Drug Information Journal最新文献

The FDA's Good Laboratory Practice Regulations (GLP) have been formally amended (once) and two formed advisory opinions have been issued. The FDA is now in the process of reviewing the GLPs to comply with both the Regulatory Flexibility Act of 1980 and Executive Order 12291 of 1981. Inspections since 1979 have revealed compliance progress; however, certain areas of the GLPs have been a problem--the definition of "raw data," the documentation process for the maintenance of "raw data," standard operating procedures, and study protocols. The increasing use of computers for supporting toxicology/pathology studies raises several questions concerning the impact of the GLPs on computerized data collection/reporting. This paper will address the above questions and discuss systems, procedures, interpretations, and some unresolved problems, as well as provide practical approaches for internal review of computer-supported nonclinical laboratory studies.

In the Australian system, the major aim is to test individual reports for quality, judged entirely by the contents of the report. Prior knowledge of the adverse drug reaction profile of the drug is excluded. The items taken into account include timing (onset of the reaction), setting (nature of the disease, drugs, and diet), and laboratory information.

Lederle's Medical Research Integrated Database Information Retrieval (MRIDIR) system provides timely and facile access to a growing body of computerized, in-house data relating to pharmaceutical discovery and development. It was created in response to a proliferation of special-purpose programs, each dealing with a specific dataset and each with its own query syntax. Written in FORTRAN and interfacing to the System-1022 Database Management System, MRIDIR provides relational links between these datasets and, from the user's viewpoint, integrates them into a single database with a simple query language. A special dataset called the "data dictionary" describes these linkages, and alterations to the database structure (eg, addition of new datasets) are smoothly accomplished through changes to the data dictionary.

Individual case reports about suspected adverse drug reactions are an important source of drug safety data. Their evaluation involves, among other things, the assessment of causality. Usually it is done by expert medical evaluators according to their knowledge and experience. Subjectivity plays a big role as demonstrated by comparison of assessments of the same cases by several evaluators or by the same evaluator at a later date. In recent years, methods of causality assessment based on algorithms were introduced. In these formal approaches, items of information contribute to the assessment in a predetermined and standardized way with a logic that allows operational application. Results obtained with different methods may differ because items of information considered may not be the same and/or strength of evidence attached to them vary from one method to another. The main advantages of standardized assessment are: clear identification of items of information involved, improved communication, reproducibility of results, and the checklist function. Various implications of standardized assessment are discussed and ways to improve their performance outlined.

The processing of Case Report Form data collected in clinical trials is a data processing task unlike any other. Conventional systems approaches to clinical data management are not responsive to user demands and require excessive amounts of manpower to support. The Clinical Data Management System implemented at Merck utilizes Infodata 's Inquire database management software, IBM's CICS communications software, IBM's VSAM file management software, and SAS Institute's SAS software. System flexibility was the paramount consideration when the CDMS was designed. Clinical data at Merck is now processed on a system that provides on-line ad hoc retrieval capabilities through a user friendly query language, and allows for drug specific database designs coupled with a common update and retrieval mechanism.

Although pharmaceuticals comprise up to 40% of the health care budget in developing countries, the majority of the population does not have access to many of the essential drugs needed to treat prevalent diseases. This situation demands the development of a national formulary of essential drugs for the public sector. The approach used in developing countries is to select drugs of choice for the treatment of prevalent morbidities and avoid therapeutic duplication, unacceptably dangerous drugs, or drugs of unproven efficacy. Drugs are selected based on a review of the prevalent morbidities, health care worker training, patient characteristics, and efficacy/risk information resulting from scientifically sound studies. An added component to the formulary is the inclusion of concise, unbiased prescribing information for each drug selected. A number of product selection guidelines were proven to be effective in establishing and maintaining an essential drug formulary for developing countries. These guidelines include: 1. Selection of drugs with proven efficacy and acceptable risk; 2. Selection of minimum number of drugs needed to treat the prevalent diseases; 3. Inclusion of new products only if they are found to have distinct advantages over products currently in use; 4. Inclusion of combination products only when they provide true benefit over single ingredients; 5. Selection of drugs with clear "drug of choice" indications for prevalent diseases; 6. Evaluation of the administrative and cost impact of products; and 7. Selection of drugs with established high quality.

One goal of the FDA's ongoing New Drug Regulations rewrite project is to facilitate and expedite drug application review. We believe that this can be aided by improved and consistent organization of the submissions. Therefore, guidelines are being developed to assist applicants in preparing well-structured summaries and full report sections. The proposed format guideline for toxicology and related studies is not intended to increase the amount of documentation beyond what is already required by the GLP regulations, but rather to provide some principles for orderly and coherent submission to aid comparative review of various types of data within and between studies. Certain of these principles may also be applicable to submission of data during the IND. The computer's role as an important, even essential, adjunct to this process is clearly evident. However, it is particular important that data automation be flexible enough to recognize and reconcile the differing perspectives of data collection and storage, and data retrieval and organization to benefit scientific evaluation of a drug application. Examples of recurring problems in the submission of computerized toxicology data are presented to illustrate their frustrating or confounding effect on the scientific evaluation of drug applications.

An international registration dossier is a comprehensive scientific document used to obtain worldwide licensing approval of a drug by diverse health authorities. Its creation, processing, compilation, and dispatch to the field by a regulatory affairs department of a major, US-based, multinational pharmaceutical company is dependent upon many interrelated activities beginning years prior to its physical assembly. The following activities are briefly discussed to show the magnitude of the task and the type of activities encountered: planning and scheduling; creating, organizing, and formatting; typing; copying and collating; working with extramural suppliers and services; and finally, shipping the document to the field. Suggestions for making the process more efficient are offered.

A telephone survey was conducted to evaluate and compare drug information received from the pharmaceutical manufacturer in response to a drug interaction question concerning concurrent administration of tetracycline and cimetidine. This study assumes that the pharmaceutical company may often be consulted by the hospital pharmacist seeking information about a particular medication. Forty-five pharmaceutical companies, all marketing tetracycline products, were selected for the study. A conversation protocol was utilized. It was designed to assure consistency and evaluate information received for accuracy, response time, clinical judgement offered, and referrals. Forty pharmaceutical manufacturers responded: 18 brand manufacturers and 22 generic companies. Eleven companies provided information on the interaction identified. Five manufacturers stated that there were no contraindications to concurrent administration of the drugs, one company identified a similar interaction, and five manufacturers successfully provided information identifying the interaction with supportive documentation. Two of the five companies offered clinical judgement as to the clinical significance of the interaction. Both reached different conclusions. The mean time of all phone calls was 4.29 minutes (range 0.39 to 15.41 minutes). The investigator was referred to outside sources by twelve companies. In this study, brand manufacturers performed better than generic companies. Results indicate that few manufacturers are organized to answer drug information requests involving current information sources in a response to a telephone request.