Models of Engagement: Patients as Partners in Clinical Research

As patients take more active roles in decision-making about health, healthcare, clinical trials, and regulatory activities, their influence has changed how sponsors and researchers view patient involvement in clinical research. Once regarded as “subjects” who had research performed on them, patients are now contributing across the spectrum of clinical development, including in the design and planning of research protocols, selection of outcomes and endpoints, development of recruitment and retention strategies, and dissemination of research results. The unique perspectives afforded by patients’ lived experiences can inform researchers’ approaches and help identify knowledge gaps. By sharing their experiences of the daily burden of disease and their perspectives regarding unmet needs, therapeutic burdens, the balance of benefit and risk, and the types of research questions most important to them, patient partners can transform the clinical development process from one directed by sponsors and investigators to one driven by the needs of patients and their caregivers.

While the concept of patients as partners in clinical research is gaining momentum, recent research points to room for improvement.¹ The development and validation of partnership models to engage patients in the design and governance of clinical research programs is still in its infancy, and approaches that can ensure meaningful and effective patient participation in research are needed.² For this reason, the Duke Clinical Research Institute (DCRI) and our research partners are exploring models of patient engagement to determine what works best for patients, their caregivers, research sponsors, and investigators, with the ultimate goal of enhancing the speed and quality of clinical research.

In this article, we describe three different patient partnership models to help researchers evaluate which method of engagement could work best for their clinical program or study. These models integrate patients and their caregivers into the governance structure of the clinical research program or study to ensure continuous partnership throughout the project life cycle. The models of patient engagement and studies profiled include:

• Patients as advisory board members: the ADAPTABLE aspirin study and CONNECT-HF trial

• Patients as steering committee members: Industry-sponsored Phase II study

• Patients as co-investigators: the PCORnet obesity studies

We discuss these models, the methods used to implement them, and outcomes to date. We also share lessons learned and explore future possibilities for patient engagement in clinical research. This paper is written from the perspective of communication professionals who work alongside research sponsors and study teams-including faculty, operations staff, researchers, clinicians, and patient advisors-to facilitate patients as partners in clinical research. We fully recognize that a commitment from all parties, including our patient partners, is necessary to a successful, lasting engagement.

PCORnet: The ADAPTABLE aspirin study

PCORnet (the National Patient-Centered Clinical Research Network) is an initiative funded by the Patient-Centered Outcomes Research Institute and is designed to build patient partnerships and harness health data to improve clinical research. PCORnet ensures that patients are directly involved in the development and execution of research by weaving requirements for patient involvement directly into the network’s governance structure. Patient members are represented on each of the overarching PCORnet governing committees, where they play an integral role in overseeing decision-making and leadership, stakeholder engagement, PCORnet’s data network, and research partnerships.

The DCRI serves as the coordinating center for PCORnet and also leads its first demonstration project, ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness; NCT02697916). A pragmatic clinical trial designed to answer an important clinical question in the “real-world” setting of patient care, ADAPTABLE is comparing the effectiveness and safety of two different daily doses of aspirin, both of which are widely used for secondary prevention of heart attack and stroke in persons living with heart disease. However, the study is also implementing a new model of patient engagement in clinical research by integrating patient partners (the Adaptors) into the study team to provide patient voices and perspectives in all aspects of the trial. The Adaptors team is facilitated by Health eHeart Alliance, a PCORnet Patient-Powered Research Network.

Eight PCORnet Clinical Data Research Networks (CDRNs) and a Health Plan Research Network are involved in the identification and recruitment of study participants. At the onset of the study, each CDRN invited a patient to join the Adaptors team. Some Adaptors have previous clinical research experience through personal or professional experiences; all consider themselves healthcare experts through their lived experiences battling chronic diseases.

Optimizing the recruitment message

By participating in ongoing study meetings, Adaptors hear firsthand about recruitment challenges and barriers to enrolling up to 15,000 patients in the ADAPTABLE study. Working with their local network researchers, Adaptors play a key role in tailoring the recruitment messages. Adaptors help develop and review recruitment

materials, anticipating questions and identifying potential points of confusion. They offer input on study materials that facilitates understanding and enhances appeal to a broad audience, such as incorporating graphics and white space, reducing jargon and legalese, and using language that emphasizes the importance of clinical trials, the role of patients in the process, and the value of the patient voice in transforming healthcare. Adaptors have also contributed as authors in peer-reviewed literature.³

Better health outcomes for all when patients partner with researchers

In addition to spreading awareness of ADAPTABLE, Adaptors are dedicated to educating others on the importance of clinical research. Their motto, "Better health outcomes for all when patients partner with researchers," conveys how patient participation in research can help answer health questions that matter most to patients and their doctors. This motto is part of the Hero's Journey Art Project, a touring art exhibit developed by Eli Lilly to honor clinical trial participants and raise awareness of clinical research.

