Assessing Drug Risks and Benefits: Lessons from Postmenopausal Hormone Therapy Studies

The issue of safety standards for new drugs remains unsettled. Limitations of biomarker or observational studies for assessing global safety and efficacy of postmenopausal hormone therapy are highlighted by contrast with randomized clinical trial results. On the other hand, requiring large-scale, long-term outcome trials for every new drug might not be practical. Randomized trials with intermediate outcomes such as coronary angiography, coronary or carotid ultrasound, or coronary calcification present attractive alternatives. Trials with intermediate outcomes can be conducted with much smaller sample sizes and shorter duration, but the adequacy of these types of trials for assessment of safety and efficacy remains a topic of ongoing discussion in the scientific and regulatory communities.