Economic Evaluation of Total Laboratory Automation in the Clinical Laboratory of a Tertiary Care Hospital.

Background: Total laboratory automation (TLA) is an innovation in laboratory technology; however, the high up-front costs restrict its widespread adoption. To examine whether the capital investment for TLA is worthwhile, we analyzed its clinical- and cost-effectiveness for the expected payback period. Methods: Clinical chemistry tests and immunoassays performed in the clinical laboratory of a tertiary care hospital were divided into a post-TLA group, including 1,182,419 tests performed during December 2019, and a pre-TLA group, including 1,151,501 tests performed during December 2018. Laboratory information system data were used to measure clinical effectiveness, and depreciation data were used to calculate TLA costs. Results: Laboratory performance improved after TLA adoption in all four key performance indicators: mean turn-around time (TAT), representing the timeliness of result reporting, decreased by 6.1%; the 99th percentile of TAT, representing the outlier rate, decreased by 13.3%; the TAT CV, representing predictability, decreased by 70.0%; and weighted tube touch moment (wTTM), representing staff safety, improved by 77.6%. Based on these effectiveness results, economic evaluation was performed using two approaches. First, the incremental cost-effectiveness ratio and wTTM were used as the most cost-effective performance indicators. Second, the expected payback period was calculated. Considering only staff cost reduction, it was anticipated that 4.75 yrs would be needed to payback the initial investment. Conclusions: TLA can significantly enhance laboratory performance, has a relatively quick payback period, and can reduce total hospital expenses in the long term. Therefore, the capital investment for TLA adoption is considered to be worthwhile.

Comparative evaluation of agar dilution and broth microdilution by commercial and in-house plates for Bacteroides fragilis group: An economical and expeditious approach for resource-limited settings.

OBJECTIVE: To compare the performance of agar dilution and broth microdilution by commercial and in-house prepared plates for the Bacteroides fragilis group. The cost analysis was performed to demonstrate that in-house prepared BMD plates were a suitable alternative to agar dilution given the high cost and low feasibility of incorporating commercial BMD plates in routine, particularly in the tertiary care institutes of many low- and middle-income countries. METHODS: Thirty B. fragilis group isolates were tested against six antibiotics, frequently used as empirical therapy for anaerobic infections including metronidazole, clindamycin, imipenem, piperacillin-tazobactam, cefoxitin, and chloramphenicol. The running consumable expenditure for all methodologies was calculated. RESULTS: The results demonstrated essential and categorical agreement of >90% for all antibiotics except cefoxitin, which showed <90% categorical agreement. No major or very major errors were observed. We observed a high agreement and strong concordance for MIC values between both methods and inter-rate reliability of >0.9 by Cohen's kappa analysis, indicating almost perfect agreement between both methods using either of the plates. In contrast to agar dilution, a 20.5 fold cost reduction was seen in BMD using in-house plates and a 5.8 fold reduction using commercial plates to test a single isolate. However, when testing 30 isolates concurrently the cost significantly increased for commercial BMD plates by 8.4 folds, and only 1.03 fold cost reduction was seen with in-house BMD plates. CONCLUSION: BMD gives comparable results to agar dilution and can be considered a method of choice to test a small number of samples. The technique is an economical option when plates are standardized in-house and could be employed for susceptibility testing of the B. fragilis group.

Mapping the PHQ-8 to EQ-5D, HUI3 and SF6D in patients with depression.

BACKGROUND: There is limited evidence of mapping clinical instruments to a generic preference-based instrument in Asian patient populations. The current study aims to map the eight-item Patient Health Questionnaire depression scale (PHQ-8) onto the EuroQol Five-Dimension (EQ-5D), the Health Utilities Index Mark 3 (HUI3) and the Short Form Six-Dimension (SF-6D) which helps to inform future cost-utility analyses of treatments for depression. METHODS: A total of 249 participants who had completed PHQ-8, EQ-5D, SF-6D and HUI3 questionnaires were included in the analyses. A beta regression mixture model was used to map the utility scores as a function of PHQ-8 total scores, PHQ-squared, age and gender. The predictive accuracy of the models was examined using mean absolute error and root mean square error. RESULTS: The results were compared against two common regression methods including Ordinary Least Square (OLS) and Tobit regression models. The mean age of the sample was 36.2 years (SD = 11.1). The mean EQ-5D-3L, EQ-5D-5L, HUI3 and SF-6D utility scores were 0.615, 0.709, 0.461 and 0.607, respectively. The EQ-5D-3L, EQ-5D-5L and SF-6D utility scores were best predicted by the beta mixture regression model consisting of PHQ-8 total sores, PHQ-squared, and covariates including age and gender. The HUI3 was best predicted by the OLS regression model. CONCLUSIONS: The current study provides important evidence to clinicians and researchers about the mapping algorithms that can be used in economic evaluation among patients with depression.

How are we evaluating the cost-effectiveness of companion biomarkers for targeted cancer therapies? A systematic review.

BACKGROUND: Despite the increasing economic assessment of biomarker-guided therapies, no clear agreement exists whether existing methods are sufficient or whether different methods might produce different cost-effectiveness results. This study aims to examine current practices of modeling companion biomarkers when assessing the cost-effectiveness of targeted cancer therapies. It investigates the current methods in modeling the characteristics of companion diagnostics based on existing economic evaluations of biomarker-guided therapies in cancer. METHODS: A literature search was performed using Medline, Embase, EconLit, Cochrane library for economic evaluations of biomarker-guided therapies with companion diagnostics in cancer. Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Studies were selected using pre-specified eligibility criteria based on the PICO framework. To make the included studies more comparable, we qualitatively synthesized the data under nine domains of methods where consensus was deemed lacking. RESULTS: Only four of the twenty-two studies included in this review were found to be of good quality with respect to incorporating the characteristics of companion biomarkers in economic evaluations. However, many evaluations focused on a pre-selected patient group rather than including all patients regardless of their biomarker status. Companion biomarker characteristics captured in evaluations were often limited to the cost or the accuracy of the test. Often, only the costs of biomarker testing were modelled. Clinical outcomes and health state utilities were often not included due to the limited data generated by clinical trials. Methods of economic evaluation were not applied consistently in assessments of companion cancer biomarkers for targeted therapies. It was also shown that conflicting cost-effectiveness results were likely depending on what comparator arm was chosen and what comparison structure was designed in the model. CONCLUSION: We found no consistent approach applied in assessing the value of companion biomarker tests and including the characteristics of biomarkers in an economic evaluation of targeted oncology therapies. Currently, many economic evaluations fail to capture the full value of companion biomarkers beyond sensitivity/specificity and cost related to biomarker testing.

