Testing approaches to sharing trial results with participants: The Show RESPECT cluster randomised, factorial, mixed methods trial.

BACKGROUND: Sharing trial results with participants is an ethical imperative but often does not happen. We tested an Enhanced Webpage versus a Basic Webpage, Mailed Printed Summary versus no Mailed Printed Summary, and Email List Invitation versus no Email List Invitation to see which approach resulted in the highest patient satisfaction with how the results were communicated. METHODS AND
FINDINGS: We carried out a cluster randomised, 2 by 2 by 2 factorial, nonblinded study within a trial, with semistructured qualitative interviews with some patients (ISRCTN96189403). Each cluster was a UK hospital participating in the ICON8 ovarian cancer trial. Interventions were shared with 384 ICON8 participants who were alive and considered well enough to be contacted, at 43 hospitals. Hospitals were allocated to share results with participants through one of the 8 intervention combinations based on random permutation within blocks of 8, stratified by number of participants. All interventions contained a written plain English summary of the results. The Enhanced Webpage also contained a short video. Both the Enhanced Webpage and Email contained links to further information and support. The Mailed Printed Summary was opt-out. Follow-up questionnaires were sent 1 month after patients had been offered the interventions. Patients' reported satisfaction was measured using a 5-point scale, analysed by ordinal logistic regression estimating main effects for all 3 interventions, with random effects for site, restricted to those who reported receiving the results and assuming no interaction. Data collection took place in 2018 to 2019. Questionnaires were sent to 275/384 randomly selected participants and returned by 180: 90/142 allocated Basic Webpage, 90/133 Enhanced Webpage; 91/141 no Mailed Printed Summary, 89/134 Mailed Printed Summary; 82/129 no Email List Invitation, 98/146 Email List Invitation. Only 3 patients opted out of receiving the Mailed Printed Summary; no patients signed up to the email list. Patients' satisfaction was greater at sites allocated the Mailed Printed Summary, where 65/81 (80%) were quite or very satisfied compared to sites with no Mailed Printed Summary 39/64 (61%), ordinal odds ratio (OR) = 3.15 (1.66 to 5.98, p < 0.001). We found no effect on patient satisfaction from the Enhanced Webpage, OR = 1.47 (0.78 to 2.76, p = 0.235) or Email List Invitation, OR = 1.38 (0.72 to 2.63, p = 0.327). Interviewees described the results as interesting, important, and disappointing (the ICON8 trial found no benefit). Finding out the results made some feel their trial participation had been more worthwhile. Regardless of allocated group, patients who received results generally reported that the information was easy to understand and find, were glad and did not regret finding out the results. The main limitation of our study is the 65% response rate.
CONCLUSIONS: Nearly all respondents wanted to know the results and were glad to receive them. Adding an opt-out Mailed Printed Summary alongside a webpage yielded the highest reported satisfaction. This study provides evidence on how to share results with other similar trial populations. Further research is needed to look at different results scenarios and patient populations. TRIAL REGISTRATION: ISRCTN: ISRCTN96189403.

Introduction

Sharing results with people who have taken part in trials is an ethical imperative [1], with the Declaration of Helsinki saying “All medical research subjects should be given the option of being informed about the general outcome and results of the study” [2]. Doing this demonstrates respect for their contribution, with some suggestion that it may increase the likelihood of participants taking part in future medical research, or recommending taking part in trials to others [3-7]. Studies have repeatedly shown that, while most participants want to receive results [3,8-12], many are not offered the opportunity to receive them [13-15].

Trial teams may be uncertain about which method to use for sharing results with participants. Most of the current evidence is based on surveys of participants or the public, prospectively asking how they would prefer to be informed, or retrospectively asking whether an approach that was used was acceptable or understandable, rather than systematically comparing outcomes from different approaches [3-6,8,11,12,14,16-21]. Most of the published evidence to date relates to sharing results with participants via mailed letters or leaflets; these studies generally report high acceptability of this approach [3,5,6,8,9,12,14,17,18,22,23]. However, sending out results by mail has resource implications. Sharing results via webpages has a number of potential advantages, including the ability to offer links to further information or support, and include audio and visual content alongside written summaries, and being discoverable by participants who have been lost to follow-up. There are also potential drawbacks in terms of accessibility for populations with low computer literacy. Fewer studies have reported sharing results via webpages. Mancini and colleagues randomised participants in a breast cancer trial to receive a letter containing a link to a website with the trial results, or no letter. They found that participants who received the letter had better understanding of the results but were not significantly more likely to have received the trial results than participants who did not receive the letter [24]. Other studies have reported low uptake of results shared via webpages [14,18], or lower levels of satisfaction with how the results were shared [12]. There is less evidence around the use of email to share results with participants; however, some studies have found that potential research participants would be happy to receive results that way [16]. Other approaches to sharing results that have been reported include face-to-face meetings [12,18,21], teleconferences [20], and individual telephone calls or helpline services [3,20,22], although the resource requirements for these approaches may be prohibitive, particularly to large trials, and uptake of these services may be low, with Dixon-Woods and colleagues reporting no calls to a telephone helpline [22].

ICON8 (ISRCTN10356387) was a Phase III randomised controlled trial looking at 3 chemotherapy regimens for up-front treatment of ovarian cancer. Results from the earlier of the 2 co-primary endpoints, progression-free survival, were published in 2019 [25], showing no difference in progression-free survival between the 3 regimens. The Show Results to Participants Engaged in Clinical Trials (Show RESPECT) study (ISRCTN96189403) sought to generate evidence to inform trial teams on how to share results with trial participants through a mixed methods cluster randomised factorial study within the ICON8 trial. Show RESPECT tested the following 3 hypotheses, in terms of participant satisfaction with how the results were communicated:

An Enhanced Webpage will be superior to a Basic Webpage;

A Mailed Printed Summary sent by post will be superior to no Mailed Printed Summary; and

An invitation to join an Email List to receive updates about the trial results will be superior to no invitation to join an Email List.

Methods

Show RESPECT was a mixed methods study, comprised of a factorial cluster randomised controlled trial within a trial to assess multiple approaches to communicating trial results, and embedded explanatory qualitative study. The data collection period for the quantitative and qualitative components was concurrent. Patients were identified for the semistructured interviews from their questionnaire responses and contact form returned alongside the questionnaire, so interviews took place after quantitative data collection for those individuals (while quantitative data collection continued for others). This paper reports both qualitative and quantitative results from data collected from trial participants. We consider the qualitative and quantitative data to have equal weight in their contribution to addressing the research aims. The full protocol for the study is available online [26] and as .

We also collected data from site staff, but results from that part of the study are beyond the scope of this paper.

Ethics approval

The study obtained ethics approval from the London-Chelsea Research Ethics Committee, MREC number 18/LO/1011.

Patient and public involvement

Substantial patient and public involvement (PPI) was carried out to design and conduct this study, including focus groups, a PPI survey, patient representation on the study steering group, and input from patient groups and individuals on the design and content of the interventions.

Quantitative methods

Trial design

Show RESPECT was a cluster randomised 2 by 2 by 2 factorial trial within a host trial, ICON8, an RCT evaluating chemotherapy schedules in ovarian cancer. We randomised each United Kingdom trial site (secondary or tertiary hospital) in ICON8 that agreed to take part in the Show RESPECT study to a combination of interventions to feedback ICON8 trial results to participants, as shown in A cluster design was chosen for this study, as it was felt that implementing individual randomisation for sharing results would be impractical for sites. Each site was a cluster. Allocation to each intervention was on a 1:1 ratio.

Show RESPECT trial schema.

Diagram showing the 3 randomisations within Show RESPECT: (1) Link to Basic Webpage or Enhanced Webpage; (2) No Mailed Printed Summary or Mailed Printed Summary; and (3) No invitation to join Email List or Invitation to join Email List.

Interventions

Participating sites sent all ICON8 patients at those sites a printed Patient Update Information Sheet thanking them for taking part in ICON8, reminding them of the aims of the ICON8 trial, informing them that trial results were now available, and how they could access them. This included the URL of their randomised webpage (Basic or Enhanced). The Patient Update Information Sheet told patients at sites randomised to the Mailed Printed Summary that they would be sent a Mailed Printed Summary of the results after 3 weeks and that they should let their ICON8 site team know if they did not want to be sent this. Patients at sites randomised to the Email List Invitation were given a URL to sign up to the email list. The Patient Update Information Sheet was based on guidance from the Health Research Authority on End of Study Information Sheets [27]. contains a detailed description of the study interventions, and links to the Basic and Enhanced Webpages. The Patient Update Information Sheet ( Mailed Printed Summary ( and results emails ( can be found in the Supporting information.

Randomisation 1—All participants in Show RESPECT received a link to either the Basic or Enhanced Webpage. The Basic Webpage contained a plain English summary of results, using the structure and headings recommended for lay summaries in the EU database of clinical trials [28]. The Enhanced Webpage used a structure adapted from the Multi-Regional Clinical Trials Center guidance on feedback of results [29], and included a short video of a doctor explaining the results, links to further information and support, 2 graphics showing the trial treatment schedules and main side effects, and the opportunity to submit questions to be answered in the page’s Frequently Asked Questions (FAQ) section.

Randomisation 2—The Mailed Printed Summary followed the same structure as the Enhanced Webpage, without the video or FAQ section, and was sent by post to participants’ homes. The Patient Update Information Sheet for sites randomised to no Mailed Printed Summary told patients that if they were unable to access the webpage or email list, and wanted to find out the results, they should contact their research nurse.

Randomisation 3—The first email sent to those who signed up to the email list followed the same structure as the Enhanced Webpage, without the video. Participants were invited to submit questions about the results, which were answered in subsequent emails.

Participants

Show RESPECT collected data from women with ovarian cancer who had taken part in the ICON8 trial, were currently still alive, and in follow-up at a site participating in Show RESPECT. ICON8 participants were not invited to join Show RESPECT if they were considered by site staff to be too unwell to be contacted about this study.

