Patient’s and researcher’s perspectives on patient involvement in research in multiple sclerosis

Patient involvement in research has received growing attention in recent years [1-4]. In 1996, the UK National Institute for Health Research (NIHR) established INVOLVE, supporting public involvement in public health and social care research [5]. A clear distinction should be made between patient involvement and participation in research [6, 7]. The variability in roles and degrees of involvement (or “co-research”) is considerable and may be graded as consultation, collaboration or “in control” [8].

In the case of fundraising, requirements for patient involvement have increased. Researchers are often required to prepare a specific plan and strategy for patient involvement, or to provide a strong justification for not involving patients in the research process. Even though patient involvement is widely used, e.g., in shared decision-making regarding treatment, it is still not an immediately incorporated part of research. Often, the understanding, terminology and need for patient involvement lag among researchers and patients alike. Therefore, when planning new research projects, patients are not automatically involved, and misunderstandings and unfulfilled expectations concerning patient involvement may occur [8]. The patient population and disease burden may also affect patients' ability and willingness to participate as co-researchers. When engaging in patient involvement, it is important to constantly evaluate and navigate to ensure that patient involvement remains beneficial rather than symbolic/tokenistic [9, 10]. Tallentyle et al. reported how patient involvement influenced the primary approach to patients – they were treated by a neurologist rather than a researcher – and led to the inclusion of patient information videos on trial website as well as feedback on study materials, publications, and updates [11].

In the present study, we describe the potential and interest for patient involvement in multiple sclerosis (MS) research in Denmark for both patients and doctors. Furthermore, we present recommendations for patient involvement in future research that are targeted at patients with (pw) MS but translational to other patients.

To strengthen the study, we have used patient involvement in the development and evaluation of the questionnaires.

Methods

We used the term “co-researcher” for involvement in research (“medforsker” in Danish). We defined that a co-researcher was not a participant in, for example, a drug trial or as participant in a questionnaire survey. Instead, examples were given in the questionnaire that co-research may include, e.g., participation in the idea phase (what needs to be researched?), the planning/design of the study, its practical execution, data collection (and/or processing), article/report writing, dissemination of research/results, etc.

An interview guide on patient involvement in research was developed based on the “Method guide for individual interviews from the patient involvement guide” published by the Capital Region, Denmark [12]. The interview guide employed open questions and allowed respondents to elaborate. Several examples or support questions were listed as needed Supplementary material.

From July to October 2023, patients recruited from the MS Clinic at Aarhus University Hospital, Denmark, participated in individual interviews after providing informed consent. They were interviewed about patient involvement in research. The interviews were all conducted by the same experienced project nurse to avoid inter-individual bias. The project nurse was neutral concerning the interview. The comments/answers were noted along the way and then reviewed with the patient to obtain their approval.

Based on the replies from the individual interviews, we prepared a questionnaire about patient involvement in MS research. The questionnaire was prepared in REDCap hosted by Aarhus University and approved for secure data storage and questionnaires [13, 14]. The first version of the questionnaire (V1) was evaluated by patients who had previously been interviewed in mid-November 2023 to improve the language, relevance and content of the questionnaire. The final version (V2) was intended for pwMS regardless of type, duration, treatment, etc. The questionnaire could be accessed via a QR code or a link to REDCap from 1 March to 24 May 2024. The estimated time to complete the form was around 10 minutes. Also, it was possible to skip questions or elaborate on answers while answering the questionnaire. Participants were included via the MS Clinic/Outpatient Clinic at Aarhus University Hospital, Goedstrup Region Hospital, and the Danish Multiple Sclerosis Society’s website (covering the whole country). The V2 questionnaire was prepared in layman's Danish. A customised version of V2 (V3) was tested on MS doctors. Subsequently, the V3 questionnaire was shared with research-active doctors through the collegial network, the Danish Multiple Sclerosis Group.

The V1, V2 and V3 of the questionnaire (Danish language) are found in the Supplementary material. Answers from doctors and patients were compared, and similarities and differences were interpreted.

Ethics

The study was approved by the Region's internal register of research projects (1-16-02- 407-21). The patients participating in the individual interview completed an informed consent form.

Statistics

Data were drawn from REDCap and presented in bar graphs. In addition, qualitative answers (i.e., free-text, in-depth answers) were categorised and listed as examples in italics. For the calculation, STATA 18.0 Standard Edition and Microsoft 365 EXCEL were used. Data are presented as median and/or mean with standard deviation (SD) and min.-max. Researchers’ and patients’ responses were compared, and for the presented data, Fisher's exact test was calculated. For this study, a p value < 0.05 is considered statistically significant. Often, the response was not limited to a single answer (multiple answers possible), so the response percentage may exceed 100%.

Trial registration: not relevant.

Results

Demographics and characteristics of the ten patients participating in individual interviews and respondents of the different versions of the questionnaires are presented in Table 1.

Due to the word limit, we have focused on the quantitative data in the main manuscript. In the Supplementary material, we provide an in-depth report comprising all responses in Danish, including both the interviews and the questionnaires. Table 1 presents the preferred study designs (blinded/non-blinded), the optimal study duration, types of visits and distances from the patients' homes. Respondents had lived with the MS diagnosis for a mean period of nine years (mean), SD 7.0 (range: 0-30 years).

Questionnaire versions 2 and 3 in combination

Patients and doctors were asked to identify important factors as co-researchers and participants. Furthermore, they were asked to describe which symptoms were important for research and to state what their preferred information source was (Table 2).

