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.
FDA released the draft
guidance Demonstrating Substantial Evidence of Effectiveness for Human
Drug and Biological Products. The document is intended to
provide guidance on the evidence to be provided to demonstrate effectiveness
when planning to file new drug applications (NDAs), biologics license
applications (BLAs), or applications for supplemental indications, and
complements and expands on the 1998 guidance entitled Providing Clinical
Evidence of Effectiveness for Human Drug and Biological Products (the 1998
During 2019 the regulatory committee held five
regular committee meetings and met with the MHRA statisticians. The committee
coordinated the review of several regulatory guidance documents (more detail
below). Committee members contributed to EMA and industry workshops, as well as
webinars; helped organize the 4th EFSPI workshop on regulatory statistics held
in Basel as well as a plenary session on Regulatory and HTA hot topics at the PSI
conference in London.
In July the chair of the regulatory committee
transferred to Christoph Gerlinger from Anna Berglind, who is now the co-chair
of the committee.
Meeting with Regulators
On Wednesday 13 November 2019 the PSI/EFSPI Regulatory
Committee met with the MHRA statisticians in London for an informal exchange of
statistical topics important for both regulators and industry. There was great
discussion on topics such as estimands, subgroup analyses and predefined
Quality Tolerance Limits as well as quality attributes, model-based dose
escalation studies, real world evidence, use of historical controls and the
lack of statisticians in many ethics’ committees in England.
The planned meeting with EMA’s biostatistics working party
was postponed to 2020 due to EMA’s business continuation plan for Brexit.
The regulatory expert working group on
subgroup analyses was still active during 2019 and continued the work on
developing best practice for subgroup analyses.
The 4th Regulatory Workshop
The 4th Regulatory Statistics Workshop took
place in Basel, Switzerland on the 23rd and 24th
September 2019. Approximately 230 delegates attended the workshop with great
discussion between regulators, academics, and industry on real-world data,
analysis of safety in clinical trials, estimands, modern approaches for rare
disease and contributed short topics.
On July 4th, 2019,
the PSI/EFSPI Regulatory Committee organized the Webinar: ‘Adaptive design:
updated draft FDA guidance and its implications’. In the webinar Jürgen Hummel
(PPD) shared an overview of the FDA’s updated guidance on adaptive design for
clinical trials of drugs and biologics, and discussed implications for industry.
This was followed by the introduction of an open-source statistical software
for adaptive designs, RPACT (an R package available on CRAN that enables the
design and analysis of confirmatory adaptive clinical trials) led by Kaspar
Rufibach (Roche). Kit Roes (Working Group Methodology of the
Dutch Medicines Evaluation Board and member of the EMA Biostatistics Working
Party) closed the webinar by commenting on the guidance from a European
In addition, Anna Berglind chaired a joint PSI/DIA
Journal Club Webinar on Subgroup Analyses on October 24, where Cynthia Huber from
the University of Göttingen discussed her paper 'A comparison
of subgroup identification methods in clinical drug development: Simulation
study and regulatory considerations', and Christoph Muysers and Bodo
Kirsch (both Bayer) shared a systematic approach for post hoc subgroup analyses
with applications in clinical case studies.
Two members of the commitee (Chrissie Fletcher and Kerry Gordon) joined James Matcham (AstraZeneca) and Caroline Pothet (GSK) in delivering the two day training course "ICH for Statisticians" on 19/20 November. Of note, 100% of attendees said they would recommend the course to others.
Review of Guidelines
The regulatory committee collated comments on the following documents during the year: