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In this article, we review and evaluate a number of methods used in the design and analysis of small three-arm parallel cluster randomized trials. We conduct a simulation-based study to evaluate restricted randomization methods including covariate-constrained randomization and a novel method for matched-group cluster randomization. We also evaluate the appropriate modelling of the data and small sample inferential methods for a variety of treatment effects relevant to three-arm trials. Our results indicate that small-sample corrections are required for high (0.05) but not low (0.001) values of the intraclass correlation coefficient and their performance can depend on trial design, number of clusters, and the nature of the hypothesis being tested. The Satterthwaite correction generally performed best at an ICC of 0.05 with a nominal type I error rate for single-period trials, and in trials with repeated measures type I error rates were between 0.04 and 0.06. Restricted randomization methods produce little benefit in trials with repeated measures but in trials with single post-intervention design can provide relatively large gains in power when compared to the most unbalanced possible allocations. Matched-group randomization improves power but is not as effective as covariate-constrained randomization. For model-based analysis, adjusting for fewer covariates than were used in a restricted randomization process under any design can produce non-nominal type I error rates and reductions in power. Where comparisons to two-arm cluster trials are possible, the performance of the methods is qualitatively very similar.

Overstating the impact of interventions through incomplete or inaccurate reporting can lead to inappropriate scale-up of interventions with low impact. Accurate reporting of the impact of interventions is of great importance in global health research to protect scarce resources. In global health, the cluster randomised trial design is commonly used to evaluate complex, multicomponent interventions, and outcomes are often binary. Complete reporting of impact for binary outcomes means reporting both relative and absolute measures. We did a systematic review to assess reporting practices and potential to overstate impact in contemporary cluster randomised trials with binary primary outcome. We included all reports registered in the Cochrane Central Register of Controlled Trials of two-arm parallel cluster randomised trials with at least one binary primary outcome that were published in 2017. Of 73 cluster randomised trials, most (60 [82%]) showed incomplete reporting. Of 64 cluster randomised trials for which it was possible to evaluate, most (40 [63%]) reported results in such a way that impact could be overstated. Care is needed to report complete evidence of impact for the many interventions evaluated using the cluster randomised trial design worldwide.

Objectives To explore the effect of introducing 24/7 resident labour ward consultant presence on neonatal and maternal outcomes in a large obstetric unit in England. Design Retrospective time sequence analysis of routinely collected data. Setting Obstetric unit of large teaching hospital in England. Participants Women and babies delivered between1 July 2011 and 30 June 2017. Births Main outcome measures The primary composite outcome comprised intrapartum stillbirth, neonatal death, babies requiring therapeutic hypothermia, or admission to neonatal intensive care within three hours of birth. Secondary outcomes included markers of neonatal and maternal morbidity. Planned subgroup analyses investigated gestation ( Results 17324 babies delivered before and 16110 after 24/7 consultant presence. The prevalence of the primary outcome increased by 0.65%, from 2.07% (359/17324) before 24/7 consultant presence to 2.72% (438/16110, P < 0.001) after 24/7 consultant presence which was consistent with an upward trend over time already well established before 24/7 consultant presence began (OR 1.09 p.a.; CI 1.04 to 1.13). Overall, there was no change in this trend associated with the transition to 24/7. However, in babies born ≥37 weeks gestation, the upward trend was reversed after implementation of 24/7 (OR 0.67 p.a.; CI 0.49 to 0.93; P = 0.017). No substantial differences were shown in other outcomes or subgroups. Conclusions Overall, resident consultant obstetrician presence 24/7 on labour ward was not associated with a change in a pre-existing trend of increasing adverse infant outcomes. However, 24/7 presence was associated with a reversal in increasing adverse outcomes for term babies.

BackgroundIn 2013, the English National Health Service launched the policy of 7-day services to improve care quality and outcomes for weekend emergency admissions.AimsTo determine whether the quality of care of emergency medical admissions is worse at weekends, and whether this has changed during implementation of 7-day services.MethodsUsing data from 20 acute hospital Trusts in England, we performed randomly selected structured case record reviews of patients admitted to hospital as emergencies at weekends and on weekdays between financial years 2012–2013 and 2016–2017. Senior doctor (‘specialist’) involvement was determined from annual point prevalence surveys. The primary outcome was the rate of clinical errors. Secondary outcomes included error-related adverse event rates, global quality of care and four indicators of good practice.ResultsSeventy-nine clinical reviewers reviewed 4000 admissions, 800 in duplicate. Errors, adverse events and care quality were not significantly different between weekend and weekday admissions, but all improved significantly between epochs, particularly errors most likely influenced by doctors (clinical assessment, diagnosis, treatment, prescribing and communication): error rate OR 0.78; 95% CI 0.70 to 0.87; adverse event OR 0.48, 95% CI 0.33 to 0.69; care quality OR 0.78, 95% CI 0.70 to 0.87; all adjusted for age, sex and ethnicity. Postadmission in-hospital care processes improved between epochs and were better for weekend admissions (vital signs with National Early Warning Score and timely specialist review). Preadmission processes in the community were suboptimal at weekends and deteriorated between epochs (fewer family doctor referrals, more patients with chronic disease or palliative care designation).Conclusions and implicationsHospital care quality of emergency medical admissions is not worse at weekends and has improved during implementation of the 7-day services policy. Causal pathways for the weekend effect may extend into the prehospital setting.

