Andrea Manca

Increasing the generalizability of economic evaluations: recommendations for the design, analysis, and reporting of studies.

OBJECTIVES Health technology assessment (HTA) is increasingly an international activity, and HTA agencies collaborate to avoid unnecessary duplication of effort. However, the sharing of the results from HTAs raises questions about their generalizability; namely, are the results of an HTA undertaken in one country relevant to another? METHODS This study presents recommendations for increasing the generalizability of economic evaluations. They represent an important component of HTAs and are commonly thought to have limited generalizability. RESULTS Recommendations are given for studies using patient-level data (i.e., evaluations conducted alongside clinical trials) and for studies using decision analytic modeling. CONCLUSIONS If implemented, the recommendations would increase the value for investments in HTA.

Quality of life, resource consumption and costs of spinal cord stimulation versus conventional medical management in neuropathic pain patients with failed back surgery syndrome (PROCESS trial)

Background: Chronic back and leg pain conditions result in patients’ loss of function, reduced quality of life and increased costs to the society.

Cost effectiveness of clinically appropriate decisions on alternative treatments for angina pectoris: prospective observational study

Objective To assess whether revascularisation that is considered to be clinically appropriate is also cost effective. Design Prospective observational study comparing cost effectiveness of coronary artery bypass grafting, percutaneous coronary intervention, or medical management within groups of patients rated as appropriate for revascularisation. Setting Three tertiary care centres in London. Participants Consecutive, unselected patients rated as clinically appropriate (using a nine member Delphi panel) to receive coronary artery bypass grafting only (n=815); percutaneous coronary intervention only (n=385); or both revascularisation procedures (n=520). Main outcome measure Cost per quality adjusted life year gained over six year follow-up, calculated with a National Health Service cost perspective and discounted at 3.5%/year. Results Coronary artery bypass grafting cost �22 000 (€33 000;

A substantial and confusing variation exists in handling of baseline covariates in randomized controlled trials: a review of trials published in leading medical journals.

43 000) per quality adjusted life year gained compared with percutaneous coronary intervention among patients appropriate for coronary artery bypass grafting only (59% probability of being cost effective at a cost effectiveness threshold of �30 000 per quality adjusted life year) and �19 000 per quality adjusted life year gained compared with medical management among those appropriate for both types of revascularisation (probability of being cost effective 63%). In none of the three appropriateness groups was percutaneous coronary intervention cost effective at a threshold of �30 000 per quality adjusted life year. Among patients rated appropriate for percutaneous coronary intervention only, the cost per quality adjusted life year gained for percutaneous coronary intervention compared with medical management was �47 000, exceeding usual cost effectiveness thresholds; in these patients, medical management was most likely to be cost effective (probability 54%). Conclusions Among patients judged clinically appropriate for coronary revascularisation, coronary artery bypass grafting seemed cost effective but percutaneous coronary intervention did not. Cost effectiveness analysis based on observational data suggests that the clinical benefit of percutaneous coronary intervention may not be sufficient to justify its cost.

Transferability of economic evaluations : approaches and factors to consider when using results from one geographic area for another

OBJECTIVE Statisticians have criticized the use of significance testing to compare the distribution of baseline covariates between treatment groups in randomized controlled trials (RCTs). Furthermore, some have advocated for the use of regression adjustment to estimate the effect of treatment after adjusting for potential imbalances in prognostically important baseline covariates between treatment groups. STUDY DESIGN AND SETTING We examined 114 RCTs published in the New England Journal of Medicine, the Journal of the American Medical Association, The Lancet, and the British Medical Journal between January 1, 2007 and June 30, 2007. RESULTS Significance testing was used to compare baseline characteristics between treatment arms in 38% of the studies. The practice was very rare in British journals and more common in the U.S. journals. In 29% of the studies, the primary outcome was continuous, whereas in 65% of the studies, the primary outcome was either dichotomous or time-to-event in nature. Adjustment for baseline covariates was reported when estimating the treatment effect in 34% of the studies. CONCLUSIONS Our findings suggest the need for greater editorial consistency across journals in the reporting of RCTs. Furthermore, there is a need for greater debate about the relative merits of unadjusted vs. adjusted estimates of treatment effect.

The health-related quality of life and cost implications of falls in elderly women

ABSTRACT Background: Geographic transferability of economic evaluation data from one country to another has the potential to make a more efficient use of national and international evaluation resources. However, inappropriate transferability of economic data can provide misleading results and lead to an inefficient use of scarce health care resources. Objectives: The objective of this study was to review, summarize and categorize the literature on: (i) factors affecting the geographic transferability of economic evaluation data; and (ii) approaches which have either been proposed or used for transferability. Methods: A systematic literature review on transferability was conducted. Electronic databases, hand searching and bibliographic searching techniques were utilized. Inclusion criteria for the review included conceptual or empirical papers with mention of factors affecting, or approaches for, transferability of economic evaluation data across geographic locations. Exclusion criteria included papers published prior to 1966, non-English language papers, pure science studies and animal studies. Three databases were involved in the primary search: Ovid MEDLINE, EMBASE, and CINAHL. In addition to the primary search, the Heath Economic Evaluation Database (OHE HEED), the NHS EED database and the EconLit databases were searched. Transferability factors were classified into major and minor categories, a classification of alternative transferability approaches was developed, and the number of empirical studies was catalogued according to this classification. Results: There is a substantial amount of literature on factors potentially affecting transferability. Based on these papers we identified 77 factors and subsequently developed a classification system which grouped these factors into five broad categories based on characteristics of the patient, the disease, the provider, the health care system and methodological conventions. Another 40 studies were identified which attempted to transfer economic evaluation data from one country to another and these were classified according to the sources for clinical efficacy, resource utilization and unit cost data. Conclusions: There is strong evidence indicating that transferability of economic evaluation data is a difficult and complex task. Approaches which have been used for transferability suggest that, at a minimum, there is a need for country-specific substitution of practice pattern data as well as unit cost data. A limitation of this review relates to the lack of empirical studies which prevents stronger conclusions regarding which transferability factors are most important to consider and under which circumstances.

