12‐month period showed an increasing level of buprenorphine abuse. The implications of these findings are discussed