It is very fitting that the strap line for the article on reassessment (1) is derived from the quote “politics is the art of the possible” attributed to Otto von Bismarck. Bismarck was the first chancellor of the unified German Empire that preserved peace in Europe until 1914. Politically deft, he persuaded the southern German states to join with his North German Confederation by provoking hostilities with France.

Background: Ethics has been part of health technology assessment (HTA) from its beginning in the 1970s, and is currently part of HTA definitions. Several methods in ethics have been used in HTA. Some approaches have been developed especially for HTA, such as the Socratic approach, which has been used for a wide range of health technologies. The Socratic approach is used in several ways, and there is a need for harmonization to promote its usability and the transferability of its results. Accordingly, the objective of this study was to stimulate experts in ethics and HTA to revise the Socratic approach.

Methods: Based on the current literature and experiences in applying methods in ethics, a panel of ethics experts involved in HTA critically analyzed the limitations of the Socratic approach during a face-to-face workshop. On the basis of this analysis a revision of the Socratic approach was agreed on after deliberation in several rounds through e-mail correspondence.

Results: Several limitations with the Socratic approach are identified and addressed in the revised version which consists of a procedure of six steps, 7 main questions and thirty-three explanatory and guiding questions. The revised approach has a broader scope and provides more guidance than its predecessor. Methods for information retrieval have been elaborated.

Conclusion: The presented revision of the Socratic approach is the result of a joint effort of experts in the field of ethics and HTA. Consensus is reached in the expert panel on an approach that is considered to be more clear, comprehensive, and applicable for addressing ethical issues in HTA.

Objectives: In many economic evaluations and reimbursement decisions, quality-adjusted life-years (QALYs) are used as a measure of benefit to assess effectiveness of novel therapies, often based on the EQ-5D 3-level questionnaire. As only five dimensions of physical and mental well-being are reflected in this tool, significant aspects of the patient experience may be missed. We evaluate the use of the EQ-5D as a measurement of clinical change across a wide range of disorders from dermatological (acne) to life-threatening (metastatic cancers).

Methods: We analyze published studies on the psychometric properties of the EQ-5D 3-level questionnaire, extracting information on the Visual Analogue Scale versus Index score, Standardized Response Mean, and Effect Size. These are compared with ranges generally accepted to represent good responsiveness in the psychometric literature.

Results: We find that only approximately one in five study populations report subjective health state valuation of patients within 5 percent of the score attributed by the EQ-5D index, and more than 40 percent of studies report unacceptable ceiling effects. In the majority of studies, responsiveness of the EQ-5D index was found to be poor to moderate, based on Effect Size (63 percent poor–moderate) and Standardized Response Mean (72 percent poor–moderate).

Conclusions: We conclude that the EQ-5D index does not adequately reflect patient health status across a range of conditions, and it is likely that a significant proportion of the subjective patient experience is not accounted for by the index. This has implications for economic evaluations of novel drugs based on evidence generated with the EQ-5D.

Background: Increasingly, healthcare decision makers demand quality evidence in a short timeframe to support urgent and emergent decisions related to procurement, clinical practice, and policy. Health technology assessment (HTA) producers are responding by developing innovative approaches to evidence synthesis that can be executed more quickly than traditional systematic review. These approaches, and the broader implications they bring to bear on health decision making and policy development, however, are generally neither well-understood nor well-described. This study intends to contribute to an emerging literature around methodological approaches to rapid review in HTA by outlining those developed and implemented by the Canadian Agency for Drugs and Technologies in Health (CADTH).

Methods: Since 2005, CADTH has developed and implemented a rapid review approach that synthesizes evidence to support informed healthcare decisions and policy. Rapid Response reports are tailored to the identified needs of Canadian health decision makers, representing a range of options with regard to depth, breadth, and time-to-delivery.

Results: Preliminary observations indicate that CADTH's approach to rapid evidence review is generally well-received by Canadian health decision makers; real-world case studies provide pragmatic examples of how health decision makers have used Rapid Response reports to support evidence-informed health decisions across Canada.

