Original Cost-effectiveness Analyses Research Articles

Cross-model validation of public health microsimulation models; comparing two models on estimated effects of a weight management intervention

BackgroundHealth economic modelling indicates that referral to a behavioural weight management programme is cost saving and generates QALY gains compared with a brief intervention. The aim of this study was to conduct a cross-model validation comparing outcomes from this cost-effectiveness analysis to those of a comparator model, to understand how differences in model structure contribute to outcomes.MethodsThe outcomes produced by two models, the School for Public Health Research diabetes prevention (SPHR) and Health Checks (HC) models, were compared for three weight-management programme strategies; Weight Watchers (WW) for 12 weeks, WW for 52 weeks, and a brief intervention, and a simulated no intervention scenario. Model inputs were standardised, and iterative adjustments were made to each model to identify drivers of differences in key outcomes.ResultsThe total QALYs estimated by the HC model were higher in all treatment groups than those estimated by the SPHR model, and there was a large difference in incremental QALYs between the models. SPHR simulated greater QALY gains for 12-week WW and 52-week WW relative to the Brief Intervention. Comparisons across socioeconomic groups found a stronger socioeconomic gradient in the SPHR model. Removing the impact of treatment on HbA1c from the SPHR model, running both models only with the conditions that the models have in common and, to a lesser extent, changing the data used to estimate risk factor trajectories, resulted in more consistent model outcomes.ConclusionsThe key driver of difference between the models was the inclusion of extra evidence-based detail in SPHR on the impacts of treatments on HbA1c. The conclusions were less sensitive to the dataset used to inform the risk factor trajectories. These findings strengthen the original cost-effectiveness analyses of the weight management interventions and provide an increased understanding of what is structurally important in the models.

The cost-effectiveness of metformin in the US diabetes prevention program trial: Simple interpretations need not apply

Based on previously published US Diabetes Prevention Program (DPP) cost-effectiveness analyses (CEAs) metformin continues to be promoted as “cost-effective.” We review the DPP within-trial CEA to assess this claim. Treatment alternatives included placebo (plus standard lifestyle advice), branded metformin and individual lifestyle modification. We added generic metformin as an alternative. Original published CEA data were taken as given and re-analyzed according to accepted principles for calculating incremental cost-effectiveness ratios (ICERs) in the economic evaluation field. With more than two treatments as in the DPP, these require attention to the rankings of interventions according to cost or effect prior to stipulating appropriate ICERs to calculate. With proper ICERs neither branded nor generic metformin was cost-effective, regardless of the value assumed for the willingness to pay for the quality-adjusted life year outcome assessed. Metformin alternatives were technically inefficient compared to placebo or the lifestyle modification alternative. Net loss calculations indicated substantial costs/health losses to using metformin instead of the optimal lifestyle alternative in response to metformin having been inaccurately labelled “cost-effective” in the original CEA. That CEA and subsequent analyses and citations of such analyses continue to claim that both metformin and lifestyle modification are cost-effective in diabetes prevention based on DPP data. Using metformin implies substantial costs and health losses compared to the cost-effective lifestyle modification. It may be that metformin has a role in cost-effective diabetes prevention, but this has yet to be shown based on DPP data.

The evolution of ICER's review process for new medical interventions and a critical review of economic evaluations (2018-2019): how stakeholders can collaborate with ICER to improve the quality of evidence in ICER's reports.