Background Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Objectives The objectives were to assess whether or not the QI programme improves 90-day survival after emergency abdominal surgery; to assess effects on 180-day survival, hospital stay and hospital readmission; and to better understand these findings through an integrated process evaluation, ethnographic study and cost-effectiveness analysis. Design This was a stepped-wedge cluster randomised trial. Hospitals were organised into 15 geographical clusters, and commenced the QI programme in random order over 85 weeks. Analyses were performed on an intention-to-treat basis. The primary outcome was analysed using a mixed-effects parametric survival model, adjusting for time-related effects. Ethnographic and economics data were collected in six hospitals. The process evaluation included all hospitals. Setting The trial was set in acute surgical services of 93 NHS hospitals. Participants Patients aged ≥ 40 years who were undergoing emergency abdominal surgery were eligible. Intervention The intervention was a QI programme to implement an evidence-based care pathway. Main outcome measures The primary outcome measure was mortality within 90 days of surgery. Secondary outcomes were mortality within 180 days, length of hospital stay and hospital readmission within 180 days. The main economic measure was the quality-adjusted life-years. Data sources Data were obtained from the National Emergency Laparotomy Audit database; qualitative interviews and ethnographic observations; quality-of-life and NHS resource use data were collected via questionnaires. Results Of 15,873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 participants in the usual care group and 7374 in the QI group. The primary outcome occurred in 1393 participants in the usual care group (16%), compared with 1210 patients in the QI group (16%) [QI vs. usual care hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.96 to 1.28]. No differences were found in mortality at 180 days or hospital readmission; there was a small increase in hospital stay in the QI group (HR for discharge 0.90, 95% CI 0.83 to 0.97). There were only modest improvements in care processes following QI implementation. The ethnographic study revealed good QI engagement, but limited time and resources to implement change, affecting which processes teams addressed, the rate of change and eventual success. In some sites, there were challenges around prioritising the intervention in busy environments and in obtaining senior engagement. The intervention is unlikely to be cost-effective at standard cost-effectiveness thresholds, but may be cost-effective over the lifetime horizon. Limitations Substantial delays were encountered in securing data access to national registries. Fewer patients than expected underwent surgery and the mortality rate was lower than anticipated. Conclusions There was no survival benefit from a QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. The modest impact of the intervention on process measures, despite good clinician engagement, may have been limited by the time and resources needed to improve patient care. Future work Future QI programmes must balance intervention complexity with the practical realities of NHS services to ensure that such programmes can be delivered with the resources available. Trial registration Current Controlled Trials ISRCTN80682973 and The Lancet protocol 13PRT/7655. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 7, No. 32. See the NIHR Journals Library website for further project information.

ObjectiveTo determine whether the higher weekend admission mortality risk is attributable to increased severity of illness.DesignRetrospective analysis of 4 years weekend and weekday adult emergency admissions to a university teaching hospital in England.Outcome measures30-day postadmission weekend:weekday mortality ratios adjusted for severity of illness (baseline National Early Warning Score (NEWS)), routes of admission to hospital, transfer to the intensive care unit (ICU) and demographics.ResultsDespite similar emergency department daily attendance rates, fewer patients were admitted on weekends (mean admission rate 91/day vs 120/day) because of fewer general practitioner referrals. Weekend admissions were sicker than weekday (mean NEWS 1.8 vs 1.7, p=0.008), more likely to undergo transfer to ICU within 24 hours (4.2% vs 3.0%), spent longer in hospital (median 3 days vs 2 days) and less likely to experience same-day discharge (17.2% vs 21.9%) (all p values The crude 30-day postadmission mortality ratio for weekend admission (OR=1.13; 95% CI 1.08 to 1.19) was attenuated using standard adjustment (OR=1.11; 95% CI 1.05 to 1.17). In patients for whom NEWS values were available (90%), the crude OR (1.07; 95% CI 1.01 to 1.13) was not affected with standard adjustment. Adjustment using NEWS alone nullified the weekend effect (OR=1.02; 0.96–1.08).NEWS completion rates were higher on weekends (91.7%) than weekdays (89.5%). Missing NEWS was associated with direct transfer to intensive care bypassing electronic data capture. Missing NEWS in non-ICU weekend patients was associated with a higher mortality and fewer same-day discharges than weekdays.ConclusionsPatients admitted to hospital on weekends are sicker than those admitted on weekdays. The cause of the weekend effect may lie in community services.

A recent systematic review identified few papers on the economic evaluation of systems for emergency transport of acutely ill or injured patients. In addition, we found no articles dealing with the methodological challenges posed by such studies in low-income or middle-income countries. We therefore carried out an analysis of issues that are of particular salience to this important topic. This is an intellectual study in which we develop models, identify their limitations, suggest potential extensions to the models and discuss priorities for empirical studies to populate models. First, we develop a general model to calculate changes in survival contingent on the reduced time to treatment that an emergency transport system is designed to achieve. Second, we develop a model to estimate transfer times over an area that will be served by a proposed transfer system. Third, we discuss difficulties in obtaining parameters with which to populate the models. Fourth, we discuss costs, both direct and indirect, of an emergency transfer service. Fifth, we discuss the issue that outcomes other than survival should be considered and that the effects of a service are a weighted sum over all the conditions and severities for which the service caters. Lastly, based on the above work, we identify priorities for research. To our knowledge, this is the first study to identify and frame issues in the health economics of acute transfer systems and to develop models to calculate survival rates from basic parameters, such as time delay/survival relationships, that vary by intervention type and context.

