Objectives: Interferon beta-1b has recently become available for the treatment of secondary progressive multiple sclerosis (SPMS). This study aims at estimating the cost-effectiveness of this new treatment that has been shown in a clinical trial to reduce the progression of the disease. Effectiveness is measured as the number of quality-adjusted life-years (QALYs) gained from the reduction in progression. Because the clinical trial period will only capture part of the treatment's effect in terms of QALYs gained, since benefits achieved during the trial will have an effect beyond it, the cost-effectiveness analysis involves modeling over the longer term using complementary data.

Methods: A Markov model with states based on disability expressed by EDSS scores was used. Transition probabilities were calculated directly from clinical trial data for the first 3 years and then extrapolated to 10 years. Mean costs and utilities for each Markov state were calculated from a population-based cross-sectional study in Sweden.

Results: The incremental cost per QALY is SEK 342,700 (US $39,250;US $1 = SEK 8.73, March 10, 2000) when all costs (direct, informal care, and indirect) are included (discounted 3%). When indirect costs are excluded, the cost per QALY is SEK 542,000 ($62,100).

Conclusions: Cost-effectiveness analysis in SPMS requires that the effect of treatment beyond clinical trials be included. Also, analysis should be done from a societal perspective, since many of the costs occur outside the healthcare system. The cost-utility ratios estimated in this analysis are at or below the mean threshold value indicated in a recent survey of health economists ($60,000).

Canada's health system is a unique combination of public financing and private provision. With the significant government role in financing health services, health technology assessment (HTA) has found a ready audience as a form of policy research. In addition, Canada has been a leader in HTA and is entering a phase of deepening and maturation of HTA activities. The relative absence of dramatic change in the overall health system, coupled with public faith in the Canadian approach has been favorable to HTA's development in Canada. Emerging issues, beyond the demographic and economic pressures facing all Organisation for Economic Co-operation and Development health systems, include the convergence of assessment modalities and organizations for drug and nondrug technologies, increasing public concerns about the viability of Canada's approach to healthcare services, and the transition of HTA from an activity targeting macro-level policy makers to a management tool for healthcare facilities and providers.

Objectives: There are no current established pathognomonic diagnostic features for uterine leiomyosarcomas in the pre- or perioperative setting. Recent inadvertent upstaging of this rare malignancy during laparoscopic morcellation of a presumed fibroid has prompted widespread debate among clinicians regarding the safety of current surgical techniques for management of fibroids. This study aims to conduct a systematic review investigating significant diagnostic features in magnetic resonance imaging (MRI) of uterine leiomyosarcomas.

Methods: A comprehensive database search was conducted guided by PRISMA recommendations for peer-reviewed publications to November 2017. Parameters available in MRI were compared for reliability and accuracy of diagnosis of leiomyosarcomas. A decision tree algorithm classifier model was constructed to investigate whether T1 and T2 MRI signal intensities are useful indicators.

Results: Nine eligible studies were identified for analysis. There appears to be a significant relationship between histopathological type and T1 and T2 intensity signals (p < .05). A decision tree model analyzing T1 and T2 signal intensity readings supports this trend, with a diagnostic specificity of 77.78 percent for uterine leiomyosarcomas. The apparent diffusion coefficient (ADC) values were not observed to have a significant relationship with tumor pathology (p = .18).

Conclusions: Various studies have investigated pre- and perioperative techniques in differentiating uterine leiomyosarcoma from benign fibroids. Given the rarity of the malignancy and lack of pathognomonic diagnostic parameters, there is difficulty in establishing definitive criteria. A decision tree model is proposed to aid diagnosis based on MRI signal intensities.

Objectives: The cost-effectiveness of fracture prevention treatments (vitamin D and calcium and hip protectors) in male and female populations older than seventy years of age in the United-Kingdom was investigated.

Methods: A Markov model was developed to follow up, over lifetime, a hypothetical cohort of males and females at high-risk and general risk of fracture. Patients could sustain hip, wrist, vertebral, and/or other fractures. Fracture rates were obtained from population surveys in the United Kingdom. Effectiveness and quality of life data were identified from the clinical literature. Costs were those incurred by the UK National Health Service, and were obtained from several published sources. Uncertainty was explored through probabilistic sensitivity analysis.

