Factors within the clinical encounter that impact upon risk assessment within child and adolescent mental health services: a rapid realist synthesis.

Background: Risk assessment is a key process when a child or adolescent presents at risk for self-harm or suicide in a mental health crisis or emergency. Risk assessment by a healthcare professional should be included within a biopsychosocial assessment. However, the predictive value of risk-screening tools for self-harm and suicide in children and adolescents is consistently challenged. A review is needed to explore how best to undertake risk assessment and the appropriate role for tools/checklists within the assessment pathway. Aims: To map research relating to risk assessment for child and adolescent mental health and to identify features that relate to a successful risk assessment. Objectives: To review factors within the clinical encounter that impact upon risk assessments for self-harm and suicide in children and adolescents: i. to conduct a realist synthesis to understand mechanisms for risk assessment, why they occur and how they vary by context ii. to conduct a mapping review of primary studies/reviews to describe available tools of applicability to the UK. Data sources: Databases, including MEDLINE, PsycINFO®, EMBASE, CINAHL, HMIC, Science and Social Sciences Citation Index and the Cochrane Library, were searched (September 2021). Searches were also conducted for reports from websites. Review methods: A resource-constrained realist synthesis was conducted exploring factors that impact upon risk assessments for self-harm and suicide. This was accompanied by a mapping review of primary studies/reviews describing risk-assessment tools and approaches used in UK child and adolescent mental health. Following piloting, four reviewers screened retrieved records. Items were coded for the mapping and/or for inclusion in the realist synthesis. The review team examined the validity and limitations of risk-screening tools. In addition, the team identified structured approaches to risk assessment. Reporting of the realist synthesis followed RAMESES guidelines. Results: From 4084 unique citations, 249 papers were reviewed and 41 studies (49 tools) were included in the mapping review. Eight reviews were identified following full-text screening. Fifty-seven papers were identified for the realist review. Findings highlight 14 explanations (programme theories) for a successful risk assessment for self-harm and suicide. Forty-nine individual assessment tools/approaches were identified. Few tools were developed in the UK, specifically for children and adolescents. These lacked formal independent evaluation. No risk-screening tool is suitable for risk prediction; optimal approaches incorporate a relationship of trust, involvement of the family, where appropriate, and a patient-centred holistic approach. The objective of risk assessment should be elicitation of information to direct a risk formulation and care plan. Limitations: Many identified tools are well-established but lack scientific validity, particularly predictive validity, or clinical utility. Programme theories were generated rapidly from a survey of risk assessment. Conclusions: No single checklist/approach meets the needs of risk assessment for self-harm and suicide. A whole-system approach is required, informed by structured clinical judgement. Useful components include a holistic assessment within a climate of trust, facilitated by family involvement. Study registration: This study is registered as PROSPERO CRD42021276671. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR135079) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information.

When young people up to 18 years of age present to health services, having tried to poison themselves, take an overdose or injure themselves, a health professional needs to work out whether this is likely to happen again (risk assessment). Lists of questions or things to look for (risk screening) have proved unreliable. Thorough discussion with the child or teenager may be helpful but takes much time. How can a health professional best use time spent with a young person to prevent further harm and make sure that they get the treatment that they need? This review focuses on young persons who use health services in the UK. Included studies report how health professionals work out whether young people are likely to harm themselves; either how to handle the overall discussion or to use memory aids or checklists (known as tools) to help the discussion. Tools developed in the USA many years ago have not been tested well enough with UK populations. Recent approaches within the UK are used inconsistently. Young persons do not like how they are assessed. Health professionals may use methods that have not been shown to work or use tools differently from how they were designed. This review identified 14 ways to help a young person have valued discussions with a health professional. Health professionals should not simply 'tick boxes'; tools should help them gain a full picture, including input from other family members. Health professionals should create a trusted relationship where the young person feels respected and heard. Tools should not label someone 'at risk' but should support care that reduces the risk of further harm. Health professionals should gather good-quality information that includes asking about thoughts of suicide. Staff should be supported by training, guidance and feedback from experienced colleagues.

Reducing unplanned hospital admissions from care homes: a systematic review.

