3.1. Governing Strategy

Because effective leadership is vital to robust governance, it is important to have overarching leadership to steer registry business and develop consensus among stakeholders. Leadership may be in the form of a single person, often the PI, or it may derive from a committee of individuals made up of, for example, co-PIs and representatives from various partners in the registry (e.g., funding sources, reporting entities, or subcontractors that handle operational aspects of the registry).

A framework to divide governance duties and to address potential areas of conflict should be developed at the registry’s inception by involved parties. In general, topics central to the governance of registries will include the research agenda, funding, data, ethics, science, and dissemination. The registry governance plan should describe how the registry will function and who will be responsible for each task or functional area. Asking the following (or similar) questions can help determine duties and solidify further governance structure:

• Research agenda: Who sets priorities and establishes the goals of the registry? What are the respective roles of the stakeholders in setting the research agenda?
• Funding: Who takes responsibility for securing the necessary funds for operating the registry, including start-up and maintenance costs? Who will manage the acquired funds, and how will they be allocated to perform the various tasks? What role in decision making, if any, does the financial sponsor(s) have?
• Data: What data are needed and how will they be collected? What technologies will be used for data collection (e.g., electronic data capture, digital devices, electronic acquisition of patient reported outcomes)? What quality assurance procedures will be used? Who owns the information collected by the registry, and, for a tissue repository, who owns the materials in it? Will the registry adapt as new data needs are identified, and, if so, how?
• Ethics: How will the registry protect patient privacy? Will informed consent be required? What ethical oversight is required (e.g., institutional review board approval)?
• Science: How will the registry ensure that enrollment and followup procedures are followed? How will recruitment and patient retention be monitored over time? How will the registry address changes in the clinical area of interest (e.g., the introduction of a new treatment, the emergence of a new research question)?
• Dissemination: Who has access to the data for research purposes? Can third parties request access for specific research purposes? Who reviews publications resulting from analyses of registry data?

In all governance models, oversight policies and procedures for decision making, operations, and reporting of results should be transparent to stakeholders. Many registries essentially operate as small businesses with complex operational components including regulatory requirements, finances, informed consent, data entry software, progress reports, periodic meetings, and scientific analyses and publications. These day-to-day operations should be conducted as a structured effort, with well-defined lines of authority and responsibility. The structure should also have the flexibility to adapt to evolving science and changing regulatory requirements, such as the periodic updates to the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule and the introduction of the EU General Data Protection Regulation (GDPR) in Europe.

3.2. Governance Committees

Many registries use committee systems to divide and assign oversight duties. The registry may use one or more advisory boards or other leadership committees comprised of representatives of all or some stakeholders in the registry depending on the purpose. Examples of various types of committees and functions are illustrated in Figure 9-1.

Figure 9-1

Committee functions comprising governance.

An Executive Steering Committee generally assumes responsibility for the major financial, administrative, legal/ethical, and scientific decisions that determine the direction of the registry. These decisions are made with appropriate input from legal, scientific, and administrative experts. Depending on their capabilities and the size and resources of the registry, this group may also assume other advisory functions. The funding source (or sources) generally have a seat on such steering committees, though whether they have a formal voting role should be considered in the context of specific areas of decision making, described in subsequent sections. An operations committee generally is used for small or less complex registries and usually takes on all the functions shown in Figure 9-1. The Principal Investigator is generally included on this steering committee.

Advisory committees may be organized to review the registry data, develop consensus statements, provide recommendations on modifications or enhancements to the registry, and/or assist in the dissemination of information and the formulation of strategies to encourage enrollment. Advisory committee actions generally are limited to making recommendations to the ultimate decision maker, whether an executive committee, financial sponsor, or the registry developer/leader. Some advisory committees make decisions by consensus rather than by a formal vote, whereas majority voting is used by others. Consensus-driven decisions can be particularly challenging when partners are not aligned, or a single member takes an intransigent position. In situations where disputes are difficult to resolve, it is helpful to be able to rely on pre-established committee voting rules to develop a path forward. Documentation (i.e., meeting minutes) should be created, distributed, and approved to memorialize decisions and actions taken for all types of advisory committees.

