Showing RESPECT: a mixed methods study into communicating the results of a Phase III clinical trial to trial participants

INTRODUCTION: Clinical trials depend on volunteers participating, often accepting increased risk and/or inconvenience. Most participants want to receive the results of trials they have participated in, while few actually receive them. There is little evidence to guide researchers on how best to share results with people taking part in trials. METHODS: I conducted a mixed methods, cluster randomised factorial trial of different approaches to sharing results with participants in the ICON8 ovarian cancer trial. (ICON8 tested two weekly chemotherapy schedules against the standard three-weekly schedule, and found no difference between the arms). I collected quantitative and qualitative data from patients and site staff. RESULTS: Patients at hospitals that were randomised to the Posted Printed Summary were more satisfied with how the results were shared and more likely to find out the results than those at hospitals not randomised to the Printed Summary. Women who received the results said that the information was easy to understand and find, and told them everything they wanted to know. Most were glad to receive the results, and did not regret finding them out, although some were, at the same time, disappointed that ICON8 interventions did not improve outcomes. This links back to their motivation for joining the trial: to benefit themselves and future patients. Site staff were supportive of sharing results with participants, seeing it as a way of respecting and valuing participants, and repaying trust. Staff at most sites found the process used to share results straight-forward and not too time-consuming. Sharing results by post increased site costs by ~£14 per participant. CONCLUSION: My findings can inform how future trials share results with participants, helping improve participants’ trial experience. Further research is required to look at how different patient populations, trial results and settings influence participant satisfaction with how results are shared

Evidence for Action on HIV Treatment and Care Systems in low and middle-income countries: background and introduction.

Despite the unprecedented scale-up of treatment for HIV in low and middle-income countries over the past decade, 49% of adults and 77% of children in need of HIV treatment still do not have access to it. ART programmes that were initially set up as an emergency response now need to be adapted to ensure that they include all the essential components and are well integrated with other health services; meet the needs of special groups, including children, adolescents, pregnant women and older people; address the mental health needs of HIV-positive people; and monitor as well as report their impact in valid and comparable ways.This supplement is an output from the Evidence for Action on HIV Treatment and Care Systems research programme consortium. Evidence for Action was a 5-year, multidisciplinary research programme, which ran from 2006 to 2011, with partners in India, Malawi, Uganda, Zambia and the United Kingdom.The primary aim of this supplement is to stimulate reflection and provide guidance on what should be in the package of HIV treatment and care systems, as national programmes look to maintain the major advances of the past decade and scale-up treatment to the other 50% of people in need of it

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

HIV treatment and care systems: the way forward.

This article summarizes the conclusions and recommendations from the articles in this supplement. It presents a call for greater clarity of thinking related to projections of future need for HIV treatment and care. The demands placed on HIV treatment and care services will increase for the foreseeable future while the resources available for this are likely to remain constant or to decline. This highlights the need for realistic budgeting by national governments. The key strategies that should be employed to sustain HIV treatment and care programmes in high HIV-prevalence low and middle-income countries over the coming decade include further decentralization, task shifting, and integration of HIV services with other chronic disease treatment services. At the same time, greater attention will need to be given to the provision of mental healthcare for those living with HIV; to the specific treatment needs of children, adolescents, pregnant women and older people; and to the standard collection of validated indicators of treatment outcomes within national programmes. For the considerable gains that have been achieved to be sustained, funders--both internal and external to the country concerned--need to prioritize investment in operations research to maximise the efficiency of their other investments in HIV treatment and care services

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

We are very thankful to the people who participated in this study and the women who contributed to our patient and public involvement activities. We are very grateful for the work of the Show RESPECT site teams in carrying out this study. We thank the members of the Show RESPECT study management group and steering group who are not authors on this manuscript: Andrew Copas, Cara Purvis, Nalinie Joharatnam-Hogan, Carlos Diaz-Montana, Archie Macnair, William J. Cragg and Conor Tweed. We thank the ICON8 trial team for their support of this project, particularly Andrew Clamp, Babasola Popoola, Francesca Schiavone, Jonathan Badrock and Rick Kaplan. We also thank the CHAPAS-4 trial team for allowing us to use CHAPAS-4 as an illustration of the application of our framework.Peer reviewe

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

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

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

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