Background: Care homes predominantly care for older people with complex health and care needs, who are at high risk of unplanned hospital admissions. While often necessary, such admissions can be distressing and provide an opportunity cost as well as a financial cost. Objectives: Our objective was to update a 2014 evidence review of interventions to reduce unplanned admissions of care home residents. We carried out a systematic review of interventions used in the UK and other high-income countries by synthesising evidence of effects of these interventions on hospital admissions; feasibility and acceptability; costs and value for money; and factors affecting applicability of international evidence to UK settings. Data sources: We searched the following databases in December 2021 for studies published since 2014: Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews; Cumulative Index to Nursing and Allied Health Literature; Health Management Information Consortium; Medline; PsycINFO; Science and Social Sciences Citation Indexes; Social Care Online; and Social Service Abstracts. 'Grey' literature (January 2022) and citations were searched and reference lists were checked. Methods: We included studies of any design reporting interventions delivered in care homes (with or without nursing) or hospitals to reduce unplanned hospital admissions. A taxonomy of interventions was developed from an initial scoping search. Outcomes of interest included measures of effect on unplanned admissions among care home residents; barriers/facilitators to implementation in a UK setting and acceptability to care home residents, their families and staff. Study selection, data extraction and risk of bias assessment were performed by two independent reviewers. We used published frameworks to extract data on intervention characteristics, implementation barriers/facilitators and applicability of international evidence. We performed a narrative synthesis grouped by intervention type and setting. Overall strength of evidence for admission reduction was assessed using a framework based on study design, study numbers and direction of effect. Results: We included 124 publications/reports (30 from the UK). Integrated care and quality improvement programmes providing additional support to care homes (e.g. the English Care Homes Vanguard initiatives and hospital-based services in Australia) appeared to reduce unplanned admissions relative to usual care. Simpler training and staff development initiatives showed mixed results, as did interventions aimed at tackling specific problems (e.g. medication review). Advance care planning was key to the success of most quality improvement programmes but do-not-hospitalise orders were problematic. Qualitative research identified tensions affecting decision-making involving paramedics, care home staff and residents/family carers. The best way to reduce end-of-life admissions through access to palliative care was unclear in the face of inconsistent and generally low-quality evidence. Conclusions: Effective implementation of interventions at various stages of residents' care pathways may reduce unplanned admissions. Most interventions are complex and require adaptation to local contexts. Work at the interface between health and social care is key to successful implementation. Limitations: Much of the evidence identified was of low quality because of factors such as uncontrolled study designs and small sample size. Meta-analysis was not possible. Future work: We identified a need for improved economic evidence and the evaluation of integrated care models of the type delivered by hospital-based teams. Researchers should carefully consider what is realistic in terms of study design and data collection given the current context of extreme pressure on care homes. Study registration: This study is registered as PROSPERO database CRD42021289418. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (award number NIHR133884) and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 18. See the NIHR Journals Library website for further project information.

Older people living in care homes often have complex health problems such as dementia and frailty, and they may need to be taken to hospital at short notice. This can lead to them being admitted for further tests and treatment. We know that some of these unplanned hospital admissions might be avoided if health and social care services worked together to meet residents' needs. We looked for published research on methods (interventions) used in health and social care to reduce these admissions. Interventions could be carried out by care home staff, general practitioners, nurses, paramedics or other specialists individually or in teams. We asked which interventions have been evaluated, how strong is the evidence that they work and how acceptable they are to care home residents, family carers and staff. We also looked for information on how easy or difficult they are to implement and whether they represent good value for money. We included 124 research studies (30 from the UK). We found that integrated care programmes linking care homes with general practitioners and community services can be effective but need time and support (such as extra money and specialist staff) to implement them. Quality improvement programmes and training to improve staff skills may also reduce admissions. For care home residents nearing the end of life, advance care planning and palliative care can ensure that wishes are followed and avoid potentially burdensome admissions to hospital. Hospital-based teams providing 'outreach' services to care homes have been evaluated in Australia and could be suitable for UK research. We found limited evidence on interventions involving paramedics and on 'value for money'. We found many barriers to implementing new services in the UK, particularly staff shortages and high staff turnover, together with care homes closing down or changing ownership. Successful interventions have often been based on existing services and relationships.

A systematic review case study of urgent and emergency care configuration found citation searching of Web of Science and Google Scholar of similar value.

BACKGROUND: Supplementary search methods, including citation searching, are essential if systematic reviews are to avoid producing biased conclusions. Little evidence exists on how to prioritise databases for citation searching or to establish whether using multiple sources is beneficial. OBJECTIVES: A systematic review examining urgent and emergency care reconfiguration was used to investigate the utility of citation searching on Web of Science (WOS) and/or Google Scholar (GS). METHODS: This case study investigated numbers of studies, additional studies and unique studies retrieved from both sources. In addition, the time to search, the ease of adding references to reference management software and obtaining abstracts of studies for screening are briefly considered. RESULTS: WOS retrieved 62 references after deduplication of the results, 52 being additional references not retrieved during the database searching. GS retrieved 134 unique references with 63 additional references. WOS and GS retrieved the same three additional included studies. WOS was less time intensive to search given the facility to restrict to English language papers and availability of abstracts. CONCLUSIONS: In a single systematic review case study, citation searching was required to identify all included studies. Citation searching on WOS is more efficient, where a subscription is available. Both databases identified the same studies but GS required additional time to remove non-English language studies and locate abstracts.

Recognition of risk and prevention in safeguarding of children and young people: a mapping review and component analysis of service development interventions aimed at health and social care professionals.

