Background: Many jurisdictions delivering health care, including Canada, have developed guidance for conducting economic evaluation, often in the service of larger health technology assessment (HTA) and reimbursement processes. Like any health intervention, personalized medical (PM) interventions have costs and consequences that must be considered by reimbursement authorities with limited resources. However, current approaches to economic evaluation to support decision making have been largely developed from population-based approaches to therapy—that is, evaluating the costs and consequences of single interventions across single populations. This raises the issue as to whether these methods, as they are or more refined, are adequate to address more targeted approaches to therapy, or whether a new paradigm for assessing value in PM is required.

Objectives: We describe specific issues relevant to the economic evaluation of diagnostics-based PM and assess whether current guidance for economic evaluation is sufficient to support decision making for PM interventions.

Methods: Issues were identified through literature review and informal interviews with national and international experts (n = 10) in these analyses. This article elaborates on findings and discussion at a workshop held in Ottawa, Canada, in January 2012.

Results: Specific issues related to better guiding economic evaluation of personalized medicine interventions include: how study questions are developed, populations are characterized, comparators are defined, effectiveness is evaluated, outcomes are valued and how resources are measured. Diagnostics-based PM also highlights the need for analyses outside of economic evaluation to support decision making.

Conclusions: The consensus of this group of experts is that the economic evaluation of diagnostics-based PM may not require a new paradigm. However, greater complexity means that existing approaches and tools may require improvement to undertake these more analyses.

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.

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 was to assess the cost-effectiveness of a class-based exercise program supplementing a home-based program when compared with a home-based program alone. In addition, we estimated the probability that the supplementary class program is cost-effective over a range of values of a decision maker's willingness to pay for an additional quality-adjusted life-year (QALY).

Methods: The resource use and effectiveness data were collected as part of the clinical trial detailed elsewhere. Unit costs were estimated from published sources. The net benefit approach to cost-effectiveness analysis is used to estimate the probability of the intervention being cost-effective.

Results: The addition of a supplementary class-based group results in an increase in QALYs and lower costs. For all plausible values of a decision maker's willingness to pay for a QALY, the supplementary class group is likely to be cost-effective.

Conclusions: The addition of a class-based exercise program is likely to be cost-effective and, on current evidence, should be implemented.

The pragmatism in health care has made health technology assessment (HTA) restrict its scope to a particular set of problems, c.q. methods. The “multidisciplinary and comprehensive nature” of HTA, as the concept is presented in certain definitions, is lacking. Health care is also dominated by a positivistic-rationalistic approach of evaluation. In contrast, social studies of evaluations learn that a major difference has to be made between scientific research on (potential) impact of a technology and valuing these effects. In this contribution, we will discuss how the positivistic scientific bias of current HTA practice can be made up with other research traditions. More specifically, we focus on the question of how social scientists and particularly how qualitative research can contribute to HTA, complementary to positivistic studies of evidence and efficacy.

Background: Decision makers in middle-income countries are using economic evaluations (EEs) in pricing and reimbursement decisions for pharmaceuticals. However, whilst many of these jurisdictions have local submission guidelines and local expertise, the studies themselves often use economic models developed elsewhere and elements of data from countries other than the jurisdiction concerned. The objectives of this study were to describe the current situation and to assess the challenges faced by decision makers in transferring data and analyses from other jurisdictions.

Methods: Experienced health service researchers in each region conducted an interview survey of representatives of decision making bodies from jurisdictions in Asia, Central and Eastern Europe, and Latin America that had at least 1 year's experience of using EEs.

Results: Representatives of the relevant organizations in twelve countries were interviewed. All twelve jurisdictions had developed official guidelines for the conduct of EEs. All but one of the organizations evaluated studies submitted to them, but 9 also conducted studies and 7 commissioned them. Nine of the organizations stated that, in evaluating EEs submitted to them, they had consulted a study performed in a different jurisdiction. Data on relevant treatment effect was generally considered more transferable than those on prices/unit costs. Views on the transferability of epidemiological data, data on resource use and health state preference values were more mixed. Eight of the respondents stated that analyses submitted to them had used models developed in other jurisdictions. Four of the organizations had a policy requiring models to be adapted to reflect local circumstances. The main obstacles to transferring EEs were the different patterns of care or wealth of the developed countries from which most economic evaluations originate.

