Comparative Effectiveness Reviews Research Articles

Identification of topics for comparative effectiveness systematic reviews in the field of cancer imaging

With rapid innovations in diagnostic and therapeutic interventions in cancer care, comparative effectiveness reviews (CERs) are essential to inform clinical practice and guide future research. However, the optimal means to identify priority CER topics are uninvestigated. We aimed to devise a transparent and reproducible process to identify ten to 12 CER topics in the area of cancer imaging relevant to a wide range of stakeholders. Environmental scans and explicit prioritization criteria supported interactions (email communications, web-based discussions and live teleconferences) with experts and stakeholders culminating in a three-phase deductive exercise for prioritization of CER topics. We prioritized 12 CER topics in breast, lung and gastrointestinal cancers that addressed screening, diagnosis, staging, monitoring and evaluating response to treatment. Our project developed and implemented a transparent and reproducible process for research prioritization and topic nomination that can be further refined to improve the relevance of future CERs.

Priorities for Comparative Effectiveness Reviews in Cardiovascular Disease

Comparative effectiveness reviews offer a systematic method to critically appraise existing research and to identify unaddressed clinical areas in cardiovascular disease where significant morbidity, mortality, and variation in the use of resources persist. To delineate and help select areas where comparative effectiveness reviews are needed, the Effective Health Care Program of the Agency for Healthcare Research and Quality involved stakeholders in prioritization of the research agenda. We involved a diverse panel of stakeholders representing a broad range of clinical, policy, and patient perspectives. To assist in prioritization of topics for evidence synthesis, we created a framework evaluating 12 cardiovascular disease subcategories that reflect American College of Cardiology/American Heart Association disease-based guidelines. We performed an environmental scan for each disease subcategory to populate this framework with existing knowledge, levels of evidence, and degrees of public interest. Through a formalized process, 4 disease subcategories were prioritized: chronic coronary artery disease, ventricular arrhythmias, heart failure, and cerebrovascular disease. Within these subcategories, 11 topics that address the comparative safety and effectiveness of existing treatments and evaluate emerging treatments were nominated by the stakeholder panel to proceed for feasibility assessment before developing comparative effectiveness reviews. Using a systematic process deriving consensus from multiple stakeholders across cardiovascular disease states, we generated a prioritized list of evidence synthesis topics to inform decision makers. The topics vetted through this process seek to determine the comparative safety and effectiveness of a range of treatments, both established and emerging, and are immediately relevant for prevalent disease states.

PRM152 Is it Just Semantics? The Use of “Efficacy” and “Effectiveness” in Comparative Effectiveness Reviews and Health Technology Assessments

To explore and quantify the extent to which the terms “efficacy” and “effectiveness” are used consistently and correctly in and Health Technology Assessments (HTAs). Efficacy describes a drug's effect in ideal and controlled circumstances (i.e. in clinical trials). Effectiveness describes the success of a drug in usual or “real world” practices in which all conditions cannot be controlled. Effectiveness is much more difficult to assess and is often measured by observational studies or calculated by a meta-analysis of clinical trial results. We examined 38 HTAs published from 2005-2011 covering 13 disease conditions from 6 agencies (AHRQ, DERP, CADTH, IQWiG, NICE, and NHS Scotland), which included 115 pharmaceutical products. We categorized each HTA based on whether their stated main objective was to measure either clinical efficacy or clinical effectiveness. These stated main objectives were then compared to the evidence actually evaluated in the reported studies (ie. RCTs and/or observational studies). We quantified and analyzed discrepancies between the stated objectives and actual objectives. Of the 38 HTAs, 37 evaluated efficacy and 1 focused on effectiveness. Eighteen reviews (47%) described their main objective, efficacy or effectiveness, consistent with the actual evidence evaluated. Twenty reviews (53%) stated their main objective was measuring clinical effectiveness, but presented evidence assessing clinical efficacy. Of the 6 agencies, NICE and NHS Scotland showed the highest percentages of discrepancies between stated objectives and evidence evaluated (80% and 100% respectively), while AHRQ and DERP had the lowest (0% and 29% respectively). Though the distinction between “efficacy” and “effectiveness” is substantial, the terms are not always used appropriately or consistently. Often, the uses of the terms in HTAs are misleading. This is a barrier to clear communication, but the implications might be broader.