BACKGROUND: The term 'safeguarding' covers the protection of health, wellbeing and human rights. Effective safeguarding enables people (particularly children, young adults and other vulnerable people) to live free from fear of abuse, harm or neglect. The UK Children Act 2004 required key agencies, including health and social care providers, to consider the need to safeguard children and promote their welfare. Within a larger evidence synthesis project, we sought to identify and map service development interventions (excluding provision of training) aimed at improving awareness of safeguarding and identifying at-risk children and young people in health and social care settings. METHODS: We searched fourteen health and social care databases from 2004 (date of Children Act) to October 2019 and updated the review via a citation search in March 2021. Studies of any design were eligible if they described or evaluated an intervention (other than training) aimed at health or social care professionals in the United Kingdom and designed to improve recognition of risk in the context of safeguarding children and young people. Studies with no intervention (e.g. qualitative studies) were included to explain why interventions work or fail to work. Included studies were summarised using narrative synthesis. Risk of bias of included studies and overall strength of evidence were assessed using standard methods. We used a 5-item checklist ("TIDieR-Lite") to map intervention components. RESULTS: Thirty-nine publications were included, of which 31 dealt with service developments, six with use of data and two with other initiatives. Promising service development initiatives include liaison nurses, assessment clinics, secondment, joint protocols and a 'hub and spoke' model. Initiatives involving use of routine data appeared promising and unlikely to generate significant additional costs. However, the quality of the evidence was generally low, with a shortage of controlled and long-term studies. CONCLUSIONS: Health and social care services wishing to improve awareness of child safeguarding issues may benefit from looking beyond high-quality training provision. Future research should focus on service-relevant outcomes and ensure the active involvement of young people and their families/carers.

Effects of service changes affecting distance/time to access urgent and emergency care facilities on patient outcomes: a systematic review.

BACKGROUND: Reconfiguration of urgent and emergency care services often increases travel time/distance for patients to reach an appropriate facility. Evidence of the effects of reconfiguration is important for local communities and commissioners and providers of health services. METHODS: We performed a systematic review of the evidence regarding effects of service reconfigurations that increase the time/distance for some patients to reach an urgent and emergency care (UEC) facility. We searched seven bibliographic databases from 2000 to February 2019 and used citation tracking and reference lists to identify additional studies. We included studies of any design that compared outcomes for people with conditions requiring emergency treatment before and after service reconfiguration with an associated change in travel time/distance to access UEC. Studies had to be conducted in the UK or other developed countries. Data extraction and quality assessment (using the Joanna Briggs Institute checklist for quasi-experimental studies) were undertaken by a single reviewer with a sample checked for accuracy and consistency. We performed a narrative synthesis of the included studies. Overall strength of evidence was assessed using a previously published method that considers volume, quality and consistency. RESULTS: We included 12 studies, of which six were conducted in the USA, two in the UK and four in other European countries. The studies used a variety of observational designs, with before-after and cohort designs being most common. Only two studies included an independent control site/sites where no reconfiguration had taken place. The reconfigurations evaluated in these studies reported relatively small effects on average travel times/distance. DISCUSSION: For studies of general UEC populations, there was no convincing evidence as to whether reconfiguration affected mortality risk. However, evidence of increased risk was identified from studies of patients with acute myocardial infarction, particularly 1 to 4 years after reconfiguration. Evidence for other conditions was inconsistent or very limited. CONCLUSIONS: We found insufficient evidence to determine whether increased distance to UEC increases mortality risk for the general population of people requiring UEC, although this conclusion may not extend to people with specific conditions.

Digital and online symptom checkers and health assessment/triage services for urgent health problems: systematic review.

OBJECTIVES: In England, the NHS111 service provides assessment and triage by telephone for urgent health problems. A digital version of this service has recently been introduced. We aimed to systematically review the evidence on digital and online symptom checkers and similar services. DESIGN: Systematic review. DATA SOURCES: We searched Medline, Embase, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Health Management Information Consortium, Web of Science and ACM Digital Library up to April 2018, supplemented by phrase searches for known symptom checkers and citation searching of key studies. ELIGIBILITY CRITERIA: Studies of any design that evaluated a digital or online symptom checker or health assessment service for people seeking advice about an urgent health problem. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment (using the Cochrane Collaboration version of QUADAS for diagnostic accuracy studies and the National Heart, Lung and Blood Institute tool for observational studies) were done by one reviewer with a sample checked for accuracy and consistency. We performed a narrative synthesis of the included studies structured around pre-defined research questions and key outcomes. RESULTS: We included 29 publications (27 studies). Evidence on patient safety was weak. Diagnostic accuracy varied between different systems but was generally low. Algorithm-based triage tended to be more risk averse than that of health professionals. There was very limited evidence on patients' compliance with online triage advice. Study participants generally expressed high levels of satisfaction, although in mainly uncontrolled studies. Younger and more highly educated people were more likely to use these services. CONCLUSIONS: The English 'digital 111' service has been implemented against a background of uncertainty around the likely impact on important outcomes. The health system may need to respond to short-term changes and/or shifts in demand. The popularity of online and digital services with younger and more educated people has implications for health equity. PROSPERO REGISTRATION NUMBER: CRD42018093564.

Towards greater understanding of implementation during systematic reviews of complex healthcare interventions: the framework for implementation transferability applicability reporting (FITAR).

