Examining the effectiveness of the Gateway conditional caution on health and well-being of young adults committing low-level offences: a randomised controlled trial.

BACKGROUND: Young adults who commit low-level offences commonly have a range of health and social needs and are significantly over-represented in the criminal justice system. These young adults may need to attend court and potentially receive penalties including imprisonment. Alternative routes exist, which can help address the underlying causes of offending. Some feel more should be done to help young adults entering the criminal justice system. The Gateway programme was a type of out-of-court disposal developed by Hampshire Constabulary, which aimed to address the complex needs of young adults who commit low-level crimes. This study aimed to evaluate the effectiveness and cost-effectiveness of the Gateway programme, issued as a conditional caution, compared with usual process. METHODS: The Gateway study was a pragmatic, parallel-group, superiority randomised controlled trial that recruited young adults who had committed a low-level offence from four sites covering Hampshire and Isle of Wight. The primary outcome was mental health and well-being measured using the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes were quality of life, alcohol and drug use, and recidivism. Outcomes were measured at 4, 16 and 52 weeks postrandomisation. RESULTS: Due to issues with retention of participants and low data collection rates, recruitment ended early, with 191 eligible participants randomised (Gateway 109; usual process 82). The primary outcome was obtained for 93 (48.7%) participants at 4 weeks, 93 (48.7%) at 16 weeks and 43 (22.5%) at 1 year. The high attrition rates meant that effectiveness could not be assessed as planned. CONCLUSIONS: Gateway is the first trial in a UK police setting to have a health-related primary outcome requiring individual data collection, rather than focusing solely on recidivism. We demonstrated that it is possible to recruit and randomise from the study population, however follow-up rates were low. Further work is needed to identify ways to facilitate engagement between researchers and vulnerable populations to collect data. TRIAL REGISTRATION NUMBER: ISRCTN11888938.

Antibiotics for lower respiratory tract infection in children presenting in primary care: ARTIC-PC RCT.

Background: Antimicrobial resistance is a global health threat. Antibiotics are commonly prescribed for children with uncomplicated lower respiratory tract infections, but there is little randomised evidence to support the effectiveness of antibiotics in treating these infections, either overall or relating to key clinical subgroups in which antibiotic prescribing is common (chest signs; fever; physician rating of unwell; sputum/rattly chest; shortness of breath). Objectives: To estimate the clinical effectiveness and cost-effectiveness of amoxicillin for uncomplicated lower respiratory tract infections in children both overall and in clinical subgroups. Design: Placebo-controlled trial with qualitative, observational and cost-effectiveness studies. Setting: UK general practices. Participants: Children aged 1-12 years with acute uncomplicated lower respiratory tract infections. Outcomes: The primary outcome was the duration in days of symptoms rated moderately bad or worse (measured using a validated diary). Secondary outcomes were symptom severity on days 2-4 (0 = no problem to 6 = as bad as it could be); symptom duration until very little/no problem; reconsultations for new or worsening symptoms; complications; side effects; and resource use. Methods: Children were randomised to receive 50 mg/kg/day of oral amoxicillin in divided doses for 7 days, or placebo using pre-prepared packs, using computer-generated random numbers by an independent statistician. Children who were not randomised could participate in a parallel observational study. Semistructured telephone interviews explored the views of 16 parents and 14 clinicians, and the data were analysed using thematic analysis. Throat swabs were analysed using multiplex polymerase chain reaction. Results: A total of 432 children were randomised (antibiotics, n = 221; placebo, n = 211). The primary analysis imputed missing data for 115 children. The duration of moderately bad symptoms was similar in the antibiotic and placebo groups overall (median of 5 and 6 days, respectively; hazard ratio 1.13, 95% confidence interval 0.90 to 1.42), with similar results for subgroups, and when including antibiotic prescription data from the 326 children in the observational study. Reconsultations for new or worsening symptoms (29.7% and 38.2%, respectively; risk ratio 0.80, 95% confidence interval 0.58 to 1.05), illness progression requiring hospital assessment or admission (2.4% vs. 2.0%) and side effects (38% vs. 34%) were similar in the two groups. Complete-case (n = 317) and per-protocol (n = 185) analyses were similar, and the presence of bacteria did not mediate antibiotic effectiveness. NHS costs per child were slightly higher (antibiotics, £29; placebo, £26), with no difference in non-NHS costs (antibiotics, £33; placebo, £33). A model predicting complications (with seven variables: baseline severity, difference in respiratory rate from normal for age, duration of prior illness, oxygen saturation, sputum/rattly chest, passing urine less often, and diarrhoea) had good discrimination (bootstrapped area under the receiver operator curve 0.83) and calibration. Parents found it difficult to interpret symptoms and signs, used the sounds of the child's cough to judge the severity of illness, and commonly consulted to receive a clinical examination and reassurance. Parents acknowledged that antibiotics should be used only when 'necessary', and clinicians noted a reduction in parents' expectations for antibiotics. Limitations: The study was underpowered to detect small benefits in key subgroups. Conclusion: Amoxicillin for uncomplicated lower respiratory tract infections in children is unlikely to be clinically effective or to reduce health or societal costs. Parents need better access to information, as well as clear communication about the self-management of their child's illness and safety-netting. Future work: The data can be incorporated in the Cochrane review and individual patient data meta-analysis. Trial registration: This trial is registered as ISRCTN79914298. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 9. See the NIHR Journals Library website for further project information.

