title: Analytical, practical and regulatory issues in prevention studies.
abstract: Prevention studies, as distinguished from studies investigating treatments for established disease, present some distinct challenges. Perhaps the most extensive experience with preventive agents is in the area of infectious diseases; vaccines have been extremely effective in preventing many such diseases. Vaccines have been, and continue to be, studied in other disease areas such as certain cancers, but as yet have not achieved success outside of infectious disease prevention. One obvious and important feature of prevention studies is that they enroll healthy individuals; thus such studies require particularly high standards for the safety of those enrolled (and those who might ultimately receive the product being tested). Prevention studies often need to be quite large, as the types of diseases most important to prevent tend to be uncommon. Large studies usually require simplified approaches; to ensure high quality of data on the key variables it may be necessary to compromise on the amount of data collected, frequency of data collection, and other aspects of trial design. The reliability of randomization and blinding may be especially important in these large studies, as bias could easily overwhelm the small effects that are usually sought. Often, biomarkers thought to indicate developing but as yet subclinical disease, will be important to evaluate; whether such markers can serve as primary endpoints in prevention studies has been a contentious issue in many contexts. Studies in older populations, such as those at risk for Alzheimer's Disease, raise challenges such as accounting for competing risks, and considering potential interactions of preventive agents with multiple medications often used by the elderly.
authors.affiliation: Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, FDA, 1401 Rockville Pike, HFM-210, Rockville, MD 20852, USA. ellenberg@cber.fda.gov
authors.forename: Susan S
authors.initials: SS
authors.lastname: Ellenberg
mesh_terms: D002986:Clinical Trials as Topic / Q000331:legislation & jurisprudence; D006801:Humans; D018579:Patient Selection; D011315:Preventive Medicine / Q000331:legislation & jurisprudence / Q000458:organization & administration*; D012449:Safety; D016896:Treatment Outcome; D014481:United States