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We lead multidisciplinary applied research and training to rethink the way health care is delivered in general practice and across the community.
Examining the Impact of Structural Uncertainty Across 10 Type 2 Diabetes Models: Results From the 2022 Mount Hood Challenge
Objectives: The Mount Hood Diabetes Challenge Network aimed to examine the impact of model structural uncertainty on the estimated cost-effectiveness of interventions for type 2 diabetes. Methods: Ten independent modeling groups completed a blinded simulation exercise to estimate the cost-effectiveness of 3 interventions in 2 type 2 diabetes populations. Modeling groups were provided with a common baseline population, cost and utility values associated with different model health states, and instructions regarding time horizon and discounting. We collated the results to identify variation in predictions of net monetary benefit (NMB) and the drivers of those differences. Results: Overall, modeling groups agreed which interventions had a positive NMB (ie, were cost-effective), Although estimates of NMB varied substantially—by up to £23 696 for 1 intervention. Variation was mainly driven through differences in risk equations for complications of diabetes and their implementation between models. The number of modeled health states was also a significant predictor of NMB. Conclusions: This exercise demonstrates that structural uncertainty between different health economic models affects cost-effectiveness estimates. Although it is reassuring that a decision maker would likely reach similar conclusions on which interventions were cost-effective using most models, the range in numerical estimates generated across different models would nevertheless be important for price-setting negotiations with intervention developers. Minimizing the impact of structural uncertainty on healthcare decision making therefore remains an important priority. Model registries, which record and compare the impact of structural assumptions, offer one potential avenue to improve confidence in the robustness of health economic modeling.
Estimating Risk Factor Time Paths Among People with Type 2 Diabetes and QALY Gains from Risk Factor Management
Objectives: Most type 2 diabetes simulation models utilise equations mapping out lifetime trajectories of risk factors [e.g. glycated haemoglobin (HbA1c)]. Existing equations, using historic data or assuming constant risk factors, frequently underestimate or overestimate complication rates. Updated risk factor time path equations are needed for simulation models to more accurately predict complication rates. Aims: (1) Update United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2) risk factor time path equations; (2) compare quality-adjusted life-years (QALYs) using original and updated equations; and (3) compare QALY gains for reference case simulations using different risk factor equations. Methods: Using pooled contemporary data from two randomised trials EXSCEL and TECOS (n = 28,608), we estimated: dynamic panel models of seven continuous risk factors (high-density lipoprotein cholesterol, low density lipoprotein cholesterol, HbA1c, haemoglobin, heart rate, blood pressure and body mass index); two-step models of estimated glomerular filtration rate; and survival analyses of peripheral arterial disease, atrial fibrillation and albuminuria. UKPDS-OM2-derived lifetime QALYs were extrapolated over 70 years using historical and the new risk factor equations. Results: All new risk factor equation predictions were within 95% confidence intervals of observed values, displaying good agreement between observed and estimated values. Historical risk factor time path equations predicted trial participants would accrue 9.84 QALYs, increasing to 10.98 QALYs using contemporary equations. Discussion: Incorporating updated risk factor time path equations into diabetes simulation models could give more accurate predictions of long-term health, costs, QALYs and cost-effectiveness estimates, as well as a more precise understanding of the impact of diabetes on patients’ health, expenditure and quality of life. Trial Registration: ClinicalTrials.gov NCT01144338 and NCT00790205
The economic burden of cancer, coronary heart disease, dementia, and stroke in England in 2018, with projection to 2050: an evaluation of two cohort studies
Background: Cancer, coronary heart disease, dementia, and stroke are major contributors to morbidity and mortality in England. We aimed to assess the economic burden (including health-care, social care, and informal care costs, as well as productivity losses) of these four conditions in England in 2018, and forecast this cost to 2050 using population projections. Methods: We used individual patient-level data from the Clinical Practice Research Datalink (CPRD) Aurum, which contains primary care electronic health records of patients from 738 general practices in England, to calculate health-care and residential and nursing home resource use, and data from the English Longitudinal Study on Ageing (ELSA) to calculate informal and formal care costs. From CPRD Aurum, we included patients registered on Jan 