This report presents the Consolidated Standards of Reporting Trials (CONSORT) extension for the stepped wedge cluster randomised trial (SW-CRT). The SW-CRT involves randomisation of clusters to different sequences that dictate the order (or timing) at which each cluster will switch to the intervention condition. The statement was developed to allow for the unique characteristics of this increasingly used study design. The guideline was developed using a Delphi survey and consensus meeting; and is informed by the CONSORT statements for individual and cluster randomised trials. Reporting items along with explanations and examples are provided. We include a glossary of terms, and explore the key properties of the SW-CRT which require special consideration in their reporting.\ud \ud

Summary Background Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding National Institute for Health Research Health Services and Delivery Research Programme.

BackgroundIn this UK study, we investigated the impact of computerised physician order entry (CPOE) and clinical decision support (CDS) implementation on the rate of 78 high-risk prescribing errors amenable to CDS.MethodsWe conducted a preintervention/postintervention study in three acute hospitals in England. A predefined list of prescribing errors was incorporated into an audit tool. At each site, approximately 4000 prescriptions were reviewed both pre-CPOE and 6 months post-CPOE implementation. The number of opportunities for error and the number of errors that occurred were collated. Error rates were then calculated and compared between periods, as well as by the level of CDS.ResultsThe prescriptions of 1244 patients were audited pre-CPOE and 1178 post-CPOE implementation. A total of 28 526 prescriptions were reviewed, with 21 138 opportunities for error identified based on 78 defined errors. Across the three sites, for those prescriptions where opportunities for error were identified, the error rate was found to reduce significantly post-CPOE implementation, from 5.0% to 4.0% (PConclusionsImplementation of CPOE with CDS was associated with clinically important reductions in the rate of high-risk prescribing errors. Given the pre-post design, these findings however need to be interpreted with caution. The occurrence of errors was found to be highly dependent on the level of restriction of CDS presented to the prescriber, with the effect that different configurations of the same CPOE system can produce very different results.

IntroductionThis protocol concerns the evaluation of increased specialist staffing at weekends in hospitals in England. Seven-day health services are a key policy for the UK government and other health systems trying to improve use of infrastructure and resources. A particular motivation for the 7-day policy has been the observed increase in the risk of death associated with weekend admission, which has been attributed to fewer hospital specialists being available at weekends. However, the causes of the weekend effect have not been adequately characterised; many of the excess deaths associated with the ‘weekend effect’ may not be preventable, and the presumed benefits of improved specialist cover might be offset by the cost of implementation.Methods/designThe Bayesian-founded method we propose will consist of four major steps. First, the development of a qualitative causal model. Specialist presence can affect multiple, interacting causal processes. One or more models will be developed from the results of an expert elicitation workshop and probabilities elicited for each model and relevant model parameters. Second, systematic review of the literature. The model from the first step will provide search limits for a review to identify relevant studies. Third, a statistical model for the effects of specialist presence on care quality and patient outcomes. Fourth, valuation of outcomes. The expected net benefits of different levels of specialist intensity will then be evaluated with respect to the posterior distributions of the parameters.Ethics and disseminationThe study was approved by the Review Subcommittee of the South West Wales REC on 11 November 2013. Informed consent was not required for accessing anonymised patient case records from which patient identifiers had been removed. The findings of this study will be published in peer-reviewed journals; the outputs from this research will also form part of the project report to the HS&DR Programme Board.

Introduction The mortality associated with weekend admission to hospital (the ‘weekend effect’) has for many years been attributed to deficiencies in quality of hospital care, often assumed to be due to suboptimal senior medical staffing at weekends. This protocol describes a case note review to determine whether there are differences in care quality for emergency admissions (EAs) to hospital at weekends compared with weekdays, and whether the difference has reduced over time as health policies have changed to promote 7-day services. Methods and analysis Cross-sectional two-epoch case record review of 20 acute hospital Trusts in England. Anonymised case records of 4000 EAs to hospital, 2000 at weekends and 2000 on weekdays, covering two epochs (financial years 2012–2013 and 2016–2017). Admissions will be randomly selected across the whole of each epoch from Trust electronic patient records. Following training, structured implicit case reviews will be conducted by consultants or senior registrars (senior residents) in acute medical specialities (60 case records per reviewer), and limited to the first 7 days following hospital admission. The co-primary outcomes are the weekend:weekday admission ratio of errors per case record, and a global assessment of care quality on a Likert scale. Error rates will be analysed using mixed effects logistic regression models, and care quality using ordinal regression methods. Secondary outcomes include error typology, error-related adverse events and any correlation between error rates and staffing. The data will also be used to inform a parallel health economics analysis. Ethics and dissemination The project has received ethics approval from the South West Wales Research Ethics Committee (REC): reference 13/WA/0372. Informed consent is not required for accessing anonymised patient case records from which patient identifiers had been removed. The findings will be disseminated through peer-reviewed publications in high-quality journals and through local High-intensity Specialist-Led Acute Care (HiSLAC) leads at the 121 hospitals that make up the HiSLAC Collaborative.

