Not All Cochrane Reviews Are Good Quality Systematic Reviews

VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6

PRM77 Not All Cochrane Reviews Are Good Quality Systematic Reviews Deshpande S1, Misso K1, Westwood M1, Stirk L1, de Kock S1, Kleijnen J1, Clayton D1, Kleijnen J2 1Kleijnen Systematic Reviews Ltd., York, UK, 2Maastricht University, Maastricht, The Netherlands

Objectives: Cochrane reviews are considered to be gold standard quality; clearly reported and methodologically better than systematic reviews (SRs) published elsewhere. We aimed to systematically compare the risk of bias (RoB) in Cochrane and non-Cochrane SRs using the dataset compiled in our database.  Methods: Comprehensive searches were conducted using a range of resources, including MEDLINE, EMBASE and CDSR, to retrieve SRs from 2010 onwards for each of the topic areas of pain, lung diseases, dementia, diabetes and mental health. For each included SR in our database, a detailed critical appraisal and risk of bias assessment was undertaken by an expert reviewer, culminating in a clinical bottom-line. Risk of bias was assessed using the validated ROBIS tool, specifically designed to assess RoB in SRs. All stages were checked by a second independent reviewer. All completed appraisals in our database were analysed based on each overall ROBIS RoB assessment classified as low, unclear or high risk.  Results: Currently, the KSR Evidence database has 17,267 (94%) non-Cochrane and 1,153 (6%) Cochrane SRs, as identified by our topic searches. This analysis included 3,836 non-Cochrane and 568 Cochrane SR critical appraisals, completed to date. The majority of Cochrane reviews were at low risk of bias (87.1%), compared to 12% of non-Cochrane reviews. Fewer Cochrane SRs were rated as high RoB (8.8%), compared to non-Cochrane reviews (84.9%). These findings were consistent across the current topic areas included in this database. Further work is ongoing to expand the database to eventually cover all SRs in the coming years.  Conclusions: Overall, the methodological quality of Cochrane reviews is good compared to the non-Cochrane reviews however, it would be inappropriate to assume all Cochrane reviews are good quality and are at low risk of bias.

PRM78 Quinolones Utilization In Two Tertiary Hospitals In Nigeria; Exploring Drug Use Towards Improved Treatment Outcomes Ogbonna B NNAMDI AZIKIWE UNIVERSITY, ANAMBRA STATE, Nigeria

Objectives: Quinolnes are broad-spectrum antibacterials with activity against many organisms resistant to aminoglycosides, antipseudomonal penicillins, and third generation cephalosporins. Any compromise in their utilization could be catastrophic in tailoring bacteria treatments to desired outcomes. This study assessed the rationality of quinolones utilization based on World Health Organization benchmark.  Methods: The study was a retrospective cross-sectional descriptive study of all eligible prescriptions with quinolones that met the inclusion criteria. Prescriptions were assessed based on prescription and utilization indicators. The prescriptions analyzed covered two years period from January 2013 to December 2014. Study lasted from July 2015 to May 2016. Data were summarized using descriptive statistics.  Results: The total number of drugs prescribed was 5229 while the mean number of drugs per prescription was 4±2.38. Drugs prescribed from the essential drug list were 4952 (95%) and generic prescriptions were 3254 (62%). The age group with the highest quinolone use was those between 18- 40 years while the least was those below 18 years. The number of antibiotics prescribed was 2280 (44%) and fraction of quinolones in antibiotics prescribed was 480 (21%). The most prescribed quinolone was Ciprofloxacin 279 (58%), followed by Ofloxacin 104 (22%). The least prescribed was Germifloxacin 3(0.6%). The most prescribed dosage form was oral tablets and suspensions 99%, parenteral 0.6% and otics 0.4%. The antibiotics most prescribed together with the quinolones were Ceftriaxone 4% and Cefuroxime 2%. The mean duration of quinolones use in prescriptions was 9±3.4 days.  Conclusions: The study indicated irrational use of quinolones characterized by polypharmacy and brands prescription, which is associated with high cost of medications in a region where majority of people live below $ 2 USD per day. This is one of the predisposing factors to medication non-adherence and therapeutic failure. It further endangers the already threatened compounds to resistance by mutant strains.

RESEARCH ON METHODS – Modeling Methods PRM79 Missing the Value of Herd Immunity in Cost-Effectiveness Analysis. A Systematic Review Nymark L aarhus university, aarhus v, Denmark

Objectives: This review aims to synthesise the available information on inclusion of herd immunity in CEAs in the literature, identify and summarise the findings of existing studies which provide analysis of herd immunity in CEAs and describe the methodological approaches that have been used to analyse herd immunity in CEAs.  Methods: Kim and Goldie conducted a systematic review from 1 January 1976 – 31 May 2007 detailing the modelling approaches used in CEAs of vaccination. We adopted their search strategy and searched databases EMBASE and MEDLINE from 1 June 2007- 1 September 2015 for CEAs for vaccines. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Included studies were reviewed for inclusion of herd immunity. Kim & Goldie identified 275 CEAs. These were screened for inclusion of herd immunity.  Results: 3870 records were identified in Medline and EMBASE databases. After deduplication 2215 records remained. After excluding 1576 abstracts, 639 full-text articles were screened for eligibility, of which 269 did not meet the inclusion criteria. 645 full-texts cost-effectiveness analyses of vaccines were screened for inclusion of herd immunity. We identified 176 articles which included herd immunity in their

