Hit it hard: qualitative patient perspectives on the optimisation of immune checkpoint inhibition.

BACKGROUND: Immune checkpoint inhibitors have transformed the treatment landscape of many cancers, including melanoma and renal cell carcinoma (RCC). Randomised trials are evaluating outcomes from reduced ICI treatment schedules with the aim of improving quality of life, tolerability, and cost-effectiveness. This study aims to provide insight into patient and carer's perspectives of these trials. METHODS: Seven focus groups were conducted with 31 people with stage IV melanoma, RCC, or caregivers for people receiving ICI. Transcripts were analysed using reflexive thematic analysis. RESULTS: Three themes were generated: 1) "Treatment and clinic visits provide reassurance": reducing hospital visits may not improve quality of life. 2) "Assessment of personal risk versus benefit": the decision to participate in an ICI optimisation trial is influenced by treatment response, experience of toxicity and perceived logistical benefits based on the individual's circumstances. 3) "Pre-existing experience and beliefs about how treatment and trials work", including the belief that more treatment is better, influence views around ICI optimisation trials. CONCLUSION: This study provides insight into recruitment challenges and recommends strategies to enhance recruitment for ongoing ICI optimisation trials. These findings will influence the design of future ICI optimisation trials ensuring they are acceptable to patients.

Use of point-of-care haemoglobin tests to diagnose childhood anaemia in low- and middle-income countries: A systematic review.

OBJECTIVES: Anaemia is a major cause of mortality and transfusion in children in low- and middle-income countries (LMICs); however, current diagnostics are slow, costly and frequently unavailable. Point-of-care haemoglobin tests (POC(Hb)Ts) could improve patient outcomes and use of resources by providing rapid and affordable results. We systematically reviewed the literature to investigate what, where and how POC(Hb)Ts are being used by health facilities in LMICs to diagnose childhood anaemia, and to explore challenges to their use. METHODS: We searched a total of nine databases and trial registries up to 10 June 2022 using the concepts: anaemia, POC(Hb)T, LMIC and clinical setting. Adults ≥21 years and literature published >15 years ago were excluded. A single reviewer conducted screening, data extraction and quality assessment (of diagnostic studies) using QUADAS-2. Outcomes including POC(Hb)T used, location, setting, challenges and diagnostic accuracy were synthesised. RESULTS: Of 626 records screened, 41 studies were included. Evidence is available on the use of 15 POC(Hb)Ts in hospitals (n = 28, 68%), health centres (n = 9, 22%) and clinics/units (n = 10, 24%) across 16 LMICs. HemoCue (HemoCue AB, Ängelholm, Sweden) was the most used test (n = 31, 76%). Key challenges reported were overestimation of haemoglobin concentration, clinically unacceptable limits of agreement, errors/difficulty in sampling, environmental factors, cost, inter-observer variability and supply of consumables. Five POC(Hb)Ts (33%) could not detect haemoglobin levels below 4.5 g/dL. Diagnostic accuracy varied, with sensitivity and specificity to detect anaemia ranging from 24.2% to 92.2% and 70% to 96.7%, respectively. CONCLUSIONS: POC(Hb)Ts have been successfully utilised in health facilities in LMICs to diagnose childhood anaemia. However, limited evidence is available, and challenges exist that must be addressed before wider implementation. Further research is required to confirm accuracy, clinical benefits and cost-effectiveness.

Site staff perspectives on communicating trial results to participants: Cost and feasibility results from the Show RESPECT cluster randomised, factorial, mixed-methods trial.

