Signalling Increases in Reporting in International Monitoring of Adverse Reactions to Therapeutic Drugs

The present »state of the art« of monitoring events based on spontaneous, voluntary, haphazard reporting is reviewed. Particular reference is made to the problem of signalling increases in reporting in the international monitoring of adverse reactions to therapeutic drugs. It is shown how a number of different avenues of research could be usefully pursued to provide signals for increases in reporting which are more specific and more sensitive than those which are currently available. In particular, the so-called »Centre-Batch« matrix is introduced, and it is shown that the information contained in it can be used with advantage to provide signals which are more informative than those which are obtained from data aggregated over several reporting centres. Other approaches introduced include methods for the detection of patterns of adverse events, the idea of using system measures for monitoring the performance of the monitoring system itself and the potentialities of signals based on quantitative data.

Die Autoren geben eine Übersicht über den »State of the art« der auf spontaner, freiwilliger und zufälliger Meldung beruhenden Warnsysteme. Dabei wird insbesondere auf das Problem der Anzeige vermehrter Meldungen an das internationale Warnsystem über Arzneimittelnebenwirkungen eingegangen. Es wird dargelegt, wie eine Anzahl verschiedener Wege der Forschung nutzbringend verfolgt werden können, tun spezifischere und empfindlichere Hinweise als die derzeit verfügbaren auf vermehrte Meldungen zu bekommen. Im besonderen wird die sogenannte »Centre-Batch« Matrix vorgestellt und dabei gezeigt, daß die darin enthaltene Information nutzbringend verwandt werden kann, um Hinweise zu geben, die informativer sind als solche, die aus von mehreren Meldezentren gesammelten Daten gewonnen werden. Unter anderem werden Methoden für die Entdeckung von Nebenwirkungskonstellationen vorgestellt, die Idee geäußert, Überwachungsmaßzahlen für die Güte des Überwachungssystems selbst zu benutzen, und die Möglichkeiten von auf quantitativen Daten basierenden Signalen diskutiert.

Key-Words

Drug Monitoring - Adverse Reactions - Signals - Centre-Batch Matrix

Schlüssel-Wörter

Arzneimittel-Warnsystem - Nebenwirkungen - Signale - »Centre-Batch Matrix«

• References

• 1 Anonymous. Official Records of the World Health Organization 140 (Annex 21). Geneva: 1904: 87-114.
• 2 Anonymous. Official Records of the World Health Organization 148(Annex 11). Geneva: 1966: 65-72.
• 3 Armitage P. Tests for, linear trends in proportions and frequencies. Biometries 11 1955; 375-386.
• 4 Feinstein A. Foundations of Information Theory. McGraw Hill & Co; New York: 1958
• 5 Finney D. J. The design and logic of α monitor of drug use. J. chron. Dis 18 1965; 77-98.
• 6 Finney D. J. Monitoring adverse reactions to drugs — its logic and its weaknesses. Proc. Europ. Soc. for study of drug toxicity VII, Excerpta Medica Int. Congress Series 115 1966; 198-207.
• 7 Finney D. J. Systematic signalling of adverse reactions to drugs. Meth. Inform. Med 13 1974; 1-10.
• 8 Finney D. J. The detection of causation of adverse events. Paper delivered to tho 39th session of the International Statistical Institute. Vienna: 1973
• 9 Finney D. J. Problems, data and inference. J. R. Stat. Soc., Series A, 137 1974; 1-23.
• 10 Hald A. Statistical Tables and Formulae. John Wiley & Sons, Inc.; New York: 1952
• 11 Hald A. Statistical Theory with Engineering Applications. John Wiley & Sons, Inc.; London: 1952
• 12 Levine A. Theory of Probability. Addison-Wesley Publishing Co.; Reading, Pa.: 1972
• 13 Levine A, Roizen P, Roze P, Christensen H. A mathematical method for analyzing questionnaires. Bull. W. H. O 47 1972; 87-97.
• 14 Levine L. Methods for Solving Engineering Problems. McGraw-Hill, Co.; New York: 1965
• 15 Mandel S. P. H. Report on Statistical Monitoring of Adverse Reactions to Drugs in the Research Centre for International Monitoring of Adverse Reactions to Drugs. Report prepared for World Health Organization. DEM/74.7. Geneva: 1974
• 16 Marshall C. W. Applied Graph Theory. John Wiley & Sons; New York: 1971
• 17 Patwary K. M. Report on Statistical Aspects of the Pilot Research Project for International Drug Monitoring. Confidential Report prepared for World Health Organization. Geneva: 1969
• 18 Royall B. W. International aspects of the study of adverse reactions to drugs. Biometrics 27 1971; 689-698.
• 19 Royall B. W, Venulet J. Methodology for international drug monitoring. Meth. Inform. Med 11 1972; 75-86.
• 20 Sarhan A. F, Greenberg B. G. Contributions to Order Statistics. John Wiley & Sons; New York: 1962
• 21 Venulet J. Adverse reactions to drugs. Int. J. clin. Pharmacol 7 1973; 253-264.