Time and Method: Adaptive Clinical Trials and the Perils of Accelerat...

Two recent biomedical movements are explicitly dedicated to the acceleration of biomedical research from discovery to implementation: translational medicine and personalized medicine. Translational initiatives have encouraged private-public partnerships and cross-disciplinary networks of research as means of “uncorking the bottleneck” of biomedical innovation. While scholars mostly agree that translational medicine does not provide epistemically novel research methods but is rather focused on external, i.e. financial and organizational measures (Solomon 2015, Robinson 2019), translational initiatives have significantly contributed to the rise of personalized medicine in the last decade. Focusing on acceleration as the starting point, we can see that the fastest translations have been the ones occurring in the domain of personalized medicine. This is largely due to novelties in the clinical assessment route in personalized medicine research. When therapies are individualized, the usual phase III randomized controlled trials will often be either impossible (in the case of rare diseases), either superfluous (since it is expected that personalized therapies work only for some and not for most patients), or even unethical, if they unjustifiably extend the time for a life-saving or otherwise high-stake therapy to become available.

The emergence of personalized medicine has led to a development in the design of early stage clinical trials which improve access and evaluate efficacy earlier than the usual clinical assessment procedures. Examples of adaptive measures in clinical trials are early stopping rules in the case of a lack of efficacy or unacceptable toxicity, as well as changing doses or drug schedules. The goal of adaptive design is to learn from the data in the early trials and apply the knowledge as soon as possible, unlike conducting phase III randomized trials that take more time, use large samples, and often fail, though (arguably) provide more reliable results. The problem with adaptive trials is that results can be difficult to interpret due to biases in research design. Adaptation also poses a problem for successful communicating of risks and benefits to the patients (Garralda et al. 2019, Thorlund et al. 2018). In this talk I highlight the benefits and perils of adaptive design trials.

References

Garralda et al. (2019), “New clinical trial designs in the era of precision medicine”, Molecular Oncology 13: 549-557.

Robinson, M. D. (2019), “Financializing epistemic norms in contemporary biomedical innovation”, Synthese 196: 4391–407.

Solomon, M. (2015), Making Medical Knowledge. Oxford University Press.

Thorlund, K.; Haggstrom, J.; Park, J. J. H. and Mills, E. J. (2018), “Key design considerations for adaptive clinical trials: a primer for clinicians”, British Medical Journal 360: k698.