Objectives: For an efficient and fair allocation of medical resources, one must know which patients benefit more from medical care. The objective of this study is to assess the differential survival benefits of a general intensive care unit (ICU) by acute diagnoses and by Acute Physiological and Chronic Health Evaluation (APACHE II) scores.

Methods: The sample included all patients triaged for admission to the Hadassah-Hebrew University Medical Center ICU during a 7-month period (n = 381). The potential effect of ICU on in-hospital survival was estimated by a bivariate (admission–survival) probit model, using crowding in the unit as the identifying variable, controlling for observable patients characteristics: age, sex, acute diagnoses, and APACHE II score. Using the estimates, the differential predicted survival benefits of ICU were calculated for selected general acute diagnoses and for different APACHE II scores.

Results: Adjusting for age, sex, and general acute diagnoses, the average potential survival benefit of ICU is 17 percentage points (pts). The benefit of ICU for patients with central nervous system problems, with sepsis, or with respiratory failure are higher than average (23 pts). Adjusting for APACHE II scores as well increases the estimated average potential benefit to 21 pts. Over the range of APACHE II scores, the highest benefit (38 pts of potential benefit) is attained for patients with scores around 22.

Conclusions: Survival benefits differ across diagnoses and APACHE II scores. Facing limited resources, admission policies should distinguish between survival probabilities (and survival maximization) and survival benefits (and maximization of ICU benefits). Actual referral and admission policies to the present ICU do not maximize the potential survival benefits of ICU resources.

The use of economic evaluation in decision making appears to have increased over the past few years and economic evaluation is looked upon as another measure to help contain costs and improve efficiency in an evidence-based decision-making environment. Following the examples of Australia and the Canadian Province of Ontario, four European Union (EU) countries (Finland, the Netherlands, Portugal, and the United Kingdom) have recently introduced economic evaluation guidelines. In addition to the Australian and Canadian guidelines, which constitute a hurdle to reimbursement, the paradigm that seems to be evolving in the four EU countries follows a similar route. Finland and the Netherlands seem to be moving toward the notion of a fourth hurdle to reimbursement, whereas the National Institute for Clinical Excellence in England and Wales was in principle meant to influence practice, although in reality this essentially acts as a hurdle to reimbursement, requiring a different data set to that used by regulatory authorities. Whereas the Portuguese guidelines were developed to assist in preparing economic submissions to support reimbursement decisions, they are unclear about when such evidence will be required and also discuss the dissemination of economic evidence to broader audiences. The introduction of these guidelines poses a number of challenges to policy makers, the implications of which are analyzed in the paper: a) to ensure that economic evaluations are carried out scientifically without industrial or political bias; b) to define an acceptable methodology that would increase their credibility; and c) to address certain practical issues ranging from deciding how to use economic evaluations in policy making to setting up new institutions or improving the coordination and dissemination of evidence. The variation in the use of economic evaluation guidelines in the four EU countries highlights the differences in national pharmaceutical policies and is in line with policy makers' continuous attempts to contain costs. While the paper critically discusses the guidelines, it also points out that a series of methodologic issues need to be addressed if economic criteria are to be introduced in policy making with the aim to improve resource allocation. The paper concludes that economic evaluation as a discipline is beginning to impact on policy, whereas the consistent use of economic evaluation results is, in principle, being adopted by policy makers but needs to go a step further to reach practitioners.

Objectives: To develop and evaluate strategies for estimating hospitalization costs in multinational clinical trials.

Methods: Hospital cost estimates for eleven diagnoses were collected from twelve countries participating in a trial of therapies for congestive heart failure. Estimates were combined with U.S.-based diagnosis-related group weights to compute country-specific unit cost estimates for all reasons for hospitalization. Variations of hospital costing methods were developed. The unit cost method assigns a country-specific unit cost estimate to each hospitalization. The other methods adjust for length of stay using a daily cost (DC) estimate for each diagnosis, based on either the mean length of stay (DC-mean method) or the median length of stay (DC-median method) for each diagnosis in each country. Additional modifications were explored through adjustment of the distribution of daily costs incurred during a hospital stay.

Results: The mean cost for all hospitalizations was $10,242 (SD, 10,042) using the unit cost method, $10,242 (SD, 12,760) using the standard DC-mean method, and $13,967 (SD, 18,762) using the standard DC-median method. In comparisons of costs for all 5,486 hospitalizations incurred by a subset of 2,352 patients in the trial, the unit cost method provided 92% power to detect a $1,000 cost difference. The standard DC-mean method provided 76% power, and the standard DC-median method provided 44% power.

