Statistical Aspects of Monitoring for Dangers in Drug Therapy^[*])

A therapeutic drug has a complicated life history, and some of the important stages of this are described in the paper. Before it can even be referred to as a drug, it must be identified as a chemical compound worth investigation as possibly having useful pharmacological properties. From among large numbers in this category, a few must be selected by a screening process. Toxicity tests and clinical trials each bring their special problems for the statistician. When a new drug has had its usefulness established, standardization of its potency by biological assay may be necessary, and this also uses statistical techniques.

Most of the paper is concerned with adverse reactions to drugs when used in medical practice, and methods for detecting these. In response to recent recognition of dangers, systems for monitoring for adverse reactions to drugs that occur during normal therapeutic use have been developed in many countries. The paper outlines the logical basis of monitoring and discusses its practical implementation. New problems of statistical inference, as well as large data handling activities, arise in connexion with the interpretation of evidence that is very heterogeneous in origin. The basic statistical problem appears to be one of collecting and evaluating information that may constitute a degree of suspicion calling for intensive and more objectively planned research. This type of inference seems closer to the mode of thought of a criminal investigation department than to orthodox practice of statistical estimation or decision-making; I think it has new features that deserve further study.

National monitoring organizations are now cooperating, through the World Health Organization, in an international project for the combination of evidence.

Ein Arzneimittel hat eine komplizierte Entwicklungsgeschichte; einige der Stadien dieser Entwicklung werden in der vorliegenden Arbeit beschrieben. Bevor es überhaupt als Droge angesprochen werden ▪ kann, muß es als chemische Substanz identifiziert sein, deren mögliche pharmakologische Eigenschaften weitere Untersuchungen rechtfertigen. Von vielen Stoffen in dieser Kategorie werden einige durch Voruntersuchungen ausgewählt. Toxizitätstests und klinische Prüfungen stellen den Statistiker vor ganz spezielle Probleme. Wenn die Nützlichkeit einer neuen Droge erwiesen ist, kann es notwendig werden, ihre Wirksamkeit im biologischen Versuch zu standardisieren; auch hierfür werden statistische Verfahren benötigt.

Die vorliegende Arbeit befaßt sich vor allem mit den Nebenwirkungen der Arzneimittel in der ärztlichen Praxis und den Methoden, diese zu erkennen. Als Reaktion auf kürzlich erkannte Gefahren sind in vielen Ländern Systeme zur Überwachung von Arzneimittel-Nebenwirkungen entwickelt worden. Die Arbeit umreißt die logische Grundlage soldier Monitor-Systeme und erörtert ihre praktische Durchführbarkeit. In Verbindung mit dem Nachweis der sehr heterogen bedingten Evidenz treten neue Probleme der statistischen Schlußfolgerung sowie der Verarbeitung großer Datenmengen auf. Als wesentlichstes statistisches Problem wird die Sammlung und Bewertung von Information erachtet, die einen Grad von Verdacht erweckt, der intensive und objektiv geplante Untersuchungen veranlaßt. Diese Art von Folgerung ähnelt mehr der Arbeitsweise eines Detektivbüros als der herkömmlichen Praxis statistischer Schätzungen bzw. Entscheidungen.

Nationale Überwachungsorganisationen arbeiten heute im Rahmen der WHO in einem internationalen Gemeinschaftsprojekt zur Drogenüberwachung zusammen.

Key-Words

Drug Screening - Drug Monitoring - Adverse Drug Reactions

Schlüssel-Wörter

Arzneimittel-Testung - Arzneimittel-Nebenwirkungen - Drogen-Überwachungs-Systeme

^*) Based on papers presented to the Seventh International Biometric Conference, Hannover, August 1970, and the Hungarian Pharmacological Society, Budapest, September 1970.

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