The ethics of ‘Trials within Cohorts’ (TwiCs): 2nd international symposium - London, UK. 7-8 November 2016

On 7-8 th November 2016, 60 people with an interest in the ‘ Trials within Cohorts ’ (TwiCs) approach for randomised controlled trial design met in London. The purpose of this 2 nd TwiCs international symposium was to share perspectives and experiences on ethical aspects of the TwiCs design, discuss how TwiCs relate to the current ethical frame- work, provide a forum in which to discuss and debate ethical issues and identify future directions for conceptual and empirical research. The symposium was supported by the Wellcome Trust and the NIHR CLAHRC Yorkshire and Humber and organised by members of the TwiCs network led by Clare Relton and attended by people from the UK, the Netherlands, Norway, Canada and USA. The two-day sympo- sium enabled an international group to meet and share experiences of the TwiCs design (also known as the ‘ cohort multiple RCT design ’ ), and to discuss plans for future research. Over the two days, invited plenary talks were interspersed by discussions, posters and mini pre- sentations from bioethicists, triallists and health research regulators. Key findings of the symposium were: (1) It is possible to make a compelling case to ethics committees that TwiCs designs are ap- propriate and ethical; (2) The importance of wider considerations around the ethics of inefficient trial designs; and (3) some questions about the ethical requirements for content and timing of informed consent for a study using the TwiCs design need to be decided on a case-by-case basis

Randomized feasibility trial of the Scleroderma Patient-centered Intervention Network hand exercise program (SPIN-HAND)

Purpose: The Scleroderma Patient-centered Intervention Network (SPIN) online hand exercise program (SPIN-HAND), is an online self-help program of hand exercises designed to improve hand function for people with scleroderma. The objective of this feasibility trial was to evaluate aspects of feasibility for conducting a full-scale randomized controlled trial of the SPIN-HAND program. Materials and Methods: The feasibility trial was embedded in the SPIN cohort and utilized the cohort multiple randomized controlled trial (cmRCT) design. In the cmRCT design, at the time of cohort enrollment, cohort participants consent to be assessed for trial eligibility and randomized prior to being informed about trials conducted using the cohort. When trials were conducted in the cohort, participants randomized to the intervention were informed and consented to access the intervention. Participants randomized to control were not informed that they have not received an intervention. All participants eligible and randomized to participate in the trial were included in analyses on an intent-to-treat basis. Cohort participants with a Cochin Hand Function Scale score ≥ 3/90 and an interest in using an online hand-exercise intervention were randomized (1:1 ratio) to be offered as usual care plus the SPIN-HAND Program or usual care for 3 months. User satisfaction was assessed with semi-structured interviews. Results: Of the 40 randomized participants, 24 were allocated to SPIN-HAND and 16 to usual care. Of 24 participants randomized to be offered SPIN-HAND, 15 (63%) consented to use the program. Usage of SPIN-HAND content among the 15 participants who consented to use the program was low; only five (33%) logged in more than twice. Participants found the content relevant and easy to understand (satisfaction rating 8.5/10, N = 6). Automated eligibility and randomization procedures via the SPIN Cohort platform functioned properly. The required technical support was minimal. Conclusions: Trial methodology functioned as designed, and the SPIN-HAND Program was feasibly delivered; however, the acceptance of the offer and use of program content among accepters were low. Adjustments to information provided to potential participants will be implemented in the full-scale SPIN-HAND trial to attempt to increase offer acceptance

The Scleroderma Patient-centered Intervention Network Self-Management (SPIN-SELF) Program: protocol for a two-arm parallel partially nested randomized controlled feasibility trial with progression to full-scale trial

Background Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. We completed an initial feasibility trial of an online self-administered version of the Scleroderma Patient-centered Intervention Network Self-Management (SPIN-SELF) Program using the cohort multiple randomized controlled trial (RCT) design. Due to low intervention offer uptake, we will conduct a new feasibility trial with progression to full-scale trial, using a two-arm parallel, partially nested RCT design. The SPIN-SELF Program has also been revised to include facilitator-led videoconference group sessions in addition to online material. We will test the group-based intervention delivery format, then evaluate the effect of the SPIN-SELF Program on disease management self-efficacy (primary) and patient activation, social appearance anxiety, and functional health outcomes (secondary). Methods This study is a feasibility trial with progression to full-scale RCT, pending meeting pre-defined criteria, of the SPIN-SELF Program. Participants will be recruited from the ongoing SPIN Cohort ( http://www.spinsclero.com/en/cohort ) and via social media and partner patient organizations. Eligible participants must have SSc and low to moderate disease management self-efficacy (Self-Efficacy for Managing Chronic Disease (SEMCD) Scale score ≤ 7.0). Participants will be randomized (1:1 allocation) to the group-based SPIN-SELF Program or usual care for 3 months. The primary outcome in the full-scale trial will be disease management self-efficacy based on SEMCD Scale scores at 3 months post-randomization. Secondary outcomes include SEMCD scores 6 months post-randomization plus patient activation, social appearance anxiety, and functional health outcomes at 3 and 6 months post-randomization. We will include 40 participants to assess feasibility. At the end of the feasibility portion, stoppage criteria will be used to determine if the trial procedures or SPIN-SELF Program need important modifications, thereby requiring a re-set for the full-scale trial. Otherwise, the full-scale RCT will proceed, and outcome data from the feasibility portion will be utilized in the full-scale trial. In the full-scale RCT, 524 participants will be recruited. Discussion The SPIN-SELF Program may improve disease management self-efficacy, patient activation, social appearance anxiety, and functional health outcomes in people with SSc. SPIN works with partner patient organizations around the world to disseminate its programs free-of-charge. Trial registration ClinicalTrials.gov NCT04246528 . Registered on 27 January 2020Medicine, Faculty ofNon UBCPsychiatry, Department ofReviewedFacultyResearcherOthe