Development and validation of a web-based patient decision aid for immunotherapy for patients with metastatic melanoma: study protocol for a multicenter randomized trial

Background Patients with metastatic melanoma and their physicians are confronted with a complex decision regarding first-line therapy. Risks and benefits vary considerably between various treatment options. With this in mind, we aim to develop and evaluate a patient decision aid (PtDA) to inform patients about the risks and benefits of treatment options, namely, immunotherapy as monotherapy, immunotherapy as combination therapy, and treatment with BRAF/MEK inhibitors. We aim to test whether the use of this PtDA before medical consultation will increase patients’ knowledge of treatment options and thus promote shared decision-making (SDM) and patient decision satisfaction. Methods In total, 128 patients with metastatic melanoma from two German cancer centers will be randomized to the intervention group (IG), receiving access to the PtDA before medical consultation, or the control group (CG), receiving treatment as usual (TAU), i.e., medical consultation alone. There will be three major assessment points (before intervention, T0; after intervention, T1; and 3 months after intervention, T2). The main outcome is the patient’s knowledge of their treatment options, measured by a self-developed, piloted multiple-choice test at T1. Secondary outcome measures will include the extent of SDM during medical consultation, assessed by Observer OPTION 5, and patient decision satisfaction, assessed by the Satisfaction with Decision Scale (SwD), at T1 and T2. Discussion This trial will assess the effectiveness of a developed PtDA to enhance patient knowledge of treatment options for metastatic melanoma, SDM, and patient decision satisfaction. If the efficacy can be proven, the PtDA will be implemented nationwide in Germany to close a relevant gap in the education and care of patients with metastatic melanoma. Trial registration ClinicalTrials.gov NCT04240717. Registered on 27 January 2020

In general: 1. The declaration of consent (p. 1) and the study protocol (p. 17) mention that pseudonymised study data may be passed on. According to the patient information, however, no data are passed on. The information must be standardised in the documents. If pseudonymised data are passed on, the recipients should be named as precisely as possible. If it is not possible to give specific details, at least the possible categories of recipients (e.g. universities, hospitals, etc.) must be named (cf. Art. 13 Para. 1e DSGVO). 2. The study protocol on page 13 describes that, in addition to the study staff, employees of the cooperation partner TAKEPART Media + Science GmbH also have access to the study data. The study participants must be informed about this in the information leaflet and must agree to this procedure in the declaration of consent. 3. The study-specific questionnaires or decision-making aids to be developed within the framework of the study (MC knowledge test, subjective risk assessment, PtDA) are to be submitted to the Ethics Committee of the Medical Faculty of Heidelberg as soon as they are available.
Study protocol: 4. Unclear questions and lack of statistical hypothesis. "For the above hypotheses, which are investigated by means of regression analyses, this targeted sample size according to Field (2013) is sufficient." This is an insufficient justification of the number of cases and the reference is missing.
. BIC SOLADEST600 IBAN DE64 6005 0101 7421 5004 29 5. p. 17, section 11: In addition to the Federal Data Protection Act, the provisions of the Basic Data Protection Regulation (DSGVO) and the Baden-Württemberg State Data Protection Act (LDSG BW) must also be observed.
Information leaflet for patients: 6. p. 2 f., section "b) Control group", see sentence "As compensation for expenses, the patients of the control group receive a meal voucher from the cafeteria of the NCT Heidelberg": Why do only patients in the control group receive a meal voucher from the cafeteria? This voucher should be given to all study participants. In addition, the value of the voucher should be indicated.
We wish you success in conducting the study.
Please forward the results of the professional consultation and the study-related correspondence to all participating physicians in our area of responsibility.
With kind regards

General notes:
• Any changes in the organisation and conduct of the study, together with an assessment of the riskbenefit balance, shall be immediately notified to the Commission. Both the application number and the amended passages should be clearly marked in the relevant documents, otherwise it will not be possible to process them expeditiously. • Within one year of the end of the study, the study director should submit a final report to the Commission, summarising the results and conclusions of the study, whether fully completed or prematurely terminated. For this purpose, the sample template "Final Report" available on the Commission's website should be used (path: -> Other studies -> Templates). • Any research project involving subjects shall be registered in a publicly accessible database before the recruitment of the first subject. • The Ethics Committee of the Medical Faculty of Heidelberg works according to national legal regulations and the ICH-GCP guidelines. Its deliberations are based on the Declaration of the World Medical Association of Helsinki in its current version. • Regardless of the outcome of the consultation, the Ethics Committee draws your attention to the fact that the ethical and legal responsibility for conducting a study lies with the study director and all participating physicians. • Data protection aspects of research projects are generally only examined cursory by the ethics committee. This vote/evaluation does not therefore replace consultation with the responsible data protection officer. Compliance with the relevant data protection laws and the implementation of the data protection concept are the responsibility of the study director/examiner or sponsor. The general instructions from the initial consultation / initial assessment with conditions apply accordingly and must be taken into account.
The Ethics Committee at the TU Dresden bases its assessment of the submitted study documents in particular on the guidelines of the Declaration of the World Medical Association of Helsinki in the currently valid version, on the radiation protection regulations and on the generally accepted guidelines for "Good Clinical Practice (GCP).
The working methods and composition of the Ethics Committee comply with the applicable legal regulations and recommendations.
It is confirmed that no members of the Ethics Committee who are involved in the above-mentioned research project have contributed to the results of the consultation or evaluation or have been involved in any other way. We wish you every success in your research project.