Background\ud Standardised mortality ratios do not provide accurate measures of preventable mortality. This has generated interest in using case-notes to assess the preventable component of mortality. But different methods of measurement have not been compared. We compared the reliability of two scales for assessing preventability and the correspondence between them.\ud Methods\ud Medical specialists reviewed case-notes of patients who had died in hospital using two instruments: a five-point Likert scale and a continuous (0-100) scale of preventability. To enhance generalisability we used two different hospital datasets with different types of acute medical patients across different epochs and in two jurisdictions (UK and US). We investigated the reliability of measurement and correspondence of preventability estimates across the two scales. Ordinal mixed effects regression methods were used to analyse the Likert scale and to calibrate it against the continuous scale. We report the estimates of the probability a death could have been prevented accounting for reviewer inconsistency.\ud Results \ud Correspondence between the two scales was strong; the Likert categories explained most of the variation (76% UK, 73% US) in the continuous scale. Measurement reliability was low but similar across the two instruments in each dataset (intra-class correlation 0.27 UK, 0.23 US). Adjusting for the inconsistency of reviewer judgements reduced the proportion of cases with high preventability, such that the proportion of all deaths judged probably or definitely preventable on the balance of probability was under 1%.\ud Conclusions \ud The correspondence is high between a Likert and continuous scale, although the low reliability of both would suggest careful measurement design would be needed to use either scale. Few to no cases are above the threshold when using a balance of probability approach to determining a preventable death, and in any case there is little evidence supporting anything more than an ordinal correspondence between these reviewer estimates of probability and the true probability. Thus, it would be more defensible to use them as an ordinal measure of the quality of care received by patients who died in the hospital.\ud

The economic evaluation of medical products and services is increasingly prioritised by healthcare decision makers and plays a key role in informing funding allocation decisions. It is well known that there are a number of methodological difficulties in the health technology assessment of medical devices, particularly in the provision of efficacy evidence. By contrasting devices with pharmaceuticals, the way in which the differing systems of innovation mould the UK's industry landscape is described and substantiated with market statistics. In recognition of the challenges faced by industry, as well as the growing need for cost-effective allocation of National Health Service (NHS) resources, the National Institute for Health and Care Excellence (NICE) led the development of the Medical Technologies Evaluation Programme (MTEP), which launched in 2009/2010. The review of the UK's medical devices market supports the programme's three principal aims: to simplify access to evaluation, speed up the process, and increase evaluative capacity for devices within NICE. However, an analysis of the output of MTEP's first 3 years suggests that it has some way to go to meet each of these aims.

This article introduces the Stata menu-driven program steppedwedge, which calculates detectable differences and power for stepped-wedge randomized trials. The command permits continuous, binary, and rate outcomes (with normal approximations) for comparisons using two-sided tests. The command allows specification of the number of clusters randomized at each step, the number of steps and the average cluster (cell) size, or an incomplete design in which the user spec-ifies the design pattern (a matrix with one row per cluster, one column per time point, and entries indicating exposure and observable data). Cluster heterogeneity can be parameterized using either the intracluster correlation or the coefficient of variation (of the outcome). The command is illustrated via examples.

Unfortunately, the original version of this article [1] contained an error in abstract S1. The corresponding author for the abstract ‘Gabriele Meyer’ was included in the 'Correspondence' section but accidentally omitted from the author list. The correct author list should be as below: Gabriele Meyer1*, Sascha Kopke2, Jane Noyes3, Jackie Chandler4 1Martin Luther University Halle-Wittenberg, Magdeburger Str. 8, D-06112 Halle (Saale), Germany 2University of Lubeck, Germany 3Bangor University, UK 4Cochrane Collaboration, Oxford, UK Correspondence: Gabriele Meyer (Gabriele.Meyer@medizin.uni-halle.de) – Martin Luther University Halle-Wittenberg, Magdeburger Str. 8, D-06112 Halle (Saale), Germany

In the 21st century, it is more obvious than ever before that health services research and its practitioners exist in an extremely complex contextual environment. Consequently, at the heart of unde ...

Background Stepped-wedge cluster randomised trials (SW-CRT) are increasingly being used in health policy and services research, but unless they are conducted and reported to the highest methodological standards, they are unlikely to be useful to decision-makers. Sample size calculations for these designs require allowance for clustering, time effects and repeated measures. Methods We carried out a methodological review of SW-CRTs up to October 2014. We assessed adherence to reporting each of the 9 sample size calculation items recommended in the 2012 extension of the CONSORT statement to cluster trials. Results We identified 32 completed trials and 28 independent protocols published between 1987 and 2014. Of these, 45 (75%) reported a sample size calculation, with a median of 5.0 (IQR 2.5–6.0) of the 9 CONSORT items reported. Of those that reported a sample size calculation, the majority, 33 (73%), allowed for clustering, but just 15 (33%) allowed for time effects. There was a small increase in the proportions reporting a sample size calculation (from 64% before to 84% after publication of the CONSORT extension, p=0.07). The type of design (cohort or cross-sectional) was not reported clearly in the majority of studies, but cohort designs seemed to be most prevalent. Sample size calculations in cohort designs were particularly poor with only 3 out of 24 (13%) of these studies allowing for repeated measures. Discussion The quality of reporting of sample size items in stepped-wedge trials is suboptimal. There is an urgent need for dissemination of the appropriate guidelines for reporting and methodological development to match the proliferation of the use of this design in practice. Time effects and repeated measures should be considered in all SW-CRT power calculations, and there should be clarity in reporting trials as cohort or cross-sectional designs.