Stance-Control Knee-Ankle-Foot Orthoses for People With Knee Instability: A Health Technology Assessment.

Background: Knee instability can arise from various causes and conditions such as neuromuscular disease, central nervous system conditions, and trauma. For people with knee instability, knee orthosis devices are prescribed to help with standing, walking, and performing tasks. We conducted a health technology assessment of stance-control knee-ankle-foot orthoses (SCKAFOs) for people with knee instability, which included an evaluation of the effectiveness, safety, and budget impact of publicly funding SCKAFOs, as well as patient preferences and values. Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Risk of Bias in Nonrandomized Studies (RoBANS) tool and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and also analyzed the budget impact of publicly funding SCKAFOs in people with knee instabilities in Ontario. We did not conduct a primary economic evaluation as there was limited comparative clinical evidence to inform an economic model. Our reference case budget impact analysis was done from the perspective of the Ontario Ministry of Health; it compared the total costs of a basic mechanical SCKAFO and locked KAFO (LKAFO) for people with knee instability. We also performed scenario analyses varying the following parameters: the price of all classes of SCKAFO (mechanical, electronic, and microprocessor), and the uptake of SCKAFO. To contextualize the potential value of SCKAFO, we spoke with people with knee instability. Results: We included four studies in the clinical evidence review. We are uncertain if SCKAFOs improve walking ability, energy consumption, or activities of daily living compared with LKAFOs (GRADE: Very low). Our economic evidence review identified one costing analysis that suggested that the costs of orthotic devices such as LKAFOs and SCKAFOs are highly variable according to the cost of materials, professional time, and customization required by the individual patient. The budget impact of publicly funding mechanical SCKAFOs in Ontario over the next 5 years (at a full device cost of $10,784) ranged from an additional $0.50 million in year 1 (at an uptake rate of 30% in the target population [429 eligible people]) to $0.83 million in year 5 (at an uptake rate of 50%), with a total budget impact of $3.34 million over 5 years. We found that the greatest increase in budget impact in the scenario analysis came from the microprocessor SCKAFO device, which had an additional cost of $10.07 million in year 1, increasing to $16.78 million in year 5. When we decreased the cost of a mechanical SCKAFO device (to $7,384), this reduced the 5-year budget impact to $0.89 million (vs. $3.34 million in the reference case). The people with knee instability with whom we spoke reported that they preferred a device that would provide a more typical gait, but starting with this type of device would be easier than switching from an existing LKAFO. Conclusions: We are uncertain if SCKAFOs improve walking ability, reduce energy consumption, or improve activities of daily living compared with LKAFOs. We estimate that the additional cost to provide public funding for a mechanical SCKAFO in people with knee instability would range from about $0.50 million in year 1 to $0.83 million in year 5, yielding a total budget impact of $3.34 million over 5 years. Depending on the class of SCKAFO and the uptake rate for the device, the budget impact may vary. People who met the criteria for the use of a SCKAFO did have a strong preference for it over an LKAFO.

Enhanced Visualization Methods for First Transurethral Resection of Bladder Tumour in Suspected Non-muscle-invasive Bladder Cancer: A Health Technology Assessment.

