Text Messages With Financial Incentives for Men With Obesity: A Randomized Clinical Trial.

Importance: Effective weight loss interventions are needed for men with obesity. Objective: To determine whether an intervention that combined text messaging with financial incentives attained significant weight loss at the 12-month follow-up compared with the control group and whether an intervention of text messaging alone attained significant weight loss at the 12-month follow-up compared with the control group. Design, Setting, and Participants: An assessor-blinded randomized clinical trial conducted in Belfast, Bristol, and Glasgow areas in the UK. A total of 585 men with body mass index (BMI) of 30 or more were enrolled between July 2021 and May 2022. Final follow-up occurred June 2023. Interventions: Participants were randomly assigned to 12 months of behavioral focused text messages combined with financial incentives (n = 196), 12 months of behavioral focused text messages alone (n= 194), or a waiting list (control group; n= 195). The financial incentive consisted of a monetary reward that was lost if weight loss targets were not met. All participants received weight management information and a pedometer at baseline. Main Outcomes and Measures: The 2 primary comparisons were the 12-month comparison of within-participant weight change between the text messaging with financial incentive group and the control group and the comparison between the text messaging alone group and the control group (minimum clinically important difference, 3%). The P value defined for statistical significance was P < .025 for each comparison. Results: Of the 585 men (mean [SD] age, 50.7 [13.3] years; mean weight, 118.5 [19.9] kg; mean BMI, 37.7 [5.7]; 525 [90%] White), 227 (39%) lived in postal code areas with lower socioeconomic status, and 426 (73%) completed the 12-month follow-up. At the 12-month follow-up, compared with the control group, the mean percent weight change was significantly greater in the text messaging with financial incentive group (mean difference, -3.2%; 97.5% CI, -4.6% to -1.9%; P < .001) but was not significantly greater in the text messaging alone group (mean difference, -1.4%; 97.5% CI, -2.9% to 0.0, P = .05). The mean (SD) weight changes were -5.7 (7.4) kg for the text messaging with financial incentives group, -3.0 (7.5) kg for the text messaging alone group, and -1.5 (6.6) kg for the control group. The 12-month mean (SD) percentage weight changes from baseline were -4.8% (6.1%) for the text messaging with financial incentives group, -2.7% (6.3%) for text messaging alone group, and -1.3% (5.5%) for the control group. Of 366 adverse events reported, the most common were infections (83 [23%]). Of the 23 serious adverse events (6.3%), 12 (52%) occurred in the text messaging with financial incentives group, 5 (22%) in the texts messaging alone group, and 6 (26%) in the control group. None were considered related to participating in a trial group. Conclusion and Relevance: Among men with obesity, an intervention with text messaging with financial incentive significantly improved weight loss compared with a control group, whereas text messaging alone was not significantly better than the control condition. These findings support text messaging combined with financial incentives to attain weight loss in men with obesity. Trial Registration: isrctn.org Identifier: ISRCTN91974895.

Effectiveness of conservative management versus laparoscopic cholecystectomy in the prevention of recurrent symptoms and complications in adults with uncomplicated symptomatic gallstone disease (C-GALL trial): pragmatic, multicentre randomised controlled trial.