Conclusions: Rapid review is becoming an increasingly important approach to evidence synthesis, both within and external to the field of HTA. Transparent reporting of the methods used to develop rapid review products will be critical to the assessment of their relevance, utility and effects in a range of contexts.

Objectives: Procedures and new medical devices are typically introduced into healthcare systems with limited evidence, when they might be ineffective or unsafe. Systematic data collection (“registers”) can provide valuable “real world” evidence, but difficulties in funding registers are a major obstacle. A good economic case for the value of registers would therefore be useful.

Methods: (i) Literature search on specific purposes of registers. (ii) Surveys (a) of senior clinicians involved with registers, seeking examples of beneficial outcomes, and (b) of administrators, regarding costs of running registers. (iii) A scoping exercise for possible methods to value (financially) the outputs of registers.

Results: Four main categories of beneficial outcomes from registers were identified. These were—safety and quality assurance; training and quality improvement; complementing trial evidence and reducing uncertainty; and supporting trial research. Explicit examples of all these are presented, together with information about the costs of registers. Combining these with the scoping exercise we present suggestions for a methodology of assessing the value of registers across each of the categories.

Conclusions: This study is unique in addressing methods for determining the financial value of registers, based on the amount they cost versus the financial benefits which may result from the evidence generated. Developing the suggested methods could support the case for funding new registers, by showing that their use can benefit healthcare systems through more efficient use of resources, so justifying their costs.

Objectives: Reporting bias potentially threatens the validity of results in health technology assessment (HTA) reports. Our study aimed to explore policies and practices of HTA agencies regarding strategies to include previously unpublished data in their assessments, focusing on requests to industry for unpublished data.

Methods: We included international HTA agencies with publicly available methods papers as well as HTA reports. From the methods papers and recent reports we extracted information on requests to industry and on searches in trial registries, regulatory authority Web sites and for conference abstracts.

Results: Eighteen HTA agencies and seventy-three reports were included. Agencies’ methods papers showed variability regarding requests to industry (requests are routinely carried out in seven cases, not mentioned in six, at the discretion of HTA authors in three, and based on manufacturer applications in two), which were reflected in the reports investigated. As reporting of requests was limited, it often remained unclear whether unpublished data had been received. Searches in trial registries, at regulatory authorities or for conference abstracts are described as a routine or optional part of the search strategy in the methods papers of 9, 11, and 8 included agencies, respectively. A total of 52 percent, 39 percent, and 16 percent of reports described searches in trial registries, at regulatory agencies, and hand searching of conference proceedings.

Conclusion: International HTA agencies currently differ considerably in their efforts to address the issue of unpublished data. Requests to industry may constitute one strategy to access and include unpublished data, while agencies can learn from each other concerning successful practice.

Objectives: When incorporating treatment effect estimates derived from a random-effect meta-analysis it is tempting to use the confidence bounds to determine the potential range of treatment effect. However, prediction intervals reflect the potential effect of a technology rather than the more narrowly defined average treatment effect. Using a case study of robot-assisted radical prostatectomy, this study investigates the impact on a cost-utility analysis of using clinical effectiveness derived from random-effects meta-analyses presented as confidence bounds and prediction intervals, respectively.

Methods: To determine the cost-utility of robot-assisted prostatectomy, an economic model was developed. The clinical effectiveness of robot-assisted surgery compared with open and conventional laparoscopic surgery was estimated using meta-analysis of peer-reviewed publications. Assuming treatment effect would vary across studies due to both sampling variability and differences between surgical teams, random-effects meta-analysis was used to pool effect estimates.

Results: Using the confidence bounds approach the mean and median ICER was €24,193 and €26,731/QALY (95%CI: €13,752 to €68,861/QALY), respectively. The prediction interval approach produced an equivalent mean and median ICER of €26,920 and €26,643/QALY (95%CI: -€135,244 to €239,166/QALY), respectively. Using prediction intervals, there is a probability of 0.042 that robot-assisted surgery will result in a net reduction in QALYs.

Conclusions: Using prediction intervals rather than confidence bounds does not affect the point estimate of the treatment effect. In meta-analyses with significant heterogeneity, the use of prediction intervals will produce wider ranges of treatment effect, and hence result in greater uncertainty, but a better reflection of the effect of the technology.

