The art and science of risk management: a US research-based industry perspective.

The research-based pharmaceutical industry in the US strongly supports the concepts of risk management and sees formal risk management as playing a major role in the development of safe medicines for the public, as well as providing a mechanism to ensure that decisions concerning individual drug benefit and risk are made based on scientific evidence. Safe medicines refer to those drugs whose benefits have been found to outweigh their risks when they are used according to the approved labelling. Risk management is the comprehensive and proactive application of scientifically based methodologies to identify, assess, communicate and minimise risk throughout the life cycle of a drug so as to establish and maintain a favourable benefit-risk balance in patients. Although there are certainly a number of global risk management initiatives in place or being undertaken, harmonisation has yet to be achieved. Industry is faced with a variety of different risk management approaches and tools. There is a need to move the focus of risk management from the post-approval arena to earlier in the development process and tools need to be developed to support risk management throughout the lifecycle of a drug. The focus in the US on risk minimalisation strategies will also be an area for methodological development. A key factor in the success of overall risk management is the dialogue between industry and regulators throughout the development, review and marketing of the product. It is through such dialogue that appropriate, efficient and effective risk management strategies will be developed and implemented and the best decisions regarding the safe use of pharmaceutical products will be made.

Monitoring outcomes of pregnancy following drug exposure: a company-based pregnancy registry program.

Women who discover they are pregnant after exposure to a drug and pregnant women who have a condition that requires continued treatment during pregnancy are told to balance the benefits and risks of the exposure to justify continuation of treatment, discontinuation of treatment or, possibly, pregnancy termination. However, there are limited data available to inform decision-making. The Merck Pregnancy Registry Program is a company-run pregnancy registry whose objective is to acquire and analyse information on drug exposures and pregnancy outcomes to better describe the safety profile of Merck products used during pregnancy. Information is collected from women and healthcare providers who call to report drug exposure during pregnancy. Prospective pregnancies are followed up to outcome and data are collected via questionnaires, telephone calls and a review of medical records. Reports are classified as prospective (information received prior to knowledge of pregnancy outcome) or retrospective (received after the outcome is known). Congenital anomaly reports are assessed for timing of exposure, maternal age and medical history, biological plausibility and concomitant medication exposures. Rates of pregnancy outcomes and birth defects in the prospective cohort are computed and confidence intervals are calculated to reflect the strength of the finding based on the sample size. Rates of pregnancy outcomes in the Pregnancy Registry are compared with the rates of pregnancy outcomes in the general US population and, if available, in subpopulations with the relevant disease states. The limitations of post-marketing surveillance are well known as voluntary reporting of individuals and healthcare professionals is known to be subject to various types of bias. Small sample size is another major limitation. However, the strength of the registry lies in its ability to gather pregnancy outcome reports early in the life of a product and to recognise and analyse unusual birth defects. Our data suggest that pregnancy registries can be used to review human exposure data in a systematic fashion so that useful information can be shared with women and their healthcare providers. The use of the pregnancy registry design has allowed for the collection and analysis of data on the effects of drug exposures on human pregnancies that have otherwise been difficult to obtain.