The mix of stakeholders (people or entities who have a stake in the findings of the registry) and experts (e.g., clinicians, epidemiologists, statisticians) involved in advisory committees relates largely to the purpose of the registry. Broad stakeholder involvement in governance committees is most desirable when the outcome or findings can impact many stakeholders. Depending on the size of the registry, governance may be assumed by various oversight committees made up of interested individuals who are part of the design team (internal governance) or who remain external to the day-to-day operations of the registry (external governance). An external advisory board can assist registry operations in two important ways: (1) providing guidance to the registry developer for the clinical, scientific and/or technical aspects of the registry operations and (2) establishing the scientific independence of the registry. The latter function is especially valuable when controversies arise, such as those relating to patient safety and treatment.

Differences in the registry purpose and scope, the research questions of interest, the relevant data sources, and many other factors will influence the degree of involvement and role of oversight groups. In other words, committee functions are described below to highlight the roles that are typically assumed by the registry governance structure; these should be modified, as appropriate, to meet the needs of a specific registry. Advisory committees may be differentiated as follows:

• Stakeholder engagement: In some registries, an advisory committee may be established to maintain relationships with key stakeholders, such as the funding source(s), healthcare providers, collaborating researchers, and patients. Some registries include representatives of these stakeholders on advisory committees, while others use a committee to coordinate stakeholder outreach activities. Examples of outreach activities include interactive workshops or exchange forums between public and private sectors, dissemination of publications and news releases, and updates at professional meetings.⁸ Plans for stakeholder engagement should be considered at the outset of the registry and documented.
• Scientific: A scientific advisory committee often includes experts in areas such as database content, clinical research or clinical care, epidemiology, and biostatistics. This group may determine the overall direction of the research program, including identifying updates that may be needed to address changes in clinical practice or newly approved treatments. This committee also may recommend or lead specific data analyses and reporting of results. In some registries, the scientific advisory committee also is responsible for data access and publications (see below).
• Adjudication: Adjudication may be used to review and confirm cases (diagnosis) and/or endpoints (outcomes) that may be difficult to classify accurately and consistently. Individuals performing this function are generally blinded to the exposure (product or process) under study so that the confirmation of outcomes is made without knowledge of exposure.
• Safety: Most registries will not require a formal safety monitoring committee. In studies of experimental drugs or devices, a formal Data Safety Monitoring Board commonly is used to detect safety problems that would indicate that the experimental product is unsafe and clinical research should not proceed. In the context of registries, situations may arise in which the registry is responsible for the primary accumulation of safety data on a specific intervention; in such situations, a safety monitoring board or individual charged with this responsibility may be useful for conducting periodic reviews (e.g., annually) to look for unusual patterns indicating a serious safety problem.
• Data Access and Publications/Dissemination of Results: The plan for disseminating registry findings should be discussed early in the planning phase of the project, since preparing results for wide dissemination requires considerable time and effort. This function, often covered by the Data Access and Publications Committee (DAPC), should address the process by which registry investigators (and possible external parties) access and perform analyses of registry data for the purpose of submitting abstracts to scientific meetings and developing manuscripts for peer-reviewed journal submission. The role of all stakeholders in the publication process should be specified, as well as any plans to allow external parties to access the data.

Many external parties may request access to registry data. For example, a government regulatory agency may request registry data to fulfill safety reporting requirements or other obligations. Pharmaceutical companies or device manufacturers may request data from patients who receive their products or may request registry data to use as controls for a clinical trial. An external investigator(s) may request permission to access registrywide aggregate data for the purposes of evaluating a new scientific question. Lastly, data requests from the media or the public are possible, although rare. Any information released to the public by the registry (via newsletters, public website, or other methods) should be reviewed prior to release to ensure that data confidentiality is not compromised.

A process for reviewing and responding to such requests from other investigators or entities should be considered in registries that may generate broad external interest, if the registry stakeholders and participants are agreeable to such use. The DAPC is often used to develop and implement policies and manage requests for data access in a transparent, consistent way that is agreeable to all stakeholders; for small registries, this function may be handled by the Operations Committee.

Depending on available resources, a registry may conduct analyses in-house to support external requests; contract with an outside agency to conduct analyses; or leave this task to the data requestors. If an outside agency or data requestor will be conducting analyses of registry data, it is essential for the Operations Committee or DAPC to retain oversight of these activities, especially those that are intended for use in manuscripts submitted to peer-reviewed publications. It is also important to ensure that data access complies with all applicable ethical, legal, and regulatory requirements and that appropriate care is taken to protect patient privacy and maintain data security and integrity.