A cost–utility analysis of tension-free vaginal tape versus colposuspension for primary urodynamic stress incontinence

SummaryFractures and falls are serious cause of morbidity and cost to society. Our results suggest that the main burden to morbidity, measured as impact on health-related quality of life, is due to fear of falling rather than falls or their sequelae, such as fractures.IntroductionFractures and falls are serious cause of morbidity and cost to society. We investigated the impact on health-related quality of life (HRQoL) associated with falls, fractures and fear of falling and falls and fractures cost.MethodsThree datasets providing longitudinal data on fear of falling, HRQoL and a common set of baseline risk factors for fracture (smoking status, weight and age) were analysed. Multilevel random effects models were used to estimate the long-term impact on HRQoL associated with falls, fractures and fear of falling. Healthcare resource use primary data were collected to estimate falls and fractures cost.ResultsOlder, low weight and smoking women reported lower HRQoL. The impact on HRQoL of a fracture was at least twice as large as that associated with falls. The largest negative effect on HRQoL was associated with self-reported fear of falling. The cost of falls was £1088. Similarly, the cost of falls leading to a fracture was £15,133, £2,753, £1,863, £1,331 and £3,498 for hip, wrist, arm, vertebral and other fractures, respectively.DiscussionThe main burden to morbidity is due to fear of falling. Interventions aimed at reducing fear of falling may produce larger gains in HRQoL.

Regression Estimators for Generic Health-Related Quality of Life and Quality-Adjusted Life Years

Objective To assess the cost effectiveness of tension‐free vaginal tape compared with open Burch colposuspension as a primary treatment for urodynamic stress incontinence.

Handling missing data in patient-level cost-effectiveness analysis alongside randomised clinical trials.

Purpose. To develop regression models for outcomes with truncated supports, such as health-related quality of life (HRQoL) data, and account for features typical of such data such as a skewed distribution, spikes at 1 or 0, and heteroskedasticity. Methods. Regression estimators based on features of the Beta distribution. First, both a single equation and a 2-part model are presented, along with estimation algorithms based on maximum-likelihood, quasi-likelihood, and Bayesian Markov-chain Monte Carlo methods. A novel Bayesian quasi-likelihood estimator is proposed. Second, a simulation exercise is presented to assess the performance of the proposed estimators against ordinary least squares (OLS) regression for a variety of HRQoL distributions that are encountered in practice. Finally, the performance of the proposed estimators is assessed by using them to quantify the treatment effect on QALYs in the EVALUATE hysterectomy trial. Overall model fit is studied using several goodness-of-fit tests such as Pearson’s correlation test, link and reset tests, and a modified Hosmer-Lemeshow test. Results. The simulation results indicate that the proposed methods are more robust in estimating covariate effects than OLS, especially when the effects are large or the HRQoL distribution has a large spike at 1. Quasi-likelihood techniques are more robust than maximum likelihood estimators. When applied to the EVALUATE trial, all but the maximum likelihood estimators produce unbiased estimates of the treatment effect. Conclusion. One and 2-part Beta regression models provide flexible approaches to regress the outcomes with truncated supports, such as HRQoL, on covariates, after accounting for many idiosyncratic features of the outcomes distribution. This work will provide applied researchers with a practical set of tools to model outcomes in cost-effectiveness analysis.

“Lost in translation”: accounting for between-country differences in the analysis of multinational cost-effectiveness data

BackgroundMissing data are potentially an extensive problem in cost-effectiveness analyses conducted alongside randomised clinical trials, where prospective collection of both resource use and health outcome information is required. There are several possible reasons for the presence of incomplete records, and the validity of the analysis in the presence of data with missing values is dependent upon the mechanism generating the missing data phenomenon. In the past, the most commonly used methods for analysing datasets with incomplete observations were relatively ad hoc (e.g. case deletion, mean imputation) and suffered from potential limitations. Recently, several alternative and more sophisticated approaches (e.g. multiple imputation) have been proposed that attempt to correct the flaws of the simple imputation methods.ObjectivesThe objectives are to provide a concise and accessible description of the quantitative methods most commonly used in trial-based cost-effectiveness analysis for handling missing data, and also to demonstrate the potential impact of these alternative approaches on the cost-effectiveness results reported in two case studies.MethodsData from two recently conducted, trial-based economic evaluations are used to explore the sensitivity of the study results to the technique used to deal with incomplete observations. A statistical framework for representing the uncertainty in the alternative methods is outlined using an approach based on net benefits and cost-effectiveness acceptability curves.ResultsThe case studies demonstrate the potential importance of the approach used to handle missing data. Although the analytical strategy did not appear to alter the results of one of the studies, the other case study showed that that the results of the cost-effectiveness analysis were sensitive to both the decision to impute and also the imputation strategy adopted.ConclusionsAnalysts should be more explicit in reporting the analytical strategies applied in the presence of missing data. The use of a multiple imputation approach is recommended in the majority of cases, so as to adequately reflect the uncertainty in the study results due to the presence of missing data.