BACKGROUND/AIMS: Sharing trial results with participants is an ethical imperative but often does not happen. Show RESPECT (ISRCTN96189403) tested ways of sharing results with participants in an ovarian cancer trial (ISRCTN10356387). Sharing results via a printed summary improved patient satisfaction. Little is known about staff experience and the costs of communicating results with participants. We report the costs of communication approaches used in Show RESPECT and the views of site staff on these approaches. METHODS: We allocated 43 hospitals (sites) to share results with trial participants through one of eight intervention combinations (2 × 2 × 2 factorial; enhanced versus basic webpage, printed summary versus no printed summary, email list invitation versus no invitation). Questionnaires elicited data from staff involved in sharing results. Open- and closed-ended questions covered resources used to share results and site staff perspectives on the approaches used. Semi-structured interviews were conducted. Interview and free-text data were analysed thematically. The mean additional site costs per participant from each intervention were estimated jointly as main effects by linear regression. RESULTS: We received questionnaires from 68 staff from 41 sites and interviewed 11 site staff. Sites allocated to the printed summary had mean total site costs of sharing results £13.71/patient higher (95% confidence interval (CI): -3.19, 30.60; p = 0.108) than sites allocated no printed summary. Sites allocated to the enhanced webpage had mean total site costs £1.91/patient higher (95% CI: -14, 18.74; p = 0.819) than sites allocated to the basic webpage. Sites allocated to the email list had costs £2.87/patient lower (95% CI: -19.70, 13.95; p = 0.731) than sites allocated to no email list. Most of these costs were staff time for mailing information and handling patients' queries. Most site staff reported no concerns about how they had shared results (88%) and no challenges (76%). Most (83%) found it easy to answer queries from patients about the results and thought the way they were allocated to share results with participants would be an acceptable standard approach (76%), with 79% saying they would follow the same approach for future trials. There were no significant effects of the randomised interventions on these outcomes. Site staff emphasised the importance of preparing patients to receive the results, including giving opt-in/opt-out options, and the need to offer further support, particularly if the results could confuse or distress some patients. CONCLUSIONS: Adding a printed summary to a webpage (which significantly improved participant satisfaction) may increase costs to sites by ~£14/patient, which is modest in relation to the cost of trials. The Show RESPECT communication interventions were feasible to implement. This information could help future trials ensure they have sufficient resources to share results with participants.

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.

Transfusion management of severe anaemia in African children: a consensus algorithm.

The phase III Transfusion and Treatment of severe anaemia in African Children Trial (TRACT) found that conservative management of uncomplicated severe anaemia [haemoglobin (Hb) 40-60 g/l] was safe, and that transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia (Hb <60 g/l) had strong but opposing effects on mortality, depending on fever status (>37·5°C). In 2020 a stakeholder meeting of paediatric and blood transfusion groups from Africa reviewed the results and additional analyses. Among all 3196 children receiving an initial transfusion there was no evidence that nutritional status, presence of shock, malaria parasite burden or sickle cell disease status influenced outcomes or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating three additional measurements of Hb post-admission, alongside clinical monitoring. The proposed algorithm should help clinicians safely implement findings from TRACT. Further research should assess its implementation in routine clinical practice.

Shifting human resources for health in the context of ART provision: qualitative and quantitative findings from the Lablite baseline study.

BACKGROUND: Lablite is an implementation project supporting and studying decentralized antiretroviral therapy (ART) rollout to rural communities in Malawi, Uganda and Zimbabwe. Task shifting is one of the strategies to deal with shortage of health care workers (HCWs) in ART provision. Evaluating Human Resources for Health (HRH) optimization is essential for ensuring access to ART. The Lablite project started with a baseline survey whose aim was to describe and compare national and intercountry delivery of ART services including training, use of laboratories and clinical care. METHODS: A cross-sectional survey was conducted between October 2011 and August 2012 in a sample of 81 health facilities representing different regions, facility levels and experience of ART provision in Malawi, Uganda and Zimbabwe. Using a questionnaire, data were collected on facility characteristics, human resources and service provision. Thirty three (33) focus group discussions were conducted with HCWs in a subset of facilities in Malawi and Zimbabwe. RESULTS: The survey results showed that in Malawi and Uganda, primary care facilities were run by non-physician clinical officers/medical assistants while in Zimbabwe, they were run by nurses/midwives. Across the three countries, turnover of staff was high especially among nurses. Between 10 and 20% of the facilities had at least one clinical officer/medical assistant leave in the 3 months prior to the study. Qualitative results show that HCWs in ART and non-ART facilities perceived a shortage of staff for all services, even prior to the introduction of ART provision. HCWs perceived the introduction of ART as having increased workload. In Malawi, the number of people on ART and hence the workload for HCWs has further increased following the introduction of Option B+ (ART initiation and life-long treatment for HIV positive pregnant and lactating women), resulting in extended working times and concerns that the quality of services have been affected. For some HCWs, perceived low salaries, extended working schedules, lack of training opportunities and inadequate infrastructure for service provision were linked to low job satisfaction and motivation. CONCLUSIONS: ART has been decentralized to lower level facilities in the context of an ongoing HRH crisis and staff shortage, which may compromise the provision of high-quality ART services. Task shifting interventions need adequate resources, relevant training opportunities, and innovative strategies to optimize the operationalization of new WHO treatment guidelines which continue to expand the number of people eligible for ART.

