We recently welcomed two new multi-stakeholder advisory panels as they met for the first time. We rely on our advisory panels to bring their experience and expertise from across the healthcare community to guide us as we decide what research to fund. The new panels, one focusing on rare diseases and the other on clinical trials, are mandated in our authorizing legislation. Both of the panels immediately got down to business and laid out ambitious agendas for themselves.
Advisory Panel on Rare Disease
The 13-member Advisory Panel on Rare Disease (defined as a condition affecting fewer than 200,000 people in the United States) is charged with helping us decide how to best manage our comparative effectiveness research on these diseases. It will also advise us on the needs and concerns of the rare disease community and identify opportunities for PCORI to collaborate with that community. The new panel includes patients, caregivers, and representatives of rare disease advocacy groups, as well as clinicians, researchers, staff members from pharmaceutical companies, and a representative of an insurer.
The special focus on rare diseases arises because clinicians often have little experience with each of the nearly 7,000 recognized rare diseases, which affect more than 25 million people overall. Researchers also experience difficulty putting together a large enough patient population for a clinical trial.
Working on rare diseases has benefits as well as difficulties. Panel member J. Russell Teagarden, DMH, MA, said, “The rare disease community is a well-connected world. We can reach out for quick feedback and tap into networks to get rapid responses and insights.”
Much of the panel’s discussion at its first meeting, on April 30, focused on patient registries. Said panel member Jacqueline Alikhaani, BA, MBA candidate, and a survivor of a rare congenital heart disease, “As a patient, it’s important to make sure registries are as diverse as possible and that they reach out to minority and underserved communities.” Yaffa R. Rubinstein, MS, PhD, added, “Patients don’t know which registry to go to; who owns it, who controls it, what happens if it loses funding.”
“Data on rare diseases is precious. We can’t afford to lose it,” said Marshall L. Summar, MD, who was recently named the panel's first chair. The panel also deliberated on what issues should command its focus initially. The following topics emerged as immediate concerns:
- Rare disease registries: usability, sustainability, ethical implications, ownership in the long term, governance, data linkage to other registries, legacy issues, Common Data Elements (CDEs), standardization of data, data accessibility, Institutional Review Board (IRB) issues around long-term registries, IRB standardization across multiple institutions, and disease definitions.
- Minimal datasets, data standards for rare disease registries.
- Landscape review on rare disease research issues: Commission a rare disease research landscape review, which would provide a solid starting point for the panel. This review could be a paper or a database or a combination of both. It could provide a gap analysis to shed light on what the panel should focus on.
- Patient proxy: Work on the implications of the active involvement of the patient’s family and other caregivers, which often takes place over the direct involvement of the patient.
- Biospecimens: Address the issue of collecting biospecimens for rare diseases, to be able to connect this dataset to the patient-reported data and the clinician-reported data.
- New treatments: Provide guidance on the type of evidence and standards needed when new treatments are introduced to the rare disease world.
- Evaluating evidence: Propose a new type of evidence grading system for rare disease research. This could provide credibility to different forms of evidence to improve access for patients and clinicians.
- Cross-validation: Provide guidance on the cross-validation of patient- and family-reported data versus investigator-reported data to test data validity.
- Missing data and dosage: Tackle the issue of missing data to determine appropriate dosing schedules.
- PCORnet: Collaborate with the task forces (in particular, the Rare Diseases and the Biorepository Task Forces) and the rare disease Patient-Powered Research Networks, and guide them on the foundational issues that the panel might work on.
The panelists also expressed interest in coordinating with PCORI’s other multi-stakeholder advisory panels that prioritize research topics. Subsequent to the meeting, the PCORI Board of Governors appointed Summar as its first chair and Vincent Del Gaizo as its first co-chair.
Advisory Panel on Clinical Trials
On May 1, 2014, our Advisory Panel on Clinical Trials met for the first time, to provide counsel on PCORI’s strategies for supporting clinical trials. A well-designed clinical trial is one of our most reliable tools for determining the comparative effectiveness of various healthcare options. However, it can be difficult to decide for which topics randomized controlled clinical trials are preferable to less costly and less time-consuming study approaches. There are also challenges in identifying, developing, and implementing the best trial design, especially for trials that take place in clinical or community settings instead of at research sites.
