Objectives: The study aims to develop an understanding of the views of children and adolescents, parents, and professionals on upper limb prosthetic devices to develop and improve device design. Previous research has found that children are dissatisfied with prostheses but has relied heavily on parent proxy reports and quantitative measures (such as questionnaires) to explore their views.

Methods: Thirty-four participants (eight children aged 8–15 years with upper limb difference, nine parents, eight prosthetists, and nine occupational therapists) contributed to the development of new devices through the BRIDGE methodology of participatory design, using focus groups and interviews.

Results: The study identified areas for improving prostheses from the perspective of children and adolescents, developed prototypes based on these and gained feedback on the prototypes from the children and other stakeholders (parents and professionals) of paediatric upper limb prostheses. Future device development needs to focus on ease of use, versatility, appearance, and safety.

Conclusions: This study has demonstrated that children and adolescents can and should be involved as equal partners in the development of daily living equipment and that rapid prototyping (three-dimensional printing or additive manufacturing), used within a participatory design framework, can be a useful tool for facilitating this.

Objectives: This article presents a cost-utility analysis from the Colombian health system perspective comparing primary prophylaxis to on-demand treatment using exogenous clotting factor VIII (FVIII) for patients with severe hemophilia type A.

Methods: We developed a Markov model to estimate expected costs and outcomes (measured as quality-adjusted life-years, QALYs) for each strategy. Transition probabilities were estimated using published studies; utility weights were obtained from a sample of Colombian patients with hemophilia and costs were gathered using local data. Both deterministic and probabilistic sensitivity analysis were performed to assess the robustness of results.

Results: The additional cost per QALY gained of primary prophylaxis compared with on-demand treatment was 105,081,022 Colombian pesos (COP) (55,204 USD), and thus not considered cost-effective according to a threshold of up to three times the current Colombian gross domestic product (GDP) per-capita. When primary prophylaxis was provided throughout life using recombinant FVIII (rFVIII), which is much costlier than FVIII, the additional cost per QALY gained reached 174,159,553 COP (91,494 USD).

Conclusions: using a decision rule of up to three times the Colombian GDP per capita, primary prophylaxis (with either FVIII or rFVIII) would not be considered as cost-effective in this country. However, a final decision on providing or preventing patients from primary prophylaxis as a gold standard of care for severe hemophilia type A should also consider broader criteria than the incremental cost-effectiveness ratio results itself. Only a price reduction of exogenous FVIII of 50 percent or more would make primary prophylaxis cost-effective in this context.

Objective: To compare two methods of measuring willingness to pay (WTP): closed-ended questions with and without follow-up.

Methods: A measurement experiment based on dichotomous choice contingent valuation survey data is reported. Marginal WTP estimates for alleviation of rheumatoid arthritis symptoms resulting from treatment with a novel anti-rheumatic agent, cA2 (TNF-α blockade), were calculated. Monte Carlo simulations were undertaken to evaluate the methods with respect to their statistical power.

Results: The estimated marginal WTP values using closed-ended questions with and without follow-up were DKK 637 (US $91) and DKK 1,268 (US $181), respectively. A Wilcoxon's signed-rank test showed that the difference of DKK 631 was significant. Moreover, including a follow-up question increases the precision of the result. Monte Carlo simulations showed that trade-offs between power (i.e., the probability of a correct rejection of a false null hypothesis), efficiency, and size may exist in the two models.

Conclusions: There was a significant difference between the WTP estimates when using closed-ended questions with and without follow-up. When choosing between the models, however, power, efficiency, and size could be used as selection criteria.

Adaptive immunity requires both specific recognition of an antigen and its translation into appropriate lymphocyte responses. This paper reviews the striking differences in B- and T-lymphocyte antigen recognition, details the pathways for conversion of protein antigens into peptide–major histocompatibility complex molecule ligands for T-cell receptors, and summarizes the roles of costimulatory signals in lymphocyte activation. This information is used to suggest new approaches for the rational design of vaccines.

A comparison of two assessment methods, consensus among experts and research synthesis of the scientific literature, was performed using a surgical procedure, carotid endarterectomy (CE), as an example. These two methods have been widely advocated as being scientifically valid. While the comparison revealed a number of areas of general agreement, important differences between the two methods emerged. For example, 30-day mortality for asymptomatic patients was considered an effective outcome (ranked first) by the synthesis, but only “quivocal” (ranked third) of six major indicators reported by the consensus method. The synthesis results are also consistent with other literature reviews as well as with recent large-scale randomized trial results. A number of factors that could account for differences between the two methods were examined. Overall, use of consensus panels may be appropriate early in the development of an intervention where the evidence is sparse, while quantitative research synthesis is preferable when a number of high-quality studies have been performed.