Authorship (including that of registry sponsors) in scientific publications should satisfy the conditions of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals.⁹ For manuscripts that are prepared by external investigators, many registries ask to review manuscripts prior to publication to ensure that the data and operations of the registry are represented correctly.

3.3. Committee Operations

Governance committees generally should be small to facilitate decision making. An odd number of members is preferable to avoid ties in voting. In practical experience, Executive Steering Committees (or entire Advisory Boards) are generally composed of fewer than ten members. It is important to recognize that these members may solicit input and advice from stakeholders or experts who are not part of the Steering Committee. Some governance committees may create formal subcommittees to develop recommendations on specific issues. In those situations, the Steering Committee member who leads those subcommittees will represent the subcommittee members at the Steering Committee meetings.

Transparency regarding any perceived or actual conflicts of interest is important for effective governance. A plan for identifying and managing actual and perceived financial or intellectual conflicts of interest (COI) should be developed at the registry outset. The plan should clearly spell out the timeline and process for obtaining completed COI and financial disclosure forms from participating members and for reviewing and addressing any potential conflicts. It may be helpful to define what constitutes a problematic COI, and this definition should be reviewed on a periodic basis and revised if needed. Committee members should promptly notify the registry developer/leader should they identify an emerging potential COI (minor or major) during their service.

3.4. Governance in Change Management

Anticipating and planning for change is good practice for all patient registries. Governance can play a critical role in identifying the need for change and providing oversight to ensure that the transition goes as smoothly as possible, with minimal disruption to registry operations.

As an example, an ongoing registry may transition to new organizational leadership or to a new source of funding. In these situations, membership of the key advisory board(s) should be reviewed to ensure appropriate representation of stakeholders. During the transition, advisory board(s) can act as advocates of change by publicly supporting the transition and helping to engage and motivate clinicians at the participating centers. External stakeholders, such as patient advocacy groups and regulatory agencies/health authorities, may also be informed of the transition and, depending on the goals of the transition, potentially enlisted as additional public advocates for the registry transition.

Of note, registry transitions may require revisiting the registry’s data access policies and procedures. If a DAPC is already in place, the committee should be charged with (1) determining how changes in the registry will affect the policies and procedures for accessing data, and (2) reviewing the operational plan for executing analysis plans with respect to the registry transition. Furthermore, if the transition involves a change in registry stakeholders, the procedures for conducting analyses and developing publications should be re-examined. New stakeholders may need to be involved in the prioritization of analysis plans, conduct of analyses, and/or the review of scientific abstracts and manuscripts.

4.1. Patient Engagementⁱ

As with many types of outcomes research, there is a growing trend to involve patients and patient advocacy groups in the planning and operation of patient registries. In some cases, patient organizations are the funding source for the registry and are actively involved in all aspects. (See Case Example 20.) In other cases, patients work as research partners with the registry, offering valuable insights on user burden (e.g., when the registry is collecting patient-reported outcomes), registry feasibility, approaches to recruitment, and patient support needs. They may also serve on advisory committees to facilitate engagement with the patient community. Working with patients brings certain unique considerations, and varying levels of patient involvement may be appropriate and/or feasible for different registries. These considerations are discussed in depth in the supplemental eBook, 21^st Century Registries,¹⁰ and summarized here in Table 9-1.

Table 9-1

Key points to consider when engaging patients in governance.

It is also important to prepare patients for team meetings and to conduct them regularly. Patients should have the opportunity to ask questions before and during meetings (particularly for those who are unfamiliar with research). Providing pre-meeting information materials will promote comfort with the topic and enable informed discussion. Team building exercises such as premeeting “icebreakers” also may be useful, especially when engaging stakeholders with differing experiences/perspectives. It is also important to create an environment where patients feel comfortable speaking up at registry team meetings.

The Arthritis Patient Partnership with Comparative Effectiveness Researchers Registry (AR-PoWER PPRN) is an example of a registry that includes patient partners in registry governance. The registry established a governance structure in collaboration with investigators and patient community members that includes an Executive Board, a Patient Governor Group, and a Research Advisory Board¹¹ as follows:

• The Executive Board includes the PI, one Co-PI, and the Executive Director and a Board Member of the Global Healthy Living Foundation, a nonprofit disease advocacy organization for arthritis patients that is a founding partner organization in the AR-PoWER Registry.
• The Patient Governor Group is a patient steering committee composed of 11 patients with conditions relevant to the research mission of the registry from a variety of professional, geographic, and demographic backgrounds. This group reviews and selects research topics to advance for further consideration based on priority of the evidence need.
• The Research Advisory Board is composed of 10 rheumatology researchers from the University of Alabama at Birmingham. It reviews topics for feasibility and funding.