Conclusions: In middle-income countries it is commonplace to deal with the issue of transferring analyses or data from other jurisdictions. Decision makers in these countries face several challenges, mainly due to differences in current standard of care, practice patterns, or gross domestic product between the developed countries where the majority of the studies are conducted and their own jurisdiction

Objectives: To identify and assess the effects of general practitioner and patient characteristics on global adherence to pharmacotherapeutic guidelines.

Methods: In a cross-sectional study in the northern Netherlands, a two-level multilevel model was applied to patients (n=269,067) in 190 practices with a total of 251 general practitioners. The dependent variable was the global adherence to pharmacotherapeutic guidelines as a measure of good prescribing in a general practice setting.

Results: The mean global adherence was 82%. Two general practice variables, organization form and degree of urbanization influenced the global adherence, whereas all patient variables (age and gender) and the patient-related prescription characteristics (costs, volume, different ATC-codes) were significant predictors for the global adherence. The total explained variance was 28%.

Conclusions: Patient characteristics have a greater influence on prescribing behavior than general practitioner characteristics.We thank the health care insurance organization (Regionaal Ziekenfonds Groningen [RZG]) for supplying the data set. We also thank Eddie Bruin from the health care insurance organization for his assistance with data collection and Tom Snijders for data analysis and statistical advice.

Objectives: The study aims at evaluating the economic evidence related to testing for genetic variants of the drug-metabolizing enzyme, TPMT. Detecting TPMT genetic variants before the administration of azathioprine (AZA) has the potential to prevent serious and costly adverse drug reactions (ADRs), such as neutropenia. In particular, our analysis concentrated on assessing the reliability of data on costs of neutropenia and performing the tests, the two main cost categories that could inform an economic evaluation of TPMT pharmacogenetic testing.

Methods: A systematic literature review was performed to gather evidence on the costs of testing and neutropenia. Articles were critically appraised for their comprehensiveness and quality. To better estimate costs of TPMT tests, a small-scale survey of European diagnostic laboratories was conducted.

Results: Only seven articles were retrieved specifying the costs associated with the management and treatment of AZA-induced neutropenia. Most of these studies are based on theoretical modeling reconstructed with key-informants or on very few cases of ADRs, and either the methodology for cost calculation is not specified or costs are based on national cost databases and tariffs. After critical appraisal of these studies, we considered €2,116 as the most reliable estimate for the cost of a case of neutropenia. Literature review accompanied by the survey of several diagnostic laboratories also provided an estimate (€68) for TPMT testing. Based on these values, the net cost per prevented case of neutropenia equals to €5,300.

Conclusions: Solid economic considerations related to TPMT pharmacogenetic testing are still limited by underreporting of ADRs and high level of approximation related to cost data. Ad hoc observational studies and the ADR recording process embedded in pharmacovigilance systems, established across Europe, should represent more reliable sources of cost data in the future.

Health systems are challenged continuously to provide the highest quality universal health care within their means. While for 30 years, health technology assessment (HTA) has contributed to the process of evidence-informed decision making and the managed entry of new technologies, its remit has not expanded to include assessment of technologies currently in use, as a means of managing their use and potentially their exit. We propose that health technology reassessment (HTR) become standard practice, an integral part of all health technology assessment agencies, and that we develop standardized models and methodologies for reassessment drawing from what we have learned from HTA.

Objectives: We assess the cost-effectiveness of smoking relapse prevention interventions designed to keep quitters from resuming the use of cigarettes. Because relapse prevention is complementary to smoking cessation efforts, the appropriate test of its cost-effectiveness is whether it reduces the incremental cost-effectiveness ratio (ICER) of smoking cessation. The major goal of the study is to carry out such a test.

Methods: Data from a randomized trial that ascertained the effectiveness of alternative modes of smoking relapse prevention are combined with ICER estimates of smoking cessation to assess whether relapse prevention is cost-effective.

