Multiple endpoints in clinical trials ­ severe adverse event potentials from the medical biometrician's perspective. / Multiple Endpunkte in klinischen Prüfungen Risiken und Nebenwirkungen aus Sicht der Medizinischen Biometrie

ABSTRACT

The clinical evaluation of medicinal drugs follows strict guidelines both concerning the clinical as well as the pharmaceutical implementation perspective. Furthermore, it underlies similarly rigid implementation guidelines from the medical biometry perspective, pertaining from the choice of minimum necessary patient numbers to the primary statistical evaluation concept. The latter, however, require the explicit parameterization of clinical endpoints, alongside which efficacy and effectiveness of the drug under investigation will then be tested for the trial at hand. In most settings, the choice of these endpoints directly arises from the clinical rationale of the investigation, but is then complemented with a rather rigid recommendation from the trial statistician's perspective, that is the restriction to only one primary clinical endpoint. The use of several parallel clinical endpoints cannot only end up in inconsistent or even contradictory clinical decision rules, but can also have crucial impact on the overall number of patients necessary in the statistical analysis of the clinical trial under consideration. Although the combination of multiple parallel endpoints may provide a solution in some clinical trial settings, the most effective recommendation can be seen in specifying only one primary clinical endpoint of maximum clinical relevance for the therapeutic intention at hand.