Outcomes

Our primary outcome measure was participants’ reported satisfaction with how the results were communicated to them, measured using a 5-point Likert-type scale (1 = very unsatisfied; 5 = very satisfied). Secondary outcome measures collected from participants were: the proportion of participants wanting to know the results that did find out; ease of finding out the results; whether the information about the trial results told participants everything they wanted to know; ease of understanding the results; how upsetting participants found the results; willingness to take part in a future trial; likelihood of recommending taking part in a clinical trial to friends and family; whether participants felt glad to have found out the results; and whether participants regretted finding out the results. Apart from proportion of those who wanted to know the results who found them out, these were measured using separate 5-point Likert-type scales. Quantitative data were collected from ICON8 participants by a questionnaire sent by site staff to their home address.

Data were collected between December 2018 to September 2019. Data collection finished 4 months after the final randomisation as it was felt that longer follow-up would run the risk of participants being unable to recall their experience of receiving results accurately.

Sample size

At trial sites, the allocated Show RESPECT intervention was offered to all eligible ICON8 participants (through the Patient Update Information Sheet). However, we did not approach all eligible participants for data collection, so as to reduce the burden on participants and staff, and because in cluster randomised trials the marginal information value of each participant declines as cluster size increases [30]. Specifically, at small sites (≤5 eligible participants), all eligible participants were invited to provide outcome data, but at medium sites (6 to 12), we aimed to collect outcome data from 6 participants, and from large sites (≥13), we aimed to collect data from 12. For medium and large sites, the individuals invited to participate were selected at random centrally. At medium and large sites, if a participant who was invited to take part chose not to, we invited the next participant from a randomly ordered, centrally held list to take part to replace the original participant, until the target number of participants at that site was reached, or no eligible participants remained.

The primary outcome measure was ordinal but for simplicity, because of lack of knowledge of its likely distribution, and to be scientifically conservative, we considered it as a binary outcome for our power calculations. We anticipated that the proportion of respondents “satisfied” without any of the research interventions would be between 20% and 80%, and in the absence of specific prior information considered values of the Intracluster Correlation Coefficient (ICC) between 0.01 and 0.05. We considered power to detect an effect for any of the 3 interventions, for simplicity considering each in turn, i.e., effectively conducting a power calculation for each intervention assuming the other two would have no effect. We also assumed no appreciable interactions between the 3 interventions. We calculated that, based on 21 sites with and without an intervention, and an average of 4 respondents per site (172 in total), at an ICC of 0.01, we would have 80% power to detect an increase from 20% to 40%, from 50% to 71%, or from 80% to 95% in the satisfied group. Should the ICC be 0.05, then this sample size would have provided 80% power to detect an increase from 20% to 42%, 50% to 73%, or 80% to 95%. Calculations were conducted in Stata using the “power two proportions” command and assumed a coefficient of variation in cluster size of 0.6. No power calculations were made for the secondary outcomes.

Randomisation

Sites were randomised in blocks of 8 (the number of allocation arms available) once sites had obtained the necessary approvals. In the first phase, we randomised 3 blocks each of one site size (small, medium, and large), but, subsequently, blocks were of mixed sizes. Randomisation was conducted through random permutation within blocks.

To ensure allocation blinding, although the Show RESPECT trial statistician generated the allocations for the blocks and was aware of which clinics featured in each block, a second statistician unaware of these allocations randomly permuted the clinic names within blocks. The allocations and clinic names for each block were then matched together by a third party and revealed to the trial team. Sites were informed of their randomised allocation and sent the matching Patient Update Information Sheet.

Clusters were recruited between September 2018 to May 2019. Sites were randomised between November 2018 to May 2019. The trial was registered in February 2019, which was after some sites had been randomised, due to human resource constraints.

Blinding

Once randomisation had been performed, it was not possible to blind site staff to the allocation of their site. ICON8 participants were not informed that the way they were being offered the results was determined by randomisation and were not aware of the interventions being offered to participants at other sites. The questionnaire contained an embedded informed consent element, in line with the UK Health Research Authority’s guidance on proportionate approaches to informed consent for self-administered questionnaire-based research [31], with completion and return of the questionnaire taken to indicate consent to use the data has been given.

Statistical analysis

The full statistical analysis plan can be found in . The primary outcome measure was defined only for participants who received the ICON8 trial results, and hence analysis for this outcome was restricted to participants who reported receiving the ICON8 results. For this reason, we describe the primary analysis as following modified intention to treat (mITT). All other secondary outcomes are similarly only defined for participants who received the ICON8 results, with the exception of “report finding out the ICON8 results,” which we present separately among participants who report they wanted to find the results out, and among participants who report they did not. To assess the overall effect of the intervention, it is important to interpret the results of the primary analysis alongside results concerning the possible effect of the interventions on whether participants actually found out the ICON8 results.

In the ICON8 setting, participants’ health may be poor and may deteriorate before the Show RESPECT interventions were received or between intervention exposure and follow-up by questionnaire. Participants who died or became too sick to complete a questionnaire were not considered “eligible” for data collection or analysis and were not considered as missing data.

There was no specific prior evidence to suggest whether or not there would be interactions between the interventions. We were unable to think of a mechanism for potential interactions, so designed the trial based on the assumption that the effect of each intervention (e.g., enhanced versus basic webpage) would not be substantially affected by whether or not the participant was allocated to the other interventions. Hence, the primary analysis was of the main effects of each intervention adjusting for the others. However, for the primary outcome measure, we also tested each of the 3 two-way interactions and report the effect of each of 7 intervention combinations relative to control (Basic Webpage only). Adjustments were not made for multiple testing as we view our 3 study hypotheses as distinct, so all confidence intervals (CIs) presented are at the standard 5% significance level.

To reflect the study design, we adjusted for site size stratum, and also first phase versus later randomisation phases. All models included random effects for site. Estimates were also adjusted for age (continuous–linear), education (graduate versus not), and internet use (daily versus less).

Effect measures for the interventions are estimated and presented based on regression models. Ordinal random effects logistic regression was used for the primary and other Likert-type scale outcomes unless the proportional odds assumption was clearly violated. Consider odds ratios (ORs) in relation to each way the outcome could be dichotomised, e.g., quite unsatisfied or better versus very unsatisfied, quite or very satisfied versus neither or worse. Under the proportional odds assumption, these ORs are all equal, and their common value is estimated through ordinal logistic regression. The response categories were merged for the regression analysis in the event of very low reporting of one or more categories (<5% of responses). All decisions about merging response categories were taken based on an initial dataset without cluster or allocation identifiers.

For the primary outcome measure only, we conducted prespecified subgroup analyses by age group (≤70 versus ≥71 years), allocated arm of the ICON8 trial, education category (graduate versus not), and reported internet use (daily versus not). For each subgroup analysis, the effect of each intervention within subgroups were presented, and an interaction test was conducted. All interactions were with binary subgroups, with the exception of age, which was used as a continuous variable. These subgroup analyses were conducted for each of the 3 interventions separately.

Statistical analyses were performed using Stata version 16.1 (Stata Corp, Texas).

Qualitative methods

Qualitative data collection

Semistructured interviews were carried out with participants either face-to-face (at the participant’s home or other location chosen by them) or by telephone by the lead qualitative researcher, AS, who holds an MPhil and MSc, is a research communication specialist, is female, and has been trained in qualitative research methods. The interviews were informed by a topic guide (), which was informed by PPI. The interviewer is a research communicator by profession and was involved in developing the interventions tested in Show RESPECT. The topic guide was amended as interviews proceeded to follow-up on issues that emerged in early interviews and to improve clarity [32]. Only the participant and interviewer were present during the interviews. No repeat interviews were carried out. Interviews lasted between 32 minutes to 102 minutes. The interviews were audio recorded, and field notes were made immediately after the interviews. The interviews were transcribed verbatim. The transcriptions were checked back against the recordings for accuracy, and any identifying data were redacted. Transcripts were not returned to participants. Free-text questions within the questionnaire were also used to collect qualitative data.

Sampling

Invitations to take part in interviews were sent out with the Show RESPECT questionnaire, with participants asked to complete a contact details form if they wanted to find out more about the interviews and return it alongside their questionnaire. Purposive sampling was carried out, based on their questionnaire responses, to include people offered the range of Show RESPECT interventions, different levels of satisfaction with how the results were communicated, education level, internet usage, and age. Respondents who completed the contact details form and filled one or more gaps in the sampling frame were contacted by telephone with more information about the study and, if they were willing to take part, a time and date was arranged for the interview. Participants gave written informed consent. Interviews were carried out until all the gaps in the sampling frame were filled, or until no more volunteers were available who would fill a gap in the sampling frame. Using the Information Power model [33] to assess the necessary sample size, the study aim was reasonably narrow, focusing on just one aspect of trial experience (receiving results), although it did look at several approaches to results communication. The sample specificity was dense, with all interviewees having highly relevant experiences. As described in the analysis section below, an established model was applied during the analysis. The quality of dialogue in most interviews was good, resulting in a rich dataset. The analysis strategy was cross-case. Taken together, these factors suggest that a moderate sample size should provide sufficient information power to meet the aims of the study.

Qualitative analysis

The first step of analysis was familiarisation with the data, by listening to the recordings and reading the transcripts a number of times, recording ideas for initial codes. A thematic analysis approach was employed [34]. Both inductive and deductive approaches were for coding the data, which was carried out by AS. Initial codes were then grouped into potential themes. Emerging themes were discussed with staff from the ICON8 and Show RESPECT trial management teams. As analysis proceeded, it was found that the Information-seeking and Communication Model (ISCM) [35] fitted the codes well, so codes were categorised using concepts from that model. The ISCM is a model of information behaviour that covers both information users and information providers, their contexts, the activities of information seeking, information use and communication, and the factors that affect them [36]. Network diagrams were produced to visualise links between codes within themes, and themes were reviewed in relation to the coded extracts. As themes were generated, we searched for cases which did not fit the existing structure. Inductive thematic saturation was reached at the 13th interview, as was data saturation. Participant checking did not take place, but a PPI discussion group was held to reflect on the emerging findings and interpretation. Analysis was conducted in Atlas.ti version 8.4 (ATLAS.ti Scientific Software Development GmbH).

