Publications by authors named "Seamus Kent"

22 Publications

  • Page 1 of 1

Cost-Effectiveness of Dopamine Agonists and Monoamine Oxidase B Inhibitors in Early Parkinson's Disease.

Mov Disord 2021 May 7. Epub 2021 May 7.

University of Oxford, Oxford, United Kingdom.

Background: The PD MED study reported small but persistent benefits in patient-rated mobility scores and quality of life from initiating therapy with levodopa compared with levodopa-sparing therapies in early Parkinson's disease (PD).

Objectives: The objective was to estimate the cost-effectiveness of levodopa-sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors compared with levodopa alone.

Methods: PD MED is a pragmatic, open-label randomized, controlled trial in which patients newly diagnosed with PD were randomly assigned between levodopa-sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors ) and levodopa alone. Mean quality-adjusted life-years and costs were calculated for each participant. Differences in mean quality-adjusted life-years and costs between levodopa and levodopa-sparing therapies and between dopamine agonists and monoamine oxidase type B inhibitors were estimated using linear regression.

Results: Over a mean observation period of 4 years, levodopa was associated with significantly higher quality-adjusted life-years (difference, 0.18; 95% CI, 0.05-0.30; P < 0.01) and lower mean costs (£3390; £2671-£4109; P < 0.01) than levodopa-sparing therapies, the difference in costs driven by the higher costs of levodopa-sparing therapies. There were no significant differences in the costs of inpatient, social care, and institutional care between arms. There was no significant difference in quality-adjusted life-years between those allocated dopamine agonists and monoamine oxidase type B inhibitors (0.02; -0.17 to 0.13 in favor of dopamine agonists; P = 0.81); however costs were significantly lower for those allocated monoamine oxidase type B inhibitors (£2321; £1628-£3015; P < 0.01) because of the higher costs of dopamine agonists. There were no significant differences between arms for other costs.

Conclusions: Initial treatment with levodopa is highly cost-effective compared with levodopa-sparing therapies. Monoamine oxidase type B inhibitors, as initial levodopa-sparing therapy was more cost-effective, with similar quality-adjusted life-years but lower costs than dopamine agonists. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28623DOI Listing
May 2021

Impact of the 2003 to 2018 Population Salt Intake Reduction Program in England: A Modeling Study.

Hypertension 2021 Apr 1;77(4):1086-1094. Epub 2021 Mar 1.

From the Institute of Population Health Sciences (S.A., B.M.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968966PMC
April 2021

Common Problems, Common Data Model Solutions: Evidence Generation for Health Technology Assessment.

Pharmacoeconomics 2021 Mar 18;39(3):275-285. Epub 2020 Dec 18.

National Institute for Health and Care Excellence, London, United Kingdom.

There is growing interest in using observational data to assess the safety, effectiveness, and cost effectiveness of medical technologies, but operational, technical, and methodological challenges limit its more widespread use. Common data models and federated data networks offer a potential solution to many of these problems. The open-source Observational and Medical Outcomes Partnerships (OMOP) common data model standardises the structure, format, and terminologies of otherwise disparate datasets, enabling the execution of common analytical code across a federated data network in which only code and aggregate results are shared. While common data models are increasingly used in regulatory decision making, relatively little attention has been given to their use in health technology assessment (HTA). We show that the common data model has the potential to facilitate access to relevant data, enable multidatabase studies to enhance statistical power and transfer results across populations and settings to meet the needs of local HTA decision makers, and validate findings. The use of open-source and standardised analytics improves transparency and reduces coding errors, thereby increasing confidence in the results. Further engagement from the HTA community is required to inform the appropriate standards for mapping data to the common data model and to design tools that can support evidence generation and decision making.
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http://dx.doi.org/10.1007/s40273-020-00981-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746423PMC
March 2021

Outpatient physiotherapy versus home-based rehabilitation for patients at risk of poor outcomes after knee arthroplasty: CORKA RCT.

Health Technol Assess 2020 11;24(65):1-116

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Background: Over 100,000 primary knee arthroplasty operations are undertaken annually in the UK. Around 15-30% of patients do not report a good outcome. Better rehabilitation strategies may improve patient-reported outcomes.

Objectives: To compare the outcomes from a traditional outpatient physiotherapy model with those from a home-based rehabilitation programme for people assessed as being at risk of a poor outcome after knee arthroplasty.

Design: An individually randomised, two-arm controlled trial with a blinded outcome assessment, a parallel health economic evaluation and a nested qualitative study.

Setting: The trial took place in 14 NHS physiotherapy departments.

Participants: People identified as being at high risk of a poor outcome after knee arthroplasty.

Interventions: A multicomponent home-based rehabilitation package delivered by rehabilitation assistants with supervision from qualified therapists compared with usual-care outpatient physiotherapy.

Main Outcome Measures: The primary outcome was the Late Life Function and Disability Instrument at 12 months. Secondary outcomes were the Oxford Knee Score (a disease-specific measure of function); Knee injury and Osteoarthritis Outcome Score; Quality of Life subscale; Physical Activity Scale for the Elderly; EuroQol-5 Dimensions, five-level version; and physical function assessed using the Figure-of-8 Walk Test, 30-Second Chair Stand Test and Single Leg Stance. Data on the use of health-care services, time off work and informal care were collected using participant diaries.

