Association between non-medical cannabis legalization and alcohol sales: Quasi-experimental evidence from Canada.

BACKGROUND: There is increasing interest in understanding the impact of non-medical cannabis legalization on use of other substances, especially alcohol. Evidence on whether cannabis is a substitute or complement for alcohol is both mixed and limited. This study provides the first quasi-experimental evidence on the impact of Canada's legalization of non-medical cannabis on beer and spirits sales. METHODS: We used the interrupted time series design and monthly data on beer sales between January 2012 and February 2020 and spirits sales between January 2016 and February 2020 across Canada to investigate changes in beer and spirits sales following Canada's cannabis legalization in October 2018. We examined changes in total sales, nationally and in individual provinces, as well as changes in sales of bottled, canned and kegged beer. RESULTS: Canada-wide beer sales fell by 96 hectoliters per 100,000 population (p=0.011) immediately after non-medical cannabis legalization and by 4 hectoliters per 100,000 population (p>0.05) each month thereafter for an average monthly reduction of 136 hectoliters per 100,000 population (p<0.001) post-legalization. However, the legalization was associated with no change in spirits sales. Beer sales reduced in all provinces except the Atlantic provinces. By beer type, the legalization was associated with declines in sales of canned and kegged beer but there was no reduction in sales of bottled beer. CONCLUSIONS: Non-medical cannabis legalization was associated with a decline in beer sales in Canada, suggesting substitution of non-medical cannabis for beer. However, there was no change in spirits sales following the legalization.

Cost-Effectiveness of Lecanemab for Individuals With Early-Stage Alzheimer Disease.

BACKGROUND AND OBJECTIVES: Little is known regarding the cost-effectiveness of lecanemab (Leqembi), a monoclonal antibody approved by the US Food and Drug Administration in January 2023 for the treatment of mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease (AD). This study aims to quantify the cost-effectiveness of lecanemab and how it varies based on the accuracy of AD testing and individuals' APOE ε4 status. METHODS: Seven alternative test-treat-target strategies defined by combinations of testing approaches (PET, CSF, or plasma assay), treatment choices (standard of care [SoC] alone or lecanemab in addition to SoC), and targeting strategies (targeting APOE ε4 noncarriers or heterozygous patients or not) were compared. A hybrid decision tree-Markov cohort model was constructed with 5 states: (1) MCI (Clinical Dementia Rating-Sum of Boxes [CDR-SB] 0-4.5); (2) mild dementia (CDR-SB 4.6-9.5); (3) moderate dementia (CDR-SB 9.6-16); (4) severe dementia (CDR-SB >16); and (5) death. Effectiveness was measured by quality-adjusted life years and costs from third-party and societal perspectives were estimated in 2022 US dollars over a lifetime horizon. RESULTS: Among the 7 test-treat-target strategies, SoC alone was the optimal strategy from a cost-effectiveness perspective. Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype was cost-effective vs SoC alone, regardless of the test used to diagnose patients with early-stage AD. However, CSF assay followed by targeted treatment would become cost-effective if lecanemab is priced below $5,100 per year. These results were robust to the accuracy of diagnostic testing and rates of lecanemab discontinuation and adverse events. DISCUSSION: Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype is cost-effective vs SoC alone for patients with MCI or mild dementia due to AD. Lecanemab would be cost-effective in some settings if priced below $5,100 per year.

British Columbia's Safer Opioid Supply Policy and Opioid Outcomes.

