Listening to patients, for the patients: The COVAD Study—Vision, organizational structure, and challenges

The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy.


| INTRODUC TI ON
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 caused a global health crisis with profound public health impacts, economic disruption, and social upheaval. 14][5][6] This uncertainty precipitated vaccine hesitancy in these high-risk patients, 7,8 which was further amplified by potentially misleading reports on social media. 9Consequently, a pressing need has emerged to answer the unaddressed questions regarding COVID-19 vaccination in individuals with AIRDs.This requires the rapid development of large-scale datasets or 'big data' comprising ethnically, geographically, and socioeconomically diverse AIRD patient populations.Generation of big data requires the setting of sustainable, measurable, achievable, relevant, and time-bound (SMART) 10 goals.This, in turn, requires a well-structured and dedicated team of individuals with a wide array of skill sets and experiences.Setting a clearly defined goal, division of resources and workload, maintaining trust, efficiency, and productivity, and cultivating ethics all ensure the team's long-term sustainability.It is along these lines that the COVID-19 vaccination in autoimmune diseases (COVAD) team was formulated.
An adequate sample size is paramount to generalizable results and identifying patterns and distinct characteristics in different patient populations to cater to their needs.In addition, any inaccuracies can be safely removed without impacting the validity of the remaining data.2][13][14] However, the vast majority of these were physician-reported, and thus, tended largely to approach these problems from a purely clinical standpoint, focusing on discrete symptomatology and risk factors for severe outcomes.This has left an unmet need to address patient-centered concerns, including flares, pain, fatigue, and quality of life (QoL).Moreover, in most studies, rare diseases such as myositis, systemic sclerosis, and lupus were not prioritized owing to their relatively smaller global disease burden than other AIRDs.The COVAD study, thus, aimed to bridge this gap by amplifying the patient voice and focusing attention on rarer, often overlooked, disease groups.Amid global lockdowns, social media have become crucial for research collaboration, enabling rapid recruitment of diverse patient populations and generating large datasets to combat COVID-19.It has also facilitated collaboration among clinicians in diverse medical settings, identifying varying patient needs.The surge in social media users and big data has accelerated the dissemination of accurate information and made disease surveillance more efficient. 15,16us, the COVAD study was designed to better understand the outcomes after COVID-19 infection and vaccination in patients with AIRDs, focusing on patient-centric concerns, rare diseases, and vulnerable populations.The COVID-19 vaccination outcomes were investigated using validated patient-reported outcomes (PROs).We delineated several underexplored perspectives and challenges of a large working group to create an easily replicable model for remote research.

| Organizational structure
The McGrath model states that a team's foundation is formed by the inputs, processes, and outcomes of teamwork, all of which hinge on the team's composition and characteristics. 17This process involves the cooperation and resourcefulness of team members in achieving specific objectives, with the output being the team's accomplishment language barriers, and authorship concerns, while highlighting the measures taken to address them.

Conclusion:
Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases.The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care.Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them.
autoimmune, collaboration, digital, PROMs, research, rheumatology, survey of its organizational goals. 17,18The input phase includes members' skills and personalities.Interpersonal dynamics, such as the team's structure, size, and reward system, form the cornerstone of the McGrath model's input phase.Group interactions lead to improved performance, delivered quickly and with minimal errors.This highquality output fosters increased bonding and satisfaction among team members.It classifies group tasks in a two-dimensional axis: conflict-cooperation and conceptual behaviors.Tasks are grouped into eight distinct types based on these axes-planning, creativity, intellective, decision-making, cognitive conflict, mixed motive, competitive, and performance (Figure 1). 17,18rther, the COVAD study group was organized into a core team, steering committee, and study collaborators (Figure 2A).These included clinicians from various specialities and rheumatology researchers based on their complementing skillsets (Figure 2A). 17,18

| The core team
The core team comprised three rheumatologists and undergraduate medical students, who were further divided into administrative, data, and writing teams.The administrative team managed study logistics and the survey platform, updated collaborators on progress, facilitated survey dissemination, and coordinated tasks such as approving new subproject requests and conference abstracts.Study logistics were managed through the COVAD study email account, used for enquiries and updates.The data team handled data processing, cleaning, and archiving, and ensured confidentiality and anonymity, maintaining a system in place to access the COVAD study database (Figure 2B).The writing team conducted data analyses and wrote the manuscript, adhering to guidelines such as strengthening the reporting of observational studies in epidemiology (STROBE), 19 checklist for reporting results of internet e-surveys (CHERRIES) 20 for the study design, and Contributor Roles Taxonomy (CRediT) 21 for authorship.
The first phase of the COVAD study was led by two principal investigators (LG and VA), who supervised core team activities, managed group governance, and obtained ethical approvals for the study and sub-projects.Regular, weekly virtual meetings with LG were held to discuss progress, distribute work efficiently, boost morale, and ensure timely task completion.These meetings also facilitated data analysis and consensus building.