Introduction Residents of care homes with diabetes are a vulnerable group, lacking comprehensive assessment, monitoring, and specialist access. This study aimed to determine whether a short-term patient centred intervention strategy might benefit people with diabetes living in residential care homes. Methods Residents with diabetes were recruited and randomised (by care home) to intervention (25 homes: 57 residents) or control (26 homes: 45 residents). The intervention consisted of a medical review and individualised resident educational programme. The control group received usual care. Measures of glycaemic control (fasting glucose and HbA1c), quality of life, functional ability, cognition, mood, and diabetes knowledge were collected at baseline and after 6 months. Results After 6 months the intervention group, compared with control, had better quality of life, mood and diabetes knowledge and a slight increase in HbA1c from a mean value of 6.84 % (1.54) to 7.49 % (1.82). Reports of hypoglycaemia were less at the end of the study in both groups. Conclusions The intervention improved patient-centred outcomes, with a small effect on glycaemic control. More research needs to be performed with care home residents to develop the evidence base for appropriate interventions in this neglected group of patients.

Product vendors and manufacturers are increasingly aware that purchasers of health care will fund new clinical treatments only if they are perceived to deliver value-for-money. This influences companies' internal commercial decisions, including the price they set for their products. Other things being equal, there is a price threshold, which is the maximum price at which the device will be funded and which, if its value were known, would play a central role in price determination. This paper examines the problem of pricing a medical device from the vendor's point of view in the presence of uncertainty about what the price threshold will be. A formal solution is obtained by maximising the expected value of the net revenue function, assuming a Bayesian prior distribution for the price threshold. A least admissible price is identified. The model can also be used as a tool for analysing proposed pricing policies when no formal prior specification of uncertainty is available. Copyright © 2011 John Wiley & Sons, Ltd.

Background. The probability of reimbursement is a key factor in determining whether to proceed with or abandon a product during its development. The purpose of this article is to illustrate how the methods of iterative Bayesian economic evaluation proposed in the literature can be incorporated into the development process of new medical devices, adapting them to face the relative scarcity of data and time that characterizes the process. Methods. A 3-stage economic evaluation was applied: an early phase in which simple methods allow for a quick prioritization of competing products; a mid-stage in which developers synthesize the data into a decision model, identify the parameters for which more information is most valuable, and explore uncertainty; and a late stage, in which all relevant information is synthesized. A retrospective analysis was conducted of the case study of absorbable pins, compared with metallic fixation, in osteotomy to treat hallux valgus. Results. The results from the early analysis suggest absorbable pins to be cost-effective under the beliefs and assumptions applied. The outputs from the models at the mid-stage analyses show the device to be cost-effective with a high probability. Late-stage analysis synthesizes evidence from a randomized controlled trial and informative priors, which are based on previous evidence. It also suggests that absorbable pins are the most cost-effective strategy, although the uncertainty in the model output increased considerably. Conclusions. This example illustrates how the method proposed allows decisions in the product development cycle to be based on the best knowledge that is available at each stage.

Not all clinically eligible patients will necessarily accept a new treatment. Cost-utility analysis recognizes this by multiplying the mean incremental expected utility (EU) by the participation rate to obtain the utility gain per head. However, the mean EU gain over all patients in a defined clinical category is traditionally used as a proxy for the mean EU gain over the subpopulation of acceptors. Even for clinically identical patients, this may lead to a biased assessment of total benefit because a patient motivated to accept the new treatment is likely to value its effects more favorably than a patient who declines. An analysis that ignores this tendency will be biased toward an underestimate of true benefits of a health technology (HT). The extent of this bias is described within a qualityadjusted life year-based utility model for a population of clinically indistinguishable patients who differ with respect to the values that they place on the possible health outcomes of an HT. The size of the bias is sensitive to the proportion of patients who accept the treatment, under both deterministic and probabilistic models of individual decision making. In all cases in which decision making is correlated with personal utility gain, the bias rises steeply as the proportion of acceptors declines.

Objectives:The headroom approach to medical device development relies on the estimation of a value-based price ceiling at different stages of the development cycle. Such price-ceilings delineate the commercial opportunities for new products in many healthcare systems. We apply a simple model to obtain critical business information as the product proceeds along a development pathway, and indicate some future directions for the development of the approach.Methods:Health economic modelling in the supply-side development cycle for new products.Results:The headroom can be used: initially as a ‘reality check’ on the viability of the device in the healthcare market; to support product development decisions using a real options approach; and to contribute to a pricing policy which respects uncertainties in the reimbursement outlook.Conclusions:The headroom provides a unifying thread for business decisions along the development cycle for a new product. Over the course of the cycle attitudes to uncertainty will evolve, based on the timing and manner in which new information accrues. Within this framework the developmental value of new information can justify the costs of clinical trials and other evidence-gathering activities. Headroom can function as a simple shared tool to parties in commercial negotiations around individual products or groups of products. The development of similar approaches in other contexts holds promise for more rational planning of service provision.

