Patient engagement in research: lessons learned from CAPTURE ALS, a longitudinal observational ALS study

Abstract

Objective: There are compelling ethical and practical reasons for patient engagement in research (PEIR), however, evidence for best practices remains limited. We investigated PEIR as implemented in CAPTURE ALS, a longitudinal observational study, from study inception through the first 2.5 years of operations. Methods: Data were drawn from three engagement initiatives: a community-led letter-writing campaign; consultation with patient and caregiver focus groups; and a study-embedded ‘participant partner advisory council’ (PPAC). Data were derived retrospectively from study documentation. We used the International Association of Public Participation (IAP2) participation spectrum as a framework for investigation. Results: 2401 letters from community members to the Canadian government affirmed study objectives and advocated for funding. Feedback from focus group consultation influenced study design and supported the study’s data-sharing plan. PPAC collaboration shaped all aspects of the study. Contributions included: co-creation of governance documents, input on study protocols and public-facing communication, and development of engagement webinars for study participants and feedback surveys. Effective communication practices fostered collaboration and helped avoid tokenistic engagement. CAPTURE ALS encompassed all IAP2 participation levels. Conclusions: CAPTURE ALS was shaped by meaningful engagement initiatives over the course of the study. Lessons learned included: begin early and embed PEIR within research; build relationships and foster mutual learning; be flexible, open to adaptation, and seek diversity. Primary challenges included funding for early implementation, time needed to maintain relationships, and attrition due to disease progression. All IAP2 participation levels contributed to meaningful PEIR. ‘Empowerment’ was demonstrated through advocacy.

Keywords:

• Advisory committees
• amyotrophic lateral sclerosis (ALS)
• patient engagement in research
• patient and public involvement
• research design

Introduction

CAPTURE ALS (Comprehensive Analysis Platform To Understand, Remedy and Eliminate ALS) is a Canadian observational study that aims to investigate the heterogeneity of amyotrophic lateral sclerosis (ALS) by detailed clinical phenotyping, building a widely available biorepository, and promoting meaningful patient engagement (1). The study depends on longitudinal data collection from people with ALS (PwALS) or related neurodegenerative disorders (collectively, PwALS), and healthy controls (1). ‘Patient engagement in research’ (PEIR) (2) refers to engaging people affected by ALS – PwALS, family members, and close surrogates – as research partners. PEIR may involve community members and/or study participants. Here we examine PEIR as implemented in CAPTURE ALS from project inception through the first 2.5 years of funding.

There are compelling ethical and practical reasons for PEIR. PEIR acknowledges people affected by health conditions as critical research stakeholders and partners (3–5). It embodies reciprocity through mutual learning for researchers and affected individuals, and by ‘giving back’ to research participants (6–8). Practically, PEIR establishes those affected by health conditions as valuable partners with specific illness-related expertise that promotes patient-centric study design. This increases research relevance (9–12), making studies more acceptable to participants (11, 13, 14) and potentially improving enrollment and retention (13–18). Further, PEIR strengthens funding applications (19, 20).

PEIR is commonly implemented via advisory councils (10), frequently for discrete tasks such as priority setting (7). Engagement activities, such as educational events, for study participants are noted in a small body of literature (8, 21–23). Despite increasing calls for PEIR, formidable barriers include time, cost, and tokenism (10, 22, 24, 25).

Growing interest in ALS PEIR is reflected in ALS clinical trial guidelines (26) and ALS lay ‘ambassadors’ who are trained as potential research collaborators (12, 27, 28). Task-specific ALS PEIR is evidenced by input on FDA draft guidance for drug development (29), design for a biomarker study (15), and an epidemiological questionnaire (30).

Many researchers, however, are unsure how to implement and evaluate PEIR (24, 31). We address these concerns by asking: How has CAPTURE ALS engaged those affected by ALS as meaningful partners in research? How has CAPTURE ALS been shaped by PEIR? And, what can be learned from this investigation that might be helpful when implementing PEIR in other studies? Further, in answer to calls for theoretical frameworks that can inform the evaluation health-related PEIR (32), we use the International Association of Public Participation’s (IAP2) participation spectrum (33, 34) as a framework for examining PEIR. This spectrum has been used to categorize stakeholder engagement along a continuum from lesser to progressively greater influence on research (7, 35–37).

Methods

Three initiatives contributed to CAPTURE ALS’ PEIR: a community-led letter-writing campaign, consultation with ALS Talk Project (ALS Talk) focus groups, and CAPTURE ALS’ Participant Partner Advisory Council (PPAC). University of Alberta Research Ethics Board approval was not required for the letter-writing campaign or advisory council. ALS Talk was approved by the University of Alberta’s Research Ethics Board (Pro0008471). All ALS Talk participants provided online informed consent.