The Patient-Governor Group and the Research Advisory Board Chairs present recommendations to the Executive Board for approval of projects to be conducted in AR-PoWER. The registry is part of PCORI’s Patient-Centered Clinical Research Network (PCORnet), and stakeholder engagements follow the PCORI Engagement Rubric, focusing on the six principles: reciprocal relationships, co-learning, partnerships, transparency, honesty, and trust.¹²

4.2. Public-Private Partnershipsⁱⁱ

“Public-private partnership” (PPP) is a broad term that refers to any partnership in which at least one entity is a public agency (e.g., a government entity) and at least one other entity is a private organization. As both government and private groups have shown increased interest in patient registries, PPPs have become more prevalent as a means to develop and support patient registries and data linkage projects. The scope can range from partnerships at the local level, including local and regional health agencies, to national and international health agencies and other private institutions or organizations (e.g., professional associations, patient advocacy groups). In a research context, a partnership implies some joint collaboration to achieve a common scientific goal. Partners may contribute intellectual capital, funding, data, or other services.

PPPs may take many forms. Some possible models include: partnerships among federal agencies to examine safety and effectiveness; partnerships among health agencies from several countries on an international level to describe the clinical course of a disease and understand whether there are any effective treatments; partnerships with state agencies for quality improvement; and partnerships for evidence development for coverage decisions. Regardless of the structure and purpose of a PPP, effective and transparent governance is necessary to enable the registry to achieve its objectives, as described in this chapter.

More information is provided in Chapter 24 of the third edition of the User’s Guide.¹³ Case Example 19 describes a PPP to develop a registry.

Case Example 19. Developing a Public-Private Partnership for Comparative Effectiveness Research

Challenge

In 2009, the Institute of Medicine disseminated a landmark report, “Initial National Priorities for Comparative Effectiveness Research,” that listed research priorities for the newly enacted American Recovery and Reinvestment Act (ARRA). Among the 100 priority research topics identified was evaluating the different treatment strategies for primary open-angle glaucoma (OAG). Since the disease disproportionately affects African-Americans, understanding the effectiveness of treatment strategies in minority populations was also of special interest. With ARRA funding, AHRQ sought to develop high-quality scientific evidence to inform decisionmaking by clinicians and patients. An approach was needed to obtain continued and expanded input from the various stakeholders while addressing existing evidence gaps.

Proposed Solution

A diverse group of stakeholders was assembled to implement the registry, provide scientific guidance, develop dissemination plans, and further key research based on study findings. The principal investigator and co-principal investigators represented AHRQ, the American Academy of Ophthalmology (AAO), the University of California at Los Angeles (UCLA) Jules Stein Eye Institute, and the Outcome DEcIDE (Developing Evidence to Inform Decisions about Effectiveness) Center. AHRQ provided oversight and financial support to the project, with scientific leadership from the principal and co-principal investigators; the Outcome DEcIDE Center managed the operational aspects of the study; AAO and UCLA engaged sites and investigators and provided guidance on clinical issues. The stakeholder committee was comprised of individual clinical advisors and representatives from the Glaucoma Research Foundation, American Glaucoma Society, National Medical Association, and State-level healthcare organizations.

Developing the study protocol, initiating startup activities and decisions, and analyzing and reporting the findings required continued communications among all stakeholders. A communication plan was developed to outline project team roles and organizational structures for each stakeholder. Regular stakeholder committee meetings created a forum to discuss design issues, share study status, solicit input on unexpected challenges, and discuss research plans. Site- and patient-recruitment efforts were designed to maximize geographic diversity and enrollment of minority populations. Quarterly study newsletters and investigator meetings coinciding with the AAO annual meeting were also implemented to maintain site interest.

Results

Launched in 2011, RiGOR was a prospective, observational, cohort study designed to compare the effectiveness of treatment strategies for primary OAG. Different treatment strategies studied in the registry included laser surgery, other procedures (such as incisional surgery or other glaucoma procedures), and medications. All treatment decisions were made at the discretion of the treating physician according to their usual practice. Data collection included patient demographics, medication, visual measures, glaucoma severity, surgical characteristics, adverse events, and patient-reported outcomes, and occurred at baseline, 3 months, 6 months, and 12 months.

