Table 2.

Applying the SHOW RESPECT adaptable framework to the ICON8 and CHAPAS-4 trials

Considerations	ICON8	CHAPAS-4
Supporting and preparing trial participants to receive results	The ICON8 Participant Information Sheet told participants that, when results were available, a summary of the results would be available from their doctor and on the MRCCTU website. However, participants will have received that several years ago, so may need reminding that they will receive the results. They will also need information about how the results will be shared, as this was not included in the PIS There is no reason to think that ICON8 participants are less likely to want to know the results than participants in previous studies, so it is probable that most will want to know. An opt-out approach is likely to be suitable for this. A written update for participants (sent by post, as participants are not attending clinic frequently at this stage of the trial) could be used to inform them the results are available, how to access them, and how to opt out. Site teams could keep track of opt-outs, as they will be responsible for sharing results with participants (see ‘Provider’ below) Most participants are still in follow-up for their trial and have access to support from their research nurse or doctor. There is also support available from ovarian cancer charity helplines. Both these sources of support should be highlighted in the results summary. Some research nurses may want to phone participants before or after the results are shared, to check whether they need additional support. However, this might not be feasible for all sites (particularly not for sites with large numbers of participants)	The Patient Information Sheet informed participants that a summary of results would be shared via the CTU website, and the results would be published in a medical journal. They were informed that they would be invited to a meeting at their trial centre, where results would be shared with them Based on previous paediatric HIV trials in these settings, we expect that most participants and their families will be keen to hear the results, and the meetings are likely to be well-attended. Sites will contact the participants’ carers by telephone to invite them to the meeting Providing the results at a participants meeting will enable participants and their caregivers to ask questions and get support if required. While children may no longer be attending the study clinics, they are still attending routine HIV clinic visits, so they can access further support from the counsellors, nurses and doctors at these clinics
HOw will the communication tool(s) reach participants?	The participant population for ICON8 is mostly older women, who are less likely than the general population to have regular access to the internet. In this context, relying solely on electronic means of communication would be likely to make the results inaccessible for some participants. However, electronic communication media (webpages and email) may be appropriate for some participants Most participants are not visiting study clinics very frequently, so to avoid unnecessary delays in sharing results we will mail them information about how to access the results	Participants and families in CHAPAS-4 trial may not have access to the internet or email, making these methods not ideal for sharing results. The postal service may not reach all participants. Participants regularly visit clinics, so that is a potential way to reach them, as is inviting them (by telephone) to attend a face-to-face meeting
Who are the trial participants?	Participants in the ICON8 trial were females with an average age of 67 at the time results were available. Education level, computer literacy and access to the internet are likely to vary widely between participants Most participants in ICON8 had stage IIIC or IV disease, meaning the cancer had spread outside the pelvis and, in the case of stage IV, to other organs. In the UK, 5-year survival for stage III disease (which includes less severe disease than IIIC) was 27% and 13% for stage IV disease, for women diagnosed during the time period during which ICON8 recruited participants. The chemotherapy regimens used in the ICON8 trial are associated with significant side-effects The Participant Information Sheet informed participants that a summary of results of the trial would be prepared, available from their doctor and published on the CTU website Many participants in ICON8 kept copies of information they were given about the trial, so would be likely to want to keep the results for future reference. They may also want to be able to share results with family members and friends	Participants in the CHAPAS-4 trial were children living with HIV aged 3–15 years in Uganda, Zambia and Zimbabwe. Their parents or primary caregivers gave consent for them to initially join the trial (some participants have since given consent themselves, when they became old enough). Not all participants or parents/caregivers will be literate. Access to the internet is likely to be limited for many participants, although some participants, parents or caregivers may have smartphones Most children in CHAPAS-4 are in good health, and side-effects were not a major problem for most children in the trial Parents and children were told in the Participant Information Sheet that they would be able to receive the results at a participants meeting Participants and families are unlikely to want to share the results with others due to the stigma around HIV. For similar reasons, they may not wish to keep physical copies of the results
REsults—what do they show?	The ICON8 results showed no benefit from the two experimental regimens. This may be a relief for those in the control arm, who have not missed out on a superior treatment. However, it is likely to be disappointing to participants who were hoping the trial would improve the treatment of ovarian cancer The results were not particularly complex, with no important heterogeneity or conflicting results	The CHAPAS-4 trial found that newer antiretroviral combinations including tenofovir alafenamide and dolutegravir are superior to older second-line options for children living with HIV. In addition, CHAPAS-4 found that combinations including the drugs darunavir or atazanavir are excellent alternative options. Overall, children in the CHAPAS-4 trial did very well. Very few children experienced their disease getting worse, or were hospitalised. The results of each individual comparison are not particularly complex, with no important heterogeneity or conflicting results These results reinforce the current WHO recommendation of dolutegravir-based regimens being preferred second-line regimen for children. They also provide new evidence for use of tenofovir alafenamide in second-line combinations for children