BACKGROUND: Since its inception in 2006, the Institute for Clinical and Economic Review (ICER) has rapidly gained influence on drug pricing and reimbursement decisions despite historical resistance to the use of cost-effectiveness thresholds in the US health care system. Although patient groups, physicians, and pharmaceutical manufacturers voiced their concerns about the potential negative effects of increased use of ICER's assessments on patient access to innovative medications, there is little guidance and consensus on how the stakeholders should collaborate with ICER to ensure that its reviews reflect the best clinical and economic evidence. OBJECTIVES: To (1) summarize the evolution of ICER's evaluation procedure, scope, and topics; (2) evaluate the effectiveness of stakeholder engagement approaches; and (3) inform stakeholders of their potential role in collaborating with ICER in estimating the cost-effectiveness of new interventions. METHODS: Publicly available ICER evaluations from 2008 to 2019 were systematically reviewed. Changes in evaluation procedures, scope, and topics were summarized. For evaluations that occurred in 2018 (n = 12) and 2019 (n = 8), key characteristics were extracted from 172 letters documenting interactions between ICER and all stakeholders who provided comments to draft reports. Stakeholder suggestions were analyzed in terms of their effectiveness indicated by ICER's reconsideration of its original cost-effectiveness analysis approach. RESULTS: The number of ICER evaluations increased consistently from 2 to 12 per year between 2008 and 2018 but declined to 8 in 2019. Stakeholder opportunity to engage with ICER increased from 1 to 3 per evaluation between 2008 and 2015. ICER initially focused on reviewing general treatment strategies but shifted its focus to specific pharmaceuticals and medical devices in 2014. In 2018 and 2019, 30% of 172 stakeholder letters resulted in a revision in the base-case analysis (49 comments in 2018, 23 in 2019); nearly half of comments in these letters included specific alternative data or a published article to rationalize recommendations. Other common types of suggestions that resulted in ICER's base-case analysis revisions included comments relating to inconsistent methods used to derive model inputs across different treatments (12/49 in 2018, 5/23 in 2019); clinical justifications (12/49 in 2018, 0/23 in 2019); and justifications based on patient perspectives (1/49 in 2018, 5/23 in 2019). These revisions rarely affected ICER's conclusions on the cost-effectiveness of evaluated interventions. Among the 20 assessments that involved 172 stakeholder engagements in 2018 and 2019, only 2% (n = 3) of the engagements (all from 2018) were associated with a change in the cost-effectiveness conclusion. CONCLUSIONS: Between 2018 and 2019, stakeholders leveraged ICER evaluations as opportunities to promote dialogue for better understanding of the value of technologies. Actionable, evidence-based recommendations were accepted more often than other recommendations. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to disclose. Findings from this study were presented as a poster at Virtual ISPOR, May 17-20, 2021.

PDB34 THE DIABETES PREVENTION PROGRAM (DPP) QUALITY OF WELL BEING (QWB) UTILITY MEASURES AND MISSING DATA CONSIDERATIONS: AVAILABLE CASE ANALYSIS (ACA) VS. MULTIPLE IMPUTATION (MI) RESULTS FOR UTILITIES AND QUALITY ADJUSTED LIFE YEARS (QALYS)

In 2003 the DPP published a within-trial 3 year cost-effectiveness analysis (CEA). The authors appear to have ignored missing data and used ACA, reporting QALYs using the QWB to measure patient utilities for placebo (PBO), lifestyle (LS), and metformin (MET). The main objective of this research is to estimate treatment utilities and QALYs using Multiple Imputation (MI) and compare these results with previous ACA findings. We had access to a 95% subset of the original data. We reproduced the original ACA results and then used MI to develop estimates for utilities and QALYs based on the QALY calculation method used in the original CEA. 5 imputed datasets were pooled into a single imputed dataset. The percentages of participants with at least one missing utility data for QWB for years 1, 2 and 3 were 36%, 10 % and 48%. The yearly utility scores using the QWB originally reported in the DPP were [0.686, 0.675, 0.657], [0.687, 0.680, 0.673] and [0.703, 0.695, 0.692] for PBO, MET, and LS. The utility scores using MI were [0.685, 0.676, 0.669], [0.688, 0.683, 0.681] and [0.705, 0.694, 0.694]. QALYs using the QWB as originally calculated were 2.018, 2.040 and 2.090 for PBO, MET and LS. The MI QALYs were 2.030, 2.053 and 2.094. The incremental QALYs using the QWB as originally calculated were 0.072, 0.022 and 0.050 for LS versus PBO, MET versus PBO, and LS versus MET. The MI incremental QALYs were 0.064, 0.023 and 0.041. The missing data and MI estimates in the DPP yielded different incremental QALYs compared to the ones reported in the original DPP study. Small differences in QALYs have been shown previously to be important in the DPP CEA conclusions. These differences may be important in their CEA implications, a subject for future research.

