An overview of patients with haemophilia A in China: Epidemiology, disease severity and treatment strategies.

INTRODUCTION: Haemophilia A (HA) is a rare X chromosome-linked bleeding disorder resulting in missing or defective clotting factor VIII (FVIII) and causes large disease burden. AIM: As a member of World Federation of Hemophilia, China seeks to understand the current epidemiology, disease profile and treatment landscape of patients with HA through the Hemophilia Treatment Center Collaboration Network of China (HTCCNC). METHODS: The HTCCNC enabled data collection on patients with HA from 166 member hospitals (2007-2019) across China. The distribution of patients across 31 divisions was summarized using a heat map. Patient demographics, disease severity and clinical and treatment information were summarized using descriptive statistics. RESULTS: HTCCNC identified 17,779 patients with HA during 2007-2019. Patients were predominantly male (99.99%), and 28.3% had a known family history of haemophilia. Among patients with lab-measured disease severity (N = 13,116), 6,519 had severe HA (49.7%), 4,788 had moderate HA (36.5%), and 1,809 had mild HA (13.8%). Among patients with information on the delays, delays in diagnosis and in treatment initiation were observed in 1,437 (28.8%) and 1,750 (39.2%) patients, respectively. On average, those patients had an 8.4 years gap between the first bleed and HA diagnosis and a delay of 8.6 years from the first bleed to treatment initiation. Additionally, 44.33% of patients relied solely on episodic treatments, and 16.2% received any prophylaxis treatments. CONCLUSIONS: Using data from the largest haemophilia registry in China, this study indicated that delayed diagnosis and treatment, together with low utilization of prophylaxis, are key challenges for patients with HA.

Real-world analysis of haemophilia patients in China: A single centre's experience.

INTRODUCTION: The management of haemophilia is critical to minimize the risk of disability and reduce the burden on China's healthcare system. AIM: This study was based on a single centre in China and was conducted to understand the evolution of real-world haemophilia care over the past 15 years. METHODS: We retrospectively analysed clinical characteristics, diagnosis, treatment and medical expenditures of 428 patients with haemophilia from January 2004 to December 2018 from the Institute of Hematology & Blood Diseases Hospital in Tianjin, China. RESULTS: The delayed diagnosis time significantly decreased from 13.3 ± 5.1 years before 2004 to 0.4 ± 0.4 year in 2014-2018 (P < .05). Among children and adults receiving prophylactic treatment, the annual factor consumption increased from 2004-2008 (168.8 IU/kg in children and 120.7 IU/kg in adults) to 2009-2013 (389.2 IU/kg in children and 316.2 IU/kg in adults) and 2014-2018 (1328.0 IU/kg in children and 878.8 IU/kg in adults, P < .001). The annual medical insurance expenditure for haemophilia had increased steadily over the past 10 years. The number of patients tested regularly for inhibitors increased from 2004 (1.9% [2/105]) to 2018 (21.5% [59/275]). The seroprevalence of hepatitis C virus (HCV) was 33.8% during the years examined, while the incidence rates of HCV among patients significantly decreased (7.3% in 2008 to 0.4% in 2018). CONCLUSION: Significant improvements in the management of haemophilia were observed from 2004 to 2018. These results highlight the joint effort of the reimbursement policy and drug regulatory management paving the way for a better future for patients with haemophilia in China.

Evaluation of Pathologic Complete Response as a Surrogate for Long-Term Survival Outcomes in Triple-Negative Breast Cancer.

BACKGROUND: Pathologic complete response (pCR) is a common efficacy endpoint in neoadjuvant therapy trials for triple-negative breast cancer (TNBC). Previous studies have shown that pCR is strongly associated with improved long-term survival outcomes, including event-free survival (EFS) and overall survival (OS). However, the trial-level associations between treatment effect on pCR and long-term survival outcomes are not well established. This study sought to evaluate these associations by incorporating more recent clinical trials in TNBC. METHODS: A literature review identified published randomized controlled trials (RCTs) of neoadjuvant therapy for TNBC that reported results for both pCR and EFS/OS. Meta-regression models were performed to evaluate the association of treatment effect on pCR and EFS/OS. Sensitivity analyses were conducted to assess the impact of divergent study designs. RESULTS: Ten comparisons from 8 RCTs (N=2,478 patients) were identified from the literature review. The log (odds ratio) of pCR was a significant predictor of the log (hazard ratio) of EFS (P=.003), with a coefficient of determination of 0.68 (95% CI, 0.41-0.95). There was a weaker association between pCR and OS (P=.18), with a coefficient of determination of 0.24 (95% CI, 0.01-0.77). Consistent results were found in the exploratory analysis and sensitivity analyses. CONCLUSIONS: This is the first study that has shown a trial-level association between pCR and survival outcomes in TNBC. By incorporating the most up-to-date RCTs, this study showed a significant trial-level association between pCR and EFS. A positive association between pCR and OS was also recorded.