Letter-writing campaign

In September 2018 community advocates initiated a letter-writing campaign asking the Canadian Government to contribute to sustained ALS research funding. In partnership with the ALS Society of Canada (ALS Canada) (38), the initiative sought to inform Canadians about CAPTURE ALS and mobilize advocacy for study funding. ALS Canada shared the community-led initiative through regional ALS Societies across Canada, emails, and social media. They provided information about CAPTURE ALS, template letters, and access to an online e-advocacy tool. The campaign was completed in February 2019.

Data pertaining to participation in the letter-writing campaign were derived from anonymized ALS Canada email records and excel spreadsheets generated from the e-advocacy tool.

ALS Talk

In March 2020 CAPTURE ALS researchers sought feedback on the funding proposal from PwALS and family caregivers participating in ALS Talk, an online, asynchronous focus group study hosted by itracks^TM (39). ALS Talk participants who answered questions in the final two weeks of the study (n = 43) were invited to answer additional optional qualitative and quantitative questions exploring research design for longitudinal observational ALS studies, communication about research opportunities, ‘giving back’ to participants, and data-sharing. After posting answers online, participants interacted on the platform with group members and moderators. Participants had 14 days to answer and discuss posted questions.

ALS Talk data were analyzed using itracks analytics and Nvivo 12. Detailed information about ALS Talk methods and analysis is available elsewhere (40, 41).

Participant partner advisory council

PPAC recruitment commenced December 2020. Research coordinators at the four CAPTURE ALS research sites were each responsible for recruiting two PPAC members (Members). They identified PwALS and people who have loved ones or friends with ALS who might have capacity for and interest in volunteering. They shared information about CAPTURE ALS and the PPAC, and provided contact information for interested individuals to CAPTURE ALS’ participant engagement team (WSJ, SKG, WL). Members were selected on a first come, first served basis.

Members were asked to participate in 1-hour virtual meetings approximately five times/year and respond to emails. We aimed for a minimum one-year commitment; however, Members could step down at any time. The first PPAC orientation occurred during the inaugural PPAC meeting in February 2021.

The PPAC Team (Team) consisted of the participant engagement team, CAPTURE ALS Project Manager, and a CAPTURE ALS Executive Committee member. The Team developed meeting agendas in collaboration with the study’s Executive Committee. Meeting dates were decided by Team and Member consensus. As needed, meeting materials were sent to Members one week in advance. Meetings were held in English. PowerPoint presentations and materials were translated for French-speaking Members. Meeting minutes were based on audio-recordings and fieldnotes. This investigation focuses on PPAC operations from January 2021 to June 2023. The initial 6-months included finalizing contracts between universities, hiring research staff, and ethics approval applications.

Data used for analyzing PPAC activities included project documentation such as meeting minutes and summaries. Data also included: PPAC input on documents including the CAPTURE ALS Charter and study protocols; recruitment, attrition, and meeting attendance records; and detailed fieldnotes. We developed a spreadsheet of topic-specific interactions occurring at PPAC meetings. Based on a preliminary reading of this data and standard qualitative methods (42), SKG and WL developed a codebook to identify the focus of meeting interactions. The codebook was reviewed by WSJ. We also examined information shared by the Team for Member training (43) and information shared by Members based on their expertise. Data were coded to consensus (SKG, WL). Results were reviewed and input provided by the PPAC. All authors reviewed the manuscript.

Theoretical framework

Based on the IAP2’s non-exclusive participation spectrum – inform, consult, involve, collaborate, and empower – and applications of the spectrum to research (7, 35–37), we examined participation levels in CAPTURE ALS.

Results

Letter-writing campaign

Supported by ALS Canada’s communication network and e-advocacy tool, 2401 letters were sent to Members of Canada’s Parliament affirming the objectives of and asking the federal government to financially support CAPTURE ALS. Letters were sent from all ten Canadian provinces and from two territories.

ALS Talk

Thirty-two ALS Talk participants (18 PwALS, 14 caregivers) from three Canadian provinces contributed their perspectives. Participants preferred to hear about research opportunities from health professionals and/or ALS Canada. They preferred assessments at home where possible and noted barriers to long-term research participation including disease progression and travel. Participants valued the interactions with health professionals and researchers that were fostered by research participation. Benefits included personal validation, opportunities for information gathering, and enhanced study engagement. Participants identified practical factors that encouraged participation in studies with duration >1 year (Figure 1). This data prompted CAPTURE ALS’ plan for optional, study participant engagement webinars and feedback surveys on participant experience. It also provided patient-based rationale for CAPTURE ALS sub-studies exploring wearables, for example the successfully funded sub-study, ‘Digital measurement of gait as a potential biomarker for progression.’ With assurance of data security, the vast majority of participants were willing to share anonymized data with both academic and industry researchers, thus affirming CAPTURE ALS’ data-sharing plan.

