BOSTON—With clinical trial protocals becoming more complex, the demands on investigative site personnel and study volunteers are leading to lengthier clinical trials and efforts to recruit and retain patients are being hampered, according to a new study by the Tufts Center for the Study of Drug Development.

Ken Getz, a senior research fellow at the Tufts Center and lead investigator on the study, tells Drug Discovery News there has been a steady increase in the number and frequency of procedures per protocol during the past 10 years, paired with a similar rise in the number of enrollment eligibility criteria and pages per case report form. These protocol design changes are largely due to the nature of diseases currently under investigation and intensifying competition among drug developers. The Tufts CSDD study is the first ever to quantify the impact of changes in protocol design on clinical trial performance. According to the survey, the annual growth rate of unique procedures per protocol grew 6.5 percent between 1999 and 2005. It also found that clinical trials are taking longer. Between 1999 and 2002 and 2003 to 2006, the total time from protocol design readiness to database lock rose from 460 to 780 days, or nearly 70 percent. Volunteer rates dropped from 75 percent in 1999 to 2002 to 59 percent in 2003 to 2006. Volunteer retention rates declined from 69 percent to 48 percent during the same period. Moreover, the work effort required of investigative site personnel to administer protocols is rising faster than the rate of growth of unique procedures or their frequency per protocol. "If anything, the implications of our analysis suggest that sponsors really need to take a closer look at the design of their studies and project the impact they believe it may have on the work burden their sites have to bear, and the patient recruitment and enrollment challenges," Getz says. "If anything, the results point to the need for companies to be much more mindful of the domino effect that occurs when protocols become more demanding and complex." As a result, Getz points out the increasing complexity of protocol designs is contributing to the growing time, cost and risk in drug development. "The rise in protocol complexity represents a significant challenge for drug developers," he says. "There are just more procedures that have to be performed to satisfy the requirements of the study." The first question that arises out of the analysis, according to Getz, is whether the added complexity of the protocol really is necessary. If the answer to the question is no, Getz contends much of the increased demands may not be critical. "It has to be determined if all of this additional complexity and the more demanding requirements of the protocol are necessary for companies to collect the data that is needed to demonstrate the safety and the efficacy of the product to get regulatory approval" Getz says.  It then raises the question of what can be simplified in the protocol."In our study, we offer some insight as to where to look first," he says. "For example, there are certain procedures that add significant burden on the investigative site personnel. You could prioritize procedures to those that are deemed important and those that have minimal impact on site personnel." DDNeditconnect: e020818