Background: Bladder cancer begins in the innermost lining of the bladder wall and, on histological examination, is classified as one of two types: non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer. Transurethral resection of bladder tumour (TURBT) is the standard treatment for people with NMIBC, but the high rate of cancer recurrence after first TURBT is a challenge that physicians and patients face. Tumours seen during follow-up may have been missed or incompletely resected during first TURBT. TURBT is conventionally performed using white light to see the tumours. However, small papillary or flat tumours may be missed with the use of white light alone. With the emergence of new technologies to improve visualization during TURBT, better diagnostic and patient outcomes may be expected. We conducted a health technology assessment of two enhanced visualization methods, both as an adjunct to white light to guide first TURBT for people with suspected NMIBC-hexaminolevulinate hydrochloride (HAL), a solution that is instilled into the bladder to make tumours fluoresce under blue-violet light, and narrow band imaging (NBI), a technology that filters light into wavelengths that can be absorbed by hemoglobin in the tumours, making them appear darker. Our assessment included an evaluation of effectiveness, safety, cost-effectiveness, and the budget impact of publicly funding these new technologies to improve patient outcomes following first TURBT. The use of NBI in diagnostic cystoscopy was out of scope for this health technology assessment. Methods: We performed a systematic literature search of the clinical evidence from inception to April 15, 2020. We searched for randomized controlled trials (RCTs) that compared the outcomes of first TURBT with the use of HAL or NBI, both as an adjunct to white light, with the outcomes of first TURBT using white light alone, or studies that made such comparison between HAL and NBI. We conducted pairwise meta-analyses using a fixed effects model where head-to-head comparisons were available. In the absence of any published RCT for comparison between HAL and NBI, we indirectly compared the two technologies through indirect treatment comparison (ITC) analysis. We assessed the risk of bias of each included study using the Cochrane risk-of-bias tool. We assessed the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-utility analysis with a 15-year time horizon from a public payer perspective. We also analyzed the budget impact of publicly funding HAL and NBI as an adjunct to white light in people undergoing their first TURBT for suspected non-muscle-invasive bladder cancer in Ontario. Results: In the clinical evidence review, we identified 8 RCTs that used HAL or NBI as an adjunct to white light during first TURBT. Pairwise meta-analysis of HAL studies showed that HAL-guided TURBT as an adjunct to white light significantly reduces recurrence rate at 12 months compared with TURBT using white light alone (risk ratio 0.70, 95% confidence interval [CI] 0.51-0.95) (GRADE: Moderate). Five-year recurrence-free survival was significantly higher when HAL was used as an adjunct to white light than when white light was used alone (GRADE: Moderate). There was little to no difference in the tumour progression rate (GRADE: Moderate).Meta-analysis of NBI studies did not show a significant difference between NBI-guided TURBT as an adjunct to white light and TURBT using white light alone in reducing the rate of recurrence at 12 months (risk ratio 0.94, 95% CI 0.75-1.19) (GRADE: Moderate). No evidence on the effect on recurrence-free survival or tumour progression rate was identified for NBI-guided TURBT. The indirect estimate from the network analysis showed a trend toward a lower rate of recurrence after HAL-guided TURBT than after NBI-guided TURBT but the difference was not statistically significant (risk ratio 0.76, 95% CI 0.51-1.11) (GRADE: Low). Studies showed that use of HAL or NBI during TURBT was generally safe.The incremental cost-effectiveness ratio of HAL-guided TURBT compared with NBI-guided TURBT, both as an adjunct to white light, is $12,618 per quality-adjusted life-year (QALY) gained. Compared with TURBT using white light alone and using adjunct NBI, the probability of HAL-guided TURBT being cost-effective is 69.1% at a willingness-to-pay value of $50,000 per QALY gained and 74.6% at a willingness-to-pay of $100,000 per QALY gained. The annual budget impact of publicly funding HAL-guided TURBT in Ontario over the next 5 years ranges from an additional $0.6 million in year 1 to $2.5 million in year 5. Conclusions: First TURBT guided by HAL as an adjunct to white light likely reduces the rate of recurrence at 12 months and increases 5-year recurrence-free survival when compared with first TURBT using white light alone. There is likely little to no difference in the tumour progression rate. First TURBT guided by NBI as an adjunct to white light likely results in little to no difference in the rate of recurrence at 12 months when compared with first TURBT using white light alone. Based on an indirect comparison, there may be little to no difference in cancer recurrence rate between HAL-guided and NBI-guided first TURBT. Use of HAL or NBI during first TURBT is generally safe. For people undergoing their first TURBT for suspected non-muscle-invasive bladder cancer, using HAL as an adjunct to white light is likely to be cost-effective compared with using white light alone or with using NBI as an adjunct to white light. We estimate that publicly funding HAL as an adjunct to white light to guide first TURBT for people in Ontario with suspected NMIBC would result in additional costs of between $0.6 million and $2.5 million per year over the next 5 years.

Multi-gene Pharmacogenomic Testing That Includes Decision-Support Tools to Guide Medication Selection for Major Depression: A Health Technology Assessment.