Conclusions: Hospital costing methods that adjust for differences in length of stay require a significantly larger sample to attain comparable statistical power as methods that assign unadjusted unit cost estimates to hospitalization events.

Background: The Centre for Reviews and Dissemination (CRD) funded through the United Kingdom National Institute for Health Research undertakes systematic reviews evaluating the research evidence on health and public health questions of national and international importance. CRD is involved in methods research and produces internationally accepted guidelines for undertaking systematic reviews. A core product of the Centre are the CRD databases; a key resource for health professionals, policy makers, and researchers around the world. Research evidence evaluating the effects and cost-effectiveness of healthcare interventions is growing year on year, and can be difficult and time consuming to identify and appraise. The databases assist decision makers by systematically identifying and critically describing systematic reviews and economic evaluations, appraising their quality and highlighting their relative strengths and weaknesses; and providing a comprehensive listing of ongoing and published health technology assessments.

Methods and Results: This article briefly outlines the processes behind each of the three databases, gives details of the records, the information they contain and the value added by CRD. An overview of the new public interface for the CRD databases to be launched later this year is given. Improvements and innovations to supplement existing functions are listed, including enhanced and new search options, the addition of quick links to relevant material from within individual records, an integrated PubMed search and the ability to select personal preferences.

Conclusions: CRD's databases provide free access to an important knowledge base and are used widely to underpin evidence informed healthcare decisions in the United Kingdom and internationally.

Objectives: This study estimates the cost-effectiveness (CE) of the adjunctive use of hyperbaric oxygen (HBO2) therapy in the treatment of diabetic ulcers based on the payer's and societal perspectives.

Methods: The study population was a hypothetical cohort of 1,000 patients sixty years of age with severe diabetic foot ulcers. A decision tree model was constructed to estimate the CE of HBO2 therapy in the treatment of diabetic ulcers at years 1, 5, and 12. Scenario and one-way sensitivity analyses were also undertaken to identify parameters that may significantly influence the estimates.

Results: The CE model estimated that the incremental cost per additional quality-adjusted life year (QALY) gained at years 1, 5, and 12, was $27,310, $5,166, and $2,255, respectively.

Conclusions: The study results indicate that HBO2 therapy in the treatment of diabetic ulcers is cost-effective, particularly based on a long-term perspective. However, the results are limited by the clinical studies that provide the basis of the CE estimation.

An economic evaluation of energy-absorbing flooring designed to prevent hip fractures revealed a payback period of 10½ years if only direct costs avoided were evaluated and just over 11 months when direct and indirect costs were included. Cost-effectiveness ratios of less than $0 per hip fracture prevented and life year saved were also estimated.

Objectives: The aim of this study was to estimate the expected cost and clinical benefits associated with the use of drotrecogin alfa (activated) (Xigris; Eli Lilly and Company; Indianapolis, IN) in the French hospital setting.

Methods: The recombinant human activated PROtein C Worldwide Evaluation in Severe Sepsis (PROWESS) study results (1,271 patients with multiple organ failure) were adjusted to 9,948 hospital stays from a database of Parisian area intensive-care units (ICUs)—the CubRea (Intensive Care Database User Group) database. The analysis features a decision tree with a probabilistic sensitivity analysis.

Results: The cost per life year gained (LYG) of drotrecogin treatment for severe sepsis with multiple organ failure (European indication) was estimated to be $11,812. At the hospital level, the drug is expected to induce an additional cost of $7,545 per treated patient. The incremental cost-effectiveness ratio ranges from $7,873 per LYG for patients receiving three organ supports during ICU stay to $17,704 per LYG for patients receiving less than two organ supports.

Conclusions: Drotrecogin alfa (activated) is cost-effective in the treatment of severe sepsis with multiple organ failure when added to best standard care. The cost-effectiveness of the drug increases with baseline disease severity, but it remains cost-effective for all patients when used in compliance with the European approved indication.