1, 2018, in a CPRD general practice with Hospital Episode Statistics (HES)-linked records, omitting all children younger than 1 year. From ELSA, we included data collected from wave 9 (2018–19). Aggregate English resource use data on morbidity, mortality, and health-care, social care, and informal care were obtained and apportioned, using multivariable regression analyses, to cancer, coronary heart disease, dementia, and stroke. Findings: We included 4 161 558 patients from CPRD Aurum with HES-linked data (mean age 41 years [SD 23], with 2 079 679 [50·0%] men and 2 081 879 [50·0%] women) and 8736 patients in ELSA (68 years [11], with 4882 [55·9 %] men and 3854 [44·1%] women). In 2018, the total cost was £18·9 billion (95% CI 18·4–19·4) for cancer, £12·7 billion (12·3–13·0) for coronary heart disease, £11·7 billion (9·6–12·7) for dementia, and £8·6 billion (8·2–9·0) for stroke. Using 2050 English population projections, we estimated that costs would rise by 40% (39–41) for cancer, 54% (53–55) for coronary heart disease, 100% (97–102) for dementia, and 85% (84–86) for stroke, for a total of £26·5 billion (25·7–27·3), £19·6 billion (18·9–20·2), £23·5 billion (19·3–25·3), and £16·0 billion (15·3–16·6), respectively. Interpretation: This study provides contemporary estimates of the wide-ranging impact of the most important chronic conditions on all aspects of the economy in England. The data will help to inform evidence-based polices to reduce the impact of chronic disease, promoting care access, better health outcomes, and economic sustainability. Funding: Alzheimer's Research UK.
Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91)
Background: The 20-year UK Prospective Diabetes Study showed major clinical benefits for people with newly diagnosed type 2 diabetes randomly allocated to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. 10-year post-trial follow-up identified enduring and emerging glycaemic and metformin legacy treatment effects. We aimed to determine whether these effects would wane by extending follow-up for another 14 years. Methods: 5102 patients enrolled between 1977 and 1991, of whom 4209 (82·5%) participants were originally randomly allocated to receive either intensive glycaemic control (sulfonylurea or insulin, or if overweight, metformin) or conventional glycaemic control (primarily diet). At the end of the 20-year interventional trial, 3277 surviving participants entered a 10-year post-trial monitoring period, which ran until Sept 30, 2007. Eligible participants for this study were all surviving participants at the end of the 10-year post-trial monitoring period. An extended follow-up of these participants was done by linking them to their routinely collected National Health Service (NHS) data for another 14 years. Clinical outcomes were derived from records of deaths, hospital admissions, outpatient visits, and accident and emergency unit attendances. We examined seven prespecified aggregate clinical outcomes (ie, any diabetes-related endpoint, diabetes-related death, death from any cause, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease) by the randomised glycaemic control strategy on an intention-to-treat basis using Kaplan–Meier time-to-event and log-rank analyses. This study is registered with the ISRCTN registry, number ISRCTN75451837. Findings: Between Oct 1, 2007, and Sept 30, 2021, 1489 (97·6%) of 1525 participants could be linked to routinely collected NHS administrative data. Their mean age at baseline was 50·2 years (SD 8·0), and 41·3% were female. The mean age of those still alive as of Sept 30, 2021, was 79·9 years (SD 8·0). Individual follow-up from baseline ranged from 0 to 42 years, median 17·5 years (IQR 12·3–26·8). Overall follow-up increased by 21%, from 66 972 to 80 724 person-years. For up to 24 years after trial end, the glycaemic and metformin legacy effects showed no sign of waning. Early intensive glycaemic control with sulfonylurea or insulin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 10% (95% CI 2–17; p=0·015) for death from any cause, 17% (6–26; p=0·002) for myocardial infarction, and 26% (14–36; p<0·0001) for microvascular disease. Corresponding absolute risk reductions were 2·7%, 3·3%, and 3·5%, respectively. Early intensive glycaemic control with metformin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 20% (95% CI 5–32; p=0·010) for death from any cause and 31% (12–46; p=0·003) for myocardial infarction. Corresponding absolute risk reductions were 4·9% and 6·2%, respectively. No significant risk reductions during or after the trial for stroke or peripheral vascular disease were observed for both intensive glycaemic control groups, and no significant risk reduction for microvascular disease was observed for metformin therapy. Interpretation: Early intensive glycaemic control with sulfonylurea or insulin, or with metformin, compared with conventional glycaemic control, appears to confer a near-lifelong reduced risk of death and myocardial infarction. Achieving near normoglycaemia immediately following diagnosis might be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible. Funding: University of Oxford Nuffield Department of Population Health Pump Priming.