The Lablite project: a cross-sectional mapping survey of decentralized HIV service provision in Malawi, Uganda and Zimbabwe.

BACKGROUND: In sub-Saharan Africa antiretroviral therapy (ART) is being decentralized from tertiary/secondary care facilities to primary care. The Lablite project supports effective decentralization in 3 countries. It began with a cross-sectional survey to describe HIV and ART services. METHODS: 81 purposively sampled health facilities in Malawi, Uganda and Zimbabwe were surveyed. RESULTS: The lowest level primary health centres comprised 16/20, 21/39 and 16/22 facilities included in Malawi, Uganda and Zimbabwe respectively. In Malawi and Uganda most primary health facilities had at least 1 medical assistant/clinical officer, with average 2.5 and 4 nurses/midwives for median catchment populations of 29,275 and 9,000 respectively. Primary health facilities in Zimbabwe were run by nurses/midwives, with average 6 for a median catchment population of 8,616. All primary health facilities provided HIV testing and counselling, 50/53 (94%) cotrimoxazole preventive therapy (CPT), 52/53 (98%) prevention of mother-to-child transmission of HIV (PMTCT) and 30/53 (57%) ART management (1/30 post ART-initiation follow-up only). All secondary and tertiary-level facilities provided HIV and ART services. In total, 58/81 had ART provision. Stock-outs during the 3 months prior to survey occurred across facility levels for HIV test-kits in 55%, 26% and 9% facilities in Malawi, Uganda and Zimbabwe respectively; for CPT in 58%, 32% and 9% and for PMTCT drugs in 26%, 10% and 0% of facilities (excluding facilities where patients were referred out for either drug). Across all countries, in facilities with ART stored on-site, adult ART stock-outs were reported in 3/44 (7%) facilities compared with 10/43 (23%) facility stock-outs of paediatric ART. Laboratory services at primary health facilities were limited: CD4 was used for ART initiation in 4/9, 5/6 and 13/14 in Malawi, Uganda and Zimbabwe respectively, but frequently only in selected patients. Routine viral load monitoring was not used; 6/58 (10%) facilities with ART provision accessed centralised viral loads for selected patients. CONCLUSIONS: Although coverage of HIV testing, PMTCT and cotrimoxazole prophylaxis was high in all countries, decentralization of ART services was variable and incomplete. Challenges of staffing and stock management were evident. Laboratory testing for toxicity and treatment effectiveness monitoring was not available in most primary level facilities.

The effectiveness of interventions to disseminate the results of non-commercial randomised clinical trials to healthcare professionals: a systematic review.

BACKGROUND: It is unclear how to disseminate the results of randomised controlled trials effectively to health professionals and policymakers to improve treatment, care or prevention through changing policy and practice. This systematic review examined the effectiveness of different methods of dissemination of clinical research results to professional audiences. METHODS: We systematically reviewed the published and grey literature from 2000 to 2022 for studies assessing different approaches for disseminating clinical study results to professional audiences (health professionals, policymakers and guideline developers). Two reviewers assessed potentially relevant full texts for inclusion. We grouped studies by intervention type, synthesising findings using effect direction plots. Outcomes were grouped into out-takes (e.g. awareness, knowledge, understanding), outcomes (e.g. attitude changes) and impact (changes in policy/practice). The quality of evidence was assessed using GRADE. RESULTS: Our search identified 13,264 unique records, of which 416 full texts were assessed for eligibility. Of 60 studies that were identified as eligible for inclusion, 20 evaluated the effectiveness of interventions to disseminate clinical research results (13 RCTs, 2 observational studies, 3 pre- and post-intervention surveys and 2 cross-sectional surveys). Studies were grouped by intervention: 7 studies that involved face-to-face meetings between the target audience and trained educators were classified as 'outreach interventions'; 5 studies that provided a summary format for systematic review findings (e.g. summary of findings tables) were grouped together. There was high certainty evidence of a small beneficial impact of outreach interventions on health and moderate certainty evidence of impact on practice (mostly prescribing). There was no evidence of impact on policy and very low certainty around benefits on outcomes and out-takes. We found no consistent benefits of summary formats for systematic review results on outcomes or out-takes (moderate quality evidence). Other interventions with less evidence are reported in the Additional Materials. CONCLUSIONS: Outreach interventions to disseminate clinical research results can lead to changes in practice and improvements in health. However, these interventions can be resource-intensive. Investment is vital to identify and implement effective and cost-effective ways to disseminate results, so that the potential benefits of trials to patients can be realised. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO), CRD42019137364.