Methods for the Drug Effectiveness Review Project

The Drug Effectiveness Review Project was initiated in 2003 in response to dramatic increases in the cost of pharmaceuticals, which lessened the purchasing power of state Medicaid budgets. A collaborative group of state Medicaid agencies and other organizations formed to commission high-quality comparative effectiveness reviews to inform evidence-based decisions about drugs that would be available to Medicaid recipients. The Project is coordinated by the Center for Evidence-based Policy (CEbP) at Oregon Health & Science University (OHSU), and the systematic reviews are undertaken by the Evidence-based Practice Centers (EPCs) at OHSU and at the University of North Carolina. The reviews adhere to high standards for comparative effectiveness reviews. Because the investigators have direct, regular communication with policy-makers, the reports have direct impact on policy and decision-making, unlike many systematic reviews. The Project was an innovator of methods to involve stakeholders and continues to develop its methods in conducting reviews that are highly relevant to policy-makers. The methods used for selecting topics, developing key questions, searching, determining eligibility of studies, assessing study quality, conducting qualitative and quantitative syntheses, rating the strength of evidence, and summarizing findings are described. In addition, our on-going interactions with the policy-makers that use the reports are described.

A Pilot Study Using Machine Learning and Domain Knowledge to Facilitate Comparative Effectiveness Review Updating

Comparative effectiveness and systematic reviews require frequent and time-consuming updating. of earlier screening should be useful in reducing the effort needed to screen relevant articles. We collected 16,707 PubMed citation classification decisions from 2 comparative effectiveness reviews: interventions to prevent fractures in low bone density (LBD) and off-label uses of atypical antipsychotic drugs (AAP). We used previously written search strategies to guide extraction of a limited number of explanatory variables pertaining to the intervention, outcome, and We empirically derived statistical models (based on a sparse generalized linear model with convex penalties [GLMnet] and a gradient boosting machine [GBM]) that predicted article relevance. We evaluated model sensitivity, positive predictive value (PPV), and screening workload reductions using 11,003 PubMed citations retrieved for the LBD and AAP updates. Results. GLMnet-based models performed slightly better than GBM-based models. When attempting to maximize sensitivity for all relevant articles, GLMnet-based models achieved high sensitivities (0.99 and 1.0 for AAP and LBD, respectively) while reducing projected screening by 55.4% and 63.2%. The GLMnet-based model yielded sensitivities of 0.921 and 0.905 and PPVs of 0.185 and 0.102 when predicting articles relevant to the AAP and LBD efficacy/effectiveness analyses, respectively (using a threshold of P ≥ 0.02). GLMnet performed better when identifying adverse effect relevant articles for the AAP review (sensitivity = 0.981) than for the LBD review (0.685). The system currently requires MEDLINE-indexed articles. We evaluated statistical classifiers that used previous classification decisions and explanatory variables derived from MEDLINE indexing terms to predict inclusion decisions. This pilot system reduced workload associated with screening 2 simulated comparative effectiveness review updates by more than 50% with minimal loss of relevant articles.

Comparative effectiveness research in spine surgery

Comparative effectiveness research (CER) has impending significance for the field of spine surgery. This article outlines the rationale for comparative effectiveness research and reviews recommended priorities of spinal surgery emphasis. It also examines recent key studies of CER in the spine surgery literature and associated cost-effectiveness studies. It concludes with a discussion of the direction of CER in the spine surgery community.

Methods Guide for Authors of Systematic Reviews of Medical Tests: A Collaboration Between the Agency for Healthcare Research and Quality (AHRQ) and the Journal of General Internal Medicine

Methods Guide for Authors of Systematic Reviews of Medical Tests: A Collaboration Between the Agency for Healthcare Research and Quality (AHRQ) and the Journal of General Internal Medicine

Chapter 11: challenges in and principles for conducting systematic reviews of genetic tests used as predictive indicators.