Special considerations	The trial had not closed early, nor received negative publicity When participants joined the trial, the PIS informed them that a previous study in Japan had found benefit from weekly chemotherapy, so results communication needs to take this into consideration	The trial had not closed early, nor received negative publicity. Dolutegravir is now widely available in routine practice, and children who did not receive this during the trial have been moved on to it Tenofovir alafenamide (TAF) is not currently available in routine care in a formulation suitable for young children. This means some participants in the TAF arm have been switched to the local standard of care
Provider—who will provide the results to participants?	Participants in ICON8 had been followed up for between 5 to 8 years, with face-to-face follow-up visits at the clinic. Their main points of contact for the trial were the site staff (oncologist, research nurse and trial administrators)—they have not had direct contact with the clinical trials unit or sponsor. Some participants will have had the same staff throughout the trial, while others will have seen different site staff over the course of their follow-up. Some site staff have developed close relationships with participants (particularly at sites where there have no been many changes in staff working on the trial). The number of participants at each site who were alive at the time results were available varied from 1 to more than 50	Participants in CHAPAS-4 have been followed up for at least 2 years, but are no longer in follow-up, and have moved back to routine care rather than research clinics. Follow-up was done face-to-face. Their main point of contact with the trial was the clinical team at their site. The site teams for this trial have begun to disperse to other studies or roles, now the trial is over. Sites had large numbers of participants (ranging from 74 to 219) Site staff are the appropriate people to provide results to participants in CHAPAS-4, because they know the parents and participants, and this is in line with what the Participant Information Sheet told participants/parents/caregivers. Site staff are also best placed to answer any questions about the results from participants/parents/caregivers, knowing both the participant and the study
Expertise and resources—what expertise and resources do you have access to for sharing results?	We had access to sufficient budget for printing and postage, but not to employ specialist filmmakers or graphic designers. We had access to expertise on the team on developing patient-facing communications tools and writing in plain language Sharing results with participants is included in CTU Standard Operating Procedures Sites were aware that they would be asked to share results with participants	We had budget available to cover the costs of translation, a graphic designer and printing The CHAPAS-4 trial has access to Youth Trial Boards who help develop materials that are suitable for children living with HIV. CHAPAS-4 also has access to expertise on the team on developing patient-facing communication tools and writing in plain language The activity is seen as important for CTU staff, and sites are aware of their role in sharing results with participants
Communication tools—which ones will you use?	We carried out patient and public involvement on the draft results summary to ensure it contained the information participants are likely to want to know. We provided the information in plain English and got input from patient representatives and ovarian cancer information specialists to ensure it was clear and easy to read We had access to people with some design skills in-house to allow us to format a clear printed summary and create the webpages. We were able to provide more than one way for participants to access results We used a combination of webpages (including links to further information and support, a short ‘talking heads’ style video alongside a plain language summary) and printed summary. We also offered an email option	We consulted with the Ugandan Youth Trial board over how to share results with participants. They recommended, in addition to meetings with participants and their families, developing an infographic or poster summarising the results graphically Once the results were known, we asked the Zimbabwe Youth Trial board to develop text summarising the results that will be of interest to participants and think about graphics for an infographic/poster. These were then passed on to a graphic designer to work on, along with translations of the text into the languages used for the Participant Information Sheet. Drafts of the posters were then shared with the Youth Trial Boards for comments, and these incorporated by the graphic designer. The posters are displayed at clinics and were shared during the participants meetings. Representatives from local ethics and regulatory bodies and local ART clinics where the children are being treated were also be invited. During the participants meetings, there was be a presentation of the results (using plain language) and other activities such as a short play by children to share their experiences of the trial. The meetings were also an opportunity to thank participants and their families and celebrate the achievements of the trial
Timing—when should results be communicated?	The results from ICON8 were unlikely to receive media coverage, given the disappointing nature of the results. The results did not have implications for the future treatment of participants. Participants were still in follow-up, but not frequently We were confident that the key message was unlikely to change during the peer review process. Given these factors, we felt it was appropriate to share results with participants after presentation and prior to publication. However, we did not want to delay sharing results until participants’ next clinic visit, as this may be several months away. We therefore decided to send the information on how to access the results by mail	The results were unlikely to receive media coverage in the mainstream media, being of more interest to specialist medical media. There are not immediate implications for participants’ treatment based on these results (most have already been switched to dolutegravir). This means it is not urgent to share results with participants, but we do not want to delay sharing results too long, as few staff will be available to share results if we leave it long. We are confident results are unlikely to change during the peer review process, so will share results between presentation and publication
Links to the interventions used	The Enhanced webpage can be found https://mrcctu.ucl.ac.uk/studies/all-studies/i/icon8/results-of-the-icon8-trial/ The printed summary can be found https://doi.org/10.1371/journal.pmed.1003798.s006 The Patient Update Information Sheet can be found https://doi.org/10.1371/journal.pmed.1003798.s005	An English version of the results poster (co-developed with Youth Trial Boards) can be found https://mrcctu.ucl.ac.uk/media/2489/chapas4results_english_a4_cmyk_3mmnobleed.pdf