Importance: In March 2020, British Columbia, Canada, became the first jurisdiction globally to launch a large-scale provincewide safer supply policy. The policy allowed individuals with opioid use disorder at high risk of overdose or poisoning to receive pharmaceutical-grade opioids prescribed by a physician or nurse practitioner, but to date, opioid-related outcomes after policy implementation have not been explored. Objective: To investigate the association of British Columbia's Safer Opioid Supply policy with opioid prescribing and opioid-related health outcomes. Design, Setting, and Participants: This cohort study used quarterly province-level data from quarter 1 of 2016 (January 1, 2016) to quarter 1 of 2022 (March 31, 2022), from British Columbia, where the Safer Opioid Supply policy was implemented, and Manitoba and Saskatchewan, where the policy was not implemented (comparison provinces). Exposure: Safer Opioid Supply policy implemented in British Columbia in March 2020. Main Outcomes and Measures: The main outcomes were rates of prescriptions, claimants, and prescribers of opioids targeted by the Safer Opioid Supply policy (hydromorphone, morphine, oxycodone, and fentanyl); opioid-related poisoning hospitalizations; and deaths from apparent opioid toxicity. Difference-in-differences analysis was used to compare changes in outcomes before and after policy implementation in British Columbia with those in the comparison provinces. Results: The Safer Opioid Supply policy was associated with statistically significant increases in rates of opioid prescriptions (2619.6 per 100 000 population; 95% CI, 1322.1-3917.0 per 100 000 population; P < .001) and claimants (176.4 per 100 000 population; 95% CI, 33.5-319.4 per 100 000 population; P = .02). There was no significant change in prescribers (15.7 per 100 000 population; 95% CI, -0.2 to 31.6 per 100 000 population; P = .053). However, the opioid-related poisoning hospitalization rate increased by 3.2 per 100 000 population (95% CI, 0.9-5.6 per 100 000 population; P = .01) after policy implementation. There were no statistically significant changes in deaths from apparent opioid toxicity (1.6 per 100 000 population; 95% CI, -1.3 to 4.5 per 100 000 population; P = .26). Conclusions and Relevance: Two years after its launch, the Safer Opioid Supply policy in British Columbia was associated with higher rates of safer supply opioid prescribing but also with a significant increase in opioid-related poisoning hospitalizations. These findings will help inform ongoing debates about this policy not only in British Columbia but also in other jurisdictions that are contemplating it.

Recreational and Medical Cannabis Legalization and Opioid Prescriptions and Mortality.

Importance: While some have argued that cannabis legalization has helped to reduce opioid-related morbidity and mortality in the US, evidence has been mixed. Moreover, existing studies did not account for biases that could arise when policy effects vary over time or across states or when multiple policies are assessed at the same time, as in the case of recreational and medical cannabis legalization. Objective: To quantify changes in opioid prescriptions and opioid overdose deaths associated with recreational and medical cannabis legalization in the US. Design, Setting, and Participants: This quasiexperimental, generalized difference-in-differences analysis used annual state-level data between January 2006 and December 2020 to compare states that legalized recreational or medical cannabis vs those that did not. Intervention: Recreational and medical cannabis law implementation (proxied by recreational and medical cannabis dispensary openings) between 2006 and 2020 across US states. Main Outcomes and Measures: Opioid prescription rates per 100 persons and opioid overdose deaths per 100 000 population based on data from the US Centers for Disease Control and Prevention. Results: Between 2006 and 2020, 13 states legalized recreational cannabis and 23 states legalized medical cannabis. There was no statistically significant association of recreational or medical cannabis laws with opioid prescriptions or overall opioid overdose mortality across the 15-year study period, although the results also suggested a potential reduction in synthetic opioid deaths associated with recreational cannabis laws (4.9 fewer deaths per 100 000 population; 95% CI, -9.49 to -0.30; P = .04). Sensitivity analyses excluding state economic indicators, accounting for additional opioid laws and using alternative ways to code treatment dates yielded substantively similar results, suggesting the absence of statistically significant associations between cannabis laws and the outcomes of interest during the full study period. Conclusions and Relevance: The results of this study suggest that, after accounting for biases due to possible heterogeneous effects and simultaneous assessment of recreational and medical cannabis legalization, the implementation of recreational or medical cannabis laws was not associated with opioid prescriptions or opioid mortality, with the exception of a possible reduction in synthetic opioid deaths associated with recreational cannabis law implementation.

