Objectives: This study was undertaken to appraise the quality of published pediatric economic evaluations.

Methods: Two independent reviewers appraised 149 randomly selected pediatric health economic studies. Data were collected from full economic evaluations published between 1980 and 1999. Economic evaluations of interventions, programs, and services aimed at neonates to adolescents were included. The Pediatric Quality Appraisal Questionnaire (PQAQ) was used for appraisal. The PQAQ is a 57-item instrument with 13 domains scored from 0 to 1 and one descriptive domain, each corresponding to a key aspect of health economic methodology. The primary outcome was the score for each domain. Additional analyses examined the global rating, the distribution of analytic technique, and the association between domain score and analytic technique.

Results: A total of 38 percent of publications were very good to excellent, whereas 43 percent were fair or worse. Although the Discounting, Target Population, Economic Evaluation, Conclusions, and Comparators domains exhibited good quality (0.74 to 0.78), the papers were of poor quality for Conflict of Interest, Incremental Analysis, and Perspective (0.32 to 0.39). Analytic technique was a significant predictor of quality for study design-related domains, with cost-utility analyses demonstrating the highest domain scores.

Conclusions: Domains closely related to the elements of economic evaluation demonstrated medium to high quality. However, domains related to analysis fared poorly and are worthy of further methodological research to improve the use of health economic methods in children.

Objectives: The aim of this study was to analyze the motives, enablers, and barriers to promote or initiate health technology assessment (HTA) in different contexts.

Methods: An observational study design was used to address the above question that included a survey questionnaire and a two-phase study. The respondents for the questionnaire and first round of the study were from HTA agencies of high income countries and those low and middle income countries that have managed to establish HTA agencies (n = 50), that are members of International Network of Agencies for Health Technology Assessment (INAHTA), EuroScan, or European network for Health Technology Assessment (EUnetHTA). The second round of the study was exclusively with respondents from low and middle income countries that were manly affiliated to Health Technology Assessment International (HTAi) interest subgroup for low and middle income countries and aimed to initiate HTA activities (n = 34).

Results: Forty-one of fifty HTA agencies answered the survey questionnaire. Thirty-three of fifty individuals belonging to HTA agencies from high income countries and sixteen of thirty-four individuals from low and middle income countries answered in the first and second phases of the study, respectively. In the promotion and/or initiation of HTA, the top three motives were the same for both high income and low and middle income countries. The top three enablers were also similar but the prioritization varies. The top three barriers were more context specific.

Conclusions: HTA promotion or initiation is influenced by the following: (i) key players that affect the time taken to establish HTA agencies; (ii) three models for HTA promotion and initiation: top-down (political interest), bottom-up (academic/research interest), and converging (political and academic/research interests); and (iii) motives, enablers, and barriers at the local context.

Objectives: To outline the development, structure, data assumptions, and application of an Australian economic model for stroke (Model of Resource Utilization, Costs, and Outcomes for Stroke [MORUCOS]).

Methods: The model has a linked spreadsheet format with four modules to describe the disease burden and treatment pathways, estimate prevalence-based and incidence-based costs, and derive life expectancy and quality of life consequences. The model uses patient-level, community-based, stroke cohort data and macro-level simulations. An interventions module allows options for change to be consistently evaluated by modifying aspects of the other modules. To date, model validation has included sensitivity testing, face validity, and peer review. Further validation of technical and predictive accuracy is needed. The generic pathway model was assessed by comparison with a stroke subtypes (ischemic, hemorrhagic, or undetermined) approach and used to determine the relative cost-effectiveness of four interventions.

Results: The generic pathway model produced lower costs compared with a subtypes version (total average first-year costs/case AUD$15,117 versus AUD$17,786, respectively). Optimal evidence-based uptake of anticoagulation therapy for primary and secondary stroke prevention and intravenous thrombolytic therapy within 3 hours of stroke were more cost-effective than current practice (base year, 1997).

Conclusions: MORUCOS is transparent and flexible in describing Australian stroke care and can effectively be used to systematically evaluate a range of different interventions. Adjusting results to account for stroke subtypes, as they influence cost estimates, could enhance the generic model.

