Digital tools for the recruitment and retention of participants in randomised controlled trials: a systematic map.

BACKGROUND: Recruiting and retaining participants in randomised controlled trials (RCTs) is challenging. Digital tools, such as social media, data mining, email or text-messaging, could improve recruitment or retention, but an overview of this research area is lacking. We aimed to systematically map the characteristics of digital recruitment and retention tools for RCTs, and the features of the comparative studies that have evaluated the effectiveness of these tools during the past 10 years. METHODS: We searched Medline, Embase, other databases, the Internet, and relevant web sites in July 2018 to identify comparative studies of digital tools for recruiting and/or retaining participants in health RCTs. Two reviewers independently screened references against protocol-specified eligibility criteria. Included studies were coded by one reviewer with 20% checked by a second reviewer, using pre-defined keywords to describe characteristics of the studies, populations and digital tools evaluated. RESULTS: We identified 9163 potentially relevant references, of which 104 articles reporting 105 comparative studies were included in the systematic map. The number of published studies on digital tools has doubled in the past decade, but most studies evaluated digital tools for recruitment rather than retention. The key health areas investigated were health promotion, cancers, circulatory system diseases and mental health. Few studies focussed on minority or under-served populations, and most studies were observational. The most frequently-studied digital tools were social media, Internet sites, email and tv/radio for recruitment; and email and text-messaging for retention. One quarter of the studies measured efficiency (cost per recruited or retained participant) but few studies have evaluated people's attitudes towards the use of digital tools. CONCLUSIONS: This systematic map highlights a number of evidence gaps and may help stakeholders to identify and prioritise further research needs. In particular, there is a need for rigorous research on the efficiency of the digital tools and their impact on RCT participants and investigators, perhaps as studies-within-a-trial (SWAT) research. There is also a need for research into how digital tools may improve participant retention in RCTs which is currently underrepresented relative to recruitment research. REGISTRATION: Not registered; based on a pre-specified protocol, peer-reviewed by the project's Advisory Board.

Peer review of health research funding proposals: A systematic map and systematic review of innovations for effectiveness and efficiency.

OBJECTIVE: To investigate methods and processes for timely, efficient and good quality peer review of research funding proposals in health. METHODS: A two-stage evidence synthesis: (1) a systematic map to describe the key characteristics of the evidence base, followed by (2) a systematic review of the studies stakeholders prioritised as relevant from the map on the effectiveness and efficiency of peer review 'innovations'. Standard processes included literature searching, duplicate inclusion criteria screening, study keyword coding, data extraction, critical appraisal and study synthesis. RESULTS: A total of 83 studies from 15 countries were included in the systematic map. The evidence base is diverse, investigating many aspects of the systems for, and processes of, peer review. The systematic review included eight studies from Australia, Canada, and the USA, evaluating a broad range of peer review innovations. These studies showed that simplifying the process by shortening proposal forms, using smaller reviewer panels, or expediting processes can speed up the review process and reduce costs, but this might come at the expense of peer review quality, a key aspect that has not been assessed. Virtual peer review using videoconferencing or teleconferencing appears promising for reducing costs by avoiding the need for reviewers to travel, but again any consequences for quality have not been adequately assessed. CONCLUSIONS: There is increasing international research activity into the peer review of health research funding. The studies reviewed had methodological limitations and variable generalisability to research funders. Given these limitations it is not currently possible to recommend immediate implementation of these innovations. However, many appear promising based on existing evidence, and could be adapted as necessary by funders and evaluated. Where feasible, experimental evaluation, including randomised controlled trials, should be conducted, evaluating impact on effectiveness, efficiency and quality.

Etelcalcetide for Treating Secondary Hyperparathyroidism: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal.

