Noninvasive Prenatal Testing for Trisomies 21, 18, and 13, Sex Chromosome Aneuploidies, and Microdeletions in Average-Risk Pregnancies: A Cost-Effectiveness Analysis.

OBJECTIVE: The cost effectiveness of noninvasive prenatal testing (NIPT) has been established for high-risk pregnancies but remains unclear for pregnancies at other risk levels. The aim was to assess the cost effectiveness of NIPT in average-risk pregnancies from the perspective of a provincial public payer in Canada. METHODS: A model was developed to compare traditional prenatal screening (TPS), NIPT as a second-tier test (performed only after a positive TPS result), and NIPT as a first-tier test (performed instead of TPS) for trisomies 21, 18, and 13; sex chromosome aneuploidies; and microdeletions in a hypothetical annual population cohort of average-risk pregnancies (142 000 to 148,000) in Ontario, Canada. A probabilistic analysis was conducted with 5000 repetitions. RESULTS: Compared with TPS, NIPT as a second-tier test detected more affected fetuses with trisomies 21, 18, and 13 (188 vs. 158), substantially reduced the number of diagnostic tests (i.e., chorionic villus sampling and amniocentesis) performed (660 vs. 3107), and reduced the cost of prenatal screening ($26.7 million vs. $27.6 million) annually. Compared with second-tier NIPT, first-tier NIPT detected an additional 80 cases of trisomies 21, 18, and 13 at an additional cost of $33 million. The incremental cost per additional affected fetus detected was $412 411. Extending first-tier NIPT to include testing for sex chromosome aneuploidies and 22q11.2 deletion would increase the total screening cost. CONCLUSIONS: NIPT as a second-tier test is cost-saving compared with TPS alone. Compared with second-tier NIPT, first-tier NIPT detects more cases of chromosomal anomalies but at a substantially higher cost.

Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a meta-analysis of randomized controlled trials over 2 decades

Background: Approximately 35% of people with depression do not respond to 2 courses of antidepressant medications of adequate dosage, and treatment-resistant depression (TRD) is still a major clinical concern with a great impact on patients, their families, society and the health system. The present meta-analysis evaluates antidepressant efficacy of unilateral and bilateral repetitive transcranial magnetic stimulation (rTMS) in patients with unipolar TRD. Methods: We searched for randomized controlled trials that compared rTMS with sham treatment and were published by Apr. 3, 2017. The primary outcome was improvement in depression scores measured using the Hamilton Rating Scale for Depression. The secondary outcomes were remission and response rates. Two independent review authors screened the studies and extracted the data. Results: Twenty-three studies met the inclusion criteria. Meta-analysis of the depression scores showed a weighted mean difference (WMD) of 3.36 (95% confidence interval [CI] 1.85­4.88) between unilateral rTMS and sham treatment. Stratified data showed that the effect was relatively higher when rTMS was used as an add-on to antidepressant medications (WMD 3.64, 95% CI 1.52­5.76) than when it was used as a stand-alone treatment (WMD 2.47, 95% CI 0.90­4.05). The WMD between bilateral rTMS and sham was 2.67 (95% CI 0.83­4.51), and all studies that contributed to this outcome used rTMS while participants were taking antidepressant medications. The pooled remission and response rates for unilateral rTMS versus sham treatment were 16.0% and 25.1% for rTMS and 5.7% and 11.0% for sham treatment, respectively. The pooled remission and response rates for bilateral rTMS versus sham treatment were 16.6% and 25.4% for rTMS and 2.0% and 6.8% for sham treatment, respectively. Conclusion: This study suggests that rTMS has moderate antidepressant effects and appears to be promising in the short-term treatment of patients with unipolar TRD.

A Non-inferiority Framework for Cost-Effectiveness Analysis.

