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Background: Most cancer drugs enter the US market first. US Food and Drug Administration (FDA) approvals of new cancer drugs may influence regulatory decisions in other settings. The study examined whether characteristics of available evidence at FDA approval influenced time-to-marketing authorisation (MA) in Brazil, and price differences between the two countries. Methods: All new FDA-approved cancer drugs from 2010 to 2019 were matched to drugs with MA and prices approved in Brazil by December 2020. Characteristics of main studies, availability of randomised controlled trials (RCTs), overall survival (OS) benefit, added therapeutic benefit, and prices were compared. Findings: Fifty-six FDA-approved cancer drugs with matching indications received a MA at the Brazilian Health Regulatory Agency (Anvisa) after a median of 522 days following US approval (IQR: 351–932). Earlier authorisation in Brazil was associated with availability of RCT (median: 506 vs 760 days, p = 0.031) and evidence of OS benefit (390 vs 543 days, p = 0.019) at FDA approval. At Brazilian marketing authorisation, a greater proportion of cancer drugs had main RCTs (75% vs 60.7%) and OS benefit (42.9% vs 21.4%) than that in the US. Twenty-eight (50%) drugs did not demonstrate added therapeutic benefit over drugs for the same indication in Brazil. Median approved prices of new cancer drugs were 12.9% lower in Brazil compared to the US (adjusted by Purchasing Power Parity). However, for drugs with added therapeutic benefit median prices were 5.9% higher in Brazil compared to the US, while 17.9% lower for those without added benefit. Interpretation: High-quality clinical evidence accelerated the availability of cancer medicines in Brazil. The combination of marketing and pricing authorisation in Brazil may favour the approval of cancer drugs with better supporting evidence, and more meaningful clinical benefit albeit with variable degree of success in achieving lower prices compared to the US. Funding: None.

Importance: Of approximately 9 million patients with cancer in China in 2020, more than half were diagnosed with late-stage cancers. Recent regulatory reforms in China have focused on improving the availability of new cancer drugs. However, evidence on the clinical benefits of new cancer therapies authorized in China is not available. Objective: To characterize the clinical benefits of cancer drugs approved in China, as defined by the availability and magnitude of statistically significant overall survival (OS) results. Design, Setting, and Participants: This mixed-methods study comprising a systematic review and cross-sectional analysis identified antineoplastic agents approved in China between January 1, 2005, and December 31, 2020, using publicly available data and regulatory review documents issued by the National Medical Products Administration. The literature published up to June 30, 2021, was reviewed to collect results on end points used in pivotal trials supporting cancer drug approvals. Main Outcomes and Measures: The primary outcome measure was a documented statistically significant positive OS difference between a new cancer therapy and a comparator treatment. Secondary outcome measures were the magnitude of OS benefit and other primary efficacy measures in pivotal trials. Results: Between 2005 and 2020, 78 cancer drugs corresponding to 141 indications were authorized in China, including 20 drugs (25.6%) (for 30 indications) approved in China only. Of all indications, 26 (18.4%) were evaluated in single-arm or dose-optimization trials, most of which were authorized after 2017. By June 30, 2021, 34 drug indications (24.1%) had a documented lack of OS gain. For 68 indications (48.2%) that had documented evidence of OS benefit, the median magnitude of OS improvement was 4.1 (range, 1.0-35.0) months. After a median follow-up of 1.9 (range, 1.0-11.1) years from approval, OS data for 13 indications (9.2%) were either not reported or were still not mature. Fewer than one-third of cancer drug indications approved in China only had documented evidence of OS benefits (9 of 30 [30.0%]), whereas more than one-half of the cancer drug indications also available in the US or Europe had OS benefits (59 of 111 [53.1%]). Conclusions and Relevance: In this study, almost half of cancer drug indications approved in China had demonstrated OS gain. With the increase of cancer drug approvals based on single-arm trials or immature survival data in recent years, these findings highlight the need to routinely monitor the clinical benefits of new cancer therapies in China

Background Childhood cancer outcomes in low-income and middle-income countries have not kept pace with advances in care and survival in high-income countries. A contributing factor to this survival gap is unreliable access to essential drugs. Methods The authors created a tool (FORx ECAST) capable of predicting drug quantity and cost for 18 pediatric cancers. FORx ECAST enables users to estimate the quantity and cost of each drug based on local incidence, stage breakdown, treatment regimen, and price. Two country-specific examples are used to illustrate the capabilities of FORx ECAST to predict drug quantities. Results On the basis of domestic public-sector price data, the projected annual cost of drugs to treat childhood cancer cases is 0.8 million US dollars in Kenya and 3.0 million US dollars in China, with average median price ratios of 0.9 and 0.1, respectively, compared with costs sourced from the Management Sciences for Health (MSH) International Medical Products Price Guide. According to the cumulative chemotherapy cost, the most expensive disease to treat is acute lymphoblastic lymphoma in Kenya, but a higher relative unit cost of methotrexate makes osteosarcoma the most expensive diagnosis to treat in China. Conclusions FORx ECAST enables needs-based estimates of childhood cancer drug volumes to inform health system planning in a wide range of contexts. It is broadly adaptable, allowing decision makers to generate results specific to their needs. The resultant estimates of drug need can help equip policymakers and health governance institutions with evidence-informed data to advance innovative procurement strategies that drive global improvements in childhood cancer drug access.

Rapid growth in pharmaceutical expenditures and high prices have greatly hampered access to medicines, especially targeted anticancer medicines. Confronted with such difficulties, the Chinese government has put more effort into supporting local research and development of cancer medicines, resulting in locally developed me-too drugs. Since 2016, the government has implemented a central reimbursement-linked drug price negotiation policy aimed at reducing the prices of expensive medicines. Locally developed me-too drugs marketed at lower prices may inject price competition and help negotiate reduced prices of similar internationally-developed products. As an example, we selected 3 tyrosine kinase inhibitors (TKIs) developed for the therapy of advanced non-small cell lung cancer harboring mutations in the epidermal growth factor receptor (EGFR). Descriptive analysis was applied to data from the Chinese Medical Economic Information database to describe the impact on the price and utilization of three TKIs after the introduction of icotinib, a locally developed me-too TKI and two national negotiations regarding the price of EGFR-TKIs in China. After two national negotiations, the daily costs of all three EGFR-TKIs were reduced to around $30. From the first quarter of 2013 to the second quarter of 2016, the market share of the purchasing volume of icotinib, China's locally developed TKI, increased from 13% to 40%, while the market shares of two internationally developed TKIs decreased from 35% to 15% and from 52% to 45%, for erlotinib and gefitinib, respectively. The prices of EGFR-TKIs decreased and China's locally developed TKI accounted for a considerable proportion of market share. Locally developed me-too drugs aid price negotiation by injecting price competition and helping negotiate reduced prices of similar internationally-developed products. Through efforts to develop me-too drugs, combined with national drug price negotiation and reimbursement policies, developing countries might improve access to more affordable targeted cancer therapies.