Children are commonly prescribed antibiotics for chest infections, but such infections are becoming resistant to antibiotics, and it is not clear if antibiotics work in treating them. A total of 432 children who saw their general practitioner with a chest infection were given either an antibiotic (amoxicillin) or a placebo (no antibiotic) for 7 days. Symptom diaries documented the infection's duration and its side effects. Children not in the placebo study were able to participate in another study that documented the same outcomes (an 'observational study'). We interviewed parents, doctors and nurses about their observations and concerns. Our patient and public involvement and engagement work with parents indicated that a 3-day symptom reduction was required to justify giving antibiotics. After seeing the doctor, parents whose children received antibiotics rated infective symptoms as moderately bad or worse for 5 days, and parents whose children received the placebo rated these for 6 days. Side effects and complications were similar in the two groups. Findings were similar when including the results of the observational study, and for children in whose chest the doctor could hear wheeze or rattles; who had fever; who were rated by the doctor as more unwell, who were short of breath, or who had had bacteria detected in the throat. The costs to the NHS per child were similar (antibiotics, £29; placebo, £26), and the wider costs to society were the same (antibiotics, £33; placebo, £33). Parents found it difficult to interpret their child's symptoms, and commonly used the sound of the cough to judge severity. Parents commonly consulted to receive an examination and reassurance, and accepted that antibiotics should be used only when 'necessary'. Clinicians noted a reduction in parents' expectations for antibiotics. Amoxicillin for chest infections in children is unlikely to be effective. General practitioners should support parents to self-manage at home and give clear communication about when and how to seek medical help if they continue to be concerned.

Determining the clinical and cost-effectiveness of nasal sprays and a physical activity and stress management intervention to reduce respiratory tract infections in primary care: A protocol for the 'Immune Defence' randomised controlled trial.

BACKGROUND: Most adults in the UK experience at least one viral respiratory tract infection (RTI) per year. Individuals with comorbidities and those with recurrent RTIs are at higher risk of infections. This can lead to more severe illness, worse quality of life and more days off work. There is promising evidence that using common nasal sprays or improving immune function through increasing physical activity and managing stress, may reduce the incidence and severity of RTIs. METHODS AND DESIGN: Immune Defence is an open, parallel group, randomised controlled trial. Up to 15000 adults from UK general practices, with a comorbidity or risk factor for infection and/or recurrent infections (3 or more infections per year) will be randomly allocated to i) a gel-based nasal spray designed to inhibit viral respiratory infections; ii) a saline nasal spray, iii) a digital intervention promoting physical activity and stress management, or iv) usual care with brief advice for managing infections, for 12 months. Participants will complete monthly questionnaires online. The primary outcome is the total number of days of illness due to RTIs over 6 months. Key secondary outcomes include: days with symptoms moderately bad or worse; days where work/normal activities were impaired; incidence of RTI; incidence of COVID-19; health service contacts; antibiotic usage; beliefs about antibiotics; intention to consult; number of days of illness in total due to respiratory tract infections over 12 months. Economic evaluation from an NHS perspective will compare the interventions, expressed as incremental cost effectiveness ratios. A nested mixed methods process evaluation will examine uptake and engagement with the interventions and trial procedures. TRIAL STATUS: Recruitment commenced in December 2020 and the last participant is expected to complete the trial in April 2024. DISCUSSION: Common nasal sprays and digital interventions to promote physical activity and stress management are low cost, accessible interventions applicable to primary care. If effective, they have the potential to reduce the individual and societal impact of RTIs. TRIAL REGISTRATION: Prospectively registered with ISRCTN registry (17936080) on 30/10/2020. SPONSOR: This RCT is sponsored by University of Southampton. The sponsors had no role in the study design, decision to publish, or preparation of the manuscript.

Economic Evaluation of Digital Health Interventions: Methodological Issues and Recommendations for Practice.

Health care interventions are increasingly being delivered through digital technologies, offering major opportunities for delivering more health gains from scarce health care resources. Digital health interventions (DHIs) raise distinct challenges for economic evaluations compared with drugs and medical devices, not least due to their interacting, evolving features. The implications of the distinctive nature of DHIs for the methodological choices underpinning their economic evaluation is not well understood. This paper provides an in-depth discussion of distinct features of DHIs and how they might impact the design, measurement, analysis and reporting of cost-effectiveness analysis conducted alongside both randomised and non-randomised studies. These include aspects related to choice of comparator, costs and benefits assessment, study perspective and type of economic analysis. We argue that typical methodological standpoints, such as taking a health service perspective, focusing on health-related benefits and adopting cost-utility analyses, as typically adopted in the economic evaluation of non-digital technologies (pharmaceutical drugs and medical devices), are unlikely to be appropriate for DHIs. We illustrate how these methodological aspects can be appropriately addressed in an evaluation of a digitally supported, remote rehabilitation programme for patients with Long Covid in England. We highlight several methodological considerations for improving practice and areas where further methodological work is required.

The SAFEST review: a mixed methods systematic review of shock-absorbing flooring for fall-related injury prevention.

BACKGROUND: Shock-absorbing flooring may minimise impact forces incurred from falls to reduce fall-related injuries; however, synthesized evidence is required to inform decision-making in hospitals and care homes. METHODS: This is a Health Technology Assessment mixed methods systematic review of flooring interventions targeting older adults and staff in care settings. Our search incorporated the findings from a previous scoping review, MEDLINE, AgeLine, and Scopus (to September 2019) and other sources. Two independent reviewers selected, assessed, and extracted data from studies. We assessed risk of bias using Cochrane and Joanna Briggs Institute tools, undertook meta-analyses, and meta-aggregation. RESULTS: 20 of 22 included studies assessed our outcomes (3 Randomised Controlled Trials (RCTs); 7 observational; 5 qualitative; 5 economic), on novel floors (N = 12), sports floors (N = 5), carpet (N = 5), and wooden sub-floors (N = 1). Quantitative data related to 11,857 patient falls (9 studies), and 163 staff injuries (1 study). One care home-based RCT found a novel underlay produced similar injurious falls rates (high-quality evidence) and falls rates (moderate-quality evidence) to a plywood underlay with vinyl overlay and concrete sub-floors. Very low-quality evidence suggested that shock-absorbing flooring may reduce injuries in hospitals (Rate Ratio 0.55, 95% CI 0.36 to 0.84, 2 studies; 27.1% vs. 42.4%; Risk Ratio (RR) = 0.64, 95% CI 0.44 to 0.93, 2 studies) and care homes (26.4% vs. 33.0%; RR 0.80, 95% CI 0.70 to 0.91, 3 studies), without increasing falls. Economic evidence indicated that if injuries are fewer and falls not increased, then shock-absorbing flooring would be a dominant strategy. Fracture outcomes were imprecise; however, hip fractures reduced from 30 in 1000 falls on concrete to 18 in 1000 falls on wooden sub-floors (OR 0.59, 95% CI 0.45 to 0.78; one study; very low-quality evidence). Staff found moving wheeled equipment harder on shock-absorbing floors leading to workplace adaptations. Very low-quality evidence suggests staff injuries were no less frequent on rigid floors. CONCLUSION: Evidence favouring shock-absorbing flooring is uncertain and of very low quality. Robust research following a core outcome set is required, with attention to wider staff workplace implications. TRIAL REGISTRATION: PROSPERO CRD42019118834 .