Background: Major depression is a substantial public health concern that can affect personal relationships, reduce people's ability to go to school or work, and lead to social isolation. Multi-gene pharmacogenomic testing that includes decision-support tools can help predict which depression medications and dosages are most likely to result in a strong response to treatment or to have the lowest risk of adverse events on the basis of people's genes.We conducted a health technology assessment of multi-gene pharmacogenomic testing that includes decision-support tools for people with major depression. Our assessment evaluated effectiveness, safety, cost-effectiveness, the budget impact of publicly funding multi-gene pharmacogenomic testing, and patient preferences and values. Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane Risk of Bias Tool and the Risk of Bias Assessment Tool for Nonrandomized studies (RoBANS) and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria.We performed a systematic literature search of the economic evidence to review published cost-effectiveness studies on multi-gene pharmacogenomic testing that includes a decision-support tool in people with major depression. We developed a state-transition model and conducted a probabilistic analysis to determine the incremental cost of multi-gene pharmacogenomic testing versus treatment as usual per quality-adjusted life-year (QALY) gained for people with major depression who had inadequate response to one or more antidepressant medications. In the reference case (with GeneSight-guided care), we considered a 1-year time horizon with an Ontario Ministry of Health perspective. We also estimated the 5-year budget impact of publicly funding multi-gene pharmacogenomic testing for people with major depression in Ontario.To contextualize the potential value of multi-gene pharmacogenomic testing that includes decision-support tools, we spoke with people who have major depression and their families. Results: We included 14 studies in the clinical evidence review that evaluated six multi-gene pharmacogenomic tests. Although all tests included decision-support tools, they otherwise differed greatly, as did study design, populations included in studies, and outcomes reported. Little or no improvement was observed on change in HAM-D17 depression score compared with treatment as usual for any test evaluated (GRADE: Low-Very Low). GeneSight- and NeuroIDgenetix-guided medication selection led to statistically significant improvements in response (GRADE: Low-Very Low) and remission (GRADE: Low-Very Low), while treatment guided by CNSdose led to significant improvement in remission rates (GRADE: Low), but the study did not report on response. Results were inconsistent and uncertain for the impact of Neuropharmagen, and no significant improvement was observed for Genecept or another unspecified test for either response or remission (GRADE: Low-Very Low). Neuropharmagen may reduce adverse events and CNSDose may reduce intolerability to medication, while no difference was observed in adverse events with GeneSight, Genecept, or another unspecified test (GRADE: Moderate-Very Low). No studies reported data on suicide, treatment adherence, relapse, recovery, or recurrence of depression symptoms.Our review included four model-based economic studies and found that multi-gene pharmacogenomic testing was associated with greater effectiveness and cost savings than treatment as usual, over long-term (i.e., 3-,5-year and lifetime) time horizons. Since none of the included studies was fully applicable to the Ontario health care system, we conducted a primary economic evaluation.Our reference case analysis over the 1-year time horizon found that multi-gene pharmacogenomic testing (with GeneSight) was associated with additional QALYs (0.03, 95% credible interval [CrI]: 0.005; 0.072) and additional costs ($1,906, 95% Crl: $688; $3,360). An incremental cost-effectiveness ratio was $60,564 per QALY gained. The probability of the intervention being cost-effective (vs. treatment as usual) was 36.8% at a willingness-to-pay amount of $50,000 per QALY (i.e., moderately likely not to be cost-effective), rising to 70.7% at a willingness-to-pay amount of $100,000 per QALY (i.e., moderately likely to be cost-effective). Evidence informing economic modeling of the reference case with GeneSight and other multi-gene pharmacogenomic tests was of low to very low quality, implying considerable uncertainty or low confidence in the effectiveness estimates. The price of the test, efficacy of the intervention on remission, time horizon, and analytic perspective were major determinants of the cost-effectiveness results. If the test price were assumed to be $2,162 (compared with $2,500 in the reference case), the intervention would be cost-effective at a willingness-to-pay amount of $50,000 per QALY; moreover, if the price decreased to $595, the intervention would be cost saving (or dominant) compared with treatment as usual.At an increasing uptake of 1% per year and a test price of $2,500, the annual budget impact of publicly funding multi-gene pharmacogenomic testing in Ontario over the next 5 years ranged from an additional $3.5 million in year 1 (at uptake of 1%) to $16.8 million in year 5. The 5-year budget impact was estimated at about $52 million.People with major depression and caregivers generally supported multi-gene pharmacogenomic testing because they believed it could provide guidance that fit their values. They hoped such guidance would speed symptom relief, would reduce side effects and help inform their medication choices. Some patients expressed concerns over maintaining confidentiality of test results and the possibility that physicians would sacrifice patient-centred care to follow pharmacogenomic guidance. Conclusions: Multi-gene pharmacogenomic testing that includes decision-support tools to guide medication selection for depression varies widely. Differences between individual tests must be considered, as clinical utility observed with one test might not apply to other tests. Overall, effectiveness was inconsistent among the six multi-gene pharmacogenomic tests we identified. Multi-gene pharmacogenomic tests may result in little or no difference in improvement in depression scores compared with treatment as usual, but some tests may improve response to treatment or remission from depression. The impact on adverse events is uncertain. The evidence, however, is uncertain, and therefore our confidence that these observed effects reflect the true effects is low to very low.For the management of major depression in people who had inadequate response to at least one medication, some multi-gene pharmacogenomic tests that include decision support tools are associated with additional costs and QALYs over the 1-year time horizon, and maybe be cost-effective at the willingness-to-pay amount of $100,000 per QALY. Publicly funding multi-gene pharmacogenomic testing in Ontario would result in additional annual costs of between $3.5 million and $16.8 million, with a total budget impact of about $52 million over the next 5 years.People with major depression and caregivers generally supported multi-gene pharmacogenomic testing because they believed it could provide guidance that fit their values. They hoped such guidance would speed symptom relief, would reduce side and help inform their medication choices. Some patients expressed concerns over maintaining confidentiality of test results and the possibility that physicians would sacrifice patient-centred care to follow pharmacogenomic guidance.

DPYD Genotyping in Patients Who Have Planned Cancer Treatment With Fluoropyrimidines: A Health Technology Assessment.

Background: Fluoropyrimidine drugs (such as 5-fluorouracil and capecitabine) are used to treat different types of cancer. However, these drugs may cause severe toxicity in about 10% to 40% of patients. A deficiency in the dihydropyrimidine dehydrogenase (DPD) enzyme, encoded by the DPYD gene, increases the risk of severe toxicity. DPYD genotyping aims to identify variants that lead to DPD deficiency and may help to identify people who are at higher risk of developing severe toxicity, allowing their treatment to be modified before it begins. Recommendations for fluoropyrimidine treatment modification are available for four DPYD variants, which are the focus of this review: DPYD∗2A, DPYD∗13, c.2846A>T, and c.1236G>A. We conducted a health technology assessment of DPYD genotyping for patients who have planned cancer treatment with fluoropyrimidines, which included an evaluation of clinical validity, clinical utility, the effectiveness of treatment with a reduced fluoropyrimidine dose, cost-effectiveness, the budget impact of publicly funding DPYD genotyping, and patient preferences and values. Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included systematic review and primary study using the Risk of Bias in Systematic Reviews (ROBIS) tool and the Newcastle-Ottawa Scale, respectively, and we assessed the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature review and conducted cost-effectiveness and cost-utility analyses with a half-year time horizon from a public payer perspective. We also analyzed the budget impact of publicly funding pre-treatment DPYD genotyping in patients with planned fluoropyrimidine treatment in Ontario. To contextualize the potential value of DPYD testing, we spoke with people who had planned cancer treatment with fluoropyrimidines. Results: We included 29 observational studies in the clinical evidence review, 25 of which compared the risk of severe toxicity in carriers of a DPYD variant treated with a standard fluoropyrimidine dose with the risk in wild-type patients (i.e., non-carriers of the variants under assessment). Heterozygous carriers of a DPYD variant treated with a standard fluoropyrimidine dose may have a higher risk of severe toxicity, dose reduction, treatment discontinuation, and hospitalization compared to wild-type patients (GRADE: Low). Six studies evaluated the risk of severe toxicity in DPYD carriers treated with a genotype-guided reduced fluoropyrimidine dose versus the risk in wild-type patients; one study also included a second comparator group of DPYD carriers treated with a standard dose. The evidence was uncertain, because the results of most of these studies were imprecise (GRADE: Very low). The length of hospital stay was shorter in DPYD carriers treated with a reduced dose than in DPYD carriers treated with a standard dose, but the evidence was uncertain (GRADE: Very low). One study assessed the effectiveness of a genotype-guided reduced fluoropyrimidine dose in DPYD∗2A carriers versus wild-type patients, but the results were imprecise (GRADE: Very low).We found two cost-minimization analyses that compared the costs of the DPYD genotyping strategy with usual care (no testing) in the economic literature review. Both studies found that DPYD genotyping was cost-saving compared to usual care. Our primary economic evaluation, a cost-utility analysis, found that DPYD genotyping might be slightly more effective (incremental quality-adjusted life years of 0.0011) and less costly than usual care (a savings of $144.88 per patient), with some uncertainty. The probability of DPYD genotyping being cost-effective compared to usual care was 91% and 96% at the commonly used willingness-to-pay values of $50,000 and $100,000 per quality-adjusted life-year gained, respectively. Assuming a slow uptake, we estimated that publicly funding pre-treatment DPYD genotyping in Ontario would lead to a savings of $714,963 over the next 5 years.The participants we spoke to had been diagnosed with cancer and treated with fluoropyrimidines. They reported on the negative side effects of their treatment, which affected their day-to-day activities, employment, and mental health. Participants viewed DPYD testing as a beneficial addition to their treatment journey; they noted the importance of having all available information possible so they could make informed decisions to avoid adverse reactions. Barriers to DPYD testing include lack of awareness of the test and the fact that the test is being offered in only one hospital in Ontario. Conclusions: Studies found that carriers of a DPYD variant who were treated with a standard fluoropyrimidine dose may have a higher risk of severe toxicity than wild-type patients treated with a standard dose. DPYD genotyping led to fluoropyrimidine treatment modifications. It is uncertain whether genotype-guided dose reduction in heterozygous DPYD carriers resulted in a risk of severe toxicity comparable to that of wild-type patients. It is also uncertain if the reduced dose resulted in a lower risk of severe toxicity compared to DPYD carriers treated with a standard dose. It is also uncertain whether the treatment effectiveness of a reduced dose in carriers was comparable to the effectiveness of a standard dose in wild-type patients.For patients with planned cancer treatment with fluoropyrimidines, DPYD genotyping is likely cost-effective compared to usual care. We estimate that publicly funding DPYD genotyping in Ontario may be cost-saving, with an estimated total of $714,963 over the next 5 years, provided that the implementation, service delivery, and program coordination costs do not exceed this amount.For people treated with fluoropyrimidines, cancer and treatment side effects had a substantial negative effect on their quality of life and mental health. Most saw the value of DPYD testing as a way of reducing the risk of serious adverse events. Barriers to receipt of DPYD genotyping included lack of awareness and limited access to DPYD testing.

