Failure to Warn is No Longer an Option

Due to recent high-profile drug safety issues, public, media and political awareness has been heightened to the immutable fact that drugs have risks. With limited public appreciation of the drug benefit/risk trade-off, some may perceive that public policy is being pushed toward a zero-tolerance approach to medicines – drugs should not have risks and regulators should not approve drugs that have risks. On the other hand, risk management experts and the FDA recognise that all drugs have dangers and that the benefit/risk balance may shift throughout the drug’s lifecycle as new populations become exposed. The key issue is whether the benefits associated with the drug outweigh the risks.

A report by the Institute of Medicine (IOM) in response to this growing public concern, found that there is a perception of crisis that has compromised the FDA’s credibility as well as that of the pharmaceutical industry (1). The report’s recommendations include labelling requirements and advertising limits for new medications, mandatory registration of clinical trial results to facilitate public access to drug safety information, and an increased role and budget for the FDA’s part in gathering and communicating additional information on marketed products’ risks and benefits.

The recommendations also call for increased access to databases and the evaluation of RiskMAPS and RiskMAP tools. Depending on how these recommendations are implemented, they could lead to delays in the drug development process, increasing development costs and discouraging the development of important therapies. In an interview in November 2006, Dr Scott Gottlieb, FDA Deputy Commissioner of Medical and Scientific Affairs, expressed his concern that “The growing use of risk management plans presents a lot of potential problems.” He added, “RiskMAPS with complicated registration systems for physicians, patients and pharmacies will overburden the healthcare system and will limit access to new drugs among patients who already face obstacles to care.”

As the debate plays out in Congress and the media, what should pharmaceutical manufacturers do? For many companies, to simply wait and see is not a viable option. Pharmaceutical manufacturers are now in need of comprehensive and proactive risk management programmes within existing US and European regulatory guidance. A cornerstone of this approach is improved information and characterisation of the benefits as well as the risks, more effective and efficient use of analytic tools, and improved communications of both the benefits and the risks of therapeutic products. A key argument in much of the litigation is that patients were not warned or aware of risks so that a more informed benefit/risk decision could be made.