The registry completed data collection in 2013. Registry data were used to examine the effectiveness of different treatment strategies and to describe practice patterns and treatment changes and quality of life and visual acuity outcomes in patients with OAG. The registry also met its objective of enrolling a high percentage of minority patients. Of the total enrolled patients, 21.5% were African-American and 8.3% were of Hispanic or Latino ethnicity. Study analyses provided valuable information regarding visual function and treatment patterns among different racial/ethnic populations.

Key Point

The public-private partnership model can be an effective approach to engaging multiple stakeholders in an effort to address a comparative effectiveness research question. When working with multiple stakeholders, it is critical to clearly identify roles and communicate regularly with all stakeholders to address any design, operational, or analytical issues, solicit input from all contributors, share study findings, and maintain stakeholder engagement.

For More Information

• Coleman AL, Lum FC, Velentgas P, et al. Impact of treatment strategies for open angle glaucoma on intraocular pressure: the RiGOR study. J Comp Eff Res. 2016;5(1):87–98. PMID: 26691269. DOI: 10.2217/cer.15.58. [PubMed: 26691269] [CrossRef]
• Coleman AL, Lum FC, Velentgas P, et al. Practice patterns and treatment changes for open-angle glaucoma: the RiGOR study. J Comp Eff Res. 2016;5(1):79–85. PMID: 26691017. DOI: 10.2217/cer.15.57. [PubMed: 26691017] [CrossRef]
• Coleman AL, Lum FC, Gliklich RE, et al. Quality of life and visual acuity outcomes in the Registry in Glaucoma Outcomes Research study. J Comp Eff Res. 2016;5(1):99–111. PMID: 26691427. DOI: 10.2217/cer.15.59. [PubMed: 26691427] [CrossRef]
• Coleman AL, Lum FC, Velentgas P, et al. RiGOR: a prospective observational study comparing the effectiveness of treatment strategies for open-angle glaucoma. J Comp Eff Res. 2016;5(1):65–78. PMID: 26690903. DOI: 10.2217/cer.15.56. [PubMed: 26690903] [CrossRef]

Case Example 20. Developing a Patient-Centered Governance Structure

Challenge

In 2014, PCORI invested in the development of a collaborative of PPRNs to support patient-centered comparative effectiveness research. By definition, PPRNs are ‘powered’ by patients and/or caregivers, which suggests that patient stakeholders should be active participants in the registry governance. However, at the time of the development of ArthritisPower, limited information was available about how best to engage patients in registry governance.

Proposed Solution

The co-PIs designed the governance structure in collaboration with patient community members. ArthritisPower established a governance structure made up of an Executive Board, a Patient Governor Group (PGG), and a Research Advisory Board (RAB). The Executive Board is composed of the Scientific Co-Principal Investigator, the patient organization executive director, and the research advisor; the Patient Co-Principal Investigator serves as the chair of the Executive Board. The PGG is the patient steering committee and is composed of 10–12 patient members of ArthritisPower who come from a variety of professional, geographic, and demographic backgrounds with conditions relevant to the research mission of the registry. The PGG collects feedback from the arthritis patient community using surveys and the “Send Feedback” function on the registry’s website and mobile application. The RAB is made up of researchers, clinicians, industry representatives and includes the PGG patient chair.

Results

Since its launch in 2015, ArthritisPower has built online tools and a mobile application to engage and educate patients and to collect information on diagnosis, symptoms, and medications. The program has captured data on over 18,000 patients and produced numerous publications and presentations.

Key Point

Patients can play an active role in registry governance, particularly in registries that are designed to enroll patients directly and support patient-centered research.

For More Information

• https://arthritispower.creakyjoints.org/.
• Nowell WB, Curtis D, Thai M, et al. Digital Interventions to Build a Patient Registry for Rheumatology Research. Rheumatic diseases clinics of North America. 2019;45(2):173–86. PMID: 30952391. [PubMed: 30952391]
• Nowell WB, Curtis JR, Crow-Hercher R. Patient Governance in a Patient-Powered Research Network for Adult Rheumatologic Conditions. Med Care. 2018;56 Suppl 10 Suppl 1:S16–s21. PMID: 30074946 PMCID: PMC6143204. [PMC free article: PMC6143204] [PubMed: 30074946]