Adverse drug reaction processing in the United States and its dependence on physician reporting: zomepirac (Zomax) as a case in point.

Because of limited premarket testing for drugs newly approved by the FDA, serious but rare side effects may not be apparent or publicized by the drug manufacturers. Therefore, only the timely reporting of adverse drug reactions by physicians, along with rapid recognition of the significance by the FDA, can ensure the effectiveness of the FDA Spontaneous Reporting System as a warning to other prescribing physicians. The experience with zomepirac (Zomax) and the unexpected incidence of severe anaphylactic reactions is recanted as an unfortunate illustrated example that has served to upgrade the adverse reaction reporting process.

Record linkage studies for postmarketing drug surveillance: data quality and validity considerations.

Large automated databases are the source of information for many record linkage studies, including postmarketing drug surveillance. Despite this reliance on prerecorded data, there have been few attempts to assess data quality and validity. This article presents some of the basic data quality and validity issues in applying record linkage methods to postmarketing surveillance. Studies based on prerecorded data, as in most record linkage studies, have all the inherent problems of the data from which they are derived. Sources of threats to the validity of record linkage studies include the completeness of data, the ability to accurately identify and follow the records of individuals through time and place, and the validity of data. This article also describes techniques for evaluating data quality and validity. Postmarketing surveillance could benefit from more attention to identifying and solving the problems associated with record linkage studies.

Influence of the assessment of the severity on the frequency of adverse drug reactions (ADRs).

Sometimes it is difficult to compare data coming from different drug monitoring studies because of differences in methods, training of the monitors and other reasons. Many algorithms have been designed for permitting the objective and reproducible assessment of the causality of ADRs, but there is a lack of this kind of assessment for the severity of ADRs. This work was developed in order to show how important the standardized assessment of the severity of ADRs could be. For that purpose the same drug surveillance data were used for obtaining the frequency, characteristics and predisposing factors of ADRs, first considering all definite and probable ADRs--independently of their severity (study I)--and excluding after those considered as mild (study II). By means of an intensive prospective drug surveillance program, 2,559 patients hospitalized at the Medicine Service of the Clinical Hospital of the University of Chile were surveyed. The found frequencies of ARDs were 34.2% and 20.6% for study I and II, respectively. In both studies gastrointestinal and metabolic systems were the most ADRs-affected systems but some differences on adverse signs and/or symptoms were observed. For example, in study I the three most frequent reactions were hyponatremia, hypochloremia and hypokalemia while in study II the three commonest reactions were hypokalemia, vomiting and hypochloremia. In both studies similar characteristics of beginning and probability of ADRs were found, and the highest part of the reactions was dose-dependent. But when mild reactions were excluded (study II) an increase on the proportion of dose-independent ADRs was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Better laboratory evaluations of instruments and kits are required.

There are many published protocols for evaluating instruments and reagent-kit sets, and a plethora of papers describe the results of evaluations performed. It might be assumed, therefore, that this facet of clinical chemistry has no problems, but examination of evaluations of instruments published in the first half of 1984 shows flaws in some aspects of experimental design and execution, statistical analysis, and interpretation of data. We believe that clinical chemists, manufacturers and suppliers, and journal editors and referees can all contribute to improvement of this situation, and we suggest some guidelines for each of these groups.

Policy issues concerning antimicrobials: problems with the regulatory process governing their introduction.

Clinicians, representatives from industry, and independent observers have voiced complaints about the cumbersome and lengthy process employed by governmental regulatory agencies before approving new antimicrobials for marketing. The currently used drug approval process is probably not entirely appropriate for antimicrobials. In fact, the situation for antimicrobials is qualitatively so different from that of other drugs that antimicrobials should almost certainly undergo review specifically designed in accordance with such differences. Modifications in the pre- and postmarketing approval process for antimicrobials are proposed.

[Functional evaluation of "tekatest", a test equipment for halothane-vaporizers (author's transl)]. / Untersuchungen mit dem Halothanmessgerät "Tekatest".

The results of investigations on the reliability of a commericially available test equipment for anaesthetic vaporizers based on the Rotameter principle (s.c. "Tekatest") are reported. In prototype devices scattered differences up to 27% between the results obtained by the Tekatest and those derived from gas chromatography and mass-spectrometry were noted; in a somewhat improved version an unidirectional error of about 24% became evident. Up to now, therefore, this test equipment cannot be recommended for recalibration of vaporizers in clinical use.

Quality assurance of clinical data: diagnostic standardization.

Diagnostic standardization requires substantial effort, including detailed specification of procedures in a written protocol and training of examiners in such procedures. Success is neither automatic nor assured. It is essential to monitor performance through replicate examinations and/or computation of examiner variance. When examiner variance exceeds permissible limits, consideration should be given to discarding the data.

Quality assurance of clinical data: internal monitoring: patient and study management at the clinic.

Adquate methods to assure the quality of data collected at the clinic need to be developed. A full understanding of the limitations of physicians as information processors and reasonable performance expectations for physicians during peak information periods will result in concentrated planning for patient visits and will limit the data that must be collected at the clinic. It is mandatory for each clinical research project that protocol treatment take into account the question of variable provider follow-up versus constant provider follow-up. It is also imperative that all clinical research providers receive special training, testing, and follow-up evaluation. The prime responsibility for the overall conduct of clinical research rests with the principal investigator. A monitoring tool that should be more fully used is the informed patient.

Aspects of clinic monitoring in large-scale multiclinic trials.

Monitoring the implementation of large-scale and the adherence of clinical centers to a common protocol should be an integral part of the study design and a primary responsibility of the coordinating center for the study. There are four basic concepts in external clinic monitoring: (1) the maintenance of open lines of communication between all study facilities, (2) "responsibility and accountability" for study implementation and for the integrity of the data, (3) evaluation of clinic operations, and (4) analysis of data quality. A monitoring scheme consisting of regular telephone calls to the screening centers. periodic visits to the screening centers, and continuing review of the data collected can be effectively used by the coordinating center.