BACKGROUND: There have been calls for greater consideration of applicability and transferability in systematic reviews, to improve their usefulness in informing policy and practice. Understanding how evidence is, or is not applicable and transferable to varying local situations and contexts, is a key challenge for systematic review synthesis in healthcare. Assessing applicability and transferability in systematic reviews is reported to be difficult, particularly in reviews of complex interventions. There is a need for exploration of factors perceived to be important by policy-makers, and for further guidance on which items should be reported. In this paper we focus on the process of development of a framework that can be used by systematic reviewers to identify and report data across studies relating to applicability and transferability. METHODS: The framework was developed by scrutinising existing literature on applicability and transferability, examining data during a systematic review of highly complex changes to health service delivery, and was informed by stakeholder engagement. The items of the framework were thus grounded in both data identified during a real review, and stakeholder input. The paper describes examples of data identified using the framework during a review of integrated care interventions, and outlines how it informed analysis and reporting of the review findings. RESULTS: The Framework for Implementation Transferability Applicability Reporting (FITAR) comprises 44 items which can be used to structure analysis and reporting across studies during systematic reviews of complex interventions. The framework prompts detailed consideration of contextual data during extraction and reporting, within areas of: patient type and populations; type of organisations and systems; financial and commissioning processes; systems leadership elements; features of services; features of the workforce; and finally elements of the interventions/initiatives. CONCLUSIONS: Use of the framework during our review of complex healthcare interventions helped the review team to surface contextual data, which may not be commonly extracted, analysed and reported. Further exploration and evaluation of systems for identifying and reporting these factors during reviews is required.

What Is the Burden of Immunoglobulin Replacement Therapy in Adult Patients With Primary Immunodeficiencies? A Systematic Review.

BACKGROUND: Primary immunodeficiency disorders (PIDs) are a group of heterogeneous rare disorders, whereby the immune system is missing or not functioning adequately. For patients requiring treatment, the most common option is immunoglobulin replacement therapy (Ig). Treatment of PIDs is simultaneously associated with both improvements in health-related quality of life (HRQoL) and increased treatment burden. OBJECTIVES: This review sought to review studies investigating the burden of Ig treatment, synthesize evidence in relation to administration routes (subcutaneous or intravenous) and instruments used, as well as make recommendations for clinical and research applications in this area for patients aged 16 years and older. METHODS: We searched Medline, EMBASE, and The Cochrane Library. Sifting of titles was performed by two reviewers, and the assessment of full-text articles by three. From a database which contained 3,770 unique results, 67 full texts were reviewed. Eventually, 17 studies were found to meet the inclusion criteria, and included in this review. Due to data heterogeneity, a narrative, descriptive synthesis of the evidence was undertaken. RESULTS: Most studies were carried out in the USA/North America, used a prospective observational design and involved patients with common variable immune deficiency. Four studies measured the burden of receiving IVIg therapy and 13 measured SCIg therapy. A wide range of measures, primarily designed to measure aspects of treatment satisfaction (e.g., life quality index or a slightly modified version) and HRQoL (e.g., The Short Form-36) had been used. CONCLUSION: Lack of a parallel control group in most studies meant that changes in outcomes could be due to factors other than changes in the treatment regimen. However, overall, PID patients appeared to report little Ig treatment burden and were satisfied with either modality. However, patient preference appeared to be the delivery of the Ig treatment in the patient's home and SCIg was preferred after switching from IVIg therapy. Individual differences appeared to affect treatment preference and therefore understanding the decision support needs of PID patients facing IG treatment choices would be valuable. Using a questionnaire specifically designed to measure the burden of Ig treatment from the patient's perspective is recommended in future research.

The effects of integrated care: a systematic review of UK and international evidence.

BACKGROUND: Healthcare systems around the world have been responding to the demand for better integrated models of service delivery. However, there is a need for further clarity regarding the effects of these new models of integration, and exploration regarding whether models introduced in other care systems may achieve similar outcomes in a UK national health service context. METHODS: The study aimed to carry out a systematic review of the effects of integration or co-ordination between healthcare services, or between health and social care on service delivery outcomes including effectiveness, efficiency and quality of care. Electronic databases including MEDLINE; Embase; PsycINFO; CINAHL; Science and Social Science Citation Indices; and the Cochrane Library were searched for relevant literature published between 2006 to March 2017. Online sources were searched for UK grey literature, and citation searching, and manual reference list screening were also carried out. Quantitative primary studies and systematic reviews, reporting actual or perceived effects on service delivery following the introduction of models of integration or co-ordination, in healthcare or health and social care settings in developed countries were eligible for inclusion. Strength of evidence for each outcome reported was analysed and synthesised using a four point comparative rating system of stronger, weaker, inconsistent or limited evidence. RESULTS: One hundred sixty seven studies were eligible for inclusion. Analysis indicated evidence of perceived improved quality of care, evidence of increased patient satisfaction, and evidence of improved access to care. Evidence was rated as either inconsistent or limited regarding all other outcomes reported, including system-wide impacts on primary care, secondary care, and health care costs. There were limited differences between outcomes reported by UK and international studies, and overall the literature had a limited consideration of effects on service users. CONCLUSIONS: Models of integrated care may enhance patient satisfaction, increase perceived quality of care, and enable access to services, although the evidence for other outcomes including service costs remains unclear. Indications of improved access may have important implications for services struggling to cope with increasing demand. TRIAL REGISTRATION: Prospero registration number: 42016037725 .

