Control Types and Arms in Pivotal Cancer Trials: 2005-2011

This is the fifth in a series of blog posts VOI Consulting will publish based on high-level examination of the company’s new insiteinvestigator™ database. This article specifically addresses the selection of control types in the comparison arm for cancer drugs gaining approval during the 2005 to 2011 period.

Control Types

Selecting a comparison arm for cancer trials is generally more challenging than in other types of drug development. On the one hand, there is a desire to demonstrate the treatment’s effect as clearly as possible, something that is best done with a placebo control. On the other hand, review boards are often very reluctant to approve these types of trials as there are serious ethical issues involved in featuring a placebo arm with patients suffering from a potentially fatal disease. Instead, common practice calls for using an active control (usually the existing standard-of-care regimen) in the control arm with the investigational agent used either in combination with the standard-of-care or, in cases where more data is available, as monotherapy.

In Figure 1 we see how these general rules are applied in practice. If we ignore single arm trials in hematologic malignancies for the moment, active controls do in fact serve as the most common type of comparison arm for both cancer types. There are also, however, a fair number of placebo controlled pivotal trials, particularly in the solid tumor area. Usually, these were for patients who had failed earlier lines of therapy but this was not always the case as two trials (both in renal cell carcinoma) achieved first-line indications via placebo-controlled trials. Placebo controlled trials were substantially more likely to be used in monotherapy (82%) than in combination therapy trials (18%). This is somewhat surprising given the aversion to giving cancer patients placebo-only treatment but may, at least in part, be reflective of the fact that there are no existing standards-of-care for certain advanced cancers.

Figure 1 - Control Types and Arms in Pivotal Cancer 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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