PDB27 THE DIABETES PREVENTION PROGRAM (DPP) QUALITY OF WELL BEING (QWB) UTILITY MEASURES AND MISSING DATA CONSIDERATIONS: AVAILABLE CASE ANALYSIS (ACA) VS. MANSKI LOWER AND UPPER BOUNDS (LMB AND UMB) RESULTS FOR UTILITIES AND QUALITY ADJUSTED LIFE YEARS (QALYS)

A within-trial cost-effectiveness analysis (CEA) of the DPP was published in 2003. The authors appear to have ignored missing data and used ACA, reporting QALYs using the QWB to measure patient utilities for placebo (PBO), lifestyle (LS), and metformin (MET). The main motivation here is to estimate treatment utilities and QALYs using Manski bounds (MB) and compare these results with DPP findings. We had access to a 95% subset of the original data. We reproduced the original ACA results and then used MB to develop estimates for utilities and QALYs based on the QALY calculation method used in the original CEA. The minimum and maximum utility scores each year for each group were used to fill the missing value for participants in their respective groups for LMB and UMB. The percentage of participants with at least one missing utility data for QWB for years 1, 2 and 3 was 36%, 10 % and 48% respectively. The yearly utility scores using the QWB originally reported in the DPP were [0.686, 0.675, 0.657], [0.687, 0.680, 0.673] and [0.703, 0.695, 0.692] for PBO, MET, and LS. The utility scores for LMB were [0.553, 0.631, 0.416], [0.560, 0.635, 0.476] and [0.560, 0.655, 0.496]. The analogous numbers for UMB were [0.797, 0.708, 0.826], [0.796, 0.715, 0.834] and [0.813, 0.725, 0.843]. QALYs using the QWB as originally calculated were 2.018, 2.040 and 2.090 for PBO, MET and LS. The LMB QALYs were 1.600, 1.671, 1.711; UMBs were 2.331, 2.345, 2.381. The minimum/maximum range versus PBO for LS was 0.050/0.781; for PBO versus MET the range was 0.014/0.745, indicating that even the relative rankings of QALYs cannot be known. The missing data and MB estimates indicate considerable uncertainty even on QALY rankings of the treatments and certainly in any CEA based on them.

Cost-effectiveness of emergency care interventions in low and middle-income countries: a systematic review.

ObjectiveTo systematically review and appraise the quality of cost–effectiveness analyses of emergency care interventions in low- and middle-income countries.MethodsFollowing the PRISMA guidelines, we systematically searched PubMed®, Scopus, EMBASE®, Cochrane Library and Web of Science for studies published before May 2019. Inclusion criteria were: (i) an original cost–effectiveness analysis of emergency care intervention or intervention package, and (ii) the analysis occurred in a low- and middle-income setting. To identify additional primary studies, we hand searched the reference lists of included studies. We used the Consolidated Health Economic Evaluation Reporting Standards guideline to appraise the quality of included studies.ResultsOf the 1674 articles we identified, 35 articles met the inclusion criteria. We identified an additional four studies from the reference lists. We excluded many studies for being deemed costing assessments without an effectiveness analysis. Most included studies were single-intervention analyses. Emergency care interventions evaluated by included studies covered prehospital services, provider training, treatment interventions, emergency diagnostic tools and facilities and packages of care. The reporting quality of the studies varied.ConclusionWe found large gaps in the evidence surrounding the cost–effectiveness of emergency care interventions in low- and middle-income settings. Given the breadth of interventions currently in practice, many interventions remain unassessed, suggesting the need for future research to aid resource allocation decisions. In particular, packages of multiple interventions and system-level changes represent a priority area for future research.

Cost-Effectiveness Analysis of a Procalcitonin-Guided Decision Algorithm for Antibiotic Stewardship Using Real-World U.S. Hospital Data.

Medical decision-making is revolutionizing with the introduction of artificial intelligence and machine learning. Yet, traditional algorithms using biomarkers to optimize drug treatment continue to be important and necessary. In this context, early diagnosis and rational antimicrobial therapy of sepsis and lower respiratory tract infections (LRTI) are vital to prevent morbidity and mortality. In this study we report an original cost-effectiveness analysis (CEA) of using a procalcitonin (PCT)-based decision algorithm to guide antibiotic prescription for hospitalized sepsis and LRTI patients versus standard care. We conducted a CEA using a decision-tree model before and after the implementation of PCT-guided antibiotic stewardship (ABS) using real-world U.S. hospital-specific data. The CEA included societal and hospital perspectives with the time horizon covering the length of hospital stay. The main outcomes were average total costs per patient, and numbers of patients with Clostridium difficile and antibiotic resistance (ABR) infections. We found that health care with the PCT decision algorithm for hospitalized sepsis and LRTI patients resulted in shorter length of stay, reduced antibiotic use, fewer mechanical ventilation days, and lower numbers of patients with C. difficile and ABR infections. The PCT-guided health care resulted in cost savings of $25,611 (49% reduction from standard care) for sepsis and $3630 (23% reduction) for LRTI, on average per patient. In conclusion, the PCT decision algorithm for ABS in sepsis and LRTI might offer cost savings in comparison with standard care in a U.S. hospital context. To the best of our knowledge, this is the first health economic analysis on PCT implementation using U.S. real-world data. We suggest that future CEA studies in other U.S. and worldwide settings are warranted in the current age when PCT and other decision algorithms are increasingly deployed in precision therapeutics and evidence-based medicine.

