The growing complexity of clinical trial protocols is making life more difficult for site personnel and study volunteers alike, warns a new study by the US-based Tufts Center for the Study of Drug Development (Tufts CSDD). The outcome, it says, is longer clinical trials and increasing problems with recruiting and retaining patients.

Published in the January/February Tufts CSDD Impact Report, the study was the first ever to quantify the impact of changes in protocol design on clinical trial performance, the Center noted. It found that the annual growth rate for unique procedures per protocol in clinical trials between 1999 and 2005 was 6.5%.

In parallel, the Tufts Center pointed out, clinical trials were taking longer. Between 1999-2002 and 2003-2006, the overall time from protocol design readiness to database lock rose by 69.6%, from 460 days to 780 days. In the same periods, volunteer enrolment rates dropped from 75% to 59% while volunteer retention rates declined from 69% to 48%.

Hand in hand with increasing complexity, the study revealed, the effort required from investigative site personnel to administer clinical trial protocols was expanding at a faster rate than the growth of unique procedures or their frequency per protocol.

“During the past decade, there has been a steady increase in the number and frequency of procedures per protocol, and a similar rise in the number of enrolment eligibility criteria and pages per case report form,” commented Ken Getz, a senior research fellow at the Tufts Center and lead investigator for the study. The protocol design changes were largely due to the nature of the diseases involved and intensifying competition among drug developers, he explained.

The rise in protocol complexity was a “significant challenge” for the pharmaceutical sector, contributing not just to longer lead times but to the growing cost and risk of drug development, Getz warned.