Background: The matching of favorable human leukocyte antigen (HLA) combinations is rarely performed in penetrating keratoplasty procedures for primary prophylaxis of immune reactions. However, clinical studies suggest that the incidence of graft rejection decreases substantially when patients receive favorably matched grafts.

Objective: The aim of this study was to assess the cost-effectiveness of HLA matching for patients undergoing penetrating keratoplasty in everyday clinical practice.

Methods: In the absence of a randomized controlled clinical trial, we used administrative data from the Freiburg University Eye Hospital in Germany. Our study population consisted of all patients who underwent their first keratoplasty between 11/2003 and 01/2010 and for whom information on HLA histocompatibility was available. We used propensity score matching to estimate a causal effect of favorable HLA matching, parametric survival regression techniques to predict graft survival and expert opinion to model incremental cost for HLA matching. Because the availability of favorable HLA histocompatibility ultimately depends on the patients’ HLA phenotype, we modeled the incremental cost-effectiveness ratio (ICER) as a function of the probability that a patient will receive a favorably matched HLA, and used expert opinion to set a point estimate.

Results: We predicted that corneal grafts with favorable HLA matching were associated with improved rejection-free graft survival time (more than 1,000 days). We estimated the incremental cost of HLA matching at EUR 1,200 and the ICER at EUR 4.62 per additional day of graft survival.

Conclusions: The ICER of HLA matching is acceptable, given the high cost of alternative treatment and the shortage of corneal donors in Germany.

Objectives: Evidence exists that telehealth interventions (e.g., telemonitoring, telediagnostics, telephone care) in disease management for chronic heart failure patients can improve medical outcomes, and we aim to give an overview of the cost-effectiveness of these interventions.

Methods: Based on the literature search on “heart failure” in combination with “cost” and “telehealth” we selected 301 titles and abstracts. Titles and abstracts were screened for a set of inclusion criteria: telehealth intervention, heart failure as the main disease, economic analysis present and a primary study performed. In the end, thirty-two studies were included for full reading, data extraction, and critical appraisal of the economic evaluation.

Results: Most studies did not present a comprehensive economic evaluation, consisting of the comparison of both costs and effects between telehealth intervention and a comparator. Data on telehealth investment costs were lacking in many studies. The few studies that assessed costs and consequences comprehensively showed that telehealth interventions are cost saving with slight improvement in effectiveness, or comparably effective with similar cost to usual care. However, the methodological quality of the studies was in general considered to be low.

Conclusions: The cost-effectiveness of telehealth in chronic heart failure is hardly ascertained in peer reviewed literature, the quality of evidence is poor and there was a difficulty in capturing all of the consequences/effects of telehealth intervention. We believe that without full economic analyses the cost-effectiveness of telehealth interventions in chronic heart failure remains unknown.

Background: Contrast-induced acute kidney injury (CI-AKI) is defined as a deterioration in renal function after administration of radiologic iodinated contrast media (CM). Iodixanol, showed a lower CI-AKI incidence than low-osmolar contrast media (LOCM). A cost-effectiveness analysis was performed comparing iodixanol and LOCM in intravenous (IV) setting in Italy.

Methods: A Markov model was developed. Patients moved across four health states: CI-AKI free, CI-AKI, myocardial infarction, and death. The simulation horizon was lifetime with 1-month cycles. Costs and outcomes were discounted at 3.5 percent rate. CI-AKI incidence was considered from published literature across different definitions. Cost-effectiveness of iodixanol was assessed in terms of incremental cost per life-year gained. Net monetary benefit (NMB) was also calculated. Both deterministic and probabilistic sensitivity analyses were performed.

Results: Base-case results showed an average survival increase of 0.51 life-years and a savings of €7.25 for iodixanol versus LOCM. The cost-effectiveness of iodixanol was confirmed when other scenarios were explored, such as varying CI-AKI definition, sub-populations with specified risk factors, CM hospital bids prices, and inclusion of adverse drug reactions of allergic nature. An NMB ranging between €6,007.25 and €30,007.25 was calculated.