OBJECTIVE: To assess the clinical and cost effectiveness of conservative management compared with laparoscopic cholecystectomy for the prevention of symptoms and complications in adults with uncomplicated symptomatic gallstone disease. DESIGN: Parallel group, pragmatic randomised, superiority trial. SETTING: 20 secondary care centres in the UK. PARTICIPANTS: 434 adults (>18 years) with uncomplicated symptomatic gallstone disease referred to secondary care, assessed for eligibility between August 2016 and November 2019, and randomly assigned (1:1) to receive conservative management or laparoscopic cholecystectomy. INTERVENTIONS: Conservative management or surgical removal of the gallbladder. MAIN OUTCOME MEASURES: The primary patient outcome was quality of life, measured by area under the curve, over 18 months using the short form 36 (SF-36) bodily pain domain, with higher scores (range 0-100) indicating better quality of life. Other outcomes included costs to the NHS, quality adjusted life years (QALYs), and incremental cost effectiveness ratio. RESULTS: Of 2667 patients assessed for eligibility, 434 were randomised: 217 to the conservative management group and 217 to the laparoscopic cholecystectomy group. By 18 months, 54 (25%) participants in the conservative management arm and 146 (67%) in the cholecystectomy arm had received surgery. The mean SF-36 norm based bodily pain score was 49.4 (standard deviation 11.7) in the conservative management arm and 50.4 (11.6) in the cholecystectomy arm. The SF-36 bodily pain area under the curve up to 18 months did not differ (mean difference 0.0, 95% confidence interval -1.7 to 1.7; P=1.00). Conservative management was less costly (mean difference -£1033, (-$1334; -€1205), 95% credible interval -£1413 to -£632) and QALYs did not differ (mean difference -0.019, 95% credible interval -0.06 to 0.02). CONCLUSIONS: In the short term (≤18 months), laparoscopic surgery is no more effective than conservative management for adults with uncomplicated symptomatic gallstone disease, and as such conservative management should be considered as an alternative to surgery. From an NHS perspective, conservative management may be cost effective for uncomplicated symptomatic gallstone disease. As costs, complications, and benefits will continue to be incurred in both groups beyond 18 months, future research should focus on longer term follow-up to establish effectiveness and lifetime cost effectiveness and to identify the cohort of patients who should be routinely offered surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN55215960.

A Systematic Review of the Evidence for Non-surgical Weight Management for Adults with Severe Obesity: What is Cost Effective and What are the Implications for the Design of Health Services?

PURPOSE OF REVIEW: Severe obesity (BMI ≥ 35 kg/m2) increases premature mortality and reduces quality-of-life. Obesity-related disease (ORD) places substantial burden on health systems. This review summarises the cost-effectiveness evidence for non-surgical weight management programmes (WMPs) for adults with severe obesity. RECENT FINDINGS: Whilst evidence shows bariatric surgery is often cost-effective, there is no clear consensus on the cost-effectiveness of non-surgical WMPs. Thirty-two studies were included. Most were short-term evaluations that did not capture the long-term costs and consequences of ORD. Decision models often included only a subset of relevant ORDs, and made varying assumptions about the rate of weight regain over time. A lack of sensitivity analyses limited interpretation of results. Heterogeneity in the definition of WMPs and usual care prevents formal evidence synthesis. We were unable to establish the most cost-effective WMPs. Addressing these limitations may help future studies provide more robust cost-effectiveness evidence for decision makers.

Effectiveness and cost-effectiveness of text messages with or without endowment incentives for weight management in men with obesity (Game of Stones): study protocol for a randomised controlled trial.

BACKGROUND: Obesity increases the risk of type 2 diabetes, heart disease, stroke, mobility problems and some cancers, and its prevalence is rising. Men engage less than women in existing weight loss interventions. Game of Stones builds on a successful feasibility study and aims to find out if automated text messages with or without endowment incentives are effective and cost-effective for weight loss at 12 months compared to a waiting list comparator arm in men with obesity. METHODS: A 3-arm, parallel group, assessor-blind superiority randomised controlled trial with process evaluation will recruit 585 adult men with body mass index of 30 kg/m2 or more living in and around three UK centres (Belfast, Bristol, Glasgow), purposively targeting disadvantaged areas. Intervention groups: (i) automated, theory-informed text messages daily for 12 months plus endowment incentives linked to verified weight loss targets at 3, 6 and 12 months; (ii) the same text messages and weight loss assessment protocol; (iii) comparator group: 12 month waiting list, then text messages for 3 months. The primary outcome is percentage weight change at 12 months from baseline. Secondary outcomes at 12 months are as follows: quality of life, wellbeing, mental health, weight stigma, behaviours, satisfaction and confidence. Follow-up includes weight at 24 months. A health economic evaluation will measure cost-effectiveness over the trial and over modelled lifetime: including health service resource-use and quality-adjusted life years. The cost-utility analysis will report incremental cost per quality-adjusted life years gained. Participant and service provider perspectives will be explored via telephone interviews, and exploratory mixed methods process evaluation analyses will focus on mental health, multiple long-term conditions, health inequalities and implementation strategies. DISCUSSION: The trial will report whether text messages (with and without cash incentives) can help men to lose weight over 1 year and maintain this for another year compared to a comparator group; the costs and benefits to the health service; and men's experiences of the interventions. Process analyses with public involvement and service commissioner input will ensure that this open-source digital self-care intervention could be sustainable and scalable by a range of NHS or public services. TRIAL REGISTRATION: ISRCTN 91974895 . Registered on 14/04/2021.