PDB80 - RE-ANALYSIS OF THE DIABETES PREVENTION PROGRAM 3 YEAR COST-EFFECTIVENESS ANALYSIS (CEA) USING IDENTICAL DATA BUT PROPER METHODS QUESTIONS ITS CONCLUSIONS

The DPP 3 year trial examined 3 interventions, placebo (PBO), metformin (MET) and individual lifestyle (ILS) added to baseline lifestyle modification advice for diabetes prevention. It found the two active interventions effective, with ILS being more effective. A trial-based cost-effectiveness analysis (CEA) indicated that both ILS and MET were cost-effective. Our work examined the conclusions of that CEA and sought to clarify misleading conclusions. We reanalyzed the CEA results, adding, as in the original paper, a group LS intervention (GLS) – modelled only (with assumed equal efficacy and reduced costs), not observed. We also examined (as in original) a generic MET alternative, MET25 (where efficacy is assumed identical, but at a cost of only 25% of the branded version), but do not use them in the same analyses as MET 25 dominates MET. Instead of presenting ICERs for MET, MET25 and ILS, GLS interventions all vs. PBO as in the original CEA, we used the original CEA data according to a process outlined in Glick (2007), clarifying conclusions by eliminating dominated alternatives. In cases with MET, GLS dominates both ILS and MET with an ICER vs. PBO within acceptable WTP thresholds ($8982/QALY). If GLS is excluded (as it was only a modeled intervention), ILS dominates MET and has an ICER likely to be acceptable ($31,512/QALY). The same qualitative results were seen for MET25. The conclusion of the original CEA was that both ILS and MET were cost-effective. We have shown this to be false, using the exact data as in the original CEA. Based on these data, there is no place for MET in diabetes prevention. We suggest that graphical depictions of results in the cost-effectiveness plane or in a less common cost-disutility plane might have driven home the correct conclusion more clearly than the numerical results.

Systematic Review and Quality Assessment of Cost-Effectiveness Analysis of Pharmaceutical Therapies for Advanced Colorectal Cancer

To systematically review and assess the quality of cost-effectiveness analyses (CEAs) of pharmaceutical therapies for metastatic colorectal cancer (mCRC). The MEDLINE, EMBASE, Cochrane, and EconLit databases were searched for the Medical Subject Headings or text key words quality-adjusted, QALY, life-year gained (LYG), and cost-effectiveness (January 1, 1999-December 31, 2009). Original CEAs of mCRC pharmacotherapy published in English were included. CEAs that measured health effects in units other than quality-adjusted life years or LYG and letters to the editor, case reports, posters, and editorials were excluded. Each article was independently assessed by 2 trained reviewers according to a quality checklist created by the Panel on Cost-Effectiveness in Health and Medicine. Twenty-four CEA studies pertaining to pharmaceutical therapies for mCRC were identified. All studies showed a wide variation in methodologic approaches, which resulted in a different range of incremental cost-effectiveness ratios reported for each regimen. We found common methodologic flaws in a significant number of CEA studies, including lack of clear description for critique of data quality; lack of method for adjusting costs for inflation and methods for obtaining expert judgment; no results of model validation; wide differences in the types of perspective, time horizon, study design, cost categories, and effect outcomes; and no quality assessment of data (cost and effectiveness) for the interventions evaluation. This study has shown a wide variation in the methodology and quality of cost-effectiveness analysis for mCRC. Improving quality and harmonization of CEA for cancer treatment is needed. Further study is suggested to assess the quality of CEA methodology outside the mCRC disease state.

