Complexity in Clinical Trials: Blind Spots, Misleading Criteria, Winners and Losers

Abstract

More than 90% of new potential therapeutic drugs have failed in clinical trials. In this study, the characteristics of failed new drugs for the treatment of seven types of cancer were first examined, followed by a review of the hazard ratios of survival in typical phase III clinical drug trials of these cancers from the last five years. The data suggested that population sizes in most clinical trials were limited to a certain level of detection. Evidently, each drug has its effect only in certain individuals with defined characteristics, and the success and failure of a new drug depend on these characteristics, such as ethnic group, sex, environmental conditions, pathological features, and genotype. Due to the complexity of the influence of multiple factors and the current limitation in understanding them, a large number of subgroups among patients may not have been recognized. Therefore, any decision only based on a few statistical comparisons, may not always provide correct judgement for a new drug. The drugs that are successful in clinical trials are “winners” regardless of how the differences in genotypes or other characteristics' influence on patients as compared to new drugs and placebos, or new and existing drugs. Drugs that are effective on certain characterizations or a specific group of patients are often categorized as a failure in clinical trials based on the current statistical criteria. Thus, previously failed drugs can be reevaluated and reutilized by analyzing whether these drugs have different effects on various genomic populations, or on patients who may emerge as subgroups based on other variables.