Objectives: Equity is one of the founding principles in most healthcare systems. Financial constraints entail an increased risk of exacerbating inequities and a greater need for evidence-based decisions. It is, therefore, both important and timely to enquire how equity can be addressed in health technology assessment (HTA) practice. We aimed to explore related practices from a broad range of HTA agencies, identify exemplary approaches and common concerns, and offer insights for future considerations.

Methods: HTA agencies for which both methodological guides and HTA reports were publicly available were selected from an initial comprehensive pool. Information was extracted on issues ranging from a general commitment to fairness to specific measures targeting both methodological and process-related elements.

Results: Methodological documents and ninety-eight reports from nineteen agencies were analyzed. Our findings indicate that equity was not a standard consideration in HTA report production. The nature of specific approaches and the amount of resources invested into including an equity perspective varied considerably. Specific measures (e.g., appropriate information sources, analytical tools, and schemes) were mentioned by almost half of the agencies analyzed. Albeit sporadic, both horizontal and vertical equity considerations were identified in included HTA reports.

Conclusions: While varying legal contexts and institutional principles can lead to different interpretations of equity at the decision point, a combination of methodological and process-related practices could contribute to more equity-sensitive evaluations, especially in conjunction with enhanced dissemination of existing methodological tools. Networking initiatives on behalf of existing collaborating platforms could play an important role in this direction.

A computer simulation model shows that the cost-effectiveness of treating hypertension is highly sensitive to different assumptions about the effectiveness of treatment, the outcome measure, the cost concept, the discounting of effects, and the duration of therapy. Cost-effectiveness analysis should be supplemented by another approach–cost-benefit analysis based on the contingent valuation (CV) method (the measurement, by survey, of willingness to pay). The CV method is tested in two empirical applications that indicate that it is possible to use the method in this area. Its results should be interpreted with caution, however, since the reliability and validity of the method is not yet established.

Objectives: Bowel cancer is the second most common cancer in England and Wales, accounting for approximately 13,000 deaths per year. Economic evaluations and national guidance have been produced for individual treatments for bowel cancer. However, it has been suggested that Primary Care Trusts develop program budgeting or equivalent methodology demonstrating a whole system approach to investment and disinvestment. The objective of this study was to provide a baseline framework for considering a whole system approach to estimate the direct costs of bowel cancer services provided by the National Health Service (NHS) in England.

Methods: A treatment pathway, developed in 2005, was used to construct a service pathway model to estimate the direct cost of bowel cancer services in England.

Results: The service pathway model estimated the direct cost of bowel cancer services to the NHS to be in excess of £1 billion in 2005. Thirty-five percent of the cost is attributable to the screening and testing of patients with suspected bowel cancer, subsequently diagnosed as cancer-free.

Conclusions: This study is believed to be the most comprehensive attempt to identify the direct cost of managing bowel cancer services in England. The approach adopted could be useful to assist local decision makers in identifying those aspects of the pathway that are most uncertain in terms of their cost-effectiveness and as a basis to explore the implications of re-allocated resources. Research recommendations include the need for detailed costs on surgical procedures, high-risk patients and the utilization of the methods used in this study across other cancers.

Several different live attenuated vaccine vectors currently are under development. These vaccines are composed of living viruses or bacteria that are innocuous to the host but can replicate in host tissues and induce immune responses. The genes encoding foreign antigens can be inserted into these vectors to produce multivalent vaccines that promise to induce immunity to more than one target disease after the administration of a single dose of vaccine.

Recombinant human erythropoietin is an efficacious therapy in treatment of the anemia of end-stage renal failure. However, the scale of impact on quality of life and medical care resources remains uncertain. By reviewing the literature we evaluate cost-effectiveness of recombinant human erythropoietin and show how previous studies may have implicitly overestimated cost-effectiveness.