Clinical and Economic Evaluation of Acupuncture for Opioid-Dependent Patients Receiving Methadone Maintenance Treatment: The Integrative Clinical Trial and Evidence-Based Data.

Objective: From the health care and societal perspectives, this study aimed to evaluate the clinical and economic effects of acupuncture as an adjunctive therapy for patients receiving methadone maintenance treatment (MMT). Methods: We conducted a parallel-arm RCT in China in 2019. Patients were included who met the diagnostic criteria and receive MMT for more than 30 days. Patients were randomly assigned to the exposed group (acupuncture plus MMT) or control group (MMT) at a 1:1 ratio. Daily methadone dosage, drug cravings using the VAS score, and insomnia using the Pittsburgh Sleep Quality Index (PSQI) were chosen as the effectiveness indexes, and the quality-adjusted life years (QALYs) was chosen as the utility index. Results: Overall, 123 patients were included. The exposed group was significantly (P < 0.05) better than the control group in the improvement of daily methadone dosage (17.68 vs. 1.07), VAS (38.27 vs. 2.64), and PSQI (2.18 vs. 0.30). The QALY was 0.0784 (95%CI: 0.0761-0.0808) for the exposed group and 0.0762 (95%CI: 0.0738-0.0787) for the control group. The total cost of the exposed group (2869.50 CNY) was higher than the control group (2186.04 CNY). The ICER of daily methadone dosage (41.15), VAS (17.86), and PSQI (313.51) were shown to be economically efficient. While ICUR (310,663.64 CNY/QYLY) was higher than the cost suggested by WHO. Conclusion: Acupuncture as an adjuvant therapy for MMT patients realizes its cost-effectiveness by reducing the dosage of methadone, improving drug cravings, and alleviating insomnia. It helps to improve quality of life, but since its cost exceeds what society is willing to pay, further study is needed.

A Systematic Review of the Evidence on the Effectiveness and Cost-Effectiveness of Mass Screen-and-Treat Interventions for Malaria Control.

Malaria elimination and eradication efforts have stalled globally. Further, asymptomatic infections as silent transmission reservoirs are considered a major challenge to malaria elimination efforts. There is increased interest in a mass screen-and-treat (MSAT) strategy as an alternative to mass drug administration to reduce malaria burden and transmission in endemic settings. This study systematically synthesized the existing evidence on MSAT, from both epidemiological and economic perspectives. Searches were conducted on six databases (PubMed, EMBASE, CINALH, Web of Science, Global Health, and Google Scholar) between October and December 2020. Only experimental and quasi-experimental studies assessing the effectiveness and/or cost-effectiveness of MSAT in reducing malaria prevalence or incidence were included. Of the 2,424 citation hits, 14 studies based on 11 intervention trials were eligible. Eight trials were conducted in sub-Saharan Africa and three trials in Asia. While five trials targeted the community as a whole, pregnant women were targeted in five trials, and school children in one trial. Transmission setting, frequency, and timing of MSAT rounds, and measured outcomes varied across studies. The pooled effect size of MSAT in reducing malaria incidence and prevalence was marginal and statistically nonsignificant. Only one study conducted an economic evaluation of the intervention and found it to be cost-effective when compared with the standard of care of no MSAT. We concluded that the evidence for implementing MSAT as part of a routine malaria control program is growing but limited. More research is necessary on its short- and longer-term impacts on clinical malaria and malaria transmission and its economic value.

Avoiding Opportunity Cost Neglect in Cost-Effectiveness Analysis for Health Technology Assessment.