Shock-absorbing flooring for fall-related injury prevention in older adults and staff in hospitals and care homes: the SAFEST systematic review.

BACKGROUND: Injurious falls in hospitals and care homes are a life-limiting and costly international issue. Shock-absorbing flooring may offer part of the solution; however, evidence is required to inform decision-making. OBJECTIVES: The objectives were to assess the clinical effectiveness and cost-effectiveness of shock-absorbing flooring for fall-related injury prevention among older adults in care settings. REVIEW METHODS: A systematic review was conducted of experimental, observational, qualitative and economic studies evaluating flooring in care settings targeting older adults and/or staff. Studies identified by a scoping review (inception to May 2016) were screened, and the search of MEDLINE, AgeLine and Scopus (to September 2019) was updated, alongside other sources. Two independent reviewers assessed risk of bias in duplicate (using Cochrane's Risk of Bias 2.0 tool, the Risk Of Bias In Non-randomized Studies - of Interventions tool, or the Joanna Briggs Institute's qualitative tool). RESULTS: Of the 22 included studies, 20 assessed the outcomes (three randomised controlled trials; and seven observational, five qualitative and five economic studies) on novel floors (n = 12), sports floors (n = 5), carpet (n = 5) and wooden subfloors (n = 1). Quantitative data related to 11,857 patient/resident falls (nine studies) and 163 staff injuries (one study). Qualitative studies included patients/residents (n = 20), visitors (n = 8) and staff (n = 119). Hospital-based randomised controlled trial data were too imprecise; however, very low-quality evidence indicated that novel/sports flooring reduced injurious falls from three per 1000 patients per day on vinyl with concrete subfloors to two per 1000 patients per day (rate ratio 0.55, 95% confidence interval 0.36 to 0.84; two studies), without increasing falls rates (two studies). One care home-based randomised controlled trial found that a novel underlay produces similar injurious falls rates (high-quality evidence) and falls rates (moderate-quality evidence) to those of a plywood underlay with vinyl overlays and concrete subfloors. Very low-quality data demonstrated that, compared with rigid floors, novel/sports flooring reduced the number of falls resulting in injury in care homes (26.4% vs. 33.0%; risk ratio 0.80, 95% confidence interval 0.70 to 0.91; three studies) and hospitals (27.1% vs. 42.4%; risk ratio 0.64, 95% confidence interval 0.44 to 0.93; two studies). Fracture and head injury outcomes were imprecise; however, hip fractures reduced from 30 per 1000 falls on concrete to 18 per 1000 falls on wooden subfloors in care homes (odds ratio 0.59, 95% confidence interval 0.45 to 0.78; one study; very low-quality evidence). Four low-quality economic studies concluded that shock-absorbing flooring reduced costs and improved outcomes (three studies), or increased costs and improved outcomes (one study). One, more robust, study estimated that shock-absorbing flooring resulted in fewer quality-adjusted life-years and lower costs, if the number of falls increased on shock-absorbing floors, but that shock-absorbing flooring would be a dominant economic strategy if the number of falls remained the same. Staff found moving wheeled equipment more difficult on shock-absorbing floors, leading to workplace adaptations. Staff injuries were observed; however, very low-quality evidence suggests that these are no less frequent on rigid floors. LIMITATIONS: Evidence favouring shock-absorbing flooring is of very low quality; thus, much uncertainty remains. CONCLUSIONS: Robust evidence is lacking in hospitals and indicates that one novel floor may not be effective in care homes. Very low-quality evidence indicates that shock-absorbing floors may be beneficial; however, wider workplace implications need to be addressed. Work is required to establish a core outcome set, and future research needs to more comprehensively deal with confounding and the paucity of hospital-based studies, and better plan for workplace adaptations in the study design. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019118834. 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. 26, No. 5. See the NIHR Journals Library website for further project information.

AIM: The aim of this study was to summarise what is known about shock-absorbing flooring for reducing injurious falls in hospitals and care homes. BACKGROUND: Falls and fall-related injuries are a major problem for older adults in both hospitals and care homes. Shock-absorbing flooring (such as carpet, sports floors or specially designed floors) provides a more cushioned surface and is one potential solution to help reduce the impact forces from a fall. METHODS: From literature searches, we identified relevant studies on shock-absorbing flooring use in hospitals and care homes. We gathered data on the quality of the studies' methods, what and who the studies involved, and the study findings. Members of the public were involved throughout the project. They helped improve the clarity of the reporting and collaborated in meetings to help guide the study team. FINDINGS: One high-quality study in a care home found that vinyl overlay with novel shock-absorbing underlay was no better at reducing injuries than vinyl overlay with plywood underlay on concrete subfloors. We found very low-quality evidence that shock-absorbing flooring may reduce injuries in hospitals and care homes, without increasing falls; if this were true, then economic evidence suggested that shock-absorbing flooring would be the best-value option for patients (lower cost and improved outcomes). There was insufficient evidence to determine the effects of shock-absorbing flooring on fractures or head injuries, although wooden subfloors resulted in fewer hip fractures than concrete subfloors. Shock-absorbing flooring made it harder for staff to move equipment such as beds and trolleys, and led to staff changing how they work. IMPLICATIONS: The evidence suggests that one type of shock-absorbing floor may not work in care homes, compared with rigid flooring; however, gaps still exist in the knowledge. The evidence in favour of shock-absorbing flooring was of very low quality, meaning it is uncertain. There is a lack of robust evidence in hospitals, which often have concrete subfloors and different population characteristics. If planning to install shock-absorbing flooring, it is important to consider the wider impacts on the workplace and how best to manage these.