Results: In total, 621 participants were randomised. A total of 309 participants were assigned to the COmmunity based Rehabilitation after Knee Arthroplasty (CORKA) home-based rehabilitation programme, receiving a median of five treatment sessions (interquartile range 4-7 sessions). A total of 312 participants were assigned to usual care, receiving a median of four sessions (interquartile range 2-6 sessions). The primary outcome, Late Life Function and Disability Instrument function total score at 12 months, was collected for 279 participants (89%) in the home-based CORKA group and 287 participants (92%) in the usual-care group. No clinically or statistically significant difference was found between the groups (intention-to-treat adjusted difference 0.49 points, 95% confidence interval -0.89 to 1.88 points;  = 0.48). There were no statistically significant differences between the groups in any of the patient-reported or physical secondary outcome measures at 6 or 12 months post randomisation. The health economic analysis found that the CORKA intervention was cheaper to provide than usual care (£66 less per participant). Total societal costs (combining health-care costs and other costs) were lower for the CORKA intervention than usual care (£316 less per participant). Adopting a societal perspective, CORKA had a 75% probability of being cost-effective at a threshold of £30,000 per quality-adjusted life-year. Adopting the narrower health and social care perspective, CORKA had a 43% probability of being cost-effective at the same threshold.

Limitations: The interventions were of short duration and were set within current commissioning guidance for UK physiotherapy. Participants and treating therapists could not be blinded.

Conclusions: This randomised controlled trial found no important differences in outcomes when post-arthroplasty rehabilitation was delivered using a home-based, rehabilitation assistant-delivered rehabilitation package or a traditional outpatient model. However, the health economic evaluation found that when adopting a societal perspective, the CORKA home-based intervention was cost-saving and more effective than, and thus dominant over, usual care, owing to reduced time away from paid employment for this group. Further research could look at identifying the risk of poor outcome and further evaluation of a cost-effective treatment, including the workforce model to deliver it.

Trial Registration: Current Controlled Trials ISRCTN13517704.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 65. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta24650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750865PMC
November 2020

Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study.

Nat Commun 2020 10 6;11(1):5009. Epub 2020 Oct 6.

Clinical Pharmacology Unit, Zealand University Hospital, Køge, Denmark.

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19.
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http://dx.doi.org/10.1038/s41467-020-18849-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538555PMC
October 2020

Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study.

Lancet Rheumatol 2020 Nov 21;2(11):e698-e711. Epub 2020 Aug 21.

Janssen Research and Development, Titusville, NJ, USA.

Background: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis.

Methods: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the value was less than 0·4.

Findings: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12-2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22-3·95]), chest pain or angina (1·15 [1·05-1·26]), and heart failure (1·22 [1·02-1·45]).

Interpretation: Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment.

Funding: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations.
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http://dx.doi.org/10.1016/S2665-9913(20)30276-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442425PMC
November 2020

An international characterisation of patients hospitalised with COVID-19 and a comparison with those previously hospitalised with influenza.

medRxiv 2020 Apr 25. Epub 2020 Apr 25.

Science Policy and Research, National Institute for Health and Care Excellence, UK.

Background: To better understand the profile of individuals with severe coronavirus disease 2019 (COVID-19), we characterised individuals hospitalised with COVID-19 and compared them to individuals previously hospitalised with influenza.

Methods: We report the characteristics (demographics, prior conditions and medication use) of patients hospitalised with COVID-19 between December 2019 and April 2020 in the US (Columbia University Irving Medical Center [CUIMC], STAnford Medicine Research data Repository [STARR-OMOP], and the Department of Veterans Affairs [VA OMOP]) and Health Insurance Review & Assessment [HIRA] of South Korea. Patients hospitalised with COVID-19 were compared with patients previously hospitalised with influenza in 2014-19.

Results: 6,806 (US: 1,634, South Korea: 5,172) individuals hospitalised with COVID-19 were included. Patients in the US were majority male (VA OMOP: 94%, STARR-OMOP: 57%, CUIMC: 52%), but were majority female in HIRA (56%). Age profiles varied across data sources. Prevalence of asthma ranged from 7% to 14%, diabetes from 18% to 43%, and hypertensive disorder from 22% to 70% across data sources, while between 9% and 39% were taking drugs acting on the renin-angiotensin system in the 30 days prior to their hospitalisation. Compared to 52,422 individuals hospitalised with influenza, patients admitted with COVID-19 were more likely male, younger, and, in the US, had fewer comorbidities and lower medication use.

Conclusions: Rates of comorbidities and medication use are high among individuals hospitalised with COVID-19. However, COVID-19 patients are more likely to be male and appear to be younger and, in the US, generally healthier than those typically admitted with influenza.
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http://dx.doi.org/10.1101/2020.04.22.20074336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239064PMC
April 2020

BMI and Cause-Specific Hospital Admissions and Costs: The UK Biobank Cohort Study.