A “following the thread” approach was used to triangulate the results of the qualitative and quantitative components of the study [37]. This was done at the analysis stage. Each data set was initially analysed using approaches applicable to the type of data to identify key themes and questions. The qualitative data were then interrogated to explore issues raised in the quantitative data (following the “thread” from one dataset to the other).

Results

Participation in Show RESPECT

shows the CONSORT diagram for the study. The 83 ICON8 sites in the UK were assessed for eligibility. Approximately 40 sites were excluded for reasons including lack of ICON8 participants eligible for Show RESPECT (5), lack of capacity (6), declining to take part (4), failing to obtain site approvals in time (12), or nonresponse to the invitation (13). About 43 (52%) ICON8 UK sites took part in Show RESPECT. shows the number of sites randomised to the interventions by site size strata, number of eligible participants who were offered the interventions, sent the questionnaire, and returned the questionnaire. Data collection took place between December 2018 and September 2019. In total, 384 ICON8 participants were offered the Show RESPECT interventions; 275 were sent the questionnaire of which 182 questionnaires were returned from 180 participants (65%) (2 of the 182 returned questionnaires were duplicates so not analysed).

CONSORT diagram for Show RESPECT.

CONSORT diagram showing flow of sites and participants through the Show RESPECT study.

Delivery of the interventions

Logs kept by sites showed that Patient Update Information Sheets went to 100% of eligible ICON8 participants at participating sites. Three ICON8 participants opted out of receiving the Mailed Printed Summary. According to site logs, all other eligible ICON8 participants at sites randomised to Mailed Printed Summaries were sent them.

Baseline characteristics of participants

shows the baseline characteristics of those who returned the questionnaire, and shows the baseline characteristics of all eligible ICON8 participants at Show RESPECT sites. The mean age of participants who returned the questionnaire was 67, with approximately one-third from each of the 3 ICON8 arms. There was a wide range of reported highest level of educational attainment, with 38 (21%) reporting no qualifications, and 41 (23%) holding a degree or higher qualification. Nearly all participants who returned the questionnaire reported English being their first language. About 61 (40%) respondents reported using the internet or email less frequently than every day, with 26 (15%) never using internet or email.

About 94 participants were invited to take part in the qualitative study, and 13 (14%) were interviewed. shows the characteristics of the interviewed participants. The parts of the sampling frame we were unable to recruit participants for were “opted out of Mailed Printed Summary,” “had used the email list,” and “aged 50 or younger.”

Primary outcome: Did the interventions improve satisfaction with how the results were shared?

Quantitative findings on satisfaction with how the results were shared

Tables shows the patient-reported outcomes relating to the experience of receiving the results, by randomised intervention. For the primary outcome of participant satisfaction with how the results were communicated, among the 3 interventions, only the Mailed Printed Summary led to a significant improvement (adjusted OR 3.15, 95% CI 1.66 to 5.98, p < 0.001). The effect sizes for the Enhanced versus Basic Webpages (adjusted OR 1.47, 95% CI 0.78 to 2.76, p = 0.235) and Email List Invitation (adjusted OR 1.38, 95% CI 0.72 to 2.63, p = 0.327) were much smaller. Furthermore, there was no evidence of interaction between any pair of interventions (interaction between webpage and printed summary p = 0.161, webpage and email p = 0.624, printed summary and email p = 0.995).

There was no evidence of heterogeneity of the effects of the interventions on the primary outcome by age, arm in ICON8, education, or reported frequency of internet or email use ( and ). When the 8 possible combinations of interventions were looked at individually, only those that contained the Mailed Printed Summary significantly improved the odds of participants reporting being satisfied with how the results were communicated ().

Qualitative findings on the reasons for satisfaction

contains a description of the categories from the qualitative data. Participants cited many reasons for their reported satisfaction, including characteristics related to the information products (clear and understandable); ease of accessing the results; receiving results in their preferred way; the process by which they received results (the Patient Update Information Sheet being sent out first to give them options); and their reflections on the emotional impact of the results and perceived impact for others. Participants who were unsatisfied with how the results were shared (16% of questionnaire respondents) cited a number of reasons, including the following: not knowing how to find out the results; problems accessing the webpage; finding the results difficult to understand; preferring to have found out the results in a different way (for example, wanting a more personal approach, such as being told the results in person or by telephone); perceived lack of timeliness in receiving the results; and the information not giving enough detail.

Did patients want the results, and did they find them out?

Nearly all participants (164/177 (93%)) reported wanting to know the results, and 145 (88%) of these 164 reported finding out the results. None of the participants who reported not wanting to know the results reported having found them out. These 13 participants were spread across the Show RESPECT interventions.

Tables shows the OR and CIs by intervention, and gives details of those who reported finding out the results by randomised intervention and subgroup. Of the 3 interventions, only the Mailed Printed Summary significantly increased the odds of finding out the results among those who wanted to know the results, with 78/83 (94%) reporting finding out the results, compared to 67/81 (83%) of those in the no Mailed Printed Summary arms, an OR of 3.57 (95% CI 1.18 to 10.77, p = 0.024), adjusted for age, education level, internet use, strata, randomisation phase, and clustering. No participants subscribed to the email list. Further information on the uptake of the interventions can be found in , and qualitative findings around participants’ desire for the results can be found in .

Did the information tell participants everything they wanted to know?

Most participants agreed that the information told them everything they wanted to know (Tables ). Participants at sites allocated to the Enhanced Webpage were more likely to agree that the information told them everything they wanted to know (adjusted OR 2.15, 95% CI 1.13 to 4.07, p = 0.019) than those allocated to the Basic Webpage. There were no significant differences between the Mailed Printed Summary versus No Mailed Printed Summary, or Email List Invitation versus No Email List Invitation. See for qualitative findings relating to this outcome.

Was the information understandable?

Approximately 80% of participants reported that they found the results easy to understand. There was no statistically significant difference in any of the randomised comparisons for this outcome (Tables ). See for qualitative findings relating to this outcome.

Was the information easy to find?

Quantitative results on whether the information was easy to find

Almost three-quarters of participants reported easily finding the results, with no significant differences between any of the Show RESPECT interventions for this outcome (Tables ).

Qualitative findings on whether the information was easy to find

The Mailed Printed Summaries were seen as accessible to everyone, as they were not reliant on people’s computer literacy or access to the internet.

“Like my mum, for instance, in her 80s, she wouldn’t have access to this [webpage], so she would only want … She would only be able to have posted results, really.” GMI02

When asked whether there were other ways in which they would have liked to have received the results, 22/91 (24%) questionnaire respondents from hospitals not randomised to the Mailed Printed Summary said they would have liked to receive the results by mail, with mail being seen as convenient and easier to access.

Rarely, questionnaire respondents reported not having been told how to access the results. It is unclear whether or not they received the Patient Update Information Sheet (which site logs record as having been sent). Others (from sites not randomised to the Mailed Printed Summary) reported receiving the Patient Update Information Sheet but missed the information on how to obtain the results that the sheet contained. About 11/180 questionnaire respondents reported difficulties accessing the webpage, either not having access to computers, or finding it hard to get onto the webpage, with some participants eventually gaining access, alone or with the help of family members, and others not succeeding. One woman decided to not try to access the results if it meant going online. Other participants, who had been able to access the results themselves, were concerned that sharing results via webpages/email alone would be inaccessible to other participants, either because of lack of computer literacy or lack of access to the internet.

“We live in quite a small community here in [County] but there’s several people that aren’t computer literate. And I think to presume that everybody has got access to web pages and what have you would be a mistake. And also, even things like the bandwidth or whatever you call it here is dire. Sometimes our connection is awful and I still know people in [County] who can’t get a connection so if they’re going to have to go to Costa Coffee to get connected to find out the results of a trial, that doesn’t feel very comfortable.” DLI01

One patient commented that the process of having to type in a URL from the Patient Update Information Sheet to get to the webpage was a barrier to accessing the results, and she would have preferred to be sent them by email without having to visit a webpage to sign up for the email list.

How did patients react to finding out the results?

While 127/145 (88%) of participants reported being glad they had found out results, only 4/138 (3%) reported regretting finding the results. About 23/140 (16%) of participants strongly or slightly agreed that they found the results upsetting, which is higher than the proportion regretting finding out the results, suggesting that while some participants were upset by the results, they did not regret having received them. There was no statistically significant difference between the arms on any of these outcomes (Tables ). See for qualitative findings around participants’ emotional responses to the results.

What did patients think about the communication interventions?

summarises the qualitative feedback from questionnaires and interviews on the interventions tested within Show RESPECT.

What were patients’ attitudes to trial participation and the ICON8 results?

With no evidence of difference between the Show RESPECT interventions (), 131/146 (90%) of respondents reported being willing to take part in future research, and 132/147 (90%) said they were likely to recommend taking part in research to others. See for qualitative findings around participants’ attitudes to the research.

Discussion

The Show RESPECT study demonstrated that sharing results with trial participants via Mailed Printed Summaries in addition to webpages increased participant satisfaction with how the results were communicated compared to webpages alone, and also enabled more participants who wanted to know the results to find them out. This satisfaction was due to the clear and understandable nature of the results summaries, ease of access, using their preferred approach, the two-stage process used, and the perceived impact of the trial (despite its “negative” results). Among women taking part in an ovarian cancer treatment trial, nearly all wanted to know the overall trial results. None of the participants who did not want to know the results found them out. It is important to look at these outcomes (satisfaction among those who received results, and proportions of people who wanted or did not want the results who received them) together, as they may not necessarily have pointed in the same direction. The two-stage process, informing participants that the results are available and how to access them, rather than automatically sending results out to all participants, was important to ensure that the wishes of the 7% of participants who did not want to find out the results were respected. This may be especially important in trials where the participant population may be vulnerable, or the results may be emotionally challenging for some participants. The additional features of the Enhanced Webpage did not increase satisfaction with how the results were communicated compared to the Basic Webpage but did lead to a higher proportion of participants reporting that it told them everything they wanted to know. The lack of uptake of the Email List Invitation suggests that for similar trial populations, it is not worth creating email lists at the end of the trial.