| Steering committee
The COVAD steering committee comprises physicians specializing in the management of AIRDs.The committee provided scientific input for the questionnaire design, pilot-tested the survey, developed data request policies, reviewed subproject proposals for feasibility, novelty, and innovation, and enhanced the scientific quality of the manuscript.To assess subproject quality, proposals were shared with committee members to evaluate the research topic, hypothesis, study design, and statistical analysis.Committee recommendations were provided to subproject heads as anonymous reviewer remarks, ensuring scientific rigor and impartial peer review within the COVAD study.
Additionally, the steering committee reviewed and provided insights on conference abstracts to be presented by collaborators at international conferences.Their contributions not only aided in knowledge dissemination but also enhanced the quality and impact of the presentations.
F I G U R E 1 Classification of responsibilities and tasks on the basis of the McGrath model.

| Study collaborators
Study collaborators were recruited using social media, and physicians from various regions worldwide participated, contributing to the multinational, multicenter collaborative effort.They served as regional leaders for their institutions, significantly expanding the study's scope and quality by contributing to a large dataset and providing expertise for analyses.Collaborators also co-led subprojects aligned with their interests and expertise.To coordinate with global collaborators, we determined suitable virtual meeting times via polls/ surveys, with meetings recorded and minutes circulated.Teams were formed to actively involve patient research partners and engage with patient study groups.

| Patient research partners
Patient research partners actively contributed to the study design and pilot testing of the survey.The questions for the second COVAD e-survey were informed by discussions in patient support groups during The Myositis Association (TMA) patient conference held virtually during the pandemic.

| Ethical considerations
The principal investigators were responsible for obtaining ethical approval from the Institutional Ethics Committee and COVAD collaborators were responsible for local IRB approvals.The first page of the survey included the participant information sheet and informed consent.The survey proceeded to additional questions after consent was obtained.The data collected were anonymized before being sent to the data cleaning and analysis team.

| Success and global impact
The COVAD study has completed two phases and is currently in its third phase.The success and global impact of the COVAD study have been exemplified by the publication of 34 papers (as of 24

| Challenges and future prospects
Like all endeavors, the COVAD study group encountered a wide array of challenges (Figure 2C).

| Ambiguity in guidelines and scientific disagreement
The study's foundation and methodology were meticulously planned with substantial input from the steering committee, leveraging their combined expertise and governance.This collaborative effort allowed the COVAD study to address numerous emerging questions that were not clearly defined initially.These questions included the prevalence and characteristics of post-COVID-19 syndrome, flares in idiopathic inflammatory myopathies (IIMs) following vaccination, and the use of PROMIS physical function in IIMs.
While steering committee members and collaborators from diverse specialties and continents ensured input from various fields, deadlines were set to maintain the study's timely progress.
Working with a multidisciplinary team occasionally led to scientific disagreements due to differing viewpoints on interpretation of the data published.For example, a glass that is half full can also be perceived as half empty by many.It is a matter of perspective.Such disagreements were resolved through discussions to reach consensus.
Incorporating these diverse inputs and suggestions regarding methodology, project reviews, writing, and statistical analyses was sometimes time-intensive, especially with a limited number of team members balancing these tasks alongside their academic and clinical responsibilities.

| Data and survey platform management
Data analysis and database management demanded statistical expertise and significant time investment.Some participants encountered difficulties completing the survey, leading to incomplete responses in the data.However, the core team members addressed these issues through a steep learning curve to acquire new skills such as survey design and loading and data management.

| Workforce
The workforce was challenged by the relatively small size of the core team compared to the study's scale and dynamic nature.Without dedicated fellows or study coordinators, full-time clinicians and students shared COVAD study tasks alongside their clinical and academic duties.These challenges were made worse by redeployment to 'front line' COVID-19 wards in overwhelmed health systems in many countries.However, these obstacles were overcome by convening weekly meetings, effective task planning and prioritization, equitable distribution of responsibilities, setting deadlines, and fostering camaraderie to create a supportive and motivating work environment conducive to timely task completion.Cooperation among team members also facilitated an effective learning environment, allowing members to acquire new skills, progress in their professional and personal development, and contribute efficiently to the team's efforts.

| Funding
As such, the lack of funding was a significant challenge for the COVAD study.However, this challenge was mitigated by limiting the expenditure on the tools used in the project management.