Does weight management research for adults with severe obesity represent them? Analysis of systematic review data.

OBJECTIVE: Our objective was to determine the extent to which current evidence from long-term randomised controlled trials (RCTs) of weight management is generalisable and applicable to underserved adult groups with obesity (body mass index (BMI) ≥35 kg/m2). METHODS: Descriptive analysis of 131 RCTs, published after 1990-May 2017 with ≥1 year of follow-up, included in a systematic review of long-term weight management interventions for adults with BMI ≥35 kg/m2 (the REBALANCE Project). Studies were identified from MEDLINE, EMBASE, PsychINFO, SCI, CENTRAL and from hand searching. Reporting of trial inclusion and exclusion criteria, trial recruitment strategies, baseline characteristics and outcomes were analysed using a predefined list of characteristics informed by the PROGRESS (Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital)-Plus framework and the UK Equality Act 2010. RESULTS: Few (6.1%) trials reported adapting recruitment to appeal to underserved groups. 10.0% reported culturally adapting their trial materials. Only 6.1% of trials gave any justification for their exclusion criteria, yet over half excluded participation for age or mental health reasons. Just over half (58%) of the trials reported participants' race or ethnicity, and one-fifth reported socioeconomic status. Where outcomes were reported for underserved groups, the most common analysis was by sex (47.3%), followed by race or ethnicity (16.8%). 3.1% of trials reported outcomes according to socioeconomic status. DISCUSSION: Although we were limited by poor trial reporting, our results indicate inadequate representation of people most at risk of obesity. Guidance for considering underserved groups may improve the appropriateness of research and inform greater engagement with health and social care services. FUNDING: National Institute for Health Research Health Technology Assessment Programme (project number: 15/09/04). PROSPERO REGISTRATION NUMBER: CRD42016040190.

A systematic review examining socioeconomic factors in trials of interventions for men that report weight as an outcome.

Weight management interventions designed specifically for men have become more common, but the extent to which socioeconomic factors are considered in trials of these interventions is unclear. We synthesized study characteristics, methods, and reporting of interventions with a behavioral component for men that report weight as an outcome, to establish the extent to which socioeconomic factors are considered during intervention design, conduct, and reporting. A comprehensive search was conducted on Medline, Embase, PsycINFO, and CENTRAL for studies published from January 2000 to July 2021. Thirty-six trials were included. Educational attainment (n = 24) was the most frequently reported socioeconomic characteristic, followed by working status (n = 14) and area level deprivation (n = 12). Seven studies did not report any socioeconomic characteristics. Most studies (n = 20) did not mention the socioeconomic profile of their samples in relation to study strengths or limitations. Few (n = 4) consulted with men from lower socioeconomic groups during intervention design. One study examined potential differential intervention effects across socioeconomic groups, with most not powered to do so. Recent feasibility trials (n = 3) targeting specific socioeconomic groups suggest a potential nascent towards a greater consideration of factors related to equity. To best inform public health policy related to health inequalities, greater consideration of socioeconomic factors is required in trials of men's weight management interventions.

Protocol for a randomised controlled trial comparing laparoscopic cholecystectomy with observation/conservative management for preventing recurrent symptoms and complications in adults with uncomplicated symptomatic gallstones (C-Gall trial).

