Exploring Design Elements of Cancer Pivotal Trials

This is the third in a series of blog posts VOI Consulting will publish based on high-level examination of the company’s new insiteinvestigator™ database. It addresses pivotal trial design for cancer drugs gaining approval during the 2005 to 2011 period.

Pivotal Trial Design

The insiteinvestigator™ database also captures elements of pivotal trial design. Using comparisons between solid tumors and hematological malignancies, the following discussion looks at several of the more important design features: primary endpoints, number of arms, and control types.

Primary Endpoints

Overall survival, defined as the time from randomization until death from any cause, is the FDA’s gold standard for drug approval in the cancer field. From a development standpoint, however, it is the most difficult and costly endpoint to demonstrate as it requires higher patient populations and longer follow-up periods.  As we have seen in the preceding section, the FDA is often willing to accept less than gold standard evidence when doing so will make new therapies available if the data is sufficient to show that these new therapies are both safe and effective.

Indeed, as shown in Figure 1, overall survival served as the primary endpoint in only 18% of all pivotal trials during our time period. Although it was the most common primary endpoint in solid tumors, it still represented just one-third of such trials, barely edging out progression free survival which was the primary endpoint in 29% of solid tumor pivotal trials. More striking is its near-total absence in hematologic malignancies where only 4% of pivotal trials featured overall survival as a primary endpoint. In these cancers, response rate and the closely related duration of response/clinical benefit are the predominant primary endpoints, having been used to support 59% of all approvals.

Figure 1 - Primary Endpoints in Cancer Pivotal Trials 2005-2011

 Insiteinvestigator is VOI’s proprietary database containing detailed information on design, endpoints, populations, size, placement, timelines, efficacy outcomes, and safety results for every pivotal trial supporting a cancer drug approved by the U.S. FDA from 2005 through 2011.

Donald Clark
Donald Clark


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