Should evidence-based proof of efficacy as defined for a specific therapeutic agent be extrapolated to encompass a therapeutic class of agents?

Abstract

Our task as clinicians would be simple if all we had to do was to follow the logical sequence of identifying a biological target, finding a drug or treatment specifically affecting that target, testing the efficacy of the drug or treatment in appropriately designed clinical trials, and then prescribing only those drugs or treatments with proven efficacy and an acceptable safety profile. Drugs that affect a given biological target could be considered as a “class,” with those that show “efficacy” in clinical trials considered as therapeutic alternatives within that class. Unfortunately, the real world is not that simple. Defining precisely what we mean by class effect and efficacy becomes increasingly problematic, for example, as we have recently witnessed with calcium channel blockers, β-blockers, angiotensin-converting enzyme inhibitors, HMG CoA reductase inhibitors, glycoprotein IIb/IIIa antagonists, low-molecular-weight heparins, and direct thrombin antagonists.1 If we identify a drug that demonstrates efficacy, are the benefits of that drug generalizable to all drugs with similar biological targets?2 If benefits are present in one clinical circumstance, are those benefits generalizable to all circumstances in which that class of drugs can be applied?3 In the modern cost-conscious arena, can we substitute less expensive, mechanistically similar agents that may not have the same weight of clinical evidence support or even the same degree of clinical benefit? When is it acceptable to generalize to a class effect, or should we adhere strictly to evidence-based therapy with individual compounds? These issues can be viewed from both scientific and clinical perspectives. ### Definition of Biological Target As our scientific knowledge grows, our traditional grouping of drugs has become, to a large extent, obsolete. For example, there are 9 different calcium channel blockers that are approved for clinical use in the United States, which can be divided into 5 general groups on the basis of …