In this paper, we discuss common challenges in and principles for conducting systematic reviews of genetic tests. The types of genetic tests discussed are those used to 1). determine risk or susceptibility in asymptomatic individuals; 2). reveal prognostic information to guide clinical management in those with a condition; or 3). predict response to treatments or environmental factors. This paper is not intended to provide comprehensive guidance on evaluating all genetic tests. Rather, it focuses on issues that have been of particular concern to analysts and stakeholders and on areas that are of particular relevance for the evaluation of studies of genetic tests. The key points include:The general principles that apply in evaluating genetic tests are similar to those for other prognostic or predictive tests, but there are differences in how the principles need to be applied or the degree to which certain issues are relevant.A clear definition of the clinical scenario and an analytic framework is important when evaluating any test, including genetic tests.Organizing frameworks and analytic frameworks are useful constructs for approaching the evaluation of genetic tests.In constructing an analytic framework for evaluating a genetic test, analysts should consider preanalytic, analytic, and postanalytic factors; such factors are useful when assessing analytic validity.Predictive genetic tests are generally characterized by a delayed time between testing and clinically important events.Finding published information on the analytic validity of some genetic tests may be difficult. Web sites (FDA or diagnostic companies) and gray literature may be important sources.In situations where clinical factors associated with risk are well characterized, comparative effectiveness reviews should assess the added value of using genetic testing along with known factors compared with using the known factors alone.For genome-wide association studies, reviewers should determine whether the association has been validated in multiple studies to minimize both potential confounding and publication bias. In addition, reviewers should note whether appropriate adjustments for multiple comparisons were used.

Comparative effectiveness research: a view from the other side of the pond

Journal of Comparative Effectiveness ResearchVol. 1, No. 3 CommentaryComparative effectiveness research: a view from the other side of the pondMichael D RawlinsMichael D RawlinsNational Institute for Health & Clinical Excellence, London, UK and London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Search for more papers by this authorEmail the corresponding author at michael.rawlins@nice.org.ukPublished Online:18 May 2012https://doi.org/10.2217/cer.12.17AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleReferences1 Doll R, Peto R. Randomised controlled trials and retrospective controls. Br. Med. J.280(6206),44 (1980).Crossref, Medline, CAS, Google Scholar2 Glasziou P, Chalmers I, Rawlins M, McCulloch P. When are randomised controlled trials unnecessary? Picking signal from noise. BMJ334(7589),349–351 (2007).Crossref, Medline, Google Scholar3 Garside R, Round A, Dalziel K, Stein K, Royle P. The effectiveness and cost–effectiveness of imatinib in chronic myeloid leukaemia. Health Technol. Assess.6(33),1–162 (2002).Crossref, Medline, CAS, Google Scholar4 Jong GW, van der Linden PD, Bakker EM et al. Unlicensed and off-label drug use in a paediatric ward of a general hospital in the Netherlands. Eur. J. Clin. Pharmacol.58(4),293–297 (2002).Crossref, Medline, Google Scholar5 Lindell-Osuagwu L, Korhonen MJ, Saano S, Helin-Tanninen M, Naaranlahti T, Kokki H. Off-label and unlicensed drug prescribing in three paediatric wards in Finland and review of the international literature. J. Clin. Pharm. Ther.34(3),277–287 (2009).Crossref, Medline, CAS, Google Scholar6 Caldwell DM, Ades AE, Higgins JP. Simultaneous comparisons of multiple treatments: combining direct and indirect evidence. BMJ331(7521),897–900 (2005).Crossref, Medline, Google Scholar7 Rawlins MD. Therapeutics, Evidence and Decision-Making. Hodder Arnold, London, UK (2011).Google Scholar8 Jansen JP, Fleurence R, Devine B et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1. Value Health14(4),417–428 (2011).Crossref, Medline, Google Scholar9 Cipriani A, Furukawa TA, Salanti G et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet373(9665),746–755 (2009).Crossref, Medline, CAS, Google Scholar10 Schwarz D, Lellouch J. Explanatory and pragmatic attitudes in therapeutic trials. J. Chronic Dis.20(8),637–648 (1967).Crossref, Medline, Google Scholar11 Quanstrum KH, Hayward RA. Lessons from the mammography wars. N. Engl. J. Med.363(11),1076–1078 (2010).Crossref, Medline, CAS, Google Scholar12 Hackshaw A. Benefits and harms of mammography screening. BMJ344,D8279 (2012).Crossref, Medline, Google Scholar13 Gotzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst. Rev.19(1),CD001877 (2011).Google Scholar101 Gingrich N, Rawlins MD. Economist Debates. This house believes that the widespread use of comparative effectiveness reviews and cost/benefit analyses will stifle medical innovation and lead to an unacceptable rationing of healthcare (2009). The Economist Newspaper Limited© (2011). www.economist.com/debate/overview/155 (Accessed February 2012)Google ScholarFiguresReferencesRelatedDetailsCited ByA translation table for patient-centered comparative effectiveness research: guidance to improve the value of research for clinical and health policy decision-makingSean R Tunis, Donna A Messner, Penny Mohr, Richard E Gliklich & Robert W Dubois18 May 2012 | Journal of Comparative Effectiveness Research, Vol. 1, No. 3 Vol. 1, No. 3 Follow us on social media for the latest updates Metrics Downloaded 142 times History Published online 18 May 2012 Published in print May 2012 Information© Future Medicine LtdFinancial & competing interests disclosureM Rawlins has been chairman of the National Institute for Health and Clinical Excellence since 1999. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download