Objective To evaluate the frequency with which relevant and accurate information about the benefits and related uncertainties of anticancer drugs are communicated to patients and clinicians in regulated information sources in Europe. Design Document content analysis. Setting European Medicines Agency. Participants Anticancer drugs granted a first marketing authorisation by the European Medicines Agency, 2017-19. Main outcome measures Whether written information on a product addressed patients’ commonly asked questions about: who and what the drug is used for; how the drug was studied; types of drug benefit expected; and the extent of weak, uncertain, or missing evidence for drug benefits. Information on drug benefits in written sources for clinicians (summaries of product characteristics), patients (patient information leaflets), and the public (public summaries) was compared with information reported in regulatory assessment documents (European public assessment reports). Results 29 anticancer drugs that received a first marketing authorisation for 32 separate cancer indications in 2017-19 were included. General information about the drug (including information on approved indications and how the drug works) was frequently reported across regulated information sources aimed at both clinicians and patients. Nearly all summaries of product characteristics communicated full information to clinicians about the number and design of the main studies, the control arm (if any), study sample size, and primary measures of drug benefit. None of the patient information leaflets communicated information to patients about how drugs were studied. 31 (97%) summaries of product characteristics and 25 (78%) public summaries contained information about drug benefits that was accurate and consistent with information in regulatory assessment documents. The presence or absence of evidence that a drug extended survival was reported in 23 (72%) summaries of product characteristics and four (13%) public summaries. None of the patient information leaflets communicated information about the drug benefits that patients might expect based on study findings. Scientific concerns about the reliability of evidence on drug benefits, which were raised by European regulatory assessors for almost all drugs in the study sample, were rarely communicated to clinicians, patients, or the public. Conclusions The findings of this study highlight the need to improve the communication of the benefits and related uncertainties of anticancer drugs in regulated information sources in Europe to support evidence informed decision making by patients and their clinicians.

This study examines the Food and Drug Administration’s accelerated approval pathway and whether preapproval initiation was associated with faster conversion to traditional approval or withdrawal for drugs with nononcology indications.

Background To strengthen appropriate medicine use (AMU) including the prescribing and dispensing quality at public sector health facilities in Uganda, the Ministry of Health introduced a multipronged approach known as the Supervision, Performance Assessment, and Recognition Strategy (SPARS). This paper assesses the impact of the first year of SPARS implementation on key AMU indicators. Methods District-based health workers trained as supervisors provide in-service training in medicines management complemented by indicator-based performance assessment and targeted supervision during each SPARS facility visit. From 2010 to 2013, health facilities that started the SPARS intervention were assessed during the first and last visit during a period of 12 months of implementing SPARS. This study examines 12 AMU indicators with 57 individual outcomes covering prescribing and dispensing quality. We also explored factors influencing 1-year improvement. Results We found an overall increase in AMU indicators of 17 percentage points (p < 0.000) between the first and last visit during a period of 12 months of supervisions, which was significant in all levels of health care facilities and in both government and private not-for-profit faith-based sectors. Appropriate dispensing (25 percentage points, p < 0.005) improved more than appropriate prescribing (12 percentage points, p = 0.13). Specific facilities that reached an average score of over 75% across all AMU measures within the first year of supervision improved from 3 to 41% from the first visit (baseline). The greatest overall impact on AMU occurred in lower-level facilities; the level of improvement varied widely across indicators, with the greatest improvements seen for the lowest baseline measures. Supervision frequency had a significant impact on level of improvement in the first year, and private not-for-profit faith-based health facilities had notably higher increases in several dispensing and prescribing indicator scores than public sector facilities. Conclusions The multipronged SPARS approach was effective in building appropriate medicine use capacity, with statistically significant improvements in AMU overall and almost all prescribing and dispensing quality measures after 12 months of supervision. We recommend broad dissemination of the SPARS approach as an effective strategy to strengthen appropriate medicine use in low-income countries.

