Description: Power and sample size calculations are well developed for various parametric tests and clinical trial designs. The literature for nonparametric tests is, however, fairly scarce and extensions to adaptive group-sequential have only been considered recently. This thesis will review the existing literature and apply novel methods to balance sample size, power and Type-I error to nonparametric tests with application to preclinical studies.

Contact: leonhard.held@uzh.ch

Description: The standard to analyse a non-inferiority (NI) trial comparing a new treatment to an establised one is the fixed margin approach, where a non-inferiority margin is selected based on historical evidence that the comparator in the historical trial was effective. The margin is often taken to be the limit of the 95%-CI of the historical trial effect which is closest to the null effect and the NI trial then has to show that the new treatment is significantly better than the fixed margin. An alternative approach is to synthesize the evidence from both trials in order to investigate whether the new treatment would have been superior to placebo in a hypothetical direct comparison (Althunian, 2017). The relevance of both approaches is reflected in recent guidelines by the FDA and EMA. This Master thesis will compare the two methods and investigate the applicability of alternative methods in this setting (e.g. square-and-add for binary outcomes).

Contact: leonhard.held@uzh.ch

References:
Althunian et al (2017). Defining the noninferiority margin and analysing noninferiority: An overview. British Journal of Clinical Pharmacology. doi: 10.1111/bcp.13280.
EMA (2025). Guideline on non-inferiority and equivalence comparisons in clinical trials (Draft). PDF
FDA (2016). Non-Inferiority Clinical Trials to Establish Effectiveness. PDF