The manufacturer of the calcimimetic drug etelcalcetide was invited to make an evidence submission as part of the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal (STA) programme. Within this submission, they reported evidence on the clinical and cost effectiveness of etelcalcetide for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on haemodialysis. The Southampton Health Technology Assessments Centre (SHTAC), part of the Wessex Institute at the University of Southampton, was the independent Evidence Review Group (ERG) commissioned to appraise the company's submission. This article describes the ERG's review and critique of the company's submission and summarises the NICE Appraisal Committee's subsequent guidance (issued in June 2017). The clinical-effectiveness evidence submitted by the company consisted of two double-blind, randomised controlled trials (RCTs) comparing etelcalcetide with placebo, one RCT comparing etelcalcetide with cinacalcet, two single-arm extension studies of the above trials, and one single-arm study evaluating the effect of switching from cinacalcet to etelcalcetide. No study specifically examined the population specified in the NICE appraisal scope: patients refractory to standard therapy with phosphate binders and vitamin D (PBVD). None of these trials were designed to collect long-term efficacy data for outcomes such as mortality, bone fractures, cardiovascular events, or parathyroidectomies. Instead, biomarker data from the trials were mapped to long-term outcomes by an assumed linear relationship between the trial outcome, reduction of parathyroid hormone (PTH) by > 30%, and the log-hazard ratios for the occurrence of clinical events derived from a large, long-term RCT of cinacalcet (the EVOLVE trial). After submission of a confidential Patient Access Scheme (PAS) discount reducing etelcalcetide drug costs, the incremental cost-effectiveness ratio (ICER) for etelcalcetide versus cinacalcet was £14,778 per quality-adjusted life-year (QALY) gained in the company's base case. While this value is lower than the NICE threshold range of £20,000 and £30,000 per QALY gained, it was the opinion of the ERG that the ICER was highly uncertain due to efficacy data limitations for etelcalcetide, inadequate synthesis of clinical-effectiveness evidence, and strong assumptions connecting short-term biomarker data with long-term clinical outcomes. The ERG produced an alternative base case for etelcalcetide versus cinacalcet, with an ICER of £22,400 per QALY gained, also subject to uncertainty. The NICE Appraisal Committee recommended etelcalcetide as an option for the treatment of SHPT in adults with CKD only if treatment with a calcimimetic is indicated and cinacalcet is not suitable, subject to the company's provision of the agreed PAS discount.

Reslizumab for Treating Asthma with Elevated Blood Eosinophils Inadequately Controlled by Inhaled Corticosteroids: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal (STA) process, the manufacturer of reslizumab (Teva) submitted evidence for its clinical and cost effectiveness for the treatment of eosinophilic asthma inadequately controlled by inhaled corticosteroids. NICE commissioned Southampton Health Technology Assessments Centre (SHTAC) as an independent Evidence Review Group (ERG) to provide a critique of the manufacturer's submitted evidence. Reslizumab is compared with best standard of care and omalizumab, for a small 'overlap' population of patients who have both eosinophilic and IgE-mediated severe asthma. This paper provides a summary of the ERG's review of the manufacturer's submission, and summarises the NICE Appraisal Committee's subsequent guidance (issued in August 2017). The ERG considered that there were limitations in the approach proposed by the manufacturer for the exacerbation rate and the utility for severe exacerbation. The company amended their initial analysis, following comments from the ERG and the NICE committee, whereby the incremental cost effectiveness ratio was £29,870 per QALY gained for reslizumab compared with best standard care. The NICE Appraisal Committee (AC) concluded that reslizumab was recommended as an option for the treatment of severe eosinophilic asthma that is inadequately controlled in adults despite maintenance therapy with high-dose inhaled corticosteroids plus another drug, only if (1) the blood eosinophil count has been recorded as 400 cells per microlitre or more and (2) the patient has had three or more asthma exacerbations in the past 12 months, and (3) the company provides reslizumab with the discount agreed in the patient access scheme.

Systematic review of the empirical investigation of resources to support decision-making regarding BRCA1 and BRCA2 genetic testing in women with breast cancer.

OBJECTIVE: Identify existing resources developed and/or evaluated empirically in the published literature designed to support women with breast cancer making decisions regarding genetic testing for BRCA1/2 mutations. METHODS: Systematic review of seven electronic databases. Studies were included if they described or evaluated resources that were designed to support women with breast cancer in making a decision to have genetic counselling or testing for familial breast cancer. Outcome and process evaluations, using any type of study design, as well as articles reporting the development of decision aids, were eligible for inclusion. RESULTS: Total of 9 publications, describing 6 resources were identified. Resources were effective at increasing knowledge or understanding of hereditary breast cancer. Satisfaction with resources was high. There was no evidence that any resource increased distress, worry or decisional conflict. Few resources included active functionalities for example, values-based exercises, to support decision-making. CONCLUSION: Tailored resources supporting decision-making may be helpful and valued by patients and increase knowledge of hereditary breast cancer, without causing additional distress. PRACTICE IMPLICATIONS: Clinicians should provide supportive written information to patients where it is available. However, there is a need for robustly developed decision tools to support decision-making around genetic testing in women with breast cancer.

Virtual chromoendoscopy for the real-time assessment of colorectal polyps in vivo: a systematic review and economic evaluation.