To assess sales of anti-cancer medicines in the 2017 World Health Organization'sWe extracted sales volume data for 39 anti-cancer medicines from the IQVIA database. We divided the total quantity sold by the reference defined daily dose to estimate the total number of defined daily doses sold, per country per year, for three types of anti-cancer therapies (traditional chemotherapy, targeted therapy and endocrine therapy). We adjusted these data by the number of new cancer cases in each country for each year.We observed an increase in sales across all types of anti-cancer therapies in all countries. The largest number of defined daily doses of traditional chemotherapy per new cancer case was sold in Thailand; however, the largest relative increase per new cancer case occurred in Indonesia (9.48-fold). The largest absolute and relative increases in sales of defined daily doses of targeted therapies per new cancer case occurred in Kazakhstan. Malaysia sold the largest number of adjusted defined daily doses of endocrine therapies in 2017, while China and Indonesia more than doubled their adjusted sales volumes between 2007 and 2017.The use of sales data can fill an important knowledge gap in the use of anti-cancer medicines, particularly during periods of insurance coverage expansion. Combined with other data, sales volume data can help to monitor efforts to improve equitable access to essential medicines.Évaluer la vente de médicaments contre le cancer figurant dans l'édition 2017 de laNous avons extrait de la base de données IQVIA les informations relatives au volume de vente pour 39 médicaments contre le cancer. Nous avons divisé le nombre total de médicaments vendus par la dose quotidienne déterminée de référence, afin d'estimer le nombre total de doses quotidiennes déterminées vendues par pays et par an, pour trois types de traitements contre le cancer (chimiothérapie conventionnelle, thérapie ciblée et endocrinothérapie). Nous avons ajusté ces données en tenant compte du nombre de nouveaux cas de cancer diagnostiqués chaque année dans chaque pays.Nous avons observé une hausse des ventes pour tous les types de traitements contre le cancer dans tous les pays. C'est la Thaïlande qui vend le plus grand nombre de doses quotidiennes déterminées en chimiothérapie conventionnelle pour chaque nouveau cas de cancer; néanmoins, c'est en Indonésie que nous avons constaté la plus grande augmentation relative pour chaque nouveau cas de cancer (nombre multiplié par 9,48). En termes d'augmentation absolue et relative des ventes de doses quotidiennes déterminées pour lathérapie ciblée, c'est au Kazakhstan qu'elle était la plus élevée. La Malaisie est le pays ayant vendu le plus grand nombre de doses quotidiennes déterminées pour l'endocrinothérapie, tandis que la Chine et l'Indonésie ont plus que doublé leur volume de vente ajusté entre 2007 et 2017.L'exploitation des données de vente peut combler un manque de connaissances dans l'utilisation de médicaments contre le cancer, surtout pendant les périodes d'élargissement de la couverture maladie. En les associant à d'autres informations, les données sur le volume de vente permettent de suivre les efforts fournis pour garantir un accès de plus en plus équitable aux médicaments essentiels.Evaluar las ventas de los medicamentos contra el cáncer que aparecen en laLos datos sobre el volumen de ventas de 39 medicamentos contra el cáncer se obtuvieron de la base de datos IQVIA. Se dividió la cantidad total que se vendió por la dosis diaria definida de referencia para estimar el número total de dosis diarias definidas que se vendieron, por país y por año, para tres tipos de tratamientos anticancerosos (quimioterapia tradicional, terapia dirigida y tratamiento endocrino). Se adaptaron estos datos por el número de nuevos casos de cáncer en cada país para cada año.Se observó un incremento en las ventas de todos los tipos de tratamientos anticancerosos en todos los países. El mayor número de dosis diarias definidas de quimioterapia tradicional por cada nuevo caso de cáncer se vendió en Tailandia; sin embargo, el mayor incremento relativo por cada nuevo caso de cáncer se registró en Indonesia (9,48 veces). Los mayores incrementos absolutos y relativos de las ventas de dosis diarias definidas de las terapias dirigidas por cada nuevo caso de cáncer se registraron en Kazajstán. Malasia vendió el mayor número de dosis diarias definidas adaptadas de los tratamientos endocrinos en 2017, mientras que China e Indonesia duplicaron con creces sus volúmenes de ventas ajustadas entre 2007 y 2017.El empleo de los datos de ventas puede llenar un importante vacío de conocimientos sobre el uso de los medicamentos contra el cáncer, en particular durante los periodos de la ampliación de la cobertura de los seguros. Los datos sobre el volumen de ventas, junto con otros datos, pueden ayudar a supervisar los esfuerzos por mejorar el acceso equitativo a los medicamentos esenciales.الغرض تقييم مبيعات أدوية مكافحة السرطان في القائمة النموذجية للأدوية الأساسية لمنظمة الصحة العالمية (WHO) لعام 2017 في كل من الصين وإندونيسيا وكازاخستان وماليزيا والفلبين وتايلند، من عام 2007 (2008 بالنسبة لكازاخستان وماليزيا) حتى عام 2017. الطريقة قمنا باستخلاص بيانات حجم المبيعات لعدد 39 دواءً مكافحاً للسرطان من قاعدة بيانات IQVIA. قمنا بتقسيم إجمالي الكمية المباعة بالجرعة اليومية المرجعية المحددة، وذلك لتقدير إجمالي عدد الجرعات اليومية المحددة المباعة، لكل بلد سنوياً، لثلاثة أنواع من العلاجات المكافحة للسرطان (العلاج الكيميائي التقليدي، والعلاج الموجه، والعلاج بالغدد الصماء). قمنا بتعديل هذه البيانات حسب عدد حالات السرطان الجديدة في كل دولة لكل عام. النتائج لاحظنا زيادة في مبيعات كل أنواع العلاجات المكافحة للسرطان في كل الدول. تم بيع أكبر عدد من الجرعات اليومية المحددة من العلاج الكيميائي التقليدي، لكل حالة سرطان جديدة، في تايلند؛ ومع ذلك، حدثت أكبر زيادة نسبية لكل حالة سرطان جديدة في إندونيسيا (9.48 ضعفاً). حدثت أكبر زيادات مطلقة ونسبية في مبيعات الجرعات اليومية المحددة من العلاجات المستهدفة لكل حالة سرطان جديدة، في كازاخستان. باعت ماليزيا أكبر عدد من الجرعات اليومية المعدلة من علاجات الغدد الصماء في عام 2017، بينما باعت الصين وإندونيسيا أكثر من ضعف حجم مبيعاتهما المعدلة بين عامي 2007 و2017. الاستنتاج إن استخدام بيانات المبيعات يمكنه أن يسد فجوة معرفية هامة في استخدام أدوية مكافحة السرطان، وخاصة خلال فترات تمديد التغطية التأمينية. يمكن لبيانات حجم المبيعات، إلى جانب بيانات أخرى، أن تساعد في مراقبة الجهود لتحسين الوصول العادل إلى الأدوية الأساسية.旨在评估世界卫生组织发布的我们从 IQVIA 数据库中选取了 39 种抗癌药物的销量数据。我们用销售总量除以此参考清单中的限定日剂量来估算每个国家三种抗癌疗法（传统化疗、靶向治疗和内分泌疗法）每年的限定日剂量总销量。我们根据每个国家每年新增癌症病例数调整了这些数据。.我们观察到所有国家各种类型的抗癌疗法的销售额都有所增长。泰国每例新增癌症患者购买传统化疗药物的限定日剂量最大；然而，印度尼西亚每例新增癌症患者的相对增幅最大（9.48 倍）。哈萨克斯坦的新增癌症患者中，靶向治疗的限定日剂量销售额呈现最大的绝对增幅和相对增幅。2017 年，马来西亚调整后的内分泌疗法限定日剂量销量最大，而中国和印度尼西亚的调整后销售量在 2007 年至 2017 年增加了一倍以上。.销售数据的使用可以填补抗癌药物使用方面的重要认知缺口，尤其是在扩大保险覆盖范围期间。结合其他数据，销量数据有助于监测改善患者平等获取基本药物方面的工作。.Оценить уровень продаж противораковых препаратов из изданного Всемирной организацией здравоохранения в 2017 годуАвторы получили данные о продажах 39 противораковых препаратов из базы данных IQVIA. Общее количество проданных единиц было разделено на эталонную условную суточную дозу для оценки общего количества условных суточных доз, проданных в конкретной стране за год. Рассматривались три типа противораковых препаратов: традиционная химиотерапия, таргетная и гормональная терапия. Данные затем были скорректированы по количеству новых случаев рака в каждой стране за каждый год.Наблюдался рост продаж по всем типам противораковых препаратов в каждой из стран. Максимальное количество условных суточных доз традиционной химиотерапии на новый случай рака было продано в Таиланде, однако максимальный относительный прирост по каждому новому случаю продемонстрировала Индонезия (рост в 9,48 раза). Максимальный абсолютный и относительный прирост продаж условных суточных доз препаратов для таргетной терапии на новый случай рака продемонстрировал Казахстан. Малайзия стала лидером по продажам скорректированных условных суточных доз препаратов для гормональной терапии в 2017 году, а в период с 2007 по 2017 год Индонезия и Китай увеличили скорректированные объемы продаж более чем вдвое.Использование данных продаж поможет восполнить значительный пробел в знаниях о применении противораковых препаратов, в частности в периоды расширения страхового покрытия. В сочетании с другими данными показатели объемов продаж помогут отслеживать усилия по обеспечению равного доступа населения к основным лекарственным средствам.