Results: The trial produced convincing evidence that relapse prevention yields statistically significant reductions in the proportion of quitters who are smoking at 24 months postquit. The intervention effects are substantial enough to raise the denominator terms of the smoking cessation ICER and, thereby, offset the amount relapse prevention adds to cost numerator terms. In this sense, smoking relapse prevention tends to pay for itself.

Conclusions: Smoking relapse prevention is a highly cost-effective addition to current efforts to curb cigarette consumption. Complementary health interventions of this sort should be assessed by different methods than those commonly found in the cost-effectiveness literature.

Objectives: To assess the cost-effectiveness of brief physiotherapy intervention versus usual physiotherapy management in patients with neck pain of musculoskeletal origin in the community setting.

Methods: A cost-effectiveness analysis was conducted alongside a multicenter pragmatic randomized controlled clinical trial. Individuals 18 years of age and older with neck pain of more than 2 weeks were recruited from physiotherapy departments with referrals from general practitioners (GPs) in the East Yorkshire and North Lincolnshire regions in the United Kingdom. A total of 139 patients were allocated to the brief intervention, and 129 to the usual physiotherapy. Resource use data were prospectively collected on the number of physiotherapy sessions, hospital stay, specialist, and GP visits. Quality-adjusted life years (QALYs) were estimated using EQ-5D data collected at baseline, 3 and 12 months from the start of the treatment. The economic evaluation was conducted from the U.K. National Health System perspective.

Results: On average, brief intervention produced lower costs (£−68; 95 percent confidence interval [CI], £−103 to £−35) and marginally lower QALYs (−0.001; 95 percent CI, −0.030 to 0.028) compared with usual physiotherapy, resulting in an incremental cost per QALY of £68,000 for usual physiotherapy. These results are sensitive to patients' treatment preferences.

Conclusions: Usual physiotherapy may not be good value for money for the average individual in this trial but could be a cost-effective strategy for those who are indifferent toward which treatment they receive.

EVIPNet (Evidence-Informed Policy Network) Africa—a network of World Health Organization (WHO)-sponsored knowledge-translation (KT) platforms in seven sub-Saharan African countries—was launched at a meeting in Brazzaville, Congo, in March 2006 (1;2). EVIPNet Africa can trace its origins to resolutions from both the Ministerial Summit on Health Research (November 2004) and the World Health Assembly (May 2005) (10;11), the spirit of which was re-affirmed at the Global Ministerial Forum on Research for Health (November 2008) (13). The World Health Assembly called for “establishing or strengthening mechanisms to transfer knowledge in support of evidence-based public health and health care delivery systems and evidence-based related policies” (10). EVIPNet Africa can trace its inspiration to a more local development: the preparatory work that led to the establishment of the East African Community–sponsored Regional East African Community Health (REACH) Policy initiative, a KT platform involving Kenya, Tanzania, and Uganda (and more recently Burundi and Rwanda as well). REACH Policy is now part of the EVIPNet Africa family.

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.

Objectives: The objective of this study is to describe the frequency of inappropriate empirical antibiotic therapy in secondary intra-abdominal infection and to identify the possible relationship between inappropriateness and some clinical outcomes.

Methods: A retrospective descriptive multicenter study was conducted using hospital secondary databases developed at two university hospitals located in northeast Spain. Participants were patients 18 years of age or older who were diagnosed with community-acquired intra-abdominal infections between January 1, 1998, and December 31, 2000, identified through computerized patient records using ICD-9 codes. Appropriateness of empirical treatment was defined according to the recommendations of the literature. The clinical outcome of each patient was classified as one of the following: (i) resolved with initial therapy, (ii) required second-line antibiotics, (iii) required re-operation, or (iv) in-hospital death. The Fisher's exact test or the Chi-squared test for categorical variables and the t-test or Mann–Whitney test for continuous variables were used for comparing groups. Conditional logistic and linear regression analyses were also applied.

