Welcome to the 26th volume of the International Journal of Technology Assessment in Health Care (IJTAHC). The editorial office has moved from the Institute of Health Economics in Alberta, Canada, to the National Institute for Health and Welfare (THL) in Finland and its Finnish Office for Health Technology Assessment (FINOHTA). It is exciting and challenging to take the helm of this journal. Knowing its history and cherishing its strengths, I wish to keep the HTA community engaged in making and using the journal as its scientific sounding board and its flagship.

Objectives: Despite the considerable and growing body of research about the clinical effectiveness of long-term psychoanalytic treatment, relatively little attention has been paid to economic evaluations, particularly with reference to the broader range of societal effects. In this cost-utility study, we examined the incremental cost-effectiveness ratio (ICER) of psychoanalysis versus psychoanalytic psychotherapy.

Methods: Incremental costs and effects were estimated by means of cross-sectional measurements in a cohort design (psychoanalysis, n = 78; psychoanalytic psychotherapy, n = 104). Quality-adjusted life-years (QALYs) were estimated for each treatment strategy using the SF-6D. Total costs were calculated from a societal perspective (treatment costs plus other societal costs) and discounted at 4 percent.

Results: Psychoanalysis was more costly than psychoanalytic psychotherapy, but also more effective from a health-related quality of life perspective. The ICER—that is, the extra costs to gain one additional QALY by delivering psychoanalysis instead of psychoanalytic psychotherapy—was estimated at €52,384 per QALY gained.

Conclusions: Our findings show that the cost-utility ratio of psychoanalysis relative to psychoanalytic psychotherapy is within an acceptable range. More research is needed to find out whether cost-utility ratios vary with different types of patients. We also encourage cost-utility analyses comparing psychoanalytic treatment to other forms of (long-term) treatment.

Objectives: Little is known about the costs and the effects of cardiovascular prevention programs targeted at medical and behavioral risk factors. The aim was to evaluate the cost-utility of a cardiovascular prevention program in a general sample of highly educated adults after 1 year of intervention.

Methods: The participants were randomly assigned to intervention (n = 208) and usual care conditions (n = 106). The intervention consisted of medical interventions and optional behavior-change interventions (e.g., a tailored Web site). Cost data were registered from a healthcare perspective, and questionnaires were used to determine effectiveness (e.g., quality-adjusted life-years [QALYs]). A cost-utility analysis and sensitivity analyses using bootstrapping were performed on the intermediate results.

Results: When adjusting for baseline utility differences, the incremental cost was €433 and the incremental effectiveness was 0.016 QALYs. The incremental cost-effectiveness ratio was €26,910 per QALY.

Conclusions: The intervention was cost-effective compared with usual care in this sample of highly educated adults after 1 year of intervention. Increased participation would make this intervention highly cost-effective.

Objective: The aim of this study was to elicit willingness to pay (WTP) for allergen-specific subcutaneous injection immunotherapy (SCIT) in a cohort of respondents suffering from allergic-rhinoconjunctivitis (a-RC)/asthma, and to investigate how patients self-select to SCIT according to need.

Methods: A random sample of the general population was screened for a-RC/asthma and asked if they were willing to consider SCIT. They were asked to state their WTP for SCIT by way of a discrete choice question (DC-q), an open-ended WTP question (o-WTP-q), and questions relating to their sociodemographic background and the severity of their a-RC/asthma. The characteristics of respondents demanding SCIT were compared with the characteristics of respondents who have actually received SCIT to establish possible barriers to demand.

Results: Our results suggest that respondents do well in self-selecting themselves to SCIT on the basis of need according to disease burden measured in terms of a-RC classification, number of contacts with a general practitioner, number of sick days, and potential quality-adjusted life-year loss. Mean WTP for SCIT was estimated at €655 (median, €267) (o-WTP-q) and €903 (95 percent confidence limit, 348–1,459) (DC-q).

Conclusion: Characteristics of respondents, who consider SCIT and are willing to pay for SCIT, suggest that allergy sufferers select themselves appropriately according to need and not according to other characteristics, such as income or education. There is a significant discrepancy between those who hypothetically consider SCIT and those demanding SCIT in real life. This study suggests that there are barriers to entry related to age and education, but not to income.