Changes in Medical Cannabis Use After Recreational Cannabis Legalization in Canada.

Background: As part of its recreational cannabis legalization in October 2018, Canada imposed an excise tax of 10% (or $1 a gram, whichever is higher) on both recreational and medical cannabis. There is little evidence to inform the ongoing debate on whether the legalization had adverse impacts on medical cannabis use. Methods: We used an interrupted time series design and data on medical cannabis shipments (i.e., mail-order deliveries of cannabis from a licensed producer to a patient authorized to obtain medical cannabis) in Canada between quarter 1 of 2014 and quarter 1 of 2020. We examined changes in medical cannabis shipments after Canada's recreational cannabis legalization both across Canada and for each province. As this study used publicly available, province-level aggregate data, ethics approval was not required. Results: Recreational cannabis legalization was associated with significant reductions in medical cannabis use in 7 out of 10 Canadian provinces. Compared with the counterfactual estimated from prelegalization trends, the reduction in quarter 1 of 2020 varied from 500 shipments per 100,000 population (95% CI=312-688 shipments per 100,000 population) or 32% (95% CI=22-43%) in Newfoundland and Labrador to 3,778 shipments per 100,000 population (95% CI=2,972-4,585 shipments per 100,000 population) or 74% (95% CI=68-79%) in Alberta. At the national level, the number of medical cannabis shipments decreased by 823 per 100,000 population (95% CI=725-921 shipments per 100,000 population) or 48% (95% CI=45-52%). Conclusions: Recreational cannabis legalization was associated with reductions in medical cannabis use. Our findings call for policy attention to address possible adverse impacts of recreational cannabis legalization on medical cannabis users.

Cost-Effectiveness of Antiobesity Drugs for Adolescents With Severe Obesity.

Importance: Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown. Objective: To quantify cost-effectiveness of different antiobesity drugs available for pediatric use. Design, Setting, and Participants: This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature. Intervention: Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY. Conclusions and Relevance: In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.

Cost-effectiveness of canagliflozin and dapagliflozin for treatment of patients with chronic kidney disease and type 2 diabetes.

AIM: To examine the cost-effectiveness of adding canagliflozin or dapagliflozin to standard of care (SoC) versus SoC alone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). MATERIALS AND METHODS: We used a Markov microsimulation model to assess the cost-effectiveness of canagliflozin plus SoC (canagliflozin + SoC), dapagliflozin plus SoC (dapagliflozin + SoC) and SoC alone. Analyses were conducted from a healthcare system perspective. Costs were measured in 2021 Canadian dollars (C$), and effectiveness was measured in quality-adjusted life-years (QALYs). RESULTS: Over a patient's lifetime, canagliflozin + SoC and dapagliflozin + SoC yielded cost savings of C$33 460 and C$26 764 and generated 1.38 and 1.44 additional QALYs compared with SoC alone, respectively. While QALY gains with dapagliflozin + SoC were higher than those with canagliflozin + SoC, this strategy was also more costly with the incremental cost-effectiveness ratio exceeding the willingness to pay threshold of C$50 000 per QALY. Dapagliflozin + SoC, however, generated cost savings and QALY gains compared with canagliflozin + SoC over shorter time horizons of 5 or 10 years. CONCLUSIONS: Dapagliflozin + SoC was not cost-effective versus canagliflozin + SoC in patients with CKD and T2D over the lifetime horizon. However, adding canagliflozin or dapagliflozin to SoC was less costly and more effective relative to SoC alone for treatment of CKD and T2D.

Estimated cost-effectiveness of point-of-care testing in community pharmacies vs. self-testing and standard laboratory testing for HIV.

