Protocol Complexity Versus Patient Enrollment

The complexity of a protocol is the measure of effort required to conduct the study and is a key component for its success from a scientific, execution, and financial planning perspective. Complexity of study protocols is primarily determined by the number/frequency and/or complexity of unique individual procedures required in the study. A more complex protocol requires bigger budgets to support the protocol procedures from a regulatory, scientific, and operational standpoint. It may also warrant a more specific and stringent selection of patients in the study and consequently impact patient recruitment—subject screening and enrollment at sites, besides increasing the associated site burden.

This month's Insights graph provides a comparative evaluation of protocol complexity against the ratio of enrolled to screened patients. This data is derived from studies in the Medidata Insights metrics warehouse between 2007 and 2011. As is evident from the graph—and was reported previously in our blog in August—the complexity of protocols has increased steadily in the past five years. Interestingly, this increase in protocol complexity is accompanied by a downward trend in the ratio of enrolled-to-screened patients. While it is important to understand that these two data trends are coming from two distinct components of the metrics warehouse, where there is not a one-to-one direct relationship or correlation between protocol complexity in a study and enrollment rates in that same study, at a macro level, this analysis highlights that increasing complexity of protocols correlates with either higher patient screening or lower patient enrollment, or both. In other words, when viewed at an aggregate level across the industry, increasing protocol complexity negatively impacts patient recruitment.

As we've discussed before, it is fair to assume that increased protocol complexity drives an increase in eCRF complexity and design timelines, monitoring costs and burden on both sites and patients—overall increasing the costs and timelines associated with clinical trials. Given that 15% to 30% of data collected in a clinical trial is never used in a new drug application, it is a bigger concern if the added complexity without corresponding increases in value, is negatively impacting patient recruitment. And of course, since patient recruitment continues to be a major concern for the industry, any factor that impacts it negatively should be carefully analyzed. Additionally, recent research from Tufts CSDD shows that up to a quarter of clinical procedures as defined in a protocol may be unnecessary, further driving up complexity and costs. It is therefore important that high quality protocols be designed with careful consideration to complexity, ensuring well-defined screening criteria optimizing subject enrollment and ultimately, patient safety.

What is your view on the relationship between protocol complexity and patient recruitment? As always, Medidata is interested to hear your take on this result. Please stay tuned as the company delves further into Insights metrics like these in 2013.

—Medidata Solutions, www.mdsol.com