Results: In the general-risk female (male) population, the incremental cost per Quality Adjusted Life Year (QALY) was $11,722 ($47,426) for hip protectors. In the male high-risk population, the incremental cost per QALY was $17,017 for hip protectors. In the female high-risk population, hip protectors were cost-saving. Vitamin D and calcium alone was dominated by hip protectors in all four subgroups.

Conclusions: Current information available on interventions to prevent fractures in the elderly in the United Kingdom, suggests that, at the decision-maker's ceiling ratio of $20,000 per QALY, hip protectors are cost-effective in the general female population and high-risk male population, and cost-saving in the high-risk female population, despite the low compliance rate with the treatment.

Objectives: The objective of this study is to assess the impact of CEDIT (French Committee for the Assessment and Dissemination of Technological Innovations) recommendations on the introduction of technological innovations within the AP-HP (Assistance Publique–Hôpitaux de Paris), the French hospital network to which this body is attached.

Methods: In 2002, a study based on semidirective interviews of fourteen people affected by these recommendations and a case study relating to thirteen recommendations issued between 1995 and 1998 were conducted.

Results: The CEDIT is very scientifically reputable among interviewees. There is generally widespread interest for the recommendations. They are used as decision-making tools by administrative staff and as negotiating instruments by doctors in their dealings with management. Based on the case study, ten of thirteen recommendations had an impact on the introduction of the technology in health establishments. One recommendation appears not to have had an impact. Furthermore, the impact of two technologies was impossible to assess.

Conclusions: This study highlights the significant impact of recommendations arising from a structure that is attached to a hospital network and the good match between CEDIT's objectives and its assignments.

Through the use of three scenarios, this paper presents the challenges for clinical practice guidelines in the 21st century. Such challenges relate to technological developments to improve the efficiency and pace of the development process, to ensure that clinical practice guidelines are kept up to date, and to facilitate implementation of guidelines in the clinical setting. To improve and ensure the validity of the content of clinical practice guidelines, we need to address the important problem of publication bias, for which researchers, granting agencies, industry, and journal editors share responsibility. This means insisting on registration of trials at their inception, and incentives backed up by rules for funding and peer review publication that would promote behaviors to avoid publication bias. The more difficult challenges for clinical practice guidelines relate to what are referred to as attitudinal factors. To achieve optimal efficiencies in development and maintenance of clinical practice guidelines, we need to promote cooperation among various information resource providers internationally and to stress partnership over leadership. Finally, there needs to be reconciliation of the different stakeholder perspectives of the value and purpose of clinical practice guidelines so that they are used appropriately as aids to decision making and are not abused as tools for controlling clinical practice.

Objectives: Although health technology assessment (HTA) has been well established in all developed countries, it has not found a firm footing in many developing countries. This is especially true of the Asia Pacific region, which has much of the world population.

Methods: The beginnings of HTA in this region go back to the work of Dr. David Banta in China and the establishment of the Asian HTA Network. The Network embarked on increasing awareness and building capacity among personnel from the region. Attempts were made to introduce HTA in countries where it did not exist, as well as to strengthen existing HTA programs. The Network had regular meetings, and also carried out a study on the diffusion and utilization of magnetic resonance imaging in the region. In an attempt to boost the efforts of the Network, the author spearheaded the organization of the Asian Regional HTA Conferences in Kuala Lumpur in 2000 and 2003, and in Manila, Philippines, in 2004. In addition, the author carried out a survey on HTA in the region. There are two broad categories of countries in the region: Australia, Malaysia, Singapore, New Zealand, China, Philippines, Korea, Thailand, and Taiwan, which have formal HTA programs, and others for which informal mechanisms or related activities exist, which include Bangladesh, Bhutan, Brunei, Cambodia, India, Indonesia, Laos, Maldives, Mongolia, Nepal, Pakistan, Sri Lanka, and Vietnam.

Results: It is important that once HTA is established, it is used effectively. Perseverance and dedication is needed to ensure the success of an HTA program.