This analysis describes the development of technology for home self-infusion of factor VIII in the treatment of hemophilia and its clinical, economic, and social consequences, and uses the case study of such home care treatment to illustrate the potentials and pitfalls of formal economic analyses of programs to treat chronically ill children. A comprehensive review of all original data on hemophilia programs, their related costs, and outcomes, conducted from 1966 through 1993, examined the economic outcomes for two hypothetical cohorts, one aged 0–4 years and the other aged 30–34 years. Including the measurement of treatment effects on the productivity of parental caregivers substantially increases the benefit-cost relationship of an intervention directed at chronically ill children. Increased economic productivity and societal return resulting from such a program for young adults exceeds those for a cohort of children, primarily due to assumptions related to discounting. However, estimation of quality-adjusted life years favors the younger age cohort, since children survive for a longer period of time and with each year survived comes a higher quality of life. Unlike simpler instances in which economic benefits can be shown to outweigh resource costs, policy decisions concerning services for chronically ill children raise an additional set of complex analytic issues. Inclusion of the benefits in productivity experienced by family caregivers provides an important added dimension to such analyses. The development of cost-benefit or cost-effectiveness analyses of these programs illustrates the importance of careful measurement of outcomes and explicit statements of underlying assumptions. Such an analysis of home care for children with hemophilia therefore demonstrates both the strengths and the limitations of this approach.

Objectives: Ongoing developments in design have improved the outlook for left-ventricular assist device (LVAD) implantation as a therapy in end-stage heart failure. Nevertheless, early cost-effectiveness assessments, based on first-generation devices, have not been encouraging. Against this background, we set out (i) to examine the survival benefit that LVADs would need to generate before they could be deemed cost-effective; (ii) to provide insight into the likelihood that this benefit will be achieved; and (iii) from the perspective of a healthcare provider, to assess the value of discovering the actual size of this benefit by means of a Bayesian value of information analysis.

Methods: Cost-effectiveness assessments are made from the perspective of the healthcare provider, using current UK norms for the value of a quality-adjusted life-year (QALY). The treatment model is grounded in published analyses of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial of first-generation LVADs, translated into a UK cost setting. The prospects for patient survival with second-generation devices is assessed using Bayesian prior distributions, elicited from a group of leading clinicians in the field.

Results: Using established thresholds, cost-effectiveness probabilities under these priors are found to be low (∼.2 percent) for devices costing as much as £60,000. Sensitivity of the conclusions to both device cost and QALY valuation is examined.

Conclusions: In the event that the price of the device in use would reduce to £40,000, the value of the survival information can readily justify investment in further trials.

Objectives: This article examines the challenges for health technology assessment (HTA) in the light of new developments of personalized health care, focusing on European HTA perspectives.

Methods: Using the example of the Integrated Genome Research Network – Mutanom (IG Mutanom) project, with focus on personalized cancer diagnostics and treatment, we assess the scope of current HTA and examine it prospectively in the context of the translation of basic and clinical research into public health genomics and personalized health care.

Results: The approaches developed within the IG-Mutanom project are based on innovative technology potentially providing targeted therapies for cancer; making translation into clinical practice requires a novel course of action, however. New models of HTA are needed that can account for the unique types of evidence inherent to individualized targeted therapies. Using constructive health technology assessment (CTA) models is an option, but further suitable models should be developed.

Conclusions: Integrative, systems biology-based approaches toward personalized medicine call for novel assessment methods. The translation of their highly innovative technologies into the practice of health care requires the development of new HTA concepts.

Objectives: Treatment switching refers to the situation in a randomized controlled trial where patients switch from their randomly assigned treatment onto an alternative. Often, switching is from the control group onto the experimental treatment. In this instance, a standard intention-to-treat analysis does not identify the true comparative effectiveness of the treatments under investigation. We aim to describe statistical methods for adjusting for treatment switching in a comprehensible way for nonstatisticians, and to summarize views on these methods expressed by stakeholders at the 2014 Adelaide International Workshop on Treatment Switching in Clinical Trials.

Methods: We describe three statistical methods used to adjust for treatment switching: marginal structural models, two-stage adjustment, and rank preserving structural failure time models. We draw upon discussion heard at the Adelaide International Workshop to explore the views of stakeholders on the acceptability of these methods.

Results: Stakeholders noted that adjustment methods are based on assumptions, the validity of which may often be questionable. There was disagreement on the acceptability of adjustment methods, but consensus that when these are used, they should be justified rigorously. The utility of adjustment methods depends upon the decision being made and the processes used by the decision-maker.

Conclusions: Treatment switching makes estimating the true comparative effect of a new treatment challenging. However, many decision-makers have reservations with adjustment methods. These, and how they affect the utility of adjustment methods, require further exploration. Further technical work is required to develop adjustment methods to meet real world needs, to enhance their acceptability to decision-makers.