Over the past decades, anti-cancer treatments have evolved rapidly from cytotoxic chemotherapies to targeted therapies including oral targeted medications and injectable immunooncology and cell therapies. New anti-cancer medications come to markets at increasingly high prices, and health insurance coverage is crucial for patient access to these therapies. State laws are intended to facilitate insurance coverage of anti-cancer therapies.Using Massachusetts as a case study, we identified five current cancer coverage state laws and interviewed experts on their perceptions of the relevance of the laws and how well they meet the current needs of cancer care given rapid changes in therapies. Interviewees emphasized that cancer therapies, as compared to many other therapeutic areas, are unique because insurance legislation targets their coverage. They identified the oral chemotherapy parity law as contributing to increasing treatment costs in commercial insurance. For commercial insurers, coverage mandates combined with the realities of new cancer medications — including high prices and often limited evidence of efficacy at approval — compound a difficult situation. Respondents recommended policy approaches to address this challenging coverage environment, including the implementation of closed formularies, the use of cost-effectiveness studies to guide coverage decisions, and the application of value-based pricing concepts. Given the evolution of cancer therapeutics, it may be time to evaluate the benefits and challenges of cancer coverage mandates.

PURPOSE: Early palliative care, concomitant with disease-directed treatments, is recommended for all patients with advanced cancer. This study assesses population-level trends in palliative care use among a large cohort of commercially insured patients with metastatic cancer, applying an expanded definition of palliative care services based on claims data. METHODS: Using nationally representative commercial insurance claims data, we identified patients with metastatic breast, colorectal, lung, bronchus, trachea, ovarian, esophageal, pancreatic, and liver cancers and melanoma between 2001 and 2016. We assessed the annual proportions of these patients who received services specified as, or indicative of, palliative care. Using Cox proportional hazard models, we assessed whether the time from diagnosis of metastatic cancer to first encounter of palliative care differed by demographic characteristics, socioeconomic factors, or region. RESULTS: In 2016, 36% of patients with very poor prognosis cancers received a service specified as, or indicative of, palliative care versus 18% of those with poor prognosis cancers. Being diagnosed in more recent years (2009-2016 v 2001-2008: hazard ratio [HR], 1.8; P < .001); a diagnosis of metastatic esophagus, liver, lung, or pancreatic cancer, or melanoma ( v breast cancer, eg, esophagus HR, 1.89; P < .001); a greater number of comorbidities (American Hospital Formulary Service classes > 10 v 0: HR, 1.71; P < .001); and living in the Northeast (HR, 1.43; P < .001) or Midwest ( v South: HR, 1.39; P < .001) were the strongest predictors of shorter time from diagnosis to palliative care. CONCLUSION: Use of palliative care among commercially insured patients with advanced cancers has increased since 2001. However, even with an expanded definition of services specified as, or indicative of, palliative care, < 40% of patients with advanced cancers received palliative care in 2016.

Purpose This study aims to illustrate the prevalence and patterns of medication use among pregnant women in mainland China. Patients and methods Hospital and drugstore service data for a nationally representative sample of basic medical insurance (BMI) beneficiaries in 2015 were obtained from the China Health Insurance Association (CHIRA) database. A total of 7946 women who had singleton deliveries in 2015, aged between 12 and 54, and whose records in the CHIRA database covered at least one trimester were included in this study. We conducted descriptive analyses of sample characteristics, medication use prevalence, and number and types of medications used. Results We found that 11.7% of women used at least one medication during the course of pregnancy (median number of medications used = 6.7). Medication use was more common among those who were older, residing in Eastern China, or employed. Most commonly used medication groups by the Anatomical Therapeutic Chemical Classification System were B (Blood and blood forming organs, 49.3%), A (Alimentary tract and metabolism, 48.1%), G (Genito urinary system and sex hormones, 38.1%) and J (Antiinfectives for systemic use, 31.6%). Intravenous solutions, vitamins and minerals, progestogens, and beta-lactam antibacterials were the most frequently used medications from each of these four ATC groups, respectively. Moreover, 7.1% used at least one medication contraindicated in pregnancy. Conclusion This study showed that around one in 10 women used medication during pregnancy in mainland China and found possible cases of inappropriate or unsafe medication use.