BACKGROUND: Gallstone disease (cholelithiasis) is common. In most people it is asymptomatic and does not require treatment, but in about 20% it can become symptomatic, causing pain and other complications requiring medical attention and/or surgery. A proportion of symptomatic people with uncomplicated gallstone disease do not experience further episodes of pain and, therefore, could be treated conservatively. Moreover, surgery carries risks of perioperative and postoperative complications. METHODS AND ANALYSIS: C-Gall is a pragmatic, multicentre, randomised controlled trial and economic evaluation to assess whether cholecystectomy is cost-effective compared with observation/ conservative management (here after referred to as medical management) at 18 months post-randomisation (with internal pilot). PRIMARY OUTCOME MEASURE: Patient-reported quality of life (QoL) (36-Item Short Form Survey (SF-36) bodily pain domain) up to 18 months after randomisation.The primary economic outcome is incremental cost per quality-adjusted life year gained at 18 months. SECONDARY OUTCOME MEASURES: Secondary outcome measures include condition-specific QoL, SF-36 domains, complications, further treatment, persistent symptoms, healthcare resource use, and costs assessed at 18 and 24 months after randomisation. The bodily pain domain of the SF-36 will also be assessed at 24 months after randomisation.A sample size of 430 participants was calculated. Computer-generated 1:1 randomisation was used.The C-Gall Study is currently in follow-up in 20 UK research centres. The first patient was randomised on 1 August 2016, with follow-up to be completed by 30 November 2021. STATISTICAL ANALYSIS: Statistical analysis of the primary outcome will be intention-to-treat and a per-protocol analysis. The primary outcome, area under the curve (AUC) for the SF-36 bodily pain up to 18 months, will be generated using the Trapezium rule and analysed using linear regression with adjustment for the minimisation variables (recruitment site, sex and age). For the secondary outcome, SF-36 bodily pain, AUC up to 24 months will be analysed in a similar way. Other secondary outcomes will be analysed using generalised linear models with adjustment for minimisation and baseline variables, as appropriate. Statistical significance will be at the two-sided 5% level with corresponding CIs. ETHICS AND DISSEMINATION: The North of Scotland Research Ethics Committee approved this study (16/NS/0053). The dissemination plans include Health Technology Assessment monograph, international scientific meetings and publications in high-impact, open-access journals. TRIAL REGISTRATION NUMBER: ISRCTN55215960; pre-results.

Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT.

BACKGROUND: Advanced chronic kidney disease is common in older people and is frequently accompanied by metabolic acidosis. Oral sodium bicarbonate is used to treat this acidosis, but evidence is lacking on whether or not this provides a net gain in health or quality of life for older people. OBJECTIVES: The objectives were to determine whether or not oral bicarbonate therapy improves physical function, quality of life, markers of renal function, bone turnover and vascular health compared with placebo in older people with chronic kidney disease and mild acidosis; to assess the safety of oral bicarbonate; and to establish whether or not oral bicarbonate therapy is cost-effective in this setting. DESIGN: A parallel-group, double-blind, placebo-controlled randomised trial. SETTING: The setting was nephrology and geriatric medicine outpatient departments in 27 UK hospitals. PARTICIPANTS: Participants were adults aged ≥ 60 years with advanced chronic kidney disease (glomerular filtration rate category 4 or 5, not on dialysis) with a serum bicarbonate concentration of < 22 mmol/l. INTERVENTIONS: Eligible participants were randomised 1 : 1 to oral sodium bicarbonate or matching placebo. Dosing started at 500 mg three times daily, increasing to 1 g three times daily if the serum bicarbonate concentration was < 22 mmol/l at 3 months. MAIN OUTCOME MEASURES: The primary outcome was the between-group difference in the Short Physical Performance Battery score at 12 months, adjusted for baseline. Other outcome measures included generic and disease-specific health-related quality of life, anthropometry, 6-minute walk speed, grip strength, renal function, markers of bone turnover, blood pressure and brain natriuretic peptide. All adverse events were recorded, including commencement of renal replacement therapy. For the health economic analysis, the incremental cost per quality-adjusted life-year was the main outcome. RESULTS: In total, 300 participants were randomised, 152 to bicarbonate and 148 to placebo. The mean age of participants was 74 years and 86 (29%) were female. Adherence to study medication was 73% in both groups. A total of 220 (73%) participants were assessed at the 12-month visit. No significant treatment effect was evident for the primary outcome of the between-group difference in the Short Physical Performance Battery score at 12 months (-0.4 points, 95% confidence interval -0.9 to 0.1 points; p = 0.15). No significant treatment benefit was seen for any of the secondary outcomes. Adverse events were more frequent in the bicarbonate arm (457 vs. 400). Time to commencement of renal replacement therapy was similar in both groups (hazard ratio 1.22, 95% confidence interval 0.74 to 2.02; p = 0.43). Health economic analysis showed higher costs and lower quality of life in the bicarbonate arm at 1 year, with additional costs of £564 (95% confidence interval £88 to £1154) and a quality-adjusted life-year difference of -0.05 (95% confidence interval -0.08 to -0.01); placebo dominated bicarbonate under all sensitivity analyses for incremental cost-effectiveness. LIMITATIONS: The trial population was predominantly white and male, limiting generalisability. The increment in serum bicarbonate concentrations achieved was small and a benefit from larger doses of bicarbonate cannot be excluded. CONCLUSIONS: Oral sodium bicarbonate did not improve a range of health measures in people aged ≥ 60 years with chronic kidney disease category 4 or 5 and mild acidosis, and is unlikely to be cost-effective for use in the NHS in this patient group. Once other current trials of bicarbonate therapy in chronic kidney disease are complete, an individual participant meta-analysis would be helpful to determine which subgroups, if any, are more likely to benefit and which treatment regimens are more beneficial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN09486651 and EudraCT 2011-005271-16. The systematic review is registered as PROSPERO CRD42018112908. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 27. See the NIHR Journals Library website for further project information.

