PSI Chair: Anna Berglind        EFSPI Chair: Christoph Gerlinger

The committee members are: 
Anna Berglind, AstraZeneca, Sweden
Olivier Collignon, GSK, UK
Erika Daly, ICON, Ireland
Anne Danniau, UCB, Belgium
Dan Evans, Pfizer, UK
Lars Endahl Laen, Novo Nordisk, Denmark
Chrissie Fletcher, GSK, UK
Christoph Gerlinger, Bayer, Germany
Kerry Gordon, IQVIA, UK
Jürgen Hummel, PPD, UK
Teppo Huttunen, 4Pharma, Finland
Mette Krog Josiassen, Lundbeck, Denmark
Murray Lowe, Phastar, UK
Frances Lynn, Orchard Therapeutics, UK
Roland Marion-Gallois, Cellgene, Switzerland
Sireesha Pamulapati, Biogen, UK
Carol Reid, Roche, UK 
Véronique Robust, Servier, France
Kaspar Rufibach, Roche, Switzerland
Tony Sabin, AstraZeneca, UK
Florian Voss, Boehringer-Ingelheim, Germany
Heike Wöhling, Novartis, Germany

Objectives

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.

2020

FDA released the draft guidance Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products.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 guidance).

2019

General

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.

Expert Groups

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 4^th Regulatory Statistics Workshop took place in Basel, Switzerland on the 23^rd and 24^th 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.

Webinars 

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) introduced. 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 Regulatory perspective.

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.

Training course

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:

• EMA’s draft Questions and Answers on Data Monitoring Committees issues 
• EMA’s draft guidance on Qualification Opinion of Clinically Interpretable Treatment Effect Measures based on Recurrent Event
  
• FDA’s draft guidance in Interacting with the FDA on Complex Innovative Trial Designs for Drugs and Biological Products
  
• FDA’s draft guidance on Patient-Focused Drug Development: Methods to Identify What Is Important to Patients.
  
• EMA’s draft guidance on Preparedness of Medicines' Clinical Trials in Paediatrics.
  
• FDA’s draft guidance on Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics with Continuous Outcomes 
  
• The Center for Drug Evaluation in the NMPA (National Medical Product Administration) in China’s ‘’’ two draft guidelines on Clinical Trial Data Monitoring Committees and on Non-inferiority Clinical Trials.