Socioeconomic inequalities in mortality, morbidity and diabetes management for adults with type 1 diabetes: A systematic review.

AIMS: To systematically review the evidence of socioeconomic inequalities for adults with type 1 diabetes in relation to mortality, morbidity and diabetes management. METHODS: We carried out a systematic search across six relevant databases and included all studies reporting associations between socioeconomic indicators and mortality, morbidity, or diabetes management for adults with type 1 diabetes. Data extraction and quality assessment was undertaken for all included studies. A narrative synthesis was conducted. RESULTS: A total of 33 studies were identified. Twelve cohort, 19 cross sectional and 2 case control studies met the inclusion criteria. Regardless of healthcare system, low socioeconomic status was associated with poorer outcomes. Following adjustments for other risk factors, socioeconomic status was a statistically significant independent predictor of mortality in 9/10 studies and morbidity in 8/10 studies for adults with type 1 diabetes. There appeared to be an association between low socioeconomic status and some aspects of diabetes management. Although only 3 of 16 studies made adjustments for confounders and other risk factors, poor diabetes management was associated with lower socioeconomic status in 3/3 of these studies. CONCLUSIONS: Low socioeconomic status is associated with higher levels of mortality and morbidity for adults with type 1 diabetes even amongst those with access to a universal healthcare system. The association between low socioeconomic status and diabetes management requires further research given the paucity of evidence and the potential for diabetes management to mitigate the adverse effects of low socioeconomic status.

Enhanced recovery after elective caesarean: a rapid review of clinical protocols, and an umbrella review of systematic reviews.

BACKGROUND: The rate of elective Caesarean Section (CS) is rising in many countries. Many obstetric units in the UK have either introduced or are planning to introduce enhanced recovery (ER) as a means of reducing length of stay for planned CS. However, to date there has been very little evidence produced regarding the necessary components of ER for the obstetric population. We conducted a rapid review of the composition of published ER pathways for elective CS and undertook an umbrella review of systematic reviews evaluating ER components and pathways in any surgical setting. METHODS: Pathways were identified using MEDLINE, EMBASE and the National Guideline Clearing House, appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool and their components tabulated. Systematic reviews were identified using the Cochrane Library and Database of Abstracts of Reviews of Effects (DARE) and appraised using The Grading of Recommendations Assessment, Development and Evaluation (GRADE). Two reviewers aggregated summaries of findings for Length of Stay (LoS). RESULTS: Five clinical protocols were identified, involving a total of 25 clinical components; 3/25 components were common to all five pathways (early oral intake, mobilization and removal of urinary catheter). AGREE II scores were generally low. Systematic reviews of single components found that minimally invasive Joel-Cohen surgical technique, early catheter removal and post-operative antibiotic prophylaxis reduced LoS after CS most significantly by around half to 1 and a half days. Ten meta-analyses of multi-component Enhanced Recovery after Surgery (ERAS) packages demonstrated reductions in LoS of between 1 and 4 days. The quality of evidence was mostly low or moderate. CONCLUSIONS: Further research is needed to develop, using formal methods, and evaluate pathways for enhanced recovery in elective CS. Appropriate quality improvement packages are needed to optimise their implementation.

Evolocumab for Treating Primary Hypercholesterolaemia and Mixed Dyslipidaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of evolocumab (Amgen) to submit evidence on the clinical and cost effectiveness of evolocumab. The appraisal assessed evolocumab as monotherapy or in combination with a statin with or without ezetimibe, or in combination with ezetimibe (without statin therapy), in adult patients with primary hypercholesterolaemia (which includes mixed dyslipidaemia), for whom statins do not provide optimal control of their low-density lipoprotein cholesterol (LDL-C) levels and/or for whom statins are contraindicated or not tolerated. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based on the company's submission to NICE. The evidence was derived mainly from four randomised controlled trials comparing evolocumab with either ezetimibe or placebo in adults with primary familial or non-familial hypercholesterolaemia, who were either able to take statins or who were statin intolerant. The clinical-effectiveness review found that evolocumab is efficacious at lowering LDL-C but that there was uncertainty regarding its impact on cardiovascular disease (CVD) outcomes. In response to the ERG's critique of the submitted health economic model, the company submitted an amended model, which also included a patient access scheme (PAS). Based on this, the deterministic incremental cost-effectiveness ratios (ICERs) for evolocumab against ezetimibe were above £74,000 and £45,000 per quality-adjusted life-year (QALY) gained within the non-familial primary and secondary prevention populations, respectively, whilst the ICER within the heterozygous familial hypercholesterolaemia (HeFH) population was approximately £23,000 per QALY gained. The final determination was that evolocumab would be a clinically and cost-effective use of UK NHS resource in certain patient subgroups.

Does access to a demand-led evidence briefing service improve uptake and use of research evidence by health service commissioners? A controlled before and after study.