Cost-effectiveness analysis of ceritinib vs. crizotinib in previously untreated anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in Hong Kong.

INTRODUCTION: Lower-dose ceritinib (450 mg) once-daily with food was approved in 2018 in Hong Kong (HK) for first-line treatment of patients with anaplastic lymphoma kinase-positive (ALK +) advanced non-small cell lung cancer (NSCLC). This study examined the cost-effectiveness of ceritinib vs. crizotinib in the first-line treatment of ALK + NSCLC from a HK healthcare service provider's or government's perspective. METHODS: Costs and effectiveness of first-line ceritinib vs. crizotinib over a 20-year time horizon was evaluated using a partitioned survival model with three health states (stable disease, progressed disease, and death). The efficacy data for ceritinib were obtained from a phase 3 trial comparing ceritinib with chemotherapy for advanced non-small cell lung cancer (ASCEND-4) and extrapolated using parametric survival models. Long-term survival associated with crizotinib were estimated using hazard ratio of crizotinib vs. ceritinib obtained from matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014 trials. Drug acquisition, administration, adverse events costs, and medical costs associated with each health state were obtained from public sources and converted to 2018 US Dollars. Incremental costs per quality-adjusted-life-year (QALY) and life-year (LY) gained were estimated for ceritinib vs. crizotinib. RESULTS: The base case results showed that ceritinib was associated with 3.22 QALYs, 4.51 LYs, and total costs of $157,581 over 20 years. Patients receiving crizotinib had 2.68 QALYs, 3.85 LYs, and $150,424 total costs over the same time horizon. The incremental cost per QALY gained for ceritinib vs crizotinib was $13,343. Results were robust to deterministic sensitivity analyses in most scenarios. CONCLUSION: Ceritinib offers a cost-effective option compared to crizotinib for previously untreated ALK + advanced NCSLC in HK.

Burden and treatment patterns of advanced basal cell carcinoma among commercially insured patients in a United States database from 2010 to 2014.

BACKGROUND: The burden of advanced basal cell carcinoma (aBCC) is not fully understood. OBJECTIVE: To compare BCC disease burden and treatment patterns for aBCC with those for non-aBCC. METHODS: A retrospective, insurance claims-based study design was used. Adults with ≥2 claims associated with a BCC diagnosis (ICD-9-CM 173.x1) separated by ≥30 days on or after October 1, 2011, were classified as aBCC or non-aBCC by using an algorithm based on metastasis diagnosis, radiation therapy use, and medical oncologist/other specialist use. Non-aBCC and aBCC patients were matched 1:1 on the basis of age, sex, and region, and assigned the same index date (date of first qualifying diagnosis or event). Comparisons were made using Wilcoxon signed-rank (continuous variables) and McNemar's (categorical variables) tests. RESULTS: In total, 847 matched aBCC/non-aBCC patient pairs were selected (mean age 75 years; 57% men; locally advanced BCC, n = 826; metastatic BCC, n = 21). During the 12-month study period following the index date, aBCC patients had a significantly higher mean Charlson Comorbidity Index (P = .0023), significantly higher mean numbers of outpatient/dermatologist/medical oncologist visits (all P < .0001), and significantly higher mean total/medical/inpatient/outpatient/BCC treatment costs (all P < .05). LIMITATIONS: This study only included information from a database on commercial insurance and Medicare claims. The algorithm criteria might have restricted patient numbers; data were not fully reflective of targeted therapy era. CONCLUSIONS: aBCC patients had a higher disease burden than non-aBCC patients. Cost differences were largely driven by higher BCC treatment costs, specifically radiation therapy.

Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison.