Despite being a fundamental tenet of economic analysis there is a lack of clarity regarding the relevance of opportunity costs to cost-effectiveness analysis for health technology assessment. We argue that this is due, in part, to the importance of the decision context in understanding the nature of opportunity costs. Taking the example of the National Institute of Health and Care Excellence (NICE) on behalf of the National Health Service (NHS) in England and Wales, we explore the implications of existing discrepancies between policy thresholds and emerging empirical evidence of health opportunity costs. In particular, we consider analysts communicating the results of cost-effectiveness analysis, and recommend that analysts provide analysis according to both the policy threshold and the latest empirical evidence until the discrepancies are better understood or resolved. A number of conceptually related, but distinct, issues are discussed and clarified.

A trial-based economic evaluation of peppermint oil for the treatment of irritable bowel syndrome.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a prevalent, chronic gastrointestinal disorder that imposes a substantial socioeconomic burden. Peppermint oil is a frequently used treatment for IBS, but evidence about cost-effectiveness is lacking. OBJECTIVE: We aimed to assess cost-effectiveness of small-intestinal release peppermint oil versus placebo in IBS patients. METHODS: In a multicenter randomized placebo-controlled trial, cost-effectiveness was evaluated from a societal perspective. The incremental cost-effectiveness ratios (ICERs) were expressed as (1) incremental costs per Quality Adjusted Life Years (QALY), and (2) incremental costs per successfully treated patient, that is per abdominal pain responder (according to FDA definitions), both after an eight-week treatment period with placebo versus peppermint oil. Cost-utility and uncertainty were estimated using non-parametric bootstrapping. Sensitivity analyses were performed. RESULTS: The analysis comprised 126 patients (N = 64 placebo, N = 62 small-intestinal release peppermint oil). Peppermint oil was a dominant treatment compared to placebo in 46% of bootstrap replications. Peppermint oil was also more effective but at higher cost in 31% of replications. The net-benefit acceptability curve showed that peppermint oil has a 56% probability of being cost-effective at a conservative willingness-to-pay threshold of €10.000/QALY. Peppermint oil was also a dominant treatment per additional successfully treated patient according to FDA definitions, that is in 51% of replications. In this case, the acceptability curve showed an 89% probability of being cost-effective. CONCLUSIONS: In patients with IBS, small-intestinal release peppermint oil appears to be a cost-effective treatment although there is uncertainty surrounding the ICER. When using abdominal pain responder as outcome measure for the ICER, peppermint oil has a high probability of being cost-effective. The use of peppermint oil, which is a low-cost treatment, can be justified by the modest QALY gains and slightly higher proportion of abdominal pain responders. More research and long-term data are necessary to confirm the cost-effectiveness of peppermint oil. NCT02716285.

Cost-utility of as-needed combination low-dose budesonide-formoterol in adolescents mild asthma.

BACKGROUND: Previously evidence has demonstrated that as-needed combination low-dose budesonide-formoterol reduced the risk of severe exacerbations compared with short-acting ß2-agonist (SABA) reliever therapy in an adolescent with mild asthma. Concerns as if the extra benefit offered by this drug outweighs the additional cost. This study aimed to evaluate the cost-effectiveness of as-needed combination low-dose budesonide-formoterol compared with short-acting ß2-agonist (SABA) reliever therapy in adolescents with mild asthma in Colombia. METHODS: A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with mild asthma in Colombia. Total costs and QALYs of low-dose budesonide-formoterol compared with short-acting ß2-agonist (SABA) were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000. RESULTS: The model suggests a potential gain of 0.03 QALYs and per patient per year on low-dose budesonide-formoterol. The cost difference per person was US$-4 per patient per year in favor of budesonide- formoterol. The position of dominance negates the need to calculate an incremental cost-effectiveness ratio. In the one-way and probabilistic sensitivity analyses, our base-case results were robust to variations of all assumptions and parameters. CONCLUSION: In conclusion, low-dose budesonide-formoterol as a reliever was found to be cost-effective when added to usual care in adolescents with mild asthma. This evidence should promote economic evaluations in developed and developing countries for the inclusion of new drugs in health insurance plans.

Review: Economic evidence of preventive interventions for anxiety disorders in children and adolescents - a systematic review.

BACKGROUND: Anxiety disorders are common in children and youth. Also, in prevention, be it universal, selective or indicated, economic evaluation supports decision-making in the allocation of scarce resources. This review identified and summarised the existing evidence of economic evaluations for the prevention of anxiety disorders in children and adolescents. METHODS: A systematic search was conducted on the EBSCO, Scopus, Web of Science, ProQuest, Cochrane and PubMed databases. We included studies that focused on children and adolescents under 18 years of age, aimed to prevent anxiety disorders and presented an incremental analysis of costs and effectiveness. A registered checklist was used that assessed the quality of the included articles. RESULTS: The search yielded 1697 articles. Five articles were included in this review. Three were RCT-based, and two were model-based studies. Out of five included interventions, one was a universal school-based intervention, two selective interventions and two indicated interventions. Universal school-based prevention of anxiety was not cost-effective compared with usual teaching. Selective parent training and indicative child- and parent-focused CBT prevention were likely cost-effective compared with usual care or doing nothing. CONCLUSION: Parent education and cognitive behaviour therapy interventions can be cautiously interpreted as being a cost-effective way of preventing anxiety in children and adolescents. However, the evidence is weakly related to cost-effectiveness as there are only a few studies, with relatively small sample sizes and short follow-ups.

A prognostic model, including quantitative fetal fibronectin, to predict preterm labour: the QUIDS meta-analysis and prospective cohort study.