Figure 1. Impact of data from ALS Talk Project on CAPTURE ALS.

Participant partner advisory council

Thirteen PPAC meetings were held during the study period. Membership ranged from 5 to 11 people (Figure 2). Reasons for attrition included inability to attend meetings regularly and/or disease progression. Three Members remained on the PPAC throughout the study period. On average, 82.5% of Members attended meetings. Research sites had varying success recruiting Members. To bolster recruitment and achieve greater geographic representation we extended recruitment to the ALS Canada Ambassadors (27) in January 2023. Three Members representing regions distant from the CAPTURE ALS research sites were recruited.

Figure 2. Participant Partner Advisory Council (PPAC) membership, attrition, and recruitment.

Activating the PPAC early in the study timeline enabled the co-creation of governance documents, such as the PPAC Terms of Reference and study Charter, as well as crucial input on study design. During the first 6-months we established communication practices. A research associate (SKG) led communication within the Team and with Members. Effective communication between the Team and Executive Committee was essential for developing actionable agenda items and communicating Member input to decision-makers. Initial PPAC meetings were loosely organized. This sometimes led to discussions beyond the scope of CAPTURE ALS. With feedback from Members, a more formal meeting structure evolved leading to effective and focused discussions. The Team shared background information, including scientific summaries, at the beginning of each meeting to support Members’ input on agenda items.

In the following two years we reinforced relationships with site-specific research coordinators by conducting ‘orientation to PEIR’ sessions and providing support for PPAC recruitment. We implemented orientation sessions for people interested in becoming Members and new supports for unilingual French Members, including use of translation software and some simultaneous translation at meetings by bilingual team members. We also learned to utilize the knowledge and experience of Members through more targeted questions. For example, when seeking input on the CAPTURE ALS research protocol, questions focused on reducing participant burden in specific areas where protocol changes were possible, including speech testing and blood collection procedures.

Outside of meetings we communicated with Members primarily by email. Members were occasionally asked for email feedback on time-sensitive issues arising between meetings, for example, on a conference abstract coauthored by the PPAC (44). SKG exchanged 904 emails with Members between November 16^th, 2020 and June 30^th, 2023. During this same period SKG exchanged 2194 emails with the Team and/or CAPTURE ALS researchers and research staff.

Thematic evaluation

Based on meeting agendas and minutes, we identified 44 interactions at the 13 PPAC meetings. From these we developed six themes (Table 1) and identified information exchange between the PPAC and Team (Figure 3). Members reported personal benefit from exchanging information with the Team and other Members: ‘I find it very helpful to be listening and talking with people who are involved in the research and also others who suffer from ALS.’

Figure 3. Information exchange by theme between the Team and Participant Partner Advisory Council (PPAC).

Table 1. Interactions at Participant Partner Advisory Council (PPAC) meetings.

Themes	Interaction description	Examples
		Activity	Outcome
Study operations	Interactions related to aspect of study operations, including study design, assessment tasks or tools, and the experience of study participants.	Team sharing information: Presentation of aims, technology, and protocol for ‘Digital measurement of gait as a potential biomarker for progression’ sub-study.	Provided PPAC Members with information to enhance the quality of their feedback on the sub-study.
		PPAC sharing expertise and feedback: Detailed feedback on proposed sub-study protocol and assessment tasks provided.	Significant modification of the at-home assessment tasks and protocol. The sub-study was successfully funded, extending the deep phenotyping in CAPTURE ALS.
Governance	Interactions related to the study’s structures, systems, and practices.	Team sharing information: Presentation on the role and importance of a Charter for a scientific study.	Provided Members with information to enable their informed feedback on the CAPTURE ALS Charter.
		PPAC sharing expertise and feedback: Members provided detailed input on the Charter draft, for example, noting inconsistencies, suggesting that roles and responsibilities be defined, and identifying the need for metrics measuring achievements/success.	Prompted revision of Charter documents and discussion within the CAPTURE ALS Team regarding success metrics.
Team building	Mutual interactions focusing on building effective working relationships.	Designated time within meetings for introduction of new Team and PPAC members.	PPAC and Team Members reported personal benefit and learning from interactions at meetings.
Public facing communication	Discussion of information for study participants or for the public.	Team sharing information: Shared details about a public presentation featuring the CAPTURE ALS PPAC.	Information contextualized and affirmed the PPAC’s contributions to CAPTURE ALS.
		PPAC sharing expertise and feedback: Members made suggestions to improve CAPTURE ALS recruitment and identified a need for ‘talking points’ – material to promote the study.	The Team developed talking points. These were shared with Members involved in advocacy.
Knowledge translation	Disseminating knowledge gained through CAPTURE ALS to groups including academic and public audiences.	Team sharing information: Presentation about knowledge translation at academic conferences.	Provided Members with information and context that they used to provide high quality feedback on an abstract and poster presentation.
		PPAC sharing expertise and feedback: Members provided input on an abstract and poster for the 33^rd International Symposium on ALS/MND.	Abstract accepted with CAPTURE ALS PPAC as coauthor (44).
Establishing context	Sharing background and contextual information to support discussions and input.	Team sharing information: Presentation on the research pipeline, using the development of tofersen as an example.	Provided members with background information on research timelines and potential outcomes from observational ALS research. Prompted discussion of time pressures faced by PwALS.

