Report: Tweaking Clinical Trial Protocols Takes Toll on Research

Tweaking even one part of a clinical trial’s protocol — which happens more than half of the time in global trials — takes a toll on research, according to an analysis from the Tufts Center for the Study of Drug Development.

The analysis examined “substantial” amendments in international clinical trials and found that changes occurred in 57 percent of trials of every stage. Most likely to happen in Phase 2, there are usually about two protocol amendments in any given study.

Changes in trial protocols can lead to delays — as much as three months compared with unmodified trials. Further, the median cost for modifications to a mid-to-late-phase trial ranges from $141,000 to $535,000. Most of that money goes toward modifying existing contracts and paying additional ethical review committee fees. Sponsors also have to pay for trial sites and additional drug supplies.

Much of this spending is unnecessary, with the report noting that 45 percent of the design changes were avoidable. That figure represents a 12 percent increase over 2010.

The analysis noted that drugmakers are trying to avoid making changes. “Drug sponsors are responding through piloted and broad use of feasibility review committees, common protocol templates, and investigative site and patient feedback panels.”

Despite these drawbacks, protocol changes can offer the chance to focus on the correct patient population, as the common type of amendments are updates to eligibility criteria and subject demographics.

“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,” says Ken Getz, associate professor and director of sponsored research at Tufts CSD.