This study compared the clinical efficacy and safety of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in children and adolescents 6-17 years of age. A systematic literature review was conducted to identify randomized controlled trials (RCTs) of pharmacologic monotherapies among children and adolescents with ADHD. A Bayesian network meta-analysis was conducted to compare change in symptoms using the ADHD Rating Scale Version IV (ADHD-RS-IV), Clinical Global Impression-Improvement (CGI-I) response, all-cause discontinuation, and adverse event-related discontinuation. Thirty-six RCTs were included in the analysis. The mean (95% credible interval [CrI]) ADHD-RS-IV total score change from baseline (active minus placebo) was -14.98 (-17.14, -12.80) for lisdexamfetamine dimesylate (LDX), -9.33 (-11.63, -7.04) for methylphenidate (MPH) extended release, -8.68 (-10.63, -6.72) for guanfacine extended release (GXR), and -6.88 (-8.22, -5.49) for atomoxetine (ATX); data were unavailable for MPH immediate release. The relative risk (95% CrI) for CGI-I response (active versus placebo) was 2.56 (2.21, 2.91) for LDX, 2.13 (1.70, 2.54) for MPH extended release, 1.94 (1.59, 2.29) for GXR, 1.77 (1.31, 2.26) for ATX, and 1.62 (1.05, 2.17) for MPH immediate release. Among non-stimulant pharmacotherapies, GXR was more effective than ATX when comparing ADHD-RS-IV total score change (with a posterior probability of 93.91%) and CGI-I response (posterior probability 76.13%). This study found that LDX had greater efficacy than GXR, ATX, and MPH in the treatment of children and adolescents with ADHD. GXR had a high posterior probability of being more efficacious than ATX, although their CrIs overlapped.

Developing a Risk Score to Guide Individualized Treatment Selection in Attention Deficit/Hyperactivity Disorder.

OBJECTIVE: To develop a risk score for treatment failure that could potentially be used to individualize treatment selection between lisdexamfetamine dimesylate (LDX) and osmotic-release oral system methylphenidate (OROS-MPH) in children and adolescents with attention deficit/hyperactivity disorder (ADHD). METHODS: The study used data from patients with ADHD receiving LDX (N = 104) or OROS-MPH (N = 107) in a phase III randomized clinical trial. A prediction model was developed to estimate risk scores for failing OROS-MPH, where treatment failure was defined as less than 25% improvement in the ADHD Rating Scale IV total score from baseline. Patients were ranked by their predicted risks of OROS-MPH failure to define high-risk subpopulations. Outcomes of LDX and OROS-MPH were compared within subpopulations. RESULTS: The prediction model for OROS-MPH failure selected seven predictors (age, disease duration, and five ADHD Rating Scale IV item scores) and had an in-sample C statistic of 0.860. Among all patients, LDX had a 17% (95% confidence interval 7.1%-27.8%) lower treatment failure rate than that of OROS-MPH; differences in failure rates ranged from 17% to 43% across subpopulations, increasingly enriched for high-risk patients. Similar heterogeneity across subgroups was observed for other efficacy measures. CONCLUSIONS: In the overall trial population, LDX was associated with a lower rate of treatment failure compared with OROS-MPH in patients with ADHD. A more pronounced benefit of LDX over OROS-MPH was observed among subpopulations with a higher predicted risk of failing OROS-MPH. The present study showed the feasibility of individualizing treatment selection. Future research is needed to prospectively verify these results.

Real-World Treatment Patterns and Outcomes Following First-Line Pertuzumab and Trastuzumab Among Patients with HER2+ Metastatic Breast Cancer.

INTRODUCTION: Many patients with human epidermal growth factor receptor-2-positive metastatic breast cancer (HER2+ mBC) require subsequent lines of therapy (LOTs) after being treated with pertuzumab and trastuzumab-based regimens in the first line (1L). Although the efficacy of the second-line (2L) therapies has been demonstrated in clinical trials, the real-world effectiveness of these treatments is understudied. This retrospective cohort study assessed the real-world treatment patterns and outcomes for patients with HER2+ mBC following 1L therapy with pertuzumab and trastuzumab-based regimens in the United States (US) during 2015-2019. METHODS: Adults with HER2+ mBC in the US who initiated 1L pertuzumab and trastuzumab-based regimens between 01/01/2015 and 09/30/2019 and had ≥ 60 days of follow-up after 1L initiation were identified from the IQVIA Oncology Electronic Medical Records database. The regimens utilized in 2L following 1L pertuzumab and trastuzumab-based regimens were described. Median treatment duration and time to treatment failure were reported for 2L based on Kaplan-Meier analyses. RESULTS: Of the 710 eligible patients who received pertuzumab and trastuzumab-based regimens in 1L (median age: 57.0 years [interquartile range: 48.0-65.0]; median follow-up: 20.3 months; median 1L duration: 15.3 months), 222 (31.3%) initiated 2L. The most common regimens in 2L were ado-trastuzumab emtansine (T-DM1)-based regimens (n = 159 [71.6%]), followed by lapatinib-based (n = 21 [9.5%]) and neratinib-based (n = 18 [8.1%]) regimens. The median treatment duration and time to treatment failure were 5.9 (95% CI: 5.0, 8.7) and 8.6 (7.3, 11.5) months, respectively, among patients initiating 2L, and 5.7 (4.7, 7.8) and 7.9 (6.5, 10.0) months among those receiving 2L T-DM1. CONCLUSIONS: Most patients with HER2+ mBC requiring additional treatments after 1L pertuzumab and trastuzumab-based regimens utilized T-DM1 in 2L during 2015-2019. The short median treatment duration and time to treatment failure highlight an unmet need that can potentially be fulfilled by recently approved treatment options.