Patients with advanced chronic kidney disease often have excessive levels of acid in their blood (acidosis). Acidosis has been associated with a range of other problems that particularly affect patients with chronic kidney disease, including weaker muscles, weaker bones, worse blood vessel health and kidney disease that worsens more quickly. For decades, acidosis has been treated with sodium bicarbonate tablets (the ingredient found in baking soda) to neutralise the excess acid. However, sodium bicarbonate is awkward to take, may cause side effects and may increase blood pressure. To clarify whether or not sodium bicarbonate caused an overall improvement in health, we carried out a study involving 300 people aged ≥ 60 years with advanced chronic kidney disease and mild acidosis. Half received sodium bicarbonate capsules and half received dummy capsules (placebo), for up to 2 years. The treatments were chosen randomly by a computer and the participants, their doctors and the researchers were not aware of the treatment received until the end of the study. We measured physical function (walking speed, ability to stand from a chair, balance) alongside quality of life, kidney function, bone and blood vessel health, side effects and health service use over 2 years. We found that sodium bicarbonate did not improve physical function or quality of life compared with placebo. Sodium bicarbonate also did not improve kidney function, bone health or blood vessel health compared with placebo. More people in the sodium bicarbonate group than in the placebo group had side effects, although blood pressure was the same in both groups. Health-care costs were higher in the sodium bicarbonate group than in the placebo group. We conclude that oral sodium bicarbonate did not significantly improve health measures compared with placebo for older people (aged ≥ 60 years) with advanced chronic kidney disease associated with mild acidosis.

Challenges of Systematic Reviews of Economic Evaluations: A Review of Recent Reviews and an Obesity Case Study.

Decision makers increasingly require cost-effectiveness evidence to inform resource allocation and the need for systematic reviews of economic evaluations (SREEs) has grown accordingly. The objective of this article is to describe current practice and identify unique challenges in conducting and reporting SREEs. Current guideline documents for SREEs were consulted and summarised. A rapid review of English-language SREEs, using MEDLINE and EMBASE, published in 2017/2018, containing at least 20 studies was undertaken to describe current practice. Information on data extraction methods, quality assessment (QA) tools and reporting methods were narratively summarised. Lessons learned from a recently conducted SREE of weight loss interventions for severely obese adults were discussed. Sixty-three publications were included in the rapid review. Substantial heterogeneity in review methods, reporting standards and QA approaches was evident. Our recently conducted SREE on weight loss interventions identified scope to improve process efficiency, opportunity for more transparent and succinct reporting, and potential to improve consistency of QA. Practical solutions may include (1) using pre-piloted data extraction forms linked explicitly to results tables; (2) consistently reporting on key assumptions and sensitivity analyses that drive results; and (3) using checklists that include topic-specific items where relevant and allow reviewers to distinguish between reporting, justification and QA. The lack of a mutually agreed, standardised set of best practice guidelines has led to substantial heterogeneity in the conduct and reporting of SREEs. Future work is required to standardise the approach to conducting SREEs so that they can generate efficient, timely and relevant evidence to support decision-making. We suggest only data extracting information that will be reported, focusing discussion around the key drivers of cost-effectiveness, and improving consistency in QA by distinguishing between what is reported, justified by authors and deemed appropriate by the reviewer.

Evaluating ethics oversight during assessment of research integrity.

We provide additional information relevant to our previous publication on the quality of reports of investigations of research integrity by academic institutions. Despite concerns being raised about ethical oversight of research published by a group of researchers, each of the four institutional investigations failed to determine and/or report whether ethics committee approval was obtained for the majority of publications assessed.

