Nonrandomized Comparative Clinical Studies - Proceedings of the International Conference on Nonrandomized Comparative Clinical Studies in Heidelberg, April 10 -11,1997

Recommendations concerning "Anwendungsbeobachtungen"

J. Windeler

Abstract

"Anwendungsbeobachtungen" (AWB) - a type of postmarketing surveillance studies - can be regarded as a speciality in Germany which has been triggered by the German Drug Law (Arzneimittelgesetz (AMG)). They should not be considered as a special research design but are characterized as a type of investigation with the purpose of collecting information during the routine administration of drugs. The practice of AWB in the last 10 years has demonstrated that:

• AWB’s were used widely for marketing purposes, i.e. to increase the prescription of drugs by the physician's participation in an AWB;
• research aims were claimed for AWB in general or in particular cases for which an AWB, as usually designed and performed, are unsuitable.

Due to this unsatisfying situation, a working group of the GMDS (Deutsche Gesellschaft für Med. Informatik, Biometrie und Epidemiologie) was asked to provide the drug authorities with recommendations for the design, conduct and analysis of AWB.

Major aspects of the recommendations which were completed in 1997 are: AWB’s are scientific observational studies.

• They should be prospective in design and therefore comprise all characteristics of a one- or two-armed cohort-study.
• The special characteristic of an AWB is that the decision when, how, and how long to treat and when and how to modify treatment is left completely to the discretion of the individual physician.

Aims of an AWB may be:

• cost assessment
• risk assessment
• gaining additional information about therapeutic effectiveness.

In order to allow valid answers to scientific research questions, structured information has to be collected. This requires an observational plan to collect information in a standard manner from all patients.

• The conduct of an AWB requires a study plan, which contains detailed information about the project including its statistical analysis.
• One of the major claims concerning AWB’s is that such studies give better information about the actual practical use of a drug compared to clinical trials. Therefore, information must be presented to show that the AWB is representative of the routine situation in question.
• There are a number of conflicts of interest in an AWB. These concern interests of the patient, the physician and the sponsor as well as problems of data protection. It may be useful for physicians involved in AWB to contact their ethics committee for advice in difficult situations.
• Procedures for quality assurance must be established. These should cover problems of internal validity (bias) as well as technical problems, such as the completeness and consistency of documentation.
• Results of an AWB should be published.

It is hoped, that the recommendations will lead to an improvement in quality in AWB’s so that these studies can, in the future be regarded as scientifically valid research instruments.