Conclusion: Base-case results show that IV iodixanol is cost-effective compared with LOCM in the Italian clinical setting of a hospital computed tomography radiology practice. However, some caution is due, mainly linked to inherent limitations of the modeling technique and to the lack of agreement on CI-AKI incidence data in the clinical literature.

Objectives: Semiautomated external defibrillators (AEDs) should be considered as a means to facilitate in-hospital early defibrillation (IHED) in areas where advanced life support rescuers are not readily available. In this study, we aimed to develop a checklist and a measurement protocol to evaluate and compare AEDs by assessing factors that may affect IHED.

Methods: A clinical and technical comparison of six AEDs was performed. Technical specifications were analyzed, while an emergency team evaluated ergonomics and appropriateness for IHED at Bambino Gesù Children's Hospital. A measurement protocol was implemented, which aimed to assess the ability of defibrillators to recognize shockable and nonshockable rhythms, accuracy of delivered energy, and charging time.

Results: Designs of AEDs differed in several features which influence their appropriateness for IHED. Some units showed poor ergonomics and instructions/feedback for cardiopulmonary resuscitation. Differences between defibrillators in recognizing shockable and nonshockable rhythms emerged for polymorphic ventricular tachycardia waveforms and when the frequency and amplitude of input signals varied. Tests for accuracy revealed poor performances at low and high impedance levels for most AEDs. Notably, differences greater than 20 seconds were found in the time from power-on to “ready for discharge.”

Conclusions: The approach we used to assess AEDs allowed us to evaluate their appropriateness with respect to the organizational context, to measure their parameters, and to compare models. Results showed that ergonomics and/or performances (timing and accuracy) could be improved in each device.

Objectives: To compare cost effectiveness models for the first-line treatment of multiple myeloma, and explore the differences between the models’ structure, parameters, assumptions and results.

Methods: Three cost effectiveness models for the treatment of multiple myeloma, were compared that had been developed to inform resource allocation in the UK for the chemotherapy regimens bortezomib, melphalan and prednisolone (BMP); and melphalan, prednisolone and thalidomide (MPT) versus melphalan and prednisolone (MP). The models used alternative approaches and assumptions to estimate the overall survival and progression-free survival for each of the interventions. Through the use of sensitivity analyses, the most influential parameters and assumptions of each of the models were identified.

Results: The models developed by the manufacturers gave conflicting results, with each manufacturer favouring their drug. The differences between the model results were determined by two parameters: the hazard ratio for overall survival for MPT vs. MP and the cost of bortezomib.

Conclusions: Using models developed for assessing treatments for multiple myeloma we demonstrated that it was feasible to compare models, which then aided decision makers in making reimbursement decisions.

Objectives: This study explores the awareness and the degree of acceptance of the idea of the medical technology cryonics—the freezing of a corpse to revive it in the future—among German citizens.

Methods: Data were collected on the basis of a representatively weighted online survey of 1,000 people aged between 16 and 69 years and resident in the Federal Republic of Germany.

Results: Forty-seven percent stated that they had already heard of cryonics; 22 percent could imagine having their bodies cryonized after their deaths. For 53 percent, participation in the latest technological developments which correlated with the approval of the conceivability of cryopreservation was important. The majority of the respondents were not skeptical or cautious about innovations in the medical field.

Conclusions: The study shows that cryonics is known and accepted to a certain extent. However, a large proportion of respondents did not believe that it was desirable to use medical technology to overcome death, and fundamentally rejected a post-mortal continuation of life.

Objectives: This study describes the health technology assessment (HTA) framework introduced by Regione Lombardia to regulate the introduction of new technologies. The study outlines the process and dimensions adopted to prioritize, assess and appraise the requests of new technologies.

Methods: The HTA framework incorporates and adapts elements from the EUnetHTA Core Model and the EVIDEM framework. It includes dimensions, topics, and issues provided by EUnetHTA Core Model to collect data and process the assessment. Decision making is instead supported by the criteria and Multi-Criteria Decision Analysis technique from the EVIDEM consortium.

