Personalized, Web-Based, Guided Self-Help for Patients With Medically Unexplained Symptoms in Primary Care: Protocol for a Randomized Controlled Trial

Background Medically unexplained symptoms (MUS) constitute a major health problem because of their high prevalence, the suffering and disability they cause, and the associated medical costs. Web-based interventions may provide an accessible and convenient tool for managing MUS. We developed a personalized, Web-based, guided self-help intervention for MUS in primary care (Grip self-help) and would compare its effectiveness with that of usual care. Objective This paper aims to describe the rationale, objectives, and design of a pragmatic randomized controlled trial (RCT) assessing the effectiveness of Grip self-help. Methods For a pragmatic multicenter RCT, 165 adult patients with mild to moderate MUS will be recruited through general practices in the Netherlands. Randomization will be performed at general practice level. Over the course of several months, patients in the intervention group will receive a personalized set of Web-based self-help exercises, targeting the unhelpful cognitions, emotions, behaviors, and social factors that are relevant to them. The intervention is guided by a general practice mental health worker. The control group will receive care-as-usual. Primary outcome is physical health-related quality of life (RAND-36 or 36-item general health survey, physical component score). Secondary outcomes include severity of physical and psychological symptoms, mental health–related quality of life, cost-effectiveness, and acceptability. Assessments will take place at baseline, end of treatment, and at 16-, 26-, and 52-week follow-ups. Results Recruitment started in December 2018, and enrolment is ongoing. The first results are expected to be submitted for publication in December 2021. Conclusions To our knowledge, this is the first study to combine the concepts of electronic health, self-help, and personalized medicine in the treatment of MUS. By improving the quality of life and reducing symptoms of patients with MUS, Grip self-help has the potential to reduce costs and conserve scarce health care resources. Trial Registration Dutch Trial Register NTR7390; https://www.trialregister.nl/trial/7390. International Registered Report Identifier (IRRID) PRR1-10.2196/13738


Objective(s) and research question(s)
Consider the following factors: • The objective is clear and specific.
• The research question is clear, verifiable and connects with the objective.
• The scope and originality of the research question(s) is clearly described.
• There is a clear hypothesis.
The applicants present an interesting grant application with the aim to evaluate an online intervention targeting patients with mild to moderate somatic symptom disorder (SSD) in a pragmatic cluster randomized design. The applicants aim to investigate a subject of high clinical relevance. SSD are a burden for sufferers, they are also difficult to treat for doctors and psychotherapists and very costly for Society. The provided theoretical background and cited literature is consistent and includes all relevant current literature on SSD. The objective of the study is clearly described. The research questions are original and clearly described.
The hypotheses with regard to effectiveness, feasibility, and cost-effectiveness are all clearly described. The research project represents an innovative personalised approach to deal with SSD in a primary care setting.

Strategy
Consider the following factors: • The research strategy is clear and connects to the research question.
• There is attention for gender differences, cultural background, age and the client perspective.
• An implementation strategy is added to the proposal: • The implementation strategy clearly describes how the project results will be distributed and secured. • The implementation strategy describes implementation activities. • It is clear how stakeholders will be involved to encourage implementation. Research design • There is a clear description of the research design.
• The research design is valid and connects to the research question. Outcomes • There is a clear description of the expected outcomes and intended results in terms of quality of care, quality of life, and satisfaction of patients. A study will be conducted to measure these outcomes and results.
Overall, the applicants present a well elaborated study design and methodology. They choose health related quality of life (measured by a well validated questionnaire) as their main outcome. All other outcomes are well described. One strength of the study is the innovative application of a personalized approach. Another strength of the study is the consideration of an elaborated cost-effectiveness analysis. In regular, online intervention studies suffer from high drop-out rates. The authors use a blended approach (with a GP mental health worker) who contacts and motivates participants at the beginning and every four weeks after the beginning of the intervention. I am absolutely convinced by the selection of the control condition, which is care as usual according to the dutch guidelines that are well presented in the grant application. In Addition, I would recommend to include a clear strategy of reminding patients to complete the intervention, if they do not fully adhere. This could be by e-mail, sms or telephone. The applicants include a carefully arranged implementation strategy. Stakeholders as well as patients were involved in the design of the intervention. I am impressed by the elaborated design, that includes qualitative and quantitative methods. • It is possible to achieve the objective(s) using this strategy, duration and budget.

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• The inclusion of participants in the research project is feasible using this strategy, duration and budget.
• Facilities/staff are available.
• The timetable is clear and realistic.
The reported fact that the intervention was created by well experienced researchers in the field of SSD in close collaboration with patients and health care professionals convinces me to assume a good feasibility of the study. Concept and milestones are clear and realistic. Recruitment of practices will be performed through healthcare Groups associated with a large Organization. In Addition electronic health records will be used to identify frequent attenders to facilitate recruitment of patients. The recruitment strategy represents a very promising Approach.

Project group
Consider the following factors: • Relevant expertise is available.
• Clients/ client representatives and/or their families are represented in the project group.
• A research organisation and healthcare institution are represented in the project group.
• All partners of the collaboration are represented in the project group.
All applicants are well experienced researchers in their individual fields and have excellent experience in interdiscipliary working fields. The main applicant is an expert of high renown in the field of SSD. The prior activities of the applicants underline their ability to successfully perform the described Project in a good and funcioning cooperation. The president of the Pain Alliance Europe (PAE) as a representative of patients is member of the Project team. Therefore, clients are well represented in the project group.

Budget
• There is a clear explanation of the requested budget.
• The requested budget is suitable for the grant application.
• If applicable: there is a clear explanation of the cofinancing.
The applicants aim to perform a large study in a Primary care setting, which is highly relevant, but also complex. Therefore, the requested budget of the study is relatively high. In my opinion, this is a down-to-earth estimation and underlines the high quality of this proposal. From my point of view, the budget is absolutely suitable for the grant application. The quality of such highly relevant research projects often suffer from inadequate financing (underfunding).

Overall quality assessment
The present Research Grant application was conducted by an excellent and highly experienced Project Team. I am impressed by the preliminary work that led to the design of the Intervention. In my opinion this is an application dealing with a highly relevant Problem in an innovative manner. The scientific quality including design, recruitment strategy, and Intervention strategy seems excellent. As a reviewer i recommend the funding of the Grant application with high priority.