Trajectories of clinical characteristics, complications and treatment choices in data-driven subgroups of type 2 diabetes
Aims/hypothesis: This study aimed to explore the added value of subgroups that categorise individuals with type 2 diabetes by k-means clustering for two primary care registries (the Netherlands and Scotland), inspired by Ahlqvist’s novel diabetes subgroups and previously analysed by Slieker et al. Methods: We used two Dutch and Scottish diabetes cohorts (N=3054 and 6145; median follow-up=11.2 and 12.3 years, respectively) and defined five subgroups by k-means clustering with age at baseline, BMI, HbA1c, HDL-cholesterol and C-peptide. We investigated differences between subgroups by trajectories of risk factor values (random intercept models), time to diabetes-related complications (logrank tests and Cox models) and medication patterns (multinomial logistic models). We also compared directly using the clustering indicators as predictors of progression vs the k-means discrete subgroups. Cluster consistency over follow-up was assessed. Results: Subgroups’ risk factors were significantly different, and these differences remained generally consistent over follow-up. Among all subgroups, individuals with severe insulin resistance faced a significantly higher risk of myocardial infarction both before (HR 1.65; 95% CI 1.40, 1.94) and after adjusting for age effect (HR 1.72; 95% CI 1.46, 2.02) compared with mild diabetes with high HDL-cholesterol. Individuals with severe insulin-deficient diabetes were most intensively treated, with more than 25% prescribed insulin at 10 years of diagnosis. For severe insulin-deficient diabetes relative to mild diabetes, the relative risks for using insulin relative to no common treatment would be expected to increase by a factor of 3.07 (95% CI 2.73, 3.44), holding other factors constant. Clustering indicators were better predictors of progression variation relative to subgroups, but prediction accuracy may improve after combining both. Clusters were consistent over 8 years with an accuracy ranging from 59% to 72%. Conclusions/interpretation: Data-driven subgroup allocations were generally consistent over follow-up and captured significant differences in risk factor trajectories, medication patterns and complication risks. Subgroups serve better as a complement rather than as a basis for compressing clustering indicators. Graphical Abstract: (Figure presented.).
Comparison of medical resources and costs among patients with coronary heart disease and impaired glucose tolerance in the Acarbose Cardiovascular Evaluation trial
Background: The Acarbose Cardiovascular Evaluation (ACE) trial (ISRCTN91899513) evaluated the alpha-glucosidase inhibitor acarbose, compared with placebo, in 6522 patients with coronary heart disease and impaired glucose tolerance in China and showed a reduced incidence of diabetes. We assessed the within-trial medical resource use and costs, and quality-adjusted life years (QALYs). Methods: Resource use data were collected prospectively within the ACE trial. Hospitalizations, medications, and outpatient visits were valued using Chinese unit costs. Medication use was measured in drug days, with cardiovascular and diabetes drugs summed across the trial by participant. Health-related quality of life was captured using the EuroQol-5 Dimension-3 Level questionnaire. Regression analyses were used to compare resource use, costs, and QALYs, accounting for regional variation. Costs and QALYs were discounted at 3% yearly. Results: Hospitalizations were 6% higher in the acarbose arm during the trial (rate ratio 1.06, p =.009), but there were no significant differences in total inpatient days (rate ratio 1.04, p =.30). Total costs per participant, including study drug, were significantly higher for acarbose (¥ [Yuan] 56 480, £6213), compared with placebo (¥48 079, £5289; mean ratio 1.18, p < 0.001). QALYs reported by participants in the acarbose arm (3.96 QALYs) were marginally higher than in the placebo arm (3.95 QALYs), but the difference was not statistically significant (0.01 QALYs; p =.58). Conclusions: Acarbose, compared with placebo, participants cost more due to study drug costs and reported no statistically significant difference in QALYs. These higher within-trial costs could potentially be offset in future by savings from the acarbose-related lower incidence of diabetes.