The qualitative findings show that participants liked the Mailed Printed Summary as an approach, as it was seen as more accessible for patients with limited access to the internet or computer literacy, and it also facilitated keeping the results for future reference, or showing to friends and family. The results sparked a range of responses, including both positive emotions and disappointment and upset, but there was no evidence to suggest that they were experienced as harmful by these individuals, and nearly all participants were glad to have received the results, even if some had found them upsetting.

Our trial employed a cluster randomised factorial design to assess 3 methods of sharing results with participants, allowing us to be confident that the differences observed were due to the interventions. Extensive PPI was carried out to ensure that the study was asking a question that was important to patients and that the interventions tested were appropriate. The interventions selected were designed to be easily replicable in other studies. The mixed methods approach allowed us to explore the reasons behind the quantitative results, while gaining an overall picture across the study population.

Budget constraints meant that we were unable to send questionnaires to all ICON8 participants at the participating sites. However, we used random selection of participants to avoid selection bias, and the characteristics of respondents in terms of age and ICON8 arm are similar to that of all eligible participants at trial sites. Our response rate of those invited to complete the questionnaire was 65%. This introduces uncertainty into the interpretation of our results, as we do not know how outcomes would vary between responders and nonresponders. However, our response rate is similar to that seen in other studies looking at communication of results to trial participants [8,38]. We cannot discern if there are differences between respondents and nonrespondents in other potentially relevant characteristics (e.g., education level, computer literacy); however, respondents cover the range of these characteristics, and the subgroup analysis showed no evidence of heterogeneity in effect by these subgroups. We do not have data on the ethnicity of participants in either the host ICON8 trial or the embedded Show RESPECT trial, meaning that we cannot assess whether ethnicity influences desire to know trial results, or how these results should be shared. We are also unable to explore the impact of what respondents’ first language was on their experience of receiving results. Future clinical trials of treatment may wish to systematically collect this information up front to assess inclusivity [39] and facilitate embedded trials, like Show RESPECT.

This randomised controlled trial contributes to the, as yet, scant evidence base on how to communicate study results to trial participants, providing high-quality evidence to a field that is dominated by observational data, surveys asking about hypothetical scenarios, and expert opinion. Our study adds comparative data around the effectiveness of different communication approaches in practice. Our results around participants’ desire for results are consistent with findings from previous studies [4]. Our participants’ positive reaction to receiving trial results is also consistent with that reported by previous studies [17,18,20,22], even in the context of potentially upsetting results [23]. lists our recommendations on points for trialists to consider around sharing results with trial participants.

Trial teams should consider when planning their study how to share results with participants, taking into account:

the characteristics of the study population, including, but not limited to, health literacy, computer literacy, access to the internet, age, and, likely, health status;

the need to offer choice to participants, allowing those who want to find out the results easy access but not forcing them on those who do not want to receive them; and

how to make it possible for participants to keep the results, so they can refer to them in the future.

Trial teams should adequately budget the necessary resources to fulfil their obligation to offer the results to study participants in a way that is appropriate to the study population—the lowest cost approaches (e.g., a basic webpage) may not be optimal for every study population.

Patient and public involvement is essential for planning how to share results with participants, identifying the outcomes and study results that are important and relevant to participants, and developing the content of results summaries.

Care is needed to ensure that the wording of results summaries is both clear to participants and sensitively written.

Show RESPECT was conducted within the context of an ovarian cancer treatment trial, where the population was women with an average age of 67 years and living in the UK. It is unclear how generalizable these results are to trials with different patient populations (e.g., all male or mixed, younger participants and participants likely more familiar with technology, trials studying non-life-threatening conditions, or where results are available soon after receiving trial treatment). Webpages are a low-cost communication approach and may be useful alongside printed summaries, giving opportunities to provide links to further information and support, and audiovisual content that Printed Summaries cannot provide. However, 4 in 10 of our respondents reported using the internet or email less than daily, with 15% never using them. Data from the UK Office for National Statistics in 2019 show that 10% of the UK population are classed as internet nonusers, having either never used the internet or not used it in the last 3 months [40]. Internet nonusers in the UK are more likely to be women, over the age of 65, have a disability, or be economically inactive (particularly those on long-term sick leave) [40]. Households with lower incomes are also less likely to have an internet connection [40]. While the number of internet nonusers has been declining in recent years, trials should be careful about relying on the internet or email to share results with participants if their trial population overlaps with some of the groups most likely to be internet nonusers. Failure to take this into account could exclude a significant proportion of participants from accessing results. If trials are to meet the ethical obligation to offer results to participants, they need to plan and budget for this in a way that is accessible to the trial population. Trials with similar patient populations should budget for Mailed Printed Summaries or ensure that alternative approaches to webpages are easily available and known to those participants for whom webpages are inaccessible. Problems accessing the internet were not the only reasons participants preferred the printed summaries; even those who use the internet daily were more likely to be satisfied with the printed summary, which made it easy for participants to file along with other trial information and to share with others.

Other trial settings may pose different challenges around sharing results; however, qualitative research from the BRACELET study, which focused on neonatal intensive care trials, found similar responses to the receipt of results among bereaved parents [41].

The ICON8 results that we were communicating (no difference between the trial regimens) may have influenced participants’ reported satisfaction, interacting with the communication interventions. The results of the ICON8 trial did not come out of the qualitative research as a major reason for satisfaction or dissatisfaction with how they were shared, and most participants in the qualitative interviews understood the importance of “negative” trial results. However, our qualitative findings do raise the question of whether modified or tailored approaches would be needed to communicate results to participants in each of the trial’s randomised groups if the trial had found a strong clinical difference. People on the poorer performing arm may need additional support or more personalised approaches to receiving results. All eventualities need to be anticipated if a feedback strategy is built into a trial protocol. Research is needed to explore whether our results are reproducible in trials that do find significant benefit or harm.

Future analysis of data collected within Show RESPECT will focus on the perspective of site staff involved in sharing the results with participants, the process used for this, and resource implications of the communication approaches used. Further research is needed to explore the issue of sharing results with the relatives of trial participants who die during a trial, to see if this is something that relatives want, and if so, how it can be done without causing unnecessary distress.

Conclusions

There is a lot of evidence that trial participants want to be offered the overall results of their trial. A common criticism is that there is not enough guidance as to how this might happen. By testing a number of approaches in a sensitive area, and finding out what is acceptable to participants, Show RESPECT moves the field forward. For the patient population of the ICON8 ovarian cancer trial, adding Mailed Printed Summaries to web-based approaches improved patient satisfaction and was better at ensuring those who wanted to know the results were able to find them out. contains recommendations based on this research.

Topic guide for qualitative interviews with patients.

(DOCX)

Click here for additional data file.

Further information on uptake of interventions.

(DOCX)

Click here for additional data file.

Further qualitative findings.

(DOCX)

Click here for additional data file.

Forest plot of satisfaction with how the results were shared, by subgroup.

(DOCX)

Click here for additional data file.

Patient Update Information Sheet.

(PDF)

Click here for additional data file.

Mailed Printed Summary.

(PDF)

Click here for additional data file.

Results email sent to those who signed up to the email list.

(PDF)

Click here for additional data file.

Show RESPECT Protocol.

(PDF)

Click here for additional data file.

Statistical analysis plan.

(PDF)

Click here for additional data file.

Description of the interventions tested in Show RESPECT.

(DOCX)

Click here for additional data file.

Baseline characteristics of all eligible participants at trial sites.

(DOCX)

Click here for additional data file.

Subgroup analyses (primary outcome only).

(DOCX)

Click here for additional data file.

Effect of combinations of interventions on satisfaction with how the results were shared.

(DOCX)

Click here for additional data file.

Qualitative data categories.

(DOCX)

Click here for additional data file.

Proportion of participants who wanted to know the results reporting finding them out, by randomisation and subgroup.

(DOCX)

Click here for additional data file.

Qualitative feedback on the interventions within Show RESPECT.

(DOCX)

Click here for additional data file.

CONSORT 2010 checklist of information to include when reporting a cluster randomised trial.

(DOCX)

Click here for additional data file.

COREQ (COnsolidated criteria for REporting Qualitative research) Checklist.

(PDF)

Click here for additional data file.

List of staff involved at Show RESPECT sites.

(DOCX)

Click here for additional data file.

17 Jun 2021

Dear Dr South,

Thank you for submitting your manuscript entitled "Show RESPECT: A cluster randomised, factorial, mixed methods trial testing approaches to sharing trial results with participants" for consideration by PLOS Medicine.

Your manuscript has now been evaluated by the PLOS Medicine editorial staff and I am writing to let you know that we would like to send your submission out for external peer review.

However, before we can send your manuscript to reviewers, we need you to complete your submission by providing the metadata that is required for full assessment. To this end, please login to Editorial Manager where you will find the paper in the 'Submissions Needing Revisions' folder on your homepage. Please click 'Revise Submission' from the Action Links and complete all additional questions in the submission questionnaire.

Please re-submit your manuscript within two working days, i.e. by Jun 21 2021 11:59PM.

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Once your full submission is complete, your paper will undergo a series of checks in preparation for peer review. Once your manuscript has passed all checks it will be sent out for review.

Feel free to email us at plosmedicine@plos.org if you have any queries relating to your submission.

Kind regards,

Callam Davidson

Associate Editor

PLOS Medicine

16 Jul 2021

Dear Dr. South,

Thank you very much for submitting your manuscript "Show RESPECT: A cluster randomised, factorial, mixed methods trial testing approaches to sharing trial results with participants" (PMEDICINE-D-21-02611R1) for consideration at PLOS Medicine.

Your paper was evaluated by an associate editor and discussed among all the editors here. It was also discussed with an academic editor with relevant expertise, and sent to independent reviewers, including a statistical reviewer. The reviews are appended at the bottom of this email and any accompanying reviewer attachments can be seen via the link below:

[LINK]

In light of these reviews, we will not be able to accept the manuscript for publication in the journal in its current form, but we would like to consider a revised version that addresses the reviewers' and editors' comments. We hope you will understand that we cannot make any decision about publication until we have seen the revised manuscript and your response, and we plan to seek re-review by one or more of the reviewers.