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial.

OBJECTIVE: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. DESIGN: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. SETTING: 76 general practices in the United Kingdom. PARTICIPANTS: 622 people with treated but poorly controlled hypertension (>140/90 mm Hg) and access to the internet. INTERVENTIONS: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. MAIN OUTCOME MEASURES: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. RESULTS: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of -3.4 mm Hg (95% confidence interval -6.1 to -0.8 mm Hg) and a mean difference in diastolic blood pressure of -0.5 mm Hg (-1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. CONCLUSIONS: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. TRIAL REGISTRATION: ISRCTN13790648.

Protocol for the SAFEST review: the Shock-Absorbing Flooring Effectiveness SysTematic review including older adults and staff in hospitals and care homes.

INTRODUCTION: Falls in hospitals and care homes are a major issue of international concern. Inpatient falls are the most commonly reported safety incident in the UK's National Health Service (NHS), costing the NHS £630 million a year. Injurious falls are particularly life-limiting and costly. There is a growing body of evidence on shock-absorbing flooring for fall-related injury prevention; however, no systematic review exists to inform practice. METHODS AND ANALYSIS: We will systematically identify, appraise and summarise studies investigating the clinical and cost-effectiveness, and experiences of shock-absorbing flooring in hospitals and care homes. Our search will build on an extensive search conducted by a scoping review (inception to May 2016). We will search electronic databases (AgeLine, CINAHL, MEDLINE, NHS Economic Evaluation Database, Scopus and Web of Science; May 2016-present), trial registries and grey literature. We will conduct backward and forward citation searches of included studies, and liaise with study researchers. We will evaluate the influence of floors on fall-related injuries, falls and staff work-related injuries through randomised and non-randomised studies, consider economic and qualitative evidence, and implementation factors. We will consider risk of bias, assess heterogeneity and explore potential effect modifiers via subgroup analyses and sensitivity analyses. Where appropriate we will combine studies through meta-analysis. We will use the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach to evaluate the quality of evidence and present the results using summary of findings tables, and adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. ETHICS AND DISSEMINATION: We will follow the ethical principles of systematic review conduct, by attending to publication ethics, transparency and rigour. Our dissemination plan includes peer-reviewed publication, presentations, press release, stakeholder symposium, patient video and targeted knowledge-to-action reports. This review will inform decision-making around falls management in care settings and identify important directions for future research. PROSPERO REGISTRATION NUMBER: CRD42019118834.

'Not clinically effective but cost-effective' - paradoxical conclusions in randomised controlled trials with 'doubly null' results: a cross-sectional study.

OBJECTIVES: Randomised controlled trials in healthcare increasingly include economic evaluations. Some show small differences which are not statistically significant. Yet these sometimes come to paradoxical conclusions such as: 'the intervention is not clinically effective' but 'is probably cost-effective'. This study aims to quantify the extent of non-significant results and the types of conclusions drawn from them. DESIGN: Cross-sectional retrospective analysis of randomised trials published by the UK's National Institute for Health Research (NIHR) Health Technology Assessment programme. We defined as 'doubly null' those trials that found non-statistically significant differences in both primary outcome and cost per patient. Paradoxical was defined as concluding in favour of an intervention, usually compared with placebo or usual care. No human participants were involved. Our sample was 226 randomised trial projects published by the Health Technology Assessment programme 2004 to 2017. All are available free online. RESULTS: The 226 projects contained 193 trials with a full economic evaluation. Of these 76 (39%) had at least one 'doubly null' comparison. These 76 trials contained 94 comparisons. In these 30 (32%) drew economic conclusions in favour of an intervention. Overall report conclusions split roughly equally between those favouring the intervention (14), and those favouring either the control (7) or uncertainty (9). DISCUSSION: Trials with 'doubly null' results and paradoxical conclusions are not uncommon. The differences observed in cost and quality-adjustedlife year were small and non-statistically significant. Almost all these trials were also published in leading peer-reviewed journals. Although some guidelines for reporting economic results require cost-effectiveness estimates regardless of statistical significance, the interpretability of paradoxical results has nowhere been addressed. CONCLUSIONS: Reconsideration is required of the interpretation of cost-effectiveness analyses in randomised controlled trials with 'doubly null' results, particularly when economics favours a novel intervention.

Feasibility trial of a digital self-management intervention 'My Breathing Matters' to improve asthma-related quality of life for UK primary care patients with asthma.

OBJECTIVE: To assess the feasibility of a randomised controlled trial (RCT) and acceptability of an asthma self-management digital intervention to improve asthma-specific quality of life in comparison with usual care. DESIGN AND SETTING: A two-arm feasibility RCT conducted across seven general practices in Wessex, UK. PARTICIPANTS: Primary care patients with asthma aged 18 years and over, with impaired asthma-specific quality of life and access to the internet. INTERVENTIONS: 'My Breathing Matters' (MBM) is a digital asthma self-management intervention designed using theory, evidence and person-based approaches to provide tailored support for both pharmacological and non-pharmacological management of asthma symptoms. OUTCOMES: The primary outcome was the feasibility of the trial design, including recruitment, adherence and retention at follow-up (3 and 12 months). Secondary outcomes were the feasibility and effect sizes of specific trial measures including asthma-specific quality of life and asthma control. RESULTS: Primary outcomes: 88 patients were recruited (target 80). At 3-month follow-up, two patients withdrew and six did not complete outcome measures. At 12 months, two withdrew and four did not complete outcome measures. 36/44 patients in the intervention group engaged with MBM (median of 4 logins, range 0-25, IQR 8). Consistent trends were observed to improvements in asthma-related patient-reported outcome measures. CONCLUSIONS: This study demonstrated the feasibility and acceptability of a definitive RCT that is required to determine the clinical and cost-effectiveness of a digital asthma self-management intervention. TRIAL REGISTRATION NUMBER: ISRCTN15698435.

Incidence and cost of medication harm in older adults following hospital discharge: a multicentre prospective study in the UK.