Conclusion: Some countries in the region have effective HTA programs, whereas in some, efforts are being made to establish HTA, or HTA-related activities are being carried out in the absence of a formal HTA program.

Objectives: Hemodialysis is a well-established treatment for 74 percent of end-stage renal disease (ESRD) patients in Greece. The purpose of this study is to provide an estimate of the direct cost of dialysis in a public hospital setting and an estimate of the loss of production for ESRD patients. The results will be useful for public health facility planning purposes.

Methods: A socioeconomic prevalence-based analysis was performed using micro-economic evaluation of health-care resources consumed to provide hemodialysis for ESRD patients in 2000. Lost productivity costs due to illness were estimated for the patient and family using the human capital approach and the friction method. Indirect morbidity costs due to absence from work and long-term were estimated, as well as mortality costs. Mean gross income was used for both patient and family.

Results: Total health-sector cost for hemodialysis in Greece exceeds €171 million, or €182 per session and €229 per inpatient day. There were 2,046 years lost due to mortality, and the potential productivity cost was estimated at €9.9 million, according to the human capital approach, and €303.000, according to the friction method. Total morbidity cost due to absence from work and early retirement was estimated at more than €273 million, according to the human capital approach, and €12.5, according to the friction method.

Conclusions: Providing hemodialysis care for 0.05 percent of the population suffering from ESRD absorbs approximately 2 percent of total health expenditure in Greece. In addition to the cost for the National Health System, production loss due to mortality and morbidity from the disease are also considerable. Promoting alternative technologies such as organ transplantation and home dialysis as well as improving hemodialysis efficiency through satellite units are strategies that may prove more cost-effective and psychologically advantageous for the patients.

Health technology assessment (HTA) has become increasingly important in the European Union as an aid to decision making. As agencies and programs have been established, there is increasing attention to coordination of HTA at the European level, especially considering the growing role of the European Union in public health in Europe. This series of papers describes and analyzes the situation with regard to HTA in the 15 members of the European Union, plus Switzerland. The final paper draws some conclusions, especially concerning the future involvement of the European Commission in HTA.

Objectives: In France, new guidelines for clinical practices concerning cystic fibrosis came out in 2002, underscoring the need for early and intensive management of this disease. Because no recent health economic studies on cystic fibrosis in France were available, we conducted a cost-analysis study before the new guidelines were put into practice, with a view to a later study on the medical and economic impact of these guidelines.

Methods: A cost-analysis study was performed of the inpatient and outpatient costs of patients with cystic fibrosis for the 2000–2001 period. The various direct costs were estimated on a sample of sixty-five adult and pediatric patients managed for cystic fibrosis in two reference medical centers. Data were obtained from medical records, and questionnaires were filled out by the patients. Analysis was made from the perspective of the French healthcare system.

Results: We studied sixty-five patients, 54 percent male patients and 72 percent children under 18 years of age. The total cost of cystic fibrosis care totaled 16,189 euros per year and per patient. Outpatient costs accounted for 88 percent of the total cost versus 12 percent for inpatient costs; medication costs were the highest with 21 percent of the total cost for home intravenous antibiotic treatments and 49 percent of the total cost for chronic medications.

Conclusions: The results show that outpatient costs were higher than inpatient costs, which could be related to the importance granted to home health care in France, notably for intravenous antibiotic treatments given for pulmonary complications.

Objectives: A recent randomized, controlled trial in chronic heart failure patients showed that NT-proBNP-guided, intensive patient management (BMC) on top of multidisciplinary care reduced all-cause mortality and heart failure hospitalizations compared with multidisciplinary care (MC) or usual care (UC). We now performed a cost-utility analysis of these interventions from a payer's perspective.

Methods: Costs related to hospitalizations, ambulatory physician and nurse visits, and NT-proBNP testing for the three management strategies were acquired for both Austria (€) and Canada ($) and combined with the survival and quality of life data from the clinical trial for cost-effectiveness analysis. Data on long-term survival, costs, and quality-adjusted life-years (QALY) were extrapolated for a 20-year time horizon using a Markov model, which simulated the progression of disease through beta-blocker use, hospitalizations, and mortality.