Cardiovascular disease burden due to productivity losses in European Society of Cardiology countries
Objective Cardiovascular disease (CVD) is the leading cause of death across Europe. We estimated lost earnings (productivity losses) associated with premature mortality due to CVD, and separately for its main sub-categories of coronary heart disease and cerebrovascular disease, across 54 country members of the European Society of Cardiology (ESC). Methods and results We used a standardized approach to estimate working years and earnings lost due to premature death resulting from CVD across the 54 ESC member countries in 2018. Our population-based approach was based on national data on the number of deaths, employment rates, and earnings by age group and sex. We discounted future working years and earnings lost to present values using a 3.5% annual rate. In 2018, there were 4.4 million deaths due to CVD across the 54 countries, with 7.1 million working years lost. This represented productivity losses due to premature death of €62 billion in 2018. Deaths due to coronary heart disease accounted for 47% (€29 billion) of all CVD costs, and cerebrovascular disease accounted for 18% (€11 billion). Approximately 60% (€37 billion) of all productivity losses occurred in the 28 European Union member states, despite accounting for only 42% (1.8 million) of deaths and 21% (1.5 million) of working years lost across the 54 countries. Conclusion Our study provides a snapshot of the economic consequences posed by premature mortality due to CVD across 54 countries in 2018. The considerable variation across countries highlights the potential gains from policies targeting prevention and care of cardiovascular diseases.
Cost-effectiveness analysis of a pragmatic randomized trial evaluating surgical reconstruction versus rehabilitation in patients with long-standing anterior cruciate ligament injury
Aims The aim of this study was to estimate the incremental use of resources, costs, and quality of life outcomes associated with surgical reconstruction compared to rehabilitation for long-standing anterior cruciate ligament (ACL) injury in the NHS, and to estimate its cost-effectiveness. Methods A total of 316 patients were recruited and randomly assigned to either surgical reconstruction or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment). Healthcare resource use and health-related quality of life data (EuroQol five-dimension five-level health questionnaire) were collected in the trial at six, 12, and 18 months using self-reported questionnaires and medical records. Using intention-to-treat analysis, differences in costs, and quality-adjusted life years (QALYs) between treatment arms were estimated adjusting for baseline differences and following multiple imputation of missing data. The incremental cost-effectiveness ratio (ICER) was estimated as the difference in costs divided by the difference in QALYs between reconstruction and rehabilitation. Results At 18 months, patients in the surgical reconstruction arm reported higher QALYs (0.052 (95% confidence interval (CI) -0.012 to 0.117); p = 0.177) and higher NHS costs (£1,017 (95% CI 557 to 1,476); p < 0.001) compared to rehabilitation. This resulted in an ICER of £19,346 per QALY with the probability of surgical reconstruction being cost-effective of 51% and 72% at a willingness-to-pay threshold of £20,000 and £30,000 per QALY, respectively. Conclusion Surgical reconstruction as a management strategy for patients with long-standing ACL injury is more effective, but more expensive, at 18 months compared to rehabilitation management. In the UK setting, surgical reconstruction is cost-effective.
Comparison of surgical or non-surgical management for non-acute anterior cruciate ligament injury: the ACL SNNAP RCT
Background: Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment. Objective(s): To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation). Design: A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1: 1 allocation. Due to the nature of the interventions, no blinding could be carried out. Setting: Twenty-nine NHS orthopaedic units in the United Kingdom. Participants: Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee. Interventions: Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol. Main outcome measures: The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage. Results: Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent (n = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% (n = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent (n = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% (n = 248; surgical, n = 128; rehabilitation, n = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; p = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent (n = 65) of surgery patients did not reach their expected activity level compared to 73% (n = 63) in the rehabilitation arm. There were no differences between groups in surgical complications (n = 1 surgery, n = 2 rehab) or clinical events (n = 11 surgery, n = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, p = 0.177), but with higher NHS healthcare costs (£1107, p < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000–30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively. Limitations: Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic. Conclusions: Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation. Future work: Confirmatory studies and those to explore the influence of fidelity and compliance will be useful. Trial registration: This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials. gov Identifier: NCT02980367. Funding: This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in Health Technology Assessment; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.
