  Conditional (European Medicines Agency) or accelerated (U.S. Food and Drug
Administration) approval of drugs allow earlier access to promising new
treatments that address unmet medical needs. Certain post-marketing
requirements must typically be met in order to obtain full approval, such as
conducting a new post-market clinical trial. We study the applicability of the
recently developed harmonic mean Chi-squared test to this conditional or
accelerated approval framework. The proposed approach can be used both to
support the design of the post-market trial and the analysis of the combined
evidence provided by both trials. Other methods considered are the two-trials
rule, Fisher's criterion and Stouffer's method. In contrast to some of the
traditional methods, the harmonic mean Chi-squared test always requires a
post-market clinical trial. If the p-value from the pre-market clinical trial
is << 0.025, a smaller sample size for the post-market clinical trial is needed
than with the two-trials rule. For illustration, we apply the harmonic mean
Chi-squared test to a drug which received conditional (and later full) market
licensing by the EMA. A simulation study is conducted to study the operating
characteristics of the harmonic mean Chi-squared test and two-trials rule in
more detail. We finally investigate the applicability of these two methods to
compute the power at interim of an ongoing post-market trial. These results are
expected to aid in the design and assessment of the required post-market
studies in terms of the level of evidence required for full approval.