Bariatric surgery, lifestyle interventions and orlistat for severe obesity: the REBALANCE mixed-methods systematic review and economic evaluation.

BACKGROUND: Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m2] have an increased risk of comorbidities and psychological, social and economic consequences. OBJECTIVES: Systematically review bariatric surgery, weight-management programmes (WMPs) and orlistat pharmacotherapy for adults with severe obesity, and evaluate the feasibility, acceptability, clinical effectiveness and cost-effectiveness of treatment. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials and the NHS Economic Evaluation Database were searched (last searched in May 2017). REVIEW METHODS: Four systematic reviews evaluated clinical effectiveness, cost-effectiveness and qualitative evidence for adults with a BMI of ≥ 35 kg/m2. Data from meta-analyses populated a microsimulation model predicting costs, outcomes and cost-effectiveness of Roux-en-Y gastric bypass (RYGB) surgery and the most effective lifestyle WMPs over a 30-year time horizon from a NHS perspective, compared with current UK population obesity trends. Interventions were cost-effective if the additional cost of achieving a quality-adjusted life-year is < £20,000-30,000. RESULTS: A total of 131 randomised controlled trials (RCTs), 26 UK studies, 33 qualitative studies and 46 cost-effectiveness studies were included. From RCTs, RYGB produced the greatest long-term weight change [-20.23 kg, 95% confidence interval (CI) -23.75 to -16.71 kg, at 60 months]. WMPs with very low-calorie diets (VLCDs) produced the greatest weight loss at 12 months compared with no WMPs. Adding a VLCD to a WMP gave an additional mean weight change of -4.41 kg (95% CI -5.93 to -2.88 kg) at 12 months. The intensive Look AHEAD WMP produced mean long-term weight loss of 6% in people with type 2 diabetes mellitus (at a median of 9.6 years). The microsimulation model found that WMPs were generally cost-effective compared with population obesity trends. Long-term WMP weight regain was very uncertain, apart from Look AHEAD. The addition of a VLCD to a WMP was not cost-effective compared with a WMP alone. RYGB was cost-effective compared with no surgery and WMPs, but the model did not replicate long-term cost savings found in previous studies. Qualitative data suggested that participants could be attracted to take part in WMPs through endorsement by their health-care provider or through perceiving innovative activities, with WMPs being delivered to groups. Features improving long-term weight loss included having group support, additional behavioural support, a physical activity programme to attend, a prescribed calorie diet or a calorie deficit. LIMITATIONS: Reviewed studies often lacked generalisability to UK settings in terms of participants and resources for implementation, and usually lacked long-term follow-up (particularly for complications for surgery), leading to unrealistic weight regain assumptions. The views of potential and actual users of services were rarely reported to contribute to service design. This study may have failed to identify unpublished UK evaluations. Dual, blinded numerical data extraction was not undertaken. CONCLUSIONS: Roux-en-Y gastric bypass was costly to deliver, but it was the most cost-effective intervention. Adding a VLCD to a WMP was not cost-effective compared with a WMP alone. Most WMPs were cost-effective compared with current population obesity trends. FUTURE WORK: Improved reporting of WMPs is needed to allow replication, translation and further research. Qualitative research is needed with adults who are potential users of, or who fail to engage with or drop out from, WMPs. RCTs and economic evaluations in UK settings (e.g. Tier 3, commercial programmes or primary care) should evaluate VLCDs with long-term follow-up (≥ 5 years). Decision models should incorporate relevant costs, disease states and evidence-based weight regain assumptions. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016040190. FUNDING: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.

Assessment of research waste part 1: an exemplar from examining study design, surrogate and clinical endpoints in studies of calcium intake and vitamin D supplementation.