Moving beyond a limited follow-up in cost-effectiveness analyses of behavioral interventions

BackgroundCost-effectiveness analyses of behavioral interventions typically use a dichotomous outcome criterion. However, achieving behavioral change is a complex process involving several steps towards a change in behavior. Delayed effects may occur after an intervention period ends, which can lead to underestimation of these interventions. To account for such delayed effects, intermediate outcomes of behavioral change may be used in cost-effectiveness analyses. The aim of this study is to model cognitive parameters of behavioral change into a cost-effectiveness model of a behavioral intervention.MethodsThe cost-effectiveness analysis (CEA) of an existing dataset from an RCT in which an high-intensity smoking cessation intervention was compared with a medium-intensity intervention, was re-analyzed by modeling the stages of change of the Transtheoretical Model of behavioral change. Probabilities were obtained from the dataset and literature and a sensitivity analysis was performed.ResultsIn the original CEA over the first 12 months, the high-intensity intervention dominated in approximately 58% of the cases. After modeling the cognitive parameters to a future 2nd year of follow-up, this was the case in approximately 79%.ConclusionThis study showed that modeling of future behavioral change in CEA of a behavioral intervention further strengthened the results of the standard CEA. Ultimately, modeling future behavioral change could have important consequences for health policy development in general and the adoption of behavioral interventions in particular.

Cost Effectiveness of Treatments for Wet Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness in people aged ≥50 years. Wet AMD in particular has a major impact on patient quality of life and imposes substantial burdens on healthcare systems. This systematic review examined the cost-effectiveness data for current therapeutic options for wet AMD. PubMed and EMBASE databases were searched for all articles reporting original cost-effectiveness analyses of wet AMD treatments. The Centre for Reviews and Dissemination and Cochrane Library databases were searched for all wet AMD health technology assessments (HTAs). Overall, 44 publications were evaluated in full and included in this review. A broad range of cost-effectiveness analyses were identified for the most commonly used therapies for wet AMD (pegaptanib, ranibizumab and photodynamic therapy [PDT] with verteporfin). Three studies evaluated the cost effectiveness of bevacizumab in wet AMD. A small number of analyses of other treatments, such as laser photocoagulation and antioxidant vitamins, were also found. Ranibizumab was consistently shown to be cost effective for wet AMD in comparison with all the approved wet AMD therapies (four of the five studies identified showed ranibizumab was cost effective vs usual care, PDT or pegaptanib); however, there was considerable variation in the methodology for cost-effectiveness modelling between studies. Findings from the HTAs supported those from the PubMed and EMBASE searches; of the seven HTAs that included ranibizumab, six (including HTAs for Australia, Canada and the UK) concluded that ranibizumab was cost effective for the treatment of wet AMD; most compared ranibizumab with PDT and/or pegaptanib. By contrast, HTAs at best generally recommended pegaptanib or PDT for restricted use in subsets of patients with wet AMD. In the literature analyses, pegaptanib was found to be cost effective versus usual/best supportive care (including PDT) or no treatment in one of five studies; the other four studies found pegaptanib was of borderline cost effectiveness depending on the stage of disease and time horizon. PDT was shown to be cost effective versus usual/best supportive care or no treatment in five of nine studies; two studies showed that PDT was of borderline cost effectiveness depending on baseline visual acuity, and two showed that PDT was not cost effective. We identified no robust studies that properly evaluated the cost effectiveness of bevacizumab in wet AMD.

A Bibliometric Review of Cost-Effectiveness Analyses in the Economic and Medical Literature: 1976-2006

Cost-effectiveness analysis (CEA) presenting a cost per quality-adjusted life year (QALY) ratio is frequently used to determine ''value for money'' in health care. Despite the proliferation of CEA research, there has been no detailed study focusing on the bibliometric properties of this literature. To describe and analyze trends in publications and coauthorship in the CEA literature from 1976 to 2006 and to identify the most prolific authors and research groups conducting CEAs. The authors used the Tufts Medical Center Registry of original CEAs published through 2006 (www.cearegistry.org). For each article, they recorded the year of publication, the journal title, and the number of contributing authors and their names. Authors were assigned credit based on their weighted contribution to the study (1 credit point for the first and last authors, (1/2) point for the second author, and ( 1)=(n) credit points for all other authors, where n reflects the number of coauthors). Approximately 1400 CEAs presenting a cost/QALY ratio were published in 420 journals through 2006. The mean number of contributing authors was 4.7 +/- 2.4. Medical journals were characterized by a higher number of coauthors, as compared with the economic and health policy journals: 4.8 +/- 2.4 v. 4.2 +/- 2.0, P < 0.001. The lowest average number of coauthors was in Medical Decision Making (3.6) and the highest in the Journal of the American College of Cardiology (8.2). The most prolific authors were affiliated with Harvard and Tufts Universities and their affiliated hospitals. The authors identified 4 major research groups that contributed substantially to the field of cost-effectiveness analysis but did not find any substantial academic relationships across these groups. The CEA literature continues to proliferate. Coauthorship trends appear to follow the rapid increase in the mean number of authors found in other publication types.