BACKGROUND: The Health and Social Care Act mandated research use as a core consideration of health service commissioning arrangements in England. We undertook a controlled before and after study to evaluate whether access to a demand-led evidence briefing service improved the use of research evidence by commissioners compared with less intensive and less targeted alternatives. METHODS: Nine Clinical Commissioning Groups (CCGs) in the North of England received one of three interventions: (A) access to an evidence briefing service; (B) contact plus an unsolicited push of non-tailored evidence; or (C) unsolicited push of non-tailored evidence. Data for the primary outcome measure were collected at baseline and 12 months using a survey instrument devised to assess an organisations' ability to acquire, assess, adapt and apply research evidence to support decision-making. Documentary and observational evidence of the use of the outputs of the service were sought. RESULTS: Over the course of the study, the service addressed 24 topics raised by participating CCGs. At 12 months, the evidence briefing service was not associated with increases in CCG capacity to acquire, assess, adapt and apply research evidence to support decision-making, individual intentions to use research findings or perceptions of CCG relationships with researchers. Regardless of intervention received, participating CCGs indicated that they remained inconsistent in their research-seeking behaviours and in their capacity to acquire research. The informal nature of decision-making processes meant that there was little traceability of the use of evidence. Low baseline and follow-up response rates and missing data limit the reliability of the findings. CONCLUSIONS: Access to a demand-led evidence briefing service did not improve the uptake and use of research evidence by NHS commissioners compared with less intensive and less targeted alternatives. Commissioners appear well intentioned but ad hoc users of research. Further research is required on the effects of interventions and strategies to build individual and organisational capacity to use research.

Degarelix for Treating Advanced Hormone-Dependent Prostate Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its Single Technology Appraisal Process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of degarelix (Ferring Pharmaceuticals) to submit evidence for the clinical and cost effectiveness of degarelix for the treatment of advanced hormone-dependent prostate cancer. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The evidence, which included a randomised controlled trial (RCT) of degarelix versus leuprorelin, found that degarelix was non-inferior to leuprorelin for reduction of testosterone levels and that degarelix achieved a more rapid suppression of prostate-specific antigen levels and subsequently decreased incidences of testosterone flare associated with luteinising hormone releasing-hormone (LHRH) agonists. However, protection against testosterone flare for the comparators in the clinical trials was not employed in line with UK clinical practice. Further claims surrounding overall survival, cardiovascular adverse events and clinical equivalence of the comparator drugs from six RCTs of degarelix should be regarded with caution because of flaws and inconsistencies in the pooling of trial data to draw conclusions. The cost-effectiveness evidence included a de novo economic model. Based on the ERG's preferred base case, the deterministic incremental cost-effectiveness analysis (ICER) for degarelix versus 3-monthly triptorelin was £14,798 per quality-adjusted life-year (QALY) gained. Additional scenario analyses undertaken by the ERG resulted in ICERs for degarelix versus 3-monthly triptorelin ranging from £17,067 to £35,589 per QALY gained. Subgroup analyses undertaken using the Appraisal Committee's preferred assumptions suggested that degarelix was not cost effective for the subgroup with metastatic disease but could be cost effective for the subgroup with spinal metastases. The company submitted further evidence to NICE following an initial negative Appraisal Committee decision. Further analyses from the Decision Support Unit found that that, whilst some evidence indicated that degarelix could be cost effective for a small subgroup of people with spinal cord compression (SCC), data on the potential size of this subgroup and the rate of SCC were insufficient to estimate an ICER based on the evidence submitted by the company and a separately commissioned systematic review. NICE recommended degarelix as an option for treating advanced hormone-dependent prostate cancer in people with spinal metastases, only if the commissioner can achieve at least the same discounted drug cost as that available to the UK NHS in June 2016.

