Principles From Clinical Trials Relevant to Clinical Practice: Part II

This last installment of a 4-part series discusses the final 5 of 11 principles derived from clinical trials during the last 2 decades of cardiovascular clinical research and the need to apply them to the care of individual patients with heart diseases. As therapies have become more biologically potent, it has become increasingly clear that every treatment can be harmful in some patients while being beneficial in others, and often both good and bad effects occur in the same patient. With many therapies, clinical characteristics can identify patients with greater expected benefit or risk, and pharmacogenetics may offer further insight into predicting which patients will achieve the greatest benefit and which will have the greatest risk of harm. For example, we know that women are at higher risk for torsades de pointes when they are treated with QT-interval-prolonging drugs, and it is likely that a genetic predisposition may be important.1 Unfortunately, however, the relative power of these findings is limited, and we are left with broad treatment guidelines that will leave patients at risk of harm that cannot be predicted in absolute terms. The recognition that therapeutics are not commonly either “good” or “bad,” but carry a mixture of good and bad effects, has spawned the concept of risk-management in therapeutics. Each clinician has the responsibility of helping the patient place these risks and benefits in perspective when making decisions about therapeutics. Inevitably, this approach will require an improved grasp of probabilities and quantitative outcome estimates by clinicians and patients. Furthermore, there is an implied responsibility, both to participate in the generation of knowledge about risks and benefits through clinical trials and to report adverse events observed in the post-marketing period. Such adverse event reporting played the critical role in identifying cisapride as a cause of sudden death2 …