OBJECTIVE: Point-of-care-testing (POCT) for HIV at community pharmacies can enhance care linkage compared with self-tests and increase testing uptake relative to standard lab testing. While the higher test uptake may increase testing costs, timely diagnosis and treatment can reduce downstream HIV treatment costs and improve health outcomes. This study provides the first evidence on the cost-effectiveness of pharmacist-led POCT vs. HIV self-testing and standard lab testing. DESIGN: Dynamic transmission model. METHODS: We compared three HIV testing strategies: POCT at community pharmacies; self-testing using HIV self-test kits; and standard lab testing. Analyses were conducted from the Canadian health system perspective over a 30-year time horizon for all individuals aged 15-64 years in Canada. Costs were measured in 2021 Canadian dollars and effectiveness was captured using quality-adjusted life-years (QALYs). RESULTS: Compared with standard lab testing, POCT at community pharmacies would save $885 million in testing costs over 30 years. Though antiretroviral treatment costs would increase by $190 million with POCT as more persons living with HIV are identified and treated, these additional costs would be partly offset by their lower downstream healthcare utilization (savings of $150 million). POCT at community pharmacies would also yield over 5000 additional QALYs. Compared with HIV self-testing, POCT at community pharmacies would generate both higher costs and higher QALYs and would be cost-effective with an incremental cost-effectiveness ratio of $47 475 per QALY gained. CONCLUSIONS: Offering POCT at community pharmacies can generate substantial cost savings and improve health outcomes compared with standard lab testing. It would also be cost-effective vs. HIV self-testing.

Cost-effectiveness of dapagliflozin and empagliflozin for treatment of heart failure with reduced ejection fraction.

BACKGROUND: The differences in cost and efficacy between dapagliflozin and empagliflozin in combination with standard of care (SoC) raise the question of which regimen would be cost-effective in treating heart failure with reduced ejection fraction (HFrEF). This study evaluates the cost-effectiveness of dapagliflozin plus SoC (dapagliflozin-SoC) versus empagliflozin plus SoC (empagliflozin-SoC) or SoC alone for treatment of HFrEF. METHODS: We developed a Markov model to estimate the cost-effectiveness of dapagliflozin-SoC, empagliflozin-SoC, and SoC alone from the healthcare system perspective over a lifetime horizon. Data on efficacy of dapagliflozin-SoC, empagliflozin-SoC, and SoC were obtained from randomized controlled trials. Costs were measured in 2022 US dollars, and effectiveness was measured in quality-adjusted life years (QALYs). RESULTS: Among three strategies, dapagliflozin-SoC was the most cost-effective strategy and dominated empagliflozin-SoC in an extended sense. Compared with SoC alone, dapagliflozin-SoC and empagliflozin-SoC had incremental cost-effectiveness ratios (ICER) of $56,782 and $89,258 per QALY, respectively. Dapagliflozin-SoC cost more $5524 but yielded more 0.20 QALYs than empagliflozin-SoC, with the ICER of $27,861 per QALY. The cost-effectiveness of dapagliflozin-SoC, empagliflozin-SoC, and SoC alone did not depend on diabetic status. However, empagliflozin-SoC was no longer cost-effective versus SoC alone in HFrEF patients without CKD, and dapagliflozin-SoC was not cost-effective versus empagliflozin-SoC in HFrEF patients with CKD. CONCLUSION: Dapagliflozin-SoC was cost-effective versus empagliflozin-SoC or SoC alone for treatment of HFrEF.

Comparative efficacy of sodium-glucose co-transporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta-analysis.