PwMS were asked: “If you could imagine yourself being a co-researcher, what should the framework be like?”. The doctors were asked: “Could you imagine using patient involvement in your future (or current) research? If so, what role do you think patients could play? (Figure 1).

PwMS were asked, "For you as a patient, what do you think is most important to be researched"? For doctors, "For you as a doctor, what do you think is most important to be researched?" and "What topics do you think patients think are most important to be researched?" (Figure 2).

Discussion

This exploratory study reports the involvement of patients in research related to MS in Denmark in 2024. Patient involvement was considered important by pwMS (8.9 on 0-10 NRS, 0 = not important at all, 10 = very important). Patients could see themselves being participants, bringing ideas, being consultants or providing input. Few could see themselves in charge of a project, evaluating, writing or presenting research. The doctors’ replies were similar to those provided by the patients. However, the doctors answered “as participants” less frequently than the patients, and none of the doctors (and very few patients) could see the patients in charge of research projects (Figure 1).

We found an agreement on what pwMS and doctors believed were the most important topics for research. Interestingly, for basic research, doctors thought that patients would find this topic less important than they did (Figure 2).

In the case of “endpoint” measures, quality of life dominated. This is notable and challenging because quality of life is a factor that can be difficult to measure and therefore often becomes a secondary endpoint that cannot be validated and compared across studies. Furthermore, quality of life is interpreted differently by each patient, is influenced by numerous factors, (e.g., depression, fatigue, physical disability, cognitive, emotional and psychological factors) and changes over time, even within the individual patient [15].

Regarding symptoms, the interest was highest in investigating fatigue and cognition. Various validated endpoints exist for measuring, e.g., cognitive skills, tiredness, fatigue, energy and sleep [16-19]. However, it is difficult to measure an overall function in everyday life. The greatest difference between doctors and pwMS regarding symptoms was found for sensory disturbances and “sexuality, sex and relationship”.

In our project, we asked about the construction of questionnaires, and - for almost all questions - it was possible to elaborate on the answer provided. According to our survey, the questionnaire should take a maximum of 15 minutes to complete (similar to findings from Skovlund et al. [20]) and allow the use of a scale, e.g., 0-10, by "clicking off a box". Furthermore, it may well offer multiple answer options, and most patients would like the option to return to the form. Regrettably, we missed the chance to incorporate that last aspect into this project. It is, however, essential to keep this in mind when designing future questionnaires. Regarding where to get information about research, both pwMS and doctors agreed on the outpatient clinic, and patients preferred distributing the questionnaire by letter/e-boks rather than via social media.

By creating an anonymised questionnaire that is accessible via a link and QR code, we gained the advantage of obtaining a considerable number of responses. We aimed for 100 responses and received 141. Even so, this is less than 1% of pwMS in Denmark. A disadvantage of this approach was that we could not avoid or monitor multiple replies from the same respondent or responses from people outside the target group (pwMS). We would have preferred to know the distribution of responses assessed by sex and geography, but this was omitted to maintain complete anonymity. Questionnaires are a strong approach for exploratory studies. However, they have limitations when interpreting significance, which is often lost when adjusting for multiple testing. Also, questionnaires (and selecting patients for individual interviews) carry a risk of bias due to exaggeration of the interest in patient involvement in research. Compared with the total population of pwMS, the respondents may be less impaired and fatigued, have better cognitive function, have previous experience with research and have a special interest in the topic. Conversely, respondents may reflect those pwMS who are, indeed, eligible for involvement in MS research. A challenge in patient participation in MS research is the highly heterogeneous impact of MS on individuals' lives. This may contribute to variation in how much pwMS think they can get involved. We found that 43% of the respondents could see themselves engaged as co-researchers. On one hand, patient involvement was described as exciting, necessary, relevant, interesting and a way to contribute to better and more patient-oriented/relevant studies. On the other hand, fatigue, reduced energy, affected cognition and the need for time management should also be considered. Using a scale for a subjective question may be a limitation, e.g., in terms of quantifying the importance of patient involvement. However, patients did request a scale or range.

Another challenge with patient involvement is the ethical and legal framework. It must be considered and clarified how to ensure confidentiality and how to obtain access to and handle data. Additionally, details about authorship should be considered, and an “exit” plan should be prepared if the co-researcher no longer wants to, or is capable of, being involved. Furthermore, it is necessary to protect the co-researcher from knowledge that they may not benefit from having [20].

We used patient involvement in this study by conducting individual interviews and having patients participate in the questionnaire evaluation. We found that patient involvement in every step of the research was challenging, as we only became aware of the various steps and possibilities as the project progressed. Skovlund et al. presented a very interesting case study of the “planning, conduct and dissemination of a clinical controlled trial”, and provided ideas for operationalising patient involvement [20]. Tallantyre et al. made recommendations for patient involvement in clinical trials in neurology [11].

One suggestion to integrate patient involvement into future research is to include it as a part of the Good Clinical Practice Guideline protocol and as part of trial master file development. Another possibility would be to create guidelines for researchers within sub-specialties on how to include patient involvement in current or future research. We recommend establishing more extensive user panels to facilitate the pairing of researchers with patients and conducting research locally to ensure that individuals from remote regions are not overlooked.

Conclusions

Many patients are aware of research in MS and have participated in studies. The interest in research involvement remains high, and doctors and patients have a common understanding about the “what, where and how”. We suggest that the awareness of patient involvement in research is supported to ensure that it may be translated into clinical practice.