Utilizing patient advocates in Parkinson’s disease: A proposed framework for patient engagement and the modern metrics that can determine its success

Abstract The wide application of patient engagement and its associated benefits has increased across government, academic and pharmaceutical research. However, neither an identified standard practice for the process of engagement, nor utilization of common metrics to assess associated outcomes, exists. Parkinson's Foundation developed a patient engagement framework and metrics to assess engagement within the academic research and drug development sectors. This approach was developed over the course of several years through assessing the literature, acquiring feedback from researchers and people with Parkinson's disease and adapting practices to be relevant and generalizable across patient engagement projects. This framework includes the: 1) creation of a scope of work, 2) establishment of guiding principles, 3) selection and training of participants, 4) co‐determination of project metrics, 5) execution of the project and 6) dissemination of project findings. Parkinson's Foundation has also worked with academic, government and pharmaceutical stakeholders to identify metrics that assess both the quality of patient engagement and outcomes associated with patient engagement on projects. By improving patient engagement project methodologies and metrics, global clinical trials can have access to evidence‐based patient engagement practices to more efficiently capture the needs of, and potentially benefit, the patient community.

In the last four decades, patient involvement in research, commonly known as patient engagement, has transitioned from advocacy to  [4][5][6] In addition to collecting patient insights and preferences, PFDD meetings were also held to identify and facilitate the use of robust methods and best practices to collect the information most important to patients. 5 PFDD Draft Guidance 1 was released in 2018, and Guidance 2-4 are scheduled to be released in the next several years. 1 The wide application of patient engagement and its associated benefits has increased the practice across government, academic and pharmaceutical research. However, even with its increasing application, 7 neither an identified standard practice for the process of engagement, nor utilization of common metrics to assess the outcomes, exists. 8 Currently, engagement and input can range from minimal activity to complex involvement. 7,9,10 In examples of minimal engagement, organization agendas are often set and defined prior to involvement, and patients have limited abilities to influence research and drug development. 9 In contrast, more active and purposeful engagement in research considers patients to have equal decision-making authority. In this higher end of the spectrum, patients work with researchers to identify priorities, set agendas and design trials. 9 Several interdisciplinary health organizations have worked in partnership to develop generalizable recommendations to foster positive patient engagement practices. Many of the deliverables developed through these partnerships are publicly available for use. The affiliated groups include Patient-Focused Medicines Development, the Clinical Trials Transformation Initiative, the aforementioned PCORI, Drug Information Association and European Patients' Academy. These organizations along with patient advocacy organizations, including Parkinson's Foundation, have led the charge in identifying, practicing and refining the foundations of patient engagement.
The Parkinson's Foundation determined that there was an urgent need for patient engagement in Parkinson's research following the work of the HIV/AIDS and breast cancer community. Patient engagement was critical in those disease communities, not only because survival rates were poor, but also because heterogeneity of disease and complex symptoms meant that a wide range of patient experience needed to be accounted for to design optimal trials. Similarly, Parkinson's disease (PD) has a wide heterogeneity of disease and complex symptom set. PD is a progressive neurological disorder affecting nearly ten million people worldwide. 11 It is characterized by motor symptoms, including slowed movement, balance and gait difficulties, rigidity and tremors. In addition, people with PD experience non-motor symptoms such as cognitive impairment, gastrointestinal issues, anxiety and depression. 11 No two people with PD experience the same set of symptoms in the same order, or with the same rate of progression.
While heterogeneity of disease and complex symptoms highlight the critical need for patient engagement, they can also make patient engagement more challenging by introducing multiple variables. A consistent approach to patient engagement that encompasses potential variables becomes crucial to ensuring patients can meaningfully engage in the research process. This, in addition to the increasing expectation of the incorporation of patient engagement in the research and drug development process by both the FDA 12,13 and patient advocacy groups, highlights the need to standardize patient engagement frameworks and methodologies and assess the affiliated outcomes through metrics. Parkinson's Foundation supports the standardization of methods and metrics that promote a high level of engagement and defines patient engagement as the inclusion of patients as equal partners in research decision making at each step of the research or drug development process. This article presents a Parkinson's Foundation-developed patient engagement framework and metrics to assess such engagement within the academic research and drug development sectors. The Foundation has a long history of sharing tools, resources and best practices with different disease communities, and the Foundation's models have proven adaptable and replicable in other disease areas. By standardizing patient engagement methods, patient engagement activities can be validated, refined and reproduced. With the identification of evidence-based practices, the value of effective patient engagement practices can be justified and widely replicated. This framework includes methods for engagement and metrics that assess both the quality and associated outcomes of patient engagement on the project. These methods include the following:

| A PROP OS ED FR AME WORK FOR PATIENT ENG AG EMENT
1. Creation of a scope of work.
3. Selection and training of participants.