BACKGROUND: Traditional decision rules have limitations when a new technology is less effective and less costly than a comparator. We propose a new probabilistic decision framework to examine non-inferiority in effectiveness and net monetary benefit (NMB) simultaneously. We illustrate this framework using the example of repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) for treatment-resistant depression. METHODS: We modeled the quality-adjusted life-years (QALYs) associated with the new intervention (rTMS), an active control (ECT), and a placebo control, and we estimated the fraction of effectiveness preserved by the new intervention through probabilistic sensitivity analysis (PSA). We then assessed the probability of cost-effectiveness using a traditional cost-effectiveness acceptability curve (CEAC) and our new decision-making framework. In our new framework, we considered the new intervention cost-effective in each simulation of the PSA if it preserved at least 75 percent of the effectiveness of the active control (thus demonstrating non-inferiority) and had a positive NMB at a given willingness-to-pay threshold (WTP). RESULTS: rTMS was less effective (i.e., associated with fewer QALYs) and less costly than ECT. The traditional CEAC approach showed that the probabilities of rTMS being cost-effective were 100 percent, 39 percent, and 14 percent at WTPs of $0, $50,000, and $100,000 per QALY gained, respectively. In the new decision framework, the probabilities of rTMS being cost-effective were reduced to 23 percent, 21 percent, and 13 percent at WTPs of $0, $50,000, and $100,000 per QALY, respectively. CONCLUSIONS: This new framework provides a different perspective for decision making with considerations of both non-inferiority and WTP thresholds.

Cost-Utility Analysis of Extending Public Health Insurance Coverage to Include Diabetic Retinopathy Screening by Optometrists.

BACKGROUND: Diabetic retinopathy (DR) is one of the leading causes of vision loss and blindness in Canada. Eye examinations play an important role in early detection. However, DR screening by optometrists is not always universally covered by public or private health insurance plans. This study assessed whether expanding public health coverage to include diabetic eye examinations for retinopathy by optometrists is cost-effective from the perspective of the health care system. METHODS: We conducted a cost-utility analysis of extended coverage for diabetic eye examinations in Prince Edward Island to include examinations by optometrists, not currently publicly covered. We used a Markov chain to simulate disease burden based on eye examination rates and DR progression over a 30-year time horizon. Results were presented as an incremental cost per quality-adjusted life year (QALY) gained. A series of one-way and probabilistic sensitivity analyses were performed. RESULTS: Extending public health coverage to eye examinations by optometrists was associated with higher costs ($9,908,543.32) and improved QALYs (156,862.44), over 30 years, resulting in an incremental cost-effectiveness ratio of $1668.43/QALY gained. Sensitivity analysis showed that the most influential determinants of the results were the cost of optometric screening and selected utility scores. At the commonly used threshold of $50,000/QALY, the probability that the new policy was cost-effective was 99.99%. CONCLUSIONS: Extending public health coverage to eye examinations by optometrists is cost-effective based on a commonly used threshold of $50,000/QALY. Findings from this study can inform the decision to expand public-insured optometric services for patients with diabetes.

Hepatitis B virus screening before adjuvant chemotherapy in patients with early-stage breast cancer: a cost-effectiveness analysis.

Most patients with hepatitis B virus (HBV) have no symptoms, and many are unaware of the infection. However, HBV can reactivate with immunosuppression; chemotherapy causes reactivation in 22 % of hepatitis B surface antigen-positive patients. HBV reactivation can be fatal. HBV reactivation can be prevented, provided that HBV is recognized prior to chemotherapy. The objective of this study is to estimate the health and economic effects of HBV screening strategies in patients receiving adjuvant chemotherapy for breast cancer. We developed a state-transition microsimulation model to examine the cost-effectiveness of three HBV screening strategies: (1) "No screening"; (2) "Screen-and-Treat to prevent reactivation" (screen-all) with either lamivudine/tenofovir (LAM/TDF) or entecavir (ETV); and (3) "Screen-and-Treat high-risk only" (screen-HR) and treat with either LAM/TDF or ETV. Model data were obtained from the published literature. We used a payer's perspective, a lifetime horizon, and a 5 % discount rate for the analysis. "Screen-all" would prevent at least 38 severe reactivations per 100,000 persons screened over the lifetime of the cohort. "Screen-all" was associated with an increase of 0.0034-0.0035 QALYs and an additional cost of C$164-C$266 per person, which translated into an incremental cost-effectiveness ratio of C$47,808/QALY-C$76,527/QALY gained compared with "No screening" depending on the antiviral therapy received. "Screen-all" was the most cost-effective strategy, while "Screen-HR" was inferior in all scenarios tested. HBV screening before adjuvant chemotherapy for breast cancer patients would prevent a significant number of reactivations, would likely be moderately cost-effective, and may extend the lives of breast cancer patients.