Background: Evaluations of cancer etiology and safety and effectiveness of cancer treatments are predicated on large numbers of patients with sufficient baseline and follow-up data. To assess feasibility of FDA's Sentinel System's electronic healthcare data for surveillance of malignancy onset and examination of product safety, this study examined patterns of enrollment surrounding new-onset cancers. Methods: Using a retrospective cohort of patients based on administrative claims, we identified incident events of 19 cancers among 292.5 million health plan members from January 2000 to February 2020 using International Classification of Diseases (ICD) diagnosis codes. Annual incident cases were stratified by sex, age, medical and drug coverage, and insurer type. Descriptive statistics were calculated for observable time prior to and following diagnosis. Results: We identified 10,697,573 incident cancer events among members with medical coverage. When drug coverage was additionally required, number of incident cancers was reduced by 41%. Medicare data contributed 61% of cases, with similar duration trends as other insurers. Mean duration of follow-up prior to diagnosis ranged from 4.0 to 4.6 years, whereas follow-up post diagnosis ranged from 1.1 to 3.3 years. Approximately a third (36.1%) had at least 2 years both prior to and following diagnosis. Conclusions: The FDA Sentinel System's electronic healthcare data may be useful for characterizing relatively short latency cancer risk, examining cancer drug utilization and safety after diagnosis, and conducting surveillance for acute adverse events among patients with cancers. Impact: A national distributed system with electronic health data, the Sentinel system provides opportunity for rapid pharmacoepidemiologic assessments relevant in oncology.

Importance Launch prices of new cancer drugs in the US have substantially increased in recent years despite growing concerns about the quantity and quality of evidence supporting their approval by the US Food and Drug Administration (FDA). Objective To assess the use of and spending on new oral targeted cancer drugs among US residents with employer-sponsored insurance between 2011 and 2018, stratified by the strength of available evidence of benefit. Design, Setting, and Participants In this cross-sectional study, dispensing claims for oral targeted cancer drugs first approved by the FDA between January 1, 2011, and December 31, 2018, were analyzed. The number of patients with drugs dispensed and the total payment for all claims were aggregated by calendar year, and these outcomes were arrayed according to evidence underlying FDA approvals, including pivotal study design (availability of randomized clinical trials) and overall survival (OS) benefit, as documented in drug labels. This study was conducted from July 17, 2019, to July 23, 2021. Main Outcomes and Measures Annual and cumulative numbers of patients who had dispensing events, and annual and cumulative sums of payment for eligible drugs. Results Of 37 348 patients who had at least 1 of the 44 new oral targeted drugs dispensed between 2011 and 2018, 21 324 were men (57.1%); mean (SD) age was 64.1 (13.1) years. Most individuals (36 246 [97.0%]) received drugs for which evidence from randomized clinical trials existed; however, a growing share of patients received drugs without documented OS benefit during the study period: from 12.7% in 2011 to 58.8% in 2018. Cumulative spending on all sample drugs totaled $3.5 billion by the end of 2018, of which 96.8% was spent on drugs that were approved based on a pivotal randomized clinical trial. Cumulative spending on drugs without documented OS benefit ($1.8 billion [51.6%]) surpassed that on drugs with documented OS benefit ($1.7 billion [48.4%]) by the end of 2018. Conclusions and Relevance The findings of this cross-sectional study suggest that drugs used for treatment of cancer without documented OS benefits are adopted in the health system and account for substantial spending.

Different from less developed countries, 80% of children with cancers in the United States are cured. Traditional chemotherapy drugs are the mainstay of therapies; new targeted medications have become available recently. Using publicly available data, we created a database of cancer drugs with paediatric malignancy indications approved by 31 October 2020 in China and the United States. We compared numbers, type, indications and listing on the World Health Organization Model List of Essential Medicines for Children (WHO EMLc) between the two countries, assessed the correlation between paediatric indications and cancer incidences, and described evidence supporting approvals of targeted medications in the two settings. Our study showed that by 31 October 2020, 31 and 39 cancer drugs available in China and the United States were approved for use in children, corresponding to 137 and 102 paediatric cancer indications, respectively. About half of these drugs (17 in China and 18 in the United States) were listed on the WHO EMLc. The correlation between indications and burden of disease was higher in the United States (r = 0.68) than China (r = 0.59). More traditional chemotherapy drugs were approved in China (n = 27) than the United States (n = 19). Of 20 targeted childhood anticancer medicines approved in the United States, mainly on the basis of single arm trials (27/32 indications, 84.4%), only four were approved for paediatric indications in China, at a median of 2.8 years after US Food and Drug Administration approval. A harmonised, evidence-based regulatory framework is needed to ensure approvals of needed, safe and efficacious childhood cancer drugs across the world.

This cross-sectional study examines how information on overall survival benefits of novel cancer drug indications is communicated in labeling.

IntroductionNew targeted therapies have changed cancer treatment in the past decades. However, high prices of targeted anticancer medications have increased economic burden for both patients and health insurance systems. In July 2017, China implemented combined medication price negotiation and mandatory reimbursement policies for 15 targeted anticancer medications. This study assesses effects of the policy on hospital procurement prices, volumes and spending.MethodsUsing a quasi-experimental interrupted time series design, we analysed procurement data from the Chinese Medical Economic Information of 789 public hospitals in 30 provinces between January 2016 and September 2018. The intervention group consisted of 15 targeted anticancer medications with negotiated prices in 2017. The comparison group consisted of six targeted anticancer medications without negotiated prices by 2018. The effective date of the policy was September 2017.ResultsAfter the implementation of the 2017 medication price negotiation and reimbursement policy, cost per defined daily dose (DDD) of the 15 targeted anticancer medications dropped US$71.21 on average from an average US$169.24/DDD before (p=0.000). Compared with what would have happened without the intervention, cost/DDD of price-negotiated medications decreased by 48.9% (p=0.000), procurement volumes increased by 143.0% (p=0.000) and hospital medication spending decreased by 6.9% (p=0.146).ConclusionsThe 2017 medication price negotiation and reimbursement policy decreased targeted medication procurement costs per DDD, increased volumes procured and at least temporarily contained spending. These changes should result in better access to and affordability of targeted anticancer medications in China.