Results: BMC was the most cost-effective strategy as it was dominant (cost-saving with improved health outcome) over both MC and UC based on both Austrian and Canadian costs. Incremental cost-effectiveness ratios for MC relative to UC were €3,746 and $5,554 per QALY gained for Austrian and Canadian costs, respectively. The probabilities for BMC being the most cost-effective strategy were 92 percent at a threshold value of Austrian €40,000 and 93 percent at a threshold value of Canadian $50,000.

Conclusions: NT-proBNP-guided, intensive HF patient management in addition to multidisciplinary care not only reduces death and hospitalization but also proves to be cost-effective.

Objectives: An important option for the medical treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) is continuous positive airway pressure (CPAP) during sleep. This study reports on the cost-effectiveness of CPAP compared with dental devices and lifestyle advice. The work was commissioned by the NHS HTA Programme to inform the National Institute of Health and Clinical Excellence's (NICE) appraisal of CPAP.

Methods: A Markov model compared the interventions over the expected patient lifetime. The primary measure of cost-effectiveness was the incremental cost per quality-adjusted life-year (QALY) gained. The QALY incorporated the impact of treatments on daytime sleepiness, blood pressure and health-related quality of life (HRQoL).

Results: On average, CPAP was associated with higher costs and QALYs compared with dental devices or lifestyle advice. In the base-case analysis, the incremental cost-effectiveness ratio (ICER) for CPAP compared with dental devices was around £4,000 per QALY (2005–06 prices). The probability that CPAP is more cost-effective than dental devices or lifestyle advice at a threshold value of £20,000 per QALY was 0.78 for men and 0.80 for women. Several sensitivity analyses were undertaken and it was found that the ICER for CPAP consistently fell below £20,000 per QALY gained, apart from in a subgroup with mild disease.

Conclusions: The model suggests that CPAP is cost-effective compared with dental devices and lifestyle advice for adults with moderate or severe symptomatic OSAHS at the cost-effectiveness thresholds used by NICE. This finding is reflected in the NICE guidance.

Objectives: The aim of the study was to compare the health-related quality of life (HRQoL) of patients undergoing coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA) before the interventions and 6 and 12 months afterward, and to compare their HRQoL also with that of the general population.

Methods: The sample (n = 615) consisted of consecutive coronary artery disease patients treated with elective CABG (n = 432) or PTCA (n = 183). The baseline data before the treatments were collected by structured interview, the follow-up data mainly by mailed self-administered questionnaires. HRQoL was measured by the 15D. For comparisons, the groups were standardized for differences in socioeconomic and clinical characteristics with a regression analysis.

Results: At baseline, the average 15D scores of the patient groups were 0.752 (95 percent confidence interval [CI], 0.743–0.761) in CABG and 0.730 (95 percent CI, 0.716–0.744) in PTCA. After standardization, the difference between the groups was statistically significant but not clinically important. These scores were significantly worse (statistically and clinically) than the score of 0.883 (95 percent CI, 0.871–0.879) in the general population sample matched with the gender and age distribution of the patients. By 6 months, the CABG and PTCA patients had experienced a statistically significant and clinically important improvement to 0.858 (95 percent CI, 0.844–0.872) and 0.824 (95 percent CI, 0.806–0.842), respectively. No significant change took place in either group from 6 to 12 months.

Conclusions: Both CABG and PTCA produces an approximately similar, clinically important improvement in HRQoL in 1-year follow-up.

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.

In an attempt to establish the extent to which patients and doctors agree on the outcome of health care, the pre- and postoperative states of health of 388 men undergoing transurethral resection of the prostate for benign disease were studied. Generally, high levels of concordance (>70%) were obtained. The strongest agreement was for clearly defined events, such as episodes of acute retention (95%); the weakest agreement occurred over the most subjective symptoms, prognostic expectations, and ambiguous terms (around 60%). The level of agreement was not associated with any characteristics of the patient, surgeon, or treatment.

