The role of the regulatory committee is to provide the PSI/EFSPI viewpoint on regulatory issues. This includes promoting best practice, reviewing regulatory policy and guidelines, driving debate on future guidance, and engaging with statisticians in European regulatory agencies.
During 2018 the regulatory committee held five regular committee meetings, as well as meetings with the EMA’s Biostatistics Working Party (BSWP) and the MHRA statisticians. The committee coordinated the review of several regulatory guidance documents (more detail below). Committee members have contributed to EMA and industry workshops, as well as webinars, on topics such as estimands, clinical trial transparency, and PROs. In addition; members of the committee helped organize the 3rd EFSPI workshop on regulatory statistics held in Basel as well as two plenary sessions at the PSI conference in Amsterdam (the regulatory town hall and an estimand role play).
In July the chair of the regulatory committee transferred to Anna Berglind from Christoph Gerlinger, who is now the co-chair of the committee.
Two regulatory expert working groups were active at the beginning of 2018: the expert group on subgroups continued the work on developing a best practice for subgroup analyses and published a paper on the topic in Pharmaceutical Statistics (1). This expert group is still active. In addition, the expert group on confidentiality of interim results established following the 2016 meeting with the BSWP was still active at the beginning of the year. The committee agreed at the committee meeting in September 2018 to pause the work in this expert group following finalizing the slides and minutes from the BSWP-meeting 2017 in which the recommendations from the group are documented.
Dane A, Spencer A, Rosenkranz G, Lipkovich I, Parke T, on behalf of the PSI/EFSPI Working Group on Subgroup Analysis. Subgroup analysis and interpretation for phase 3 confirmatory trials: White paper of the EFSPI/PSI working group on subgroup analysis. Pharmaceutical Statistics. 2018;1–14. https://doi.org/10.1002/pst.1919
Meetings with statisticians from regulatory agencies
On September 19, 2018, the PSI/EFSPI regulatory regulatory committee met with the MHRA statisticians in London. Topics discussed included: the use of historical / dynamic borrowing / synthetic control arms for regulatory decision making, innovative study designs, quality tolerance limits and risk based monitoring, estimands, protocols for device (non-drug) studies, statistical assessment of quality attributes, treatment switching in oncology, parametric modelling for estimation of treatment benefit in survival analyses, the increase in innovative adaptive designs to evaluate biomarkers, how to analyse multiple occurrences of hospitalization in CV trials, the use of trimmed means to handle missing data, and CRF standards for reason for withdrawals.
In addition, the regulatory committee met with the EMA’s BSWP on October 8, 2018. Topics discussed included: implications of EMA’s Brexit preparedness business continuity plan on statistics, use of external (“real world”) evidence in confirmatory studies, and sharing blinded data of an ongoing study.
The regulatory committee collated comments on the following documents during the year:
FDA’s draft guidance on Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics; draft Guidance for Industry
FDA’s draft guidance on Adaptive Designs for Clinical Trials of Drugs and Biologics; draft guidance for industry
FDA’s draft guidance on Meta-Analyses of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products Guidance for Industry
FDA’s draft guidance on Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer Promotional Labeling and Advertisements Guidance for Industry
EMA’s draft Questions and Answers on Data Monitoring Committees issues
Special thanks to Anne Danniau, Jϋrgen Hummel, Tony Sabin and Kaspar Rufibach for collating comments for the committee.