Objectives Smokers report that smoking is therapeutic; a recent meta-analysis suggests the contrary. However, the association in that review may be explained by group-membership bias and confounding. Propensity score matching (PSM) aims to produce causal estimates from observational data. We examined the association between cessation and change in mental health before and after PSM. Design A secondary analysis of prospective data from 5 placebo-controlled randomised trials for smoking reduction. Participants All participants were adult smokers and had smoked for at least 3 years. Participants were excluded if they were pregnant, breast feeding, under psychiatric care, deemed to be unfit by a general practitioner or part of a cessation programme. In total, 937 participants provided smoking data at both 6-month and 12-month follow-ups. Of these, 68 were confirmed as abstinent at both 6 and 12 months and 589 as continuous smokers at both follow-ups. Primary outcome Change in mental health (36-item Short Form Survey (SF-36), scored 0–100) from baseline (while all participants were smokers) to 12-month follow-up (after cessation) was compared between quitters and continuing smokers with and without adjustment, and after PSM. Results Before matching, quitters’ mental health scores improved compared with continuing smokers’, the mean difference and 95% CI was 5.5 (1.6 to 9.4). After adjustment, the difference was 4.5 (0.6 to 8.5), and after PSM, the difference was 3.4 (−2.2 to 8.9). Conclusions Improvements in mental health after smoking cessation may be partly but not completely explained by group membership bias and confounding.

The stepped wedge cluster randomised trial is a novel research study design that is increasingly being used in the evaluation of service delivery type interventions. The design involves random and sequential crossover of clusters from control to intervention until all clusters are exposed. It is a pragmatic study design which can reconcile the need for robust evaluations with political or logistical constraints. While not exclusively for the evaluation of service delivery interventions, it is particularly suited to evaluations that do not rely on individual patient recruitment. As in all cluster trials, stepped wedge trials with individual recruitment and without concealment of allocation (or blinding of the intervention) are at risk of selection biases. In a stepped wedge design more clusters are exposed to the intervention towards the end of the study than in its early stages. This implies that the effect of the intervention might be confounded with any underlying temporal trend. A result that initially might seem suggestive of an effect of the intervention may therefore transpire to be the result of a positive underlying temporal trend. Sample size calculations and analysis must make allowance for both the clustered nature of the design and the confounding effect of time. The stepped wedge cluster randomised trial is an alternative to traditional parallel cluster studies, in which the intervention is delivered in only half the clusters with the remainder functioning as controls. When the clusters are relatively homogeneous (that is, the intra-cluster correlation is small), parallel studies tend to deliver better statistical performance than a stepped wedge trial. However, if substantial cluster-level effects are present (that is, larger intra-cluster correlations) or the clusters are large, the stepped wedge design will be more powerful than a parallel design, even one in which the intervention is preceded by a period of baseline control observations.

BACKGROUND: The possibility of conception following selective salpingography and tubal catheterization is believed to decline sharply a few months after the procedure. This observation may be due to the relatively small number of patients and short follow-up of previous studies. Furthermore, couples with other causes of infertility apart from proximal tubal blockage have usually been excluded. METHODS: Survival analysis of conceptions of 218 consecutive infertile women with proximal tubal blockage who underwent selective salpingography and tubal catheterization was performed. There were no exclusion criteria. Follow-up ranged from 16 to 56 months. RESULTS: A total of 47.2% of spontaneous conceptions and 43.2% of all conceptions, apart from those achieved by IVF or ICSI treatments, occurred after the first 12 months following selective salpingography and tubal catheterization. The decline in the possibility of pregnancy during the study period (conception hazard rate) was only minimal. CONCLUSIONS: In a population of infertile women with proximal tubal blockage, a significant proportion of conceptions occur after the first 12 months following selective salpingography and tubal catheterization. The presence of any additional causes of infertility in the couple should not be regarded as an absolute contraindication to the procedure.

Objective To assess whether there are differences in the results of cardiovascular trials between Europe and Asia using data from an extensive collection of randomised controlled trials. Study design and setting All meta-analyses containing randomised controlled trials (RCT9s) for the treatment or prevention of cardiovascular diseases were searched for in The Cochrane Library (2000–2008) and MEDLINE (2005–2008). Analysis was then conducted within and over each meta-analysis which satisfied given criteria. Separate estimates of treatment effect were calculated for Europe and Asia in each meta-analysis and then compared. Estimates of a common inter-continental difference over all meta-analyses were also calculated and meta-regression was performed. This was performed for both fatal and non-fatal end points. Results The literature search identified 59 meta-analyses that satisfied the inclusion criteria. After exclusion, the number of meta-analyses reporting greater effect sizes in Asia than in Europe was significantly more than would be expected by chance (fatal 12/14, p=0.013; non-fatal 23/32, p=0.020). Conclusions This study provides some evidence that for cardiovascular interventions treatment effect estimation differs between Europe and Asia, with respect to both fatal and non-fatal end points.

We reviewed the literature for the impact of service delivery initiatives (SDIs) on patients’ waiting times within radiology departments. We searched MEDLINE, EMBASE, CINAHL, INSPEC and The Cochrane Library for relevant articles published between 1995 and February, 2013. The Cochrane EPOC risk of bias tool was used to assess the risk of bias on studies that met specified design criteria. Fifty-seven studies met the inclusion criteria. The types of SDI implemented included extended scope practice (ESP, three studies), quality management (12 studies), productivity-enhancing technologies (PETs, 29 studies), multiple interventions (11 studies), outsourcing and pay-for-performance (one study each). The uncontrolled pre- and post-intervention and the post-intervention designs were used in 54 (95 %) of the studies. The reporting quality was poor: many of the studies did not test and/or report the statistical significance of their results. The studies were highly heterogeneous, therefore meta-analysis was inappropriate. The following type of SDIs showed promising results: extended scope practice; quality management methodologies including Six Sigma, Lean methodology, and continuous quality improvement; productivity-enhancing technologies including speech recognition reporting, teleradiology and computerised physician order entry systems. We have suggested improved study design and the mapping of the definitions of patient waiting times in radiology to generic timelines as a starting point for moving towards a situation where it becomes less restrictive to compare and/or pool the results of future studies in a meta-analysis.