Data relevant to economic evaluation are being collected alongside clinical trials with increasing frequency. When these trials involve health outcomes and resource utilization in many different countries, numerous methodologic problems arise. This paper describes and discusses the methodology for economic evaluation that will be used in the Economic Substudy of GUSTO llb, as an example of how to address the problems that arise in economic evaluations linked to international trials.

Objectives: The purpose of this review was to examine whether studies from the medical literature focusing on efficiency of diagnostic facilities reported economic evaluation methods appropriately, following guidelines for conducting and reporting economic evaluations.

Methods: A Medline search was conducted, and studies that concerned a diagnostic technology and fulfilled the Drummond criteria were selected for methodological review. The reliability of selection and methodological review based on the abstracts was determined by scoring a random sample of both abstracts and full articles. lnterrater reliability was determined by scoring a random sample of abstracts by both authors. Kappa values were calculated. Nine methodological aspects were reviewed: study design, the type of economic evaluation, the comparison made, the study's perspective, the cost-effectiveness ratio used, the definition of cost-effective, the types of costs analyzed, the cost calculation method, and the use of sensitivity analysis.

Results: Two hundred fifty studies published between 1992 and 1997 were found regarding efficiency of diagnosticfacilities; 134 studiesfulfilled the Drummond criteriaand were selected for methodological review. Kappavalues showed reliability of selection and methodological review and interrater reliability. The existing literatue on the economic evaluation of diagnostic facilities does not adhere well to guidelines for economic evaluation. In 95%, no perspective was mentioned, in 50% of the cases no ratio was given, in 82% the cost calculation method was not mentioned, and in 66% no sensitivity analysis was reported.

Conclusions: Our review suggests that to improve the quality of reporting economic evaluations, editorial boards could issue and enforce guidelines for standard reporting of such studies.

Objectives: Zika virus (ZikaV) is currently one of the most important emerging viruses in the world which has caused outbreaks and epidemics and has also been associated with severe clinical manifestations and congenital malformations. Traditional approaches to combat the ZikaV outbreak are not effective for detection and control. The aim of this study is to propose a cloud-based system to prevent and control the spread of Zika virus disease using integration of mobile phones and Internet of Things (IoT).

Methods: A Naive Bayesian Network (NBN) is used to diagnose the possibly infected users, and Google Maps Web service is used to provide the geographic positioning system (GPS)-based risk assessment to prevent the outbreak. It is used to represent each ZikaV infected user, mosquito-dense sites, and breeding sites on the Google map that helps the government healthcare authorities to control such risk-prone areas effectively and efficiently.

Results: The performance and accuracy of the proposed system are evaluated using dataset for 2 million users. Our system provides high accuracy for initial diagnosis of different users according to their symptoms and appropriate GPS-based risk assessment.

Conclusions: The cloud-based proposed system contributed to the accurate NBN-based classification of infected users and accurate identification of risk-prone areas using Google Maps.

Objectives: To describe a methodology used to keep practice guidelines up to date and to summarize data collected during the first year of implementing this plan with a cancer practice guidelines program.

Methods: The updating strategy includes regular searches of peer-reviewed literature and meeting proceedings, review and interpretation of new evidence, review and revision of clinical recommendations, and notification to practitioners and policy makers about new evidence and its impact on recommendations.

Results: Eighty pieces of new evidence were found relating to seventeen of the twenty guidelines included in this study. On average, four pieces of new evidence were found per guideline, but there was considerable variation across the guidelines. Of the eighty pieces, nineteen contributed to modifications of clinical recommendations in six practice guidelines, whereas the remaining evidence served to support the original recommendations. None of the modifications led to changes that advised against original recommendations. MEDLINE, the Cochrane Library, and meeting proceedings yielded many pieces of evidence, whereas CancerLit and HealthStar did not contribute significantly to the overall yield. Furthermore, key pieces of evidence that led to modifications to the recommendations were often identified by members of the disease site groups before appearing in electronic databases.

Conclusions: The updating process is resource intensive but yields important findings. In response to this evaluation, the updating protocol has been revised such that literature searches are conducted quarterly and the scope of sources searched routinely is restricted to MEDLINE, the Cochrane Library, and meeting proceedings.