Comparative effectiveness research (CER): a summary of AHRQ's CER on therapies for rheumatoid arthritis.

In recent years, the U.S. government has designated funding of several large-scale initiatives for comparative effectiveness research (CER) in health care. The American Recovery and Reinvestment Act (ARRA) of 2009 apportioned more than $1 billion to support CER programs administered by the Department of Health and Human Services (DHHS), the National Institutes of Health (NIH), and the Agency for Healthcare Research and Quality (AHRQ). CER is generally defined as the undertaking of original research or systematic reviews of published literature in order to compare the benefits and risks of different approaches to preventing, diagnosing, or treating diseases. These approaches may include diagnostic tests, medications, medical devices, and surgeries. The overall goals of CER are to support informed health care decisions by patients, clinicians, payers, and policy makers and to apply its evidence to ultimately improve the quality, effectiveness, and efficiency of health care. To (a) provide managed care professionals with general definitions of CER, specifically as it is administered by AHRQ; (b) discuss the importance of CER to clinical and managed care pharmacists; and (c) summarize key methods and findings from AHRQ's 2007 comparative effectiveness review on therapies for rheumatoid arthritis (RA). As supported by AHRQ, CER is conducted in order to synthesize comprehensive evidence on the comparative benefits and harms of treatment interventions. The findings from comparative effectiveness reviews can thus contribute to informing therapeutic strategies and treatment decisions. In 2007, a multitude of RA treatment options and studies motivated AHRQ to commission a systematic comparative effectiveness review. Conducted by investigators at the RTI-University of North Carolina Evidence-Based Practice Center, the review included comparisons of synthetic disease-modifying antirheumatic drugs (DMARDs), biologic agents, synthetic DMARDs versus biologic agents, and various combination therapies. Head-to-head comparisons of synthetic DMARDs generally revealed no significant differences in long-term clinical and radiographic outcomes, or in functional capacity or health-related quality of life. Two nonrandomized prospective cohort studies and 1 open-label effectiveness trial reported no differences in ACR20 and ACR50 response rates in patients treated with the tissue necrosis factor (TNF)-alpha inhibitors etanercept and infliximab. Comparisons of TNF-alpha inhibitors generally indicated no significant differences in rates of adverse events, including serious infections, and no increases in rates over time. In comparisons of a biologic agent combined with methotrexate versus a biologic agent alone, combination therapies were generally associated with better clinical response rates and better outcomes of functional capacity and quality of life. The most common adverse events observed in studies on biologic agents were diarrhea, headache, nausea, rhinitis, injection site reactions, and upper respiratory tract infections.