Key PPAC contributions included input on the study Charter, protocols including assessment tasks and tools, public facing communication, and development of participant engagement webinars and feedback surveys. In addition to providing input on agenda items, the PPAC provided unanticipated contributions. For example, following discussion of prolonged ethics approval processes, Members reflected on research timelines versus the ‘race against time’ experienced by PwALS. They emphasized the mismatch between slow research processes and the urgency experienced by people affected by ALS. This patient-centered perspective on ‘time’ was impactful for researchers. Also, prompted by PPAC discussion of public facing communication and philanthropic fundraising, ALS Canada’s role in CAPTURE ALS was formally defined.

IAP2 participation spectrum

CAPTURE ALS encompassed all IAP2 participation levels. The letter-writing campaign presented a serendipitous opportunity to inform the ALS community across Canada about CAPTURE ALS and empower community advocacy. Feedback from focus group consultation influenced study design and affirmed the study’s data-sharing plan. PPAC Members’ understanding of ALS research increased through their involvement and collaboration with researchers. Further, PPAC involvement empowered community-based advocacy for some members (Figure 4).

Figure 4. Modified participation spectrum for CAPTURE ALS PEIR.

*Description of participation goals is adapted from the International Association for Public Participation (IAP2) spectrum for public participation (34) and the research-relevant modified IAP2 Spectrum (35).

**Italicized text represents additions to the research-relevant IAP2 spectrum based on current findings.

Discussion

CAPTURE ALS has been shaped by meaningful input from and collaboration with people affected by ALS. Findings demonstrate different ways that PEIR was implemented over the course of the study. Here we discuss three lessons learned, implementation challenges, and the IAP2 spectrum as a framework for PEIR.

Lesson 1: begin early and embed PEIR within research

CAPTURE ALS’ early emphasis on PEIR demonstrated the value researchers placed on involving those affected by ALS (45) and affirmed the ethical imperative to include those impacted by health conditions as research partners (3, 5). Important factors contributing to successful engagement included embedding PEIR as a primary research objective (1), and consultation with PwALS and caregivers to inform the funding application. These early steps facilitated critical human and financial resources (10, 32). Further, early implementation allowed the co-creation of governance documents and formalized the PPAC within CAPTURE’s organizational structure (46). Finally, early emphasis on engagement promoted documentation and facilitated assessment (9, 47).

Challenges

Funding early PEIR is a challenge. To overcome this barrier, researchers supported PEIR through existing funds, including philanthropic, prior to the release of grant funding. Measuring the impact of PEIR on recruitment and retention is also challenging (6, 18). Our investigation, however, demonstrated that the PPAC impacted study protocols and operations, providing critical feedback that shaped the project to maximize research feasibility, acceptability, rigor, and relevance.

Lesson 2: build relationships and foster mutual learning

Establishing a consistent Team contact person (31) facilitated Member support and effective Team communication. For example, close communication with the Project Manager helped maintain focus on PEIR as the project progressed. Ongoing communication with the Executive Committee was critical to avoid tokenistic engagement (10, 25, 48). Further, communication with new researchers involved in the sub-studies promoted PEIR beyond the original CAPTURE ALS protocol.

Findings also highlight the value of training (9, 49) and mutual learning (43). Orientation sessions for Members and research staff fostered understanding of PEIR. Information shared by the Team at PPAC meetings enabled knowledgeable Member input. And, information shared by Members increased researchers’ understanding of ALS lived experience and drove the alignment of CAPTURE ALS with the priorities and needs of people affected by ALS (7, 14, 50). Critically, Members brought a new lens to the research enterprise through their recontextualizing of ‘time’ and focus on expediting research processes.