In revising the manuscript for further consideration, your revisions should address the specific points made by each reviewer and the editors. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments, the changes you have made in the manuscript, and include either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please submit a clean version of the paper as the main article file; a version with changes marked should be uploaded as a marked up manuscript.

In addition, we request that you upload any figures associated with your paper as individual TIF or EPS files with 300dpi resolution at resubmission; please read our figure guidelines for more information on our requirements: http://journals.plos.org/plosmedicine/s/figures. While revising your submission, please upload your figure files to the PACE digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at PLOSMedicine@plos.org.

We hope to receive your revised manuscript by Aug 06 2021 11:59PM. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

We ask every co-author listed on the manuscript to fill in a contributing author statement, making sure to declare all competing interests. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. If new competing interests are declared later in the revision process, this may also hold up the submission. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT. You can see our competing interests policy here: http://journals.plos.org/plosmedicine/s/competing-interests.

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Your article can be found in the "Submissions Needing Revision" folder.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

We look forward to receiving your revised manuscript and please don't hesitate to contact me with any questions.

Sincerely,

Callam Davidson,

Associate Editor

PLOS Medicine

plosmedicine.org

-----------------------------------------------------------

Requests from the editors:

The feeling amongst the editorial team was that the manuscript needs to be better organized and condensed before publication can be considered. Please aim to streamline the manuscript where possible, taking into account the comments from peer reviewers. One suggestion may be to separate out the presentation of the quantitative and qualitative aspects and relocate some of the qualitative work to the supplementary materials section.

In your data availability statement, please include details of where the CTU’s ‘Data Sharing Policy’ can be located (https://www.ctu.mrc.ac.uk/our-research/other-research-policy/data-sharing).

Please revise your title according to PLOS Medicine's style. Your title must be nondeclarative and not a question. It should begin with main concept if possible. I would suggest ‘Testing approaches to sharing trial results with participants: The RESPECT cluster randomised, factorial, mixed methods trial’.

Please structure your abstract using the PLOS Medicine headings (Background, Methods and Findings, Conclusions).

Abstract Background: Provide the context of why the study is important. The final sentence should clearly state the study question.

Abstract Methods and Findings:

* Please ensure that all numbers presented in the abstract are present and identical to numbers presented in the main manuscript text (e.g. 72% is included in the abstract but I could not locate this in the main text).

* Please include the years during which the study took place and length of follow up.

* In the last sentence of the Abstract Methods and Findings section, please describe the main limitation(s) of the study's methodology."

At this stage, we ask that you include a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript (you currently include something similar but please update to match the Author Summary format). This text is subject to editorial change and should be distinct from the scientific abstract. Please see our author guidelines for more information: https://journals.plos.org/plosmedicine/s/revising-your-manuscript#loc-author-summary

Please relocate paragraph 1 (lines 406-410) of the Results section into the Methods section.

Please specify whether informed consent was written or oral.

Please begin the Discussion with a short, clear summary of the article's findings and ensure the strengths and limitations of the study are clearly described in their own paragraph later in the Discussion.

Thanks for providing a CONSORT checklist. Please update the checklist to use section and paragraph numbers, rather than page numbers (as these will change in subsequent revisions).

As part of your revision, please complete and submit a copy of the COREQ Guidelines checklist, a document that aims to improve reporting of qualitative studies for purposes of post-publication data analysis and reproducibility: https://www.equator-network.org/reporting-guidelines/coreq/

Your trial appears to have been registered after the participants were randomized. Please explain in the paper why your trial was registered late.

The sample size listed in the submitted manuscript and the trial registry differ. This discrepancy appears to be due to the manuscript reporting participants offered the intervention as well as those that returned questionnaires. Please ensure it is made clear throughout the manuscript how many participants were included in your analyses.

Please include the study protocol document and analysis plan, with any amendments, as Supporting Information to be published with the manuscript if accepted.

Comments from the reviewers:

Reviewer #1: Thank you for the opportunity to review this manuscript. The authors tackle an important question regarding offering research results to participants. As ICON8 was a high-impact, and large trial, I think the experience in this manuscript will be useful to investigators considering how to communicate results to participants in planned trials.

I do not think that the manuscript is suitable for publication in its current form. There is way too much text here; over 100 pages were included in the pdf for my review: the manuscript itself is ~7500 words and the tables are large and confusing to navigate. The authors' important results will not be communicated effectively if the reader (even if familiar with gynecologic cancers and communication of research results) cannot make it through the manuscript. It may be that the qualitative component should be presented in a separate submission; in my opinion the quantitative component is more important and likely to influence research practice. Suggest a target of ~3000 words for these data.

A few additional comments:

- Suggest considering using "mailed" or "sent via post" instead of "posted." For most of the early part of this paper I thought that "posted" meant "tacked to a wall in a public place" rather than "sent via postal service."

- Description of ICON8 in lines 141-143 is confusing as written, and q 3 week chemo is not always standard of care... this is beside the point of this article and distracting to a reader familiar with the trial. Perhaps better to say RCT of three chemotherapy regimens for up-front treatment of ovarian cancer and leave it at that.

- Table 4 and according locations in the text: what do the odds ratios represent?

- The Discussion undersells the impact of making conclusions on hard-copy versus website/email list in a population primary composed of older women. I would want to see a little more specific discussion of which populations might benefit from (cheaper) more technologically-focused methods of results communication, and which might require results sent by post.

- Would be interesting to read whether the authors believe that there is an ethical obligation to budget for sending out trial results by mail in a similar patient population.

Reviewer #2: PMEDICINE-D-21-02611R1

It is great to see a robust SWAT comparing different approaches to the dissemination of results to trial participants. Overall, I found the manuscript very well presented and most of my comments are minor.

o Major comment:

* My only major comment relates to missing data. Participants are lost at two stages: 1. a number of participants who were offered the intervention were not sent the questionnaire and 2. A number who were sent the questionnaire did not return it. I understand that only a random sample of those offered the intervention were included due to logistical constrains; however, this departs from the ITT principle. Out of the 274 participants who were sent a questionnaire, only 180 (66%) returned it. This large amount of missing data creates substantial uncertainty and would probably warrant further sensitivity analyses as well as more recognition in the discussion.

o Minor/specific comments:

* Abstract, Results: I am not sure it is necessary to provide a breakdown of returned questionnaire by randomised arm in the abstract itself.

* Abstract, Conclusion: can we really say that the study "provides *clear* evidence on how to share results". I find the wording too strong considering some of the potential limitations (e.g. missing data / potential selection biases). I would suggest rewording to "the study *some* evidence"

* I note that the webpage comparison involved an enhanced webpage compared to a basic webpage (active comparator) whereas the printed summary was compared to no summary at all. The authors conclude that the printed summary had the greatest effect on satisfaction; however, I wonder this is due to the choice of comparator. Would a fairer comparison have been webpage vs no-webpage?

* I am surprised to see that the detectable differences are almost the same with an ICC of 0.01 or 0.05 (see sample size calculation). According to my calculations, with an average cluster size of 4 patients, the inflation factor due to the cluster design goes from 1.03 to 1.15 with an ICC of 0.01 and 0.05, respectively. While this is a moderate increase, I would expect it to have more impact on the detectable difference. Please confirm/clarify.

* At the start of the analysis section (line 306), the analysis population (mITT) is defined as participants who reported receiving the ICON8 results. Should not the primary analysis population include all who were sent the printed Patient Update Information Sheet (ITT), regardless of whether they actually accessed any result? Or at least all who were sent the questionnaire? If this is a missing data issue (i.e. no satisfaction data was collected in those who did not actually receive the results), some sensitivity analyses may be required (e.g. missing data imputations).

* Table 2 shows the baseline characteristics of those who returned the questionnaire. It would be interesting to compare these to participants who did not return the questionnaire to assess the potential for biases.

* I cannot find the results of the interaction test between interventions referred to on line 460. Please consider including them.

* Please consider replacing (or augmenting) Supplementary Table 3 with a forest plot to allow an easier comparison of effects across interventions. The forest plot could potentially be included as a figure in the body of the manuscript. I note that none of the interaction tests were significant; however, these are likely underpowered and therefore unlikely to detect existing interactions.

* Table 6 shows the results of those who reported finding out the results among those who wanted to know. Can you please clarify why the analysis is limited to those who wanted to know instead of all enrolled? Also, the text mentions odds ratios and 95% CI which do not appear in Table 6 which instead shows data by subgroups. I wonder whether data by subgroups should be in the supplement (were these pre-specified?). Please also consider adding the results of the logistic regression to Table 4 together with the other outcomes.

* Please consider shortening the results section as well as rearranging it to have all quantitative results together followed by all qualitative results.

* Please consider discussing the impact of missing data as a limitation.

* In the conclusion, I am not sure one can write that Posted Printed Summaries (PPS) were superior to web-based approaches in terms of patient satisfaction and ensuring those who wanted to know the results were able to find them out as there is no direct comparison between posted printed summaries and web-based approaches. In fact, when comparing the raw distribution between enhanced web-based and PPS, the numbers look very similar and one could argue that the two are equivalent and potentially both better than no active intervention. What we can conclude is that PPS showed better satisfaction than no PPS and that there was no significant difference between enhanced web display vs standard display

-Laurent Billot

Reviewer #3: This study takes on a very important topic: How do different methods of sharing trial results' influence trial participants' satisfaction with receiving results? The study design and implementation are very complex. Due to practical considerations related to studying participants in an existing randomized controlled trial, the study makes several necessary deviations from an idealized textbook study design and implementation. However, these limitations are outweighed by the novel approach to prospectively randomly assigning trial participants to several types of results sharing activities. These findings do add new information to what is already known, particularly by taking a random assignment approach rather than an observational/single-arm approach.

Below are some suggestions that may enhance the clarity of presentation of this complex study:

*The abstract does not immediately and clearly explain how the interventions were deployed. It would be good to make clear early on that the study is a site-level cluster randomized 2x2x2 such that participants at each site received one of eight possible combinations of communication activities.