PHP121 The Role of Molecular Tests in Shaping Comparative Effectiveness Review (CER)

1) Perform a comprehensive review of the US molecular testing environment; 2) Infer from Diagnostic/treatment areas most likely to include comparative effectiveness reviews (CER) involving molecular testing, how CER will be shaped by molecular diagnostics, evidence used in coverage decisions; and 3) Determine global generalizability of US trends. We reviewed: 1) All non-perinatal molecular tests with actual or potential for CER interface, all Medicare national (NCDs) and selected local coverage decisions (LCDs) involving molecular tests and CER, and US government and related agency high priority disease areas for CER, assessing actual or potential molecular testing inclusion, and 2) We inferred: Clinical areas most likely involving molecular diagnostics and CER,iImpact of molecular testing on CER, evidence required for Medicare/other payer coverage, and universality of US findings. 1) Inventory indicates 442 molecular tests/combinations of interest; 259 have potential degrees of CER interface; 2) Medicare database yielded: 2 NCDs (Screening DNA Stool Test for Colorectal Cancer, Pharmacogenetic Testing for Warfarin Response), 9 LCDs and articles: many denials of molecular test coverage, denials cite lack of evidence, including trials, clinical utility, and few cite cost-effectiveness data; 3) Five governmental or health technology assessment organizations point to 14 clinical areas as highest CER priorities: six known to have associated molecular tests; 5 already involved CER activity, and another 7 predicted to have future molecular testing and CER activity per identified priority areas for research. Expect molecular testing: to play an increasing future role in CER, particularly in 7 areas (cancer and hematopathology most prominently, inclusion will necessitate more methodologically sophisticated CER, will make cost-effectiveness part of CER, will require strong clinical utility evidence for payer coverage, and trends will be universal and more pronounced ex-US.

PHP120 The Past As Prologue: Use of Comparative Effectiveness Reviews (CER) in National Coverage Decision Making by Medicare in the United States and Predictions on Future Use of CER

PHP120 The Past As Prologue: Use of Comparative Effectiveness Reviews (CER) in National Coverage Decision Making by Medicare in the United States and Predictions on Future Use of CER

Development of the RTI item bank on risk of bias and precision of observational studies

ObjectiveTo create a practical and validated item bank for evaluating the risk of bias and precision of observational studies of interventions or exposures included in systematic evidence reviews. Study Design and SettingThe item bank, developed at RTI International, was created based on 1,492 questions included in earlier instruments, organized by the quality domains identified by Deeks et al. Items were eliminated and refined through face validity, cognitive, content validity, and interrater reliability testing. ResultsThe resulting item bank consisting of 29 questions for evaluating the risk of bias and precision of observational studies of interventions or exposures (1) captures all of the domains critical for evaluating this type of research, (2) is comprehensive and can be easily lifted “off the shelf” by different researchers, (3) can be adapted to different topic areas and study types (e.g., cohort, case–control, cross-sectional, and case series studies), and (4) provides sufficient instruction to apply the tool to varied topics. ConclusionOne bank of items, with specific instructions for focusing abstractor evaluations, can be created to judge the risk of bias and precision of the variety of observational studies that may be used in systematic and comparative effectiveness reviews.