AIM: To compare the relative efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and non-steroidal mineralocorticoid receptor antagonists (nsMRAs) in improving the cardiovascular and renal outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). MATERIALS AND METHODS: We searched PubMed, Embase and Cochrane Library from inception through 25 November 2022. We selected randomized controlled trials that studied patients with CKD and T2D with a follow-up of at least 24 weeks and compared SGLT-2is, GLP-1RAs and nsMRAs with each other and with placebo. Primary outcomes were major adverse cardiovascular events (MACE) and composite renal outcomes (CRO). Secondary outcomes were cardiovascular death, all-cause death, stroke, myocardial infarction and heart failure hospitalization (HFH). A frequentist approach was used to pool risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Twenty-nine studies with 50 938 participants for MACE and 49 965 participants for CRO were included. SGLT-2is did not significantly reduce MACE but were associated with significantly lower risks of CRO compared with GLP-1RAs (RR, 0.77; 95% CI, 0.64-0.91; P = .003) and nsMRAs (RR, 0.78; 95% CI, 0.68-0.90; P = .001). Compared with GLP-1RAs and nsMRAs, SGLT-2is significantly reduced risks of HFH by 31% (RR, 0.69; 95% CI, 0.55-0.88; P = .002) and 22% (RR, 0.78; 95% CI, 0.63-0.95; P = .016), respectively, but did not significantly reduce other secondary outcomes. There were no significant differences between GLP-1RAs and nsMRAs in lowering all outcomes. CONCLUSIONS: SGLT-2is were associated with better cardiorenal protection than GLP-1RAs and nsMRAs in patients with CKD and T2D.

Short-Term Effects of Recreational Cannabis Legalization on Youth Cannabis Initiation.

PURPOSE: As recreational cannabis is legalized, it is critical to know the impacts of legalization on youth cannabis use. Existing research generates conflicting results and does not shed light on channels of effects. This study investigates the impacts of legalization on youth cannabis initiation and overall cannabis use prevalence. METHODS: We used Interrupted Time Series design and data from nationally-representative repeated cross-sectional Canadian surveys spanning 16 years. The primary outcomes were cannabis initiation rates and cannabis use prevalence among youths. The secondary outcomes were self-reported age of first cannabis use, ease of cannabis access, and perception of cannabis harm among youths. RESULTS: After legalization, cannabis initiation rate among youths was 2.7 percentage points (95% confidence interval: 1.7-3.7; p < .01) or 69% higher, although there was no significant increase in the overall prevalence of cannabis use. Furthermore, there was a 4-month delay in the average age of first cannabis use among youths aged 17-18 years (95% confidence interval: 2.6-5.5 months; p < .01). The legalization was associated with greater perception of cannabis harm but also easier access to cannabis. DISCUSSION: The impacts of legalization on youth cannabis use after 1 year are mixed. Although we observed an increase in cannabis initiation among youths who had never used cannabis, there was no change in the overall prevalence of cannabis use, implying a possible offsetting increase in cannabis cessation among existing users. To achieve legalization's goal of reducing youth cannabis use, policy measures are needed to curb youth cannabis access and initiation.

Changes in Youth Cannabis Use After an Increase in Cannabis Minimum Legal Age in Quebec, Canada.

Importance: In January 2020, Quebec raised the minimum legal age (MLA) for cannabis from 18 to 21 years. Evidence is needed to inform the ongoing debate on this policy. Although proponents believe that a higher MLA will protect youths from the harms of cannabis use, critics argue that it will push them back to the illegal market. Objective: To investigate changes in youth cannabis use after an increase in MLA for cannabis in Quebec. Design, Setting, and Participants: This cross-sectional study with difference-in-differences analysis compared changes in cannabis use among youths aged 15 to 20 years in Quebec vs all other Canadian provinces before and after Quebec's increase in MLA. All estimates in descriptive and regression analyses were weighted. Nationally representative data from the National Cannabis Surveys 2018-2020 were used. Intervention: Increase in MLA for cannabis in Quebec implemented in January 2020. Main Outcomes and Measures: Past-3-month cannabis use. Results: The study sample included 1005 respondents (mean [SD] age, 17.5 [1.7] years; 50.2% [SD, 50.0%] male). After policy implementation, the increase in past-3-month cannabis use among youths aged 18 to 20 was 16.4 percentage points (95% CI, -27.3 to -5.5 percentage points; P = .01), or 51%, lower in Quebec than in other provinces. Meanwhile, no significant change in cannabis use among youths aged 15 to 17 years was found. The results were robust to several checks, including accounting for possible confounding effects of the COVID-19 pandemic on cannabis use. Conclusions and Relevance: In this study, an increase in the MLA from 18 to 21 years in Quebec was associated with a significantly lower increase in cannabis use among youths aged 18 to 20 years but no change in cannabis use among those aged 15 to 17 years. These findings can help to alleviate concerns that youths would switch to illegal markets in response to a higher MLA.

