Real-World Treatment Patterns, Survival, and Costs for Ovarian Cancer in Canada: A Retrospective Cohort Study Using Provincial Administrative Data

**Background:** In 2020, approximately 3100 Canadian women were diagnosed with ovarian cancer (OC), with 1950 women dying of this disease. Prognosis for OC remains poor, with 70% to 75% of cases diagnosed at an advanced stage and an overall 5-year survival of 46%. Current standard of care in Canada involves a combination of cytoreductive surgery and platinum-based chemotherapy. **Objective:** There are few studies reporting current OC costs. This study sought to determine patient characteristics and costs to the health system for OC in Ontario, Canada. **Methods:** Women diagnosed with OC in Ontario between 2010 and 2017 were identified. The cohort was linked to provincial administrative databases to capture treatment patterns, survival, and costs. Overall total and mean cost per patient (unadjusted) were reported in 2017 Canadian dollars, using a macro-based costing methodology called GETCOST. It is programmed to determine the costs of short-term and long-term episodes of health-care resources utilized. **Results:** Of the 2539 OC patients included in the study, the mean age at diagnosis was 60.4±11.35 years. The majority were diagnosed with stage III disease (n=1247). The only treatment required for 74% of stage I patients and 54% of stage II patients was first-line (1L) platinum chemotherapy; in advanced stages (III/IV) 24% and 20%, respectively, did not receive further treatment after 1L therapy. The median overall survival (mOS) for the whole cohort was 5.13 years. Survival was highest in earlier stage disease (mOS not reached in stage I/II), and dropped significantly in advanced stage patients (stage III: mOS=4.09 years; stage IV: mOS=3.47 years). Overall mean costs in patients stage I were CAD $58 099 compared to CAD $124 202 in stage IV. **Discussion:** The majority of OC patients continue to be diagnosed with advanced disease, which is associated with poor survival and increased treatment costs. Increased awareness and screening could facilitate diagnosis of earlier stage disease and reduce high downstream costs for advanced disease. **Conclusion:** Advanced OC is associated with poor survival and increased costs, mainly driven by hospitalizations or cancer clinic visits. The introduction of new targeted therapies such as olaparib could impact health system costs, by offsetting higher downstream costs while also improving survival.

Quality of Life in Wilson’s Disease: A Systematic Literature Review

**Background:** Wilson’s disease (WD) is a rare inherited genetic disorder characterized by the progressive accumulation of copper in the brain, liver, and other major organ systems. To date, there have been no comprehensive studies synthesizing evidence pertaining to the quality of life (QOL) in WD. **Objective:** We conducted a systematic literature review to identify and synthesize the evidence on QOL in patients with WD. **Methods:** To address this gap in the literature, we conducted a systematic literature review in MEDLINE and EMBASE to identify observational studies and clinical trials reporting QOL outcomes among people living with WD. **Results:** A total of 442 publications were identified, 41 publications were eligible for full-text screening, and 7 articles, representing 7 studies, met all inclusion criteria. QOL questionnaires used across studies included the 12-Item Short Form Health Survey Questionnaire (version 1) (SF-12) (n=2), the 36-Item Short Form Health Survey Questionnaire (version 1) (SF-36) (n=3), Global Assessment Scale (GAS) (n=1), and World Health Organization QOL brief questionnaire (WHO-QOL-BREF) (n=1). Overall, the pattern in QOL from most studies demonstrated a worse QOL in WD patients compared with the general population, a deterioration in QOL for patients presenting with neurologic symptoms, and more frequent psychiatric symptoms compared with the ones with hepatic symptoms. **Discussion:** Although our understanding of the underlying pathophysiology of WD has advanced, and novel therapeutics are on the horizon, our understanding of how WD affects overall QOL remains limited. Evidence from this review demonstrates the substantial heterogeneity in reporting outcomes pertaining to the QOL associated with WD. These differences may be attributable to the fact that QOL is not typically assessed and the lack of a standardized method for assessing QOL in WD. **Conclusion:** This review demonstrates a need for more up-to-date studies with larger sample sizes to further evaluate QOL in patients with WD. The study also demonstrates the need for a WD-specific instrument to measure the QOL in WD patients.