Clinical Outcomes, Resource Utilization, and Treatment Over the Disease Course of Symptomatic Obstructive Hypertrophic Cardiomyopathy in the United States.

We sought to describe the clinical outcomes, resource utilization, and treatment options for patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) over the course of their disease. Adults with obstructive HCM who were symptomatic were identified from the IBM MarketScan Commercial and Medicare supplemental database (January 2009 to March 2019). The index date was the initial obstructive HCM diagnosis date. Patients were required to have ≥12-month continuous eligibility before and after the index date. Incidence rates (IRs) and cumulative risk of cardiovascular events, healthcare resource utilization, and pharmacotherapy were assessed after index and compared with matched controls. Among 4,617 eligible patients with obstructive HCM, 2,917 (63.2%, mean age 60, 47.2% women) were symptomatic at index date. The most common cardiovascular events were atrial fibrillation/flutter (IR:1.421 per person-year [PPY], heart failure (IR: 0.895 PPY), and dyspnea (IR:0.797 PPY). Patients incurred higher resource use with frequent tests and monitoring, hospitalizations (0.454 PPY), and emergency room visits (0.611 PPY). The use of pharmacotherapy increased from 61.2% in the 6-month preindex period to 83.9% in the 6-month postindex period and remained stable after diagnosis. These events ranged from 3 to over 60-fold higher compared with controls, with the largest difference observed in arrhythmic events. The majority of patients were symptomatic at the time of obstructive HCM diagnosis, resulting in significantly increased cardiovascular complications and frequent disease monitoring after diagnosis versus controls. In conclusion, healthcare resource utilization was substantial, and these findings suggest a higher clinical and economic burden over the disease course among patients with symptomatic obstructive HCM, despite current treatment.

Treatment Patterns and Adverse Event-Related Hospitalization Among Patients with Epidermal Growth Factor Receptor (EGFR)-Mutated Metastatic Non-small Cell Lung Cancer After Treatment with EGFR Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy Regimens.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR TKIs) are established first-line treatments among patients with metastatic non-small cell lung cancer harboring EGFR-sensitizing mutations. Upon EGFR TKI resistance, there are scant data supporting a standard of care in subsequent lines of therapy. OBJECTIVE: We aimed to characterize real-world treatment patterns and adverse events associated with hospitalization in later lines of therapy. METHODS: This retrospective analysis of administrative claims included adults with metastatic non-small cell lung cancer who initiated a next line of therapy (index line of therapy) following EGFR TKI and platinum-based chemotherapy discontinuation on/after 1 November, 2015. Treatment regimens and adverse event rates during the index line of therapy were described. RESULTS: Among 195 eligible patients (median age: 59 years; female: 60%), the five most common index line of therapy regimens were immune checkpoint inhibitor monotherapy (29%), EGFR TKI monotherapy (21%), platinum-based chemotherapy (19%), non-platinum-chemotherapy (13%), and EGFR TKI combinations (9%). The overall median (95% confidence interval) time to discontinuation of the index line of therapy was 2.8 (2.1-3.2) months. Common adverse events associated with hospitalizations included infection/sepsis, pneumonia/pneumonitis, and anemia (2.9, 2.8, and 2.0 per 100 person-months, respectively). CONCLUSIONS: Among EGFR TKI-resistant patients who discontinued platinum-based chemotherapy, the duration of the next line of therapy was short, treatment was highly variable, and re-treatment with EGFR TKIs and platinum-based regimens was common, suggesting a lack of standard of care in later lines. Adverse event rates associated with hospitalization were high, especially among platinum-treated patients. These results underscore the unmet need for new therapies in a later line of treatment to reduce the clinical burden among patients in this population.

Frequency and clinicoeconomic impact of delays to definitive diagnosis of obstructive hypertrophic cardiomyopathy in the United States.

