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Commentary on “Statistics at FDA: Reflections on the Past Six Years”

About a year after Dr. LaVange joined the FDA as a Director of Office of Biostatistics at Center for Drug Evaluation and Research (CDER), I asked her to write an article about responsibilities of statisticians at the FDA and the role of statistics in regulatory decision making. The article opened a special issue on Statistics in Therapeutic Innovation and Regulatory Science journal published in January 2014 (LaVange 2014). Looking at the topics Lisa highlighted in the article published in 2014 and the topics that she wrote about in her recent article (LaVange 2019), one can notice a lot of similarity and enormous progress in most areas. In this commentary, I would like to highlight some work that has been done by the Office of Biostatistics under Dr. LaVange leadership and describe some events that steered industry activities and influenced current thinking. Statisticians at the FDA are responsible for the accurate and timely review of applications submitted to the agency. In addition to reviews of sponsor submissions, FDA statisticians contribute to the development of new policies, white papers and guidance documents. Several important statistical guidance documents were drafted or finalized within the last six years. For instance, the draft guidance on Multiple Endpoints in Clinical Trials was released in 2016, the final guidance on NonInferiority Clinical Trials to Establish Effectiveness was released in 2016, the second draft guidance on Adaptive Designs for Clinical Trials of Drugs and Biologics, and a draft guidance on Meta-Analyses of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products were released in 2018. The draft guidance on Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drug and Biologics was procedural guidance to which the FDA statisticians contributed, and it was also released in 2018. In addition to preparing statistical guidance documents and contributing to nonstatistical guidance documents, the FDA statisticians look for other venues to foster innovation and improve regulatory decision making. In 2016, the FDA issued a qualification of statistical approach MCP-MOD, an efficient statistical methodology for model-based design and analysis of Phase II dose-finding trials that support dose selection for Phase III trials (FDA, 2016a). The proposal came from statisticians at Janssen Pharmaceuticals and Novartis Pharmaceuticals who co-developed the methodology (Bretz Pinheiro, and Branson 2005; Pinheiro et al. 2006). Today many pharmaceutical companies including Bayer use this