BACKGROUND: Current clinical practice is to remove a colorectal polyp detected during colonoscopy and determine whether it is an adenoma or hyperplastic by histopathology. Identifying adenomas is important because they may eventually become cancerous if untreated, whereas hyperplastic polyps do not usually develop into cancer, and a surveillance interval is set based on the number and size of adenomas found. Virtual chromoendoscopy (VCE) (an electronic endoscopic imaging technique) could be used by the endoscopist under strictly controlled conditions for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps to replace histopathological diagnosis. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of the VCE technologies narrow-band imaging (NBI), flexible spectral imaging colour enhancement (FICE) and i-scan for the characterisation and management of diminutive (≤ 5 mm) colorectal polyps using high-definition (HD) systems without magnification. DESIGN: Systematic review and economic analysis. PARTICIPANTS: People undergoing colonoscopy for screening or surveillance or to investigate symptoms suggestive of colorectal cancer. INTERVENTIONS: NBI, FICE and i-scan. MAIN OUTCOME MEASURES: Diagnostic accuracy, recommended surveillance intervals, health-related quality of life (HRQoL), adverse effects, incidence of colorectal cancer, mortality and cost-effectiveness of VCE compared with histopathology. DATA SOURCES: Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and Database of Abstracts of Reviews of Effects were searched for published English-language studies from inception to June 2016. Bibliographies of related papers, systematic reviews and company information were screened and experts were contacted to identify additional evidence. REVIEW METHODS: Systematic reviews of test accuracy and economic evaluations were undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-analyses were conducted, where possible, to inform the independent economic model. A cost-utility decision-analytic model was developed to estimate the cost-effectiveness of VCE compared with histopathology. The model used a decision tree for patients undergoing endoscopy, combined with estimates of long-term outcomes (e.g. incidence of colorectal cancer and subsequent morbidity and mortality) derived from University of Sheffield School of Health and Related Research's bowel cancer screening model. The model took a NHS perspective, with costs and benefits discounted at 3.5% over a lifetime horizon. There were limitations in the data on the distribution of adenomas across risk categories and recurrence rates post polypectomy. RESULTS: Thirty test accuracy studies were included: 24 for NBI, five for i-scan and three for FICE (two studies assessed two interventions). Polyp assessments made with high confidence were associated with higher sensitivity and endoscopists experienced in VCE achieved better results than those without experience. Two economic evaluations were included. NBI, i-scan and FICE are cost-saving strategies compared with histopathology and the number of quality-adjusted life-years gained was similar for histopathology and VCE. The correct surveillance interval would be given to 95% of patients with NBI, 94% of patients with FICE and 97% of patients with i-scan. LIMITATIONS: Limited evidence was available for i-scan and FICE and there was heterogeneity among the NBI studies. There is a lack of data on longer-term health outcomes of patients undergoing VCE for assessment of diminutive colorectal polyps. CONCLUSIONS: VCE technologies, using HD systems without magnification, could potentially be used for the real-time assessment of diminutive colorectal polyps, if endoscopists have adequate experience and training. FUTURE WORK: Future research priorities include head-to-head randomised controlled trials of all three VCE technologies; more research on the diagnostic accuracy of FICE and i-scan (when used without magnification); further studies evaluating the impact of endoscopist experience and training on outcomes; studies measuring adverse effects, HRQoL and anxiety; and longitudinal data on colorectal cancer incidence, HRQoL and mortality. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016037767. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Educational interventions to improve quality of life in people with chronic inflammatory skin diseases: systematic reviews of clinical effectiveness and cost-effectiveness.

