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Objective To assess whether weight loss interventions for adults with obesity affect all cause, cardiovascular, and cancer mortality, cardiovascular disease, cancer, and body weight.Design Systematic review and meta-analysis of randomised controlled trials (RCTs) using random effects, estimating risk ratios, and mean differences. Heterogeneity investigated using Cochran’s Q and I2 statistics. Quality of evidence assessed by GRADE criteria.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, and full texts in our trials’ registry for data not evident in databases. Authors were contacted for unpublished data.Eligibility criteria for selecting studies RCTs of dietary interventions targeting weight loss, with or without exercise advice or programmes, for adults with obesity and follow-up ≥1 year.Results 54 RCTs with 30 206 participants were identified. All but one trial evaluated low fat, weight reducing diets. For the primary outcome, high quality evidence showed that weight loss interventions decrease all cause mortality (34 trials, 685 events; risk ratio 0.82, 95% confidence interval 0.71 to 0.95), with six fewer deaths per 1000 participants (95% confidence interval two to 10). For other primary outcomes moderate quality evidence showed an effect on cardiovascular mortality (eight trials, 134 events; risk ratio 0.93, 95% confidence interval 0.67 to 1.31), and very low quality evidence showed an effect on cancer mortality (eight trials, 34 events; risk ratio 0.58, 95% confidence interval 0.30 to 1.11). Twenty four trials (15 176 participants) reported high quality evidence on participants developing new cardiovascular events (1043 events; risk ratio 0.93, 95% confidence interval 0.83 to 1.04). Nineteen trials (6330 participants) provided very low quality evidence on participants developing new cancers (103 events; risk ratio 0.92, 95% confidence interval 0.63 to 1.36).Conclusions Weight reducing diets, usually low in fat and saturated fat, with or without exercise advice or programmes, may reduce premature all cause mortality in adults with obesity.Systematic review registration PROSPERO CRD42016033217.

ObjectivesTo systematically review published pretrial qualitative research studies and explore how their findings were used to inform recruitment and retention processes in full-scale trials.DesignQualitative evidence synthesis using thematic analysis.Data sources and eligibility criteriaWe conducted a comprehensive search of databases; Dissertation Abstracts International, CINAHL, Embase, MEDLINE, Sociological Abstracts and PsycINFO. We included all reports of pretrial qualitative data on recruitment and retention in clinical trials up to March 2018.Data extraction and synthesisTwo authors independently extracted data using a predefined data extraction form that captured study aims, design, methodological approach and main findings, including barriers and facilitators to recruitment and or retention. The synthesis was undertaken using Thomas and Harden’s thematic synthesis method and reported following the Enhancing Transparency in Reporting the Synthesis of Qualitative Research guidelines. Confidence was assessed using Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research approach.ResultsThirty-five papers (connected to 31 feasibility studies) from three different countries, published between 2010 and 2017 were included. All studies were embedded in pilot or feasibility studies to inform design aspects in preparation for a subsequent full-scale trial. Twelve themes were identified as recruitment barriers and three as recruitment facilitators. Two themes were identified as barriers for retention and none as retention facilitators. The findings from qualitative research in feasibility or pilot trials are often not explicitly linked to proposed changes to the recruitment and retention strategies to be used in the future or planned full-scale trial.ConclusionsMany trial teams do pretrial qualitative work with the aim of improving recruitment and retention in future full-scale trials. Just over half of all reports of such work do not clearly show how their findings will change the recruitment and retention strategy of the future trial. The scope of pretrial work needs to expand beyond looking for problems and also look for what might help and spend more time on retention.

Retention of participants is essential to ensure the statistical power and internal validity of clinical trials. Poor participant retention reduces power and can bias the estimates of intervention effect. There is sparse evidence from randomised comparisons of effective strategies to retain participants in randomised trials. Currently, non-randomised evaluations of trial retention interventions embedded in host clinical trials are rejected from the Cochrane review of strategies to improve retention because it only included randomised evaluations. However, the systematic assessment of non-randomised evaluations may inform trialists' decision-making about retention methods that have been evaluated in a trial context.Therefore, we performed a systematic review to synthesise evidence from non-randomised evaluations of retention strategies in order to supplement existing randomised trial evidence. We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2007 to October 2017. Two reviewers independently screened abstracts and full-text articles for non-randomised studies that compared two or more strategies to increase participant retention in randomised trials. The retention trials had to be nested in real 'host' trials ( including feasibility studies) but not hypothetical trials. Two investigators independently rated the risk of bias of included studies using the ROBINS-I tool and determined the certainty of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Fourteen non-randomised studies of retention were included in this review. Most retention strategies (in 10 studies) aimed to increase questionnaire response rate. Favourable strategies for increasing questionnaire response rate were telephone follow-up compared to postal questionnaire completion, online questionnaire follow-up compared to postal questionnaire, shortened version of questionnaires versus longer questionnaires, electronically transferred monetary incentives compared to cash incentives, cash compared with no incentive and reminders to non-responders (telephone or text messaging). However, each retention strategy was evaluated in a single observational study. This, together with risk of bias concerns, meant that the overall GRADE certainty was low or very low for all included studies. This systematic review provides low or very low certainty evidence on the effectiveness of retention strategies evaluated in non-randomised studies. Some strategies need further evaluation to provide confidence around the size and direction of the underlying effect.

