The impact generated by public and charity-funded research in the UK: A systematic literature review

Objective: To identify, synthesize and critically assess the empirical evidence of the impact generated by public and charity funded health research in the United Kingdom. Methods: We conducted a systematic literature review of the empirical evidence published in English in peer-reviewed journals between 2006 and 2017. Studies meeting the inclusion criteria were selected and their findings were analysed using the Payback Framework into five main categories: knowledge, benefits to future research and research use, benefits from informing policy and product development, health and health sector benefits and broader economic benefits. We assessed the studies for risk of selection, reporting and funding bias. Results: Thirteen studies met the inclusion criteria. The majority of the studies (10 out of 13) assessed impact at multiple domains including the main 5 key themes of the Payback Framework. All of them showed a positive impact of funded research on outcomes. Of those studies, one presented low risk of bias (8%), 6 studies were classified as presenting moderate risk of bias (46%) and 6 studies presented high risk of bias (46%). Conclusions: Empirical evidence on the impact of public and charity funded research is still limited and subject to funding and selection bias. More work is needed to establish the causal effects of funded research on academic outcomes, policy, practice and the broader economy

Prognostic value of pathological lymph node status and primary tumour regression grading following neoadjuvant chemotherapy – results from the MRC OE02 oesophageal cancer trial

Aims: Neoadjuvant chemotherapy (NAC) remains an important therapeutic option for advanced oesophageal cancer (OC). Pathological tumour regression grade (TRG) may offer additional information by directing adjuvant treatment and/or follow‐up but its clinical value remains unclear. We analysed the prognostic value of TRG and associated pathological factors in OC patients enrolled in the Medical Research Council (MRC) OE02 trial. Methods and results: Histopathology was reviewed in 497 resections from OE02 trial participants randomised to surgery (S group; n = 244) or NAC followed by surgery [chemotherapy plus surgery (CS) group; n = 253]. The association between TRG groups [responders (TRG1–3) versus non‐responders (TRG4–5)], pathological lymph node (LN) status and overall survival (OS) was analysed. One hundred and ninety‐five of 253 (77%) CS patients were classified as ‘non‐responders’, with a significantly higher mortality risk compared to responders [hazard ratio (HR) = 1.53, 95% confidence interval (CI) = 1.05–2.24, P = 0.026]. OS was significantly better in patients without LN metastases irrespective of TRG [non‐responders HR = 1.87, 95% CI = 1.33–2.63, P < 0.001 versus responders HR = 2.21, 95% CI = 1.11–4.10, P = 0.024]. In multivariate analyses, LN status was the only independent factor predictive of OS in CS patients (HR = 1.93, 95% CI = 1.42–2.62, P < 0.001). Exploratory subgroup analyses excluding radiotherapy‐exposed patients (n = 48) showed similar prognostic outcomes. Conclusion: Lymph node status post‐NAC is the most important prognostic factor in patients with resectable oesophageal cancer, irrespective of TRG. Potential clinical implications, e.g. adjuvant treatment or intensified follow‐up, reinforce the importance of LN dissection for staging and prognostication

Telecare motivational interviewing for diabetes patient education and support : a randomised controlled trial based in primary care comparing nurse and peer supporter delivery

Background: There is increasing interest in developing peer-led and 'expert patient'-type interventions, particularly to meet the support and informational needs of those with long term conditions, leading to improved clinical outcomes, and pressure relief on mainstream health services. There is also increasing interest in telephone support, due to its greater accessibility and potential availability than face to face provided support. The evidence base for peer telephone interventions is relatively weak, although such services are widely available as support lines provided by user groups and other charitable services. Methods/Design: In a 3-arm RCT, participants are allocated to either an intervention group with Telecare service provided by a Diabetes Specialist Nurse (DSN), an intervention group with service provided by a peer supporter (also living with diabetes), or a control group receiving routine care only. All supporters underwent a 2-day training in motivational interviewing, empowerment and active listening skills to provide telephone support over a period of up to 6 months to adults with poorly controlled type 2 diabetes who had been recommended a change in diabetes management (i.e. medication and/or lifestyle changes) by their general practitioner (GP). The primary outcome is self-efficacy; secondary outcomes include HbA1c, total and HDL cholesterol, blood pressure, body mass index, and adherence to treatment. 375 participants (125 in each arm) were sought from GP practices across West Midlands, to detect a difference in self-efficacy scores with an effect size of 0.35, 80% power, and 5% significance level. Adults living with type 2 diabetes, with an HbA1c > 8% and not taking insulin were initially eligible. A protocol change 10 months into the recruitment resulted in a change of eligibility by reducing HbA1c to > 7.4%. Several qualitative studies are being conducted alongside the main RCT to describe patient, telecare supporter and practice nurse experience of the trial. Discussion and implications of the research: With its focus on self-management and telephone peer support, the intervention being trialled has the potential to support improved self-efficacy and patient experience, improved clinical outcomes and a reduction in diabetes-related complications