BACKGROUND: Research waste is estimated to be very common, but assessments of its prevalence and scope are rare. As an example, we assessed research waste in clinical research on calcium intake (assessing study design and endpoint type) and vitamin D supplementation (assessing endpoint type). METHODS: We examined 404 randomised controlled trials (RCTs) and observational studies of calcium intake (diet or supplements) and bone mineral density (BMD) or fracture, and 547 RCTs of vitamin D supplements, and assessed the proportion of studies that used surrogate or clinical endpoints. For studies with BMD or fracture as an endpoint, we estimated when the 'tipping' point occurred indicating the need for RCTs with fracture as an endpoint (based on cumulative meta-analyses of BMD RCTs, and chronological review of observational studies), and whether each study published at least 5y after the tipping point was novel, added new clinical knowledge or was research waste. RESULTS: Observational studies of calcium intake and BMD or fracture outnumbered RCTs by 3.3-4.5 times. For both calcium intake and vitamin D supplements, studies using surrogate endpoints outnumbered studies using clinical endpoints by 1.6-3 times. Of 41 RCT publications of calcium intake and BMD or fracture published at least 5y after the tipping point in 1994, we considered that 19 (46%) lacked novelty, another 13 (32%) added no new clinical knowledge, and 30 (73%) were research waste. Of 204 observational study publications of calcium intake and BMD or fracture, 197 (96%) lacked novelty, another 5 (2%) added no new clinical knowledge, and 202 (99%) were research waste. Of 39 RCTs of vitamin D supplementation and BMD or fracture published at least 5y after the tipping point in 1999, 14 (36%) lacked novelty, another 13 (33%) added no new clinical knowledge, and 27 (69%) were research waste. CONCLUSIONS: A high proportion of studies of calcium intake since 2000 (95%) and trials of vitamin D supplements since 2005 (69%) on BMD or fracture represent research waste.

Assessment of research waste part 2: wrong study populations- an exemplar of baseline vitamin D status of participants in trials of vitamin D supplementation.

BACKGROUND: Research waste can occur when trials are conducted in the wrong populations. Vitamin D deficient populations are most likely to benefit from vitamin D supplementation. We investigated waste attributable to randomised controlled trials (RCTs) of supplementation in populations that were not vitamin D deficient. METHODS: In December 2015, we searched Pubmed, recent systematic reviews, and three trial registries for RCTs of vitamin D with clinical endpoints in adults, and 25-hydroxvitamin D (25OHD) survey data relevant to large (N ≥ 1000) RCTs. We investigated the proportion of RCTs that studied vitamin D deficient populations, temporal trends in baseline 25OHD, and whether investigators in large RCTs considered relevant 25OHD survey data or systematic reviews in their trial justifications. RESULTS: Of 137 RCTs of vitamin D with clinical endpoints, 118 (86%) reported baseline mean/median 25OHD, which was < 25, 25-49, 50-74, and ≥ 75 nmol/L in 12 (10%), 62 (53%), 36 (31%), and 8 (7%) RCTs, respectively. In 70% of RCTs, baseline 25OHD was > 40 nmol/L. Baseline 25OHD increased over time. Before 2006, 38%, 62%, 0% and 0% of RCTs had baseline 25OHD < 25, 25-49, 50-74, and ≥ 75 nmol/L respectively; in 2011-15, the respective proportions were 9%, 49%, 37%, and 6%. Of 12 RCTs with baseline 25OHD < 25 nmol/L, 8 had neutral findings. Of 25 large RCTs (18 completed, 7 ongoing), 1 was undertaken in a vitamin D deficient population, 3 in vitamin D insufficient populations, and 17 had, or probably will have, baseline 25OHD > 40 nmol/L. 44% (8/18) of large completed RCTs cited relevant prior population 25OHD data, and only 3/10 (30%) relevant prior systematic reviews. CONCLUSIONS: Up to 70% of RCTs of vitamin D with clinical endpoints, 71% of large completed RCTs, and 100% of ongoing large RCTs could be considered research waste because they studied cohorts that were not vitamin D deficient.

A mixed-methods evaluation of a community pharmacy signposting service to a commercial weight-loss provider.

