Positive Clinical Trials
This is a very interesting article (at least for science geeks) about assessing the outcomes of clinical trials. Specifically, when are positive outcomes truly positive and helpful for patients? There are all too many trials that suggest improved survival, but, with close reading, you will see that the improvement in length of life is measured in weeks or even days. Although that is certainly better than nothing, it is definitely not what we are hoping for when we subject ourselves to new treatments.
Here is the abstract and a link to read it all:
When Are "Positive" Clinical Trials in Oncology Truly Positive?
- Alberto Ocana and Ian F. Tannock
The approval of a new drug for cancer treatment by the regulatory authorities, such as the United States Food and Drug Administration or European Medicines Agency, is usually based on the positive results of one or more randomized phase III clinical trials comparing the investigational treatment with the standard treatment. A clinical trial is presented as positive if the new drug tested on an experimental group shows a statistically significant difference with the control group (P < .05) in the primary endpoint, which is usually a time-to-event endpoint (overall survival or progression-free survival). Such apparently positive clinical trials disregard whether the final value of the difference in the primary endpoints between the experimental and control groups (Δ) meets the criterion that was predefined in the protocol. Currently, the trend is to design large trials that may detect statistically significant, but often trivial, differences in survival endpoints. However, recent appeals have been made in the oncology literature for the design of smaller clinical trials to detect or exclude only larger, clinically important, values of Δ. Here, we have evaluated 18 randomized phase III clinical trials that were used for the approval of molecular-targeted anticancer drugs by the United States Food and Drug Administration. Results showed that in some of the articles the magnitude of the reported values of Δ were lower than the values predefined in the protocol. We suggest that trials should not be declared positive based only on a statistically significant P value, but should also require detection of a difference in survival outcome that equals or exceeds a clinically important value that is specified in the protocol.
Recent commentaries in the oncology literature have argued that randomized phase III clinical trials should be designed to detect only substantial clinically important differences in endpoints such as overall survival (OS) or progression-free survival (PFS) between the experimental and control groups (1). We support this argument, and also question the use of the word "positive" to describe a clinical trial that failed to demonstrate a difference in OS or PFS between the two groups that was specified in the protocol, regardless of the statistical significance of the result. Here, we review published articles that report randomized phase III clinical trials whose results were used to support the approval of new molecular-targeted anticancer drugs for treatment of solid tumors between January 1, 2000, and March 31, 2010. We have determined whether or not these trials detected a difference in outcome between the experimental and control groups that was equal to or greater than the value predefined in the protocol.