Effects of e-cigarette use on mental health among youths: quasi-experimental evidence from Canada.

BACKGROUND AND AIMS: Existing research on mental health comorbidities of youth e-cigarette use is subject to confounding bias and reverse causality. This study aimed to measure the effects of e-cigarette use on youth mental health, using e-cigarette minimum legal age (MLA) law in Canada as a natural experiment. DESIGN: We used difference-in-differences (DD), difference-in-differences-in-differences (DDD) and two-sample instrumental variables (TSIV) methods. SETTING: Data were from nationally representative Canadian Community Health Surveys 2008-2019 and Canadian Student Tobacco Alcohol and Drugs Surveys 2008-2019. PARTICIPANTS: The study sample comprised of respondents aged 15 to 18 (in DD analysis; n = 33 858) and aged 15 to 24 (in DDD analysis; n = 78 689). MEASUREMENTS: Primary outcomes were self-reported mood disorders and anxiety disorders. Secondary outcomes were cannabis use, illicit drug use, cigarette use and strength of peer relationships at schools. FINDINGS: After the e-cigarette MLA laws, risks of mood disorders declined by 1.9 percentage points (95% CI, 0.0-3.8; P = 0.05) in the DD analysis and by 2.6 percentage points (95% CI, 0.2-5.0; P = 0.03) in the DDD analysis. For anxiety disorders, while the DD estimate was negative but imprecisely estimated, the MLA law reduced risks of anxiety disorder by 3.6 percentage points (95% CI, 0.9-6.2; P = 0.01) in the DDD analysis. Youths in provinces with MLA laws were also less likely to report cannabis use and illicit drug use and more likely to feel being part of schools. TSIV analysis indicates that youth e-cigarette use increased the likelihood of mood and anxiety disorders by 44% and 37%, respectively. CONCLUSION AND RELEVANCE: In Canada, the e-cigarette minimum legal age law appears to have reduced risks of mood and anxiety disorders, lowered substance use and improved peer relationships at schools. Combined with previous evidence of lower e-cigarette use following the minimum legal age law, our findings indicate that youth e-cigarette use increases risks of mood and anxiety disorders.

Cost-effectiveness of using artificial intelligence versus polygenic risk score to guide breast cancer screening.

BACKGROUND: Current guidelines for mammography screening for breast cancer vary across agencies, especially for women aged 40-49. Using artificial Intelligence (AI) to read mammography images has been shown to predict breast cancer risk with higher accuracy than alternative approaches including polygenic risk scores (PRS), raising the question whether AI-based screening is more cost-effective than screening based on PRS or existing guidelines. This study provides the first evidence to shed light on this important question. METHODS: This study is a model-based economic evaluation. We used a hybrid decision tree/microsimulation model to compare the cost-effectiveness of eight strategies of mammography screening for women aged 40-49 (screening beyond age 50 follows existing guidelines). Six of these strategies were defined by combinations of risk prediction approaches (AI, PRS or family history) and screening frequency for low-risk women (no screening or biennial screening). The other two strategies involved annual screening for all women and no screening, respectively. Data used to populate the model were sourced from the published literature. RESULTS: Risk prediction using AI followed by no screening for low-risk women is the most cost-effective strategy. It dominates (i.e., costs more and generates fewer quality adjusted life years (QALYs)) strategies for risk prediction using PRS followed by no screening or biennial screening for low-risk women, risk prediction using AI or family history followed by biennial screening for low-risk women, and annual screening for all women. It also extendedly dominates (i.e., achieves higher QALYs at a lower incremental cost per QALY) the strategy for risk prediction using family history followed by no screening for low-risk women. Meanwhile, it is cost-effective versus no screening, with an incremental cost-effectiveness ratio of $23,755 per QALY gained. CONCLUSIONS: Risk prediction using AI followed by no breast cancer screening for low-risk women is the most cost-effective strategy. This finding can be explained by AI's ability to identify high-risk women more accurately than PRS and family history (which reduces the possibility of delayed breast cancer diagnosis) and fewer false-positive diagnoses from not screening low-risk women.