Objectives: The aim of this study was to compare the predictive value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein (hs-CRP)-screening in addition to traditional risk factor screening in apparently healthy persons as a means of preventing coronary artery disease.

Methods and Results: The systematic review was performed according to internationally recognized methods. Seven studies on risk prediction, one clinical decision-analytic modeling study, and three decision-analytic cost-effectiveness studies were included. The adjusted relative risk of high hs-CRP-level ranged from 0.7 to 2.47 (p < .05 in four of seven studies). Adding hs-CRP to the prediction models increased the areas under the curve by 0.00 to 0.027. Based on the clinical decision analysis, both individuals with elevated hs-CRP-levels and those with hyperlipidemia have a similar gain in life expectancy following statin therapy. One high-quality economic modeling study suggests favorable incremental cost-effectiveness ratios for persons with elevated hs-CRP and higher risk. However, many model parameters were based on limited evidence.

Conclusions: Adding hs-CRP to traditional risk factors improves risk prediction, but the clinical relevance and cost-effectiveness of this improvement remain unclear.

Objectives: The aim of this study was to compare the cost and the effectiveness of two biennial fecal occult blood screening tests for colorectal cancer: a guaiac nonrehydrated test (G-FOBT) and an immunochemical test (I-FOBT) with the absence of screening.

Methods: A Markov model was developed to compare these strategies in a general population of subjects aged 50 to 74 over a 20-year period.

Results: Compared with the absence of screening, G-FOBT and I-FOBT were associated with a decrease in colorectal cancer mortality of 17.4 percent and 25.2 percent, respectively. With regard to cost-effectiveness, expressed as cost per life-year gained, I-FOBT was the most effective and most costly alternative. Compared with no screening, G-FOBT and I-FOBT presented similar discounted incremental cost-effectiveness ratios: €2,739 and €2,819 respectively per life-year gained. When compared with G-FOBT, I-FOBT presented an incremental cost-effectiveness ratio of €2,988 per life-year gained. Sensitivity analyses showed the strong influence of the I-FOBT lead time, of the participation rate to screening for I-FOBT, and of the purchase price of the I-FOBT on the discounted incremental cost-effectiveness ratios.

Conclusions: Compared with the absence of screening and with G-FOBT, the biennial two-stool immunochemical test can be considered a promising method for mass screening for colorectal cancer.

Background: Most industrialized countries, including France, have undertaken to generalize colorectal cancer screening using guaiac fecal occult blood tests (G-FOBT). However, recent researches demonstrate that immunochemical fecal occult blood tests (I-FOBT) are more effective than G-FOBT. Moreover, new generation I-FOBT benefits from a quantitative reading technique allowing the positivity threshold to be chosen, hence offering the best balance between effectiveness and cost. We aimed at comparing the cost and the clinical performance of one round of screening using I-FOBT at different positivity thresholds to those obtained with G-FOBT to determine the optimal cut-off for I-FOBT.

Methods: Data were derived from an experiment conducted from June 2004 to December 2005 in Calvados (France) where 20,322 inhabitants aged 50–74 years performed both I-FOBT and G-FOBT. Clinical performance was assessed by the number of advanced tumors screened, including large adenomas and cancers. Costs were assessed by the French Social Security Board and included only direct costs.

Results: Screening using I-FOBT resulted in better health outcomes and lower costs than screening using G-FOBT for thresholds comprised between 75 and 93 ng/ml. I-FOBT at 55 ng/ml also offers a satisfactory alternative to G-FOBT, because it is 1.8-fold more effective than G-FOBT, without increasing the number of unnecessary colonoscopies, and at an extra cost of €2,519 per advanced tumor screened.

Conclusions: The use of an automated I-FOBT at 75 ng/ml would guarantee more efficient screening than currently used G-FOBT. Health authorities in industrialized countries should consider the replacement of G-FOBT by an automated I-FOBT test in the near future.

Objectives: The objective of this study was to estimate the cost-effectiveness of infliximab use in patients with rheumatoid arthritis (RA) in Swedish clinical practice, based on patient-level data from the Stockholm TNF-alpha follow-up registry (STURE).

