.

 

CONSERVE-SPIRIT Extension: 20 October 2021
Item	Item title	Description			Page No.
I.	Extenuating Circumstances	Describe the circumstances and how they constitute extenuating circumstances. - As a result of the COVID19 outbreak, research activity relating to COSTAR Project pilot cRCT ceased in Rwanda and Uganda on the 16 and 20 March 2020 respectively. In addition, the Sponsor (University of Liverpool) of the research announced on 20 March that all recruitment to clinical trials must temporarily stop until further notice. - The pausing of the trial activity in the two sites severely impacted on the integrity of the pilot trial. The vast majority of the clusters that had been randomised as part of the internal pilot had received less than half of the required 15 community-based sociotherapy sessions, or 15 inactive group meetings. In addition, it has not been possible to commence the 18-week post-randomisation follow-up assessments. As such, we have not had the opportunity to determine whether Criterion 2 (relating to participant retention) of the ‘stop/go criteria’ has been met
II.	Important Modifications	a. Describe how the modifications are important modifications. - The primary analysis for the trial is based on outcomes collected at 18 weeks post-randomisation. The absence of these outcomes for the pilot phase due to the disruption caused by the COVID19 outbreak means these clusters cannot contribute anything to the analysis. To address the predicament, we discussed the possibility of the internal pilot becoming an ‘external pilot’. The key difference being that the data collected during the pilot phase would now not be included in the trial analysis on the basis that COVID19-related disruption (to the delivery of the intervention and control sessions, inability to complete follow-up assessments etc.) has prevented a fair evaluation of the intervention during the pilot phase.
		b. Describe the impacts mitigating strategies, including their rationale and implications for the trial. - The initial power calculation conducted prior to trial commencement had indicated that 72 clusters were required (24 of which were the internal pilot) to adequately power the trial statistical analysis. This was based on conservative estimates of relevant parameters. - Mitigations: We revisited the power calculation and determined that at least 60 clusters will provide sufficient power for the statistical analyses we planned. This is 25% more than the additional 48 clusters that we had planned to recruit if the pilot data had been included in the analyses. However, we believe that this additional work can be accommodated. We would aim to recruit 64 clusters using a steeper recruitment curve in the time remaining. - Implication: Inclusion of a section in the Participant Information Sheet on ethical conduct related to compliance with recommended COVID19 preventive measures by the Uganda and Rwanda Government. The COVID19 guideline that are reflective of respective national governments and research ethical committees were circulated to teams at trial sites and along with it; an associated training was delivered across trial sites. In addition, a COVI19 evaluation form containing 6 items to assess participants level of concerns about COVID19 was added to the assessment battery for the definitive trial.			(see below)
		c. Provide a modification timeline. - Date when extenuating circumstance was identified: March 2020 Date when the circumstances took effect: May 2020 Number of participants/clusters enrolled to trial before the extenuating circumstance: 24 clusters - Project timelines was extended to run through 31st March 2022. Previously project duration was 30 months set to run from 1 September 2019–28 February 2021.
III.	Responsible Parties	State who planned, reviewed and approved the modifications. - Planned by: Principal Investigator and local PIs at the Trial Site - Reviewed and approved by: Members of the independent joint Trial Steering Committee/ Data Management and Ethics Committee (TSC/DMEC) and the funder (ESRC GCFR), and ethical committees from Liverpool University (Sponsor), University of Rwanda, Makerere University
IV.	Interim data	If modifications were informed by trial data, describe how the interim data were used, including whether they were examined by study group, and whether the individuals reviewing the data were blinded to the treatment allocation. Not applicable.
SPIRIT Item and Number		For each row, if important modifications occurred, check one or both of ‘impact’ and/or ‘mitigating strategy’ and describe the changes in the protocol. Check ‘no change’ for items that are unaffected in the extenuating circumstance.			Page No.
		No Change	Impact*	Mitigating Strategy**
1	Title	✓
2	Trial registration	✓
3	Protocol version		✓	Version 13, dated 28 May 2020 changes on: - Trial sample size (i.e. number of clusters) - Trial design reconfiguration - Participant Information Sheet for Definitive Trial updated to include information on COVID19 preventive measures - Circulation and training on guideline on COVID19 preventive measure to promote adherence through end of study period Version 14, dated 15 September 2020. Addition of: - Six COVID19 related impact questions Version 16, dated 23 July 2021 - Increased data collection method options to include telephone interviews whenever face-to-face interviews not feasible.
4	Funding	✓
5	Roles and responsibilities	✓
6	Background and rationale	✓
7	Objectives	✓
8	Trial design		✓	Permission was sought to abandon activity on the pilot trial and instead recruit 64 new clusters to undertake a fully powered definitive trial with no pilot phase’
9	Study setting	✓
10	Eligibility criteria	✓
11	Interventions	✓
12	Outcomes	✓

13	Participant timeline		✓	Suspension and then resumption of activities at different point in the study duration affected the schedule of previously planned activities. We sought updated ethical approval for revised timelines/ procedures from all committees overseeing the project
14	Sample size		✓	Prior to V13 of the protocol (May 2020) the plan had been to recruit 72 clusters (including 24 clusters recruited as part of an internal pilot). However due to COVID19 related disruption, permission was sought to abandon activity on the pilot trial and instead recruit 64 new clusters to undertake a fully powered definitive trial with no internal pilot phase. In March 2021, it was announced that four clusters recruited to the definitive cRCT in Gihembe, Rwanda were part of a scheme to relocate members of the Congolese refugee communities to Mahama refugee camp in Rwanda. These individuals were in the end lost to follow-up. To ensure that the definitive trial is adequately powered for the planned analyses, the number of clusters recruited in Kyangwali, Uganda were increased from 32 to 42. It was not possible to increase the number of clusters recruited in Gihembe due to the limited number of clusters available. This then brought the total number of clusters recruited in the definitive trial across both sites from 64 to 70. We sought updated ethical approval for from all committees overseeing the project
15	Recruitment	✓
16	Allocation	✓
17	Blinding (masking)	✓
18	Data collection methods		✓	For process evaluation, telephone was added to face-face as an options for data collection method from individual interviews. This was all depending on COVID-19 restriction. We sought updated ethical approval for from all committees overseeing the project
19	Data management	✓
20	Statistical methods	✓
21	Data monitoring	✓
22	Harms	✓
23	Auditing	✓
24	Research ethics approval		✓	For revised study design, revised timelines/ procedures we sought updated ethical approval for from all committees overseeing the project
25	Protocol amendments		✓	Amendments relating to activities and schedule changes as a consequence to COVID-19 in-country guidelines were made and sought ethical approval for all revisions from all committees overseeing the project. We sought updated ethical approval for from all committees overseeing the project
26	Consent or assent		✓
27	Confidentiality	✓
28	Declaration of interests	✓
29	Access to data	✓
30	Ancillary and post-trial care	✓
31	Dissemination policy	✓
32	Informed consent materials		✓	Addition of a paragraph to participant information sheet (PIS) compliance with measures aimed at minimising spread of COVID19 in order to protect research participants and the research team. We sought updated ethical approval for from all committees overseeing the project
33	Biological specimens	✓

*Aspects of the trial that are directly affected or changed by the extenuating circumstance and are not under the control of investigators, sponsor or funder.

**Aspects of the trial that are modified by the study investigators, sponsor or funder to respond to the extenuating circumstance or manage the direct impacts on the trial.

The CONSERVE-SPIRIT Checklist is licenced by the CONSERVE Group under the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International licence.