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cost-effectiveness analysis. Broken down by vaccine type pneumococcal, HPV and measles cost-effectiveness analyses constituted the majority of the studies. Costeffectiveness analyses of pneumococcal, HPV and rotavirus vaccines represented 36%, 17% and 10% of the studies which considered herd immunity, respectively. Overall, 27% of the studies considered herd immunity while 73% did not include herd immunity. Our findings demonstrate that 95 of 176 economic evaluations utilised a static model while 57 applied a dynamic model.  Conclusions: The majority of the studies included in this systematic review did not consider herd immunity which is problematic because we are not capturing the full value of vaccines. PRM80 Analysis of the Relationship Between Blood Pressure in Health Checkup and Effectiveness of Antihypertensives Iwasaki K1, Nakamura Y1, Hiroi S2, Uda A2, Shimasaki Y2, Koizumi H1 1Milliman, Tokyo, Japan, 2Takeda Pharmaceutical Company Ltd., Tokyo, Japan

Objectives: An appropriate risk adjustment based on real-world data is required to analyze effectiveness of antihypertensives by drug type because backgrounds vary in each patients’ group. We aimed to develop a model of blood pressure (BP) fluctuation and estimate its parameters to analyze time-series changes of BP and effect of antihypertensives.  Methods: We used Japanese claims database including 2.8 million people. The patients included were those who had an ICD-10 code of I10I15, prescribed antihypertensives, had at least one year without any hypertensive medication before prescription, and had health checkup information within one year before and after the first prescription. Antihypertensives were defined by ATC code. The difference in BP before the prescription was modeled using stochastic differential equation. The parameter of drift coefficient for each patient, which represents natural incremental BP of aging, was estimated by using hierarchical bayesian time series models with WinBUGS 1.4.3. The effectiveness of the antihypertensive was calculated by linear regression with explanatory variables of age, sex, drugs, and BP before prescription.  Results: Average systolic BP (SBP) and diastolic BP (DBP) before prescription of antihypertensives were 142.1 mmHg and 89.7 mmHg, both of which were significantly decreased after prescription to 133.5 mmHg (p< 0.0001) and 83.8 mmHg (p< 0.0001). The natural annual increasing rate for SBP and DBP (mean ± standard deviation) were 2.39 ± 0.53%, and 2.70 ± 0.56%. The result of linear regression from the calculation of intercept and coefficient of the BP before prescription suggested that the antihypertensives were effective for patients with SBP over 133 mmHg.  Conclusions: We confirmed the effectiveness of antihypertensives based on claims data with annual health checkup data. BP before prescription was an important factor that impacted the change of BP. We were able to estimate the effectiveness of antihypertensives by the adjustment of background using the model’s coefficients. PRM81 Implications of Introducing Patient Heterogeneity in Cost Effectiveness Modeling Foos V1, McEwan P2, Lamotte M3 Health, Zaventem, Belgium, 2Health Economics and Outcomes Research Ltd, Cardiff, UK, 3IMS Health, Vilvoorde, Belgium

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Objectives: In cost-effectiveness (CE) modelling, sampling patient baseline characteristics and treatment effects is routinely undertaken for probabilistic sensitivity analysis (PSA) yet standard base case (BC) analyses typically propagate mean values through the model. Real world populations are heterogeneous and this should be reflected in modeling to avoid biased predictions; particularly in relation to nonlinear relationships often present within CE models. The objective of our study is to quantify outcome differences in analyses with and without established baseline heterogeneity within a hypothetical CE scenario.  Methods: Lifetime analyses comparing the CE of metformin+sulphonylurea (M+S) versus metformin + DPP-4 (M+D) was undertaken using the IMS-CORE-Diabetes-Model (CDM). Basal insulin rescue therapy (BI) was applied to both arms at HbA1c threshold levels of 8.0%. Efficacy data for dual therapy was sourced from a published mixed treatment comparison; HbA1c and BMI change of -0.8% and 0.199kg/m2 (M+D);-0.79% and 0.707kg/ m2 (M+S) and -0.82 and 0.545 kg/m2 (M+S), respectively, were applied. CE analyses were performed with and without sampling of patient baseline characteristics and treatment effects. Random samples of baseline HbA1c levels and related treatment effects were correlated. Discounting was applied at 3.0%.  Results: Ignoring patient heterogeneity resulted in quality adjusted life expectancy (QALE) of 9.335 and 9.280 in patients treated with M+D and M+S. This compared to 9.127 and 9.074 in analyses when sampling patient baseline characteristics and treatment effects. Total direct lifetime costs were estimated at $119,261 and $110,548 for M+D and M+S, respectively, in analyses ignoring heterogeneity and $124,521and $114,750 in analyses with established heterogeneity. The incremental-cost-effectiveness-ratio (ICER) comparing M+D vs. M+S was projected at $157,543 in analyses without heterogeneity and $185,394 in analyses with established heterogeneity.  Conclusions: Failure to accommodate patient heterogeneity and their associated nonlinear effects within the model can significantly bias predicted cost effectiveness findings. PRM82 A Systematic Review on the Evidence of Adequate Discount Rates for Vaccines in Germany Koerber F, Redeker M, Wieninger E, Welte R GSK, München, Germany

Objectives: Prophylactic health technologies (e.g. vaccines) differ in several ways from therapeutic interventions. A key aspect concerns the timing of the occurrence of costs and benefits. Consequently, analysts have suggested adapting the methods of health economic evaluation for vaccines. There is an ongoing debate in Germany about the appropriate discount rate for the evaluation of vaccines. This study aims to contribute by reviewing evidence and providing an overview of arguments.  Methods: A systematic literature review was performed in PubMed for