The Merit-based Incentive Payment System: Pearson’s Chi-Square and Categorical Dependent Variable Models Analyzed for Domains—Effective Clinical Care and Efficiency/Cost Reduction

Background: Following the 2015 repeal of the Sustainable Growth Rate formula, the US Centers for Medicare & Medicaid Services’ formula under which physicians were reimbursed, two payment systems were put in place to incentivize physicians, one of which was the Merit-based Incentive Payment System (MIPS). MIPS emphasizes high-quality care that is accessible, affordable, and supports a healthier population. Objectives: This research aims to measure characteristics of MIPS relevant to National Quality Strategy (NQS) domains, quality measure types, and clinical specialties; categorize MIPS with NQS domains and quality measure types by MIPS specialty types; and quantify the relationship between MIPS specialties, measure types, and two NQS domains, Effective Clinical Care (ECC) and Efficiency/Cost Reduction (E/CR), for years 2017 through 2020. Methodology: The Pearson’s chi-square test examined distributions of the analyzed categorical variables. The Categorical Dependent Variable Method examined the association between the dependent and independent variables. Results: The Pearson’s chi-square test showed statistically significant distributions between ECC and E/CR when analyzed with the types of quality measures. There were more process measures (93.81% vs 89.64% [P=.000]) in 2018 versus 2017. This changed minutely with significantly less process measures (93.75% vs 93.81% [P=.000]) in 2019 versus 2018. Finally, measure types changed minutely but significantly with less process measures (93.81% vs 93.75% [P=.000]) in 2020 versus 2019. The regression model showed that ECC was significantly associated with outcome measures through all analyzed years of this research. Conclusion: The above findings show scope for including additional outcome measures, given its importance in MIPS. There is potential to increase the percentage allocation for reporting more outcome measures in quality. This re-allotment infers reporting more outcome measures aligning with priority outcome measures (PROMs). Re-allocating the incentive formula to report more outcome measures aligned with PROMs shows potential to increase reporting of more outcome measures under MIPS.

Cost-Effectiveness of Apomorphine Sublingual Film as an "On-Demand" Treatment for "OFF" Episodes in Patients with Parkinson's Disease

Background: “On-demand” treatments approved in the United States (US) for “OFF” episodes in Parkinson’s disease (PD) include apomorphine hydrochloride injection (SC-APO), apomorphine sublingual film (APL), and levodopa inhalation powder (CVT-301). APL received US approval in 2020, and its cost-effectiveness has not been compared with SC-APO and CVT-301. Objective: To develop a cost-effectiveness analysis model comparing APL versus SC-APO and CVT-301 for treatment of patients with PD experiencing “OFF” episodes from a US payer perspective. Methods: The model estimated total costs and effectiveness for each comparator arm, informed from the treatments’ pivotal studies or literature, over a 10-year horizon. Total and incremental patient costs (in 2020 US dollars), total time spent without “OFF” episode symptoms, and quality-adjusted life years (QALY) gained were summarized and compared. Incremental cost-effectiveness ratios for APL versus SC-APO and CVT-301 were estimated and expressed as incremental patient costs per patient QALY gained and incremental cost per “OFF” hour avoided. Scenario analyses varying inputs and including caregiver costs were also conducted. Results: In the base case, APL had the lowest total “on-demand” treatment costs ($42,095) compared with SC-APO ($276,320; difference: –$234,225) and CVT-301 ($69,577; difference: –$27,482) over the 10-year horizon. APL was also associated with the highest utility, with incremental QALYs of 0.019 versus SC-APO and 0.235 versus CVT-301. APL was dominant over CVT-301 in terms of incremental cost per “OFF” hour, and dominant over both CVT-301 and SC-APO in terms of incremental cost per QALY gained. In all scenario analyses, APL was dominant against both SC-APO and CVT-301, confirming the robustness of the base-case results. Discussion: APL was dominant compared with both comparator arms, being less costly and more effective on average than SC-APO and CVT-301 in terms of QALYs. For SC-APO, cost-effectiveness of APL was driven by lower “on-demand” treatment costs and adverse event–related disutilities. For CVT-301, cost-effectiveness of APL was driven by lower “on-demand” treatment costs and substantially higher efficacy. Conclusions: From a US payer perspective, APL represents a cost-effective option compared with SC-APO and CVT-301 for treatment of “OFF” episodes in patients with PD.