The purpose of this study was to monitor changes in preoperative routines following recommendations given in 1989 by the Swedish Council on Technology Assessment and by the Swedish Consensus Conference on Preoperative Routines, both suggesting a more individualized utilization of preoperative testing. This was a multicenter, prospective, repetitive study conducted at seven Swedish hospitals providing surgical care. The subjects included all patients presenting at the operating theaters for surgical interventions requiring general or regional anesthesia. The main outcome measures were the frequency of reports of performed preoperative ECG, chest x-ray, and analysis of serum concentration of potassium. Before general recommendations were issued in 1989, 47% of the patients had had a preoperative ECG, 26% had had a chest x-ray, and in 61% serum potassium concentration had been measured. In 1991 these frequencies had been reduced by 5,6, and 9 percentage points, respectively (all figures given standardized for age and sex). Large differences were found between indidividual hospitals. Although recommendations suggesting a more restrictive and individualized utilization of preoperative testing have sparked important revisions in Swedish hospitals, there seems to be substantial potential remaining for further reduction of perfunctory use of preoperative screening.

Objectives: Analysis of and understanding the utilization patterns of diagnostic imaging technologies is important for planning health systems especially in middle- and low-income countries. Almost all published studies have been focused on utilization trends or utilization rates of magnetic resonance imaging (MRI) over time and little has been published about utilization patterns of MRI. This study aims to identify and describe the utilization pattern of MRI in Iran.

Methods: Data was collected from referrals and MRI reports of the population covered by one of the largest insurance organizations (Social Security Organization [SSO]) with more than 27 million beneficiaries in the Country. We focused on patients who had undergone an MRI examination during 1 month (October 13 to November 12), 2005. The data collected consisted of 1,656 referrals for MR imaging and 1,547 MRI reports.

Results: No clear association was found between the number of referrals per 100,000 population and the number of MRI machines per 100,000 population (r = 0.30; p = .13). Neurosurgeons, orthopedists, and neurologists contributed to more than 88 percent of MRI utilization. The Spinal column (55 percent), brain (25.5 percent), and knee (11.0 percent) were the most common parts of the body scanned by MRI.

Conclusions: Having identified some of the most frequent users of MRI technology, any plan for modifying or improving MRI use should focus mainly on these specialties. International evidence on using the technology for examining brain and spine indicate that MRI is mainly used in diagnosing the central nervous system (CNS) diseases.

Background: Cardiovascular disease is one of the most common causes of death worldwide, with many individuals having experienced acute coronary syndrome (ACS). How patients with a history of ACS value aspects of their medical treatment have been evaluated rarely. The aim of this study was to determine patient priorities for long-term drug therapy after experiencing ACS.

Methods: To identify patient-relevant treatment characteristics, a systematic literature review and qualitative patient interviews were conducted. A questionnaire was developed to elicit patient's priorities for different characteristics of ACS treatment using Analytic Hierarchy Process (AHP). To evaluate the patient-relevant outcomes, the eigenvector method was applied.

Results: Six-hundred twenty-three patients participated in the computer-assisted personal interviews and were included in the final analysis. Patients showed a clear priority for the attribute “reduction of mortality risk” (weight: 0.402). The second most preferred attribute was the “prevention of a new myocardial infarction” (weight: 0.272), followed by “side effect: dyspnea” (weight: 0.165) and “side effect: bleeding” (weight: 0.117). The “frequency of intake” was the least important attribute (weight: 0.044).

Conclusion: In conclusion, this study shows that patients strongly value a reduction of the mortality risk in post-ACS treatment. Formal consideration of patient preferences and priorities can help to inform a patient-centered approach, clinical practice, development of future effective therapies, and health policy for decision makers that best represents the needs and goals of the patient.

Objectives: The INTEGRATE-HTA project recommends that complexity be taken into account when conducting health technology assessments (HTAs) and suggests a five-step process for doing that. This study examines whether the approach suggested by INTEGRATE-HTA could be useful, appropriate, and feasible in the context of low- and middle-income countries (LMIC) given some of the typical challenges that healthcare systems face in those countries.

Methods: A nonexhaustive literature review was performed on the implementation in low and middle income countries of the five aspects recommended by the INTEGRATE-HTA project, using the following search terms: national health planning, health sector strategy, health sector performance, assessment criteria, health (management) information, complexity, context, stakeholder consultation.

Results: HTA is being practiced in LMIC in various ways and through different mechanisms, for example in health sector reviews, even though it is usually not referred to as HTA. It does not necessarily follow the five steps distinguished in the INTEGRATE-HTA model (scoping; defining the initial logic model; providing concepts and methods to identify, collect, and synthesize evidence in relation to various dimensions; extracting and presenting evidence in respect of agreed assessment criteria; providing guidance to draw conclusions and formulate recommendations).