Cost-effectiveness of screening for hepatitis C in Canada.

BACKGROUND: The seroprevalence of hepatitis C virus (HCV) infection among Canadians is estimated at 0.3% to 0.9%. Of those with chronic HCV infection, 10% to 20% will experience advanced liver disease by 30 years of infection. Targeted screening seems a plausible strategy. We aimed to estimate the health and economic effects of various screening and treatment strategies for chronic HCV infection in Canada. METHODS: We used a state-transition model to examine the cost-effectiveness of 4 screening strategies: no screening; screen and treat with pegylated interferon plus ribavarin; screen and treat with pegylated interferon and ribavarin-based direct-acting antiviral agents; and screen and treat with interferon-free direct-acting antivirals. We considered Canadian residents in 2 age groups: 25-64 and 45-64 years of age. We obtained model data from the literature. We predicted deaths related to chronic HCV infection, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios. RESULTS: We found that screening and treating would prevent at least 9 HCV-related deaths per 10,000 persons screened over the lifetime of the cohort. Screening was associated with QALY increases of 0.0032 to 0.0095 and cost increases of $124 to $338 per person, which translated to an incremental cost-effectiveness ratio of $34,359 to $44,034 per QALY gained, relative to no screening, depending on age group screened and antiviral therapy received. INTERPRETATION: A selective one-time HCV screening program for people 25-64 or 45-64 years of age in Canada would likely be cost-effective. Identification of silent cases of chronic HCV infection and the offer of treatment when appropriate could extend the lives of Canadians at reasonable cost.

An update of "Cost-effectiveness of rotavirus vaccination in the Netherlands: the results of a Consensus Rotavirus Vaccine model".

BACKGROUND: To update a cost-effectiveness analysis of rotavirus vaccination in the Netherlands previously published in 2011. METHODS: The rotavirus burden of disease and the indirect protection of older children and young adults (herd protection) were updated. RESULTS: When updated data was used, routine infant rotavirus vaccination in the Netherlands would potentially become an even more cost-effective strategy than previously estimated with the incremental cost per QALY at only €3,000-4,000. Break-even total vaccination costs were indicated at €92-122, depending on the applied threshold. CONCLUSIONS: We concluded that the results on potentially favourable cost-effectiveness in the previous study remained valid, however, the new data suggested that previous results might represent an underestimation of the economic attractiveness of rotavirus vaccination.

Comparative review of three cost-effectiveness models for rotavirus vaccines in national immunization programs; a generic approach applied to various regions in the world.

BACKGROUND: This study aims to critically review available cost-effectiveness models for rotavirus vaccination, compare their designs using a standardized approach and compare similarities and differences in cost-effectiveness outcomes using a uniform set of input parameters. METHODS: We identified various models used to estimate the cost-effectiveness of rotavirus vaccination. From these, results using a standardized dataset for four regions in the world could be obtained for three specific applications. RESULTS: Despite differences in the approaches and individual constituting elements including costs, QALYs Quality Adjusted Life Years and deaths, cost-effectiveness results of the models were quite similar. Differences between the models on the individual components of cost-effectiveness could be related to some specific features of the respective models. Sensitivity analysis revealed that cost-effectiveness of rotavirus vaccination is highly sensitive to vaccine prices, rotavirus-associated mortality and discount rates, in particular that for QALYs. CONCLUSIONS: The comparative approach followed here is helpful in understanding the various models selected and will thus benefit (low-income) countries in designing their own cost-effectiveness analyses using new or adapted existing models. Potential users of the models in low and middle income countries need to consider results from existing studies and reviews. There will be a need for contextualization including the use of country specific data inputs. However, given that the underlying biological and epidemiological mechanisms do not change between countries, users are likely to be able to adapt existing model designs rather than developing completely new approaches. Also, the communication established between the individual researchers involved in the three models is helpful in the further development of these individual models. Therefore, we recommend that this kind of comparative study be extended to other areas of vaccination and even other infectious disease interventions.