Cost-Effectiveness of Hypochlorous Acid Preserved Wound Cleanser versus Saline Irrigation in Conjunction with Ultrasonic Debridement for Complex Wounds

Objective: Low-frequency ultrasound debridement with irrigation is an effective method of wound bed preparation. A recent clinical study compared hypochlorous acid preserved wound cleanser (HAPWOC) to saline and found HAPWOC to be a more effective adjunct to low frequency ultrasound debridement. However, HAPWOC has an added cost. The primary objective of this study was to assess the cost-effectiveness of HAPWOC as an irrigation modality with low-frequency ultrasound debridement for the treatment of severely complex wounds that were destined to be closed primarily via a flap. The secondary objective of this study was to estimate the number needed to treat (NNT) to avoid a wound-related complication and its expected cost per NNT. Methods: A patient-level Monte-Carlo simulation model was used to conduct a cost-effectiveness analysis from the US health system perspective. All clinical data were obtained from a prospective clinical trial. Cost data were obtained from the publicly available data sources in 2021 US dollars. The effect measure was the avoidance of wound-related complications at 14-days post-debridement. The primary outcome was the incremental cost-effectiveness ratio (ICER), a measure of the additional cost per benefit. The secondary outcomes were the NNT and expected cost per NNT to avoid one complication (complementary to the ICER in assessing cost-effectiveness). Deterministic and probabilistic sensitivity analyses (PSA) were performed to gauge the robustness and reliability of the results. Results: The ICER for HAPWOC versus saline irrigation was US$90.85 per wound complication avoided. The expected incremental cost per patient in the study and effect was US$49.97 with 55% relative reduction in wound-related complications at day 14 post debridement procedure. The NNT and cost per NNT were 2 and US$99.94, respectively. Sensitivity analyses demonstrated that these results were robust to variation in model parameters. Conclusion: HAPWOC was a cost-effective strategy for the treatment of complex wounds during ultrasonic debridement. For every two patients treated with HAPWOC, one complication was avoided.

Estimating the Economic and Clinical Value of Reducing Antimicrobial Resistance to Three Gram-negative Pathogens in Japan

Background: Antimicrobial resistance (AMR) represents a significant global public health crisis. Despite ample availability of Gram-positive antibiotics, there is a distinct lack of agents against Gram-negative pathogens, including carbapenem-resistant Enterobacterales, which remains a real threat in Japan. The AMR Action Plans aim to mitigate the growing public health concern posed by AMR. Objective: This study aims to estimate the clinical and economic outcomes of drug-resistant Gram-negative pathogens forecasts for Japan to guide resource allocation defined within the upcoming National AMR Action Plan. Methods: A previously published and validated dynamic health economic model was adapted to the Japanese setting. The model used a 10-year time horizon with a willingness-to-pay threshold of ¥5 000 000 (US $46 827) and discounting was applied at a rate of 2% to costs and benefits. Clinical and economic outcomes were assessed as a function of varying AMR levels of three Gram-negative pathogens in Japan by up to 100% of the current level. Results: Reducing drug-resistant Gram-negative pathogens in Japan has the potential to save 4 249 096 life years, corresponding to 3 602 311 quality-adjusted life years. The associated maximum clinical and economic gains were estimated at up to 4 422 284 bed days saved, up to 3 645 480 defined daily doses of antibiotics avoided, up to ¥117.6 billion (US $1.1 billion) saved in hospitalization costs, and a net monetary benefit of up to ¥18.1 trillion (US $169.8 billion). Discussion: Learnings from this study can be used by the Japanese government to help inform decision-making on the strategies that may be included in the upcoming National AMR Action Plan and facilitate allocation of the required budget. Conclusions: This analysis demonstrated the considerable economic and clinical value of reducing AMR levels of three Gram-negative pathogens in Japan and could be utilized to support the valuation of antimicrobial treatment and resistance in Japan and more broadly.