Obesity (Silver Spring) 2020 07 21;28(7):1332-1341. Epub 2020 May 21.

Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Objective: To estimate the effect of BMI on cause-specific hospital admissions and costs in men and women is not well understood, and this study's aim is to address this.

Methods: For 451,320 men and women aged 40 years or older recruited into the UK Biobank, followed up for 6 years on average, this study estimated annual rates and costs (at 2016 UK prices) of hospital admissions, overall and by diagnostic category (using International Classification of Diseases, Tenth Revision chapters), in relation to BMI.

Results: Among those who were never smokers, a 2-kg/m higher BMI (above 20 kg/m ) was associated with a 6.2% (99% CI: 5.3% to 7.2%) higher admission rate and an 8.6% (99% CI: 7.3% to 10.0%) higher annual cost in men and with a 5.7% (99% CI: 4.9% to 6.6%) higher admission rate and an 8.4% (99% CI: 7.5% to 9.3%) higher annual cost in women. Higher BMI was associated with higher admission rates and costs for many types of health conditions, particularly for endocrine, skin, and musculoskeletal disorders in both men and women and for circulatory diseases in men.

Conclusions: BMI beyond healthy weight is strongly associated with higher annual rates of hospital admission and higher costs in both men and women across a wide range of health conditions.
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http://dx.doi.org/10.1002/oby.22812DOI Listing
July 2020

Total versus partial knee replacement in patients with medial compartment knee osteoarthritis: the TOPKAT RCT.

Health Technol Assess 2020 04;24(20):1-98

Health Services Research Unit, University of Aberdeen, Aberdeen, UK.

Background: Late-stage medial compartment knee osteoarthritis can be treated using total knee replacement or partial (unicompartmental) knee replacement. There is high variation in treatment choice and insufficient evidence to guide selection.

Objective: To assess the clinical effectiveness and cost-effectiveness of partial knee replacement compared with total knee replacement in patients with medial compartment knee osteoarthritis. The findings are intended to guide surgical decision-making for patients, surgeons and health-care providers.

Design: This was a randomised, multicentre, pragmatic comparative effectiveness trial that included an expertise component. The target sample size was 500 patients. A web-based randomisation system was used to allocate treatments.

Setting: Twenty-seven NHS hospitals (68 surgeons).

Participants: Patients with medial compartment knee osteoarthritis.

Interventions: The trial compared the overall management strategy of partial knee replacement treatment with total knee replacement treatment. No specified brand or subtype of implant was investigated.

Main Outcome Measures: The Oxford Knee Score at 5 years was the primary end point. Secondary outcomes included activity scores, global health measures, transition items, patient satisfaction (Lund Score) and complications (including reoperation, revision and composite 'failure' - defined by minimal Oxford Knee Score improvement and/or reoperation). Cost-effectiveness was also assessed.

Results: A total of 528 patients were randomised (partial knee replacement,  = 264; total knee replacement,  = 264). The follow-up primary outcome response rate at 5 years was 88% and both operations had good outcomes. There was no significant difference between groups in mean Oxford Knee Score at 5 years (difference 1.04, 95% confidence interval -0.42 to 2.50). An area under the curve analysis of the Oxford Knee Score at 5 years showed benefit in favour of partial knee replacement over total knee replacement, but the difference was within the minimal clinically important difference [mean 36.6 (standard deviation 8.3) ( = 233), mean 35.1 (standard deviation 9.1) ( = 231), respectively]. Secondary outcome measures showed consistent patterns of benefit in the direction of partial knee replacement compared with total knee replacement although most differences were small and non-significant. Patient-reported improvement (transition) and reflection (would you have the operation again?) showed statistically significant superiority for partial knee replacement only, but both of these variables could be influenced by the lack of blinding. The frequency of reoperation (including revision) by treatment received was similar for both groups: 22 out of 245 for partial knee replacement and 28 out of 269 for total knee replacement patients. Revision rates at 5 years were 10 out of 245 for partial knee replacement and 8 out of 269 for total knee replacement. There were 28 'failures' of partial knee replacement and 38 'failures' of total knee replacement (as defined by composite outcome). Beyond 1 year, partial knee replacement was cost-effective compared with total knee replacement, being associated with greater health benefits (measured using quality-adjusted life-years) and lower health-care costs, reflecting lower costs of the index surgery and subsequent health-care use.

Limitations: It was not possible to blind patients in this study and there was some non-compliance with the allocated treatment interventions. Surgeons providing partial knee replacement were relatively experienced with the procedure.

Conclusions: Both total knee replacement and partial knee replacement are effective, offer similar clinical outcomes and have similar reoperation and complication rates. Some patient-reported measures of treatment approval were significantly higher for partial knee replacement than for total knee replacement. Partial knee replacement was more cost-effective (more effective and cost saving) than total knee replacement at 5 years.

Future Work: Further (10-year) follow-up is in progress to assess the longer-term stability of these findings.

Trial Registration: Current Controlled Trials ISRCTN03013488 and ClinicalTrials.gov NCT01352247.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 20. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta24200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232134PMC
April 2020

The Challenge of Transparency and Validation in Health Economic Decision Modelling: A View from Mount Hood.