Perceptions of Cardiovascular Healthcare Professionals Regarding Clinical Trials: A Survey-Based Study from the Middle East
Background: Low-middle income countries harbor the highest burden of cardiovascular diseases globally, but there is an under-representation of these countries in cardiovascular clinical trials. This limits the generalizability of the trial results to these countries. There is a lack of data on insights of cardiologists in these countries regarding conducting and participating in clinical trials. We sought the views of cardiovascular healthcare professionals in Iraq on participation in clinical trials. Method: Cardiovascular professionals in Iraq were identified and contacted, via special platforms on social media specified for them, to answer a 30-item online survey. Results: We surveyed n = 255specialists (20% were women); interventional cardiologists constituted 44.7%, followed by cardiology trainees at 31%. Almost 30% reported having been involved in clinical trials, with data collection being the more frequently reported role (21.2%). Prior participation was not significantly associated with respondent gender, academic affiliation, or presence of institutional ethical committee. Of the total, 95.7% thought that clinical trials should be conducted in Iraq, with 58.8% reporting that they would participate if invited. The most common barriers to respondents’ participation in trials were lack of electronic health records (52.2% of those surveyed) and time (51.4%), followed by the requirement of additional followup visits or investigations (34.1%). The most common motivators were establishing electronic health records (86.27%), education and training of the general population about clinical trials (84.7%), and dedicated training for healthcare providers about clinical trial basics (84.3%). Conclusion: Our work helps pave the path to implementing a robust clinical trial ecosystem in Iraq. Institutional and financial factors and a lack of dedicated research time are related to the cardiovascular clinical trial lag in Iraq. Future qualitative research can help in getting a deeper understanding of what is needed to create the right infrastructure.
Patient journey and costs through a brain health clinic compared with a memory clinic: a costing study
BACKGROUND: Dementia and Alzheimer's disease are the leading cause of death in England, with prevalence estimated to rise with an ageing population. 2021 cost estimates were £25 billion, rising to an estimated £47 billion in 2050. Brain health clinics (BHC) offer patients with memory concerns access to higher quality memory assessment and imaging than memory clinics, which are the usual care. BHCs aim to offer patients a more accurate and timely diagnosis, resulting in more specific treatment options. BHCs also offer patients the opportunity to take part in research. We aimed to compare the cost of a patient journey through a BHC and a memory clinic as part of an evaluation of the BHC model. METHODS: For this costing study, we consulted staff from one BHC and one memory clinic in the south of England in March 2023, to identify the patient journey and estimate clinical and research resources, time, and costs. We estimated personnel costs using time-per-task estimations multiplied by staff salary and verified with full-time-equivalent estimations for clinical and research tasks overall. BHC costs included both the BHC appointment and a follow-up appointment of reduced duration at the memory clinic. Memory clinic costs included a memory clinic appointment of normal duration. We estimated costs for both clinical (memory clinics and BHC) and research (BHC) tasks (not shown here). FINDINGS: BHC costs were 3·5 times more expensive (£1428) than memory clinic costs (£414). Approximately 150 patients are seen in BHCs yearly (total cost £214 200) compared with 600 patients seen in memory clinics yearly (total cost £248 400). BHC patients re-entering the memory clinic pathway required shorter appointments, thus offering cost savings of £230 per appointment in the memory clinic. INTERPRETATION: BHC costs were higher due to a lower throughput of patients and higher cost of high-quality imaging and assessment compared with memory clinics. However, these costs might prove to provide value for money when considering the gains in quality of life for patients and carers. Future work is planned to gather further outcome data to understand the added value of BHCs. Limitations include only assessing costs for one BHC and one memory clinic; further cost estimates are preferrable.None.