AIMS: Polypharmacy is increasingly common in older adults, placing them at risk of medication-related harm (MRH). Patients are particularly vulnerable to problems with their medications in the period following hospital discharge due to medication changes and poor information transfer between hospital and primary care. The aim of the present study was to investigate the incidence, severity, preventability and cost of MRH in older adults in England postdischarge. METHODS: An observational, multicentre, prospective cohort study recruited 1280 older adults (median age 82 years) from five teaching hospitals in Southern England, UK. Participants were followed up for 8 weeks by senior pharmacists, using three data sources (hospital readmission review, participant telephone interview and primary care records), to identify MRH and associated health service utilization. RESULTS: Overall, 413 participants (37%) experienced MRH (556 MRH events per 1000 discharges), of which 336 (81%) cases were serious and 214 (52%) potentially preventable. Four participants experienced fatal MRH. The most common MRH events were gastrointestinal (n = 158, 25%) or neurological (n = 111, 18%). The medicine classes associated with the highest risk of MRH were opiates, antibiotics and benzodiazepines. A total of 328 (79%) participants with MRH sought healthcare over the 8-week follow-up. The incidence of MRH-associated hospital readmission was 78 per 1000 discharges. Postdischarge MRH in older adults is estimated to cost the National Health Service £396 million annually, of which £243 million is potentially preventable. CONCLUSIONS: MRH is common in older adults following hospital discharge, and results in substantial use of healthcare resources.

MENOS4 trial: a multicentre randomised controlled trial (RCT) of a breast care nurse delivered cognitive behavioural therapy (CBT) intervention to reduce the impact of hot flushes in women with breast cancer: Study Protocol.

BACKGROUND: Women who have been treated for breast cancer may identify vasomotor symptoms, such as hot flushes and night sweats (HFNS), as a serious problem. HFNS are unpleasant to experience and can have a significant impact on daily life, potentially leading to reduced adherence to life saving adjuvant hormonal therapy. It is known that Cognitive Behavioural Therapy (CBT) is effective for the alleviation of hot flushes in both well women and women who have had breast cancer. Most women with breast cancer will see a breast care nurse and there is evidence that nurses can be trained to deliver psychological treatments to a satisfactory level, whilst also maintaining treatment fidelity. The research team will assess whether breast care nurses can effectively deliver a CBT intervention to alleviate hot flushes in women with breast cancer. METHODS: This study is a multi-centre phase III individually randomised controlled trial of group CBT versus usual care to reduce the impact of hot flushes in women with breast cancer. 120-160 women with primary breast cancer experiencing seven or more problematic HFNS a week will be randomised to receive either treatment as usual (TAU) or participation in the group CBT intervention plus TAU (CBT Group). A process evaluation using May's Normalisation Process Theory will be conducted, as well as practical and organisational issues relating to the implementation of the intervention. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost effectiveness of the intervention will also be assessed. DISCUSSION: There is a need for studies that enable effective interventions to be implemented in practice. There is good evidence that CBT is helpful for women with breast cancer who experience HFNS, yet it is not widely available. It is not yet known whether the intervention can be effectively delivered by breast care nurses or implemented in practice. This study will provide information on both whether the intervention can effectively help women with hot flushes and whether and how it can be translated into routine clinical practice. TRIAL REGISTRATION: ISRCTN 12824632 . Registered 25-01-2017.

National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme research funding and UK burden of disease.

BACKGROUND: HTA Programme funding is governed by the need for evidence and scientific quality, reflecting funding of the National Institute for Health Research (NIHR) by the NHS. The need criterion incorporates covering the spectrum of diseases, but also taking account of research supported by other funders. This study compared the NIHR HTA Programme portfolio of research with the UK burden of disease as measured by Disability-adjusted Life Years (DALYs). METHODS: A retrospective cross-sectional study using a cohort of all funded primary research and evidence syntheses projects received by the HTA Programme from April 2011 to March 2016 (n = 363); to determine the proportion of spend by disease compared with burden of disease in the UK calculated using 2015 UK DALY data. RESULTS: The programme costing just under £44 million broadly reflected UK DALY burden by disease. Spend was lower than disease burden for cancer, cardiovascular and musculoskeletal diseases, which may reflect the importance of other funders, notably medical charities, which concentrate on these diseases. CONCLUSION: The HTA Programme spend, adjusted for other relevant funders, broadly matches disease burden in the UK; no diseases are being neglected.

A comparison of the clinical effectiveness and cost of specialised individually delivered parent training for preschool attention-deficit/hyperactivity disorder and a generic, group-based programme: a multi-centre, randomised controlled trial of the New Forest Parenting Programme versus Incredible Years.

The objective of this study is to compare the efficacy and cost of specialised individually delivered parent training (PT) for preschool children with attention-deficit/hyperactivity disorder (ADHD) against generic group-based PT and treatment as usual (TAU). This is a multi-centre three-arm, parallel group randomised controlled trial conducted in National Health Service Trusts. The participants included in this study were preschool children (33-54 months) fulfilling ADHD research diagnostic criteria. New Forest Parenting Programme (NFPP)-12-week individual, home-delivered ADHD PT programme; Incredible Years (IY)-12-week group-based, PT programme initially designed for children with behaviour problems were the interventions. Primary outcome-Parent ratings of child's ADHD symptoms (Swanson, Nolan & Pelham Questionnaire-SNAP-IV). Secondary outcomes-teacher ratings (SNAP-IV) and direct observations of ADHD symptoms and parent/teacher ratings of conduct problems. NFPP, IY and TAU outcomes were measured at baseline (T1) and post treatment (T2). NFPP and IY outcomes only were measured 6 months post treatment (T3). Researchers, but not therapists or parents, were blind to treatment allocation. Analysis employed mixed effect regression models (multiple imputations). Intervention and other costs were estimated using standardized approaches. NFPP and IY did not differ on parent-rated SNAP-IV, ADHD combined symptoms [mean difference - 0.009 95% CI (- 0.191, 0.173), p = 0.921] or any other measure. Small, non-significant, benefits of NFPP over TAU were seen for parent-rated SNAP-IV, ADHD combined symptoms [- 0.189 95% CI (- 0.380, 0.003), p = 0.053]. NFPP significantly reduced parent-rated conduct problems compared to TAU across scales (p values < 0.05). No significant benefits of IY over TAU were seen for parent-rated SNAP, ADHD symptoms [- 0.16 95% CI (- 0.37, 0.04), p = 0.121] or parent-rated conduct problems (p > 0.05). The cost per family of providing NFPP in the trial was significantly lower than IY (£1591 versus £2103). Although, there were no differences between NFPP and IY with regards clinical effectiveness, individually delivered NFPP cost less. However, this difference may be reduced when implemented in routine clinical practice. Clinical decisions should take into account parental preferences between delivery approaches.

