A Smartphone App for Self-Monitoring of Rheumatoid Arthritis Disease Activity to Assist Patient-Initiated Care: Protocol for a Randomized Controlled Trial

Background Telemedicine based on self-measurement of disease activity could be one of the key components to create the health care system of the future. Previous publications in various medical fields have shown that it is possible to safely telemonitor patients while reducing the number of outpatient clinic visits. For this purpose, we developed a mobile phone app for patients with rheumatoid arthritis (RA), which allows them to self-monitor their disease. Objective The objective of this study is to assess the safety and efficacy of self-initiated care assisted by a smartphone app in patients with RA. Methods This is a randomized controlled trial that will be performed for 1 year. A total of 176 patients with RA will be randomized to either self-initiated care with only one scheduled follow-up consultation assisted by our app or usual care. The coprimary outcome measures are the number of outpatient clinic consultations with a rheumatologist taking place during the trial period and the mean disease activity score as measured by the disease activity score 28 (DAS28) at 12 months. The secondary outcomes are patient satisfaction, adherence, patient empowerment, and cost evaluation of health care assisted by the app. Results Recruitment started in May 2019, and up to 18 months will be required for completion of recruitment. Thus far, 78 patients have been randomized, and thus far, experiences with the app have been positive. The study results are expected to be published by the end of 2021. Conclusions The completion of this study will provide important data regarding the following: (1) safety of self-initiated care supported by a smartphone app in terms of DAS28 and (2) efficacy of lowering health care usage with this new strategy of providing health care. Trial Registration Netherlands Trial Register NL7715; https://www.trialregister.nl/trial/7715 International Registered Report Identifier (IRRID) DERR1-10.2196/15105

Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities This trial is an investigator initiated study funded by AbbVie. AbbVie had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Outcomes are well defined and logically derived from our hypothesis' as explained in the introduction.

Participant timeline
13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for participants. A schematic diagram is highly recommended (see Figure) [V] Provided in phase 3 -timeline Data will be recorded on site directly into thea webbased database CASTOR EDC. The database will be used to monitor the progression of the study and the completeness of the data. The principale investigator (WB), research monitors, the inspection for health and youth, and coinvestigators have access to the source data, and the key of the code is safeguarded by the PI and a the PhD student [(BS)]. The code will consist of a three-3 letter identification (with letters from the study, SMR) combined with a code that is based on on the basis ofthe inclusion-sequence (SMR#001 and up). This code will be registered for each participant in a separate database. All data will be stored on the servers at the study location (Reade For the two primary outcome measures, the mean number of outpatient clinic visits in the 12 months trial period and the mean DAS28 at T=12 months will be compared between the intervention and the control group. 20b Methods for any additional analyses (eg, subgroup and adjusted analyses) For each outcome measure, we will also adjust for disease duration and activity at baseline, and sex and any variables that are statistically different from each other in unadjusted analyses.
20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation) The primary analysis will be using both intent-totreat (ITT) and per protocol (PP) analysis. In the ITT analysis, missing data (if over 10%) will be imputed using a random intercept mixed model.

Methods: Monitoring
Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed No DMC is needed since the risk analysis placed the study in the 'neglectable risk category' 21b Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial As the risk of the study is neglectable no stopping guidelines have been predefined. The authors (BS and WB) will have access to the interim results, which will be made public. WB has the final decision to terminate the trial.
Harms 22 Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct Adverse events will be collected during outpatient clinic visits (as per use). No extra adverse events are expected.
Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent from investigators and the sponsor No predefined plan for audits has been made. Monitoring will take place at the start, each year during and at the end of the trial. In case of important protocol modification(s) the ethics committee will be contacted and, in that case, the alterations will be (clearly) described in the manuscript.

Consent or assent
26a Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and how (see Item 32) B. Seppen. As described in Phase 3study procedure. *It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items. Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons "Attribution-NonCommercial-NoDerivs 3.0 Unported" license.