When is critical care medicine cost-effective? A systematic review of the cost-effectiveness literature*

Receiving care in an intensive care unit can greatly influence patients' survival and quality of life. Such treatments can, however, be extremely resource intensive. Therefore, it is increasingly important to understand the costs and consequences associated with interventions aimed at reducing mortality and morbidity of critically ill patients. Cost-effectiveness analyses (CEAs) have become increasingly common to aid decisions about the allocation of scarce healthcare resources. To identify published original CEAs presenting cost/quality-adjusted life year or cost/life-year ratios for treatments used in intensive care units, to summarize the results in an accessible format, and to identify areas in critical care medicine that merit further economic evaluation. We conducted a systematic search of the English-language literature for original CEAs of critical care interventions published from 1993 through 2003. We collected data on the target population, therapy or program, study results, analytic methods employed, and the cost-effectiveness ratios presented. We identified 19 CEAs published through 2003 with 48 cost-effectiveness ratios pertaining to treatment of severe sepsis, acute respiratory failure, and general critical care interventions. These ratios ranged from cost saving to 958,423 US dollars/quality-adjusted life year and from 1,150 to 575,054 US dollars/life year gained. Many studies reported favorable cost-effectiveness profiles (i.e., below 50,000 US dollars/life year or quality-adjusted life year). Specific interventions such as activated protein C for patients with severe sepsis have been shown to provide good value for money. However, overall there is a paucity of CEA literature on the management of the critically ill, and further high-quality CEA is needed. In particular, research should focus on costly interventions such as 24-hr intensivist availability, early goal-directed therapy, and renal replacement therapy. Recent guidelines for the conduct of CEAs in critical care may increase the number and improve the quality of future CEAs.

Quality of Abstracts of Papers Reporting Original Cost-Effectiveness Analyses

Although many peer-reviewed journals have adopted standards for reporting cost-effectiveness analyses (CEAs), guidelines do not exist for the accompanying abstracts. Abstracts are the most easily accessed portion of journal articles, yet little is known about their quality. The authors examined the extent to which abstracts of published CEAs include key data elements (intervention, comparator, target population, study perspective) and assessed the effect of journal characteristics on reporting quality. Systematic review of the English-language medical literature from 1998 through 2001. The authors searched MEDLINE for original CEAs reported in costs per quality-adjusted life years(i.e., cost-utility analyses). Two independent readers abstracted data elements and met to resolve discrepancies. Among the 303 abstracts reviewed, a clear description of the intervention was present in 94%, comparator in 71%, target population in 85%, and study perspective in 28%. All 4 data elements were reported in 20% of abstracts, 3 elements in 49%, 2 in 22%, and 0 or 1 in 9%. In journals with CEA-specific abstract reporting requirements, structured abstract requirements, or impact factors>or=10, significantly more data were included in abstracts than in journals without these features (P<0.01 for all comparisons). Abstracts of published CEAs frequently omit data elements critical to proper study interpretation. An explicit core set of reporting standards is needed, based on the standards by the US Public Health Service's Panel on Cost-Effectiveness for reporting of CEAs, but specific to the accompanying abstracts.