Methods: Real-world patient-level data on infliximab use from the STURE registry were implemented in a Markov cohort model, in which health states of functional status were classified according to the Health Assessment Questionnaire Disability Index (HAQ—five categories) and twenty-eight joint count Disease Activity Score (DAS28). The transition probabilities between HAQ and DAS28 states during treatment, as well as discontinuation rates were modeled based on data from the registry for patients using infliximab as their first-line biological treatment. The transition probabilities in the comparator arm, that is, disease progression without biologic treatment, as well as mortality rates, costs, and utilities were based on published literature. The analysis had a societal cost perspective.

Results: Infliximab was associated with an incremental gain in quality-adjusted life-years of 1.02 and an incremental cost of €23,264 per patient compared with progression without biologic treatment, producing an incremental cost-effectiveness ratio (ICER) of €22,830 (SEK211,136 or US$31,230). Sensitivity analyses of input parameters and model assumptions produced ICERs in the range from €18,000 to €47,000.

Conclusions: Results from base-case and sensitivity analyses fell well below established benchmarks for cost-effectiveness in Sweden. The results, therefore, indicated that infliximab treatment for RA has provided good societal value for money in Swedish clinical practice, compared with a scenario of no biological treatment.

Objectives: Type 2 diabetes is the main cause of end-stage renal disease in Europe and the United States. Angiotensin-converting enzyme (ACE) inhibitors slow down the progression of renal disease and, therefore, provide a renal-protective effect. The aim of this study was to assess the most cost-effective time to start an ACE inhibitor (or an angiotensin II receptor blocker in the event of cough) in patients with type 2 diabetes in Germany.

Methods: Three strategies were compared: treating all patients at the time of diagnosing type 2 diabetes, screening for microalbuminuria, and screening for macroalbuminuria. A lifetime Markov decision model with simulated 50-year-old patients with newly diagnosed diabetes mellitus was developed using published data on costs and health outcomes and simulating the progression of renal disease. A statutory health insurance perspective was adopted.

Results: In the base-case analysis, the treat-all strategy is associated with the lowest costs and highest benefit and, therefore, dominates screening both for macroalbuminuria and microalbuminuria. A multivariate sensitivity analysis shows that the probability of savings is 89 percent.

Conclusions: Patients with type 2 diabetes should receive an ACE inhibitor immediately after diagnosis if they do not have contraindications. The potential for cost savings would be even larger if the prevention of cardiovascular events were considered.

Previously, our group—the International Working Group for HTA Advancement—proposed a set of fifteen Key Principles that could be applied to health technology assessment (HTA) programs in different jurisdictions and across a range of organizations and perspectives. In this commentary, we investigate the extent to which these principles are supported and used by fourteen selected HTA organizations worldwide. We find that some principles are broadly supported: examples include being explicit about HTA goals and scope; considering a wide range of evidence and outcomes; and being unbiased and transparent. Other principles receive less widespread support: examples are addressing issues of generalizability and transferability; being transparent on the link between HTA findings and decision-making processes; considering a full societal perspective; and monitoring the implementation of HTA findings. The analysis also suggests a lack of consensus in the field about some principles—for example, considering a societal perspective. Our study highlights differences in the uptake of key principles for HTA and indicates considerable room for improvement for HTA organizations to adopt principles identified to reflect good HTA practices. Most HTA organizations espouse certain general concepts of good practice—for example, assessments should be unbiased and transparent. However, principles that require more intensive follow-up—for example, monitoring the implementation of HTA findings—have received little support and execution.

Objectives: The aim of this study was to describe the current issues surrounding Coverage with Evidence Development (CED). CED is characterized by restricted coverage for a new technology in parallel with targeted research when the stated goal of the research or data collection is to provide definitive evidence for the clinical or cost-effectiveness impact of the new technology.