The SHOW RESPECT adaptable framework of considerations for planning how to share trial results with participants, based on qualitative findings from trial participants and site staff.

BACKGROUND: Sharing trial results with participants is a moral imperative, but too often does not happen in appropriate ways. METHODS: We carried out semi-structured interviews with patients (n = 13) and site staff (n = 11), and surveyed 180 patients and 68 site staff who were part of the Show RESPECT study, which tested approaches to sharing results with participants in the context of the ICON8 ovarian cancer trial (ISRCTN10356387). Qualitative and free-text data were analysed thematically, and findings used to develop the SHOW RESPECT adaptable framework of considerations for planning how to share trial results with participants. This paper presents the framework, with illustrations drawn from the Show RESPECT study. RESULTS: Our adaptable 'SHOW RESPECT' framework covers (1) Supporting and preparing trial participants to receive results, (2) HOw will the results reach participants?, (3) Who are the trial participants?, (4) REsults-what do they show?, (5) Special considerations, (6) Provider-who will share results with participants?, (7) Expertise and resources, (8) Communication tools and (9) Timing of sharing results. While the data upon which the framework is based come from a single trial, many of our findings are corroborated by findings from other studies in this area, supporting the transferability of our framework to trials beyond the UK ovarian cancer setting in which our work took place. CONCLUSIONS: This adaptable 'SHOW RESPECT' framework can guide researchers as they plan how to share aggregate trial results with participants. While our data are drawn from a single trial context, the findings from Show RESPECT illustrate how approaches to communication in a specific trial can influence patient and staff experiences of feedback of trial results. The framework generated from these findings can be adapted to fit different trial contexts and used by other researchers to plan the sharing of results with their own participants. TRIAL REGISTRATION: ISRCTN96189403. Registered on February 26, 2019. Show RESPECT was supported by the Medical Research Council (MC_UU_12023/24 and MC_UU_00004/08) and the NIHR CRN.

Voluntariness of consent in paediatric HIV clinical trials: a mixed-methods, cross-sectional study of participants in the CHAPAS-4 and ODYSSEY trials in Uganda.

OBJECTIVES: To examine the voluntariness of consent in paediatric HIV clinical trials and the associated factors. DESIGN: Mixed-methods, cross-sectional study combining a quantitative survey conducted concurrently with indepth interviews. SETTING AND PARTICIPANTS: From January 2021 to April 2021, we interviewed parents of children on first-line or second-line Anti-retroviral therapy (ART) in two ongoing paediatric HIV clinical trials [CHAPAS-4 (ISRCTN22964075) and ODYSSEY (ISRCTN91737921)] at the Joint Clinical Research Centre Mbarara, Uganda. OUTCOME MEASURES: The outcome measures were the proportion of parents with voluntary consent, factors affecting voluntariness and the sources of external influence. Parents rated the voluntariness of their consent on a voluntariness ladder. Indepth interviews described participants' lived experiences and were aimed at adding context. RESULTS: All 151 parents randomly sampled for the survey participated (84% female, median age 40 years). Most (67%) gave a fully voluntary decision, with a score of 10 on the voluntariness ladder, whereas 8% scored 9, 9% scored 8, 6% scored 7, 8% scored 6 and 2.7% scored 4. Trust in medical researchers (adjusted OR 9.90, 95% CI 1.01 to 97.20, p=0.049) and male sex of the parent (adjusted OR 3.66, 95% CI 1.00 to 13.38, p=0.05) were positively associated with voluntariness of consent. Prior research experience (adjusted OR 0.31, 95% CI 0.12 to 0.78, p=0.014) and consulting (adjusted OR 0.25. 95% CI 0.10 to 0.60, p=0.002) were negatively associated with voluntariness. Consultation and advice came from referring health workers (36%), spouses (29%), other family members (27%), friends (15%) and researchers (7%). The indepth interviews (n=14) identified the health condition of the child, advice from referring health workers and the opportunity to access better care as factors affecting the voluntariness of consent. CONCLUSIONS: This study demonstrated a high voluntariness of consent, which was enhanced among male parents and by parents' trust in medical researchers. Prior research experience of the child and advice from health workers and spouses were negatively associated with the voluntariness of parents' consent. Female parents and parents of children with prior research experience may benefit from additional interventions to support voluntary participation.