Background To evaluate the effectiveness of the Enhanced Primary Healthcare (EnPHC) interventions on process of care and intermediate clinical outcomes among type 2 diabetes patients. Research Design and Methods This was a quasi-experimental controlled study of multi-pronged interventions conducted in 20 intervention and 20 control public primary care clinics in Malaysia from November 2016 to June 2019. Malaysian patients aged 30 years and above with a diagnosis of type 2 diabetes were selected via systematic random sampling. We conducted difference-in-differences analyses of data on process of care and intermediate clinical outcomes extracted from medical records. Results We reviewed 12,017 medical records of patients with type 2 diabetes. Process of care measures improved: HbA1c tests performed within the past three months (odds ratio (OR) 3.31, 95% CI 2.13, 5.13); lipid test (OR 4.59, 95% CI 2.64, 7.97), LDL (OR 4.33, 95% CI 2.16, 8.70), and urine albumin (OR 1.99, 95% CI 1.12, 3.55) tests within the past year; BMI measured within the past six months (OR 15.80, 95% CI 4.78, 52.24); cardiovascular risk assessment (OR 174.65, 95% CI 16.84, 1810.80); and exercise counselling (OR 1.18, 95% CI 1.04, 1.33). We found no statistically significant changes in intermediate clinical outcomes. Conclusions EnPHC interventions were effective in improving process of care but not intermediate clinical outcomes for type 2 diabetes patients. The intervention package was successful in enhancing the quality of care in diabetes from the health provider perspective. Patient engagement and self-management support may be needed to bring forth changes in patient outcomes.

PURPOSE: There is limited evidence on the intensity of end-of-life (EOL) care for women < 65 years old, who account for about 40% of breast cancer deaths in the United States. Using established indicators, we estimated the intensity of EOL care among these women. METHODS: We used 2000-2014 claims data from a large US insurer to identify women with metastatic breast cancer who, in the last month of their lives, had more than one hospital admission, emergency department visit, or an intensive care unit (ICU) admission and/or used antineoplastic therapy in the last 14 days of life. Using multivariate logistic regression, we assessed whether intensity of EOL care differed by demographic characteristics, socioeconomic factors, or regions. RESULTS: Adjusted estimates show an increase in EOL ICU admissions between 2000-2003 and 2010-2014 from 14% (95% CI, 10% to 17%) to 23% (95% CI, 20% to 26%) and a small increase in emergency department visits from 10% (95% CI, 7% to 13%) to 12% (95% CI, 9% to 15%), both statistically significant. There was no statistically significant change in the proportions of women experiencing more than one EOL hospitalization (14% in 2010-2014; 95% CI, 11% to 17%) and of those receiving EOL antineoplastic treatment (24% in 2010-2014; 95% CI, 21% to 27%). Living in predominantly mixed, Hispanic, Black, or Asian neighborhoods correlated with more intense care (odds ratio, 1.39; 95% CI, 1.10 to 1.77 for ICU). CONCLUSION: Consistent with findings in the Medicare population, our results suggest an overall increase in the number of ICU admissions at the EOL over time. They also suggest that patients from non-White neighborhoods receive more intense acute care.

Evaluating the benefits, risks, and costs of two drugs to treat spinal muscular atrophy raises questions about the future of rare disease medicines.

COVID-19 coronavirus pandemic has virtually locked down the entire world of human population, and through its rapid and unstoppable spread COVID-19 has essentially compartmentalised the population merely into susceptible, exposed, infected and recovered classes. Adapting the classical epidemic modelling framework, two distinct routes of COVID-19 transmission are incorporated into a model: (a) direct person-to-person contact transmission, and (b) indirect airborne and fomites-driven transmission. The indirect non-contact transmission route needs to explored in models of COVID-19 spread, because evidences show that this route of transmission is entirely viable with hugely uncertain level of relative contribution. This theoretical study based on model simulations demonstrates the following: (1) Not incorporating indirect transmission route in the model leads to underestimation of the basic reproduction number, and hence will impact on the COVID-19 mitigation decisions; (2) Lockdown measures can suppress the primary infection peak, but will lead to a secondary peak whose relative strength and time of occurrence depend on the success and duration of the lockdown measures; (3) To make lockdown effective, a considerable level of reduction in both contact and non-contact transmission rates over a long period is required; (4) To bring down the infection cases below any hypothetical health-care capacity, reduction of non-contact transmission rate is key, and hence active measures should be taken to reduce non-contact transmission (e.g., extensive uses of areal and aerosol disinfectant in public spaces to improve contaminated surfaces and air); (5) Any premature withdrawal of lockdown following the sign of a brief retracement in the infection cases can backfire, and can lead to a quicker, sharper and higher secondary peak, due to reactivation of the two transmission routes. Based on these results, this study recommends that any exit policy from lockdown, should take into account the level of transmission reduction in both routes, the absolute scale of which will vary among countries depending on their health-service capacity, but should be computed using accurate time-series data on infection cases and transmission rates.

A strong pharmaceutical sector is a precondition for effective and efficient health care and financing systems, and thus for achieving the best possible health of a population. Supported by visionary, long-term donor funds, in conjunction with mutual trust, the USAID-funded Securing Ugandans Rights to Essential Medicines (SURE) and Uganda Health Supply Chain (UHSC) program engaged in a close, more than 10 year-long (in 2018) collaboration with the Ministry of Health of Uganda. Over time, the partnership implemented numerous multi-pronged comprehensive changes in the pharmaceutical sector and conducted research to document successes and failures. We describe the evolution and key characteristics of the SURE/UHSC interventions.

High-deductible health plan (HDHP) enrollment is expanding rapidly and might substantially increase out-of-pocket (OOP) payment burden. We examined trends in total and OOP health service expenditures overall and by insurance coverage type among women with metastatic breast cancer. We used a longitudinal time series design to examine measures among 5364 women with metastatic breast cancer insured by a large US health insurer from 2004 to 2011. We measured outcomes during the 12 months after a first identified metastatic breast cancer diagnosis and required women to have at least 6 months of prior enrollment. We plotted enrollment measures and adjusted total and OOP spending. We fit trend lines using linear autoregressive models. Between 2004 and 2011, the percentage of women with metastatic breast cancer enrolled in employer-mandated HDHPs increased from 8 to 23% while the percentage enrolled in employer-mandated low-deductible plans (LDHPs) decreased from 69 to 37%. Over the same time period, estimated annual inflation-adjusted total health service spending among women with metastatic breast cancer whose employers only offered HDHPs or LDHPS increased from $96,899 to $104,688 (increase of $1197 per year; 95% confidence interval [CI]: $47,$2,348). Corresponding OOP spending values among these women with employer-mandated deductible levels were $4,496 and $5,151 ($91 per year trend; 95% CI -$13,$195). From 2004–2011, women in HDHPs and LDHPs had unchanged annual OOP spending, estimated at of $6642 (95% CI $6,268,$7016) and $4,247 (95% CI $3956,$4538), respectively. Thus, women in HDHPs experienced 55% (44%, 66%) more OOP spending than women in LDHP. OOP spending among women with metastatic breast cancer and employer-mandated deductible levels was 55% higher among HDHP than LDHP members, and employer-mandated HDHP enrollment increased substantially from 2004 to 2011. Stakeholders and policymakers should design health plans that protect financially vulnerable cancer patients from high OOP costs.