AIMS: The diagnostic history in the years leading up to the definitive diagnosis of patients with obstructive hypertrophic cardiomyopathy (HCM) has not been studied. METHODS: Patients with a delay in the definitive diagnosis of obstructive HCM from January 2009 to March 2019 were identified in the US IBM MarketScan Commercial and Medicare Supplemental Databases if they had an alternative diagnosis indicating a misdiagnosis during the 24 months before the definitive obstructive HCM diagnosis. Resource use and costs associated with the delay were estimated during the same period. RESULTS: Of 3,888 eligible patients with obstructive HCM, 59.5% had a delay in definitive diagnosis. Patients received a mean of 4.0 misdiagnoses before the definitive obstructive HCM diagnosis, most of which were other cardiovascular conditions. Consequently, 15.7% of patients may have received inappropriate treatment. Approximately 78.4% of patients visited a cardiologist (mean 4.7 visits) before the definitive obstructive HCM diagnosis. Additionally, 26.8% and 32.1% of patients had an inpatient and emergency room visit, respectively. Annualized healthcare costs associated with the delay were $4,379 per patient. LIMITATIONS: The current study used administrative claims data for a commercially insured population. Therefore, the results may not be generalizable to other populations (e.g. those insured by Medicare or Medicaid and the uninsured). Like other database studies, the current study may have suffered from miscoding or undercoding, which may have caused misclassification of patients. Owing to insufficient data, the study could not evaluate all potential consequences of a delay in definitive diagnosis. CONCLUSIONS: Most patients with obstructive HCM had a delay of ≤ 2 years before receiving the definitive diagnosis. The diagnostic journey involved multiple potential misdiagnoses, predominantly cardiovascular, as well as a substantial clinical and economic burden on patients and the healthcare system.

Event-Free Survival as a Surrogate for Overall Survival in Gastric and Gastroesophageal Junction Adenocarcinoma: A Meta-analysis in the Neoadjuvant ± Adjuvant Setting.

PURPOSE: This study assessed the trial-level association between event-free survival (EFS) and overall survival (OS) in gastric or gastroesophageal junction (GEJ) adenocarcinoma in the neoadjuvant ± adjuvant settings. EXPERIMENTAL DESIGN: A systematic literature review was conducted to identify randomized controlled trials (RCT) that evaluated neoadjuvant therapies with or without adjuvant therapies for gastric or GEJ adenocarcinoma. A meta-analysis was performed using weighted linear regressions of the treatment effect of OS on the treatment effect of EFS. The coefficient of determination (R²) and associated 95% confidence interval (CI) were used to evaluate the association between treatment effects of EFS and OS. The threshold used for defining good trial-level surrogacy was a correlation coefficient (R) of 0.8 or R² of 0.65, based on prior literature. Sensitivity analyses were performed to assess the robustness of the association with divergent study designs, including study population, inclusion of adjuvant therapy, and definitions of EFS and OS. RESULTS: The main analysis included 16 comparisons from 15 RCTs. The log(HR) of EFS was a significant predictor of log(HR) of OS, with an estimated coefficient of 0.72 (P < 0.001) and R² = 0.75 (95% CI, 0.49-0.95), indicating that EFS was a good surrogate outcome for OS. The results of the sensitivity analyses were consistent with the primary results, with R² ranging from 0.76 to 0.89. CONCLUSIONS: This study suggests that EFS is a good surrogate for OS in gastric or GEJ adenocarcinoma in the neoadjuvant ± adjuvant setting.

Matching-adjusted indirect comparisons: a new tool for timely comparative effectiveness research.

OBJECTIVE: In the absence of head-to-head randomized trials, indirect comparisons of treatments across separate trials can be performed. However, these analyses may be biased by cross-trial differences in patient populations, sensitivity to modeling assumptions, and differences in the definitions of outcome measures. The objective of this study was to demonstrate how incorporating individual patient data (IPD) from trials of one treatment into indirect comparisons can address several limitations that arise in analyses based only on aggregate data. METHODS: Matching-adjusted indirect comparisons (MAICs) use IPD from trials of one treatment to match baseline summary statistics reported from trials of another treatment. After matching, by using an approach similar to propensity score weighting, treatment outcomes are compared across balanced trial populations. This method is illustrated by reviewing published MAICs in different therapeutic areas. A novel analysis in attention deficit/hyperactivity disorder further demonstrates the applicability of the method. The strengths and limitations of MAICs are discussed in comparison to those of indirect comparisons that use only published aggregate data. RESULTS: Example applications were selected to illustrate how indirect comparisons based only on aggregate data can be limited by cross-trial differences in patient populations, differences in the definitions of outcome measures, and sensitivity to modeling assumptions. The use of IPD and MAIC is shown to address these limitations in the selected examples by reducing or removing the observed cross-trial differences. An important assumption of MAIC, as in any comparison of nonrandomized treatment groups, is that there are no unobserved cross-trial differences that could confound the comparison of outcomes. CONCLUSIONS: Indirect treatment comparisons can be limited by cross-trial differences. By combining IPD with published aggregate data, MAIC can reduce observed cross-trial differences and provide decision makers with timely comparative evidence.