The Agency for Healthcare Research and Quality (AHRQ) Effective Health Care (EHC) Program Methods Guide for Comparative Effectiveness Reviews: keeping up-to-date in a rapidly evolving field

A challenge for any research program is to ensure consistent use of the most current scientific methods, especially in a rapidly evolving field. Systematic review is a field that is moving into maturity from its adolescence. This issue of the Journal of Clinical Epidemiology includes 5 papers that nearly complete version 1.0 of theAgency forHealthcare Research and Quality (AHRQ) Effective Health Care Program Methods Guide for Comparative Effectiveness Reviews (Methods Guide). The Methods Guide is a collaborative effort among participating scientists at the 14 Evidencebased Practice Centers (EPCs) andAHRQ to identify the best methods for conducting systematic reviews on comparative effectiveness of interventions. The AHRQ-funded EPC Programwas established in 1997. These articles address areas of unnecessary variation, uncertainty, and areas of controversy raised by peer or public review of early Comparative EffectivenessReviews.Thebest approacheswereguidedby a combination of non-systematic review of empiric research and EPC experience and best practices in performing complex systematic reviews of comparative interventions. This methods guidance is intended to help advance the science and practice of systematic reviews, especially within the AHRQ EPC program. The first draft of theMethods Guide was originally posted for public comment in 2007. Subsequently, the draft was broken up into individual papers and each paper revised based on peer and public comments received. Since the draft was posted there has been growth in methods of systematic review, with development of guidance and standards by many different organizations around the world. The Methods Guide builds on work by others also established in the field, such as the Grading of Recommendations Assessment,

Risk management and comparative effectiveness research: implications of the new collaborative FDA-CMS initiative

Abstract The US Food and Drug Administration's (FDA's) expanded authority to require Risk Evaluation and Mitigation Strategies (REMS) and the increasing importance of comparative effectiveness research and reviews (CERs) under the Affordable Care Act raise a number of public policy issues for prescription drug safety. In addition, the formalization of an interface between the Centers for Medicare and Medicaid Services (CMS) and the FDA to expedite early coverage of drugs, devices and diagnostics raises a number of questions about the extension of CERs into post-marketing drug surveillance requirements. In this commentary, we address the potential applications of CERs and REMS in risk-benefit assessments.

Observational studies in systemic reviews of comparative effectiveness: AHRQ and the Effective Health Care Program

Objective Systematic reviewers disagree about the ability of observational studies to answer questions about the benefits or intended effects of pharmacotherapeutic, device, or procedural interventions. This study provides a framework for decision making on the inclusion of observational studies to assess benefits and intended effects in comparative effectiveness reviews (CERs). Study Design and Setting The conceptual model and recommendations were developed using a consensus process by members of the methods workgroup of the Effective Health Care Program of the Agency for Healthcare Research and Quality. Results In considering whether to use observational studies in CERs for addressing beneficial effects, reviewers should answer two questions: (1) Are there gaps in the evidence from randomized controlled trials (RCTs)? (2) Will observational studies provide valid and useful information? The latter question involves the following: (a) refocusing the study questions on gaps in the evidence from RCTs, (b) assessing the risk of bias of the body of evidence of observational studies, and (c) assessing whether available observational studies address the gap review questions. Conclusions Because it is unusual to find sufficient evidence from RCTs to answer all key questions concerning benefit or the balance of benefits and harms, comparative effectiveness reviewers should routinely assess the appropriateness of inclusion of observational studies for questions of benefit. Furthermore, reviewers should explicitly state the rationale for inclusion or exclusion of observational studies when conducting CERs.

Decisions to update comparative drug effectiveness reviews vary based on type of new evidence

Objective To determine the time to and key factors associated with decision to update comparative effectiveness of reviews of drugs based on periodic scans of new evidence. Study Design and Setting Based on periodic scans of new evidence, we analyzed 69 decisions on whether to update for 41 comparative effectiveness reviews conducted for the Drug Effectiveness Review Project. We used the Kaplan–Meier product limit method to estimate mean time to update and generalized estimating equation logistic regression to estimate associations between updating decisions and review topic or characteristics of new evidence. Results Mean time to update was 24.9 months. Significant predictors of a decision to update were identification of a new drug (odds ratio [OR]: 5.71; 95% confidence interval [CI]: 1.68–19.44) and the number of new relevant trials (OR: 1.06; 95% CI: 1.03–1.10). Compared with nonpsychiatric topics, psychiatric topics were most rapidly developing (mean new relevant citations: 38.4 vs. 8.2; P = 0.0127) and were updated at a faster pace (mean survival time: 10.2 vs. 27.5 months; P < 0.0001). Conclusion Using periodic scans of new evidence, updating should be considered yearly for rapidly developing topics and biannually for other topics.