OBJECTIVE: To determine whether cognitive impairment is associated with changes in self-care behaviour and use of health and social services in older subjects with diabetes mellitus. RESEARCH DESIGN AND METHODS: This was a community based, case-control study of subjects registered with general practices participating in the All Wales Research into Elderly (AWARE) Diabetes Study. The 396 patients aged 65 years or older with known diabetes mellitus were compared with 393 age- and sex-matched, non-diabetic controls. Adjusted odds ratio estimates of normal performance on Mini-Mental State Examination (MMSE) and Clock Drawing Test (numbers and hands) were determined. Information on self-care behaviours and use of services was obtained. RESULTS: A total of 283 (71%) diabetic subjects scored 24 or more on MMSE, compared with 323 (88%) of controls (OR 0.54, P

Assessments of cost effectiveness are increasingly used to get the most value from limited health resources. Could adjusting for people who wouldn't want the treatment improve the process?

The headroom method offers medical device developers a simple way to integrate health economics into the decision of whether or not to develop a medical device. By estimating the maximum reimbursable price (MRP) for a new device idea, and comparing this reimbursement opportunity with a developer’s expected costs, the method offers a way to ensure developers invest only in devices that are commercially viable. This paper explains the headroom method, and describes a study whose aim was to evaluate the method by applying it retrospectively to a large and diverse set of case studies. The method was applied systematically to 20 devices / diagnostics that were invented in the past (identified from the UK National Horizon Scanning Centre (NHSC)’s 2000 to 2009 database). Predicted ‘headroom’ was then compared with later UK National Health Service (NHS) uptake, in order to assess the performance of the method as a predictive tool. The headroom method predicted uptake with a sensitivity of 92% and a negative predictive value of 67%. When numerical headroom assessments were considered alongside the more qualitative factors identified (which generally reflected the clinical and market context), the method offered a good indication of commercial opportunity.

Stepped wedge cluster randomised trials (SW-CRTs) are being used with increasing frequency in health service evaluation. Conventionally, these studies are designed with equally spaced steps, with an equal number of clusters randomised at each step, and data collected at each and every step. Here we introduce several variations on this design and consider implications for power. One modifiction we consider is where the number of clusters varies at each step, or where at some steps data are not collected. We show that the parallel CRT with staggered, but balanced randomisation, can be considered a special case of the incomplete SW-CRT. And, we extend these designs to allow for multiple layers of clustering, for example wards within a hospital. Building on results for complete designs, power and detectable difference are derived using Wald-test and obtaining the variance-covariance matrix of the treatment effect assuming a generalised linear mixed model. These variations are illustrated by several real examples.

Objective To evaluate mildly abnormal liver function test (LFT) results in general practice among patients who do not have known liver disease. Design Prospective cohort study of people with abnormal LFT results identified in primary care. Participants were intensively investigated using a common protocol and followed up for 2 years. Substudies investigated the psychological sequelae of abnormal test results, clinicians' reasons for testing, decision options when LFT results were abnormal and early detection of liver fibrosis. Setting Eleven primary-care practices: eight in Birmingham and three in Lambeth. Participants Adults with abnormal LFT results who did not have pre-existing or obvious liver disease. Eight analytes were included in the panel of LFTs. Main outcome measures Statistical tests were used to identify the interactions between clinical features, the initial pattern of abnormal LFT results and (1) specific viral, genetic and autoimmune diseases, such as viral hepatitis, haemochromatosis and primary biliary cirrhosis; (2) a range of other serious diseases, such as metastatic cancer and hypothyroidism; (3) ‘fatty liver’ not associated with the above; and (4) the absence of detectable disease. Results Fewer than 5% of people with abnormal LFT results had a specific disease of the liver, and many of these were unlikely to need treatment. The diagnostic potential of the LFT panel is largely subsumed into just two analytes: alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Gamma-glutamyltransferase (GGT) offers a small increase in sensitivity at the margin at the cost of a large loss of specificity. Eighty-four per cent of abnormal LFT results remain abnormal on retesting 1 month later. In many cases, carrying out a definitive or specific test will be more efficient than repeating LFTs, with a view to specific testing only if the test remains abnormal. An ultrasound diagnosis of ‘fatty liver’ was present in nearly 40% of patients with abnormal LFTs and a small amount of weight loss over 2 years was associated with a reduced incidence of liver fat. There was a J-shaped relationship between alcohol intake and fatty liver in men. An abnormal LFT result causes temporary anxiety, which does not appear to promote sustained behaviour change. Conclusions Liver disease is rare among people with abnormal LFT results in primary care. Only two analytes (ALT and ALP) are helpful in identifying the majority of liver disease. GGT adds little information in return for a high false-positive rate but it is sensitive to alcohol intake. LFT results seldom revert from abnormal to normal over a 1-month period, and modelling shows that repeating an abnormal LFT panel, as recommended in the current guidelines, is inefficient. LFTs are often undertaken to meet perceived patient need for a blood test, but as they are neither specific nor indicative of any particular disease they are among the least suitable tests for this purpose. Obesity and raised ALT provide strong evidence for a presumptive diagnosis of ‘fatty’ liver. Abnormal LFTs and ‘fatty’ liver provoke only short-term anxiety and neither is associated with sustained weight loss. Even a small amount of weight loss reduces liver fat. Future work recommendations (1) the cases of ‘fatty liver’ and controls should be followed up in the long term to identify features that predict development of hepatosteatosis and then cirrhosis; (2) the acceptability of replacing the traditional six- to eight-analyte LFT panel with a drop down menu including the ALT/ALP combination should be evaluated. Funding The National Institute for Health Research Health Technology Assessment programme.

