Optimizing Clinical Trials In Chronic Disease
Clinical trials are the standard for testing the safety and effectiveness of interventions. In recent years, a large proportion of National Institutes of Health (NIH)–funded clinical trials have not achieved target enrollment within the allotted time or budget, and some have been terminated early for futility (Pemberton VL, Evans F, Gulin J, Rosenberg E, Addou E, Burns KM, Gordon DJ, Pearson GD, Kaltman JR. Performance and predictors of recruitment success in National Heart, Lung, and Blood Institute’s cardiovascular clinical trials. Clin Trials. 2018 Oct;15(5):444-451. doi: 10.1177/1740774518792271. Epub 2018 Aug 7. PMID: 30084662).
For example, only 26 percent of National Heart, Lung, and Blood Institute trials were successfully defined as achieving 100 percent enrollment in the target time allowed. Because clinical trials are expensive and require significant time and effort, most especially from patients, it is critical to optimize their success. The first step is to ensure that they have a good start. Current review criteria for funding announcements specific to clinical trials do not include NIH-established best practices as required elements, and investigators may be unclear how much guidance they can request or expect before submitting their applications. Many investigators may not be aware that NIH program office has limited ability to provide advice once the application has been submitted.
This workshop will identify areas of improvement in planning better clinical trials and will consider the key factors that are critical to a successful trial, including patient and stakeholder engagement, pretrial analysis of the study population and landscape, with a focus on better planning and achieving optimal recruitment. NIDDK staff are available to help you regardless of the clinical trial funding mechanism or stage.
- Engage the investigative community, patients, and concerned stakeholders in discussions about best practices for planning, preparing, and implementing clinical trials addressing NIDDK diseases. The focus will be on how to realistically identify potential participants, appropriate patient-centered outcomes, clinically important outcomes, and how to anticipate potential delays and obstacles.
- Discuss how to enroll and retain the appropriate population.
- What are the steps to design clinical trials that are realistic and can enroll and retain the appropriate population with reasonable expectation of reproducibility in the real world (including fidelity metrics and how to handle comparison groups)?
- How can clinical trials be designed to increase the likelihood of implementation (adaptation) in clinical practice?
- What are the critical elements for implementation? What makes trials reproducible by other researchers and implementable (i.e., useful) in clinical practice? How can those trials be done on time, effectively, efficiently, and affordably and be informative?
- Is it a mandate that clinical trials be generalizable and implementable?
- Discuss what trial success means to various stakeholders in the context of the trial phase (patients, investigators, payors, trial sponsor, all health care professionals involved).
- Ideas for how to solicit ways to disseminate and share best practices and tools for clinical trials, expanding from U01s to R01s, including R01 small clinical trials funding announcement (PA-20-183, grants.nih.gov/grants/guide/pa-files/pa-20-183.html), which expires 8 May, 2024, to improve clinical trial preparation and chances for success. Examples include the Clinical and Translational Science Awards (CTSA), National Center for Advancing Translational Sciences, Collaboratory, Trial Innovation Network, Recruitment Innovation Centers, and ENACT (Evolve to Next-Gen ACT; a federated system to ask queries across the entire CTSA network), TIN (Trial Innovation Network, https://trialinnovationnetwork.org/ ),as well as such strategies as specifying and longitudinally monitoring detailed processes in both intervention and control. This could also include modeling the impact of various inclusion/exclusion criteria before submitting application. Export practices and models of both patient engagement and research coordinator engagement from consortia.
- Develop a definition of clinical trial “success” or “completion” that can be used by investigators and NIDDK program staff for planning purposes and evaluating clinical trial status at the time of the project’s final progress report. This could be included in the revised announcement above for guidance.
- Develop a definition of clinical trial “success” or “completion” that can be used by investigators and NIDDK program staff for planning purposes and evaluating clinical trial status at the time of the project’s final progress report (for definitive positive or negative trials, not those that are indeterminate). Current requirements are that “summary results of NIH-supported clinical trials be submitted to ClinicalTrials.gov within 365 days of the actual primary completion date.” However, per policy, these “summary results” could be from trials that are terminated early.