Corticosteroid responsiveness following mepolizumab in severe eosinophilic asthma—a randomized, placebo-controlled crossover trial (MAPLE)

Mepolizumab inhibits interleukin-5 (IL-5) activity, reduces exacerbation frequency and maintenance oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma (SEA). Some patients remain dependent on OCS despite anti-IL-5 treatment suggesting residual corticosteroid responsive mechanisms. We aimed to determine the clinical and anti-inflammatory effects of OCS in patients with SEA on mepolizumab. We conducted a randomised, triple-blind, placebo-controlled crossover trial of prednisolone (0.5mg/kg/day, maximum 40mg/day, for 14±2 days) in adults with SEA after ≥12 weeks of mepolizumab. We compared change in asthma symptoms, quality of life, lung function measured by spirometry and airwave oscillometry, FeNO, and blood and sputum eosinophil cell count after prednisolone and placebo. 27 patients completed the study. Prednisolone did not improve ACQ-5 (mean difference in change for prednisolone vs placebo -0.23, 95% CI -0.58 to 0.11), mini-AQLQ (0.03, 95% CI -0.26 to 0.42), SGRQ (0.24, 95% CI -3.20 to 3.69) or VAS scores for overall asthma symptoms (0.11, 95% CI -0.58 to 0.80). The mean difference for FEV in favour of prednisolone was 105ml (95% CI -4 to 213 ml); FEF 484ml/s (95% CI 151 to 816 ml/s); FeNO reduction 41% (95% CI 25 to 54%); blood eosinophil count reduction 49% (95% CI 31 to 62%); and percentage of sputum eosinophil reduction 71% (95% CI 26 to 89%). OCS improved small airway obstruction and reduced biomarkers of type 2 inflammation but had no significant effect on symptoms or quality of life in patients with severe eosinophilic asthma receiving treatment with mepolizumab. [Abstract copyright: Copyright © 2022. Published by Elsevier Inc.

Design considerations in a clinical trial of a cognitive behavioural intervention for the management of low back pain in primary care : Back Skills Training Trial

Background Low back pain (LBP) is a major public health problem. Risk factors for the development and persistence of LBP include physical and psychological factors. However, most research activity has focused on physical solutions including manipulation, exercise training and activity promotion. Methods/Design This randomised controlled trial will establish the clinical and cost-effectiveness of a group programme, based on cognitive behavioural principles, for the management of sub-acute and chronic LBP in primary care. Our primary outcomes are disease specific measures of pain and function. Secondary outcomes include back beliefs, generic health related quality of life and resource use. All outcomes are measured over 12 months. Participants randomised to the intervention arm are invited to attend up to six weekly sessions each of 90 minutes; each group has 6–8 participants. A parallel qualitative study will aid the evaluation of the intervention. Discussion In this paper we describe the rationale and design of a randomised evaluation of a group based cognitive behavioural intervention for low back pain

Increasing boys' and girls' intention to avoid teenage pregnancy: a cluster randomised control feasibility trial of an interactive video drama based intervention in post-primary schools in Northern Ireland