The effects of adalimumab treatment and psoriasis severity on self-reported work productivity and activity impairment for patients with moderate to severe psoriasis.

BACKGROUND: Psoriasis significantly impairs work productivity and daily activities. OBJECTIVES: We sought to examine the effects of adalimumab on psoriasis-related work productivity and activity impairment and associations between the impairment and psoriasis severity in patients with moderate to severe psoriasis. METHODS: Data were from the first 16 weeks of the Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis TriAL (REVEAL). Outcomes as measured by the Work Productivity and Activity Impairment Questionnaire for Psoriasis (WPAI-Psoriasis) included employment status, total work productivity impairment, and total activity impairment. Logistic regression and analyses of covariance were used to assess the effects of adalimumab and treatment response (≥ 75% improvement in Psoriasis Area and Severity Index responders) on WPAI-Psoriasis outcomes. Longitudinal generalized estimating equations and Pearson correlation coefficients were used to assess associations between WPAI outcomes and psoriasis severity. RESULTS: Greater improvements in total work productivity impairment and total activity impairment were observed with adalimumab treatment versus placebo (15.5 and 11.1 percentage points, respectively; P < .001). Unemployment rate, total work productivity impairment, and total activity impairment were significantly associated with greater baseline psoriasis severity. Changes in WPAI outcomes were significantly correlated with greater psoriasis severity. The Dermatology Life Quality Index had stronger associations with changes in WPAI outcomes compared with clinical severity measures (Psoriasis Area and Severity Index and Physician Global Assessment). LIMITATIONS: REVEAL only included WPAI data for 16 weeks. Therefore, long-term impact of adalimumab treatment on productivity outcomes could not be assessed. In addition, information on occupational job title or industry was not collected and data were not adjusted for psoriatic arthritis. CONCLUSIONS: Adalimumab reduced psoriasis-related work productivity and activity impairment in patients with moderate to severe psoriasis.

Comparative effectiveness research using matching-adjusted indirect comparison: an application to treatment with guanfacine extended release or atomoxetine in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder.

OBJECTIVES: To illustrate a matching-adjusted indirect comparison by comparing the efficacy of guanfacine extended release (GXR) and atomoxetine (ATX) in reducing oppositional symptoms in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder. METHODS: Individual patient data were used from a GXR trial; only published summary data were used from ATX trials. In a matching-adjusted indirect comparison, individual patients from the GXR trial were weighted such that their mean baseline characteristics matched those published for ATX trials. Placebo-arm outcomes were then compared to further assess balance between the matched populations. Changes in the Conners' Parent Rating Scale-Revised Short Form Oppositional Subscale from baseline to endpoint among GXR-treated and ATX-treated patients were then compared. RESULTS: Before matching, the GXR (n = 143) and ATX (n = 98) trial populations had significant differences in baseline characteristics and placebo-arm outcomes. After matching, baseline characteristics were well balanced across trials, and placebo-arm outcomes became nearly identical. Comparing active treatment arms across the matched populations, GXR was associated with a significantly greater reduction in mean Conners' Parent Rating Scale-Revised Short form oppositional subscale compared with ATX {-5.0 [95% confidence interval (CI): -6.6 to -3.4] vs. -2.4 [CI: -3.7 to -1.1], p = 0.01, effect size = 0.58}. CONCLUSIONS: In the absence of head-to-head randomized trials, matching-adjusted indirect comparisons can provide timely and reliable comparative evidence for decision makers and can be applied even when very few trials are available for the treatments of interest.

The challenges and opportunities in using real-world data to drive advances in healthcare in East Asia: expert panel recommendations.

