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Pitman R.,Oxford Outcomes | Fisman D.,University of Toronto | Zaric G.S.,University of Western Ontario | Postma M.,University of Groningen | And 3 more authors.
Medical Decision Making | Year: 2012

The transmissible nature of communicable diseases is what sets them apart from other diseases modeled by health economists. The probability of a susceptible individual becoming infected at any one point in time (the force of infection) is related to the number of infectious individuals in the population, will change over time, and will feed back into the future force of infection. These nonlinear interactions produce transmission dynamics that require specific consideration when modeling an intervention that has an impact on the transmission of a pathogen. Best practices for designing and building these models are set out in this paper.


Szabo S.M.,Oxford Outcomes | Levy A.R.,Oxford Outcomes | Gooch K.L.,Abbott Laboratories | Bradt P.,Adzoe Inc. | And 2 more authors.
Paediatric Respiratory Reviews | Year: 2013

Severe respiratory syncytial virus (RSV) infection in infancy is associated with substantial morbidity worldwide; whether it is a risk factor for childhood asthma is contentious. A systematic review of 28 articles was conducted, summarizing estimates of asthma risk after RSV hospitalization during infancy. Prevalence estimates of asthma, among those hospitalized for RSV in infancy, were from 8% to 63%, 10% to 92%, and 37%, at ages <5, 5 to 11, and ≥12 years, respectively. These rates were higher than those among non-hospitalized comparisons. The attributable risk of asthma due to RSV ranged from 13% to 22% and from 11% to 27% among children aged ≤5 and aged 5 to 11, respectively, and was 32% among children ≥ 12 years of age. Overall, 59% of asthma prevalence estimates from those previously hospitalized for RSV exceeded 20%, compared to only 6% of non-hospitalized comparison estimates. Despite variability in asthma prevalence estimates after RSV-related hospitalization, available data suggest a link between severe RSV infection in infancy and childhood asthma. © 2013 Elsevier Ltd.


Goring S.,Oxford Outcomes | Hawkins N.,Oxford Outcomes | Wygant G.,Bristol Myers Squibb | Roudaut M.,Bristol Myers Squibb | And 3 more authors.
Diabetes, Obesity and Metabolism | Year: 2014

Aims: Indirect evidence from randomized controlled trials (RCTs) was used to estimate the effect of dapagliflozin, a new agent with a novel mechanism of action (SGLT-2 inhibition), relative to other anti-diabetes therapies after 1 year of treatment. Methods: A systematic literature review and Bayesian network meta-analysis (NMA) of RCTs involving anti-diabetes treatments added to metformin were conducted. RCTs enrolling subjects with type 2 diabetes inadequately controlled on metformin monotherapy were included. Comparators included dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones (TZDs), sulphonylureas, glucagon-like peptide-1 (GLP-1) analogues and dapagliflozin. Outcomes of interest were mean change from baseline HbA1c, weight and systolic blood pressure, and incidence of hypoglycaemia. Results: From 4270 abstracts, six RCTs were included in the primary analysis; no RCTs involving GLP-1 analogues met primary inclusion criteria. All RCTs were actively controlled with sulphonylureas. The mean change in HbA1c from baseline was similar across comparators. The treatment effect (95% credible interval) of dapagliflozin on HbA1c was -0.08% (-0.25, 0.10) relative to DPP-4 inhibitors, -0.02% (-0.24, 0.21) relative to TZDs and 0.00% (-0.16, 0.16) relative to sulphonylureas. Non-sulphonylureas showed significantly lower risk of hypoglycaemia relative to sulphonylureas. Dapagliflozin had a significant effect on weight change: the relative difference was -2.74kg (-5.35, -0.10) compared with DPP-4 inhibitors, and -4.67kg (-7.03, -2.35) compared with sulphonylureas. Systolic blood pressure was not meta-analysed due to infrequent reporting. Conclusion: Compared with DPP-4 inhibitors, TZDs and sulphonylureas, dapagliflozin offers similar HbA1c control after 1 year, with similar or reduced risk of hypoglycaemia and the additional benefit of weight loss, when added to metformin. © 2013 John Wiley & Sons Ltd.


Punekar Y.S.,Schering | Hawkins N.,Oxford Outcomes
European Journal of Health Economics | Year: 2010

Background: Infliximab has been shown to be efficacious in acute exacerbations of ulcerative colitis (UC). Aim: To evaluate the cost-effectiveness of infliximab treatment in patients hospitalised with acute exacerbations of UC. Methods: A decision analysis model was constructed to simulate the progression of acute UC patients treated with infliximab induction regimen over 1 year. Infliximab treatment was compared with standard care, ciclosporin and surgery using transitions derived from infliximab and ciclosporin randomised trials. Costs and outcomes were discounted at 3.5%. Intermediate outcomes of colectomy and post-surgery complications were translated into the primary effectiveness measurement, which was quality-adjusted life years (QALYs) estimated using EQ-5D. One-way and probabilistic sensitivity analyses were performed to estimate the uncertainty around the results. Results: The incremental cost effectiveness ratio (ICER) for infliximab was £19,545 per QALY compared to ciclosporin, which in turn dominated standard care. Sensitivity analysis indicated patient body weight, utility estimates and treatment effect of alternative treatment strategies to be the most important factors affecting cost-effectiveness. Conclusion: Infliximab induction regimen appears to be a cost-effective treatment option for UC patients hospitalised with an acute exacerbation. © 2009 Springer-Verlag.