Background: Adolescent men have a vital yet neglected role in reducing unintended teenage pregnancy (UTP). There is a need for gender-sensitive educational interventions. Objectives: To determine the value and feasibility of conducting an effectiveness trial of the If I Were Jack Relationship and Sexuality Education (RSE) intervention in a convenience quota sample of post-primary schools in Northern Ireland. Secondary objectives were to assess acceptability to schools, pupils (male/female, aged 14–15 years) and parents/guardians; to identify optimal delivery structures and systems; to establish participation rates and reach, including equality of engagement of different socioeconomic and religious types; to assess trial recruitment and retention rates; to assess variation in normal RSE practice; to refine survey instruments; to assess differences in outcomes for male and female pupils; to identify potential effect sizes that might be detected in an effectiveness trial and estimate appropriate sample size for that trial; and to identify costs of delivery and pilot methods for assessing cost-effectiveness. Design: Cluster randomised Phase II feasibility trial with an embedded process and economic evaluation. Intervention: A teacher-delivered classroom-based RSE resource – an interactive video drama (IVD) with classroom materials, teacher training and an information session for parents – to immerse young people in a hypothetical scenario of Jack, a teenager whose girlfriend is unintentionally pregnant. It addresses gender inequalities in RSE by focusing on young men and is designed to increase intentions to avoid UTP by encouraging young people to delay sexual intercourse and to use contraception consistently in sexual relationships. Main outcome measures: Abstinence from sexual intercourse (delaying initiation of sex or returning to abstinence) or avoidance of unprotected sexual intercourse (consistent correct use of contraception). Secondary outcomes included Knowledge, Attitudes, Skills and Intentions. Results: The intervention proved acceptable to schools, pupils and parents, as evidenced through positive process evaluation. One minor refinement to the parental component was required, namely the replacement of the teacher-led face-to-face information session for parents by online videos designed to deliver the intervention to parents/guardians into their home. School recruitment was successful (target 25%, achieved 38%). No school dropped out. Pupil retention was successful (target 85%, achieved 93%). The between-group difference in incidence of unprotected sex of 1.3% (95% confidence interval 0.55% to 2.2%) by 9 months demonstrated an effect size consistent with those reported to have had meaningful impact on UTP rates (resulting in an achievable sample size of 66 schools at Phase III). Survey instruments showed high acceptability and reliability of measures (Cronbach’s alpha: 0.5–0.7). Economic evaluation at Phase III is feasible because it was possible to (1) identify costs of delivering If I Were Jack (mean cost per pupil, including training of teachers, was calculated as £13.66); and (2) develop a framework for assessing cost-effectiveness. Conclusion: Trial methods were appropriate, and recruitment and retention of schools and pupils was satisfactory, successfully demonstrating all criteria for progression to a main trial. The perceived value of culture- and gender-sensitive public health interventions has been highlighted. Future work: Progression to a Phase III effectiveness trial. Trial registration: Current Controlled Trials ISRCTN99459996. Funding: This project was funded by the NIHR Public Health Research programme and will be published in full in Public Health Research; Vol. 5, No. 1. See the NIHR Journals Library website for further project information

The decreased molar ratio of phytate:zinc improved zinc nutriture in South Koreans for the past 30 years (1969-1998)

For the assessment of representative and longitudinal Zn nutriture in South Koreans, Zn, phytate and Ca intakes were determined using four consecutive years of food consumption data taken from Korean National Nutrition Survey Report (KNNSR) every 10 years during 1969-1998. The nutrient intake data are presented for large city and rural areas. Zn intake of South Koreans in both large city and rural areas was low during 1969-1988 having values between 4.5-5.6 mg/d, after then increased to 7.4 (91% Estimated Average Requirements for Koreans, EAR = 8.1 mg/d) and 6.7 mg/d (74% EAR) in 1998 in large city and rural areas, respectively. In 1968, Zn intake was unexpectedly higher in rural areas due to higher grain consumption, but since then until 1988 Zn intake was decreased and increased back in 1998. Food sources for Zn have shifted from plants to a variety of animal products. Phytate intake of South Koreans during 1969-1978 was high mainly due to the consumption of grains and soy products which are major phytate sources, but decreased in 1998. The molar ratios of phytate:Zn and millimmolar ratio of phytate×Ca:Zn were decreased due to the decreased phytate intake in South Koreans, which implies higher zinc bioavailability. The study results suggest that Zn nutriture has improved by increased dietary Zn intakes and the decreased molar ratio of phytate:Zn in South Koreans in both large city and rural areas

The feasibility of a randomised controlled trial of physiotherapy for adults with joint hypermobility syndrome