Barriers and motivators for participation of cardiovascular healthcare providers in clinical trials in Iraq: a survey-based study
Background Low-middle income countries harbour the highest burden of cardiovascular diseases globally but there is an under-representation of these countries in cardiovascular clinical trials. This limits the generalizability of the trial results to these countries. There is lack of data on insights of cardiologists in these countries regarding conducting and participating in clinical trials. We sought the views of cardiovascular healthcare professionals in Iraq on participation in clinical trials. Method Cardiovascular professionals in Iraq were identified and contacted, via special platforms on social media specified for them , to answer a 30-item online survey. Results n=255 (20% women), interventional cardiologists constituted 44.7% followed by cardiology trainees (31%). Almost 30% reported having been involved in clinical trials, with data collection being the more frequently reported role (21.2%). Prior participation was not significantly associated with respondent gender, academic affiliation, or presence of institutional ethical committee. 95.7% thought that clinical trials should be conducted in Iraq, with 58.8% reporting that they would participate if invited. The most common barriers to respondents' participation in trials were lack of electronic health records (52.2%) and time (51.4%), and the requirement of additional follow-up visits or investigations (34.1%). The most common motivators were establishing electronic health records (86.27%), education and training of the general population about clinical trials (84.7%), and dedicated training for healthcare providers about clinical trial basics (84.3%). Conclusion Our work helps pave the path to implementing a robust clinical trial ecosystem in Iraq. Institutional and financial factors and a lack of dedicated research time are related to the cardiovascular clinical trial lag in Iraq. Future qualitative research can help in getting a deeper understanding of what is needed to create the right infrastructure.
Potential Value of Identifying Type 2 Diabetes Subgroups for Guiding Intensive Treatment: A Comparison of Novel Data-Driven Clustering With Risk-Driven Subgroups
OBJECTIVE To estimate the impact on lifetime health and economic outcomes of different methods of stratifying individuals with type 2 diabetes, followed by guideline-based treatment intensification targeting BMI and LDL in addition to HbA1c . RESEARCH DESIGN AND METHODS We divided 2,935 newly diagnosed individuals from the Hoorn Diabetes Care System (DCS) cohort into five Risk Assessment and Progression of Diabetes (RHAPSODY) data-driven clustering subgroups (based on age, BMI, HbA1c, C-peptide, and HDL) and four risk-driven subgroups by using fixed cutoffs for HbA1c and risk of cardiovascular disease based on guidelines. The UK Prospective Diabetes Study Outcomes Model 2 estimated discounted expected lifetime complication costs and quality-adjusted life-years (QALYs) for each subgroup and across all individuals. Gains from treatment intensification were compared with care as usual as observed in DCS. A sensitivity analysis was conducted based on Ahlqvist subgroups. RESULTS Under care as usual, prognosis in the RHAPSODY data-driven subgroups ranged from 7.9 to 12.6 QALYs. Prognosis in the risk-driven subgroups ranged from 6.8 to 12.0 QALYs. Compared with homogenous type 2 diabetes, treatment for individuals in the high-risk subgroups could cost 22.0% and 25.3% more and still be cost effective for data-driven and risk-driven subgroups, respectively. Targeting BMI and LDL in addition to HbA1c might deliver up to 10-fold increases in QALYs gained. CONCLUSIONS Risk-driven subgroups better discriminated prognosis. Both stratification methods supported stratified treatment intensification, with the risk-driven subgroups being somewhat better in identifying individuals with the most potential to benefit from intensive treatment. Irrespective of stratification approach, better cholesterol and weight control showed substantial potential for health gains.