P03-97 - Comparative efficacy, effectiveness and harms of second-generation antidepressants in the pharmacologic treatment of adult depression

IntroductionSecond-generation antidepressants dominate the medical management of major depressive disorder (MDD). Two published comparative effectiveness reviews (CER) provide conflicting evidence about the comparative efficacy and safety of second-generation antidepressants for treating MDD.ObjectivesTo compare the benefits and harms of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for the treatment of MDD in adults.MethodsWe updated a CER published in 2007 by the Agency for Healthcare Research and Quality searching MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias. If data were sufficient, we conducted meta-analyses of head-to-head trials of the relative benefit of response to treatment. In addition, we conducted mixed treatment comparisons to derive indirect estimates of the comparative efficacy among all second-generation antidepressants.ResultsOverall, no substantial differences in efficacy could be detected among second-generation antidepressants. Statistically significant differences in response rates between some compared drugs are small and likely not clinically relevant. Differences exist in the incidence of specific adverse events and the onset of action. Venlafaxine leads to higher rates of nausea and vomiting, sertraline to higher rates of diarrhea, and mirtazapine to higher rates of weight gain than comparator drugs. Bupropion caused lower rates of sexual dysfunction than other antidepressants.ConclusionsOur findings indicate that the existing evidence does not warrant the choice of one second-generation antidepressant over another based on greater efficacy and effectiveness.

An Integrated Evidence Rating to Frame Comparative Effectiveness Assessments for Decision Makers

An important challenge facing the research community is how to make comparative effectiveness reviews "fit for purpose"--how to translate the results into a format that can provide actionable guidance for all stakeholders trying to improve the quality and value of health care. To communicate transparently the overall judgments on the findings from a comparative effectiveness review, the Institute for Clinical and Economic Review (ICER) uses an integrated evidence rating that combines separate ratings of comparative clinical effectiveness and comparative value. These integrated ratings look somewhat like bond ratings, and are suited to foster more direct consideration by all decision makers for potential application to patient information, clinical guidelines, and value-based coverage and payment policies. ICER Integrated Evidence Ratings have supported coverage decision-making processes in a limited number of public and private payers, and demonstration efforts are underway to link reviews to patient information and revised payment policies. Several important challenges to rating have been encountered and addressed. Early feedback has suggested that the rating format helps decision makers understand the key issues underlying judgments about the comparative effectiveness of alternative interventions. Decision makers need comparative effectiveness reviews to be objective and rigorous; they also need key judgments regarding the evidence to be translated so all stakeholders can understand and consider them fully. A rating format that captures key judgments about comparative clinical effectiveness and comparative value could prove an effective method for helping ensure that comparative effectiveness reviews are understandable and useful to all stakeholders.

Evaluating New Medicines for Use in Australian Hospitals: Lessons from North America

ABSTRACTSeveral centres were visited in North America to identify strategies that could improve the processes used by Australian hospitals when evaluating new medicines for clinical and economic benefits. The centres visited included hospitals, a managed care organisation and the Canadian Agency for Drugs and Technologies in Health. All of the hospitals visited used a formulary to manage medicines and took a similar approach to evaluating new medicines for formulary listing and monitoring decisions. The institutional pharmacy and therapeutics committees were responsible for decision‐making and were guided by detailed drug monographs prepared by pharmacy staff. There was limited use of pharmacoeconomic data in decision‐making. Resources used to guide decision‐making included standard guidelines for formulary submission, comparative effectiveness reviews and a checklist. A more consistent and rigorous approach to assessing medicines and determining cost‐effectiveness could be achieved in Australian hospitals by using a standard format for submissions. Australian drug and therapeutics committees' members need to be educated about the utility of pharmacoeconomic studies in the evaluation of new medicines.