Execution of the project.
6. Dissemination of project findings. *A detailed case example detailing each step of the framework can be found in Table 1.  For patient engagement to be effective and beneficial to both patient advocates and researchers or pharmaceutical staff, additional time to train both parties in the execution of patient engagement is often required and should not be overlooked when designing a patient engagement plan. 17,18,[24][25][26] It is important that all parties have access to resources and terminology that will promote informative bi-directional conversations. 17

A Case Example for Fostering Positive Patient Engagement Practices Utilizing Framework Steps One Through Six
Two stakeholder groups, Parkinson's Foundation and an unnamed pharmaceutical company (Company X), utilized a structured collaborative approach to patient engagement in research.
Step 1: Over the course of six months, Parkinson's Foundation and Company X worked to create a scope of work. Company X was looking to get feedback on a study protocol for a drug in Phase II clinical trials prior to issuing a protocol amendment. Parkinson's Foundation communicated with the legal, research and accounting teams to determine project expectations. Together, Parkinson's Foundation and Company X decided that a one-day audio-recorded focus group with six patient advocates, three Parkinson's Foundation staff and three Company X researchers would be most conducive to eliciting the type of feedback requested. Parkinson's Foundation and Company X together agreed that the project would be completed within three months.
Step 2: Of the several principles discussed in Step 2, Parkinson's Foundation worked with Company X to focus on creating a capacity for positive accessible engagement, respect and transparency in communication. To create a capacity for positive accessible engagement, it was agreed upon that the focus group would be hosted at Parkinson's Foundation (a location many advocates were already comfortable and familiar with), all focus group questions would be co-created over the course of several virtual meetings between Parkinson's Foundation staff and Company X researchers, any materials pertinent to the focus group would be provided to patient advocates in advance, and the focus group would be facilitated by Parkinson's Foundation staff. To promote respect, it was agreed upon that all focus group attendees would be addressed by first name only (no titles or degrees), patient advocates could ask questions to researchers about the study, and at the end of the focus group, all three researchers would share something they had learned throughout the course of the day. Lastly, to promote transparency in communication, it was agreed upon that all materials would be presented at an appropriate health literacy level, Company X would provide as much detail as possible about the study and investigational drug, and any protocol amendments attributed to the focus group would be shared back with the patient advocates within six months after the project execution stage.
Step 3: Parkinson's Foundation identified ten patient advocates that met the criteria Company X had requested and shared anonymized patient advocate profiles with Company X. Company X then selected the six patient advocates they preferred to collaborate with. Through a virtual group call, Parkinson's Foundation staff then worked with the patient advocates to review research content that would be relevant to the focus group. Background information and materials were also provided to patient advocates in advance of the focus group. Parkinson's Foundation also worked with Company X researchers to generate questions at an appropriate health literacy level that could capture patient sentiments and feelings while informing the clinical trial protocol. Company X then adjusted their presentations accordingly.
Step 4: Parkinson's Foundation worked with Company X to determine a plan to assess how feedback influenced protocol decisions for both study drugs. It was decided that quality metrics would be assessed through follow-up phone calls and surveys assessing satisfaction and perceived quality of contribution to the project. Due to limitations in timing, it was decided that outcomes would be measured through whether protocol amendments were made as a result of feedback provided at the focus group.
Step 5: Six patient advocates, three Parkinson's Foundation staff and three Company X researchers attended a one-day, audio-recorded, in-person focus group. The day was broken into six separate sessions: five of which were facilitated by Parkinson's Foundation staff and one of which was a presentation facilitated by a Company X researcher. All questions and talking points were scripted. Patient advocates participated in a variety of activities to share feedback including speaking, flip chart activities, diagrams and patient demonstrations. Breakfast and lunch were provided. At the end of the focus group, Company X researchers shared what they had learned from patient advocates that day.
Step 6: Parkinson's Foundation analysed all audio and drafted a report detailing topics discussed throughout the day. Parkinson's Foundation also identified eight recommendations for clinical trial improvement based upon themes from focus group discussions. Company X then followed up with patient advocates within six months of project execution to share three protocol changes that occurred as a result of patient advocate feedback. Results of this project were shared in two co-authored poster publications at the International Conference on Alzheimer's and Parkinson's Diseases and the International Congress of Parkinson's Disease and Movement Disorders. Two additional patient engagement speaking opportunities with Company X later occurred as a result of the positive project experiences between patient advocates, Company X researchers and Parkinson's Foundation.

| ME A SURING THE SUCCE SS OF PATIENT ENG AG EMENT
Within this identified patient engagement framework, several metrics can be captured to assess the quality and associated out- foundational metrics that can be used to measure the success of a patient engagement project (see Table 2).

| Quality of patient engagement
Within a patient engagement project, the quality of patient engagement should be captured through metrics that assess project performance. These metrics inform whether all parties executed the framework steps and planned patient engagement practices successfully. Each party receives questions specific to their attitudes, assigned roles and project expectations. Parkinson's Foundation leads the collection and analysis of quality metrics; however, the party assigned to this role (most often assigned in the scope of work) will depend on that party's capacity to design, administer and analyse metrics for each of the involved parties in an unbiased manner.
Areas of quality to assess include the following: form of patient  Table 3 for sample survey questions). These findings are then reported back to all involved parties for the purpose of informing future patient engagement projects. Quality findings are also shared publicly through publications and conferences.

| Outcomes of patient engagement
Within a project, metrics should be captured to identify changes made as a result of patient engagement. This can be more difficult to assess as it may take years for research to be completed and, as a result, the outcomes of the related engagement to be determined.

| FUTURE OPP ORTUNITIE S
The practice of patient engagement has increased in the past decade and has slowly been utilized to support the success of global clinical trials. Patient engagement has the potential to positively impact research; however, it is not currently standard practice to include and report on patient engagement. 8 Several researchers have incorporated patient engagement practices into their work, but many have only identified metrics that assess reach and count. 7   priorities, utilize stronger patient-reported outcomes and meaningful endpoints, reduce study burden, and enhance recruitment and retention. 27 By improving patient engagement project metrics, trials can be more efficiently designed to capture the needs of and ultimately benefit the patient community.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing is not applicable to this article as no new data were created or analysed in this study.