Cost-Effectiveness of Low-Dose Antithymocyte Globulin Versus Other Immunotherapies for Treatment of New-Onset Type 1 Diabetes.

Objective: Several immunotherapies have shown efficacy in slowing C-peptide decline in new-onset type 1 diabetes. Although most of these biologic drugs are expensive, they offer the opportunity to reduce downstream disease management costs and risk of complications. The objective of this study is to examine the cost-effectiveness of immunotherapies versus no treatment for patients with new-onset type 1 diabetes. Methods: Using Markov microsimulation modeling and efficacy data from immunotherapy trials, we examined the cost-effectiveness of six immunotherapies for new-onset type 1 diabetes, namely, low-dose (2.5 mg/kg) antithymocyte globulin (ATG), high-dose (6.5 mg/kg) ATG, abatacept, alefacept, rituximab, and teplizumab, versus no treatment. Effectiveness was measured by quality-adjusted life-years (QALYs). Costs were estimated from a health system perspective. Results: Low-dose ATG treatment saves US$10,270, on average, over a patient's lifetime and generates 0.09 additional QALYs compared with no treatment. These cost savings arise as low-dose ATG generates downstream savings in disease management costs that more than offset its cost. In contrast, treatment with other immunotherapies yields smaller QALY gains (0.02-0.05 additional QALYs) and increases lifetime costs by US$9500-US$168,380 relative to no treatment, with incremental cost-effectiveness ratios that exceed the willingness-to-pay threshold of US$100,000 per QALY. Conclusions: Low-dose ATG treatment is both less costly and more effective relative to other immunotherapies and no treatment for new-onset type 1 diabetes.

Cost-effectiveness of procedure-less intragastric balloon therapy as substitute or complement to bariatric surgery.

BACKGROUND: Procedure-less intragastric balloon (PIGB) eliminates costs and risks of endoscopic placement/removal and involves lower risk of serious complications compared with bariatric surgery, albeit with lower weight loss. Given the vast unmet need for obesity treatment, an important question is whether PIGB treatment is cost-effective-either stand-alone or as a bridge to bariatric surgery. METHODS: We developed a microsimulation model to compare the costs and effectiveness of six treatment strategies: PIGB, gastric bypass or sleeve gastrectomy as stand-alone treatments, PIGB as a bridge to gastric bypass or sleeve gastrectomy, and no treatment. RESULTS: PIGB as a bridge to bariatric surgery is less costly and more effective than bariatric surgery alone as it helps to achieve a lower post-operative BMI. Of the six strategies, PIGB as a bridge to sleeve gastrectomy is the most cost-effective with an ICER of $3,781 per QALY gained. While PIGB alone is not cost-effective compared with bariatric surgery, it is cost-effective compared with no treatment with an ICER of $21,711 per QALY. CONCLUSIONS: PIGB can yield cost savings and improve health outcomes if used as a bridge to bariatric surgery and is cost-effective as a stand-alone treatment for patients lacking access or unwilling to undergo surgery.

Cost Effectiveness of Teplizumab for Prevention of Type 1 Diabetes Among Different Target Patient Groups.

