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Are More Complex Protocols Hurting Enrollment?

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Protocol complexity is a measure of the relative effort needed to conduct a study—specifically, the number and complexity of procedures that investigative sites are required to administer to study subjects. As you might expect, a more complex protocol requires bigger budgets to support the protocol procedures from a regulatory, scientific and operational standpoint. We have also anticipated that since increased complexity puts greater burden on both site personnel and patients, it likely has a negative impact on subject recruitment efforts.

So we recently decided to look into the correlation between protocol complexity and the ratio of enrolled to screened patients. What we found—using data available in the Medidata Insights metric warehouse comprising over 5,000 studies—clearly supported our expectations. In particular, and as was reported last August in our monthly Applied Clinical Trials online Medidata Insights metrics series, protocol complexity across the industry has increased steadily in the past five years. This increase in protocol complexity is accompanied by a downward trend in the ratio of enrolled-to-screened patients, going from roughly 71 percent in 2007 to about 62 percent in 2011. This lower ratio translates to a higher ratio of screen failures, indicating that fewer subjects are continuing into study enrollment. I should be clear that these two data trends are coming from two distinct sections of the metrics warehouse, so we cannot prove a one-to-one direct relationship between protocol complexity in a study and enrollment rates in that same study. But, at a macro level, this analysis highlights that increasing complexity of protocols correlates with either higher patient screening or lower patient enrollment, or both.

As we’ve discussed on this blog, we feel confident that increased protocol complexity also drives an increase in eCRF complexity and drags out study start-up timelines, increasing monitoring costs and burden on both sites and patients. Given that a significant portion of the data collected in a clinical trial (up to 30 percent) is never used in a new drug application, it’s even more concerning if this situation 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 significant amount of clinical procedures in a protocol may be unnecessary, which of course further drives up complexity and costs. So it’s obviously important that high quality protocols be designed with careful consideration to complexity, ensuring well-defined screening criteria optimizing subject enrollment and ultimately, and perhaps most importantly, patient safety.

What is your view on the relationship between protocol complexity and patient recruitment? As always, we want to hear about your experiences.

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