Methods: Presented here is information summarized and interpreted from presentations and discussions at the 2008 Health Technology Assessment International (HTAi) meeting and additional information from the medical literature. This study describes the differences between CED and other conditional coverage agreements, provides a brief history of CED, describes real-world examples of CED, describes the areas of consensus between the stakeholders, discusses the areas for future negotiation between stakeholders, and proposes criteria to assist stakeholders in determining when CED could be appropriate.

Results: Payers could interpret the evidence obtained from a CED program either positively or negatively, and a range of possible changes to the reimbursement status of the new technology may result. Striking an appropriate balance between the demands for prompt access to new technology and acknowledging that some degree of uncertainty will always exist is a critical challenge to the uptake of this innovative form of conditional coverage.

Conclusions: When used selectively for innovative procedures, pharmaceuticals, or devices in the appropriate disease areas, CED may provide patients access to promising medicines or technologies while data to minimize uncertainty are collected.

Objectives: The aim of this study was to test the feasibility of conducting rigorous, nonrandomized studies (NRSs) of healthcare interventions using existing clinical databases in terms of the following: recruiting a large representative sample of hospitals, identifying eligible cases, matching cases to controls to achieve similar baseline characteristics, making meaningful comparisons of outcomes, and carrying out subgroup analyses.

Methods: Data were extracted from the Intensive Care National Audit & Research Centre's Case Mix Programme Database to investigate the impact of management with a pulmonary artery catheter (PAC) in intensive care unit (ICU) patients. Participating ICUs were invited to collect additional data for the analysis. Patients managed with a PAC were matched to control patients on their propensity score. Hospital mortality was then compared between the two groups.

Results: Of 117 eligible ICUs, 68 (58 percent) agreed to participate, of which 57 (84 percent) collected additional data. Although a slightly higher proportion of larger ICUs in university hospitals participated, the patient case-mix was similar to that in nonparticipating ICUs. Almost all patients managed with a PAC (98 percent) were successfully matched to patients managed without a PAC. The two groups were similar for baseline characteristics. However, hospital mortality was worse for PAC patients than for non-PAC patients (odds ratio, 1.28; 95 percent confidence interval, 1.06–1.55). Subgroup analysis suggested that the impact of management with a PAC was modified by severity of illness.

Conclusions: Rigorous NRSs are feasible if they are based on data from high-quality clinical databases. However, the reliability of estimated treatment effects from such studies requires further investigation.

Objectives: This study reviews the coverage and usefulness of a short-term register, established specifically for health technology assessment of a novel interventional procedure (minimally invasive repair of pectus excavatum, or the Nuss procedure).

Methods: Coverage of the register during 2004–07 was assessed by comparison with Hospital Episodes Statistics (HES) for England. Its usefulness was assessed by comparing safety and efficacy data with the published literature and by feedback from committee members who in 2009 were involved in reviewing NICE's original guidance from 2003.

Results: The register reported 260 cases from thirteen UK hospitals during nearly 9 years. During a coverage evaluation period of 3 years, there were 152 registered Nuss procedures. An additional 246 repairs of pectus excavatum were undertaken in twenty-six previously unidentified hospitals. Of the 246, 23 were Nuss procedures (from two hospitals), 140 were open procedures (from eleven hospitals), and 3 were coding errors. No details were available for eighty cases undertaken at ten hospitals. The quantity of published literature had increased substantially since publication of original guidance in 2003. It related mostly to technical and safety outcomes, whereas the register included patient reported outcomes. The literature and the register reported similar rates of major adverse events such as bar displacement (2–10 percent). Committee members considered that the Register made a useful contribution to guidance development.

Conclusions: This study shows that a register set up to support a health technology assessment process can produce useful data both about safety and about patient-reported outcomes. Coverage may be improved by active follow-up based on routine hospital statistics. Improvement in coding for new procedures is needed in the United Kingdom.

Objectives: The aim of this study was to identify and compare health technology assessments of the same new interventional procedures produced in different countries.

Methods: We selected five new interventional procedures and studied related assessments produced in different countries.