Pharmacoeconomics 2019 11;37(11):1305-1312

Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Transparency in health economic decision modelling is important for engendering confidence in the models and in the reliability of model-based cost-effectiveness analyses. The Mount Hood Diabetes Challenge Network has taken a lead in promoting transparency through validation with biennial conferences in which diabetes modelling groups meet to compare simulated outcomes of pre-specified scenarios often based on the results of pivotal clinical trials. Model registration is a potential method for promoting transparency, while also reducing the duplication of effort. An important network initiative is the ongoing construction of a diabetes model registry (https://www.mthooddiabeteschallenge.com). Following the 2012 International Society for Pharmacoeconomics and Outcomes Research and the Society of Medical Decision Making (ISPOR-SMDM) guidelines, we recommend that modelling groups provide technical and non-technical documentation sufficient to enable model reproduction, but not necessarily provide the model code. We also request that modelling groups upload documentation on the methods and outcomes of validation efforts, and run reference case simulations so that model outcomes can be compared. In this paper, we discuss conflicting definitions of transparency in health economic modelling, and describe the ongoing development of a registry of economic models for diabetes through the Mount Hood Diabetes Challenge Network, its objectives and potential further developments, and highlight the challenges in its construction and maintenance. The support of key stakeholders such as decision-making bodies and journals is key to ensuring the success of this and other registries. In the absence of public funding, the development of a network of modellers is of huge value in enhancing transparency, whether through registries or other means.
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http://dx.doi.org/10.1007/s40273-019-00825-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6860461PMC
November 2019

The clinical and cost-effectiveness of total versus partial knee replacement in patients with medial compartment osteoarthritis (TOPKAT): 5-year outcomes of a randomised controlled trial.

Lancet 2019 08 17;394(10200):746-756. Epub 2019 Jul 17.

Health Services Research Unit, University of Aberdeen, Aberdeen, UK.

Background: Late-stage isolated medial knee osteoarthritis can be treated with total knee replacement (TKR) or partial knee replacement (PKR). There is high variation in treatment choice and little robust evidence to guide selection. The Total or Partial Knee Arthroplasty Trial (TOPKAT) therefore aims to assess the clinical effectiveness and cost-effectiveness of TKR versus PKR in patients with medial compartment osteoarthritis of the knee, and this represents an analysis of the main endpoints at 5 years.

Methods: Our multicentre, pragmatic randomised controlled trial was done at 27 UK sites. We used a combined expertise-based and equipoise-based approach, in which patients with isolated osteoarthritis of the medial compartment of the knee and who satisfied general requirements for a medial PKR were randomly assigned (1:1) to receive PKR or TKR by surgeons who were either expert in and willing to perform both surgeries or by a surgeon with particular expertise in the allocated procedure. The primary endpoint was the Oxford Knee Score (OKS) 5 years after randomisation in all patients assigned to groups. Health-care costs (in UK 2017 prices) and cost-effectiveness were also assessed. This trial is registered with ISRCTN (ISRCTN03013488) and ClinicalTrials.gov (NCT01352247).

Findings: Between Jan 18, 2010, and Sept 30, 2013, we assessed 962 patients for their eligibility, of whom 431 (45%) patients were excluded (121 [13%] patients did not meet the inclusion criteria and 310 [32%] patients declined to participate) and 528 (55%) patients were randomly assigned to groups. 94% of participants responded to the follow-up survey 5 years after their operation. At the 5-year follow-up, we found no difference in OKS between groups (mean difference 1·04, 95% CI -0·42 to 2·50; p=0·159). In our within-trial cost-effectiveness analysis, we found that PKR was more effective (0·240 additional quality-adjusted life-years, 95% CI 0·046 to 0·434) and less expensive (-£910, 95% CI -1503 to -317) than TKR during the 5 years of follow-up. This finding was a result of slightly better outcomes, lower costs of surgery, and lower follow-up health-care costs with PKR than TKR.

Interpretation: Both TKR and PKR are effective, offer similar clinical outcomes, and result in a similar incidence of re-operations and complications. Based on our clinical findings, and results regarding the lower costs and better cost-effectiveness with PKR during the 5-year study period, we suggest that PKR should be considered the first choice for patients with late-stage isolated medial compartment osteoarthritis.

Funding: National Institute for Health Research Health Technology Assessment Programme.
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http://dx.doi.org/10.1016/S0140-6736(19)31281-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727069PMC
August 2019

Cost-effectiveness of lipid lowering with statins and ezetimibe in chronic kidney disease.

Kidney Int 2019 07 12;96(1):170-179. Epub 2019 Mar 12.

Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, UK; Centre for Primary Care and Public Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK. Electronic address:

Statin-based treatments reduce cardiovascular disease (CVD) risk in patients with non-dialysis chronic kidney disease (CKD), but it is unclear which regimen is the most cost-effective. We used the Study of Heart and Renal Protection (SHARP) CKD-CVD policy model to evaluate the effect of statins and ezetimibe on quality-adjusted life years (QALYs) and health care costs in the United States (US) and the United Kingdom (UK). Net costs below $100,000/QALY (US) or £20,000/QALY (UK) were considered cost-effective. We investigated statin regimens with or without ezetimibe 10 mg. Treatment effects on cardiovascular risk were estimated per 1-mmol/L reduction in low-density lipoprotein (LDL) cholesterol as reported in the Cholesterol Treatment Trialists' Collaboration meta-analysis, and reductions in LDL cholesterol were estimated for each statin/ezetimibe regimen. In the US, atorvastatin 40 mg ($0.103/day as of January 2019) increased life expectancy by 0.23 to 0.31 QALYs in non-dialysis patients with stages 3B to 5 CKD, at a net cost of $20,300 to $78,200/QALY. Adding ezetimibe 10 mg ($0.203/day) increased life expectancy by an additional 0.05 to 0.07 QALYs, at a net cost of $43,600 to $91,500/QALY. The cost-effectiveness findings and policy implications in the UK were similar. In summary, in patients with non-dialysis-dependent CKD, the evidence suggests that statin/ezetimibe combination therapy is a cost-effective treatment to reduce the risk of CVD.
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http://dx.doi.org/10.1016/j.kint.2019.01.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595178PMC
July 2019

Is Doctor Referral to a Low-Energy Total Diet Replacement Program Cost-Effective for the Routine Treatment of Obesity?

Obesity (Silver Spring) 2019 03;27(3):391-398

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

Objective: The study objective was to estimate the cost-effectiveness of a commercially provided low-energy total diet replacement (TDR) program compared with nurse-led behavioral support.

Methods: A multistate life table model and the weight reduction observed in a randomized controlled trial were used to evaluate the quality-adjusted life-years and direct health care costs (in United Kingdom 2017 prices) over a lifetime with TDR versus nurse-led support in adults who had obesity, assuming that (i) weight returns to baseline over 5 years and (ii) a 1-kg weight loss is maintained after 5 years following TDR.

Results: The per-person costs of the TDR and nurse-led programs were £796 and £34, respectively. The incremental cost-effectiveness ratio of TDR was £12,955 (95% CI: £8,082-£17,827) assuming that all weight lost is regained and £3,203 (£2,580-£3,825) assuming that a 1-kg weight loss is maintained after 5 years. TDR was estimated to be more cost-effective (i.e., lower incremental cost-effectiveness ratios) in older adults and those with a higher BMI, with little difference by gender.

Conclusions: At current retail prices and with plausible long-term weight regain trajectories, TDR is projected to be cost-effective in adults with obesity and could be considered as an option to treat obesity in routine health care settings.
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http://dx.doi.org/10.1002/oby.22407DOI Listing
March 2019

Body mass index and use and costs of primary care services among women aged 55-79 years in England: a cohort and linked data study.

Int J Obes (Lond) 2019 09 19;43(9):1839-1848. Epub 2018 Dec 19.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Oxford, OX3 7LF, USA.

Background: Excess weight is associated with poor health and increased healthcare costs. There are no reliable data describing the association between BMI and the use and costs of primary care services in the United Kingdom.

Methods: Among 69,440 participants in the Million Women Study with primary care records in the Clinical Practice Research Datalink between April 2006 (mean age 64 years) and March 2014, the annual rates and costs of their primary care consultations, prescription medications, and diagnostic and monitoring tests were estimated in relation to their self-reported body mass index (BMI) at recruitment in 1996-2001 (mean age 56 years). Associations of BMI with annual costs were projected to all women in England aged 55-79 years in 2013.

Results: Over an average follow-up of 6.0 years, annual rates and mean costs were lowest for women with a BMI of 20 to <22.5 kg/m for consultations (7.0 consultations, 99% CI 6.8-7.1; £288, £280-£295) and prescription medications (27.0 prescribed items, 26.0-27.9; £227, £216-£237). Above 20 kg/m, a 2 kg/m higher BMI (a 5 kg change in weight for a woman of average height) was associated with 5.2% (4.8-5.6) and 9.9% (9.2-10.6) higher mean annual consultation and prescription medication costs, respectively. Annual rates and mean costs of diagnostic and monitoring tests were similar for women with different BMIs. Among all women aged 55-79 years in England, excess weight accounted for an estimated 11% (£229 million/£2.2 billion) of all consultation costs and 20% (£384 million/£1.9 billion) of all prescription medication costs, of which 27% were for diabetes drugs, 19% for circulatory system drugs, and 13% for analgesics.

Conclusions: Excess body weight is associated with higher use and costs of primary care services among women in England. Reducing the prevalence of excess weight could improve the health of women and reduce pressures on primary care.
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http://dx.doi.org/10.1038/s41366-018-0288-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451629PMC
September 2019

Hospital costs in relation to body-mass index in 1·1 million women in England: a prospective cohort study.

Lancet Public Health 2017 05 5;2(5):e214-e222. Epub 2017 Apr 5.

Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Excess weight is associated with poor health and increased health-care costs. However, a detailed understanding of the effects of excess weight on total hospital costs and costs for different health conditions is needed.