Do accurate HIV and antiretroviral therapy knowledge, and previous testing experiences increase the uptake of HIV voluntary counselling and testing? Results from a cohort study in rural Tanzania.

BACKGROUND: Despite the introduction of free antiretroviral therapy (ART), the use of voluntary counselling and testing (VCT) services remains persistently low in many African countries. This study investigates how prior experience of HIV and VCT, and knowledge about HIV and ART influence VCT use in rural Tanzania. METHODS: In 2006-7, VCT was offered to study participants during the fifth survey round of an HIV community cohort study that includes HIV testing for research purposes without results disclosure, and a questionnaire covering knowledge, attitudes and practices around HIV infection and HIV services. Categorical variables were created for HIV knowledge and ART knowledge, with "good" HIV and ART knowledge defined as correctly answering at least 4/6 and 5/7 questions about HIV and ART respectively. Experience of HIV was defined as knowing people living with HIV, or having died from AIDS. Logistic regression methods were used to assess how HIV and ART knowledge, and prior experiences of HIV and VCT were associated with VCT uptake, with adjustment for HIV status and socio-demographic confounders. RESULTS: 2,695/3,886 (69%) men and 2,708/5,575 women (49%) had "good" HIV knowledge, while 613/3,886 (16%) men and 585/5575 (10%) women had "good" ART knowledge. Misconceptions about HIV transmission were common, including through kissing (55% of women, 43% of men), or mosquito bites (42% of women, 34% of men).19% of men and 16% of women used VCT during the survey. After controlling for HIV status and socio-demographic factors, the odds of VCT use were lower among those with poor HIV knowledge (aOR = 0.5; p = 0.01 for men and aOR = 0.6; p < 0.01 for women) and poor ART knowledge (aOR = 0.8; p = 0.06 for men, aOR = 0.8; p < 0.01 for women), and higher among those with HIV experience (aOR = 1.3 for men and aOR = 1.6 for women, p < 0.01) and positive prior VCT experience (aOR = 2.0 for all men and aOR = 2.0 for HIV-negative women only, p < 0.001). CONCLUSIONS: Two years after the introduction of free ART in this setting, misconceptions regarding HIV transmission remain rife and knowledge regarding treatment is worryingly poor, especially among women and HIV-positive people. Further HIV-related information, education and communication activities are urgently needed to improve VCT uptake in rural Tanzania.

Patients' priorities around drug-resistant tuberculosis treatment: A multi-national qualitative study from Mongolia, South Africa and Georgia.

We conducted qualitative research exploring the treatment experience of people with DR-TB. We held nine focus group discussions with 57 adults undergoing/recently completed treatment for DR-TB in Georgia, Mongolia and South Africa. Translated transcripts were analysed using thematic analysis. We identified three higher order themes: (1) Treatment experience and the role of good relationships with healthcare providers: Treatment duration, pill burden and side-effects were challenging aspects of treatment. Side-effects/symptoms that were visible signs of illness were particularly troubling. Good relations with clinical staff helped combat fear and uncertainty regarding treatment. (2) Mental distress and opportunities for wellbeing: The shame, stigma and isolation people experienced as a result of their DR-TB diagnosis was an important cause of mental distress. No longer being infectious enabled people to resume work and socialising. Positive emotions emerged with good treatment outcomes. (3) Fear and worry along the treatment journey: Participants expressed fears about TB: infecting others; whether they would be able to endure treatment; side-effects; health consequences of treatment. Worries mostly disappeared with successful treatment. Alongside measuring side-effects, time to culture conversion and cure rates, future trials of DR-TB treatments should capture how quickly visible symptoms resolve, quality of life measures, and mental health outcomes.

Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units.

