Modern Clinical Trials
Key persons: Werner Vach
Collaborators: Oke Gerke (Odense University Hospital, Denmark), Poul Flemming Hoilund-Carlsen (Odense University Hospital, Denmark)
Randomized clinical trials are a cornerstone of medical research aiming at establishing new, beneficial therapies. However, the environment to conduct clinical trials is becoming more and more complex, for example by the need of results synthesis as part of the approval process, the internationalization of the drug approval process, the emergence of individualized treatment strategies to be tested, the differences in requirements by regulatory agencies and health policy makers, and so on. Hence the methodology of clinical trials needs a continuous adaptation to the challenges of a modern world.
In particular we try to address the following topics:
- The progress in molecular biology has opened the vision of highly individualized treatment strategies using profiles of molecular markers to select optimal treatments for each single patient. As any other new treatment, also these new strategies have to demonstrate their benefit in clinical trials. However, we cannot expect that a proposed strategy is beneficial for all patients. So the question is now not longer whether the new strategy is beneficial at all, but how we can find a subset for which we can recommend to follow the strategy.
- Clinical studies are today typically performed as multi center trials involving many hospitals, often in different countries. The question when and how to take this into account in the design and analysis of clinical trails have been a matter of debate for decades, without obtaining a real consensus.
- Regulatory agencies and health policy makers require today several clinical trials before a new drug can be approved, and in many areas treatment recommendations are based on meta analyses of a dozen of trials or more. So a single trial is rarely used for the decision about a new treatment recommendation. Nevertheless the focus on the design and analysis of most studies is on hypotheses testing, reflecting the situation to justify a decision based on a single trial. Hence there is a need to adapt the philosophy of analysing single trials to the typical embedding in a series of trials.
- In comparative effectiveness research it is a common requirement to replace conventional randomized trials by so called randomized real world trials. Whereas the first are often characterized by highly selected populations and highly standardized and specifalized treatments, the latter aim to conduct trials with popularions and interventions similar as much as possible to the conditions of daily clinical routine. The latter are of more relevant for health policy decision making, but their planing and analysis rises more challenges due to an increased heterogeneity in both patient characteristics and treatment modalities. This has to be taken into account in the planning and analysis of such trials.