The clinical utility and cost impact of cystatin C measurement in the diagnosis and management of chronic kidney disease: A primary care cohort study.

BACKGROUND: To reduce over-diagnosis of chronic kidney disease (CKD) resulting from the inaccuracy of creatinine-based estimates of glomerular filtration rate (GFR), UK and international guidelines recommend that cystatin-C-based estimates of GFR be used to confirm or exclude the diagnosis in people with GFR 45-59 ml/min/1.73 m2 and no albuminuria (CKD G3aA1). Whilst there is good evidence for cystatin C being a marker of GFR and risk in people with CKD, its use to define CKD in this manner has not been evaluated in primary care, the setting in which most people with GFR in this range are managed. METHODS AND FINDINGS: A total of 1,741 people with CKD G3a or G3b defined by 2 estimated GFR (eGFR) values more than 90 days apart were recruited to the Renal Risk in Derby study between June 2008 and March 2010. Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, we compared GFR estimated from creatinine (eGFRcreat), cystatin C (eGFRcys), and both (eGFRcreat-cys) at baseline and over 5 years of follow-up. We analysed the proportion of participants with CKD G3aA1 reclassified to 'no CKD' or more advanced CKD with the latter two equations. We further assessed the impact of using cystatin-C-based eGFR in risk prediction equations for CKD progression and all-cause mortality and investigated non-GFR determinants of eGFRcys. Finally, we estimated the cost implications of implementing National Institute for Health and Care Excellence (NICE) guidance to use eGFRcys to confirm the diagnosis in people classified as CKD G3aA1 by eGFRcreat. Mean eGFRcys was significantly lower than mean eGFRcreat (45.1 ml/min/1.73 m2, 95% CI 44.4 to 45.9, versus 53.6 ml/min/1.73 m2, 95% CI 53.0 to 54.1, P < 0.001). eGFRcys reclassified 7.7% (50 of 653) of those with CKD G3aA1 by eGFRcreat to eGFR ≥ 60 ml/min/1.73 m2. However, a much greater proportion (59.0%, 385 of 653) were classified to an eGFR category indicating more severe CKD. A similar pattern was seen using eGFRcreat-cys, but lower proportions were reclassified. Change in eGFRcreat and eGFRcys over 5 years were weakly correlated (r = 0.33, P < 0.001), but eGFRcys identified more people as having CKD progression (18.2% versus 10.5%). Multivariable analysis using eGFRcreat as an independent variable identified age, smoking status, body mass index, haemoglobin, serum uric acid, serum albumin, albuminuria, and C reactive protein as non-GFR determinants of eGFRcys. Use of eGFRcys or eGFRcreat-cys did not improve discrimination in risk prediction models for CKD progression and all-cause mortality compared to similar models with eGFRcreat. Application of the NICE guidance, which assumed cost savings, to participants with CKD G3aA1 increased the cost of monitoring by £23 per patient, which if extrapolated to be applied throughout England would increase the cost of testing and monitoring CKD by approximately £31 million per year. Limitations of this study include the lack of a measured GFR and the potential lack of ethnic diversity in the study cohort. CONCLUSIONS: Implementation of current guidelines on eGFRcys testing in our study population of older people in primary care resulted in only a small reduction in diagnosed CKD but classified a greater proportion as having more advanced CKD than eGFRcreat. Use of eGFRcys did not improve risk prediction in this population and was associated with increased cost. Our data therefore do not support implementation of these recommendations in primary care. Further studies are warranted to define the most appropriate clinical application of eGFRcys and eGFRcreat-cys.

A randomised controlled study of the effectiveness of breathing retraining exercises taught by a physiotherapist either by instructional DVD or in face-to-face sessions in the management of asthma in adults.

BACKGROUND: Asthma control is suboptimal, resulting in quality of life (QoL) impairment and costs. Breathing retraining exercises have evidence of effectiveness as adjuvant treatment, but are infrequently used. OBJECTIVES: To transfer the contents of a brief (three-session) physiotherapist-delivered breathing retraining programme to a digital versatile disc (DVD) and booklet format; to compare the effectiveness of the self-guided intervention with that of 'face-to-face' physiotherapy and usual care for QoL and other asthma-related outcomes; to perform a health economic assessment of both interventions; and to perform a process evaluation using quantitative and qualitative methods. DESIGN: Parallel-group three-arm randomised controlled trial. SETTING: General practice surgeries in the UK. PARTICIPANTS: In total, 655 adults currently receiving asthma treatment with impaired asthma-related QoL were randomly allocated to the DVD (n = 261), physiotherapist (n = 132) and control (usual care) (n = 262) arms in a 2 : 1 : 2 ratio. It was not possible to blind participants but data collection and analysis were performed blinded. INTERVENTIONS: Physiotherapy-based breathing retraining delivered through three 'face-to-face' respiratory physiotherapist sessions or a self-guided programme (DVD plus our theory-based behaviour change booklet) developed by the research team, with a control of usual care. MAIN OUTCOME MEASURES: The primary outcome measure was asthma-specific QoL, measured using the Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes included asthma symptom control [Asthma Control Questionnaire (ACQ)], psychological state [Hospital Anxiety and Depression Scale (HADS)], hyperventilation symptoms (Nijmegen questionnaire), generic QoL [EuroQol-5 Dimensions (EQ-5D)], assessments of airway physiology (spirometry) and inflammation (exhaled nitric oxide) and health resource use and costs. Assessments were carried out at baseline and at 3, 6 and 12 months post randomisation. Patient engagement and experience were also assessed using quantitative and qualitative methods. RESULTS: Primary efficacy analysis was between-group comparison of changes in AQLQ scores from baseline to 12 months in the intention-to-treat population with adjustments for prespecified covariates. Significant improvements occurred in the DVD group compared with the control group [adjusted mean difference 0.28, 95% confidence interval (CI) 0.11 to 0.44; p < 0.001] and in the face-to-face physiotherapy group compared with the control group (adjusted mean difference 0.24, 95% CI 0.04 to 0.44; p < 0.05), with equivalence between the DVD and the face-to-face physiotherapy groups (adjusted mean difference 0.04, 95% CI -0.16 to 0.24). In all sensitivity analyses, both interventions remained significantly superior to the control and equivalence between the interventions was maintained. In other questionnaire outcome measures and in the physiological measures assessed, there were no significant between-group differences. Process evaluations showed that participants engaged well with both of the active interventions, but that some participants in the DVD arm would have liked to receive tuition from a professional. Asthma health-care costs were lower in both intervention arms than in the control group, indicating 'dominance' for both of the interventions compared with the control, with lowest costs in the DVD arm. The rate of adverse events was lower in the DVD and face-to-face physiotherapy groups than in the control group. CONCLUSIONS: Only 10% of the potentially eligible population responded to the study invitation. However, breathing retraining exercises improved QoL and reduced health-care costs in adults with asthma whose condition remains uncontrolled despite standard pharmacological therapy, were engaged with well by patients and can be delivered effectively as a self-guided intervention. The intervention should now be transferred to an internet-based platform and implementation studies performed. Interventions for younger patients should be developed and trialled. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88318003. FUNDING: This project was primarily funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 53. See the NIHR Journals Library website for further project information. Additional financial support was received from Comprehensive Local Research Networks.