BACKGROUND: Late-phase platform protocols (including basket, umbrella, multi-arm multi-stage (MAMS), and master protocols) are generally agreed to be more efficient than traditional two-arm clinical trial designs but are not extensively used. We have gathered the experience of running a number of successful platform protocols together to present some operational recommendations. METHODS: Representatives of six UK clinical trials units with experience in running late-phase platform protocols attended a 1-day meeting structured to discuss various practical aspects of running these trials. We report and give guidance on operational aspects which are either harder to implement compared to a traditional late-phase trial or are specific to platform protocols. RESULTS: We present a list of practical recommendations for trialists intending to design and conduct late-phase platform protocols. Our recommendations cover the entire life cycle of a platform trial: from protocol development, obtaining funding, and trial set-up, to a wide range of operational and regulatory aspects such as staffing, oversight, data handling, and data management, to the reporting of results, with a particular focus on communication with trial participants and stakeholders as well as public and patient involvement. DISCUSSION: Platform protocols enable many questions to be answered efficiently to the benefit of patients. Our practical lessons from running platform trials will support trial teams in learning how to run these trials more effectively and efficiently.

Designing and implementing a communications strategy: lessons learnt from HIV and Sexual and Reproductive Health Research Programme Consortia.

In recent years there has been increasing recognition of the importance of strategic research communication. Health research organisations need to be able to communicate their research effectively to increase the probability that the findings influence policy and practice, and benefit those in greatest need. Many research funders are making communications a requirement of research funding. This paper reflects on the experience in developing and implementing communications strategies of several Research Programme Consortia funded by the Department for International Development.Different research topics will require different communications approaches in order to be effective. This is reflected in the diversity of strategies employed by different research programmes. Strategic research communications designed to influence policy and practice require different skills and expertise from those required for carrying out research and writing it up for publication in academic journals. Therefore researchers involved in communicating research should be supported in this work. One of the ways in which research programme consortia have sought to do this is through convening workshops to develop the communications skills of researchers from partner organisations. These have proven invaluable. Another way of providing ongoing support to those involved in communicating research is through a Communications Community of Practice. Where this has been used it has proven a good way to support researchers both with ideas and resources, but also a strong sense of belonging to a community that shares a common concern with communication. Developing strong partnerships with research users, other research organisations, knowledge intermediaries and other stakeholders is vital for effective communication.Embracing the challenges and opportunities presented by communicating research to influence policy practice is vital if research is to have maximum possible impact, and demonstrate its worth at a time when funding for health and development activities is at risk. Sharing lessons learnt in this process between research programmes is important to support this work.

Providing trial results to participants in phase III pragmatic effectiveness RCTs: a scoping review.

BACKGROUND: There is an ethical imperative to offer the results of trials to those who participated. Existing research highlights that less than a third of trials do so, despite the desire of participants to receive the results of the trials they participated in. This scoping review aimed to identify, collate, and describe the available evidence relating to any aspect of disseminating trial results to participants. METHODS: A scoping review was conducted employing a search of key databases (MEDLINE, EMBASE, PsycINFO, and the Cumulative Index to Nursing & Allied Health Literature (CINAHL) from January 2008 to August 2019) to identify studies that had explored any aspect of disseminating results to trial participants. The search strategy was based on that of a linked existing review. The evidence identified describes the characteristics of included studies using narrative description informed by analysis of relevant data using descriptive statistics. RESULTS: Thirty-three eligible studies, including 12,700 participants (which included patients, health care professionals, trial teams), were identified and included. Reporting of participant characteristics (age, gender, ethnicity) across the studies was poor. The majority of studies investigated dissemination of aggregate trial results. The most frequently reported mode of disseminating of results was postal. Overall, the results report that participants evaluated receipt of trial results positively, with reported benefits including improved communication, demonstration of appreciation, improved retention, and engagement in future research. However, there were also some concerns about how well the dissemination was resourced and done, worries about emotional effects on participants especially when reporting unfavourable results, and frustration about the delay between the end of the trial and receipt of results. CONCLUSIONS: This scoping review has highlighted that few high-quality evaluative studies have been conducted that can provide evidence on the best ways to deliver results to trial participants. There have been relatively few qualitative studies that explore perspectives from diverse populations, and those that have been conducted are limited to a handful of clinical areas. The learning from these studies can be used as a platform for further research and to consider some core guiding principles of the opportunities and challenges when disseminating trial results to those who participated.

"PROUD to have been involved": an evaluation of participant and community involvement in the PROUD HIV prevention trial.