© Queen’s Printer and Controller of HMSO 2016. Background: Joint hypermobility syndrome (JHS) is a heritable disorder associated with laxity and pain in multiple joints. Physiotherapy is the mainstay of treatment, but there is little research investigating its clinical effectiveness. Objectives: To develop a comprehensive physiotherapy intervention for adults with JHS; to pilot the intervention; and to conduct a pilot randomised controlled trial (RCT) to determine the feasibility of conducting a future definitive RCT. Design: Patients’ and health professionals’ perspectives on physiotherapy for JHS were explored in focus groups (stage 1). A working group of patient research partners, clinicians and researchers used this information to develop the physiotherapy intervention. This was piloted and refined on the basis of patients’ and physiotherapists’ feedback (stage 2). A parallel two-arm pilot RCT compared ‘advice’ with ‘advice and physiotherapy’ (stage 3). Random allocation was via an automated randomisation service, devised specifically for the study. Owing to the nature of the interventions, it was not possible to blind clinicians or patients to treatment allocation. Setting: Stage 1 – focus groups were conducted in four UK locations. Stages 2 and 3 – piloting of the intervention and the pilot RCT were conducted in two UK secondary care NHS trusts. Participants: Stage 1 – patient focus group participants (n = 25, three men) were aged > 18 years, had a JHS diagnosis and had received physiotherapy within the preceding 12 months. The health professional focus group participants (n = 16, three men; 14 physiotherapists, two podiatrists) had experience of managing JHS. Stage 2 – patient participants (n = 8) were aged > 18 years, had a JHS diagnosis and no other musculoskeletal conditions causing pain. Stage 3 – patient participants for the pilot RCT (n = 29) were as for stage 2 but the lower age limit was 16 years. Intervention: For the pilot RCT (stage 3) the advice intervention was a one-off session, supplemented by advice booklets. All participants could ask questions specific to their circumstances and receive tailored advice. Participants were randomly allocated to ‘advice’ (no further advice or physiotherapy) or ‘advice and physiotherapy’ (an additional six 30-minute sessions over 4 months). The physiotherapy intervention was supported by a patient handbook and was delivered on a one-to-one patient–therapist basis. It aimed to increase patients’ physical activity through developing knowledge, understanding and skills to better manage their condition. Main outcome measures: Data from patient and health professional focus groups formed the main outcome from stage 1. Patient and physiotherapist interview data also formed a major component of stages 2 and 3. The primary outcome in stage 3 related to the feasibility of a future definitive RCT [number of referrals, recruitment and retention rates, and an estimate of the value of information (VOI) of a future RCT]. Secondary outcomes included clinical measures (physical function, pain, global status, self-reported joint count, quality of life, exercise self-efficacy and adverse events) and resource use (to estimate cost-effectiveness). Outcomes were recorded at baseline, 4 months and 7 months. Results: Stage 1 – JHS is complex and unpredictable. Physiotherapists should take a long-term holistic approach rather than treating acutely painful joints in isolation. Stage 2 – a user-informed physiotherapy intervention was developed and evaluated positively. Stage 3 – recruitment to the pilot RCT was challenging, primarily because of a perceived lack of equipoise between advice and physiotherapy. The qualitative evaluation provided very clear guidance to inform a future RCT, including enhancement of the advice intervention. Some patients reported that the advice intervention was useful and the physiotherapy intervention was again evaluated very positively. The rate of return of questionnaires was low in the advice group but reasonable in the physiotherapy group. The physiotherapy intervention showed evidence of promise in terms of primary and secondary clinical outcomes. The advice arm experienced more adverse events. The VOI analysis indicated the potential for high value from a future RCT. Such a trial should form the basis of future research efforts. Conclusion: A future definitive RCT of physiotherapy for JHS seems feasible, although the advice intervention should be made more robust to address perceived equipoise and subsequent attrition. Trial registration: Current Controlled Trials ISRCTN29874209. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 47. See the NIHR Journals Library website for further project information

An intervention to promote patient participation and self-management in long term conditions: development and feasibility testing

<p>Abstract</p> <p>Background</p> <p>There is worldwide interest in managing the global burden of long-term conditions. Current health policy places emphasis on self-management and supporting patient participation as ways of improving patient outcomes and reducing costs. However, achieving genuine participation is difficult. This paper describes the development of an intervention designed to promote participation in the consultation and facilitate self-management in long-term conditions. In line with current guidance on the development of complex interventions, our aim was to develop and refine the initial intervention using qualitative methods, prior to more formal evaluation.</p> <p>Methods</p> <p>We based the intervention on published evidence on effective ways of improving participation. The intervention was developed, piloted and evaluated using a range of qualitative methods. Firstly, focus groups with stakeholders (5 patients and 3 clinicians) were held to introduce the prototype and elucidate how it could be improved. Then individual 'think aloud' and qualitative interviews (n = 10) were used to explore how patients responded to and understood the form and provide further refinement.</p> <p>Results</p> <p>The literature highlighted that effective methods of increasing participation include the use of <it>patient reported outcome measures </it>and <it>values clarification exercises</it>. The intervention (called PRISMS) integrated these processes, using a structured form which required patients to identify problems, rate their magnitude and identify their priority. PRISMS was well received by patients and professionals. In the individual qualitative interviews the main themes that emerged from the data related to (a) the content of the PRISMS (b) the process of completing PRISMS and how it could be operationalised in practice and (c) the outcomes of completing PRISMS for the patient. A number of different functions of PRISMS were identified by patients including its use as an aide-memoire, to provide a focus to consultations, to give permission to discuss certain issues, and to provide greater tailoring for the patient.</p> <p>Conclusions</p> <p>There was evidence that patients found the PRISMS form acceptable and potentially useful. The challenge encountered by patients in completing PRISMS may encourage exploration of these issues within the consultation, complementing the more 'task focussed' aspects of consultations resulting from introduction of clinical guidelines and financial incentives. Further research is required to provide a rigorous assessment of the ability of tools like PRISMS to achieve genuine change in the process and outcome of consultations.</p