Randomised control trials are regarded as the gold standard for evaluating the effectiveness and efficacy of healthcare interventions with thousands of trials published every year. Despite significant investment in infrastructure, a staggering number of clinical trials continue to face challenges with retention. Dropouts could lead to negative consequences-from lengthy delays to missing data that can undermine the results and integrity of the trial. Summarising evidence from non-randomised evaluations of retention strategies could provide complementary information to randomised evaluations that could guide trialists to the most effective ways of increasing retention of participants in clinical trials. The following electronic databases will be searched for relevant studies: EMBASE, MEDLINE, the Cochrane Controlled Trials Register, and Cochrane Methodology Register and the search will be limited to English-published studies during the last 10 years to increase relevance to current trials. Non-randomised studies (observational studies) including a comparison of two or more strategies to increase participant retention in randomised trials or comparing one or more strategies with no strategy will be included. The primary outcome will be the proportion of participants remained at the primary analysis as determined in each retention study. This review aims to gather and evaluate evidence on the effect of retention strategies examined in non-randomised studies. It is imperative to collect evidence from obseravational studies to infer whether or not these studies could be considered a practical way to complement or even replace a broadly favourable randomised design. If we find that non-randomised studies to be included in this review are of high quality with adequate control of biases, we will recommend to trialists and others not to rely exclusively on randomised studies and to give meticulous attention to the plentiful evidence that can be obtained from non-randomised studies. Should the results of this review suggest that evaluating retention strategies in observational studies provides insufficient evidence to trialists planning their retention strategies, we will be able to say that there is little point in conducting non-randomised studies and that they would do better to invest their time and resources in a randomised evaluation if possible. Where a non-randomised study design is chosen, the review authors will offer recommendations to trialists and others regarding how to ensure that these studies are conducted in a way that can minimise the risk of bias and increase confidence in the findings. PROSPERO 2017: CRD42017072775 .

Randomised controlled trials (RCTs) are widely accepted as the preferred study design for evaluating healthcare interventions. When the sample size is determined, a (target) difference is typically specified that the RCT is designed to detect. This provides reassurance that the study will be informative, i.e., should such a difference exist, it is likely to be detected with the required statistical precision. The aim of this review was to identify potential methods for specifying the target difference in an RCT sample size calculation. A comprehensive systematic review of medical and non-medical literature was carried out for methods that could be used to specify the target difference for an RCT sample size calculation. The databases searched were MEDLINE, MEDLINE In-Process, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Methodology Register, PsycINFO, Science Citation Index, EconLit, the Education Resources Information Center (ERIC), and Scopus (for in-press publications); the search period was from 1966 or the earliest date covered, to between November 2010 and January 2011. Additionally, textbooks addressing the methodology of clinical trials and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) tripartite guidelines for clinical trials were also consulted. A narrative synthesis of methods was produced. Studies that described a method that could be used for specifying an important and/or realistic difference were included. The search identified 11,485 potentially relevant articles from the databases searched. Of these, 1,434 were selected for full-text assessment, and a further nine were identified from other sources. Fifteen clinical trial textbooks and the ICH tripartite guidelines were also reviewed. In total, 777 studies were included, and within them, seven methods were identified-anchor, distribution, health economic, opinion-seeking, pilot study, review of the evidence base, and standardised effect size. A variety of methods are available that researchers can use for specifying the target difference in an RCT sample size calculation. Appropriate methods may vary depending on the aim (e.g., specifying an important difference versus a realistic difference), context (e.g., research question and availability of data), and underlying framework adopted (e.g., Bayesian versus conventional statistical approach). Guidance on the use of each method is given. No single method provides a perfect solution for all contexts.