Pitman R.J.,Oxford Outcomes | White L.J.,University of Oxford | Sculpher M.,Oxford Outcomes | Sculpher M.,University of York
Vaccine | Year: 2012

Influenza causes a significant burden of disease each year in England and Wales, with the young and the elderly suffering the greatest burden. Children are recognised as playing an important role in the dissemination of the influenza virus. This study examines the population impact of implementing a programme of paediatric vaccination. A dynamic transmission model was used to simulate the impact of vaccination programmes with varying levels of coverage across pre-school and school age children. These analyses suggest that vaccinating as few as 50% of 2-18 year olds could result in a substantial reduction in the annual incidence of influenza related morbidity and mortality across the population. Herd immunity may extend this protection to the young and the elderly. It is assumed that such programmes would be implemented in concert with the current strategy of vaccinating the elderly and younger at risk groups with an inactivated vaccine. In England and Wales, paediatric vaccination of two to eighteen year olds reduced the estimated number of general practice consultations, hospitalisations and deaths arising from influenza A and B infections by up to 95%. This translates into an annual average reduction of approximately 52,000, 1500 and 1200 events, respectively. A policy of paediatric vaccination could significantly reduce the clinical burden of influenza in England and Wales, in all age groups, with the added value of herd immunity helping to protect the young and the elderly who are at highest risk of complications. © 2011 Elsevier Ltd.


Peters M.,University of Oxford | Crocker H.,University of Oxford | Jenkinson C.,University of Oxford | Doll H.,Oxford Outcomes | Fitzpatrick R.,University of Oxford
BMJ Open | Year: 2014

Objectives: To evaluate the feasibility of using patient-reported outcome measures (PROMs) for longterm conditions (LTCs) in primary care. Design: A cohort postal survey conducted from September 2010 to April 2012. Setting: Primary care practices (n=33) in London and the North-West of England. Participants: 4484 patients with a diagnosis of asthma, chronic obstructive pulmonary disease, diabetes, epilepsy, heart failure or stroke were sent a survey at baseline. Main outcome: The main outcome was to evaluate the feasibility of and the recruitment strategies for collecting PROMs data in LTCs by assessing the response rates for the baseline and follow-up surveys. Secondary outcomes were the evaluation of change scores of the EQ-5D index and visual analogue scale (VAS) between baseline and follow-up surveys. Results: The baseline survey achieved a response rate of 38.4% (n=1721/4485) and at follow-up 71.5% (n=1136/1589). Response rates varied by LTC. Little change was found in health-related quality of life for the total sample (-0.001 for the EQ-5D index score and 0.12 for the EQ-5D VAS) between patients responding to both the baseline and follow-up surveys. Conclusions: The response rate to the baseline survey was similar to that of other general practice surveys. Current UK policy aims to assess health service performance in LTCs by means of using PROMs. It thus would be desirable to improve response rates by making the invitation to self-reports of health-related quality of life more engaging for patients. Results on the EQ-5D score raise questions about optimal indicators for LTCs and appropriate timelines for assessment.


Dewilde S.,Services in Health Economics | Hawkins N.,Oxford Outcomes
Journal of Clinical Epidemiology | Year: 2012

Objective: To identify confounding factors that may explain the incoherence between direct and indirect evidence in a published analysis comparing extended-release dipyridamole (ERDP) plus aspirin to clopidogrel for the reduction of stroke. Study Design and Setting: An existing analysis was updated with new studies from a systematic literature review. Clinicians reviewed the studies for potential confounders. Network meta-analyses were conducted including or excluding potential confounders, and were estimated based on direct, indirect, or a combination of direct and indirect evidence. Model fit was compared using the residual deviance and the deviance information criterion (DIC); node splitting was used to test for incoherence between the networks. Results: Six trials and one meta-analysis were identified; aspirin dosage was identified as a potential confounder. The odds ratio (OR) for stroke of aspirin plus ERDP vs. clopidogrel based on indirect evidence without aspirin dosage adjustment is 0.85 (0.68-1.05); when accounting for the aspirin dose-response relationship it is 0.96 (0.73-1.25); and the direct evidence based on PRoFESS resulted in an OR of 1.02 (0.93-1.12). Conclusion: When analyzing networks of evidence, attention should be paid to identifying and adjusting for potentially confounding factors. Investigating rather than ignoring inconsistency in the data set leads to clearer insight into relative efficacy. © 2012 Elsevier Inc. All rights reserved.