*Because no participants actually subscribed to the email list, the "Email List" intervention might be best described as the "Email List Invitation" intervention or similar throughout the entire article and supporting materials. The abstract itself might be improved by making clear that no patients signed up for the email list.

*Line 322: This assumption is stated without explaining its justification. The reader would likely be helped by providing a brief rationale why "the prior assumption in the Show RESPECT trial design is that there will not be any important interactions between the three interventions."

*Line 500: It may be useful to clarify why there was so much missing data (40%) on the question about accessing the web pages. The quantity of missing data makes the percentages reported in the Results for this question relatively uninterpretable.

*In the Discussion, it is important to note that the specific results of the ICON8 trial may have influenced participants' satisfaction in general. The content of ICON8's specific results may have interacted with the communication intervention activities to influence participants' perceptions. This is not a major limitation, but should be clearly noted.

*In the Discussion, it may be useful to elaborate on the decision that "the primary outcome measure was defined only for participants who received the ICON8 trial results, and hence analysis for this outcome was restricted to participants who reported receiving the ICON8 results. For this reason, we describe the primary analysis as following modified intention to treat (mITT)." The main outcome could have been defined with respect to satisfaction with the overall approach by which that results sharing was handled in the trial, which would have allowed for inclusion of people who opted out or didn't receive results. From an ethical and/or funder perspective, this broader, more inclusive outcome may be at least as important as satisfaction with how results were communicated.

*Line 698: It is interesting to consider the importance of the finding that participants made a distinction between features they used vs what they thought others would like to use. This may have implications for how researchers work with participants to design results sharing activities for participants in their own studies.

*Line 721: The word "interventions" is used here to refer to the ICON8 trial, generating some confusion because "interventions" is mostly used to refer to the interventions in the results sharing trial. The authors might consider rephrasing to improve clarity.

*Line 827: The conclusion states: "Box 1 contains recommendations based on this research for trial teams, research funders and ethics committees." However, Box 1 contains advice that extends well beyond what was learned from this study. The researchers may consider removing points that are not directly supported by study findings or could make clear that these recommendations are drawn from other sources. Most of Box 1 reports broad suggestions that are not derived directly from the current study's specific findings and are available in existing resources for results sharing that could be cited in the paper rather than being reprinted here in a paper that already includes a great deal of detailed information.

Any attachments provided with reviews can be seen via the following link:

[LINK]

6 Aug 2021

Submitted filename: Responses to Reviewers comments v1.docx

Click here for additional data file.

2 Sep 2021

Dear Dr. South,

Thank you very much for re-submitting your manuscript "Testing approaches to sharing trial results with participants: The Show RESPECT cluster randomised, factorial, mixed methods trial" (PMEDICINE-D-21-02611R2) for review by PLOS Medicine.

I have discussed the paper with my colleagues and the academic editor and it was also seen again by two reviewers. I am pleased to say that provided the remaining editorial and production issues are dealt with we are hoping to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

We hope to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript.

Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.

We look forward to receiving the revised manuscript by Sep 09 2021 11:59PM.

Sincerely,

Callam Davidson,

Associate Editor

PLOS Medicine

cdavidson@plos.org

------------------------------------------------------------

Requests from Editors:

Please provide legends for all figures (including those in Supporting Information files).

Thank you for providing an author summary – this needs to be trimmed slightly (each section ideally should comprise 2-3 single sentence bullet points). Suggestions for shortening are as follows:

• Please merge the bullet points on lines 94 and 96 to form a single sentence (‘Previous research has shown that most people who take part in clinical trials want to be told the results of those trials, but many participants never get to find them out’).

• Please shorten the bullet/sub-bullets beginning on line 102 to ‘We randomly assigned hospitals that were part of the ovarian cancer trial to share results with the women taking part in different ways: a basic webpage or an enhanced webpage; a printed summary of the results by mail; and an email list to receive the results.’

• Please combine the bullets on lines 111 and 113 as follows: ‘Women at hospitals which sent out the printed summary by mail were more likely to be satisfied with how the results were shared and were more likely to find out the results than those at other hospitals.’

• Please make the bullet on line 115 a single sentence (‘Women who received the results said that the information was easy to understand and find, were glad, and did not regret finding out the results.

• The bullet style appears to be different in the ‘What do these findings mean?’ section.

Lines 779-801: Please remove the ‘Data availability’ and ‘Funding source’ sections from your manuscript main body – in the event of publication, this information will be published as metadata based on your responses to the submission form.

Data availability statement: ‘The individual participant data … will be available beginning 12 months after publication following the CTU’s standard moderated access approach’ - Apologies in advance if I have missed it, but I could not find any reference to the 12 month delay period in the link provided (https://www.ctu.mrc.ac.uk/our-research/other-research-policy/data-sharing/) - could you please provide further rationale for not making the data available on publication?

Lines 20 – 47: Please remove the ‘Contributor and guarantor information’, ‘Copyright’ and ‘Competing interests’ sections from the main body of your manuscript. In the event of publication, author contributions and competing interests will be published as metadata based on your submission form responses (so please ensure all relevant information is captured in your answers). PLOS applies the Creative Commons Attribution (CC BY) license to articles and other works we publish – please see https://journals.plos.org/plosmedicine/s/licenses-and-copyright for more information.

Lines 90-91: Please remove the funding information and ensure it is captured in your response to the submission form.

Comments from Reviewers:

Reviewer #1: Thank you for the opportunity to re-review this manuscript. All my previous questions/comments have been addressed satisfactorily.

Reviewer #3: This manuscript has been thoroughly revised to address the editorial staff's and reviewers' comments. Each of the comments has been thoughtfully addressed in a way that improves the manuscript. While the manuscript includes extra details (e.g. describing that the lead qualitative researcher "holds an MPhil and MSC" [Line 384]) and could be shortened further, the level of detail appears to be in service of transparency and promoting reproducibility. I am unsure whether many readers will persist through the entire manuscript. However, a trial-within-a-trial requires a great deal of explanation, and this study's design and findings advance the field. It would be a good thing if other researchers see this paper and develop similar studies building off of this one.

Any attachments provided with reviews can be seen via the following link:

[LINK]

2 Sep 2021

Submitted filename: PLOS Medicine Resubmission Covering letter v1 020921.pdf

Click here for additional data file.

7 Sep 2021

Dear Dr South,

On behalf of my colleagues and the Academic Editor, Dr Aaron S Kesselheim, I am pleased to inform you that we have agreed to publish your manuscript "Testing approaches to sharing trial results with participants: The Show RESPECT cluster randomised, factorial, mixed methods trial" (PMEDICINE-D-21-02611R3) in PLOS Medicine.

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Table 1

Recruitment of sites and participants to Show RESPECT, by site size.

	Overall	Webpage		Mailed Printed Summary		Email List Invitation
	n (%)	Basic Webpage n (%)	Enhanced Webpage n (%)	No Mailed Printed Summary n (%)	Mailed Printed Summary n (%)	No Invitation n (%)	Invitation n (%)
Number of sites
TOTAL	43 (100)	22	21	21	22	21	22
Small sites	17 (40)	8 (36)	9 (43)	8 (38)	9 (41)	9 (43)	8 (36)
Medium sites	13 (30)	7 (32)	6 (29)	6 (29)	7 (32)	6 (29)	7 (32)
Large sites	13 (30)	7 (32)	6 (29)	7 (33)	6 (27)	6 (29)	7 (32)
Number of eligible participants (offered interventions)
TOTAL	384	190	194	201	183	157	227
Small sites	54 (14)	24 (13)	30 (15)	27 (13)	27 (15)	32 (20)	22 (10)
Medium sites	76 (20)	45 (24)	31 (16)	37 (18)	39 (21)	35 (22)	41 (18)
Large sites	254 (66)	121 (64)	133 (69)	137 (68)	117 (64)	90 (57)	164 (72)
Number of participants sent the questionnaire
TOTAL	275	142	133	141	134	129	146
Small sites	53 (19)	24 (17)	29 (22)	26 (18)	27 (20)	31 (24)	22 (15)
Medium sites	67 (24)	40 (28)	27 (20)	30 (21)	37 (28)	33 (26)	34 (23)
Large sites	155 (56)	78 (55)	77 (58)	85 (60)	70 (52)	65 (50)	90 (62)
Number of participants who returned the questionnaire (number analysed)
TOTAL	180	90	90	91	89	82	98
Small sites	40 (22)	15 (17)	25 (28)	21 (23)	19 (21)	21 (26)	19 (19)
Medium sites	49 (27)	30 (33)	19 (21)	23 (25)	26 (29)	26 (32)	23 (23)
Large sites	91 (51)	45 (50)	46 (51)	47 (52)	44 (49)	35 (43)	56 (57)
Response rate (percent of questionnaires sent that were returned)
TOTAL	65%	63%	68%	65%	66%	64%	67%
Small sites	75%	63%	86%	81%	70%	68%	86%
Medium sites	73%	75%	70%	77%	70%	79%	68%
Large sites	59%	58%	60%	55%	63%	54%	62%

1Small sites had 5 or fewer ICON8 patients, medium sites 6–12 ICON8 patients, and large sites 13 or more ICON8 patients alive at the time of the site agreeing to be part of Show RESPECT.

Table 2

Baseline characteristics of participants who returned the questionnaire.