The widespread implementation of rationing and priority-setting policies in health care opposes the stochastic practice of medicine induced by professional uncertainty and professional vested interests in market-oriented clinical environments. It also clashes with consumers' overly optimistic and “mythical” view of the effectiveness of medicine, which is bound to support a potentially unlimited provision of health services. Thus, for consumers and society at large, it is necessary to create conditions favorable for a more conscious demand of evidence-based health care. In pursuit of this goal, we suggest the adoption of a community-oriented strategy based upon delivery of information to the public in order a) to generate greater awareness (“healthy skepticism”) among consumers, through disclosure of data on the true effectiveness of health care interventions and on the existing variation in their utilization, and b) to provide tools to empower consumers in dealing better with both the uncertainty in their own individual patient-physician relationships and with the health policy issues to be faced in the future. Such a community-oriented strategy could also reinforce and support, through the generation of a “bottom-up” pressure from consumers toward physicians, a wider adoption of evidence-based interventions by health care professionals. This paper, using data from surveys on public opinions and attitudes toward the practice of medicine, focuses on how consumer demand for more evidence-based medical practice can be promoted.

Objectives: To investigate doctors' and nurses' attitudes toward 14 potential prioritization criteria.

Methods: This study was performed by using the random paired scenario method. The respondents received a questionnaire with 12 pairs of scenarios, imaginary patient cases, each of which contained two to three different prioritization criteria (e.g., child, old patient, poor patient). Respondents were asked which one of each scenario pair they would choose if only one patient could be treated. The scenarios were randomly put into 30 different questionnaire sets. There was a random selection of 241 doctors and 151 nurses in Finland, with response rates of 60.3% and 50.3%, respectively.

Results: Doctors prioritized young patients, severe disease, expensive treatments and posteriorized (negatively prioritized) demented or institutionalized patients, and patients having a self-caused disease. Children were strongly prioritized, even over serious diseases. Expensive treatments appeared to be favored by doctors, and this result cannot be explained by severity of disease. Nurses' attitudes were similar to those of doctors.

Conclusions: Children were strongly prioritized. Elderly persons were posteriorized if they had dementia or were living in institutions. Patients having a self-caused disease are posteriorized, more often by nurses than by doctors.

Objectives: Early awareness and alert (EAA) activities are increasingly recognized to be an important component of the health technology assessment (HTA) process. Sharing information on methods used in this discipline is vital to ensure the development of sustainable systems. The objectives of this study is to outline the approach taken to share the different methods that members of the EuroScan International Network use by producing a methods toolkit; and to provide an overview of the similarities and differences in methods adopted by EAA systems.

Methods: A Delphi technique was used to develop the methods toolkit. Structured questionnaires were used to identify the sources used in the identification of emerging technologies and to determine the methods used by agencies to carry out EAA activities.

Results: A methods toolkit incorporating guidance on all of the stages described by EuroScan members was produced. The toolkit and an accompanying checklist presents users with different methods that can be adopted to suit their needs. The comparative analysis demonstrates that different methods are being used by EAA systems dependent on resources available and customer requirements. Differences in identification, filtration, prioritization, and assessment are apparent along with the role of collaborators in these processes.

Conclusions: The methods used by EAA systems are not homogeneous resulting in a toolkit constructed on the basis of “one size doesn't fit all.” Methods in this discipline are developing continually to accommodate changes in health systems and the HTA world. Differences between agencies and the sharing of ideas and experiences enable EAA agencies to adapt to these developments.

Objectives: Local health technology assessment (HTA) to determine whether new health technologies should be adopted is now a common practice in many healthcare organizations worldwide. However, little is known about hospital-based HTA activities in France. The objective of this study was to explore hospital-based HTA activities in French university hospitals and to provide a picture of organizational approaches to the assessment of new and innovative medical devices.

Methods: Eighteen semi-structured interviews with hospital pharmacists were conducted from October 2012 to April 2013. Six topics were discussed in depth: (i) the nature of the institution concerned; (ii) activities relating to innovative medical devices; (iii) the technology assessment and decision-making process; (iv) the methodology for technology assessment; (v) factors likely to influence decisions and (vi) suggestions for improving the current process. The interview data were coded, collated and analyzed statistically.

Results: Three major types of hospital-based HTA processes were identified: medical device committees, innovation committees, and “pharmacy & management” processes. HTA units had been set up to support medical device and innovation committees for technology assessment. Slow decision making was the main limitation to both these committee-based approaches. As an alternative, “pharmacy & management” processes emerged as a means of rapidly obtaining a formal assessment.