Methods: Women in England aged 50-64 years were recruited into the prospective Million Women Study cohort in 1996-2001 through 60 NHS breast cancer screening centres. Participants were followed up and annual hospital costs and admission rates were estimated for April 1, 2006, to March 31, 2011, in relation to body-mass index (BMI) at recruitment, overall and for categories of health conditions defined by the International Classification of Diseases 10th revision chapter of the primary diagnosis at admission. Associations of BMI with hospital costs were projected to the 2013 population of women aged 55-79 years in England.

Findings: 1 093 866 women who provided information on height and weight, had a BMI of at least 18·5 kg/m, and had no previous cancer at recruitment, were followed up for an average of 4·9 years from April 1, 2006 (12·3 years from recruitment), during which time 1·84 million hospital admissions were recorded. Annual hospital costs were lowest for women with a BMI of 20·0 kg/m to less than 22·5 kg/m (£567 per woman per year, 99% CI 556-577). Every 2 kg/m increase in BMI above 20 kg/m was associated with a 7·4% (7·1-7·6) increase in annual hospital costs. Excess weight was associated with increased costs for all diagnostic categories, except respiratory conditions and fractures. £662 million (14·6%) of the estimated £4·5 billion of total annual hospital costs among all women aged 55-79 years in England was attributed to excess weight (BMI ≥25 kg/m), of which £517 million (78%) arose from hospital admissions with procedures. £258 million (39%) of the costs attributed to excess weight were due to musculoskeletal admissions, mainly for knee replacement surgeries.

Interpretation: Excess body weight is associated with increased hospital costs for middle-aged and older women in England across a broad range of conditions, especially knee replacement surgery and diabetes. These results provide reliable up-to-date estimates of the health-care costs of excess weight and emphasise the need for investment to tackle this public health issue.

Funding: Cancer Research UK; Medical Research Council; National Institute for Health Research.
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http://dx.doi.org/10.1016/S2468-2667(17)30062-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196771PMC
May 2017

A policy model of cardiovascular disease in moderate-to-advanced chronic kidney disease.

Heart 2017 12 5;103(23):1880-1890. Epub 2017 Aug 5.

Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Objective: To present a long-term policy model of cardiovascular disease (CVD) in moderate-to-advanced chronic kidney disease (CKD).

Methods: A Markov model with transitions between CKD stages (3B, 4, 5, on dialysis, with kidney transplant) and cardiovascular events (major atherosclerotic events, haemorrhagic stroke, vascular death) was developed with individualised CKD and CVD risks estimated using the 5 years' follow-up data of the 9270 patients with moderate-to-severe CKD in the Study of Heart and Renal Protection (SHARP) and multivariate parametric survival analysis. The model was assessed in three further CKD cohorts and compared with currently used risk scores.

Results: Higher age, previous cardiovascular events and advanced CKD were the main contributors to increased individual disease risks. CKD and CVD risks predicted by the state-transition model corresponded well to risks observed in SHARP and external cohorts. The model's predictions of vascular risk and progression to end-stage renal disease were better than, or comparable to, those produced by other risk scores. As an illustration, at age 60-69 years, projected survival for SHARP participants in CKD stage 3B was 13.5 years (10.6 quality-adjusted life years (QALYs)) in men and 14.8 years (10.7 QALYs) in women. Corresponding projections for participants on dialysis were 7.5 (5.6 QALYs) and 7.8 years (5.4 QALYs). A non-fatal major atherosclerotic event reduced life expectancy by about 2 years in stage 3B and by 1 year in dialysis.

Conclusions: The SHARP CKD-CVD model is a novel resource for evaluating health outcomes and cost-effectiveness of interventions in CKD.

Trial Registration Number: NCT00125593 and ISRCTN54137607; Post-results.
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http://dx.doi.org/10.1136/heartjnl-2016-310970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749372PMC
December 2017

Body mass index and healthcare costs: a systematic literature review of individual participant data studies.

Obes Rev 2017 08 22;18(8):869-879. Epub 2017 May 22.

Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Excess weight is associated with increased total healthcare costs, but it is less well known how the associations between excess weight and costs vary across different types of healthcare service. We reviewed studies using individual participant data to estimate associations between body mass index and healthcare costs, and summarized how annual healthcare costs for overweight (body mass index 25 to <30 kg/m ) and obese (≥30 kg/m ) individuals compared with those for healthy weight individuals (18.5 to <25 kg/m ). EMBASE and MEDLINE were searched from January 1990 to September 2016, and 75 studies were included in the review. Of these, 34 studies presented adequate information to contribute to a quantitative summary of results. Compared with individuals at healthy weight, the median increases in mean total annual healthcare costs were 12% for overweight and 36% for obese individuals. The percentage increases in costs were highest for medications (18% for overweight and 68% for obese), followed by inpatient care (12% and 34%) and ambulatory care (4% and 26%). Percentage increases in costs associated with obesity were higher for women than men. The substantial costs associated with excess weight in different healthcare settings emphasize the need for investment to tackle this major public health problem.
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http://dx.doi.org/10.1111/obr.12560DOI Listing
August 2017

Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs.

