Adverse reactions: Published data

Last updated: Sunday, July 05, 2015

Don't simply accept data about ADRs that you find in published studies. Remember to assess the relative importance of different sources of information on adverse reactions:

Clinical trials

These give a helpful indication of common reactions with a guide to incidence, but:

  • The comparatively small patient population involved in most cases means that serious, but uncommon, reactions are unlikely to be discovered.

  • The patients involved in clinical trials are highly selective and not representative of the real patient population.

  • The procedures for ADR monitoring and reporting in clinical trials are variable and may not be sufficiently robust.

Case reports

Case reports can be useful in raising suspicion but in most cases they are insufficient to establish a causal association for the following reasons:

  • There is no comparison group not exposed to the drug to allow for a quantitative estimate of risk.

  • There is no reliable denominator of drug-exposed patients from which an incidence rate can be estimated.

  • Prone to bias. A single case report linking a reaction to a drug could be just coincidence, or due to one of a large number of confounding influences.

Epidemiological studies

Given the limitations of clinical trials and case reports, post-marketing epidemiological studies generally provide the best source of quantitative information on ADRs. These fall into two broad categories:

  • Follow-up (cohort) studies. Groups defined by exposure status to a particular drug are followed and subsequent events recorded and compared. For example 750 patients on leflunomide are scrutinised for adverse events.

  • Case-control studies. Groups defined by their outcomes are enrolled and prior drug exposures ascertained and compared. For example, 4,000 patients with upper GI bleeding are investigated in an attempt to identify factors that may have caused it.