	Webpage		Mailed Printed Summary		Email List Invitation		Overall
	Basic Webpage n (%)	Enhanced Webpage n (%)	No printed summary n (%)	Printed summary n (%)	No Invitation n (%)	Invitation n (%)	n (%)
Age
Mean (IQR)	67 (61–74)	68 (62–74)	67 (61–74)	68 (62–74)	68 (63–75)	67 (61–73)	67 (62–74)
≤70 years	52 (58)	51 (57)	52 (57)	51 (57)	43 (52)	60 (61)	103 (57)
>70 years	38 (42)	39 (43)	39 (43)	38 (43)	39 (48)	38 (39)	77 (43)
ICON8 arm
Standard treatment	26 (29)	31 (34)	29 (32)	28 (31)	25 (30)	32 (33)	57 (32)
Dose fractionated paclitaxel	33 (37)	28 (31)	32 (35)	29 (33)	28 (34)	33 (34)	61 (34)
Dose fractionated carboplatin and paclitaxel	31 (34)	31 (34)	30 (33)	32 (36)	29 (35)	33 (34)	62 (34)
Highest level of educational attainment
No qualifications	14 (16)	24 (27)	25 (27)	13 (15)	19 (23)	19 (20)	38 (21)
GCSE or equivalent	28 (31)	29 (33)	26 (29)	31 (36)	32 (40)	25 (26)	57 (32)
A-level or equivalent	25 (28)	17 (19)	18 (20)	24 (28)	17 (21)	25 (26)	42 (24)
Undergraduate degree	11 (12)	13 (15)	11 (12)	13 (15)	8 (10)	16 (16)	24 (13)
Postgraduate degree	11 (12)	6 (7)	11 (12)	6 (7)	5 (6)	12 (12)	17 (10)
English as first language
Yes	82 (93)	90 (100)	85 (96)	87 (98)	78 (98)	94 (96)	172 (97)
No	6 (7)	0 (0)	4 (4)	2 (2)	2 (3)	4 (4)	6 (3)
Use of internet or email
Never	17 (19)	9 (10)	13 (14)	13 (15)	11 (13)	15 (15)	26 (15)
Once per month at most	3 (3)	4 (4)	4 (4)	3 (3)	6 (7)	1 (1)	7 (4)
More than once per month, but not as often as every week	1 (1)	10 (11)	6 (7)	5 (6)	0 (0)	11 (11)	11 (6)
Once per week or more, but not as often as every day	10 (11)	17 (19)	15 (17)	12 (13)	16 (20)	11 (11)	27 (15)
Every day	58 (65)	50 (56)	52 (58)	56 (63)	49 (60)	59 (61)	108 (60)

Table 3

Characteristics of qualitative interviewees.

Characteristics	No. of interviewees
Total number of interviewees	13
Interventions offered 1
Basic Webpage	8
Enhanced Webpage	5
Mailed Printed Summary	6
No Mailed Printed Summary	7
Email List Invitation	9
No Email List Invitation	4
Interventions used 2
Basic Webpage	5
Enhanced Webpage	2
Mailed Printed Summary	6
Opted out of Mailed Printed Summary	0
Email list	0
Had not found out the results prior to interview	2
Reported satisfaction with how the results were shared (from quantitative questionnaire) 3
Very unsatisfied, quite unsatisfied, or neither satisfied nor unsatisfied	5
Quite satisfied or very satisfied	5
Reported highest level of education 4
A levels or lower	6
Degree or higher	6
Reported frequency of internet/email use
Less than once a week	2
More than once a week	11
ICON8 randomised allocation
Three-weekly chemotherapy (control arm)	3
Weekly chemotherapy (ICON8 intervention arms)	10
Age group
≤50	0
51–60	2
61–70	6
≥71	5

1Adds up to >13 as some participants were offered more than one intervention.

2Adds up to >13 as some participants used more than one intervention.

3Data missing from 3 participants’ questionnaires.

4Data missing from 1 participant’s questionnaire.

Table 4

Reported outcomes relating to experience of receiving the results by randomised intervention: Enhanced versus Basic Webpage.

	Basic Webpage n. (%)	Enhanced Webpage n. (%)	uOR1 (95% CI) p-value	aOR2 (95% CI) p-value	Overall n (%)
Proportion of patients who reported finding out the results		Number for whom data were available for this outcome:			180
Wanted results	71 (89)	74 (88)	0.85 (0.31 to 2.32) p = 0.753	0.91 (0.33 to 2.54) p = 0.864	145 (88)
Did not want results	0	0			0 (0)
Reported satisfaction with how the results were communicated (primary outcome)		Number for whom data were available for this outcome:			145
Very unsatisfied	6 (9)	6 (8)	1.39 (0.75 to 2.59) p = 0.295	1.47 (0.78 to 2.76) p = 0.235	12 (8)
Quite unsatisfied	8 (12)	4 (5)			12 (8)
Neither	11 (16)	6 (8)			17 (12)
Quite satisfied	16 (23)	24 (32)			40 (28)
Very satisfied	28 (41)	36 (47)			64 (44)
The information told me everything I wanted to know 3		Number for whom data were available for this outcome:			146
Strongly disagree	0 (0)	3 (4)	2.13 (1.13 to 4.00) p = 0.019	2.15 (1.13 to 4.07) p = 0.019	3 (2)
Slightly disagree	5 (7)	2 (3)			7 (5)
Neither	16 (23)	10 (13)			26 (18)
Slightly agree	21 (30)	13 (17)			34 (23)
Strongly agree	28 (40)	48 (63)			76 (52)
The information was easy to understand 3		Number for whom data were available for this outcome:			146
Strongly disagree	2 (3)	4 (5)	0.92 (0.47 to 1.81) p = 0.817	1.05 (0.53 to 2.08) p = 0.895	6 (4)
Slightly disagree	4 (6)	1 (1)			5 (3)
Neither	10 (14)	8 (11)			18 (12)
Slightly agree	10 (14)	16 (21)			26 (18)
Strongly agree	44 (63)	47 (62)			91 (62)
It was easy to find the trial results		Number for whom data were available for this outcome:			144
Strongly disagree	5 (7)	3 (4)	1.34 (0.71 to 2.53) p = 0.373	1.75 (0.90 to 3.42) p = 0.100	8 (6)
Slightly disagree	5 (7)	4 (5)			9 (6)
Neither	14 (21)	7 (9)			21 (15)
Slightly agree	8 (12)	19 (25)			27 (19)
Strongly agree	36 (53)	43 (57)			79 (55)
I am glad I found out the trial results 4		Number for whom data were available for this outcome:			145
Strongly disagree	0 (0)	2 (3)	0.79 (0.38 to 1.65) p = 0.533	0.84 (0.40 to 1.75) p = 0.638	2 (1)
Slightly disagree	1 (1)	1 (1)			2 (1)
Neither	7 (10)	7 (9)			14 (10)
Slightly agree	12 (17)	13 (17)			25 (17)
Strongly agree	50 (71)	52 (69)			102 (70)
I regret finding out the trial results 5		Number for whom data were available for this outcome:			138
Strongly disagree	53 (79)	48 (68)	1.51 (0.74 to 3.01) p = 0.253	1.41 (0.68 to 2.92) p = 0.354	101 (73)
Slightly disagree	3 (4)	9 (13)			12 (9)
Neither	9 (13)	12 (17)			21 (15)
Slightly agree	2 (3)	1 (1)			3 (2)
Strongly agree	0 (0)	1 (1)			1 (1)
I found the results upsetting		Number for whom data were available for this outcome:			140
Strongly disagree	40 (59)	35 (49)	1.26 (0.66 to 2.41) p = 0.485	1.24 (0.65 to 2.39) p = 0.514	75 (54)
Slightly disagree	5 (7)	7 (10)			12 (9)
Neither agree nor disagree	11 (16)	19 (26)			30 (21)
Slightly agree	7 (10)	9 (13)			16 (11)
Strongly agree	5 (7)	2 (3)			7 (5)

1Adjusted for strata, randomisation phase (early vs late), and clustering.

2Adjusted for age, education level, and internet use as well as strata, randomisation phase (early vs late), and clustering.

3For producing the ORs for this variable, the strongly and slightly disagree categories were merged.

4For calculating the ORs, the strongly disagree, slightly disagree, and neither agree nor disagree categories were merged for this variable.

5For calculating the ORs, the neither agree nor disagree, slightly agree, and strongly agree categories were merged for this variable.

aOR, adjusted OR; OR, odds ratio; uOR, unadjusted OR.

Table 5

Reported outcomes relating to experience of receiving the results by randomised intervention: Mailed Printed Summary versus no Mailed Printed Summary.

	No Mailed Printed Summary n. (%)	Mailed Printed Summary n.(%)	uOR1 (95% CI) p-value	aOR2 (95% CI) p-value	Overall n (%)
Proportion of patients who reported finding out the results		Number for whom data were available for this outcome:			180
Wanted results	67 (83)	78 (94)	3.27 (1.10 to 9.70) p = 0.032	3.57 (1.18 to 10.77) p = 0.024	145 (88)
Did not want results	0.	0			0 (0)
Reported satisfaction with how the results were communicated (primary outcome)		Number for whom data were available for this outcome:			145
Very unsatisfied	6 (9)	6 (7)	3.27 (1.74 to 6.16) p < 0.001	3.15 (1.66 to 5.98) p < 0.001	12 (8)
Quite unsatisfied	7 (11)	5 (6)			12 (8)
Neither	12 (19)	5 (6)			17 (12)
Quite satisfied	23 (36)	17 (21)			40 (28)
Very satisfied	16 (25)	48 (59)			64 (44)
The information told me everything I wanted to know 3		Number for whom data were available for this outcome:			146
Strongly disagree	0 (0)	3 (4)	1.32 (0.70 to 2.46) p = 0.391	1.32 (0.70 to 2.48) p = 0.394	3 (2)
Slightly disagree	1 (2)	6 (7)			7 (5)
Neither	15 (23)	11 (14)			26 (18)
Slightly agree	20 (31)	14 (17)			34 (23)
Strongly agree	29 (45)	47 (58)			76 (52)
The information was easy to understand 4		Number for whom data were available for this outcome:			146
Strongly disagree	2 (3)	4 (5)	1.60 (0.82 to 3.11) p = 0.167	1.66 (0.84 to 3.27) p = 0.144	6 (4)
Slightly disagree	4 (6)	1 (1)			5 (3)
Neither	10 (14)	8 (11)			18 (12)
Slightly agree	10 (14)	16 (21)			26 (18)
Strongly agree	44 (63)	47 (62)			91 (62)
It was easy to find the trial results		Number for whom data were available for this outcome:			144
Strongly disagree	3 (5)	5 (6)	1.15 (0.61 to 2.18) p = 0.662	1.37 (0.71 to 2.66) p = 0.345	8 (6)
Slightly disagree	7 (11)	2 (3)			9 (6)
Neither	6 (9)	15 (19)			21 (15)
Slightly agree	14 (22)	13 (16)			27 (19)
Strongly agree	34 (53)	45 (56)			79 (55)
I am glad I found out the trial results 5		Number for whom data were available for this outcome:			145
Strongly disagree	0 (0)	2 (3)	1.69 (0.81 to 3.50) p = 0.161	1.69 (0.81 to 3.53) p = 0.162	2 (1)
Slightly disagree	0 (0)	2 (3)			2 (1)
Neither	9 (14)	5 (6)			14 (10)
Slightly agree	14 (21)	11 (14)			25 (17)
Strongly agree	43 (65)	59 (75)			102 (70)
I regret finding out the trial results 6		Number for whom data were available for this outcome:			138
Strongly disagree	45 (70)	56 (76)	0.93 (0.46 to 1.88) p = 0.850	0.94 (0.46 to 1.91) p = 0.856	101 (73)
Slightly disagree	7 (11)	5 (7)			12 (9)
Neither	10 (16)	11 (15)			21 (15)
Slightly agree	2 (3)	1 (1)			3 (2)
Strongly agree	0 (0)	1 (1)			1 (1)
I found the results upsetting		Number for whom data were available for this outcome:			140
Strongly disagree	35 (55)	40 (53)	1.21 (0.64 to 2.30) p = 0.564	1.31 (0.68 to 2.51) p = 0.421	75 (54)
Slightly disagree	6 (9)	6 (8)			12 (9)
Neither agree nor disagree	15 (23)	15 (20)			30 (21)
Slightly agree	8 (13)	8 (11)			16 (11)
Strongly agree	0 (0)	7 (9)			7 (5)