Through the ADAPTABLE patient-research partnership, patient partners have come to appreciate how their experiences can inform research questions, protocol design, and the collection of patient-reported outcomes. Researchers have come to understand that patients may have their own perspectives on what study outcomes or endpoints are most important. For example: an investigator might assume that the most important question to ask during a therapeutic trial is whether the intervention results in an improvement in mortality. However, a patient might be more concerned with quality-of-life issues-if they experience a stroke, will they have to live with a disability, and what will the impact on their family be?

The CONNECT-HF trial

The Care Optimization Through Patient and Hospital Engagement Clinical Trial for Heart Failure (CONNECT-HF; NCT03035474) is a nationwide pragmatic clinical trial funded by Novartis and coordinated by the DCRI. CONNECT-HF employs digital and quality improvement approaches to enhance care for patients with heart failure, with the goal of improving outcomes and reducing the number of hospital readmissions. The CONNECT-HF trial team worked closely with a team of patient advisers while designing the study. To establish the patient advisory group, physicians on the trial steering committee were asked to nominate patients from their practices who they felt would be engaged and interested in giving back to help others with heart failure. Although there were no official requirements for selection, the team aimed to identify advisers who had similar characteristics to the expected trial population, including a similar degree of diversity with regard to age, sex, race/ethnicity, and geographical location.

The resulting group of eight patient advisers-the “Cardi-Yacks”-were not professional patient advocates, and most had never participated in a clinical trial. A DCRI patient engagement liaison facilitated interactions between the trial team and the Cardi-Yacks by orienting them to their roles, outlining expectations, answering questions, scheduling meetings, and conveying requests for input from the trial team. The Cardi-Yacks, in turn, offered their experiences and advice on aspects such as eligibility criteria and the follow-up phone call schedule to help researchers design a trial that would be both useful for patients and easy for them to participate in.

An in-person meeting was organized for the Cardi-Yacks at the trial coordinating center, where they met with the project team and gave feedback on the trial enrollment process and patient-facing educational materials. The meeting included individual mock enrollment sessions with each Cardi-Yack to replicate the patient experience of enrollment. The Cardi-Yacks then participated in a facilitated focus group to provide input on the enrollment process and draft patient-facing materials that would make them more useful and patient-friendly. In addition, the Cardi-Yacks piloted patient-facing mobile applications that are part of the trial interventions and gave input directly to the application designers. The Cardi-Yacks expressed positive feelings about being partners in the trial and helping others with heart failure through their involvement. After trial enrollment began, the Cardi-Yacks continued to work with the trial team on recruitment, adherence, and retention.

Industry-sponsored Phase II study

DCRI is spearheading an engagement initiative for a patient to serve as a member of a Phase II study’s steering committee. The selected individual would give input on protocol design, anticipated burden for study participants, recruitment and retention tactics, and other key areas. DCRI would be responsible for the engagement and education of this patient representative, whose views would carry as much weight as those of other steering committee members. 

Internal selection process

The DCRI team, working in close collaboration with the principal investigators and other study stakeholders, has developed a customized internal process according to the therapeutic area, patient population, and protocol (see table below). This customized process enabled us to establish a profile for an “ideal” patient representative, develop selection criteria, identify potentially suitable candidates, and clearly define the role of nominated persons.

Value to patients and research

While this patient engagement initiative is still in the early stages of the nomination process, the DCRI is optimistic about the benefits the patient representative could bring to the study. The study team believes this additional layer of patient engagement could strengthen partnerships between patients and study staff, demonstrating the value of patients’ viewpoints in clinical research. It could also facilitate effective communication between the patient representative and the steering committee members. 

PCORnet obesity studies

In addition to the ADAPTABLE aspirin study, PCORnet is also conducting a pair of observational studies on obesity. Like many PCORnet demonstration projects, these studies require a patient or caregiver to be included as a co-principal investigator (PI).

The Antibiotics and Childhood Obesity Study, led by Harvard Pilgrim Health Care, examines the relationship between antibiotic use in the first two years of life and weight gain in later childhood. The parent co-PI for the study is a special education teacher and the parent of a teenage son who has experienced childhood obesity for most of his life. As a co-PI, he oversees patient engagement efforts and works to address potential barriers to patient involvement by openly discussing concerns about data security and anonymity and by creating a patient- and family-friendly glossary of acronyms commonly used within the medical community. 