Results: Of 376 cases, 51 cases (13.6 percent, 95 percent confidence interval, 10–17 percent) received inappropriate empirical antibiotic therapy according to the scientific literature. Inappropriate initial empirical treatment was significantly associated with the need for a second line of antibiotics (p<.001), although not with re-operation, mortality, or length of hospitalization.

Conclusions: Approximately 14 percent of the patients received inappropriate empirical antibiotic treatment. Worse clinical outcomes consistently were observed in the group of patients receiving inappropriate empirical treatment. The appropriateness of antibiotic treatment for a given infection, in light of the availability of clearly defined clinical guidelines is an easily evaluated aspect of the quality of care.

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: The aim of this study was to evaluate the long-term cost-utility of liraglutide versus glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM), based on the results of clinical trial conducted in Asian population.

Methods: The validated UKPDS Outcomes Model was used to project life expectancy, quality adjusted life-years (QALYs), incidence of diabetes-related complication and cost of complications in patients receiving those regimens. Baseline cohort characteristics and treatment effects were derived from an Asian study. China-specific complication costs and utility score were taken from local studies. Patients’ outcomes were modeled for 30 years and incremental cost-effectiveness ratios were calculated for liraglutide compared with glimepiride from the healthcare system perspective. Both future costs and clinical benefits were discounted at 3 percent. Sensitivity analyses were performed.

Results: Over a period of 30 years, compared with glimepiride, liraglutide 1.8 mg was associated with improvements in life expectancy (0.1 year) and quality adjusted life-year (0.168 QALY), and a reduced incidence of diabetes-related complications leading to an incremental cost-effectiveness ratio per QALY gained versus glimepiride of CNY 25,6871 (DEC 2010, 1 USD = 6.6227 CNY).

Conclusions: Long-term projections indicated that liraglutide was associated with increased life expectancy, QALYs, and reduced complication incidences comparing with glimepiride. When the UK cost of liraglutide was discounted by 38 percent, liraglutide would be a cost-effective option in China from the healthcare system perspective using the 3X GDP/capita per QALY as the WTP threshold.

Objectives: This study outlines the needs and current development of the “fourth hurdle” (i.e., requirement of effectiveness and cost-effectiveness data for drug coverage policy decisions) in Hungary, describes the legal background and seeks to address some of the most important questions in this field.

Methods: The study draws on international experiences and discusses five issues that a given jurisdiction needs to consider before introducing the “fourth hurdle” for pharmaceuticals.

Results: The “fourth hurdle” is very relevant in Hungary because many existing drugs are unevaluated and many new, expensive drugs are becoming available. On the other hand, the existing resources for health technology assessment, including economic evaluation, are quite limited. All the five issues are relevant in the Hungarian setting and were helpful in determining exactly how the “fourth hurdle” should be applied.

Conclusions: The most important issue seems to be that the implementation of the “fourth hurdle” needs to be achieved in a way consistent with the limited resources for HTA in Hungary. Specifically this means that, in setting priorities for drugs to evaluate, additional criteria need to be applied. In particular, priority should be given to assessing drugs that have been evaluated in other countries, because this affords the opportunity to adapt existing studies or models to the Hungarian situation.

Italy is one of the few countries that have matured substantial experience of risk-sharing agreements so far. The first performance-based arrangement was agreed in July 2006, and as of October 2010, eighteen contracts have been in force.

The complex management of discount schemes is entirely based on Web registries run by AIFA, the Italian drug agency. The system validates each prescription and automatically requests the hospital pharmacy by e-mail to release the drug. If a patient meets nonresponder criteria, the hospital pharmacist should apply for pay-back to the manufacturer.

There are still some important question marks to address. First of all, nonresponders have to be documented by health authorities, otherwise any undocumented nonresponder will be paid as a success. Another question concerns pre-set timing. Although the scientific rationale of the nonresponder criteria for each drug has not been made public, time frames appear too short to allow a reliable assessment. Another question is whether regions, which are financially accountable in Italy for pharmaceutical expenditure, are really able to claw back refunds from manufacturers. Unfortunately here again there are no official figures, and regions do not seem yet able to quantify the amount of pay-back matured in the 4 previous years. The delayed and incomplete availability of pay-back procedures may be one explanation.