OBJECTIVE: To provide recommendations for overcoming the challenges associated with the generation and use of real-world evidence (RWE) in regulatory approvals, health technology assessments (HTAs), and reimbursement decision-making in East Asia. METHODS: A panel of experts convened at the International Society for Pharmacoeconomics and Outcomes Research Asia Pacific 2020 congress to discuss the challenges limiting the use of RWE in healthcare decision-making and to provide insights into the perspectives of regulators, HTA agencies, the pharmaceutical industry, and physicians in China, Japan, and Taiwan. A nonsystematic literature review was conducted to expand on the themes addressed. RESULTS: The use of RWE in regulatory approvals, HTAs, and reimbursement decision-making remains limited by legal/regulatory, technical, and attitudinal challenges in East Asia. CONCLUSIONS: We recommend approaches and initiatives that aim to drive improvements in the utilization of RWE in healthcare decision-making in East Asia and other regions. We encourage large-scale collaborations that leverage the full range of skills offered by different stakeholders. Government agencies, hospitals, research organizations, patient groups, and the pharmaceutical industry must collaborate to ensure appropriate access to robust and reliable real-world data and seek alignment on how to address prioritized evidence needs. Increasingly, we believe that this work will be conducted by multidisciplinary teams with expertise in healthcare research and delivery, data science, and information technology. We hope this work will encourage further discussion among all stakeholders seeking to shape the RWE landscape in East Asia and other regions and drive next-generation healthcare.

Prevalence, severity, and associated factors in women in East Asia with moderate-to-severe vasomotor symptoms associated with menopause.

OBJECTIVE: To understand prevalence, severity, impact, and treatment of vasomotor symptoms associated with menopause, using cross-sectional survey data. METHODS: This online, two-part survey was conducted in East Asia among women 40-65 years recruited from established online panels (Edelman, Beijing; Hankook Research, Seoul; Rakuten Insight, Taipei) using stratified sampling. Part I collected demographics/disease characteristics, including menopausal status and vasomotor symptom severity. Women with moderate-to-severe vasomotor symptoms completed Part II, including clinical characteristics, health-related quality of life, and healthcare-seeking behavior. Primary endpoints included vasomotor symptom prevalence and severity and proportions of women eligible and willing to take hormone therapy. Results are presented for each of the three online panels separately and as a pooled total. All analyses are descriptive with no formal hypothesis testing across groups. RESULTS: Numbers of peri- versus postmenopausal women completing Part I were Edelman, 1,588 (55.1% vs 44.9%); Hankook Research, 1,000 (43.6% vs 56.4%); Rakuten Insight, 773 (61.7% vs 38.3%). Vasomotor symptom prevalence was =80% in each region; overall moderate-to-severe vasomotor symptom prevalence was 55%; >50% of women were untreated. Most of those treated used non-prescription treatments. Menopausal hormone therapy use was reported by 11.6% of peri- and 7.2% of postmenopausal women. In peri- and postmenopausal women with moderate-to-severe vasomotor symptoms, 8.6% and 3.4%, respectively, were hormone therapy-willing, 19.3% and 16.8% hormone therapy-contraindicated, 25.4% and 23.0% hormone therapy-cautious, and 10.2% and 8.3% hormone therapy-averse. Women experienced significant burden on health-related quality of life and substantial impairment of work productivity and daily activities. CONCLUSIONS: Vasomotor symptoms associated with menopause affected =80% of women aged 40 to 65 years. A substantial proportion of women are unsuitable for, or choose not to take, menopausal hormone therapy, resulting in an unmet need for nonhormonal treatment options.

Real-World Data for Healthcare Research in China: Call for Actions.

OBJECTIVES: This study aimed to provide an overview of major data sources in China that can be potentially used for epidemiology, health economics, and outcomes research; compare them with similar data sources in other countries; and discuss future directions of healthcare data development in China. METHODS: The study was conducted in 2 phases. First, various data sources were identified through a targeted literature review and recommendations by experts. Second, an in-depth assessment was conducted to evaluate the strengths and limitations of administrative claims and electronic health record data, which were further compared with similar data sources in developed countries. RESULTS: Secondary databases, including administrative claims and electronic health records, are the major types of real-world data in China. There are substantial variations in available data elements even within the same type of databases. Compared with similar databases in developed countries, the secondary databases in China have some general limitations such as variations in data quality, unclear data usage mechanism, and lack of longitudinal follow-up data. In contrast, the large sample size and the potential to collect additional data based on research needs present opportunities to further improve real-world data in China. CONCLUSIONS: Although healthcare data have expanded substantially in China, high-quality real-world evidence that can be used to facilitate decision making remains limited in China. To support the generation of real-world evidence, 2 fundamental issues in existing databases need to be addressed-data access/sharing and data quality.

