Drug Information Journal最新文献

In the clinical development of new drugs for market approval, it is frequently impossible to design trials to provide definitive information about safety--particularly about adverse events. It is possible, however, to design most trials to provide definitive information about efficacy. Efficacy trials with new drugs should therefore be monitored for safety, and the safety profile described within and across trials. Confidence intervals are recommended as the appropriate statistical methodology for doing this. Such intervals provide an interval estimate on the unknown incidences of adverse experiences among patients who could be treated with each regimen, as well as permit a conclusion that two regimens are different.

Reporting of adverse events occurring during clinical trials of investigational drugs is a complex and controversial issue. Even the interpretation of the term, "adverse event," cannot be agreed upon by researchers. The ultimate adverse event, death, presents even a greater challenge. This paper presents an actual case of death during a clinical trial to illustrate a methodological approach to deal with such an event.

The responsibilities of sponsors, clinical investigators, and institutional review boards (IRBs) in the conduct of clinical research are summarized and some of the problems which each of these parties has experienced in the conduct of clinical research are described. The paper concludes with specific recommendations to secure appropriate relationships among sponsors, clinical investigators, and IRBs.

Heightened concern about drug abuse during the late 1960s prompted community leaders to request that the University of Cincinnati's Drug Information Center extend its services to the public. More than 500,000 inquiries have been handled by the Center since it first offered these services. The Center's "hotline" provides information, advice, counseling, and/or emergency treatment and referral information and is extensively involved in community outreach and prevention efforts. Providing reliable, authoritative, and beneficial information requires that all staff be professionally qualified and receive extensive training, pass specialized certification tests, follow structured policies and guidelines, and effectively use consultants. Impressions of the roles, impact, and need for such services in the 1980s are discussed.

The information contained in package inserts varies from country to country in Europe, although other regulatory aspects of data presentation are quite similar. West Germany's Drug Law of 1976 requires 11 items to be included in the package insert for both patient and health professional: name/address of manufacturer; drug name; active constituents; indications; contraindications; side effects; drug interactions; dosage instructions; method and duration of application; statement that drug should not be used after expiration date; and statement that drug should be kept out of reach of children. All information must be submitted to the Health Office at the time of application or the applicant is liable for criminal prosecution. Documentation of side effects must be complete, although no special form is required. Similarly, causality assessment needs to be made even though specific algorithms are not required. Proposed amendments to the Drug Law will include additional information to physicians concerning the overdose instructions, pharmacological properties, and bioavailability of the drug. Registration procedures are the same throughout Europe and are called Summary of Products Characteristics. Assessment reports are also required for each new chemical entity in the European Community.

The purpose of this paper is to describe some methods for analyzing and summarizing adverse event rates from clinical trials, emphasizing, in particular, serious adverse drug events and their time of occurrence, and the impact of differential subject exposure and pretreatment status on the estimation of rates.

The Food and Drug Administration (FDA) regulations on Institutional Review Boards (IRBs) and Informed Consent (IC) were published on January 27, 1981 and became operational on July 27, 1981. The historical development of these regulations began in August 1978 when the FDA proposed standards for IRBs. During the comment period, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research submitted its report and recommendations on IRBs and informed consent. In its report, the National Commission recommended revision of the Department of Health and Human Services (DHHS) regulations and one uniform standard for IRBs. On August 14, 1979, the FDA withdrew the 1978 proposal and published a revised proposal that it had developed in conjunction with the DHHS in response to the recommendations made by the National Commission. Following consideration of the comments received on the 1979 proposal, the new regulations were published as final. I would like to discuss how these regulations relate to the FDA's mandate and regulatory responsibilities, to the work of IRBs, and to the protection of human subjects involved in the FDA-regulated research. I will also mention the FDA's internal organization to deal with IRB issues and, finally, what we may look forward to in the future.