BACKGROUND: The PROUD trial, a HIV prevention trial in men who have sex with men and trans women, set out to involve community representatives and trial participants in several ways. PROUD also aimed to evaluate participant involvement, to learn lessons and make recommendations for future clinical trials. METHODS: Two structured surveys, one of participant and community representatives involved in the PROUD study, and the other of researchers from the PROUD team, were carried out in 2017. The results from the surveys were reviewed quantitatively and qualitatively, and themes emerging from the data identified and synthesised. RESULTS: Survey invitations were sent to 88 involved participants, 11 community representatives and 10 researchers. The overall response rate was 55% (60/109). Overall, participants were younger than community representatives, and the majority were from Greater London. As expected, participants were predominantly involved in participant involvement meetings and community representatives in management committees.Participants and community representatives cited different motivations for getting involved in PROUD. Overall, participants were positive about their involvement; only two participants rated their experience unfavourably. Community representatives were also broadly positive. Most participants and all community representatives felt their involvement made a difference to the trial, themselves and / or the organisations they represented. However, some participant answers reflected the impact of participation in the trial rather than involvement in PPI activities.Researchers felt that PPI had positive impact across the entire trial cycle. Half felt they would have liked there to have been more PPI activity in PROUD. Researchers noted some challenges and recommendations for the future, including need for adequate funding, more engagement in PPI by all researchers, the need for PPI expertise to facilitate involvement activities and training and mentoring in PPI. CONCLUSIONS: Involving clinical trial participants and wider community representatives as active partners in PPI is feasible and valuable in trials. Researchers are encouraged to consider and appropriately resource participant involvement and prospectively evaluate all PPI within their trials.

Effectiveness and acceptability of methods of communicating the results of clinical research to lay and professional audiences: protocol for a systematic review.

BACKGROUND: Phase III randomised controlled trials aim not just to increase the sum of human knowledge, but also to improve treatment, care or prevention for future patients through changing policy and practice. To achieve this, the results need to be communicated effectively to several audiences. It is unclear how best to do this while not wasting scarce resources or causing avoidable distress or confusion. The aim of this systematic review is to examine the effectiveness, acceptability and resource implications of different methods of communication of clinical research results to lay or professional audiences, to inform practice. METHODS: We will systematically review the published literature from 2000 to 2018 for reports of approaches for communicating clinical study results to lay audiences (patients, participants, carers and the wider public) or professional audiences (clinicians, policymakers, guideline developers, other medical professionals). We will search Embase, MEDLINE, PsycINFO, ASSIA, the Cochrane Database of Systematic Reviews and grey literature sources. One reviewer will screen titles and abstracts for potential eligibility, discarding only those that are clearly irrelevant. Potentially relevant full texts will then be assessed for inclusion by two reviewers. Data extraction will be carried out by one reviewer using EPPI-Reviewer. Risk of bias will be assessed using the relevant Cochrane Risk of Bias 2.0 tool, ROBINS-1, AXIS Appraisal Tool or Critical Appraisals Skills Programme Qualitative Checklist, depending on study design. We will decide whether to meta-analyse data based on whether the included trials are similar enough in terms of participants, settings, intervention, comparison and outcome measures to allow meaningful conclusions from a statistically pooled result. We will present the data in tables and narratively summarise the results. We will use thematic synthesis for qualitative studies. DISCUSSION: Developing the search strategy for this review has been challenging as many of the concepts (patients, clinicians, clinical studies, and communication) are widely used in literature that is not relevant for inclusion in our review. We expect there will be limited comparative evidence, spread over a wide range of approaches, comparators and populations and, therefore, do not anticipate being able to carry out meta-analysis. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews PROSPERO ( CRD42019137364 ).

When participants get involved: reconsidering patient and public involvement in clinical trials at the MRC Clinical Trials Unit at UCL.

BACKGROUND: Patient and public involvement (PPI) in clinical trials aims to ensure that research is carried out collaboratively with patients and/or members of the public. However, current guidance on involving clinical trial participants in PPI activities is not consistent. METHODS: We reviewed the concept of participant involvement, based on our experience. Two workshops were held at the MRCCTU at UCL with the aim of defining participant involvement, considering its rationale; benefits and challenges; and identifying appropriate models for participant involvement in clinical trials. We considered how participant involvement might complement the involvement of other public contributors. Both workshops were attended by two patient representatives and seven staff members with experience of PPI in trials. Two of the staff members had also been involved in studies that had actively involved participants. They shared details of that work to inform discussions. RESULTS: We defined trial participants as individuals taking part in the study in question, including those who had already completed their trial treatment and/or follow-up. Because of their direct experience, involving participants may offer advantages over other public contributors; for example, in studies of new interventions or procedures, and where it is hard to identify or reach patient or community groups that include or speak for the study population. Participant involvement is possible at all stages of a trial; however, because there are no participants to involve during the design stage of a trial, prior to enrolment, participant involvement should complement and not replace involvement of PPI stakeholders. A range of models, including those with managerial, oversight or responsive roles are appropriate for involving participants; however, involvement in data safety and monitoring committees may not be appropriate where there is a potential risk of unblinding. Involvement of participants can improve the trial experience for other participants; optimising study procedures, improving communications; however, there are some specific, notably, managing participant confidentiality and practicalities relating to payments. CONCLUSIONS: Participant involvement in clinical trials is feasible and complements other forms of PPI in clinical trials. Involving active participants offers significant advantages, particularly in circumstances where trials are assessing new, or otherwise unavailable, therapies or processes. We recommend that current guidance on PPI should be updated to routinely consider including participants as valid stakeholders in PPI and potentially useful approach to PPI.