A patient co-PI for PCORnet’s Bariatric Study, led by Kaiser Permanente Washington Health Research Institute, is building evidence on which of three different bariatric surgical procedures results in the best outcomes for specific patient communities. A church pastor, community advocate, and bariatric surgery patient herself, the patient co-PI shares her story, “Why patients need a louder voice in medical research,” which explores her experience of being part of an underrepresented patient community seeking bariatric surgery, the knowledge gaps that exist in the current medical literature, and the importance of patient partnership in clinical research. 

The PCORnet obesity study co-PIs have built strong collaborations between patients, clinicians, and healthcare system leaders. One of the unifying messages shared by both co-PIs is how they have learned that these partnerships benefit not just patients but all stakeholders-everybody wins. The model has demonstrated the power of patients’ unique voices when they are thoughtfully integrated into the fabric of decision-making and governance. PCORnet and the DCRI plan to continue to share news on patient engagement strategies, best practices, and lessons learned, highlighting personal stories from throughout the PCORnet partner networks and studies.

The future of patient engagement in research

The DCRI has been exploring approaches to patient engagement for some time. Large-scale initiatives with DCRI involvement, such as PCORnet, have been characterized by extensive partnerships with communities and individuals to shape, inform, and improve research design and conduct.

More recently, the DCRI appointed Bray Patrick-Lake, MFS, as director of stakeholder engagement in June 2017. A former trial participant who later became a patient advocate, Patrick-Lake led a multi-stakeholder team of experts from industry, academia, patient groups, the NIH, and the FDA to develop Best Practices for Effective Engagement with Patient Groups around Clinical Trials for the Clinical Trials Transformation Initiative (CTTI). She also developed successful patient engagement models and strategies for PCORnet studies, co-chaired the Advisory Committee to the NIH Director responsible for authoring the vision of the Precision Medicine Initiative Cohort Program (now called All of Us), and served as the interim director of engagement during the program’s pilot phase. Under her leadership, DCRI faculty, investigators, and operational teams are working to institutionalize a set of guiding principles for involving patients as partners in clinical research (see table).

The DCRI is working to catalyze the adoption of a gold standard of partnership with patients in research design, conduct, oversight, and dissemination, while raising the bar on participant experience in research. Although including patients in the governance of clinical studies is just one approach to advancing patient partnerships in clinical research, we have found it to be an effective tool for supporting high-quality, efficient, patient-centered research. Patient input in clinical research has many potential benefits, such as making it possible to achieve higher rates of retention and compliance through enhanced value and improved participant experience; improving data quality by minimizing patient dropout and enhancing participant adherence to protocol; and inspiring scientists to pursue research opportunities and approaches that might not have been obvious. Finally, we anticipate that continuous patient input could drive more rapid research innovation cycles and accelerate the development and appropriate scaling of novel methods and tools. Effectively integrating patient partners into clinical research requires thoughtful approaches and bidirectional learning. Their participation throughout the clinical development life cycle is proving invaluable to improving clinical studies and forging new paths in biomedical research.

Lindsay Singler, Associate Director, Clinical Research Communications; PattyMcAdams, Clinical Research Communications Specialist; Gina Uhlenbrauck, Clinical Research Communications Manager; Kirk Jernigan, Clinical Research Communications Specialist; and Julie Schulman, Clinical Research Communications Specialist, all with Duke Clinical Research Institute (DCRI)

* The authors would like to acknowledge the following individuals for their leadership in implementing the models of engagement profiled in this paper: Adrian F. Hernandez, MD, MHS; Matthew T. Roe, MD, MHS; William Schuyler Jones, MD; Holly Robertson, PhD; Madelaine Faulkner, MPH; the Adaptors; Jane Anau, BS; David Arterburn, MD, MPH; Jason Block, MD, MPH; Doug Lunsford; Juliane Reynolds, MPH; Neely Williams; Beth Martinez, PMP; Adam DeVore, MD; Linda Davidson-Ray; Tracy Hofmann; Renee Leverty; the Cardi-Yacks; and Susan Landis.

References

1. Calaprice-Whitty D, Byrne J, Gilbert J. Bridging the gap for better patient engagement. Applied Clinical Trials. May 31, 2017. Available at: http://www.appliedclinicaltrialsonline.com/bridging-gap-better-patient-engagement. Accessed October 13, 2017.

2. Domecq JP, Prutsky G, Elraiyah T, et al. Patient engagement in research: a systematic review. BMC Health Serv Res. 2014 Feb 26;14:89.

3. Hernandez AF, Cruz HP. Engagement, research, and evidence: Leveraging the National Patient-Centered Clinical Research Network for better cardiovascular health. Circulation 2017;135(16):1478-1480.