Measuring the Incidence, Causes, and Repercussions of Protocol Amendments

Abstract

Drug development companies frequently amend finalized clinical trial protocols. Yet the incidence, causes, and impact of protocol amendments have never been quantified. Tufts Center for the Study of Drug Development (Tufts CSDD) conducted a study, in collaboration with 17 large and midsized pharmaceutical and biotechnology companies, examining more than 3,400 clinical trial protocols across development phases and therapeutic areas. Data on protocol characteristics, the number of amendments, the nature and incidence of changes per amendment, the causes of amendments, and the time and cost to implement amendments were among those analyzed. Tufts CSDD found that more than 40% of protocols were amended prior to the first subject/first visit, and one third of amendments were avoidable. Each amended protocol had an average of 2.3 amendments resulting in 4 months of incremental time to implement. Protocol amendments translate into significant unplanned expense and delays for research sponsors and unexpected burden for investigative sites. These findings underscore the substantial impact of protocol amendments on drug development efficiency and present an opportunity to realize substantial cycle time and cost savings.