Pitman R.J.,Oxford Outcomes | Nagy L.D.,Oxford Outcomes | Sculpher M.J.,Oxford Outcomes | Sculpher M.J.,University of York
Vaccine | Year: 2013

This study uses a dynamic influenza transmission model to directly compare the cost-effectiveness of various policies of annual paediatric influenza vaccination in England and Wales, varying the target age range and level of coverage. The model accounts for both the protection of those immunised and the indirect protection of the rest of the population via herd immunity. The impact of augmenting current practice with a policy to vaccinate pre-school age children, on their own or with school age children, was assessed in terms of quality adjusted life years and health service costs. Vaccinating 2-18 year olds was estimated to be the most cost-effective policy in an incremental cost-effectiveness analysis, at an assumed annual vaccine uptake rate of 50%. The mean incremental cost-effectiveness ratios for this policy was estimated at £251/QALY relative to current practice. Paediatric vaccination would appear to be a highly cost-effective intervention that directly protects those targeted for vaccination, with indirect protection extending to both the very young and the elderly. © 2012 Elsevier Ltd.


Schnitzler M.A.,Saint Louis University | Johnston K.,Oxford Outcomes | Axelrod D.,Dartmouth Hitchcock Medical Center | Gheorghian A.,Saint Louis University | Lentine K.L.,Saint Louis University
Transplantation | Year: 2011

Background. Improved early kidney transplant outcomes limit the contemporary utility of standard clinical endpoints. Quantifying the relationship of renal function at 1 year after transplant with subsequent clinical outcomes and healthcare costs may facilitate cost-benefit evaluations among transplant recipients. Methods. Data for Medicare-insured kidney-only transplant recipients (1995-2003) were drawn from the United States Renal Data System. Associations of estimated glomerular filtration rate (eGFR) level at the first transplant anniversary with subsequent death-censored graft failure and patient death in posttransplant years 1 to 3 and 4 to 7 were examined by parametric survival analysis. Associations of eGFR with total health care costs defined by Medicare payments were assessed with multivariate linear regression. Results. Among 38,015 participants, first anniversary eGFR level demonstrated graded associations with subsequent outcomes. Compared with patients with 12-month eGFR more than or equal to 60 mL/min/1.73 m, the adjusted relative risk of death-censored graft failure in years 1 to 3 was 31% greater for eGFR 45 to 59 mL/min/1.73 m (P<0.0001) and 622% greater for eGFR 15 to 30 mL/min/1.73 m (P<0.0001). Associations of first anniversary eGFR level with graft failure and mortality remained significant in years 4 to 7. The proportions of recipients expected to return to dialysis or die attributable to eGFR less than 60 mL/min/1.73 m over 10 years were 23.1% and 9.4%, respectively, and were significantly higher than proportions attributable to delayed graft function or acute rejection. Reduced eGFR was associated with graded and significant increases in health care spending during years 2 and 3 after transplant (P<0.0001). Conclusion. eGFR is strongly associated with clinical and economic outcomes after kidney transplantation. Copyright © 2011 by Lippincott Williams & Wilkins.


Shingler S.,Oxford Outcomes
The Cochrane database of systematic reviews | Year: 2013

Compression hosiery or stockings are often the first line of treatment for varicose veins in people without either healed or active venous ulceration. Evidence is required to determine whether the use of compression stockings can effectively manage and treat varicose veins in the early stages. This is an update of a review first published in 2011. To assess the effectiveness of compression stockings for the only and initial treatment of varicose veins in patients without healed or active venous ulceration. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched August 2013) and CENTRAL (2013, Issue 5). Randomised controlled trials (RCTs) were included if they involved participants diagnosed with primary trunk varicose veins without healed or active venous ulceration (Clinical, Etiology, Anatomy, Pathophysiology (CEAP) classification C2 to C4). Included trials assessed compression stockings versus no treatment, compression versus placebo stockings, or compression stockings plus drug intervention versus drug intervention alone. Trials comparing different lengths and pressures of stockings were also included. Trials involving other types of treatment for varicose veins (either as a comparator to stockings or as an initial non-randomised treatment), including sclerotherapy and surgery, were excluded. Two authors assessed the trials for inclusion and quality (SS and LR). SS extracted the data, which were checked by LR. Attempts were made to contact trial authors where missing or unclear data were present. Seven studies involving 356 participants with varicose veins without healed or active venous ulceration were included. Different levels of pressure were exerted by the stockings in the studies, ranging from 10 to 50 mmHg. One study assessed compression hosiery versus no compression hosiery. The other six compared different types or pressures of stockings. The methodological quality of all included trials was unclear, mainly because of inadequate reporting.The symptoms subjectively improved with the wearing of stockings across trials that assessed this outcome, but these assessments were not made by comparing one randomised arm of a trial with a control arm and are therefore subject to bias.Meta-analyses were not undertaken due to inadequate reporting and actual or suspected high levels of heterogeneity. There is insufficient, high quality evidence to determine whether or not compression stockings are effective as the sole and initial treatment of varicose veins in people without healed or active venous ulceration, or whether any type of stocking is superior to any other type. Future research should consist of a large RCT of participants with trunk varices either wearing or not wearing compression stockings to assess the efficacy of this intervention. If compression stockings are found to be beneficial, further studies assessing which length and pressure is the most efficacious could then take place.

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