Results: There were twenty assessments (range, 3–5 per procedure) from nine countries—fourteen from Australia, Canada, and United Kingdom. The number of primary RCTs cited by the assessments ranged from 0 to 13. In the assessment reports, “headline” statements about the strength of evidence for efficacy (73 percent) were made more frequently than for safety (53 percent). These statements were scored for their apparent judgment of the strength of the evidence—1 (poor) to 5 (strong)—and received scores of 3 or less in all but four cases. Recommendations about additional research were included in 55 percent of the assessments. Statements in assessments about other aspects of use of the procedures were included more infrequently—in 35 percent for patient selection, in 20 percent for consent issues, and in 15 percent for types of clinical teams. Recommendations about appropriate healthcare settings, or about operator training, were included only in assessments produced by a single organization.

Conclusion: There was a only small number of assessments world-wide, for a range of new procedures with potentially high impact. Where available, assessments were produced on a relatively poor evidence base. International collaboration in evidence appraisal and review, and in the gathering of new data through research or registers, could improve the advice available to healthcare systems worldwide about the adoption of new interventional procedures.

Objectives: Nonpublication of results of clinical trials can contribute to inappropriate medical decisions. The primary aim of this systematic review was to investigate publication delays between conference abstracts and full journal publications from randomized controlled trial results of new anticancer agents for breast cancer. The review was restricted to anticancer agents previously, or due to be, appraised in the United Kingdom by the National Institute for Health and Clinical Excellence. A secondary objective was to identify whether there are any apparent biases in the publication and reporting of these trials.

Methods: We searched six electronic databases up to August 2007, including Medline and the Cochrane Library. Two reviewers independently selected studies, extracted and assessed the data.

Results: Six anticancer treatments were identified: docetaxel, paclitaxel, trastuzumab, gemcitabine, lapatinib, and bevacizumab. Of eighteen included trials, only four publications from three trials reported the same outcomes in both abstract and full publication. Time delays ranged from 5 to 19 months. Eleven trial abstracts were still without a full publication at the end of our searches, varying from 3 to 38 months since abstract publication. Observational analysis revealed no particular publishing biases.

Conclusions: Whereas delays in publication appear reasonable over a period of months, many were not published in full over a period of years and others would appear to be unlikely to ever be published. Further research should investigate the impact of publication delays on the availability of new drug treatments in clinical practice.

Objectives: The aim of this study was to estimate an empirical relationship and degree of agreement between the TTO values of patients’ own health and their 15D scores.

Methods: A total of 863 hospital patients aged 18–93 years filled in the 15D questionnaire to establish their 15D score and valued their present health with TTO. Wilcoxon signed rank test, the Spearman rank correlation coefficient and Tobit models were used to analyze the relation between the 15D and TTO scores.

Results: The null hypothesis of no tendency for one set of scores to be higher or lower than the other set could not be rejected. Apart from dummies for few patients groups, no additional information to the 15D score was found that would have explained significantly the variance in the TTO valuations of patients’ own health. The agreement between these to sets of scores turned out quite good at the aggregate level.

Conclusions: To the extent that mean TTO valuations of patients own health are valid for QALY calculations as they at least theoretically should be, and if experience of health states to be valued counts, the 15D scores are also valid without any transformation in a large group of heterogeneous patients. However, in certain patient groups, the agreement was not as good as overall.

Objectives: Post-listing assessment of pharmaceuticals depends on national habits. In England, the assessment is based on estimates of cost per quality-adjusted life-year. These are made some considerable time after listing (negative list). In France, effectiveness, and then efficiency, is assessed immediately after listing (positive list). We propose a new formal method—the REAL method—that can help make early comparisons of the effectiveness of medical treatments.

Methods: Relative efficacies are first obtained from randomized controlled trials (RCTs). Members of the Transparency Committee (French National Authority for Health) are then consulted by questionnaire on the transposability of these results to real life. The RCT results and experts’ ratings are entered into an effect model to obtain estimates of relative effectiveness, using unidimensional scaling, and bootstrap procedures.

Results: Application of the REAL method to the example of a new drug to treat Parkinson's disease and three comparators used in the same indication provided graphs of the distributions of their relative efficacy and relative effectiveness. The new drug was found to provide no added value.

Conclusions: The REAL method is a rational, transparent, and practical procedure for comparing the effectiveness of pharmaceuticals in an immediate post-listing setting.