The Collaboratory has made available all the presentations from their recent Steering Committee meeting held in Bethesda May 1-2, 2019.
Highlights of Day 1 included updates on the progress and sustainability of the NIH Collaboratory, perspectives on the landscape of embedded PCTs (ePCTs) and the need for real-world evidence, challenges and lessons learned from the UH3 Demonstration Projects, updates on progress and transition plans from the UG3 Demonstration Projects, and discussions on data sharing policy and planning. Day 2 featured an intensive workshop hosted by the NIH with the goal of starting discussions on statistical issues with ePCTs.
The workshop will include a series of moderated discussions that focus on issues of measuring trial outcomes from available data sources, potential randomization strategies, specific ePCT design considerations, and unique challenges associated with ePCTs. Panel discussions will utilize case examples from the Collaboratory repertoire and beyond to illustrate how clinical investigators and biostatisticians work to address research questions posed by specific trials.
The Workshop Website provides information on meeting logistics, agenda, and registration. There is also an option to attend the workshop remotely via the NIH Videoconference Center, and those details are also available at the Workshop Website.
Members of the NIH Collaboratory’s Biostatistics and Study Design Core contributed 3 new sections to the Living Textbook exploring issues in the design and analysis of pragmatic clinical trials. The new sections offer insights into emerging issues in embedded pragmatic clinical trials and lessons learned from the NIH Collaboratory’s first round of Demonstration Projects.
The Designing to Avoid Identification Bias section addresses a type of selection bias that can occur in pragmatic clinical trials that use information from electronic health records to determine study population eligibility and in which the study intervention influences who undergoes screening or receives a diagnosis in clinical care.
The Alternative Cluster Randomized Designs section describes alternative design choices for cluster randomized trials and their implications for statistical power and sample size calculations. Modified cluster randomized designs, such as cluster randomization with crossover, may reduce the sample size required for a pragmatic clinical trial and may be particularly feasible in trials embedded in healthcare systems with electronic health records.
In addition to contributing content to the Living Textbook, the Biostatistics and Study Design Core works with the NIH Collaboratory Demonstration Projects to address challenges in their statistical plans and study designs during the planning phase and to develop guidance and technical documents related to study design and biostatistical issues relevant to pragmatic clinical trials.
The NIH Collaboratory is pleased to announce the availability of a new self-paced, 10-module introductory course on how to design, conduct, and disseminate embedded PCTs (ePCTs). This course presents condensed material from the inaugural ePCT Training Workshop held in 2018 and provides users with important things to know and do when designing an ePCT, along with helpful links to additional learning resources within the Living Textbook.
Renee Mitchell, MT(ASCP), CLS(NCA)
Boston Scientific Corporation, Inc.
Terrie Reed, MSIE
Senior Advisor for UDI Adoption
U.S. Food and Drug Administration (FDA)
Roseann White, MA
Director of Innovative Clinical Trial Statistics
Duke Clinical Research Institute
MDEpiNet RAPID and SPEED Projects: Leveraging Real World Evidence to Get Better, Faster, Cheaper Medical Devices for Physicians and Patients
Medical devices; Real-world evidence; Medical Device Epidemiology Network; MDEpiNet; Unique device identifier; UDI
In partnership, clinicians, device developers, and FDA can benefit from the use of real-world evidence on medical devices:
Clinicians can contribute to the generation of real-world evidence.
Device manufacturers can use real-world evidence to evaluate and release new devices and expand indications.
Regulatory bodies can increase the use of patient-level data for device approval.
Unique device identifiers (UDIs) make it possible to follow medical devices longitudinally, advancing the quality of real-world evidence and allowing more sophisticated analyses.
The vision for the future is that registries will transform into big data solutions using multiple sources and will be more robustly integrated with electronic health records (EHRs). Both EHRs and registries will play a role.
More organizations as partners brings greater diversity, advancing better data and results. When stakeholders work together, learning curves can be accelerated toward a transformational approach to real-world evidence.
Registration is open for the 3rd Seattle Symposium on Health Care Data Analytics. The symposium will bring together biostatisticians, health informaticists, epidemiologists, and other data scientists to discuss health research and methods that involve large health care databases.
Experts involved in national research initiatives that use large health care databases will discuss methodological challenges encountered in this setting and share ideas for addressing them. Speakers will share their research on:
statistical approaches to learning from electronic health care data;
We recently asked Dr. Liz DeLong, Chair of the Biostatistics and Study Design Core, to reflect on the first 5 years of the Core’s work and the challenges ahead. She says the biggest impact of the Core has been working with the individual Demonstration Projects to provide a sounding board to discuss statistical challenges. Further, Core members have contributed to new knowledge through manuscripts that address key methodological issues related to pragmatic clinical trials. She’s hoping the Core will continue to push the boundaries of statistical methods in the coming years.
“The statisticians on the individual trials have not only developed excellent statistical methods for their own studies, but also contributed substantively to the Core.” Dr. Liz DeLong
Investigators from the STOP CRC pragmatic trial, an NIH Collaboratory Demonstration Project, have recently published an article in the journal eGEMs describing solutions to issues that arose in the trial’s implementation phase. STOP CRC tests a program to improve colorectal cancer screening rates in a collaborative network of Federally Qualified Health Centers by mailing fecal immunochemical testing (FIT) kits to screen-eligible patients at clinics in the intervention arm. Clinics in the control arm provided opportunistic colorectal-cancer screening to patients at clinic visits in Year 1 and implemented the intervention in Year 2. In this cluster-randomized trial, clinics are the unit of analysis, rather than individual patients, with the primary outcome being the proportion of screen-eligible patients at each clinic who complete a FIT.
The team dealt with various challenges that threatened the validity of their primary analysis, one of which related to potential contamination of the primary outcome due to the timing of the intervention rollout: for control participants, the Year 2 intervention actively overlapped with the Year 1 control measurements. The other challenge was due to a lack of synchronization between the measurement and accrual windows. To deal with these issues, the team had to slightly modify the study design in addition to developing a few sensitivity analyses to better estimate the true impact of the intervention.
“While the nature of the challenges we encountered are not unique to pragmatic trials, we believe they are likely to be more common in such trials due to both the types of designs commonly used in such studies and the challenges of implementing system-based interventions within freestanding health clinics.” (Vollmer et al. eGEMs 2015)
The Publish EDM Forum Community publishes eGEMs (generating evidence & methods to improve patient outcomes) and provides free and open access to this methods case study. Readers can access the article here.