Study finds majority of clinical trial protocols are amended during clinical trials

The study, which was conducted by the Tufts University Center for the Study of Drug Development (CSDD) in order to quantify the impact of protocol changes on clinical trials, found that completed protocols across all clinical trials incur an average of 2.3 amendments, with each requiring an average of 6.9 changes to the protocol, and this leads to significant unplanned expense and delay.

The Tufts Center for the Study of Drug Development at Tufts University in Boston provides strategic information to help drug developers, regulators, and policy makers improve the quality and efficiency of pharmaceutical development, review, and utilization.

Ken Getz, who carried out the study, commented that “although amendments to protocols of clinical trials are sometimes necessary to optimise study results and ensure patient safety and ethical treatment, study sponsors can minimise the number of protocols through better initial study design and improved recruitment of study volunteers”. Mr Getz is a senior research fellow at Tufts CSDD and assistant professor at the University.

Mr Getz forecasts that a high incidence of protocol amendments is likely to continue, given the analysis’ finding that the mean number of amendments was positively and significantly correlated with the rising number of procedures per protocol, study length and number of investigative sites participating in each clinical trial.

The research has been reported in the September/October issue of the Tufts CSDD Impact Report and mentions that until now, the incidence, causes and impact of protocol amendments have never been systematically quantified across the pharmaceutical and biotechnology industry.

The other findings from the study’s are that:

  • across all phases of clinical trials, 43% of protocol amendments occur before first patients are enrolled, with amendments more likely to occur in Phase I;
  • more than half of all protocols require one or more amendments, with Phase III studies requiring the highest number, at 8.5 changes per amendment;
  • one-third of all amendments relate to protocol description and patient eligibility criteria; and
  • the median total cycle time for identifying and resolving a protocol problem is 61 days.


Industry News