The Health Burden of Invasive Meningococcal Disease: A Systematic Review.

OF KEY POINTS: Although relatively rare, invasive meningococcal disease continues to be a health concern, especially in young children. This systematic review clearly delineates both the near- and long-term morbidities that can occur after, and persist beyond, the period of acute illness. BACKGROUND: Although rare, invasive meningococcal disease (IMD) continues to be a health concern in high-income countries because of its severe morbidity and relatively high case fatality rate, especially in young children. However, studies measuring sequelae of IMD across the spectrum of invasive syndromes have not been systematically reviewed. We conducted a systematic review of sequelae attributable to IMD and quality of life (QoL) in IMD survivors in high-income countries. METHODS: We searched Medline, Embase, and HealthSTAR for primary studies that assessed sequelae or QoL in individuals of any age with and without IMD. Two independent reviewers screened articles, abstracted data, and performed quality appraisal. The findings were summarized qualitatively. RESULTS: Of 1884 citations screened, 17 studies were included. The most commonly assessed sequelae were hearing impairment, cognitive impairment, and psychological problems. In general, children with IMD had a greater incidence of hearing loss and psychological disorders, including attention-deficit/hyperactivity disorder. However, its effects on intelligence in children remain unclear. No statistical differences in overall cognitive function in adults were reported. The odds of death were significantly increased with IMD at hospital discharge and up to 30 years after disease. Lower overall QoL was observed in those who had IMD versus controls. CONCLUSIONS: The results of this systematic review delineate both the short- and long-term morbidities that can occur after, and persist beyond, the period of acute illness. A better understanding of the full spectrum of IMD sequelae is critical for assessing the burden of IMD and supporting healthcare planning and decision making in light of new vaccines.

Early economic evaluation of emerging health technologies: protocol of a systematic review.

BACKGROUND: The concept of early health technology assessment, discussed well over a decade, has now been collaboratively implemented by industry, government, and academia to select and expedite the development of emerging technologies that may address the needs of patients and health systems. Early economic evaluation is essential to assess the value of emerging technologies, but empirical data to inform the current practice of early evaluation is limited. We propose a systematic review of early economic evaluation studies in order to better understand the current practice. METHODS/DESIGN: This protocol describes a systematic review of economic evaluation studies of regulated health technologies in which the evaluation is conducted prior to regulatory approval and when the technology effectiveness is not well established. Included studies must report an economic evaluation, defined as the comparative analysis of alternatives with respect to their associated costs and health consequences, and must evaluate some regulated health technology such as pharmaceuticals, biologics, high-risk medical devices, or biomarkers. We will conduct the literature search on multiple databases, including MEDLINE, EMBASE, the Centre for Reviews and Dissemination Databases, and EconLit. Additional citations will be identified via scanning reference lists and author searching. We suspect that many early economic evaluation studies are unpublished, especially those conducted for internal use only. Additionally, we use a chain-referral sampling approach to identify authors of unpublished studies who work in technology discovery and development, starting out with our contact lists and authors who published relevant studies. Citation screening and full-text review will be conducted by pairs of reviewers. Abstracted data will include those related to the decision context and decision problem of the early evaluation, evaluation methods (e.g., data sources, methods, and assumptions used to identify, measure, and value the likely effectiveness and the costs and consequences of the new technology, handling of uncertainty), and whether the study results adequately address the main study question or objective. Data will be summarized overall and stratified by publication status. DISCUSSION: This study is timely to inform early economic evaluation practice, given the international trend in early health technology assessment initiatives.