Conceptual Framework and Methodological Challenges for Modeling Effectiveness in Oncology Treatment Sequence Models.

In this review, we summarize the challenges faced by existing oncology treatment sequence decision models and introduce a general framework to conceptualize such models. In the proposed framework, patients with cancer receive at least two lines of therapy (LOTs) followed by palliative care throughout their lifetime. Patients cycle through progression-free and progressive disease health states in each LOT before death. Under this framework, four broad aspects of modeling effectiveness of treatment sequences need exploration. First, disease progression, treatment discontinuation, and the relationship between the two events should be considered. Second, the effectiveness of each LOT depends on its placement in a treatment sequence as the effectiveness of later LOTs may be influenced by the earlier LOTs. Third, the treatment-free interval (TFI; time between discontinuation of earlier LOT and initiation of later LOT) may impact a therapy's effectiveness. Fourth, in the absence of head-to-head trials directly comparing LOTs, indirect treatment comparison (ITC) of outcomes for a specific LOT or even for the entire treatment sequence is important to consider. A search of decision models that estimated effectiveness of at least two lines of oncology therapy was conducted in PubMed (N = 20) and technology appraisals by the National Institute for Health and Care Excellence (N = 26) to assess four methodological aspects related to the model framework: (1) selection of outcomes for effectiveness in a treatment sequence, (2) approaches to adjust the efficacy of a treatment in consideration of its place in the sequence, (3) approaches to address TFIs between LOTs, and (4) incorporation of ITCs to estimate comparators' effectiveness in the absence of direct head-to-head evidence. Most models defined health states based on disease progression on different LOTs while estimating treatment duration outside of the main model framework (30/46) and used data from multiple data sources in different LOTs to model efficacy of a treatment sequence (41/46). No models adjusted efficacy for the characteristics of patients who switched from an earlier LOT to a later LOT or adjusted for the impact of prior therapies, and just six models considered TFIs. While 11 models applied ITC results to estimate efficacy in comparator treatment sequences, the majority limited the ITC to one LOT in the sequence. Thus, there is substantial room to improve the estimation of effectiveness for treatment sequences using existing data when comparing effectiveness of alternative treatment sequences.

Assessing health-related quality-of-life in patients with symptomatic obstructive hypertrophic cardiomyopathy: EQ-5D-based utilities in the EXPLORER-HCM trial.

AIMS: To assess the effects of mavacamten on health-related quality-of-life (HRQoL) in symptomatic obstructive hypertrophic cardiomyopathy (HCM) and estimate health utilities by New York Heart Association (NYHA) functional class. MATERIALS AND METHODS: Patients with symptomatic obstructive HCM were randomized to 30 weeks of mavacamten or to placebo treatment, with or without beta-blocker or calcium channel blocker monotherapy, in EXPLORER-HCM (ClinicalTrials.gov identifier: NCT03470545). Health utility was measured using the EuroQoL 5-dimension 5-level (EQ-5D-5L) index score with the US value set. The 30-week changes in EQ-5D-5L index score and EuroQoL visual analog scale (EQ-VAS) score were compared between the two arms using linear regression, and the proportions of patients with a meaningful improvement were compared using logistic regression. The meaningful change thresholds were estimated using both distribution- and anchor-based approaches. Mean utilities by NYHA class were estimated for each arm using a generalized estimating equation. RESULTS: Compared with placebo (N = 89), patients receiving mavacamten (N = 96) had significantly greater 30-week improvement in EQ-5D-5L index score (mavacamten = 0.084; placebo = 0.009; adjusted difference = 0.073 [95% confidence interval = 0.027-0.118]) and EQ-VAS score (mavacamten = 8.5; placebo = 0.7; adjusted difference = 7.5 [95% confidence interval = 1.8-13.2]), and a significantly higher proportion of these patients showed meaningful improvement in EQ-5D-5L index score and EQ-VAS score. Both outcomes were correlated with the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS) and HCM Symptom Questionnaire Shortness-of-Breath (HCMSQ SoB) subscore, two patient-reported anchor variables. Additionally, mean utilities significantly decreased with higher NYHA functional class (values for NYHA class I, II, and III/IV - mavacamten = 0.950, 0.866, and 0.708; placebo = 0.952, 0.850, and 0.704). CONCLUSIONS: Compared with placebo, mavacamten significantly improved EQ-5D-5L index score and EQ-VAS score - and thus HRQoL - among patients with symptomatic obstructive HCM. Patients with a higher NYHA functional class had a lower health utility value.