Cabazitaxel for Hormone-Relapsed Metastatic Prostate Cancer Previously Treated With a Docetaxel-Containing Regimen: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana®, Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the company's submission to NICE. Clinical evidence for cabazitaxel was derived from a multinational randomised open-label phase III trial (TROPIC) of cabazitaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone, which was assumed to represent best supportive care. The NICE final scope identified a further three comparators: abiraterone in combination with prednisone or prednisolone; enzalutamide; and radium-223 dichloride for the subgroup of people with bone metastasis only (no visceral metastasis). The company did not consider radium-223 dichloride to be a relevant comparator. Neither abiraterone nor enzalutamide has been directly compared in a trial with cabazitaxel. Instead, clinical evidence was synthesised within a network meta-analysis (NMA). Results from TROPIC showed that cabazitaxel was associated with a statistically significant improvement in both overall survival and progression-free survival compared with mitoxantrone. Results from a random-effects NMA, as conducted by the company and updated by the ERG, indicated that there was no statistically significant difference between the three active treatments for both overall survival and progression-free survival. Utility data were not collected as part of the TROPIC trial, and were instead taken from the company's UK early access programme. Evidence on resource use came from the TROPIC trial, supplemented by both expert clinical opinion and a UK clinical audit. List prices were used for mitoxantrone, abiraterone and enzalutamide as directed by NICE, although commercial in-confidence patient-access schemes (PASs) are in place for abiraterone and enzalutamide. The confidential PAS was used for cabazitaxel. Sequential use of the advanced hormonal therapies (abiraterone and enzalutamide) does not usually occur in clinical practice in the UK. Hence, cabazitaxel could be used within two pathways of care: either when an advanced hormonal therapy was used pre-docetaxel, or when one was used post-docetaxel. The company believed that the former pathway was more likely to represent standard National Health Service (NHS) practice, and so their main comparison was between cabazitaxel and mitoxantrone, with effectiveness data from the TROPIC trial. Results of the company's updated cost-effectiveness analysis estimated a probabilistic incremental cost-effectiveness ratio (ICER) of £45,982 per quality-adjusted life-year (QALY) gained, which the committee considered to be the most plausible value for this comparison. Cabazitaxel was estimated to be both cheaper and more effective than abiraterone. Cabazitaxel was estimated to be cheaper but less effective than enzalutamide, resulting in an ICER of £212,038 per QALY gained for enzalutamide compared with cabazitaxel. The ERG noted that radium-223 is a valid comparator (for the indicated sub-group), and that it may be used in either of the two care pathways. Hence, its exclusion leads to uncertainty in the cost-effectiveness results. In addition, the company assumed that there would be no drug wastage when cabazitaxel was used, with cost-effectiveness results being sensitive to this assumption: modelling drug wastage increased the ICER comparing cabazitaxel with mitoxantrone to over £55,000 per QALY gained. The ERG updated the company's NMA and used a random effects model to perform a fully incremental analysis between cabazitaxel, abiraterone, enzalutamide and best supportive care using PASs for abiraterone and enzalutamide. Results showed that both cabazitaxel and abiraterone were extendedly dominated by the combination of best supportive care and enzalutamide. Preliminary guidance from the committee, which included wastage of cabazitaxel, did not recommend its use. In response, the company provided both a further discount to the confidential PAS for cabazitaxel and confirmation from NHS England that it is appropriate to supply and purchase cabazitaxel in pre-prepared intravenous-infusion bags, which would remove the cost of drug wastage. As a result, the committee recommended use of cabazitaxel as a treatment option in people with an Eastern Cooperative Oncology Group performance status of 0 or 1 whose disease had progressed during or after treatment with at least 225 mg/m2 of docetaxel, as long as it was provided at the discount agreed in the PAS and purchased in either pre-prepared intravenous-infusion bags or in vials at a reduced price to reflect the average per-patient drug wastage.

Evolocumab for Treating Primary Hypercholesterolaemia and Mixed Dyslipidaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of evolocumab (Amgen) to submit evidence on the clinical and cost effectiveness of evolocumab. The appraisal assessed evolocumab as monotherapy or in combination with a statin (HMG-CoA reductase inhibitor) with or without ezetimibe, or in combination with ezetimibe (without statin therapy), in adult patients with primary hypercholesterolaemia (which includes mixed dyslipidaemia), for whom statins do not provide optimal control of their low-density lipoprotein cholesterol (LDL-C) levels and/or for whom statins are contraindicated or not tolerated. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology, based on the company's submission to NICE. The evidence was derived mainly from four randomised controlled trials comparing evolocumab either with ezetimibe or placebo in adults with primary familial or non-familial hypercholesterolaemia, who were either able to take statins or who were statin-intolerant. The clinical effectiveness review found that evolocumab is efficacious at lowering LDL-C but that there was uncertainty regarding its impact on cardiovascular disease outcomes. In response to the ERG's critique of the submitted health economic model, the company submitted an amended model, which also included a Patient Access Scheme (PAS). Based on this, the deterministic incremental cost-effectiveness ratios (ICERs) for evolocumab against ezetimibe were above £74,000 and £45,000 per quality-adjusted life-year (QALY) gained within the non-familial primary and secondary prevention population, respectively, whilst the ICERs within the heterozygous familial hypercholesterolaemia population were approximately £23,000 per QALY gained. The final determination was that evolocumab would be a clinically and cost effective use of UK National Health Service resources in certain patient subgroups.

Service user engagement in health service reconfiguration: a rapid evidence synthesis.

OBJECTIVE: To assess what is known about effective patient and public engagement in health service reconfiguration processes and identify implications for further research and health care practice. METHODS: Rapid systematic review of published and grey literature to identify methods or approaches to engagement in decisions about health service reconfiguration; and to examine how engagement has worked or not worked in specific examples of system change. Following a search for literature published in English from 2000 to March 2014, eight systematic reviews, seven primary studies and 24 case studies (of which 6 were exemplars) were included. We undertook a narrative synthesis to consider five aspects of engagement with health service reconfiguration. RESULTS: Engagement varied in nature and intensity, and efforts generally involved multiple methods. There was no evidence on the isolated impact of any particular engagement method or collection of methods. In general, engagement was most likely to be successful when started early, when led and supported by clinicians, and when it offered opportunities for genuine interaction. The impact of engagement was variably measured and demonstrated, and frequently defined as process measures rather than the outcomes of proposals for service reconfiguration. Little was reported on the potential negative impact of service user engagement. CONCLUSIONS: Patients and the public can be engaged through various methods. Problems often arise because decision-makers paid insufficient attention to issues considered important by patients and the public. Guidance setting out the stages of reconfiguration and opportunities for service user input could be a helpful practical framework for future engagement activity. Future evaluation and explicit reporting of engagement and impact is needed.