Systematic reviews consistently indicate that interventions to change healthcare professional (HCP) behaviour are haphazardly designed and poorly specified. Clarity about methods for designing and specifying interventions is needed. The objective of this review was to identify published methods for designing interventions to change HCP behaviour. A search of MEDLINE, Embase, and PsycINFO was conducted from 1996 to April 2015. Using inclusion/exclusion criteria, a broad screen of abstracts by one rater was followed by a strict screen of full text for all potentially relevant papers by three raters. An inductive approach was first applied to the included studies to identify commonalities and differences between the descriptions of methods across the papers. Based on this process and knowledge of related literatures, we developed a data extraction framework that included, e.g. level of change (e.g. individual versus organization); context of development; a brief description of the method; tasks included in the method (e.g. barrier identification, component selection, use of theory). 3966 titles and abstracts and 64 full-text papers were screened to yield 15 papers included in the review, each outlining one design method. All of the papers reported methods developed within a specific context. Thirteen papers included barrier identification and 13 included linking barriers to intervention components; although not the same 13 papers. Thirteen papers targeted individual HCPs with only one paper targeting change across individual, organization, and system levels. The use of theory and user engagement were included in 13/15 and 13/15 papers, respectively. There is an agreement across methods of four tasks that need to be completed when designing individual-level interventions: identifying barriers, selecting intervention components, using theory, and engaging end-users. Methods also consist of further additional tasks. Examples of methods for designing the organisation and system-level interventions were limited. Further analysis of design tasks could facilitate the development of detailed guidelines for designing interventions.

Background Robot assisted laparoscopic (RAL) surgery developed to overcome the limitations of laparoscopy to assist in surgical procedures, has high capital and operating costs. Systematically assembled evidence demonstrating its clinical and cost effectiveness would be helpful for its adoption by decision makers. Objective To summarise the evidence on the cost-effectiveness of robot-assisted laparoscopic (RAL) surgery compared with relevant alternatives. Methods and results of identified studies were assessed to identify the deficiencies in evidence and areas for further research. Methods Studies reporting both costs and outcomes for comparisons of RAL with laparoscopy and/or open surgery were systematically identified. Searches were conducted in February 2015 on MEDLINE, EMBASE and NHS EED. Quality of the included studies was assessed against a standard checklist for economic analyses. Length of hospital stay and operating time (determinants of cost), cost of intervention, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were extracted. To aid comparison, costs were converted into a common currency and price year (2014 US dollars). Results Forty-seven eligible studies were identified (full economic evaluation n  = 6 and cost analysis n  = 41). Economic models were used in 11 (23 %) studies. Only three studies used a model considered representative of the disease and clinical pathway with a time-horizon allowing capture of relevant differences in outcomes across strategies. The cost of RAL varied substantially between uses, ranging from US$7011 for hysterectomy to over US$30,000 for radical cystectomy. The majority of estimates were between US$15,000 and US$25,000 per person. In part this difference is explained by the difference between studies in which costs were included. It was also identified to have higher costs than the alternatives it was compared against. Incremental cost per QALY for RAL radical prostatectomy was US$28,801–$31,763 over a 10-year period assuming 200 cases per annum. Conclusion The clinical evidence available for RAL overall and used within included studies is limited. RAL surgery costs were consistently higher than open and laparoscopic surgery. Therefore, in adopting the robotic technology decision makers need to take into account the cost effectiveness within their own systems. Economic models generated and published for radical prostatectomy and hysterectomy may be adapted to other health systems if the care pathway is similar to provide locally relevant data.

Background Gallstone disease is a common gastrointestinal disorder in industrialised countries. Although symptoms can be severe, some people can be symptom free for many years after the original attack. Surgery is the current treatment of choice, but evidence suggests that observation is also feasible and safe. We reviewed the evidence on cholecystectomy versus observation for uncomplicated symptomatic gallstones and conducted a cost-effectiveness analysis. Methods We searched six electronic databases (last search April 2014). We included randomised controlled trials (RCTs) or non-randomised comparative studies where adults received either cholecystectomy or observation/conservative management for the first episode of symptomatic gallstone disease (biliary pain or cholecystitis) being considered for surgery in secondary care. Meta-analysis was used to combine results. A de novo Markov model was developed to assess the cost effectiveness of the interventions. Results Two RCTs (201 participants) were included. Eighty-eight percent of people randomised to surgery and 45 % of people randomised to observation underwent cholecystectomy during the 14-year follow-up period. Participants randomised to observation were significantly more likely to experience gallstone-related complications (RR = 6.69, 95 % CI = 1.57–28.51, p  = 0.01), in particular acute cholecystitis (RR = 9.55, 95 % CI = 1.25–73.27, p  = 0.03), and less likely to undergo surgery (RR = 0.50, 95 % CI = 0.34–0.73, p  = 0.0004) or experience surgery-related complications (RR = 0.36, 95 % CI = 0.16–0.81, p  = 0.01) than those randomised to surgery. Fifty-five percent of people randomised to observation did not require surgery, and 12 % of people randomised to cholecystectomy did not undergo surgery. On average, surgery costs £1,236 more per patient than conservative management, but was more effective. Conclusions Cholecystectomy is the preferred treatment for symptomatic gallstones. However, approximately half the observation group did not require surgery or suffer complications indicating that it may be a valid alternative to surgery. A multicentre trial is needed to establish the effects, safety and cost effectiveness of observation/conservative management relative to cholecystectomy.