Comparative Efficacy: What We Know, What We Need to Know, and How We Can Get There

In the past decade, the number of medications to treat osteoporosis has markedly increased (1). These drugs have distinct mechanisms of action. However, information on the efficacy of these compounds relative to one another remains limited, which frustrates physicians who want to practice according to the evidence.

Some may attribute this gap to the U.S. Food and Drug Administration's regulatory mandate requiring well-controlled studies to assess both efficacy and safety for registration trials (2). Although the use of placebo is not a mandate, studies largely rely on placebo as a comparator. There is no doubt that the application of this regulation since 1962 dramatically and positively changed the way medicines are developed and led to the approval of many new drugs.

We are all aware that a particular study design will be able to answer a set of questions, and that no single study can answer all of the questions. An extensive literature discusses different approaches for designing clinical trials and the use of placebos and active controls (3, 4). I believe that placebo-controlled trials are an invaluable tool for defining a drug's efficacy during the drug development process. Nonetheless, some question the ethics and utility of using efficacy relative to placebo as the only hurdle to clear before bringing a drug to the market (5, 6). They ask why we deny a patient a known effective treatment—in the form of an active comparator—while missing a golden opportunity to assess relative efficacy.

A pharmaceutical company takes a substantial risk when it compares a new product with an established drug. Failure to demonstrate superiority over a less expensive agent could be financially ruinous. Providers and patients may not embrace a new therapy when it proves to be inferior …