Background We explored the use of routine blood tests and national early warning scores (NEWS) reported within ±24 hours of admission to predict in-hospital mortality in emergency admissions, using empirical decision Tree models because they are intuitive and may ultimately be used to support clinical decision making. Methodology A retrospective analysis of adult emergency admissions to a large acute hospital during April 2009 to March 2010 in the West Midlands, England, with a full set of index blood tests results (albumin, creatinine, haemoglobin, potassium, sodium, urea, white cell count and an index NEWS undertaken within ±24 hours of admission). We developed a Tree model by randomly splitting the admissions into a training (50%) and validation dataset (50%) and assessed its accuracy using the concordance (c-) statistic. Emergency admissions (about 30%) did not have a full set of index blood tests and/or NEWS and so were not included in our analysis. Results There were 23248 emergency admissions with a full set of blood tests and NEWS with an in-hospital mortality of 5.69%. The Tree model identified age, NEWS, albumin, sodium, white cell count and urea as significant (p

The frequency of visits to Emergency Departments (ED) varies greatly between populations. This may reflect variation in patient behaviour, need, accessibility, and service configuration as well as the complex interactions between these factors. This study investigates the relationship between distance, socio-economic deprivation, and proximity to an alternative care setting (a Minor Injuries Unit (MIU)), with particular attention to the interaction between distance and deprivation. It is set in a population of approximately 5.4 million living in central England, which is highly heterogeneous in terms of ethnicity, socio-economics, and distance to hospital. The study data set captured 1,413,363 ED visits made by residents of the region to National Health Service (NHS) hospitals during the financial year 2007/8. Our units of analysis were small units of census geography having an average population of 1,545. Separate regression models were made for children and adults. For each additional kilometre of distance from a hospital, predicted child attendances fell by 2.2% (1.7%–2.6% p

Internationally, countries are investing in electronic medication management (eMMS; also known as CPOE/ePrescribing) systems to improve medication safety. These organisational-wide interventions impact the work of all involved in the medication pathway and can significantly impact workflows. Hospital pharmacists’ work is particularly likely to be affected, yet little research has attempted to quantify the nature of these changes, or their impact on medication service efficiency or safety. Cross-country research in health informatics is rare. As a result, many small-scale studies are replicated in different locations. Variations in methods and outcomes, …

Risk-adjustment schemes are used to monitor hospital performance, on the assumption that excess mortality not explained by case mix is largely attributable to suboptimal care. We have developed a model to\ud estimate the proportion of the variation in standardised mortality ratios (SMRs) that can be accounted for by variation in preventable mortality. The model was populated with values from the literature to estimate a\ud predictive value of the SMR in this context— specifically the proportion of those hospitals with SMRs among the highest 2.5% that fall among the worst 2.5% for preventable mortality. The extent to which SMRs reflect preventable mortality rates is highly sensitive to the proportion of deaths that are preventable. If 6% of hospital deaths are preventable (as suggested by the literature), the predictive value of\ud the SMR can be no greater than 9%. This value could rise to 30%, if 15% of deaths are preventable. The model offers a ‘reality check’ for case mix adjustment schemes designed to isolate the preventable\ud component of any outcome rate.

Background Randomised controlled trials are being increasingly used to evaluate new surgical interventions. There are a number of problematic methodological issues specific to surgical trials, the most important being identifying whether patients are eligible for recruitment into the trial. This is in part due to the diversity in practice patterns across institutions and the enormous range of available interventions that often leads to a low level of agreement between clinicians about both the value and the appropriate choice of intervention. We argue that a clinician should offer patients the option of recruitment into a trial, even if the clinician is not individually in a position of equipoise, if there is collective (clinical) equipoise amongst the wider clinical community about the effectiveness of a proposed intervention (the clinical equipoise principle). We show how this process can work using data collected from an ongoing trial of a surgical intervention. Results We describe a statistical framework for the assessment of uncertainty prior to patient recruitment to a clinical trial using a panel of expert clinical assessors and techniques for eliciting, pooling and modelling of expert opinions. The methodology is illustrated using example data from the UK Heel Fracture Trial. The statistical modelling provided results that were clear and simple to present to clinicians and showed how decisions regarding recruitment were influenced by both the collective opinion of the expert panel and the type of decision rule selected. Conclusions The statistical framework presented has potential to identify eligible patients and assist in the simplification of eligibility criteria which might encourage greater participation in clinical trials evaluating surgical interventions.