An Overview of Economic Evaluations for Drugs Used in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease that affects approximately 0.5-1% of the adult population. The introduction of new disease-modifying antirheumatic drugs (DMARDs) such as leflunomide, anakinra and the tumour necrosis factor (TNF)-alpha antagonists (infliximab, etanercept and adalimumab) have transformed the management of RA. In particular, the last class of agents has generated substantial controversy. Costing between 16,000 US dollars and 20,000 US dollars per patient-year (2001 values), the potential greater efficacy of treatment with TNFalpha antagonists comes at much higher drug costs, making these agents natural candidates for cost-effectiveness analyses (CEAs).A MEDLINE search (until 31 January 2004) identified six original CEAs evaluating TNFalpha antagonists in RA. The aim of a CEA is to facilitate the allocation of scarce health resources and to inform policy decisions. However, to enhance the reliability and relevance of these analyses to policy makers, there must be similarity between the methodologies used. Recently, the OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) group produced a document to define such a reference case; the OMERACT document was used as a foundation to structure comparisons and highlight discrepancies. The methodologies employed in each analysis differed; in particular, disparate time horizons, comparators, quantities of drug and treatment sequences prohibit the comparison of cost effectiveness between studies. Outcomes also differed between the analyses. Most reported health-related quality of life (HR-QOL) in quality-adjusted life-years (QALYs). The QALYs metric was based on preference scores that were typically derived from linear regressions using the Health Assessment Questionnaire (HAQ). However, models also used American College of Rheumatology (ACR) criteria, as well as the disease activity score (DAS). Common to all studies was the lack of data from long-term randomised studies where efficacy and resource consumption in comparison with standard care has been investigated. As such, investigators combined short-term randomised control trial data with that of a long-term observational cohort, and modelled cost effectiveness over an appropriate time horizon. In addition, most analyses lacked rigorous sensitivity analysis to examine the impact of uncertainty in the parameters. Those analyses that examined time horizons of 6 months and 1 year published incremental cost-effectiveness ratios (ICERs) of 34,800 US dollars per ACR 70% response criteria (ACR70) weighted response (duration 6 months, 1999 values) and 96,166 US dollars (duration 1 year, 2002 values). Analyses that modelled costs and health outcomes beyond the first year reported ICER estimates ranging between 26,800 US dollars (patients' lifetime, 1998 values) and 40,308 US dollars (10 years, 2002 values). In terms of HR-QOL, the analyses reported incremental QALYs that ranged from 0.116 (over 19 years) to 1.6 (over 10 years). Discounted costs of therapy ranged from 30,362 US dollars (10 years, 2002 values) to 93,000 US dollars (22 years, 1998 values), and comparator costs ranged from 22,593 US dollars (10 years, 2002 values) to 84,000 US dollars (22 years, 1998 values).

A review of cost-effectiveness analyses in rheumatology and related disciplines.

A MEDLINE search of the 1996 and 1997 literature yielded two reviews of the methodology of cost-effectiveness analyses (CEAs) in the field of rheumatology and eight original CEAs evaluating slow-acting antirheumatic agents (two studies), total hip arthroplasty for patients with osteoarthritis (one study), educational intervention for patients with fibromyalgia (one study), interventions for patients with low back pain (three studies), and hormone replacement therapy for women with osteoporosis (one study). Most CEAs relied on modelling of data that were assembled from various sources; however, in one CEA a cost-effectiveness comparison was based on data collected prospectively within a randomized clinical trial. Extensive sensitivity analyses were conducted by a majority of the studies. The CEAs of slow-acting antirheumatic agents provided results that were difficult to interpret given extensive modelling and reliance on expert estimates. Only one CEA was supported by an industry grant. Most of the studies were of high quality and met current methodologic requirements, including the use of discounting, sensitivity analysis, and incremental analysis. However, the major shortcoming of these recent studies continues to be the use of estimated costs instead of prospectively measured resource utilization data presented in terms of separate physical units.

Are methods for estimating QALYs in cost-effectiveness analyses improving?

The objectives of this study were to examine variations in the methods used by researchers to estimate QALYs in published cost-effectiveness analyses, and to investigate whether the methods have improved over time. Using a MEDLINE search, the authors identified 86 original cost-effectiveness analyses, published between 1975 and 1995, that used QALYs as the measure of effectiveness. For each study, they recorded the health-state classification system, the source of the preference weights, the measurement technique, and the discount rate. The methods used were compared with the recommendations of the U.S. Panel on Cost-Effectiveness in Health and Medicine. Only 20% of the studies used "generic" health-state classification systems (e.g., health utilities index); 21% relied on community-based weights; 40% used formal measurement techniques (e.g., time-tradeoff method); and 88% discounted both future costs and QALYs. There was little evidence that methods had improved over time. The results illustrate extensive variation in the construction of QALYs in cost-effectiveness analyses and reveal that most studies have not adhered to practices now recommended by leaders in the field. There is a need for more methodologic rigor and consistency if the results of such studies are to be compared and used for purposes of allocating resources.