This panel has 10 members with diverse experiences in health care and research. More than half are biostatisticians or epidemiologists or have other technical expertise in conducting clinical trials. Two others represent patients, patient advocates, or family caregivers, and another is an expert in the ethical aspects of such clinical trials. The panelists come from medical and research centers, a university, a pharmaceutical company, an association, a consulting group, a nonprofit education network, and the Food and Drug Administration. Two members of PCORI’s Methodology Committee have joined the advisory panel in an ex officio capacity.
The new advisory panel is charged with providing expertise in the selection, design, and implementation of trials. The panel may examine trials in our growing research portfolio and advise us on strategies for implementing the standards set forth in the PCORI Methodology Report.
“I care about whether a study answers the question it’s purporting to answer," said Elizabeth Stuart, PhD, AM, who was recently named the panel's first chair. "Is the question important? Is the design the best to get at it?” she added.
Panel member Merrick Zwarenstein, MBBCh, MSc, PhD, noted, “We need to tease out issues in the design that affect applicability of research findings.”
During its discussion, the new advisory panel agreed to a variety of initial priorities, including:
- Collaboration with other PCORI entities: Panel members expressed a strong interest in collaborating and possibly meeting in conjunction with the Advisory Panel on Rare Disease, the PCORnet Task Force, and possibly PCORI’s multi-stakeholder advisory panels that help set PCORI’s research priorities.
- Usual care as the comparator arm: Advise PCORI on whether and how PCORI should provide clarity on the definition and use of usual care as the comparator arm in clinical trials.
- Innovative study designs: Generalize lessons and generate white papers, contribute to the design of merit reviewer training, and define the settings in which innovative designs, such as pragmatic or adaptive designs, may be useful.
- Clinical trials methodology standards: The panel was particularly interested in discussing minimum standards for trial design, conduct, and analysis, especially for pragmatic trials.
- Clinical trials as case studies: The panel suggested that they could learn from the experience of the current PCORI-funded clinical trials and identify particular case studies with educational value.
- The PCORI Funding Announcement (PFA) for Pragmatic Clinical Studies and Large Simple Trials to Evaluate Patient-Centered Outcomes: Advise PCORI on how to provide more details regarding what we are looking for in terms of pragmatic trials, critique the PFA and provide comments on how to improve it, and work through the complex issues faced when designing a pragmatic study to be genuinely applicable and easily disseminated.
- Data and Safety Monitoring Boards (DSMBs): Review and advise on PCORI’s policy regarding DSMBs.
- Ethics: Perform some ethical analysis of low-risk trials, and think about what the philosophical and ethical implications are for these, especially in regards to those that are part of PCORnet.
Subsequent to the meeting, the Board appointed Stuart as its first chair and John Lantos, MD, as its first co-chair.
The panels came up with potential collaboration areas. The Advisory Panel on Clinical Trials suggested it might develop methodological standards specific to rare disease clinical trials in collaboration with the Advisory Panel on Rare Disease. The Advisory Panel on Rare Disease suggested it could collaborate with the Advisory Panel on Clinical Trials to provide guidance on standards of evidence and common data sets, and leverage existing resources that have been validated and used nationally and internationally.
We look forward to the future contributions from these panels as they share their expertise to guide our activities.
- Advisory Panel on Rare Disease
- Summary of Advisory Panel on Rare Disease Spring 2014 Meeting
- Archived Teleconference of Advisory Panel on Rare Disease Spring 2014 Meeting
- Advisory Panel on Clinical Trials
- Summary of Advisory Panel on Clinical Trials Spring 2014 Meeting
- Archived Teleconference of Advisory Panel on Clinical Trials Spring 2014 Meeting
Luce served as PCORI’s Chief Science Officer from May 2013 – September 2015