The differential staining cytotoxicity (DiSC) assay involves in vitro drug panel testing against patient tumor cells to identify optimal therapy. This observational study investigated whether DiSC assay guided treatment could improve outcome in patients with chronic lymphocytic leukemia. A cohort of 178 patients were categorized either as sensitive to drugs in vitro and receiving a sensitive drug in vivo, sensitive in vitro but not treated with a sensitive drug, or having disease resistant to all drugs tested in vitro. Response and survival for these patient categories were compared using multivariate regression techniques. Patients receiving a sensitive drug, compared with those who though having sensitivity did not, had a higher remission rate (odds ratio, 6.5; 95% CI, 2.91–14.53) and reduced death rate (hazard ratio, 0.29; 95% CI, 0.16–0.53). Having adjusted for all known confounding factors, the results suggest that in vitro drug sensitivity is an important independent prognostic variable to include in future trials, and that the DiSC assay may be a cost-effective use of health resources: the estimated incremental cost-effectiveness was £1,470 per life-year gained. A randomized controlled trial is required to confirm the benefit and estimate reliably the potential impact of assay-guided choice of therapy.

Objectives: This paper explores the use of evidence, focusing on economic evidence in particular, in the development of local health policies through an in-depth study of Health Improvement Programmes (HImPs) in England.

Methods: A questionnaire was sent to the person responsible for coordinating the development of the HImP in each of the 102 English health authorities. In addition, semi-structured interviews were conducted with 10 HImP leaders, and a random sample of 26 HImP documents was reviewed using a standard pro forma.

Results: Of the 102 mail questionnaires sent out, 68 (67%) were returned. It was found that those developing HImPs had multiple objectives, only some of which (e.g., efficiency in healthcare provision) would necessarily require evidence. Where evidence was used, this was a mixture of internal (experiential) and external (empirical) evidence, with the balance (66%) being in favor of the latter. Government reports and guidance from the National Institute for Clinical Excellence (NICE), were the main sources of external evidence, rather than published papers. Key barriers to the use of economic evidence were lack of time and availability and the difficulties in synthesizing information at the local level.

Conclusions: Based on responses to our survey, the main ways of increasing the use of evidence in the development of local health policies in England are to produce more evidence-based national guidance and to produce accessible summaries of the available literature for local decision makers.

Objectives: Hospital readmission rate is currently used as a quality of care indicator, although its validity has not been established. Our aims were to identify the frequency and characteristics of potential avoidable readmissions and to compare the assessment of quality of care derived from readmission rate with other measure of quality (judgment of experts).

Methods: Design: cross-sectional observational study; Setting: acute care hospital located in Marbella, South of Spain; Study participants: random sample of patients readmitted at the hospital within six months from discharge (n=363); Interventions: review of clinical records by a pair of observers to assess the causes of readmissions and their potential avoidability; Main measures: logistic regression analysis to identify the variables from the databases of hospital discharges which are related to avoidability of readmissions. Determination of sensitivity and specificity of different definitions of readmission rate to detect avoidable situations.

Results: Nineteen percent of readmissions were considered potentially avoidable. Variables related to readmission avoidability were (i) time elapsed between index admission and readmission and (ii) difference in diagnoses of both episodes. None of the definitions of readmission rate used in this study provided adequate values of sensitivity and specificity in the identification of potentially avoidable readmissions.

Conclusions: Most readmissions in our hospital were unavoidable. Thus, readmission rate might not be considered a valid indicator of quality of care.

Objectives: An overview was produced of indicators currently used to assess disease management programs and, based on these findings, provide a framework regarding sets of indicators that should be used when taking the aims and types of disease management programs into account.

Methods: A systematic literature review was performed.

Results: Thirty-six studies met the inclusion criteria. It appeared that a link between aims of disease management and evaluated structure, process, as well as outcome indicators does not exist in a substantial part of published studies on disease management of diabetes and asthma/chronic obstructive pulmonary disease, especially when efficiency of care is concerned. Furthermore, structure indicators are largely missing from the evaluations, although these are of major importance for the interpretation of outcomes for purposes of decision-making. Efficiency of disease management is mainly evaluated by means of process indicators; the use of outcome indicators is less common. Within a framework, structure, process, and outcome indicators for effectiveness and efficiency are recommended for each type of disease management program.

Conclusions: The link between aims of disease management and evaluated structure, process, and outcome indicators does not exist in a substantial part of published studies on disease management. The added value of this study mainly lies in the development of a framework to guide the choice of indicators for health technology assessment of disease management.

