Data Monitoring Committees in the Changing Landscape of Clinical Trials

Implementing data monitoring committees (DMCs) during the COVID-19 pandemic and planning for them in future clinical trials presents unique challenges. PRA has developed strategies to address these challenges, and will present these latest developments in this upcoming webinar.

DMCs are changing rapidly, along with the current clinical trial changes seen in recent years, accelerated further since the onset of COVID-19. These changes can be seen from DMC data delivery to DMC data analysis, DMC planning and setup and ultimately DMC management.

DMCs have always suffered from the conflicting objectives of monitoring trial data via interim analyses for safety, ethical and scientific integrity purposes without interfering with the weight of evidence designed into the trial prospectively. Both these objectives must be met in the highly regulated “post-ICH” environment of clinical research for drug approvals and post-marketing research, requiring documentation, version control and standard operating procedures (SOPs) for DMC handling, based on published regulatory guidance.

In recent years, research on novel clinical trial and clinical development plan designs to address unmet medical needs in rare diseases, personalized medicine, virtual trials and incorporation of Real World Evidence has accelerated greatly, leading to a myriad of novel adaptive, Bayesian and innovative statistical designs. These have led to a reassessment of DMC-handling paradigms established over the long period since the earliest cardiovascular trial DMCs in the 1990s, and the need for new paradigms taking into account potential new DMC objectives such as monitoring adaptive algorithms during the trial and monitoring subprotocol objectives for Master Protocol designs.

Due to the changes in trial designs and regulatory demands, old standard processes to run a DMC are also changing. The new paradigms, including adaptive designs and virtual trials, have impacted the objectives and demands of DMC processing. These novel trial designs have a more complex data flow with unique challenges in analysis and delivery. The DMC manager has a more challenging role in planning, organizing and supporting the DMC and documenting properly the key discussion points that often include more interim analyses and more complex interims statistically. All of this is now coupled with the need for expedited processes that arose from the current vaccine trial experience during COVID. It is now more important than ever to begin planning and establishing the DMC as soon as possible.

As a result of these developments, an urgent need has arisen to train clinical trial professionals to support DMCs using both standard paradigms AND paradigms appropriate for the rapidly changing designs that are arising.

Register for this webinar to learn how we can respond to these challenges in the design and implementation of a DMC.

Speakers

John Constant, PhD, Vice President, Scientific Affairs, Statistical Consulting, PRA Health Sciences

Dr. John Constant, PRA’s Vice President of Scientific Affairs and Statistical Consulting, has over 40 years’ experience in applied statistics, with 30 years in pharmaceutical research and 20 at PRA. He was Senior Statistical Consultant at Bayer Corporation, Berkeley, California for 8 years (and primary statistical FDA liaison) and has taught at McGill University and University of Waterloo, Canada and for 10 years as Visiting Professor in Statistics at UC Berkeley, California.

He has served on Advisory Committees and Data Monitoring Committees and as statistical advisor to various biotechnology and pharmaceutical companies, interacting with regulatory agencies on their behalf frequently. His experience includes design, analysis, reporting and regulatory agency representation on national and global trials and submissions in oncology, CNS, CV and other indications. His professional experience also includes Data Monitoring Committe/DSMB/IDMC work as a voting member and with Prof. Stephen George, Prof. Ed Gehan, Prof. KyungMann Kim, Prof Tom Fleming, Prof Scott Emerson and others.

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Karen Shaffer, RN, MHA, Associate Director of Operations, DMC Unit, PRA Health Sciences

Ms. Shaffer joined PRA as an Associate Director of Operation overseeing the DMC Unit. She has overseen, developed and managed DMC groups for over 15 years. She has DMC expertise in Virology, Microbiology, Immunology, CNS and Pediatrics, to name a few. Her expertise spans across multiple types of safety committees from phase 1 to phase IV global trials. She also has expertise in pharmacovigilance, clinical research development and operations.

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Lance Dado, DMC Project Manager, PRA Health Sciences

Mr. Dado is the PRA Project Manager in the DMC unit, with more than 9 years’ experience in pharmaceutical research. He has contributed, overseen and facilitated over 70 trials with DMC components on global trials with varying indications.

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