Conclusions: This study provides an overview of hospital-based HTA initiatives in France. We hope that it will help to promote hospital-based HTA activities in France and discussions about ways to improve and harmonize practices, through the development of national guidelines and/or a French mini-HTA tool, for example.

Objectives: Mechanical circulatory support through left ventricular assist devices (LVADs) improves survival and quality of life for patients with end-stage heart failure who are ineligible for cardiac transplantation. Our aim was to calculate the cost-effectiveness of continuous-flow LVADs.

Methods: A cost-utility analysis from a societal perspective was performed. A lifetime Markov model was set up in which continuous-flow LVAD was compared with optimal medical therapy (OMT). The treatment effect was modeled indirectly combining the results of the REMATCH trial comparing OMT with a pulsatile-flow LVAD and the HeartMate II Destination Therapy Trial comparing a pulsatile-flow LVAD with a continuous-flow LVAD. Cost data were based on real-world financial data of sixty-nine patients with a HeartMate II implantation from the University Medical Centre Utrecht (the Netherlands). One-way and probabilistic sensitivity analyses were performed.

Results: Comparing the continuous-flow HeartMate II with OMT, 3.23 (95 percent confidence interval [CI], 2.18–4.49) life-years were gained (LYG) or 2.83 (95 percent CI, 1.91–3.90) quality-adjusted life-years (QALYs). The cost of an LVAD implant was approximately €126,000, of which the device itself represented the largest cost, being €70,000. Total incremental costs amounted to €299,100 (95 percent CI, 190,500–521,000). This resulted in an incremental cost-effectiveness ratio of €94,100 (95 percent CI, 59,100–160,100) per LYG or €107,600 (95 percent CI, 66,700–181,100) per QALY. Sensitivity analyses showed these results were robust.

Conclusions: Although LVAD destination therapy improves survival and quality of life, it remains a relatively expensive intervention which renders the reimbursement of this therapy questionable.

Objectives: This study compared the relative cost-effectiveness of stroke care provided in London and Copenhagen.

Methods: Hospitalized stroke patients at centers in London (1995–96) and Copenhagen (1994–95) were included. Each patient's use of hospital and community health services was recorded for 1 year after stroke. Center-specific unit costs were collected and converted into dollars using the Purchasing Power Parity Index. An incremental cost-effectiveness ratio (ICER) was calculated comparing a Copenhagen model of stroke care to a London model, using regression analysis to adjust for case-mix differences.

Results: A total of 625 patients (297 in Copenhagen, 328 in London) were included in the analysis. Most patients in London (85%) wereadmitted to general medical wards, with 26% subsequently transferred to a stroke unit. In Copenhagen, 57% of patients were directly admitted to a stroke or neurology unit, with 23% then transferred to a separate rehabilitation hospital. The average length of total hospital stay was 11 days longer in Copenhagen. Patients in Copenhagen were less likely to die than those in London; for patients with cerebral infarction the hazard ratio after case-mix adjustment was 0.53 (95% CI from 0.35 to 0.80). However, a lower proportion of patients with hemorrhagic stroke died in London. The ICER of using the Copenhagen compared with the London model of care ranged from $21,579 to $37,444 per life-year gained for patients with cerebral infarctions.

Conclusions: The ICERs of the Copenhagen compared with the London model of care were within a range generally regarded as cost-effective.

Objectives: The aim of this study was to determine how evidence from systematic review (SR) is perceived and negotiated by expert stakeholders in considering a technology for potential disinvestment.

Methods: An evidence-informed stakeholder engagement examined results from a diagnostic accuracy SR of vitamin B12 and folate tests. Pathologists deliberated around the SR findings to generate an informed contribution to future policy for the funding of B12 and folate tests. Deliberations were transcribed and subject to qualitative analysis.

Results: Pathologists did not engage with findings from the SR in depth; rather they sought to contest the terms of the problem driving the review and attempted to reframe it. Pathologists questioned the usefulness of SR outcomes given the variable definitions of B12 deficiency and deferred addressing disinvestment options specifically pertaining to B12 testing. However, folate testing was proffered as a potential disinvestment candidate, based upon pathologists' definition of “appropriate” evidence beyond the bounds of the SR.