OBJECTIVE: Teplizumab was recently shown to be the first-ever drug to prevent or delay type 1 diabetes mellitus onset in at-risk individuals, especially those with certain genetic and antibody characteristics. However, its potentially high price may pose challenges for coverage and reimbursement for payers and policymakers. Thus, it is critical to investigate the cost effectiveness of this drug for different target individuals. RESEARCH DESIGN AND METHODS: Using Markov microsimulation modeling, we compared the cost effectiveness of five options for choosing target individuals (i.e., all at-risk individuals, individuals without human leukocyte antigen (HLA)-DR3 or with HLA-DR4 allele, individuals without HLA-DR3 and with HLA-DR4 allele, individuals with anti-zinc transporter 8 (ZnT8) antibody negative, and no provision at all) at different possible prices of teplizumab. Effectiveness was measured by quality-adjusted life-years. Costs were estimated from a health system perspective. RESULTS: If the price of teplizumab is below US$48,900, treating all at-risk individuals is cost effective. However, it will be cost effective to treat only individuals without HLA-DR3 or with HLA-DR4 alleles for prices between US$48,900 and US$58,200, only individuals both without HLA-DR3 and with HLA-DR4 alleles for prices between US$58,200 and US$88,300, and only individuals with negative ZnT8 antibody status for prices between US$88,300 and US$193,700. CONCLUSIONS: Cost-effective provision of teplizumab to target individuals depends on the price of teplizumab and genetic and antibody characteristics of treated individuals. As the drug makes its way to the market, findings from this study will help inform policymakers and payers on cost-effective ways to provide this innovative but expensive drug to at-risk individuals.

Too young for Cannabis? Choice of minimum legal age for legalized non-medical Cannabis in Canada.

BACKGROUND: Choice of minimum legal age (MLA) for cannabis use is a critical and contentious issue in legalization of non-medical cannabis. In Canada where non-medical cannabis was recently legalized in October 2018, the federal government recommended age 18, the medical community argued for 21 or even 25, while public consultations led most Canadian provinces to adopt age 19. However, no research has compared later life outcomes of first using cannabis at these different ages to assess their merits as MLAs. METHODS: We used doubly robust regression techniques and data from nationally representative Canadian surveys to compare educational attainment, cigarette smoking, self-reported general and mental health associated with different ages of first cannabis use. RESULTS: We found different MLAs for different outcomes: 21 for educational attainment, 19 for cigarette smoking and mental health and 18 for general health. Assuming equal weight for these individual outcomes, the 'overall' MLA for cannabis use was estimated to be 19 years. Our results were robust to various robustness checks. CONCLUSION: Our study indicated that there is merit in setting 19 years as MLA for non-medical cannabis.

Heritable thrombophilia test utilization and cost savings following guideline-based restrictions: An interrupted time series analysis.

OBJECTIVE: Existing guidelines provide indications for appropriate heritable thrombophilia (HT) testing but testing practices often do not conform to these guidelines. The Canadian province of Newfoundland and Labrador (NL) implemented a new 'hard-stop' guideline-based approach to HT testing whereby tests ordered outside specific guidelines were rejected. The objective of this study was to evaluate the effectiveness of this intervention and the associated cost savings. METHODS: Using data on number of HT tests ordered and performed in NL between December 1, 2014 and February 28, 2018, we conducted interrupted time series analyses to analyze changes in number of HT tests ordered and performed following the intervention. Cost savings were estimated by comparing cost of tests actually performed after enforcement of guidelines with the cost of counterfactual number of tests that would have been performed without guidelines. RESULTS: Guideline-based restrictions on HT testing were associated with a 86-98% decline in the number of tests performed (p < 0.05). Contrary to previous softer, educational approaches to restricting HT testing, number of Protein C and Factor V Leiden/Prothrombin G20210A tests ordered also declined post-guideline implementation (p < 0.05). Annual cost savings associated with reductions in tests performed were estimated to be $205,154 for NL from a societal perspective. We estimated that if this model was expanded across Canada, annual cost savings could be as large as $14.2 million from a societal perspective. CONCLUSIONS: A 'hard-stop' guideline-based approach to restricting HT testing is associated with significant reductions in HT testing and meaningful cost savings.