Protocol Complexity

This month we focus on the increasing protocol complexity in the past decade, something that has garnered a lot of attention over the past few years. Perhaps not surprisingly, Phase II and Phase III data from the Medidata Insights metrics warehouse show that clinical studies have grown significantly in complexity over the past decade. What caught our eyes was that after the large increase in metrics in the first half of the past decade—and despite continued warnings from experts on the topic—complexity continues on an upward, though admittedly less steep, trend.

The protocol complexity value—a new addition to the Medidata Insights metrics warehouse—provides a quantifiable, repeatable measure of effort required to conduct a study. The calculation takes the quantity of each trial procedure and clinical research activity conducted per completed patient and multiplies each by a relative value unit (RVU). RVU is a mathematical expression of the site work effort required to conduct each procedure and clinical research activity. Thus, the measure indicates the overall effort required to conduct a study and the associated burden on sites.

So what's the impact of increased protocol complexity? According to the Tufts Center for the Study of Drug Development, increased execution burden on sites can lead to more costly clinical trials and potentially greater issues with site training and performance ("Assessing the Impact of Protocol Design Changes on Clinical Trial Performance," Tufts CSDD). Additionally, it is estimated that 15% to 30% of data collected during the average clinical trial process is never used in a new drug application. This increase in added complexity without corresponding added value increases direct costs while negatively impacting patient recruitment and retention. This happens as increased procedure frequency and invasiveness negatively impact the patient experience in clinical trials—for example, the screen-to-complete ratio was 52% from 1999 to 2002 and dropped to 28% from 2003 to 2006 ("Trends and Implications of Increasingly Complex Protocol Designs," Tufts CSDD). Screen failure rates are significantly costly for sponsors; we estimate the average cost per failure across the industry to be roughly $1,200.

Protocol complexity in Phase II/III trials, 2000-2011.

As shared in previous posts, data from the Insights metrics warehouse indicate that three other key metrics are steadily rising: eCRF complexity, number of on–site monitoring days, and the amount of SDV during each on-site day. A correlation among these measures is a reasonable conclusion and, furthermore, it is a plausible deduction that an increase in protocol complexity is driving an increase in eCRF complexity and design timelines, monitoring costs and the burden on both sites and patients.

Despite the significant amount of discussion on the increasing complexity of protocols across the industry—and the need to address this situation—the trend continues. Given the pressure to control costs and streamline trials, is there any way clinical R&D organizations can reduce the cost of clinical trials and the burden on sites and patients when protocol complexity continues to increase steadily?

What is your experience with protocol complexity? Do you find your protocols, or those of your partners, to be more complex? If so, how does increasing complexity impact other aspects of your clinical operations downstream?

As always, Medidata is interested to hear your take on this result. Please also stay tuned as the company delves further into the Insights metric data through 2012.

—Medidata Solutions, www.mdsol.com