The impact on healthcare, policy and practice from 36 multi-project research programmes: findings from two reviews.

BACKGROUND: We sought to analyse the impacts found, and the methods used, in a series of assessments of programmes and portfolios of health research consisting of multiple projects. METHODS: We analysed a sample of 36 impact studies of multi-project research programmes, selected from a wider sample of impact studies included in two narrative systematic reviews published in 2007 and 2016. We included impact studies in which the individual projects in a programme had been assessed for wider impact, especially on policy or practice, and where findings had been described in such a way that allowed them to be collated and compared. RESULTS: Included programmes were highly diverse in terms of location (11 different countries plus two multi-country ones), number of component projects (8 to 178), nature of the programme, research field, mode of funding, time between completion and impact assessment, methods used to assess impact, and level of impact identified. Thirty-one studies reported on policy impact, 17 on clinician behaviour or informing clinical practice, three on a combined category such as policy and clinician impact, and 12 on wider elements of impact (health gain, patient benefit, improved care or other benefits to the healthcare system). In those multi-programme projects that assessed the respective categories, the percentage of projects that reported some impact was policy 35% (range 5-100%), practice 32% (10-69%), combined category 64% (60-67%), and health gain/health services 27% (6-48%). Variations in levels of impact achieved partly reflected differences in the types of programme, levels of collaboration with users, and methods and timing of impact assessment. Most commonly, principal investigators were surveyed; some studies involved desk research and some interviews with investigators and/or stakeholders. Most studies used a conceptual framework such as the Payback Framework. One study attempted to assess the monetary value of a research programme's health gain. CONCLUSION: The widespread impact reported for some multi-project programmes, including needs-led and collaborative ones, could potentially be used to promote further research funding. Moves towards greater standardisation of assessment methods could address existing inconsistencies and better inform strategic decisions about research investment; however, unresolved issues about such moves remain.

Randomised controlled trial and economic analysis of an internet-based weight management programme: POWeR+ (Positive Online Weight Reduction).

BACKGROUND: Behavioural counselling with intensive follow-up for obesity is effective, but in resource-constrained primary care settings briefer approaches are needed. OBJECTIVES: To estimate the clinical effectiveness and cost-effectiveness of an internet-based behavioural intervention with regular face-to-face or remote support in primary care, compared with brief advice. DESIGN: Individually randomised three-arm parallel trial with health economic evaluation and nested qualitative interviews. SETTING: Primary care general practices in the UK. PARTICIPANTS: Patients with a body mass index of ≥ 30 kg/m2 (or ≥ 28 kg/m2 with risk factors) identified from general practice records, recruited by postal invitation. INTERVENTIONS: Positive Online Weight Reduction (POWeR+) is a 24-session, web-based weight management intervention completed over 6 months. Following online registration, the website randomly allocated participants using computer-generated random numbers to (1) the control intervention (n = 279), which had previously been demonstrated to be clinically effective (brief web-based information that minimised pressure to cut down foods, instead encouraging swaps to healthier choices and increasing fruit and vegetables, plus 6-monthly nurse weighing); (2) POWeR+F (n = 269), POWeR+ supplemented by face-to-face nurse support (up to seven contacts); or (3) POWeR+R (n = 270), POWeR+ supplemented by remote nurse support (up to five e-mails or brief telephone calls). MAIN OUTCOME MEASURES: The primary outcome was a modelled estimate of average weight reduction over 12 months, assessed blind to group where possible, using multiple imputation for missing data. The secondary outcome was the number of participants maintaining a 5% weight reduction at 12 months. RESULTS: A total of 818 eligible individuals were randomised using computer-generated random numbers. Weight change, averaged over 12 months, was documented in 666 out of 818 participants (81%; control, n = 227; POWeR+F, n = 221; POWeR+R, n = 218). The control group maintained nearly 3 kg of weight loss per person (mean weight per person: baseline, 104.4 kg; 6 months, 101.9 kg; 12 months, 101.7 kg). Compared with the control group, the estimated additional weight reduction with POWeR+F was 1.5 kg [95% confidence interval (CI) 0.6 to 2.4 kg; p = 0.001] and with POWeR+R was 1.3 kg (95% CI 0.34 to 2.2 kg; p = 0.007). By 12 months the mean weight loss was not statistically significantly different between groups, but 20.8% of control participants, 29.2% of POWeR+F participants (risk ratio 1.56, 95% CI 0.96 to 2.51; p = 0.070) and 32.4% of POWeR+R participants (risk ratio 1.82, 95% CI 1.31 to 2.74; p = 0.004) maintained a clinically significant 5% weight reduction. The POWeR+R group had fewer individuals who reported doing another activity to help lose weight [control, 47.1% (64/136); POWeR+F, 37.2% (51/137); POWeR+R, 26.7% (40/150)]. The incremental cost to the health service per kilogram weight lost, compared with the control group, was £18 (95% CI -£129 to £195) for POWeR+F and -£25 (95% CI -£268 to £157) for POWeR+R. The probability of being cost-effective at a threshold of £100 per kilogram was 88% and 98% for POWeR+F and POWeR+R, respectively. POWeR+R was dominant compared with the control group. No harms were reported and participants using POWeR+ felt more enabled in managing their weight. The qualitative studies documented that POWeR+ was viewed positively by patients and that health-care professionals generally enjoyed supporting patients using POWeR+. STUDY LIMITATIONS: Maintenance of weight loss after 1 year is unknown. FUTURE WORK: Identifying strategies for longer-term engagement, impact in community settings and increasing physical activity. CONCLUSION: Clinically valuable weight loss (> 5%) is maintained in 20% of individuals using novel written materials with brief follow-up. A web-based behavioural programme and brief support results in greater mean weight loss and 10% more participants maintain valuable weight loss; it achieves greater enablement and fewer participants undertaking other weight-loss activities; and it is likely to be cost-effective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21244703. 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. 21, No. 4. See the NIHR Journals Library website for further project information.

