1. Data Mining and Signal Detection in Pharmacovigilance
Dr. Bhaswat S. Chakraborty
Sr. Vice President, R&D, Cadila Pharmaceuticals
Evidence based medicine – novel entity, new delivery system or equivalent generics alike – needs to
be potent, efficacious and safe. However, when it comes to assurance of safety, pre-market clinical
trials despite their designs cannot capture all the adverse drug reactions (ADRs) causally related to
the experimental drug. For a complete qualitative and quantitative mapping of all ADRs, post-
marketing surveillance of safety is legally required. The primary responsibility of such surveillance
lies with the sponsor or manufacturer of the drug. However, if patient groups, scientists, physicians
and regulatory agencies do not take active interest in this activity, the sponsors alone cannot
accomplish it entirely.
Currently, the reporting of ADRs is mainly done on a voluntary basis – albeit the legal requirement.
The voluntary reports go to the national (usually part of the national regulatory agencies) and
international (e.g., WHO Uppsala Monitoring Centre (UMC)) where the individual case report forms,
background data and particular organ based data are organized, analyzed and interpreted for the use
of medical practitioners and patients. Voluntary reports are also published in medical journals. In
recent years, there has been an increased effort to analyze the data bases from the likes of
aforementioned sources for potential ADR signals that were not apparent during clinical or
epidemiology trials. Such efforts are known as signal detection (SD) in pharmacovigilance.
The role of SD and PV do not end by establishing a drug–ADR pair only, prompt
regulatory actions need to be taken to appropriately restrict or ban the use of that drug. In the
recent past, critical opinions have been aired about the sale of many drugs from some countries
that have been banned in other countries. In the developed world, nimesulide has been
withdrawn, but unfortunately it still continues to be sold in many developing countries. Another
drug (rofecoxib) that has been voluntarily withdrawn recently by the manufacturer is still sold in
India.
The presentation will examine whether the present premarket approval by the regulatory
agencies often allows premature conclusions about safety. It will look at the timeframes of
“black-box” warnings in PDR. As the main body of the presentation, different approaches to data
mining for SD will be discussed with an analysis of relative merits and demerits. Some important
problems related to quantitative SD and their plausible solutions will be discussed.
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