January 14, 2016

Protocol Amendments Improve Elements of Clinical Trial Feasibility, But at High Economic and Cycle Time Cost

BOSTON – Jan. 14, 2016 – Research sponsors implement at least one substantial global amendment for nearly 60% of all clinical trial protocols, substantially reducing the number of actual patients screened and enrolled, but leading to significantly longer clinical trial durations and higher costs, a newly completed analysis by the Tufts Center for the Study of Drug Development concludes.

The total median direct cost to implement a substantial amendment for Phase II and Phase III protocols is $141,000 and $535,000, respectively, according to the Tufts CSDD analysis, which defined a substantial amendment as any change to a protocol on a global level requiring internal approval, followed by approval from the institutional or ethical review board or regulatory authority.

In addition, nearly half of all substantial amendments—most often undertaken to modify study volunteer demographics, eligibility criteria, and safety assessment activity—are deemed avoidable by sponsor organizations, Tufts CSDD said.

“The positive news is that unplanned delays, disruptions, and costs associated with protocol amendments have spurred the research-based biopharmaceutical industry to identify new approaches to simplify protocol design and reduce the frequency of amendments,” said Ken Getz, associate professor and director of sponsored research at Tufts CSDD. “Our new analysis provides more detailed insight into the impact of amendments and how to anticipate and manage them.”

Among actions drug sponsors are taking to reduce protocol amendments, are piloted and broad use of feasibility review committees, common protocol templates, and investigative site and patient feedback panels, Getz said.

Other findings from the analysis, reported in the January/February Tufts CSDD Impact Report, released today, include the following:

  • Phase II protocols have the highest incidence of substantial amendments (77%), averaging 2.2 amendments per protocol.
  • Protocols with even one amendment experience a substantially lower actual number of patients screened and enrolled relative to plan, compared to protocols without any amendments.
  • Study conduct durations for protocols with at least one substantial amendment take on average three months longer, compared to protocols without any amendments.
  • Thirty-eight percent of changes made as a result of substantial protocol amendments are related to safety assessment activity and 21% are related to efficacy assessments.

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About the Tufts Center for the Study of Drug Development

The Tufts Center for the Study of Drug Development ( at Tufts University provides strategic information to help drug developers, regulators, and policy makers improve the quality and efficiency of pharmaceutical development, review, and utilization. Tufts CSDD, based in Boston, conducts a wide range of in-depth analyses on pharmaceutical issues and hosts symposia, workshops, and public forums, and publishes Tufts CSDD Impact Reports, a bi-monthly newsletter providing analysis and insight into critical drug development issues.



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