Health Economics as Rhetoric: The Limited Impact of Health Economics on Funding Decisions in Four European Countries.

BACKGROUND: A response to the challenge of high-cost treatments in health care has been economic evaluation. Cost-effectiveness analysis presented as cost per quality-adjusted life-years gained has been controversial, raising heated support and opposition. OBJECTIVES: To assess the impact of economic evaluation in decisions on what to fund in four European countries and discuss the implications of our findings. METHODS: We used a protocol to review the key features of the application of economic evaluation in reimbursement decision making in England, Germany, the Netherlands, and Sweden, reporting country-specific highlights. RESULTS: Although the institutions and processes vary by country, health economic evaluation has had limited impact on restricting access of controversial high-cost drugs. Even in those countries that have gone the furthest, ways have been found to avoid refusing to fund high-cost drugs for particular diseases including cancer, multiple sclerosis, and orphan diseases. Economic evaluation may, however, have helped some countries to negotiate price reductions for some drugs. It has also extended to the discussion of clinical effectiveness to include cost. CONCLUSIONS: The differences in approaches but similarities in outcomes suggest that health economic evaluation be viewed largely as rhetoric (in D.N. McCloskey's terms in The Rhetoric of Economics, 1985). This is not to imply that economics had no impact: rather that it usually contributed to the discourse in ways that differed by country. The reasons for this no doubt vary by perspective, from political science to ethics. Economic evaluation may have less to do with rationing or denial of medical treatments than to do with expanding the discourse used to discuss such issues.

Models and applications for measuring the impact of health research: update of a systematic review for the Health Technology Assessment programme.

BACKGROUND: This report reviews approaches and tools for measuring the impact of research programmes, building on, and extending, a 2007 review. OBJECTIVES: (1) To identify the range of theoretical models and empirical approaches for measuring the impact of health research programmes; (2) to develop a taxonomy of models and approaches; (3) to summarise the evidence on the application and use of these models; and (4) to evaluate the different options for the Health Technology Assessment (HTA) programme. DATA SOURCES: We searched databases including Ovid MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature and The Cochrane Library from January 2005 to August 2014. REVIEW METHODS: This narrative systematic literature review comprised an update, extension and analysis/discussion. We systematically searched eight databases, supplemented by personal knowledge, in August 2014 through to March 2015. RESULTS: The literature on impact assessment has much expanded. The Payback Framework, with adaptations, remains the most widely used approach. It draws on different philosophical traditions, enhancing an underlying logic model with an interpretative case study element and attention to context. Besides the logic model, other ideal type approaches included constructionist, realist, critical and performative. Most models in practice drew pragmatically on elements of several ideal types. Monetisation of impact, an increasingly popular approach, shows a high return from research but relies heavily on assumptions about the extent to which health gains depend on research. Despite usually requiring systematic reviews before funding trials, the HTA programme does not routinely examine the impact of those trials on subsequent systematic reviews. The York/Patient-Centered Outcomes Research Institute and the Grading of Recommendations Assessment, Development and Evaluation toolkits provide ways of assessing such impact, but need to be evaluated. The literature, as reviewed here, provides very few instances of a randomised trial playing a major role in stopping the use of a new technology. The few trials funded by the HTA programme that may have played such a role were outliers. DISCUSSION: The findings of this review support the continued use of the Payback Framework by the HTA programme. Changes in the structure of the NHS, the development of NHS England and changes in the National Institute for Health and Care Excellence's remit pose new challenges for identifying and meeting current and future research needs. Future assessments of the impact of the HTA programme will have to take account of wider changes, especially as the Research Excellence Framework (REF), which assesses the quality of universities' research, seems likely to continue to rely on case studies to measure impact. The HTA programme should consider how the format and selection of case studies might be improved to aid more systematic assessment. The selection of case studies, such as in the REF, but also more generally, tends to be biased towards high-impact rather than low-impact stories. Experience for other industries indicate that much can be learnt from the latter. The adoption of researchfish® (researchfish Ltd, Cambridge, UK) by most major UK research funders has implications for future assessments of impact. Although the routine capture of indexed research publications has merit, the degree to which researchfish will succeed in collecting other, non-indexed outputs and activities remains to be established. LIMITATIONS: There were limitations in how far we could address challenges that faced us as we extended the focus beyond that of the 2007 review, and well beyond a narrow focus just on the HTA programme. CONCLUSIONS: Research funders can benefit from continuing to monitor and evaluate the impacts of the studies they fund. They should also review the contribution of case studies and expand work on linking trials to meta-analyses and to guidelines. FUNDING: The National Institute for Health Research HTA programme.