BACKGROUND: The diagnosis of preterm labour is challenging. False-positive diagnoses are common and result in unnecessary, potentially harmful treatments (e.g. tocolytics, antenatal corticosteroids and magnesium sulphate) and costly hospital admissions. Measurement of fetal fibronectin in vaginal fluid is a biochemical test that can indicate impending preterm birth. OBJECTIVES: To develop an externally validated prognostic model using quantitative fetal fibronectin concentration, in combination with clinical risk factors, for the prediction of spontaneous preterm birth and to assess its cost-effectiveness. DESIGN: The study comprised (1) a qualitative study to establish the decisional needs of pregnant women and their caregivers, (2) an individual participant data meta-analysis of existing studies to develop a prognostic model for spontaneous preterm birth within 7 days in women with symptoms of preterm labour based on quantitative fetal fibronectin and clinical risk factors, (3) external validation of the prognostic model in a prospective cohort study across 26 UK centres, (4) a model-based economic evaluation comparing the prognostic model with qualitative fetal fibronectin, and quantitative fetal fibronectin with cervical length measurement, in terms of cost per QALY gained and (5) a qualitative assessment of the acceptability of quantitative fetal fibronectin. DATA SOURCES/SETTING: The model was developed using data from five European prospective cohort studies of quantitative fetal fibronectin. The UK prospective cohort study was carried out across 26 UK centres. PARTICIPANTS: Pregnant women at 22+0-34+6 weeks' gestation with signs and symptoms of preterm labour. HEALTH TECHNOLOGY BEING ASSESSED: Quantitative fetal fibronectin. MAIN OUTCOME MEASURES: Spontaneous preterm birth within 7 days. RESULTS: The individual participant data meta-analysis included 1783 women and 139 events of spontaneous preterm birth within 7 days (event rate 7.8%). The prognostic model that was developed included quantitative fetal fibronectin, smoking, ethnicity, nulliparity and multiple pregnancy. The model was externally validated in a cohort of 2837 women, with 83 events of spontaneous preterm birth within 7 days (event rate 2.93%), an area under the curve of 0.89 (95% confidence interval 0.84 to 0.93), a calibration slope of 1.22 and a Nagelkerke R 2 of 0.34. The economic analysis found that the prognostic model was cost-effective compared with using qualitative fetal fibronectin at a threshold for hospital admission and treatment of ≥ 2% risk of preterm birth within 7 days. LIMITATIONS: The outcome proportion (spontaneous preterm birth within 7 days of test) was 2.9% in the validation study. This is in line with other studies, but having slightly fewer than 100 events is a limitation in model validation. CONCLUSIONS: A prognostic model that included quantitative fetal fibronectin and clinical risk factors showed excellent performance in the prediction of spontaneous preterm birth within 7 days of test, was cost-effective and can be used to inform a decision support tool to help guide management decisions for women with threatened preterm labour. FUTURE WORK: The prognostic model will be embedded in electronic maternity records and a mobile telephone application, enabling ongoing data collection for further refinement and validation of the model. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015027590 and Current Controlled Trials ISRCTN41598423. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 52. See the NIHR Journals Library website for further project information.

Cost-effectiveness Analysis of Genotype-Specific Surveillance and Preventive Strategies for Gynecologic Cancers Among Women With Lynch Syndrome.

Importance: With the expansion of multigene testing for cancer susceptibility, Lynch syndrome (LS) has become more readily identified among women. The condition is caused by germline pathogenic variants in DNA mismatch repair genes (ie, MLH1, MSH2, MSH6, and PMS2) and is associated with high but variable risks of endometrial and ovarian cancers based on genotype. However, current guidelines on preventive strategies are not specific to genotypes. Objective: To assess the cost-effectiveness of genotype-specific surveillance and preventive strategies for LS-associated gynecologic cancers, including a novel, risk-reducing surgical approach associated with decreased early surgically induced menopause. Design, Setting, and Participants: This economic evaluation developed a cohort-level Markov simulation model of the natural history of LS-associated gynecologic cancer for each gene, among women from ages 25 to 75 years or until death from a health care perspective. Age was varied at hysterectomy and bilateral salpingo-oophorectomy (hyst-BSO) and at surveillance initiation, and a 2-stage surgical approach (ie, hysterectomy and salpingectomy at age 40 years and delayed oophorectomy at age 50 years [hyst-BS]) was included. Extensive 1-way and probabilistic sensitivity analyses were performed. Interventions: Hyst-BSO at ages 35 years, 40 years, or 50 years with or without annual surveillance beginning at age 30 years or 35 years or hyst-BS at age 40 years with oophorectomy delayed until age 50 years. Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER) between management strategies within an efficiency frontier. Results: For women with MLH1 and MSH6 variants, the optimal strategy was the 2-stage approach, with respective ICERs of $33 269 and $20 008 compared with hyst-BSO at age 40 years. Despite being cost-effective, the 2-stage approach was associated with increased cancer incidence and mortality compared with hyst-BSO at age 40 years for individuals with MLH1 variants (incidence: 7.76% vs 3.84%; mortality: 5.74% vs 2.55%) and those with MSH6 variants (incidence: 7.24% vs 4.52%; mortality: 5.22% vs 2.97%). Hyst-BSO at age 40 years was optimal for individuals with MSH2 variants, with an ICER of $5180 compared with hyst-BSO at age 35 years, and was associated with 4.42% cancer incidence and 2.97% cancer mortality. For individuals with PMS2 variants, hyst-BSO at age 50 years was optimal and all other strategies were dominated; hyst-BSO at age 50 years was associated with an estimated cancer incidence of 0.68% and cancer mortality of 0.29%. Conclusions and Relevance: These findings suggest that gene-specific preventive strategies for gynecologic cancers in LS may be warranted and support hyst-BSO at age 40 years for individuals with MSH2 variants. For individuals with MLH1 and MSH6 variants, these findings suggest that a novel 2-stage surgical approach with delayed oophorectomy may be an alternative to hyst-BSO at age 40 years to avoid early menopause, and for individuals with PMS2 variants, the findings suggest that hyst-BSO may be delayed until age 50 years.

Controversy Over Using Quality-Adjusted Life-Years In Cost-Effectiveness Analyses: A Systematic Literature Review.