| Language and social barriers
While the internationally collaborative nature of the COVAD initiative ensured a geographically diverse dataset, language barriers had to be overcome for wide dissemination of the survey.Given that English is not the first language for many potential respondents, the survey is planned to require translation into over 20 languages before dissemination, which entailed significant time and effort.Furthermore, to ensure that the questionnaire is not misinterpreted due to cultural diversity, regional translation leads were appointed for the study.They assisted us to ensure the meaning of the question was translated accurately and validated PROs were used where applicable.This approach enhanced the precision of the survey, and led to the inclusion of underrepresented demographics within the research team.

| Authorship issues
Authorship attribution is often a point of contention, especially for multicenter studies with a large number of collaborators.While a significant number of collaborators assured a diverse dataset, limitations on the number of authors in certain journals, while also ensuring that fair credit is given to all, was a challenge.Hence, to resolve any discrepancies, authorship was decided according to the ICMJE guidelines and CrediT taxonomy of contribution to the study design, manuscript writing, and statistical analysis.Authorship criteria for subprojects were further refined through discussions between the core team and steering committee.These policies and processes were then shared with all the collaborators in the study to maintain transparency.
This study aimed to develop an online, long-term, multinational collaborative study group.The success of COVAD initiative illustrates the impact of digital crowdsourcing of virtual professional networks online, with the ability to build a team and deliver expedited results in a restricted time. 11,18,22[25] The COVAD survey also reinforces the importance of physician-patient relationship, which has been at the center of the healthcare system since its inception.Integrating the patient voice in clinical care settings fosters a greater sense of empowerment among patients and may thereby bridge the communication gap between healthcare provider and patient. 26[29] Needless to say, this innovative project encountered unique challenges when delving into the uncharted territory of online research on a global scale.The lack of guidelines, logistic barriers, workforce, and funding limitations, as well as issues regarding massive dataset management and manuscript drafting, were some challenges in the course of this project.

| Novelty
The COVAD study is one of its kind patient-focused study having a large global dataset conducted through a remote online methodology.It includes rare autoimmune diseases setting itself apart from other studies conducted during the pandemic.The third phase of COVAD studies has further expanded its research focus as mentioned previously.

| Limitations
As an online self-reported patient-administered survey, the COVAD study suffers from a couple of limitations.The recruitment method of the survey which includes social media, physician networks, and patient groups can cause selection bias limiting the generalizability of its findings.The survey responses may suffer from recall bias as it is self-reported.

| Future directive
There are several prospects for the COVAD study to ensure it continues to serve novel and unexplored, patient-centered research.It aims to expand the study group to include more disease-specific collaborators and collaborators from underrepresented regions of the world to ensure diverse study objectives in terms of inclusivity and research questions answered.Efforts are ongoing to secure funding which will enable better maintenance of the dataset and ongoing use of survey platforms.Dissemination of our survey's findings to underrepresented groups will be aided by establishing a larger social media presence moving forward.

| CON CLUS ION
Collaborative virtual models offer a dynamic new frontier in medical research that is vital to studying rare diseases.The establishment of uniform, impartial, and inclusive guidelines for managing large international datasets can help provide a framework to better facilitate this process.The care of patients is our central motivation, and it is essential to recognize their voice as equal stakeholders and valued partners in the study of the conditions that profoundly affect them, through harnessing their lived experience.
March 2024) with 200 citations currently.This is further evidenced by increased patient engagement with the COVAD survey, resulting in over 39 096 responses in our previous surveys.The results have been widely shared at physician and patient conferences, such as F I G U R E 2 (A) Structure of the COVAD study group; (B) Parameters collected in the COVAD survey; (C) Challenges encountered by the COVAD study.COVAD: COVID-19 vaccination in autoimmune diseases; IS: immunosuppressants; QoL: quality of life; PROMIS: Patient-Reported Outcome Measurement Information System; SLE: Systemic Lupus Erythematosus.American College of Rheumatology (ACR), EULAR, Journal of Clinical Rheumatology (JCR), Myositis UK, and The Myositis Association, to name a few.The COVAD study, thus, presents an opportunity for global centers to collaborate effectively.The COVAD-1 and COVAD-2 studies aimed to generate information on short-term and long-term adverse effects postvaccination and their determinants in patients with AIRDs.COVAD-3 aims to expand beyond clinical and biological factors, exploring how sociodemographic, mental and reproductive health, social security, and other personal factors influence subjective well-being (SWB) in patients with AIRDs.It is a multipart survey, consisting of 125 questions and involving 203 collaborators from 86 countries.The study is expected to be open until December 2024.

1 Byramjee
AUTH O R CO NTR I B UTI O N S Conceptualization: LG and VA.Funding acquisition: N/A.Methodology: LG and VA.Validation: LG and VA.Writing-original draft: LG, MJ, ND, and SS.Writing-review and editing: all authors.A FFI LI ATI O N S Jeejeebhoy Government Medical College and Sassoon General Hospitals, Pune, India 2 Seth Gordhandhas Sunderdas Medical College and King Edwards Memorial