Estimating the Impact of Randomised Control Trial Results on Clinical Practice: Results from a Survey and Modelling Study of Androgen Deprivation Therapy plus Radiotherapy for Locally Advanced Prostate Cancer.

BACKGROUND: Recent trials have shown that the addition of external beam radiotherapy (EBRT) to androgen deprivation therapy (ADT) improves survival among men with locally advanced prostate cancer. OBJECTIVE: To examine the potential impact of these trials on changes in clinical practice and life-years saved. DESIGN SETTING AND PARTICIPANTS: A model was developed to examine the impact of changes in clinical practice in the UK. A survey of clinicians who treat men with prostate cancer in the UK and Canada was performed. MEASUREMENTS: Outcomes of interest were the proportion of patients treated with different approaches and the predicted number of life-years saved due to changes in clinical practice. Survey data were cross-tabulated and Pearson's χ2 tests were applied. RESULTS AND LIMITATIONS: The survey was completed by 193 clinicians (105 from the UK, 80 from Canada), of whom 70% were clinical/radiation oncologists, 8% were medical oncologists, and 15% were urologists. UK respondents were more likely to report a change in practice in response to the results (44% UK vs 21% Canada). Canadians were more likely to have already been using ADT plus radiotherapy (77% Canada vs 56% UK). The increase in the proportion of patients in the UK treated with ADT + EBRT could result in around 3730-5177 extra life-years at 15 yr from a cohort of 7930 men diagnosed in a single calendar year, compared to if all had been treated with ADT alone. CONCLUSIONS: Trial findings have changed clinical practice, meaning that men with locally advanced prostate cancer are likely to survive longer. PATIENT SUMMARY: Doctors in the UK have changed practice in response to evidence on the superiority of hormone therapy plus radiotherapy to hormone therapy alone. These changes will improve the survival of men with locally advanced prostate cancer. Further reductions in the use of hormone therapy alone could further improve survival.

Models and impact of patient and public involvement in studies carried out by the Medical Research Council Clinical Trials Unit at University College London: findings from ten case studies.

BACKGROUND: Patient and public involvement (PPI) in studies carried out by the UK Medical Research Council Clinical Trials Unit (MRC CTU) at University College London varies by research type and setting. We developed a series of case studies of PPI to document and share good practice. METHODS: We used purposive sampling to identify studies representing the scope of research at the MRC CTU and different approaches to PPI. We carried out semi-structured interviews with staff and patient representatives. Interview notes were analysed descriptively to categorise the main aims and motivations for involvement; activities undertaken; their impact on the studies and lessons learned. RESULTS: We conducted 19 interviews about ten case studies, comprising one systematic review, one observational study and 8 randomised controlled trials in HIV and cancer. Studies were either open or completed, with start dates between 2003 and 2011. Interviews took place between March and November 2014 and were updated in summer 2015 where there had been significant developments in the study (i.e. if the study had presented results subsequent to the interview taking place). A wide range of PPI models, including representation on trial committees or management groups, community engagement, one-off task-focused activities, patient research partners and participant involvement had been used. Overall, interviewees felt that PPI had a positive impact, leading to improvements, for example in the research question; study design; communication with potential participants; study recruitment; confidence to carry out or complete a study; interpretation and communication of results; and influence on future research. CONCLUSIONS: A range of models of PPI can benefit clinical studies. Researchers should consider different approaches to PPI, based on the desired impact and the people they want to involve. Use of multiple models may increase the potential impacts of PPI in clinical research.