Conclusions: The value of SR to informing disinvestment deliberations by expert stakeholders may be a function of timing as well as content. Engagement of stakeholders in co-produced evidence may be required at two levels: (i) Early in the synthesis phase to help shape the SR and harmonize expert views with the available evidence (including gaps); (ii) Collaboration in primary research to fill evidence-gaps thus supporting evidence-based disinvestment. Without this, information asymmetry between clinically engaged experts and decision makers may preclude the collaborative, informed, and technical discussions required to generate productive policy change.

Objectives: One barrier to economic evaluation alongside neonatal randomized controlled trials is the expense of collecting detailed patient resource information. To reduce this data collection burden, we identified the key resource items that predict daily ancillary costs for extremely low birth weight infants.

Methods: Participants were 385 infants enrolled in the Trial of Indomethacin Prophylaxis for Preterms in nine tertiary level neonatal intensive care units in Canada. Information on eighty-nine nonpersonnel resource items was abstracted from the hospital chart from admission to tertiary hospital discharge. Unit costs were derived from a provincially standardized cost accounting system. Using stepwise linear regression, models correlating total daily ancillary costs with key resource items were constructed for each of five periods of admission. Models were derived in a randomly split half of the total sample of patient days and validated against the remainder.

Results: The 385 infants contributed resource information from 23,354 admission days. The regression model for weeks one to twelve included the covariates surfactant, chest radiograph, red blood cell transfusion, cranial ultrasound, abdominal radiograph, parenteral amino acid infusion, surgery, platelet transfusion, and echocardiogram and explained 91% of the variability in daily nonpersonnel costs (P<.0001). Models for other admission periods similarly included between four and eight covariates, were highly significant (P<.0001) and explained between 76% and 94% of daily ancillary cost variability. The regression equations showed excellent predictive power when applied to the second half of the patient data set.

Conclusions: Daily nonpersonnel costs for extremely low birth weight infants are driven by a limited number of key resource variables. The ability to predict total ancillary costs with minimal data collection will facilitate inclusion of economic evaluations in neonatal trials.

Objective: Renal replacement therapy (RRT) is essential for maintenance of life for those with end-stage renal disease. However, there remain many areas of uncertainty about which method of RRT should be chosen. This paper reports an economic model based on a systematic review that attempts to determine which method of dialysis, continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis, a patient should have as the initial method of RRT.

Methods: A systematic review and a costing exercise carried out in a Scottish hospital were used to populate a Markov model. Scenario analysis was used to model plausible variations in variables included in the model.

Results: In 8 of the 16 scenarios developed hemodialysis dominated CAPD. In a further eight scenarios, the cost per life-year displayed considerable variability, ranging from between £5,000 to £51,000. The higher costs per life-year were associated with minimum estimates of additional survival for a patient starting RRT on hospital hemodialysis.

Conclusion: It may be more cost-effective to manage patients starting on RRT with hospital hemodialysis than CAPD. This has particular implications for the United Kingdom, given that up to 50% of new patients receive CAPD.

Objectives: The aim of this study was to evaluate the comparative effectiveness of anti-vascular endothelial growth factor therapy in the treatment of diabetic macular edema (DME).

Methods: Searches focused on reports concerning treatment of DME with aflibercept, bevacizumab, pegaptanib, or ranibizumab published between January 2000 and June 30, 2012, with comparisons to laser photocoagulation, sham injection, or other control (e.g., triamcinolone). Effectiveness was based on best-corrected visual acuity (BCVA), in terms of letters gained. Direct meta-analyses were conducted on BCVA for each anti-vascular endothelial growth factor (VEGF) agent; indirect comparisons also were performed for each anti-VEGF pair.

Results: A total of fifteen randomized controlled trials (eleven fair- or good-quality) and eight observational studies were included. No direct comparative studies were identified. Improvement in visual acuity versus control was seen with all agents (range: 4–9 letters); outcomes were consistent across multiple timepoints. Meta-analyses showed no statistically significant and/or consistent differences between agents in BCVA changes or the percentage of patients gaining more than ten letters. No discernible differences in the potential harms of anti-VEGFs, including ocular events, MI, stroke, and other cardiovascular events, as well as death, were noted between aflibercept, pegaptanib, and ranibizumab. Data on harms for bevacizumab were underreported.

Conclusions: All anti-VEGF agents are effective in improving visual acuity in comparison to laser photocoagulation. Evidence is insufficient to distinguish the performance of any single anti-VEGF agent over others. The safety of bevacizumab remains the greatest element of uncertainty.

