The Future of Clinical Trial Design: The Transition from Hard Endpoints to Value-Based Endpoints.

Clinical trials have been conducted since 500 BC. Currently, the methodological gold standard is the randomized controlled clinical trial, introduced by Austin Bradford Hill. This standard has produced enormous amounts of high-quality evidence, resulting in evidence-based clinical guidelines for physicians. However, the current trial paradigm needs to evolve because of the ongoing decrease of the incidence of hard endpoints and spiraling trial costs. While new trial designs, such as adaptive clinical trials, may lead to an increase in efficiency and decrease in costs, we propose a shift towards value-based trial design: a paradigm that mirrors value-based thinking in business and health care. Value-based clinical trials will use technology to focus more on symptoms and endpoints that patients care about, will incorporate fewer research centers, and will measure a state or consequence of disease at home or at work. Furthermore, they will measure the subjective experience of subjects in relation to other objective measurements. Ideally, the endpoints are suitable for individual assessment of the effect of an intervention. The value-based clinical trial of the future will have a low burden for participants, allowing for the inclusion of neglected populations such as children and the elderly, will be data-rich due to a high frequency of measurements, and can be conducted with technology that is already available.