Effects of a demand-led evidence briefing service on the uptake and use of research evidence by commissioners of health services: protocol for a controlled before and after study.

BACKGROUND: Clinical Commissioning Groups (CCGs) are mandated to use research evidence effectively to ensure optimum use of resources by the National Health Service (NHS), both in accelerating innovation and in stopping the use of less effective practices and models of service delivery. We intend to evaluate whether access to a demand-led evidence service improves uptake and use of research evidence by NHS commissioners compared with less intensive and less targeted alternatives. METHODS/DESIGN: This is a controlled before and after study involving CCGs in the North of England. Participating CCGs will receive one of three interventions to support the use of research evidence in their decision-making: 1) consulting plus responsive push of tailored evidence; 2) consulting plus an unsolicited push of non-tailored evidence; or 3) standard service unsolicited push of non-tailored evidence. Our primary outcome will be changed at 12 months from baseline of a CCGs ability to acquire, assess, adapt and apply research evidence to support decision-making. Secondary outcomes will measure individual clinical leads and managers' intentions to use research evidence in decision making. Documentary evidence of the use of the outputs of the service will be sought. A process evaluation will evaluate the nature and success of the interactions both within the sites and between commissioners and researchers delivering the service. DISCUSSION: The proposed research will generate new knowledge of direct relevance and value to the NHS. The findings will help to clarify which elements of the service are of value in promoting the use of research evidence. Those involved in NHS commissioning will be able to use the results to inform how best to build the infrastructure they need to acquire, assess, adapt and apply research evidence to support decision-making and to fulfil their statutory duties under the Health and Social Care Act.

Effectiveness and implementation of enhanced recovery after surgery programmes: a rapid evidence synthesis.

OBJECTIVES: To assess the evidence on the impact of enhanced recovery programmes for patients undergoing elective surgery in acute hospital settings in the UK. DESIGN: Rapid evidence synthesis. Eight databases were searched from 1990 to March 2013 without language restrictions. Relevant reports and guidelines, websites and reference lists of retrieved articles were scanned to identify additional studies. Systematic reviews, RCTs not included in the systematic reviews, economic evaluations and UK NHS cost analysis, implementation case studies and surveys of patient experience in a UK setting were eligible for inclusion. PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed the impact of enhanced recovery programmes on health or cost-related outcomes, and assessed implementation case studies and patient experience in UK settings. Studies were quality assessed where appropriate using the Centre for Reviews and Dissemination Database of Abstracts of Reviews of Effects critical appraisal process. RESULTS: 17 systematic reviews and 12 additional RCTs were included. Ten relevant economic evaluations were included. No cost analysis studies were identified. Most of the evidence focused on colorectal surgery. 14 innovation case studies and 15 implementation case studies undertaken in National Health Service settings described factors critical to the success of an enhanced recovery programme. Evidence for colorectal surgery suggests that enhanced recovery programmes may reduce hospital stays by 0.5-3.5 days compared with conventional care. There were no significant differences in reported readmission rates. Other surgical specialties showed greater variation in reductions in length of stay reflecting the limited evidence identified. Findings relating to other outcomes were hampered by a lack of robust evidence and poor reporting. CONCLUSIONS: There is consistent, albeit limited, evidence that enhanced recovery programmes can reduce length of patient hospital stay without increasing readmission rates. The extent to which managers and clinicians considering implementing enhanced recovery programmes in UK settings can realise savings will depend on length of stay achieved under their existing care pathway.

An overview and methodological assessment of systematic reviews and meta-analyses of enhanced recovery programmes in colorectal surgery.

OBJECTIVES: To identify and critically assess the extent to which systematic reviews of enhanced recovery programmes for patients undergoing colorectal surgery differ in their methodology and reported estimates of effect. DESIGN: Review of published systematic reviews. We searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA) Database from 1990 to March 2013. Systematic reviews of enhanced recovery programmes for patients undergoing colorectal surgery were eligible for inclusion. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was length of hospital stay. We assessed changes in pooled estimates of treatment effect over time and how these might have been influenced by decisions taken by researchers as well as by the availability of new trials. The quality of systematic reviews was assessed using the Centre for Reviews and Dissemination (CRD) DARE critical appraisal process. RESULTS: 10 systematic reviews were included. Systematic reviews of randomised controlled trials have consistently shown a reduction in length of hospital stay with enhanced recovery compared with traditional care. The estimated effect tended to increase from 2006 to 2010 as more trials were published but has not altered significantly in the most recent review, despite the inclusion of several unique trials. The best estimate appears to be an average reduction of around 2.5 days in primary postoperative length of stay. Differences between reviews reflected differences in interpretation of inclusion criteria, searching and analytical methods or software. CONCLUSIONS: Systematic reviews of enhanced recovery programmes show a high level of research waste, with multiple reviews covering identical or very similar groups of trials. Where multiple reviews exist on a topic, interpretation may require careful attention to apparently minor differences between reviews. Researchers can help readers by acknowledging existing reviews and through clear reporting of key decisions, especially on inclusion/exclusion and on statistical pooling.