Because of the rising costs of cancer care and ongoing challenges in ensuring access to quality care, there is an increasing need to prioritize spending and define the benefits of therapy in proportion to costs. The term "value" has gained favor as means to define the relative utility of a medical intervention in terms of benefits, risks, and financial costs, which in turn can help clinicians, patients, and policy makers prioritize "high-value" care. While numerous value concepts have been proposed, a comprehensive discussion of value initiatives along the care continuum is missing. In this Commentary, we propose a health system taxonomy of value initiatives in cancer care to discuss what the field needs to progress.

OBJECTIVE: High-deductible health plans (HDHP) have become the predominant commercial health insurance arrangement in the United States. HDHPs require substantial out-of-pocket (OOP) costs for most services but often exempt medications from high cost sharing. We examined effects of HDHPs on OOP costs and utilization of adjuvant hormonal therapy (AHT), which are fundamental care for patients with breast cancer. METHODS: This controlled quasi-experimental study used claims data (2003–2012) from a large national health insurer. We included 986 women with incident early-stage breast cancer, age 25 to 64 years, insured by employers that mandated a transition from low-deductible (=$1000/year) coverage, and 3,479 propensity-score matched controls whose employers offered only low-deductible plans. We examined AHT utilization and OOP costs per person-year before and after the HDHP switch. RESULTS: At baseline, the OOP costs for AHT were $40.41 and $36.55 per person-year among the HDHP and control groups. After the HDHP switch, the OOP costs for AHT were $91.76 and $72.98 per person-year among the HDHP and control groups, respectively. AHT OOP costs increased among HDHP members relative to controls but the change was not significant (relative change: 13.72% [95% CI: −9.25%, 36.70%]). AHT use among HDHP members did not change compared to controls (relative change of 2.73% [95% CI: −14.01%, 19.48%]); the change in AI use was −11.94% (95% CI: −32.76%, 8.88%) and the change in tamoxifen use was 20.65% (95% CI: −8.01%, 49.32%). CONCLUSION: We did not detect significant changes in AHT use after the HDHP switch. Findings might be related to modest increases in overall AHT OOP costs, the availability of low-cost generic tamoxifen, and patient awareness that AHT can prolong life and health. Minimizing OOP cost increases for essential medications might represent a feasible approach for maintaining medication adherence among HDHP members with incident breast cancer.

This exploratory study assesses estimated Medicare spending on 10 cancer drug indications that lacked overall survival benefit after receiving US Food and Drug Administration accelerated approval.

BACKGROUND: Managing expenditures on pharmaceuticals is important for health systems to sustain universal access to necessary medicines. We sought to estimate the size and sources of differences in expenditures on primary care medications among high-income countries with universal health care systems. METHODS: We compared data on the 2015 volume and cost per day of primary care prescription drug therapies purchased in 10 high-income countries with various systems of universal health care coverage (7 from Europe, in addition to Australia, Canada and New Zealand). We measured total per capita expenditure on 6 categories of primary care prescription drugs: hypertension treatments, pain medications, lipid-lowering medicines, noninsulin diabetes treatments, gastrointestinal preparations and antidepressants. We quantified the contributions of 5 drivers of the observed differences in per capita expenditures. RESULTS: Across countries, the average annual per capita expenditure on the primary care medicines studied varied by more than 600%: from $23 in New Zealand to $171 in Switzerland. The volume of therapies purchased varied by 41%: from 198 days per capita in Norway to 279 days per capita in Germany. Most of the differences in average expenditures per capita were driven by a combination of differences in the average mix of drugs selected within therapeutic categories and differences in the prices paid for medicines prescribed. INTERPRETATION: Significant international differences in average expenditures on primary care medications are driven primarily by factors that contribute to the average daily cost of therapy, rather than differences in the volume of therapy used. Average expenditures were lower among single-payer financing systems that appeared to promote lower prices and the selection of lower-cost treatment options.

Background With the launch of very highly priced therapies and sudden price increases of generics, pressures on health systems have drastically increased. Objectives We aimed to elicit opinions of key decision makers responsible for national assessment and funding decisions on their experiences to adapt to these new realities. Methods/setting Through interviews with decision makers of pharmaceutical assessment and/or funding agencies, we describe the challenges systems are currently facing, systems’ responses and systems’ characteristics facilitating or hindering responses to changes and overarching topics for the future. Results Among the most common challenges are increased funding pressures, increased uncertainty and lack of transparency in decision-making. Systems’ responses include utilization management, changing of assessment processes, stakeholder engagement and a focus on outcomes and on coordinated negotiations. Integrated delivery systems, fixed health care budgets and geographic and historical characteristics facilitate or sometimes hinder responses to change. Future policy emphasis lays on expanding data structures, managing the exit of drugs funded early, and implementing processes for communications with patients and the public. Conclusions Going forward emphasis has to be given to structured communications with all stakeholders with a specific emphasis on the broader public and patients about financial limits and priority setting in health care.