OBJECTIVE: Community pharmacies could provide access for clients to commercial weight management organizations. We evaluated recruitment, referral and outcomes of adults provided with free vouchers by community pharmacies to attend Scottish Slimmers classes. DESIGN: Prospective cohort design with qualitative interviews with clients and pharmacy personnel. Scottish Slimmers collected weight and attendance data. SETTING: Pharmacies in Aberdeen City, Scotland. SUBJECTS: Clients aged ≥18 years with BMI≥30 kg/m2. RESULTS: Ten of twenty-three pharmacies were recruited; eight successfully recruited clients. Of 129 clients recruited, ninety-seven (75 %) attended at least one class and fifty-one (40 %) attended all twelve classes. At baseline, clients' mean weight was 99·4 (sd 17·5) kg, mean BMI was 37·8 (sd 6·0) kg/m2. After 12 weeks, mean weight change was -3·7 % (last observation carried forward) or -2·8 % (baseline observation carried forward) for all ninety-seven clients. Client interviews indicated that many individuals would have not addressed their weight problems if this referral service had not been available. They had positive attitudes towards the pharmacy signposting service, attributed to the use of consultation rooms for privacy, receiving professional service from personnel and ongoing support and encouragement. The free provision of 12-week access facilitated participation. Service providers had positive attitudes and indicated their willingness to provide this service in future. CONCLUSIONS: Community pharmacies could be used to increase access to weight management services, with pharmacy personnel providing additional support to clients. Future provision of pharmacy referral schemes should be evaluated on a larger scale with an economic evaluation.

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial.

BACKGROUND: Metabolic acidosis is more common with advancing chronic kidney disease, and has been associated with impaired physical function, impaired bone health, accelerated decline in kidney function and increased vascular risk. Although oral sodium bicarbonate is widely used to correct metabolic acidosis, there exist potential risks of therapy including worsening hypertension and fluid overload. Little trial evidence exists to decide whether oral bicarbonate therapy is of net benefit in advanced chronic kidney disease, particularly in older people who are most commonly affected, and in whom physical function, quality of life and vascular health are at least as important outcomes as decline in renal function. METHODS/DESIGN: BiCARB is a multi-centre, double-blind, placebo controlled, randomised trial evaluating the clinical and cost-effectiveness of oral sodium bicarbonate in the management of older people with chronic kidney disease and severely reduced glomerular filtration rate (GFR) who have a mild degree of metabolic acidosis. The trial will recruit 380 patients from renal, Medicine for the Elderly, and primary care services across centres in the United Kingdom. Male and female patients aged 60 years and older with an estimated glomerular filtration rate of <30 mL/min/1.73 m(2), not on dialysis, and with serum bicarbonate concentrations <22 mmol/L will be eligible for participation. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at 12 months. Secondary outcomes include muscle strength, quality of life measured using the EQ-5D score and KDQoL tools, cost effectiveness, renal function, presence of albuminuria and blood pressure. Markers of bone turnover (25-hydroxyvitamin D, 1,25-hydroxyvitamin D, tartrate-resistant acid phosphatase-5b and bone-specific alkaline phosphatase) and vascular health (B-type natriuretic peptide) will be measured. Participants will receive a total of 24 months of either bicarbonate or placebo. The results will provide the first robust test of the overall clinical and cost-effectiveness of this commonly used therapy in older patients with severely reduced kidney function. TRIAL REGISTRATION: www.isrctn.com; ISRCTN09486651, registered 17 February 2012.

A systematic review of the cost-effectiveness of non-surgical obesity interventions in men.

BACKGROUND: Increasing obesity related health conditions have a substantial burden on population health and healthcare spending. Obesity may have a sex-specific impact on disease development, men and women may respond differently to interventions, and there may be sex-specific differences to the cost-effectiveness of interventions to address obesity. There is no clear indication of cost-effective treatments for men. METHODS: This systematic review summarises the literature reporting the cost-effectiveness of non-surgical weight-management interventions for men. Studies were quality assessed against a checklist for appraising decision modelling studies. RESULTS: Although none of the included studies explicitly set out to determine the cost-effectiveness of treatment for men, seven studies reported results for subgroups of men. Interventions were grouped into lifestyle interventions (five studies) and Orlistat (two studies). The retrieved studies showed promising evidence of cost-effectiveness, especially when interventions were targeted at high-risk groups, such as those with impaired glucose tolerance. There appears to be some sex-specific elements to cost-effectiveness, however, there were no clear trends or indications of what may be contributing to this. CONCLUSION: The economic evidence was highly uncertain, and limited by variable methodological quality of the included studies. It was therefore not possible to draw strong conclusions on cost-effectiveness. Future studies are required to demonstrate the cost-effectiveness of interventions specifically targeted towards weight loss for men.

Systematic review of the clinical and cost effectiveness of cholecystectomy versus observation/conservative management for uncomplicated symptomatic gallstones or cholecystitis.

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.