Challenges

Maintaining relationships and fostering mutual learning required significant time investment. While this might be mitigated by enlisting feedback from lay experts trained through voluntary programs (15), this investigation demonstrated the sustained inputs that can be achieved by project-embedded PEIR. Moreover, as researchers became increasingly familiar with PEIR, they demonstrated tacit acknowledgement of value through ongoing PPAC consultation. Members also reported benefits, including increased knowledge as a result of their participation.

Lesson 3: be flexible, open to adaptation, and seek diversity

Findings suggest that flexible participation for Members and Team learning and adaptation was central to effective PEIR. Unlike ALS clinical trials, which favor participants who are younger, earlier in the disease course, and with slower disease progression (51, 52), we promoted PEIR that was representative of the target population (53). We accommodated the uncertainty of the disease trajectory (54), augmentative and alternative communication aids (55), life commitments and caregiving responsibilities (56, 57), a geographically dispersed population, and Canada’s two official languages. Managing PPAC recruitment to maintain >8 Members resulted in robust meeting attendance and impactful discussions. Although PEIR emphasizes experience with the health condition under investigation (14, 58), the PPAC was also enriched by research expertise that developed over time and Members’ diverse, preexisting expertise. Further, whereas the target for engagement is typically patients (2), we involved others affected by ALS, for example, caregivers.

Challenges

ALS PEIR is challenged by rapid disease progression, a median overall survival of 30 months after symptom onset, and a 5–10% survival rate one decade after diagnosis (54, 55). Succession planning and intermittent recruitment can therefore be challenging. Further, while we fostered diversity through accessibility, racial or ethnic diversity may be more challenging for ALS research (59). Finally, despite high levels of altruism among those affected by ALS (12), it is important to acknowledge the burden of loss for those who contribute to ALS PEIR.

IAP2 participation spectrum: a framework for PEIR

The IAP2 spectrum provided a useful way to categorize and examine PEIR. Although higher levels of participation may be desirable (60), we found that all levels contributed to meaningful PEIR. Inform and consult, for example, critically enabled other engagement levels. Further, empower – pertaining to final decision-making power (33) – was outside CAPTURE ALS’ research mandate. However, we found that empowerment was demonstrated through advocacy. Whereas previous research defines advocacy as a separate participation level (7), we represent it in Figure 4 as it is perceived by the ALS community: an expression of empowerment (61).

Limitations

Examining PEIR within one longitudinal observational study may have limited findings. For example, investigation of PEIR within clinical trials may yield different results. Moreover, qualitative results may not be generalized directly to other populations or research studies. Also, despite explicit efforts for diversity, people participating in PEIR were self-selected and may not represent the target population. Additionally, evaluation was derived retrospectively from study documentation. Overall, while prospective evaluative tools (24) may provide insight into the experience of individuals involved in PEIR, they position PEIR partners as study participants. Involving the PPAC as a coauthor is in keeping with the ethical imperative for PEIR (3, 5, 10, 50) which informs CAPTURE ALS.

Conclusions

This investigation furthers knowledge of PEIR by describing how CAPTURE ALS engaged people affected by ALS as meaningful research partners, examining the engagement initiatives that shaped CAPTURE ALS, and identifying ‘lessons learned’ and challenges. We demonstrated engagement across the IAP2 participation spectrum and at different stages in study’s lifecycle. Early emphasis on PEIR, for example, enabled input on study design and protocols. Sustained interaction with the PPAC helped researchers align CAPTURE ALS operations with the needs of study participants and highlighted an urgent need to expedite research processes. This investigation supports the ethical and practical arguments for implementing PEIR and may have implications for funders and for studies involving other patient populations. Further research is needed to determine the impact of PEIR on study recruitment and retention, and to improve understanding of effective PEIR during later research stages, for example, knowledge translation.

Acknowledgements

We are grateful to the ALS Talk participants who generously shared their experiences and insights, and to the ALS community who advocated for CAPTURE ALS funding. Thank you to the CAPTURE ALS research team who has and continues to promote and support participant engagement. We are indebted to Members of the CAPTURE ALS PPAC, past and present, who not only contribute substantively to CAPTURE ALS, but continue to inspire the research team. Finally, thank you for financial support from Health Canada, through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and from ALS Canada, Alnylam Pharmaceuticals, Regeneron, and the James and Jeanie Brown ALS Research Fund (via the University Hospital Foundation).

Data availability statement

The data that support the findings of this study are available from the corresponding author (WSJ) upon reasonable request.

Disclosure statement

The authors report there are no conflicts of interest.