1Adjusted for strata, randomisation phase (early vs late), and clustering.

2Adjusted for age, education level, and internet use as well as strata, randomisation phase (early vs late), and clustering.

3For producing the ORs for this variable, the strongly and slightly disagree categories were merged.

4For producing the ORs for this variable, the strongly and slightly disagree categories were merged.

5For calculating the ORs, the strongly disagree, slightly disagree, and neither agree nor disagree categories were merged for this variable.

6For calculating the ORs, the neither agree nor disagree, slightly agree, and strongly agree categories were merged for this variable.

aOR, adjusted OR; OR, odds ratio; uOR, unadjusted OR.

Table 6

Reported outcomes relating to experience of receiving the results by randomised intervention: Email List Invitation versus no Email List Invitation.

	No Email List Invitation n. (%)	Email List Invitation n. (%)	uOR1 (95% CI) p-value	aOR2 (95% CI) p-value	Overall n (%)
Proportion of patients who reported finding out the results		Number for whom data were available for this outcome:			180
Wanted results	65 (88)	80 (89)	0.96 (0.35 to 2.61) p = 0.935	0.78 (0.27 to 2.22) p = 0.641	145 (88)
Did not want results	0	0			0 (0)
Reported satisfaction with how the results were communicated (primary outcome)		Number for whom data were available for this outcome:			145
Very unsatisfied	8 (12)	4 (5)	1.33 (0.71 to 2.47) p = 0.373	1.38 (0.72 to 2.63) p = 0.327	12 (8)
Quite unsatisfied	8 (12)	4 (5)			12 (8)
Neither	8 (12)	9 (11)			17 (12)
Quite satisfied	13 (20)	27 (34)			40 (28)
Very satisfied	29 (44)	35 (44)			64 (44)
The information told me everything I wanted to know 3		Number for whom data were available for this outcome:			146
Strongly disagree	1 (1)	2 (3)	1.12 (0.60 to 2.10) p = 0.728	1.11 (0.58 to 2.12) p = 0.759	3 (2)
Slightly disagree	3 (4)	4 (5)			7 (5)
Neither	13 (19)	13 (16)			26 (18)
Slightly agree	16 (24)	18 (23)			34 (23)
Strongly agree	34 (51)	42 (53)			76 (52)
The information was easy to understand 3		Number for whom data were available for this outcome:			146
Strongly disagree	2 (3)	4 (5)	0.85 (0.43 to 1.66) p = 0.627	0.79 (0.39 to 1.59) p = 0.500	6 (4)
Slightly disagree	3 (4)	2 (3)			5 (3)
Neither	8 (12)	10 (13)			18 (12)
Slightly agree	10 (15)	16 (20)			26 (18)
Strongly agree	44 (66)	47 (59)			91 (62)
It was easy to find the trial results		Number for whom data were available for this outcome:			144
Strongly disagree	5 (8)	3 (4)	0.81 (0.42 to 1.54) p = 0.511	0.70 (0.36 to 1.38) p = 0.306	8 (6)
Slightly disagree	4 (6)	5 (6)			9 (6)
Neither	6 (9)	15 (19)			21 (15)
Slightly agree	11 (17)	16 (20)			27 (19)
Strongly agree	39 (60)	40 (51)			79 (55)
I am glad I found out the trial results 4		Number for whom data were available for this outcome:			145
Strongly disagree	1 (2)	1 (1)	0.80 (0.39 to 1.67) p = 0.555	0.76 (0.36 to 1.62) p = 0.475	2 (1)
Slightly disagree	0 (0)	2 (3)			2 (1)
Neither	5 (8)	9 (11)			14 (10)
Slightly agree	13 (20)	12 (15)			25 (17)
Strongly agree	47 (71)	55 (70)			102 (70)
I regret finding out the trial results 5		Number for whom data were available for this outcome:			138
Strongly disagree	48 (76)	53 (71)	1.51 (0.74 to 3.08) p = 0.253	1.51 (0.72 to 3.16) p = 0.279	101 (73)
Slightly disagree	7 (11)	5 (7)			12 (9)
Neither	8 (13)	13 (17)			21 (15)
Slightly agree	0 (0)	3 (4)			3 (2)
Strongly agree	0 (0)	1 (1)			1 (1)
I found the results upsetting		Number for whom data were available for this outcome:			140
Strongly disagree	39 (61)	36 (47)	1.68 (0.87 to 3.23) p = 0.123	1.54 (0.79 to 3.00) p = 0.206	75 (54)
Slightly disagree	4 (6)	8 (11)			12 (9)
Neither agree nor disagree	14 (22)	16 (21)			30 (21)
Slightly agree	2 (3)	14 (18)			16 (11)
Strongly agree	5 (8)	2 (3)			7 (5)

1Adjusted for strata, randomisation phase (early vs late), and clustering.

2Adjusted for age, education level, and internet use as well as strata, randomisation phase (early vs late), and clustering.

3For producing the ORs for this variable, the strongly and slightly disagree categories were merged.

4For calculating the ORs, the strongly disagree, slightly disagree, and neither agree nor disagree categories were merged for this variable.

5For calculating the ORs, the neither agree nor disagree, slightly agree, and strongly agree categories were merged for this variable.

aOR, adjusted OR; OR, odds ratio; uOR, unadjusted OR.

Table 7

Reported outcomes relating to take part in or recommend taking part in research.

	Webpage			Mailed Printed Summary (MPS)			Email List Invitation			Overall n (%)
	Basic Webpage n (%)	Enhanced Webpage n (%)	uOR1 (95% CI) p-value aOR2 (95% CI) p-value	No MPS n (%)	MPS n (%)	uOR3 (95% CI) p-value aOR4 (95% CI) p-value	No Invitation n (%)	Invitation n (%)	uOR3 (95% CI) p-value aOR4 (95% CI) p-value
How willing are you to take part in future research? 5						Number for whom data were available for this outcome:				146
Very unwilling	1 (1)	2 (3)	uOR: 0.77 (0.37 to 1.62) p = 0.494 aOR: 0.80 (0.38 to 1.70) p = 0.567	3 (5)	0 (0)	uOR: 1.11 (0.54 to 2.30) p = 0.777 aOR: 1.09 (0.52 to 2.28) p = 0.827	2 (3)	1 (1)	uOR: 0.72 (0.34 to 1.51) p = 0.380 aOR: 0.70 (0.33 to 1.53) p = 0.375	3 (2)
Quite unwilling	1 (1)	1 (1)		1 (2)	1 (1)		1 (1)	1 (1)		2 (1)
Not sure	6 (8)	4 (5)		2 (3)	8 (10)		3 (4)	7 (9)		10 (7)
Quite willing	9 (13)	16 (21)		13 (20)	12 (15)		10 (15)	15 (19)		25 (17)
Very willing	54 (76)	52 (69)		47 (71)	59 (74)		51 (76)	55 (70)		106 (73)
How likely are you to recommend taking part in research to others? 6						Number for whom data were available for this outcome:				147
Very unlikely	3 (4)	3 (4)	uOR: 1.13 (0.55 to 2.31) p = 0.739 aOR: 1.17 (0.56 to 2.44) p = 0.671	5 (7)	1 (1)	uOR: 1.28 (0.63 to 2.62) p = 0.491 aOR: 1.23 (0.59 to 2.57) p = 0.579	2 (3)	4 (5)	uOR: 0.82 (0.40 to 1.69) p = 0.594 aOR: 0.77 (0.36 to 1.65) p = 0.507	6 (4)
Quite unlikely	1 (1)	1 (1)		0 (0)	2 (3)		1 (1)	1 (1)		2 (1)
Not sure	6 (8)	1 (1)		2 (3)	5 (6)		4 (6)	3 (4)		7 (5)
Quite likely	11 (15)	17 (23)		15 (22)	13 (16)		11 (16)	17 (21)		28 (19)
Very likely	51 (71)	53 (71)		45 (67)	59 (74)		49 (73)	55 (69)		104 (71)

1Adjusted for strata, randomisation phase (early vs late), and clustering.

2Adjusted for age, education level, and internet use as well as strata, randomisation phase (early vs late), and clustering.

3Adjusted for age, education level, and internet use as well as strata, randomisation phase (early vs late), and clustering.

4For producing the ORs for this variable, the strongly and slightly disagree categories were merged.

5For calculating the ORs, the very unwilling, quite unwilling, and not sure were merged for this variable.

6 For calculating the ORs, the very unlikely, quite unlikely, and not sure were merged for this variable.

aOR, adjusted OR; uOR, unadjusted OR.