This, the forth in a series of blog posts VOI Consulting will publish based on high-level examination of the company’s new insiteinvestigator™ database addresses multiple versus single arm trials as it relates to FDA approval of oncology drugs.
Figure 1 shows the frequency of multiple and single arm trials in cancer pivotal trials. Two arm trials dominate the solid tumor category with 84% of all studies falling into this category with the remainder being split equally between single and double arm trials. The picture is quite different in hematologic malignancies, however, where single arm trials account for 49% of all hematologic pivotal studies and are as common in these cancers as two arm trials. It is important to note that the data in Figure 1 is based on individual pivotal trials and, as we have seen, indications are often approved on the basis of more than one trial. However, there were eight approvals in our time period that were made on the basis of a sole, single arm trial. Most were for hematologic cancers and these applications tended to be for conditions with small populations or for use in second line or later patients.
Also of interest is the 5% of trials in the dataset that featured three arms, all but one of which were in the solid tumor category. Three arms were used to test different doses of the investigational drug or in cases where the agent was included in both monotherapy and combination regimens. In each of these instances, a single arm received approval, a fact that suggests more extensive testing at an earlier phase might have allowed for cost savings through the elimination of the third arm. Of course, this must be weighed against the additional time required to conduct further research before moving into the pivotal study. However, three arm trials also slow the process by diverting scarce patients into an arm that will ultimately be discarded. Data on recruitment times and accrual rates, discussed later in this article, may assist planners in evaluating the time trade-off between conducting additional small studies or moving directly into the pivotal trial with a three arm study.
Figure 1 - Number of Arms 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.