Researchers and policy makers in the US are exploring the implementation of health technology assessment and value-based pricing to negotiate drug prices and limit spending. Objections made to the quality-adjusted life-year (QALY), the most frequently used health economic outcome for such assessments, are a barrier to the adoption of these tools. This literature review identifies and addresses the range of criticisms made against QALYs. Methods-based criticisms require attention from stakeholders to address well-known shortcomings of the QALY and ensure consistency. Ethical criticisms, however, do not apply only to the QALY and require political decisions about societal values. Understanding and overcoming criticisms of the QALY to enable its use as part of health technology assessment and value-based pricing will be crucial as US policy makers seek to address high drug costs and health care spending.

Paludiculture as paludifuture on Dutch peatlands: An environmental and economic analysis of Typha cultivation and insulation production.

Paludiculture, the cultivation of crops on rewetted peatlands, is often proposed as a viable climate change mitigation option that reduces greenhouse gas emissions (GHGe), while simultaneously providing novel agricultural business options. In West Europe, experiments are ongoing in using the paludicrop cattail (Typha spp.) as feedstock for insulation panel material. Here, we use a Dutch case study to investigate the environmental potential and economic viability of shifting the use of peat soils from grassland (for dairy production) to Typha paludiculture (for cultivation and insulation panel production). Using a life cycle assessment and cost-benefit analysis, we compared the global warming potential (GWP), yearly revenues and calculated Net Present Value (NPV) of 1 ha Dutch peat soil used either for dairy production or for Typha paludiculture. We estimated that changing to Typha paludiculture leads to a GWP reduction of ~32% (16.4 t CO2-eq ha-1), mainly because of lower emissions from peat decomposition as a result of land-use management (-21.6 t CO2-eq ha-1). If biogenic carbon storage is excluded, the avoided impact of conventional insulation material is insufficient to compensate the impact of cultivating and processing Typha (9.7 t CO2-eq ha-1); however, this changes if biogenic carbon storage is included (following PAS2050 guidelines). Typha paludiculture is currently not competitive with dairy production, mainly due to high cultivation costs and low revenues, which are both uncertain, and will likely improve as the system develops. Its NPV is negative, mainly due to high investment costs. This can be improved by introducing carbon credits, with carbon prices for Typha paludiculture (30 years) comparable to EU-ETS prices. In conclusion, Dutch Typha paludiculture has a significant climate change mitigation potential by reducing emissions from deep drained peatlands. Nevertheless, attention is needed to increase its economic viability as this is a key aspect of the system change.

Economic evaluation of an online single-session intervention for depression in Kenyan adolescents.

Objective: To evaluate the costs and cost-effectiveness of Shamiri-Digital, an online single-session intervention (SSI) for depression among Kenyan adolescents. Method: Data were drawn from a randomized clinical trial with n = 103 Kenyan high school students (64% female, Mage = 15.5). All students were eligible to participate, regardless of baseline depression symptomatology. We estimated delivery costs in 2020 U.S. dollars from multiple perspectives. To account for uncertainty, we performed sensitivity analyses with different cost assumptions and definitions of effectiveness. Using number needed to treat (NNT) estimates, we also evaluated the cost required to achieve a clinically meaningful reduction in depressive symptoms. Results: In the base-case (the most realistic cost estimate), it costs U.S. $3.57 per student to deliver Shamiri-Digital. Depending on the definition of clinically meaningful improvement, 7.1-9.7 students needed to receive the intervention for one student to experience a clinically meaningful improvement, which translated to a cost of U.S. $25.35 to U.S. $34.62 per student. Under a worst-case scenario (i.e., assuming the highest treatment cost and the strictest effectiveness definition), the cost to achieve clinically meaningful improvement was U.S. $92.05 per student. Conclusions: Shamiri-Digital is a low-cost intervention for reducing depression symptomatology. The public health benefit of empirically supported SSIs is especially important in low-income countries, where funding for mental health care is most limited. Future research can compare the cost-effectiveness of online SSIs to higher-cost treatments and estimate the robustness of Shamiri-Digital's effects over a longer time horizon. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Economic evaluations of psychological treatments for common mental disorders in low- and middle-income countries: protocol for a systematic review.

BACKGROUND: Common mental disorders (CMDs) are highly prevalent conditions that constitute a major public health and economic burden on society in low- and middle-income countries (LMICs). Despite the increased demand for economic evidence to support resource allocation for scaled-up implementation of mental health services in these contexts, economic evaluations of psychological treatments for CMDs remain scarce. OBJECTIVE: The proposed systematic review aims to synthesize findings on methods and outcomes of economic evaluations of psychological treatments for CMDs in LMICs and appraise quality. METHODS: We will identify, select, and extract data from published economic evaluations of psychological interventions for CMDs conducted in LMICs. We will search bibliographic databases (PubMed, EMBASE, CINAHL, Web of Science, EconLit, PsycINFO, Africa-Wide Information, Cochrane library, Centre for Reviews and Dissemination (CRD), Cost Effectiveness Analysis (CEA) Registry), and the African Journals Online (AJOL) and Google Scholar platforms. Only full economic evaluations (Cost-Effectiveness Analysis (CEA), Cost-Utility Analysis (CUA), Cost-Consequence Analysis (CCA), or Cost-Benefit Analysis (CBA)) of psychological treatments for CMDs (defined as depressive, anxiety, and substance use disorders) conducted in LMICs will be included. There will be no restrictions based on date of publication, perspective, follow-up duration or sample size. Data extraction will be guided by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: The results presented will be examined using a narrative synthesis approach. The quality of included studies will be assessed using the Drummond & Jefferson checklist. CONCLUSION: The fledgling evidence base in this area provides an opportunity to promote improved economic evaluation methods in line with repeated calls for economic evidence alongside effectiveness evidence in these settings. A rigorously developed economic evaluation evidence base will support resource allocation decisions for scaled up implementation of psychological interventions in LMIC settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020185277.