The Cost of Abandoning Clinical Trials
In the second blog of this series focused on recruiting and retaining volunteers in cancer (and other difficult) trials, we shall review another aspect of pharmaceutical development, the cost of abandoning clinical trials that end up generating uninterpretable results because they miss the enrollment needed to demonstrate statistical significance at a predefined level of efficacy. For a thorough review of the roots of this problem, see Fogel et al. (1).
The situation is particularly bad for cancer trials where one in four trials fails to enroll enough participants (2). An Institute of Medicine report indicates that overall, 40% of National Cancer Institute-sponsored trials are not completed. There probably are a multitude of reasons behind this situation. Among them is the apparent reluctance of cancer patients to participate (2%–5%). It is generally acknowledged that less than 10% of eligible research volunteers are recruited in clinical trials. Another reason, itself a consequence of precision medicine and its need to find tumors with precise characteristics susceptible to respond to narrow drug effects, is that enrollment fractions (the number of enrollees divided by the number of subjects screened) can be very low (less than 5%).
Generating enough information to decide whether one should continue in clinical development is important at each stage of the clinical trial process. The investments of resources, time, and funding increase with successive stages. And the cost of a phase 3 clinical trial that generates interpretable results indicating that the drug should be abandoned is not just the cost associated with the trial itself but the cost of all prior trials as well as the cost of lost time pursuing unviable alternatives. It is generally estimated that half of the total average cost of bringing a new drug to market is attributable to opportunity costs associated with foregone investments over the drug development period. One should also consider that the cost of a phase 3 trial that does NOT generate interpretable results has an additional and undetermined component, in case the drug is dropped from the portfolio, the opportunity cost of scrapping further development for lack of guiding clinical results …. unless the drug is eventually tested in a better clinical trial by the originator (after a reversal of decision) or by a licensee that sees a missed opportunity, or a competitor.
Besides cost and investment issues, these abandonments of clinical trials also create ethical and public relations issues regarding patient involvement. They also can discourage investigators about future participation. Patients generally have an expectation that their participation in a trial will lead to an advancement of knowledge based on the trial’s successful completion.
A trial generating uninterpretable results fails to fulfill these expectations.
1. Fogel, D.B. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: A review. Contemporary Clinical Trials Communications. Open access article.
2. Feller, S. http.//upi.com/Health News/2015/12/30
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