Conclusions: The conditions for functional HTA are not always fulfilled in LMICs. At least four aspects would require special attention: (a) the scope and quality of routine health information that can support and be fed into health technology assessments and strategic planning; (b) consensus on health system performance assessment frameworks and their main criteria, in particular the inclusion of social disparities/equity and sustainability; (c) institutional capacity to set evidence-based priorities based on a variety of explicit criteria; (d) political will to engage with stakeholders in a transparent and inclusive consultation process about health priorities.

Little is known about the value patients, physicians, and payers place on intangible attributes of care. Differences in valuations among these groups and misperceptions of value of intangible attributes to other groups can contribute to conflicts about treatment recommendations or coverage decisions. We surveyed patients, physicians, and managed care executives to assess their willingness to pay (WTP) for diagnostic certainty for peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). To determine if patients, physicians, and payers accurately perceive each other's valuations of diagnostic certainty, participants were also asked to estimate the WTP of each of the other types of respondents. Patients were most likely, and executives least likely, to value diagnostic certainty. For PUD, 84% of patients, 61% of physicians, and 43% of executives expressed a positive WTP. Median WTP was low for all three groups ($1–9 for patients and physicians; $0 for payers). Physicians and executives both correctly predicted patient WTP. For GERD, 87% of patients, 52% of physicians, and 29% of executives expressed a positive WTP. Executives underestimated patient WTP. For both diseases, physicians' WTP was overestimated by patients and underestimated by executives. The inconsistency in the value that patients, physicians, and managed care executives place on diagnostic certainty indicates the potential for conflict over practice guidelines or access to services. WTP surveys can provide information to aid in anticipating and addressing areas of disagreement.

Objectives: Internationally, funders require stakeholder involvement throughout health technology assessment (HTA). We report successes, challenges, and lessons learned from extensive stakeholder involvement throughout a palliative care case study that demonstrates new concepts and methods for HTA.

Methods: A 5-step “INTEGRATE-HTA Model” developed within the INTEGRATE-HTA project guided the case study. Using convenience or purposive sampling or directly / indirectly identifying and approaching individuals / groups, stakeholders participated in qualitative research or consultation meetings. During scoping, 132 stakeholders, aged ≥ 18 years in seven countries (England, Italy, Germany, The Netherlands, Norway, Lithuania, and Poland), highlighted key issues in palliative care that assisted identification of the intervention and comparator. Subsequently stakeholders in four countries participated in face–face, telephone and / or video Skype meetings to inform evidence collection and / or review assessment results. An applicability assessment to identify contextual and implementation barriers and enablers for the case study findings involved twelve professionals in the three countries. Finally, thirteen stakeholders participated in a mock decision-making meeting in England.

Results: Views about the best methods of stakeholder involvement vary internationally. Stakeholders make valuable contributions in all stages of HTA; assisting decision making about interventions, comparators, research questions; providing evidence and insights into findings, gap analyses and applicability assessments. Key challenges exist regarding inclusivity, time, and resource use.

Conclusion: Stakeholder involvement is feasible and worthwhile throughout HTA, sometimes providing unique insights. Various methods can be used to include stakeholders, although challenges exist. Recognition of stakeholder expertise and further guidance about stakeholder consultation methods is needed.

Objectives: The aim of this study was to assess the cost-effectiveness of laparoscopic surgery compared with open surgery for the treatment of colorectal cancer.

Methods: A Markov model was developed to model cost-effectiveness over 25 years. Data on the clinical effectiveness of laparoscopic and open surgery for colorectal cancer were obtained from a systematic review of the literature. Data on costs came from a systematic review of economic evaluations and from published sources. The outcomes of the model were presented as the incremental cost per life-year gained and using cost-effectiveness acceptability curves to illustrate the likelihood that a treatment was cost-effective at various threshold values for society's willingness to pay for an additional life-year.

Results: Laparoscopic surgery was on average £300 more costly and slightly less effective than open surgery and had a 30 percent chance of being cost-effective if society is willing to pay £30,000 for a life-year. One interpretation of the available data suggests equal survival and disease-free survival. Making this assumption, laparoscopic surgery had a greater chance of being considered cost-effective. Presenting the results as incremental cost per quality-adjusted life-year (QALY) made no difference to the results, as utility data were poor. Evidence suggests short-term benefits after laparoscopic repair. This benefit would have to be at least 0.01 of a QALY for laparoscopic surgery to be considered cost-effective.

Conclusions: Laparoscopic surgery is likely to be associated with short-term quality of life benefits, similar long-term outcomes, and an additional £300 per patient. A judgment is required as to whether the short-term benefits are worth this extra cost.