Results: The HTA framework moves along three process stages: (i) prioritization of requests, (ii) assessment of prioritized technology, (iii) appraisal of technology in support of decision making. Requests received by Regione Lombardia are first prioritized according to their relevance along eight dimensions (e.g., costs, efficiency and efficacy, organizational impact, safety). Evidence about the impacts of the prioritized technologies is then collected following the issues and topics provided by EUnetHTA Core Model. Finally, the Multi-Criteria Decision Analysis technique is used to appraise the novel technology and support Regione Lombardia decision making.

Conclusions: The VTS (Valutazione delle Tecnologie Sanitarie) framework has been successfully implemented at the end of 2011. From its inception, twenty-six technologies have been processed.

Introduction: Genetic factors affecting warfarin maintenance dose have been well established, but patient acceptance is a necessary consideration for the successful clinical implementation of warfarin pharmacogenetic testing (WPGT). In this study, we aimed to determine the attitudes toward WPGT among Singaporean Chinese.

Methods: A total of 194 warfarin patients and 187 members of the public completed a structured survey on paper and the Internet, respectively. Attitudes were expressed as willingness to undergo WPGT (single item with 5-point response) and expectations and concerns about WPGT (two multi-item scales). Relationships between attitudes and socio-demographic and clinical variables were explored using Fisher's exact test, Student's t-test, one-way analysis of variance or Pearson's correlation.

Results: Majority of respondents were willing to or neutral about undergoing WPGT. Both patients and public had relatively high expectations (mean [SD]: 3.77 [0.63], and 3.97 [0.55], respectively) and moderately high concerns (mean [SD]: 3.30 [0.69] and 3.33 [0.68], respectively) about WPGT. Willingness to undergo WPGT was associated with gender, educational status, length of warfarin treatment, and number of chronic diseases among warfarin patients, and with history of adverse drug reactions and number of chronic diseases among the public. Higher expectation of WPGT was associated with higher willingness (p < .001 in both populations), while higher concern was associated with lower willingness to undergo WPGT among the public (p = .004) but not among patients (p = .072).

Conclusion: Patient acceptance is not a major barrier to clinical implementation of WPGT but patient education is necessary and the ethical, social, and legal issues should be addressed.

Objectives: This study reports on the development of a critical process for health technologies incorporation concerning an Argentinean Provincial Ministry of Health (MOH) in collaboration with the University of Lanús from 2008 to 2010.

Methods: We describe the approach developed to adapt selected international experiences to provincial scenario. Bibliographic review, regulations examination, key informants interviews and iterative adjustments after various stages of consultation and consensus building with main local players, contribution from foreign experts, and piloting of process and instruments for ultimate fine-tuning are described. We examine final proposal in the light of new updated studies.

Results: Analysis of regulations revealed that rules governing the provincial system were historically linked to administrative resolutions in relation to procurement with poor consideration to clinical, epidemiological, organizational, and health policy aspects. Key informants from hospitals, MOH, and other governmental agencies agreed on the lack of a process capable of guaranteeing a decision about health technology incorporation based on a transparent use of the best available information, ready to deal with competitive pressures. This adaptation provided a structured and explicit process (introduction, implementation, and development) as well as essential and supporting tools.

Conclusions: MOH adopted the proposal for its progressive implementation while institutional evaluation capacity develops. Further studies are needed on the value placed on health technology assessment–based processes and recommendations by clinicians, managers, policy makers, and patients.

In some countries, reimbursement of drugs is based on cost-effectiveness analysis (CEA), in others not. In times of ageing populations, increasing number of possible interventions, and limited resources, it seems likely that CEA will be more and more important as a basis for decision making.

In our article “Romiplostim and eltrombopag for immune thrombocytopenia: methods for indirect comparison” published in the Journal (1), we presented an indirect comparison of the effectiveness of eltrombopag and romiplostim in raising platelet counts in patients with immune thrombocytopenia (ITP). Indirect comparison analyses are recommended by the National Institute for Health and Care Excellence (NICE) in cases where randomized head-to-head studies do not exist, and were used by NICE in their guidance for the eltrombopag Single Technology Appraisal submission (2).