Circ Cardiovasc Qual Outcomes 2016 07 12;9(4):348-54. Epub 2016 Jul 12.

From the Health Economics Research Centre (S.K., A.G., B.M.) and Clinical Trial Service Unit and Epidemiological Studies Unit (R.H., J.C.H., S.P., M.J.L., R.C., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom.

Background: Extended-release niacin with laropiprant did not significantly reduce the risk of major vascular events and increased the risk of serious adverse events in Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), but its net effects on health and healthcare costs are unknown.

Methods And Results: 25 673 participants aged 50 to 80 years with previous cardiovascular disease were randomized to 2 g of extended-release niacin with 40 mg of laropiprant daily versus matching placebo, in addition to effective statin-based low-density lipoprotein cholesterol-lowering treatment. The net effects of niacin-laropiprant on quality-adjusted life years and hospital care costs (2012 UK £; converted into US $ using purchasing power parity index) during 4 years in HPS2-THRIVE were evaluated using estimates of the impact of serious adverse events on health-related quality of life and hospital care costs. During the study, participants assigned niacin-laropiprant experienced marginally but not statistically significantly lower survival (0.012 fewer years [standard error (SE) 0.007]), fewer quality-adjusted life years (0.023 [SE 0.007] fewer using UK EQ-5D scores; 0.020 [SE 0.006] fewer using US EQ-5D scores) and accrued greater hospital costs (UK £101 [SE £37]; US $145 [SE $53]). Stroke, heart failure, musculoskeletal events, gastrointestinal events, and infections were associated with significant decreases in health-related quality of life in both the year of the event and in subsequent years. All serious vascular and nonvascular events were associated with substantial increases in hospital care costs.

Conclusions: In HPS2-THRIVE, the addition of extended-release niacin-laropiprant to statin-based therapy reduced quality of life-adjusted survival and increased hospital costs.

Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT00461630.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.115.002592DOI Listing
July 2016

Cost-effectiveness of Simvastatin plus Ezetimibe for Cardiovascular Prevention in CKD: Results of the Study of Heart and Renal Protection (SHARP).

Am J Kidney Dis 2016 Apr 18;67(4):576-84. Epub 2015 Nov 18.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Background: Simvastatin, 20mg, plus ezetimibe, 10mg, daily (simvastatin plus ezetimibe) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease (CKD) in the Study of Heart and Renal Protection (SHARP), but its cost-effectiveness is unknown.

Study Design: Cost-effectiveness of simvastatin plus ezetimibe in SHARP, a randomized controlled trial.

Setting & Population: 9,270 patients with CKD randomly assigned to simvastatin plus ezetimibe versus placebo; participants in categories by 5-year cardiovascular risk (low, <10%; medium, 10%-<20%; or high, ≥20%) and CKD stage (3, 4, 5 not on dialysis, or on dialysis therapy).

Model, Perspective, & Timeline: Assessment during SHARP follow-up from the UK perspective; long-term projections.

Intervention: Simvastatin plus ezetimibe (2015 UK £1.19 per day) during 4.9 years' median follow-up in SHARP; scenario analyses with high-intensity statin regimens (2015 UK £0.05-£1.06 per day).

Outcomes: Additional health care costs per major atherosclerotic event avoided and per quality-adjusted life-year (QALY) gained.

Results: In SHARP, the proportional reductions per 1mmol/L of low-density lipoprotein (LDL) cholesterol reduction with simvastatin plus ezetimibe in all major atherosclerotic events of 20% (95% CI, 6%-32%) and in the costs of vascular hospital episodes of 17% (95% CI, 4%-28%) were similar across participant categories by cardiovascular risk and CKD stage. The 5-year reduction in major atherosclerotic events per 1,000 participants ranged from 10 in low-risk to 58 in high-risk patients and from 28 in CKD stage 3 to 36 in patients on dialysis therapy. The net cost per major atherosclerotic event avoided with simvastatin plus ezetimibe compared to no LDL-lowering regimen ranged from £157,060 in patients at low risk to £15,230 in those at high risk (£30,500-£39,600 per QALY); and from £47,280 in CKD stage 3 to £28,180 in patients on dialysis therapy (£13,000-£43,300 per QALY). In scenario analyses, generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost.

Limitations: High-intensity statin-alone regimens were not studied in SHARP.

Conclusions: Simvastatin plus ezetimibe prevented atherosclerotic events in SHARP, but other less costly statin regimens are likely to be more cost-effective for reducing cardiovascular risk in CKD.
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http://dx.doi.org/10.1053/j.ajkd.2015.09.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801501PMC
April 2016

Mapping from the Parkinson's Disease Questionnaire PDQ-39 to the Generic EuroQol EQ-5D-3L: The Value of Mixture Models.

Med Decis Making 2015 10 29;35(7):902-11. Epub 2015 Apr 29.

Health Economics and Health Technology Assessment, University of Glasgow, Glasgow, Scotland, UK (EM)

Objective: To compare a range of statistical models to enable the estimation of EQ-5D-3L utilities from responses to the Parkinson's Disease Questionnaire 39 (PDQ-39).