BACKGROUND: Inflammatory skin diseases include a broad range of disorders. For some people, these conditions lead to psychological comorbidities and reduced quality of life (QoL). Patient education is recommended in the management of these conditions and may improve QoL. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of educational interventions to improve health-related quality of life (HRQoL) in people with chronic inflammatory skin diseases. DATA SOURCES: Twelve electronic bibliographic databases, including The Cochrane Library, MEDLINE and EMBASE, were searched to July 2014. Bibliographies of retrieved papers were searched and an Advisory Group contacted. REVIEW METHODS: Systematic reviews were conducted following standard methodologies. Clinical effectiveness studies were included if they were undertaken in people with a chronic inflammatory skin condition. Educational interventions that aimed to, or could, improve HRQoL were eligible. Studies were required to measure HRQoL, and other outcomes such as disease severity were also included. Randomised controlled trials (RCTs) or controlled clinical trials were eligible. For the review of cost-effectiveness, studies were eligible if they were full economic evaluations, cost-consequence or cost analyses. RESULTS: Seven RCTs were included in the review of clinical effectiveness. Two RCTs focused on children with eczema and their carers. Five RCTs were in adults. Of these, two were of people with psoriasis, one was of people with acne and two were of people with a range of conditions. There were few similarities in the interventions (e.g. the delivery mode, the topics covered, the duration of the education), which precluded any quantitative synthesis. Follow-up ranged from 4 weeks to 12 months, samples sizes were generally small and, overall, the study quality was poor. There appeared to be positive effects on HRQoL in participants with psoriasis in one trial, but no difference between groups in another trial in which participants had less severe psoriasis. Carers of children in one RCT of eczema showed improvement in HRQoL; however, in a RCT evaluating a website intervention there were no demonstrable effects on HRQoL. Neither the RCT in those adults with acne nor the RCT in those adults with mixed skin conditions demonstrated an effect on HRQoL. One RCT reported subgroups with atopic dermatitis or psoriasis and education was effective for psoriasis only. Other outcomes also showed mixed results. It is unclear how clinically meaningful any of the observed improvements are. Three studies of cost-effectiveness were included. The interventions, comparators and populations varied across the studies and, overall, the studies provided limited information on cost-effectiveness. The studies did provide detailed information on resources and costs that could be useful to inform a future cost-effectiveness evaluation in this area. LIMITATIONS: The application of the inclusion criterion around whether the interventions were aimed at improving HRQoL or the inference that they could improve HRQoL was difficult as information was rarely reported. CONCLUSIONS: There is uncertainty regarding whether educational interventions addressing issues that could improve HRQoL in people with chronic skin conditions are effective. Tentative conclusions about the best approach to delivering these kinds of interventions are that face-to-face, group, sessions may be beneficial; however, text messages may also be effective. Delivery over a period of time and by a multidisciplinary team may also be associated with positive outcomes. There is uncertainty over whether or not educational interventions are cost-effective. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014007426. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Surgery for weight loss in adults.