Objective: The Israeli National Health Insurance Law stipulates a National List of Health Services (NLHS) to which all residents are entitled from their HMOs. This list has been updated annually for almost a decade using a structured review and decision-making process. Although this process has been described in detail in previous papers, none of these have fully addressed legitimacy and fairness. We examine the legitimacy and fairness of the process of updating the NLHS in Israel.

Methods: We assessed the priority-setting process for compliance with the four conditions of accountability for reasonableness outlined by Daniels and Sabin (relevance, publicity, appeals, and enforcement). These conditions emphasize transparency and stakeholder engagement in democratic deliberation.

Results: Our analysis suggests that the Israeli process for updating the NLHS does not fulfill the appeals and enforcement conditions, and only partially follows the publicity and relevance conditions, outlined in the accountability for reasonableness framework. The main obstacles for achieving these goals may relate to the large number of technologies assessed each year within a short time frame, the lack of personnel engaged in health technology assessment, and the desire for early adoption of new technologies.

Conclusions: The process of updating the NLHS in Israel is unique and not without merit. Changes in the priority-setting process should be made to increase its acceptability among the different stakeholders.

A decision analysis was performed to assess the risks, costs, and effects of no prophylaxis, oral penicillin, and cephalexin regimens currently being debated for dental patients at risk for late prosthetic joint infection (LPJI). The analysis suggests that there is a very small risk of LPJI (29.3 cases per 106 dental visits), which is outweighed by a greater risk of death with an oral penicillin strategy than with a “no prophylaxis” strategy (2.31:1.93). An oral cephalosporin appears to spare life and limb but does so at an extremely high cost. Over $500,000 must be spent to spare one year of life, while $480,000 needs to be spent to prevent one case of LPJI. Some individual dental patients may still be at a much greater risk for LPJI than others. However, from the evidence to date, routine predental antibiotic prophylaxis for all prosthetic joint patients is a very expensive preventive strategy and is not cost-effective. However, clinical experience suggests that antibiotic prophylaxis may be appropriate in some situations.

Objectives: To describe the development and application of health technology assessment (HTA) in Australia.

Methods: Review of relevant literature and other documents related to HTA in Australia.

Results: Most HTA activity in Australia has been associated with provision of advice for the two national subsidy programs, Medicare, and the Pharmaceutical Benefits Scheme (PBS). National advisory bodies established by the federal government have had a prominent role. Assessments from the advisory bodies have had a major influence on decisions related to Medicare and the PBS, and in some other areas. Technologies without links to the national subsidy schemes, and those that are widely distributed, have been less well covered by HTA. To some extent these are addressed by evaluations supported by state governments, but details of approaches taken are not readily available.

Conclusions: HTA in Australia now has a long history and is well established as a source of advice to health decision makers. Challenges remain in extending the scope of assessments, developing more transparent approaches in some areas, and consistently applying appropriate standards.

Objectives: The aim of this study is to examine the cost-effectiveness of a group-based peer support intervention in general practice for patients with type 2 diabetes.

Methods: Incremental cost utility analysis combining within trial and beyond trial components to compare the lifetime costs and benefits of alternative strategies: Control: standardized diabetes care; Intervention: group-based peer support in addition to standardized diabetes care. Within trial analysis was based on a cluster randomized controlled trial of 395 patients with type 2 diabetes in the east of Ireland. Beyond trial analysis was conducted using the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model. Uncertainty was explored using a range of sensitivity analyses and cost-effectiveness acceptability curves were generated.

Results: Compared with the control strategy, the intervention was associated with an increase of 0.09 (95 percent confidence interval [CI], −0.05 to 0.25) in mean quality-adjusted life-years per patient and savings of €637.43 (95 percent CI, −2455.19 to 1125.45) in mean healthcare cost per patient and €623.39 (95 percent CI, −2507.98 to 1298.49) in mean total cost per patient respectively. The likelihood of the intervention being cost-effective was appreciably higher than 80 percent for a range of potential willingness-to-pay cost-effectiveness thresholds.

Conclusions: Our results suggest that while a group-based peer support intervention shows a trend toward improved risk factor management, we found no significant differences in final cost or effectiveness endpoints between intervention and control. The probabilistic results suggest that the intervention was more cost-effective, with probability values of higher than 80 percent across a range of potential cost-effectiveness threshold values.