Objectives: Cost studies of positron emission tomography (PET) imaging are important for resource and operational planning; the most relevant cost analysis in this regard is the marginal cost. Operating within a regulatory environment can add considerably to the costs of providing PET services. Previously published research has not examined the marginal cost structure of PET nor have they described the implications of regulatory compliance to operational costs. The purpose of this study was to conduct a comprehensive cost estimation of PET imaging with 18F-fluorodeoxyglucose (18F-FDG) to better identify the fixed and variable cost components, the marginal cost structure, and the added costs of satisfying regulatory requirements.

Methods: Financial data on capital and operating expenses were collected for the PET center at the Cross Cancer Institute in Edmonton, Alberta, Canada.

Results: The total per-service cost for clinical operations ranged between $7,869 (400 annual scans) and $1,231 (3,200 annual scans). The marginal cost for the center remained steady as volume increased up to the throughput capacity.

Conclusions: Results indicate that economies from increased volumes did not arise. Regulatory requirements added significant costs to operating an 18F-FDG-PET center.

Background: Keeping clinical practice recommendations up-to-date with a continually evolving evidence base presents challenges. Resources required to update recommendations compete with those needed to evaluate newer treatments.

Methods: We describe an approach developed by the UK National Institute for Health and Clinical Excellence (NICE) for updating clinical practice recommendations for new interventional procedures and we evaluate relevant initial experience of using this system. Depending on whether evidence for a procedure is judged adequate or inadequate for safety and efficacy, use in clinical practice is usually recommended with either “normal” or “special” arrangements for patient consent, data collection and institutional oversight, respectively. We examined whether differences in the state of the evidence at the initial and the updated appraisal of procedures were associated with changed recommendations.

Results: Since 2008, updating of recommendations focuses on procedures with initially inadequate evidence. “Special arrangements” recommendations about eleven procedures were updated after 3.3–6.5 years (median, 5.3 years), and recommendations for six were changed to “normal arrangements.” Overall, procedures with changed (“special-to-normal”) recommendations had a greater increase in the number of patients included in observational studies published since the initial guidance.

Conclusions: Procedures with changed (“special-to-normal”) recommendations generally had greater increases in their evidence base. Although uncertainties about optimal methods for keeping evidence-based recommendations up-to-date remain, this experience should be useful to policy makers in developing processes for prioritizing scarce resources for updating clinical practice recommendations. Further studies are needed about the value placed on “updated” recommendations by clinicians, policy-makers, and patients.

Objectives: Treatment switching occurs when patients in a randomized clinical trial switch from the treatment initially assigned to them to another treatment, typically from the control to experimental treatment. This study discusses the issues this raises and possible approaches to addressing them in trials of cancer drugs.

Methods: Stakeholders from around the world were invited to a 1.5-day Workshop in Adelaide, Australia. This study attempts to capture the key points from the discussion and the perspectives of the various stakeholder groups, but is not a formal consensus statement.

Results: Treatment switching raises challenging ethical issues with arguments for and against allowing it. It is increasingly common in cancer drug trials and presents challenges for the interpretation of results by regulators, clinicians, patients, and payers. Proposals are offered for good practice in the design, management, and analysis of trials and wider development programs for cancer drugs in which treatment switching has occurred or is likely to. Recommendations are also offered for further action to improve understanding of the importance and challenges of treatment switching and to promote agreement between key stakeholders on guidelines and other steps to address these challenges.

Conclusions: The handling of treatment switching in trials is of concern to all stakeholders. On the basis of the discussions at the Adelaide International Workshop, there would appear to be common ground on approaches to addressing treatment switching in cancer trials and scope for the development of formal guidelines to inform the work of regulators, payers, industry, trial designers and other stakeholders.

Many new hip prostheses are now available for use in total hip replacement. The majority remain untested relative to standard prostheses; however, many new prostheses are substantially more costly. We examine how much more effective new prostheses must be, in terms of reducing the need for revision operations, in order to justify this increased cost.

To the Editor:

In a recent study in this Journal, Drummond and colleagues (5) attempt to address the question “Whether the standard methods of HTA are adequate for assisting decisions on patient access to and funding of orphan drugs” before proposing “a research agenda to help understand the societal value of orphan drugs and issues surrounding their development, funding, and use.”