Methods: Linear regression, beta regression, mixtures of linear regressions and beta regressions, and multinomial logistic regression were compared in terms of their ability to accurately predict EQ-5D-3L utilities from responses to the PDQ-39 using mean error (ME), mean absolute error (MAE), and mean square error (MSE), overall and by Hoehn and Yahr stage. Models were estimated using data from the PD MED trial (n = 9123) and assessed on both the estimation data as well as external data from the PD SURG trial (n = 917).

Results: Overall, the differences in the metrics of fit between models were small in both data sets, with performance poorer for all models in PD SURG. The performance across Hoehn and Yahr stages 1 to 3 were also similar, but multinomial logistic regression was found to exhibit less bias and better individual-level predictive accuracy in PD MED for those in Hoehn and Yahr stages 4 or 5. Overall, the multinomial logistic regression reported an ME of 0.038 out of sample and MAEs of 0.128 and 0.164 and MSEs of 0.030 and 0.044 in the estimation and external data sets, respectively. Poorer levels of the mobility domain score of the PDQ-39 were associated with increased odds of reporting problems for all EQ-5D domains except anxiety/depression.

Conclusions: Finite mixture models with only few components can approximate the distribution of EQ-5D-3L utilities well but did not demonstrate improvements in predictive accuracy compared with multinomial logistic regression in the present data set.
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http://dx.doi.org/10.1177/0272989X15584921DOI Listing
October 2015

What is the impact of chronic kidney disease stage and cardiovascular disease on the annual cost of hospital care in moderate-to-severe kidney disease?

BMC Nephrol 2015 Apr 29;16:65. Epub 2015 Apr 29.

Health Economics Research Centre (HERC), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Reliable estimates of the impacts of chronic kidney disease (CKD) stage, with and without cardiovascular disease, on hospital costs are needed to inform health policy.

Methods: The Study of Heart and Renal Protection (SHARP) randomized trial prospectively collected information on kidney disease progression, serious adverse events and hospital care use in a cohort of patients with moderate-to-severe CKD. In a secondary analysis of SHARP data, the impact of participants' CKD stage, non-fatal cardiovascular events and deaths on annual hospital costs (i.e. all hospital admissions, routine dialysis treatments and recorded outpatient/day-case attendances in United Kingdom 2011 prices) were estimated using linear regression.

Results: 7,246 SHARP patients (2,498 on dialysis at baseline) from Europe, North America, and Australasia contributed 28,261 years of data. CKD patients without diabetes or vascular disease incurred annual hospital care costs ranging from £403 (95% confidence interval: 345-462) in CKD stages 1-3B to £525 (449-602) in CKD stage 5 (not on dialysis). Patients in receipt of maintenance dialysis incurred annual hospital costs of £18,986 (18,620-19,352) in the year of initiation and £23,326 (23,231-23,421) annually thereafter. Patients with a functioning kidney transplant incurred £24,602 (24,027-25,178) in hospital care costs in the year of transplantation and £1,148 (978-1,318) annually thereafter. Non-fatal major vascular events increased annual costs in the year of the event by £6,133 (5,608-6,658) for patients on dialysis and by £4,350 (3,819-4,880) for patients not on dialysis, and were associated with increased costs, though to a lesser extent, in subsequent years.

Conclusions: Renal replacement therapy and major vascular events are the main contributors to the high hospital care costs in moderate-to-severe CKD. These estimates of hospital costs can be used to inform health policy in moderate-to-severe CKD.
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http://dx.doi.org/10.1186/s12882-015-0054-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424521PMC
April 2015

Are value of information methods ready for prime time? An application to alternative treatment strategies for NSTEMI patients.

Int J Technol Assess Health Care 2013 Oct;29(4):435-42

Health Economics Research Centre, University of Oxford.

Objectives: The use of value of information methods to inform trial design has been widely advocated but there have been few empirical applications of these methods and there is little evidence they are widely used in decision making. This study considers the usefulness of value of information models in the context of a real clinical decision problem relating to alternative diagnostic strategies for patients with a recent non-ST elevated myocardial infarction.

Methods: A pretrial economic model is constructed to consider the cost-effectiveness of two competing strategies: coronary angiography alone or in conjunction with fractional flow reserve measurement. A closed-form solution to the expected benefits of information is used with optimal sample size estimated for a range of models reflecting increasingly realistic assumptions and alternative decision contexts.

Results: Fractional flow reserve measurement is expected to be cost-effective with an incremental cost-effectiveness ratio of GBP 1,621, however, there is considerable uncertainty in this estimate and consequently a large expected value to reducing this uncertainty via a trial. The recommended sample size is strongly affected by the reality of the assumptions of the expected value of information (EVI) model and the decision context.

Conclusions: Value of information models can provide a simple and flexible approach to clinical trial design and are more consistent with the constraints and objectives of the healthcare system than traditional frequentist approaches. However, the variation in sample size estimates demonstrates that it is essential that appropriate model parameters and decision contexts are used in their application.
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http://dx.doi.org/10.1017/S0266462313000433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846382PMC
October 2013