BACKGROUND: Bariatric (weight loss) surgery for obesity is considered when other treatments have failed. The effects of the available bariatric procedures compared with medical management and with each other are uncertain. This is an update of a Cochrane review first published in 2003 and most recently updated in 2009. OBJECTIVES: To assess the effects of bariatric surgery for overweight and obesity, including the control of comorbidities. SEARCH METHODS: Studies were obtained from searches of numerous databases, supplemented with searches of reference lists and consultation with experts in obesity research. Date of last search was November 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing surgical interventions with non-surgical management of obesity or overweight or comparing different surgical procedures. DATA COLLECTION AND ANALYSIS: Data were extracted by one review author and checked by a second review author. Two review authors independently assessed risk of bias and evaluated overall study quality utilising the GRADE instrument. MAIN RESULTS: Twenty-two trials with 1798 participants were included; sample sizes ranged from 15 to 250. Most studies followed participants for 12, 24 or 36 months; the longest follow-up was 10 years. The risk of bias across all domains of most trials was uncertain; just one was judged to have adequate allocation concealment.All seven RCTs comparing surgery with non-surgical interventions found benefits of surgery on measures of weight change at one to two years follow-up. Improvements for some aspects of health-related quality of life (QoL) (two RCTs) and diabetes (five RCTs) were also found. The overall quality of the evidence was moderate. Five studies reported data on mortality, no deaths occurred. Serious adverse events (SAEs) were reported in four studies and ranged from 0% to 37% in the surgery groups and 0% to 25% in the no surgery groups. Between 2% and 13% of participants required reoperations in the five studies that reported these data.Three RCTs found that laparoscopic Roux-en-Y gastric bypass (L)(RYGB) achieved significantly greater weight loss and body mass index (BMI) reduction up to five years after surgery compared with laparoscopic adjustable gastric banding (LAGB). Mean end-of-study BMI was lower following LRYGB compared with LAGB: mean difference (MD) -5.2 kg/m² (95% confidence interval (CI) -6.4 to -4.0; P < 0.00001; 265 participants; 3 trials; moderate quality evidence). Evidence for QoL and comorbidities was very low quality. The LRGYB procedure resulted in greater duration of hospitalisation in two RCTs (4/3.1 versus 2/1.5 days) and a greater number of late major complications (26.1% versus 11.6%) in one RCT. In one RCT the LAGB required high rates of reoperation for band removal (9 patients, 40.9%).Open RYGB, LRYGB and laparoscopic sleeve gastrectomy (LSG) led to losses of weight and/or BMI but there was no consistent picture as to which procedure was better or worse in the seven included trials. MD was -0.2 kg/m² (95% CI -1.8 to 1.3); 353 participants; 6 trials; low quality evidence) in favour of LRYGB.  No statistically significant differences in QoL were found (one RCT). Six RCTs reported mortality; one death occurred following LRYGB. SAEs were reported by one RCT and were higher in the LRYGB group (4.5%) than the LSG group (0.9%). Reoperations ranged from 6.7% to 24% in the LRYGB group and 3.3% to 34% in the LSG group. Effects on comorbidities, complications and additional surgical procedures were neutral, except gastro-oesophageal reflux disease improved following LRYGB (one RCT). One RCT of people with a BMI 25 to 35 and type 2 diabetes found laparoscopic mini-gastric bypass resulted in greater weight loss and improvement of diabetes compared with LSG, and had similar levels of complications.Two RCTs found that biliopancreatic diversion with duodenal switch (BDDS) resulted in greater weight loss than RYGB in morbidly obese patients. End-of-study mean BMI loss was greater following BDDS: MD -7.3 kg/m² (95% CI -9.3 to -5.4); P < 0.00001; 107 participants; 2 trials; moderate quality evidence). QoL was similar on most domains. In one study between 82% to 100% of participants with diabetes had a HbA1c of less than 5% three years after surgery. Reoperations were higher in the BDDS group (16.1% to 27.6%) than the LRYGB group (4.3% to 8.3%). One death occurred in the BDDS group.One RCT comparing laparoscopic duodenojejunal bypass with sleeve gastrectomy versus LRYGB found BMI, excess weight loss, and rates of remission of diabetes and hypertension were similar at 12 months follow-up (very low quality evidence). QoL, SAEs and reoperation rates were not reported. No deaths occurred in either group.One RCT comparing laparoscopic isolated sleeve gastrectomy (LISG) versus LAGB found greater improvement in weight-loss outcomes following LISG at three years follow-up (very low quality evidence). QoL, mortality and SAEs were not reported. Reoperations occurred in 20% of the LAGB group and in 10% of the LISG group.One RCT (unpublished) comparing laparoscopic gastric imbrication with LSG found no statistically significant difference in weight loss between groups (very low quality evidence).  QoL and comorbidities were not reported. No deaths occurred. Two participants in the gastric imbrication group required reoperation. AUTHORS' CONCLUSIONS: Surgery results in greater improvement in weight loss outcomes and weight associated comorbidities compared with non-surgical interventions, regardless of the type of procedures used. When compared with each other, certain procedures resulted in greater weight loss and improvements in comorbidities than others. Outcomes were similar between RYGB and sleeve gastrectomy, and both of these procedures had better outcomes than adjustable gastric banding. For people with very high BMI, biliopancreatic diversion with duodenal switch resulted in greater weight loss than RYGB. Duodenojejunal bypass with sleeve gastrectomy and laparoscopic RYGB had similar outcomes, however this is based on one small trial. Isolated sleeve gastrectomy led to better weight-loss outcomes than adjustable gastric banding after three years follow-up. This was based on one trial only.  Weight-related outcomes were similar between laparoscopic gastric imbrication and laparoscopic sleeve gastrectomy in one trial. Across all studies adverse event rates and reoperation rates were generally poorly reported. Most trials followed participants for only one or two years, therefore the long-term effects of surgery remain unclear.

Are trainee teachers being adequately prepared to promote the health and well-being of school children? A survey of current practice.

BACKGROUND: Teachers are a key part of the wider public health workforce in England. We conducted a survey to find out how they are trained for this role during their initial teacher education (ITE). METHODS: Between 2011 and 2012, we sent an online questionnaire to 220 ITE course managers and conducted semi-structured interviews with a purposive sample of 19 course managers to explore issues in more depth. RESULTS: The response rate to the questionnaire was 34% (n = 74). Although most of the course managers felt inclusion of health and well-being training in ITE was important, provision across courses was variable. Topics which are public health priorities [e.g. sex and relationships education (SRE) and drugs, alcohol and tobacco] were covered by fewer courses than other topics (e.g. child protection, emotional health and anti-bullying). Perceived barriers to training included lack of time and a belief that health and well-being were low priorities in educational policy. CONCLUSIONS: Not all of tomorrow's teachers are being adequately prepared for their role in helping to address public health priorities. Educational policy does not appear to be supporting the priorities of public health policy, and this is a key barrier to health promotion training in ITE. Keywords children, educational settings, health promotion.