Produced by the Royal College of Physicians of Edinburgh and Royal College of Physicians and Surgeons of Glasgow

Challenges in Ensuring Drug Safety

  • Dr K Beard, Consultant Physician, Victoria Infirmary, Glasgow, Scotland
  • Dr P Waller, Consultant in Pharmacoepidemiology, Southampton, England


In recent years concerns have been expressed about the safety of some commonly used drugs. How safe are the drugs which we use? What systems are in place to monitor and review their safety, once on the market, and are such safeguards sufficient? Dr Keith Beard and Dr Patrick Waller review the evidence.

Key Points

  • Previously unsuspected toxicity, real and imagined, from drugs and vaccines has raised the profile of drug safety.
  • Pharmacovigilance (detecting and preventing adverse drug reactions) and pharmacoepidemiology (safe drug use in populations) are primary methods for studying and improving drug safety.
  • Effective communication about drug safety requires the availability of trusted valid information from many sources including the medicines regulatory authorities and the pharmaceutical industry.
  • Conflicts of interest for the pharmaceutical industry, regulatory bodies, patient groups and health professionals require careful consideration.
  • Better education and training for health professionals, and better patient information should help in the processes of balancing benefits and risks, and in making sensible treatment choices.

Declaration of interests: K Beard is a member of Expert Advisory Groups of the Commission on Human Medicines, and of the Pharmacovigilance Working Party of the Committee on Human Medicinal Products in Europe. P Waller was formerly employed by the UK regulatory authority and currently holds a consultant contract with the Medicines and Healthcare products Regulatory Agency. Views expressed here are personal and do not reflect the views of any other group.


Concern about drug safety has gained a high profile in the recent past, and several issues have served to exemplify this. The publicity, controversy and possible lasting damage to public health done by the MMR vaccine incident rumbles on. Other prominent and recent examples have included rofecoxib (Vioxx), marketed in 1999 and withdrawn from use in 2004 amid concerns about cardiovascular safety, and the evolution of the risks and communication about suicidal ideation with selective serotonin reuptake inhibitor (SSRI) antidepressants such as paroxetine (Seroxat). The ‘Northwick Park incident’, when healthy young subjects suffered unexpected and severe adverse effects during a phase I clinical trial, raised public awareness about safety of medicines in general, but is not directly relevant in the context of this discussion on post-authorisation safety of medicines.1 The report of the House of Commons Health Select Committee in 2005 on the influence of the pharmaceutical industry has brought these and many other aspects of the theme into focus.2 The rofecoxib story stimulated many to ask what are the key problems in assessing drug safety, why problems cannot be spotted sooner, and what can be done to prevent the same sort of thing happening again. Some aspects of this complex picture are discussed here:

  • Science and regulation.

  • Communication.

  • Conflicts of interest.

  • Education and training.

Pharmacovigilance and Pharmacoepidemiology

Developing the science of pharmacovigilance, that is the detection, evaluation, understanding, and prevention of adverse drug reactions, is necessary because clinical trials cannot give us all the answers about safety at the time medicines are licensed. Those trials study too few patients to give all the answers we need, and the subjects that are studied are likely to be unrepresentative of, and healthier than, the general population likely to be treated. Most trials are also too brief to have any hope of detecting long-term side effects. The upshot of all this is that only side-effects that are common will be detected in clinical trials, so other methods are required once medicines are in regular clinical use.

Pharmacoepidemiology, the science of studying drug safety and use in the population, is a relatively young discipline but is recognised as an important tool for promoting public health in relation to medicines. Spontaneous reporting of adverse reactions (‘yellow cards’ in the UK) is the system whereby health professionals, and now patients, can report to the regulatory authority their suspicions that a medicine may have caused a patient some harm. New methods of interrogating such data have evolved and these methods help in the early detection of ‘signals’ of possible safety problems. While there are clear limitations to these systems, many important safety signals have been detected over the years. Arguably, however, too much of the available resource is being channelled in this direction, and more emphasis needs to be given to the development of the data resources (e.g. large multipurpose databases) and observational research methodologies that are needed to investigate signals. In this way, a signal or suspicion that there may be a problem with a particular drug could be quickly tested in a robust scientific manner. This current imbalance of inputs between adverse reaction reporting systems and other methods could potentially be addressed by a single European reporting system. This would require investment but should be more efficient and economical, both for regu