A 2022 OIG report “The National Institutes of Health Did Not Ensure That All Clinical Trial Results Were Reported in Accordance With Federal Requirements” states, “After our systems had been implemented, a total of 530 trials had results information due in FY 2020, FY 2021 or FY 2022. Our analyses show that of these trials, 96% had results information submitted to ClinicalTrials.gov (see Table 1). This is in stark comparison to compliance rates before our policies were enacted. But we note that still only a minority of trials (37%) submitted results information on time.” Significant feedback on the blog suggests that the interface for trial completion submission is cumbersome and confusing.
- Ideas for how to inform investigators of the availability of these best practices, their upcoming importance for application evaluation, and how to best prepare for successful clinical trials. This especially means contacting NIDDK before submitting the application, and ideally during the idea development stage after the specific aims are identified.
- Identify and propose solutions to gaps between planned study surveillance estimates and real-world obstacles to enrollment, as well as anticipate and plan how to surmount other causes of study delays. This could include setting up a periodic discussion group (at least twice a year) for investigators and NIDDK staff.
- Establish a publication committee (before the completion of the workshop) with the goal of submitting proceedings to a peer-reviewed journal. Per recent policy, NIDDK cannot and should not directly participate.
Brigitte Schiller, Fresenius Medical Care
Barbara Bierer, Professor of Medicine, Harvard Medical School
With Acknowledgement to: Susan Landis, Executive Director, Association of Clinical Research Professionals (ACRP)
Janice Lea, Professor of Medicine, Emory University
Diana Clynes, American Association of Kidney Patients (AAKP)
Erin Kahle, AAKP
Ashley Moultrie, CCRP, Clinical Operations Leader, Javara
Jeri Burr, Utah Trial Innovation Center, HEAL Pain Effectiveness Research Network Data Coordinating Center (DCC)
Paul Conway, Chair of Policy and Global Affairs; Immediate Past President, AAKP; Chair of Virginia Renal Disease Council
Glenda Roberts, Director - External Relations and Patient Engagement
Kidney Research Institute
Aynur Unalp-Arida, NIDDK
Kathy Cronin, National Cancer Institute (NCI)
Dawn Corbett, Office of the Director
Nihalani Deepak, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mary Evans, NIDDK
Debbie Gipson, NIDDK
Shannon Givens-Bradley, NIDDK
Raquel Greer, NIDDK
Ying Huang, NCI
Katherine Kavounis, National Heart, Lung, and Blood Institute
Sharon Lawlor, NIDDK
Barbara Linder, NIDDK
Jaron Lockett, NIDDK
Maureen Monaghan Center, NIDDK
Shah Neha, NIDDK
Jenna Norton, NIDDK
Voula Osganian, NIDDK
Rebecca Rodriguez, NIDDK
Minkyung (Min) Song, NCI
Kenneth Wilkins, NIDDK
Susan Yanovski, NIDDK
Erin Kahle, Diana Clynes, and Janice Lea (Emory University) on behalf of AAKP* and invited patient speakers/panelists
Ashley Moultrie, Director, DEI & Community Engagement, Javara
Jeri Burr, Utah Trial Innovation Center, HEAL Pain Effectiveness Research Network DCC
Laura Dember, The University of Pennsylvania
Ebony Boulware, Wake Forest School of Medicine
Charles Scales, Duke University
Alison Huang, University of California, San Francisco
Salina Waddy, National Center for Advancing Translational Sciences (NCATS)
Ken Wiley, NCATS
Paul Harris, Vanderbilt University
Elizabeth Lorenzi, Berry Consultants, LLC
Rekha Kambhampati, U.S. Food and Drug Administration (FDA)
Doug Silverstein, FDA
Eric Pittman, FDA
Shawn Paladini, Country Lead Monitor, Bayer
Barbara Bierer, Professor of Medicine, Harvard Medical School
July 23, 2023
The link to join the webinar will be distributed via email prior to the date of the event.
Kevin Abbott, M.D., M.P.H.
The Scientific Consulting Group, Inc.