ACL Surgery Necessity in Non-Acute Patients (ACL SNNAP): a statistical analysis plan for a randomised controlled trial
Background: Rupture of the anterior cruciate ligament (ACL) is a common injury, primarily affecting young, active individuals. Despite surgical intervention being the more common treatment for patients suffering ACL ruptures, current management is based on limited and generally low-quality evidence. We describe a statistical analysis plan (SAP) for the ACL SNNAP randomised controlled trial, which aims to investigate the necessity of surgical management in patients with ACL injuries. Methods/design: ACL SNNAP is a pragmatic, multi-centre, superiority, parallel-group randomised controlled trial in participants with a symptomatic non-acute ACL deficient knee. Participants are allocated in a 1:1 ratio to either non-surgical management (rehabilitation) or surgical management (reconstruction) with the aim of assessing the efficacy and cost-effectiveness. The primary outcome of the study is the Knee Injury and Osteoarthritis Outcome Score (KOOS4) at 18 months post-randomisation. The KOOS4 score at 18 months will be evaluated using a linear regression model adjusting for recruitment centre and baseline KOOS4 scores, allowing for intra-centre correlation. A secondary analysis of the primary outcome will be carried out using an area under the curve (AUC) approach using treatment estimates obtained from a mixed model using baseline, 6 months, 12 months, and 18 months post-randomisation outcome data. Secondary outcomes will be measured at 18 months and will include return to activity/level of sport participation, intervention-related complications, the EQ-5D-5L questionnaire, all 5 individual subscales of the KOOS questionnaire, the ACL-QOL score, expectations of return to activity and cost-effectiveness of the interventions. Missing primary outcome data will be investigated through a sensitivity analysis. Full details of the planned methods for the statistical analysis of clinical outcomes are presented in this paper. The study protocol for the ACL SNNAP trial has been published previously. Discussion: The methods of analysis for the ACL SNNAP trial have been described here to minimise the risk of data-driven results and reporting bias. Any deviations from the analysis methods described in this paper will be described in full and justified in the publications of the trial results. Trial registration: ISRCTN ISRCTN10110685. Registered on 16 November 2016
Hospital costs associated with adverse events in people with diabetes in the UK
Aim: To estimate the annual hospital costs associated with a range of adverse events for people with diabetes in the UK. Methods: Annual hospital costs (2019/2020) were derived from 15 436 ASCEND participants from 2005 to 2017 (120 420 person-years). The annual hospital costs associated with cardiovascular events (myocardial infarction, coronary revascularization, transient ischaemic attack [TIA], ischaemic stroke, heart failure), bleeding (gastrointestinal [GI] bleed, intracranial haemorrhage, other major bleed), cancer (GI tract cancer, non-GI tract cancer), end-stage renal disease (ESRD), lower limb amputation and death (vascular, non-vascular) were estimated using a generalized linear model following adjustment for participants' sociodemographic and clinical factors. Results: In the year of event, ESRD was associated with the largest increase in annual hospital cost (£20 954), followed by lower limb amputation (£17 887), intracranial haemorrhage (£12 080), GI tract cancer (£10 160), coronary revascularization (£8531 if urgent; £8302 if non-urgent), heart failure (£8319), non-GI tract cancer (£7409), ischaemic stroke (£7170), GI bleed (£5557), myocardial infarction (£4913), other major bleed (£3825) and TIA (£1523). In subsequent years, most adverse events were associated with lasting but smaller increases in hospital costs, except for ESRD, where the additional cost remained high (£20 090). Conclusions: Our study provides robust estimates of annual hospital costs associated with a range of adverse events in people with diabetes that can inform future cost-effectiveness analyses of diabetes interventions. It also highlights the potential cost savings that could be derived from prevention of these costly complications.
Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial
Background: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. Methods: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. Findings: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. Interpretation: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. Funding: The UK National Institute for Health Research Health Technology Assessment Programme.
An Intuitive Risk Communication Tool to Enhance Patient–Provider Partnership in Diabetes Consultation
Introduction: This technology report introduces an innovative risk communication tool developed to support providers in communicating diabetes-related risks more intuitively to people with type 2 diabetes mellitus (T2DM). Methods: The development process involved three main steps: (1) selecting the content and format of the risk message; (2) developing a digital interface; and (3) assessing the usability and usefulness of the tool with clinicians through validated questionnaires. Results: The tool calculates personalized risk information based on a validated simulation model (United Kingdom Prospective Diabetes Study Outcomes Model 2) and delivers it using more intuitive risk formats, such as “effective heart age” to convey cardiovascular risks. Clinicians reported high scores for the usability and usefulness of the tool, making its adoption in routine care promising. Conclusions: Despite increased use of risk calculators in clinical care, this is the first time that such a tool has been developed in the diabetes area. Further studies are needed to confirm the benefits of using this tool on behavioral and health outcomes in T2DM populations.