Основные лекарства удовлетворяют приоритетные потребности населения в области здравоохранения. Политика, основанная на концепции основных лекарств, имеет решающее значение в улучшении здоровья и достижении устойчивого развития. Цель устойчивого развития 3.8 конкретно упоминает важность «доступности безопасных, эффективных, качественных и доступных по цене основных лекарств и вакцин для всех» в качестве центрального компонента всеобщего охвата медицинской помощью (ВОМП), а цель устойчивого развития 3.b подчёркивает необходимость разработки лекарств для устранения постоянно возникающих пробелов в отношении лечения. Признание важности основных лекарств - не новость. В 1985 г. на конференции в Найроби по рациональному использованию лекарств представители правительств и другие заинтересованные стороны предложили всеобъемлющий комплекс мер по разработке политики в области основных лекарств. Через 30 лет была созвана «Комиссия журнала Ланцет (Lancet) по основным лекарствам» (далее Комиссия) для изучения следующих вопросов: Какого прогресса удалось достичь? Какие проблемы ещё остаются для решения? Какие уроки были извлечены для информирования будущих подходов? И как можно использовать политику в области основных лекарств для продвижения ВОМП и внесения вклада в повестку глобального устойчивого развития? В настоящем докладе рассмотрены эти вопросы с намерением репозиционировать политику в области основных лекарств в повестке глобального развития. Комиссия определила пять областей, имеющих решающее значение для политики в области основных лекарств: оплата корзины основных лекарств, обеспечение ценовой доступности основных лекарств, гарантия их качества и безопасности, мероприятия, способствующие их качественному использованию, и разработка недостающих (отсутствующих) основных лекарств. Комиссия позиционировала политику в области основных лекарств в контексте текущих глобальных дебатов о балансировании политики в области торговли и интеллектуальной собственности с правами человека, об обеспечении безопасности здравоохранения, укреплении систем здравоохранения, ориентированных на людей, и улучшении доступности основных технологий. Во всех областях политики особое внимание было уделено совершенствованию принципов равенства и справедливости в доступе, укреплению соответствующих институтов и созданию подотчётности. В каждой из определённых областей Комиссия сформулировала рекомендации к действию, подтвердив тем самым позицию политики в области основных лекарств в качестве центрального компонента глобального здоровья и здравоохранения и повестки развития.

Methods Using an interrupted time series design, we conducted segmented regression analyses of utilization changes of targeted anti-cancer medicines covered by the provincial government health insurance program during 2013 to 2016 in 69 hospitals with more than 100 beds in Hangzhou, the capital city of Zhejiang province of China. The WHO/Health Action International Project on Medicine Prices and Availability methodology was used to measure patient affordability of the study medicines. Results In March 2015, the utilization of all study medicines increased by 15.58 (95% CI = 3.86, 27.30, P = 0.01) to 439.14 standard units (95% CI = 311.79, 566.49, P

Background Public health care payer organizations face increasing pressures to make transparent and sustainable coverage decisions about ever more expensive prescription drugs, suggesting a need for public engagement in coverage decisions. However, little is known about countries’ approaches to integrating public preferences in existing funding decisions. The aim of this study was to describe how Belgium and New Zealand used deliberative processes to engage the public and to identify lessons learned from these countries’ approaches. Methods To describe two countries’ deliberative processes, we first reviewed key country policy documents and then conducted semi-structured interviews with five leaders of the processes from Belgium and New Zealand. We assessed each country’s rationales for and approaches to engaging the public in pharmaceutical coverage decisions and identified lessons learned. We used qualitative content analysis of the interviews to describe key themes and subthemes. Results In both countries, the national public payer organization initiated and led the process of integrating public preferences into national coverage decision making. Reimbursement criteria considered outdated and changing societal expectations prompted the change. Both countries chose a deliberative process of public engagement with a multi-year commitment of many stakeholders to develop new reimbursement processes. Both countries’ new reimbursement processes put a stronger emphasis on quality of life, the separation of individual versus societal perspectives, and the importance of final reimbursement decisions being taken in context rather than based largely on cost-effectiveness thresholds. Conclusions To face the growing financial pressure of sustainable funding of medicines, Belgium’s and New Zealand’s public payers have developed processes to engage the public in defining the reimbursement system’s priorities. Although these countries differ in context and geographic location, they came up with overlapping lessons learnt which include the need for 1) political commitment to initiate change, 2) broad involvement of all stakeholders, and 3) commitment of all to engage in a long-term process. To evaluate these changes, further research is required to understand how coverage decisions in systems with and without public engagement differ.

10031 Background: Asparaginase (ASN) is a crucial component of pediatric acute lymphoblastic leukemia (ALL) protocols. ASN is available in three enzyme formulations: native from Escherichia Coli ( E. coli), PEGylated from E. coli (PEG), and native erwinia from Erwinia chrysanthemi (Erwinase). PEG is typically preferred in high-income countries, while E. coli is more accessible in low and middle income countries (LMICs). Erwinase is reserved for patients who develop hypersensitivity. Short shelf lives, high prices, intermittent availability, and concern for substandard formulations in LMICs have created a need for proactive ASN demand estimates, particularly in LMICs. Methods: We modified FORxECAST, a publicly available tool that forecasts pediatric cancer drug quantity and cost, to estimate ASN quantity required to treat pediatric ALL in 2021 across all LMICs. Incidence data is based on the Global Childhood Cancer microsimulation model, which extrapolates country registries to estimate diagnosed pediatric ALL patients. We forecast ASN quantity for both a base regimen (BR), recommended by the International Pediatric Oncology Society (SIOP), and a more aggressive regimen (AR) used in some LMICs with more advanced supportive care capacity. For both BR and AR, we estimate ASN quantity across four scenarios, outlining how quantity would vary based on formulation and ability to switch in cases of hypersensitivity. Results: The estimated quantity of ASN required to treat all children diagnosed with ALL in LMICs in 2021, across scenarios and regimens, is provided (Table). If E. coli were used to treat all diagnosed pediatric ALL patients across LMICs, required quantity would range from 1,198 M IU (BR) to 1,661 M IU (AR) (Scenario 1). If PEG were used, required quantity would range 150 M IU (BR) to 473 M IU (AR) (Scenario 2). Accounting for hypersensitivity would require 77 M IU (BR) to 137 M IU (AR) Erwinase (Scenarios 3 and 4). Conclusions: We adapted FORxECAST to be ASN-specific and estimated demand in LMICs for a range of scenarios, including for second line Erwinase; accounting for hypersensitivity is particularly important because discontinuation typically results in lower cure rates. We also estimated how quantity of ASN required would increase with treatment intensity. These results provide the first quantification of ASN need for pediatric ALL in LMICs, creating a demand estimate that can inform private and public efforts to produce a reliable supply of high quality ASN for all children with ALL.[Table: see text]

Racial disparities in breast cancer mortality persist and are likely related to multiple factors. Over the past decade, progress has been made in treating metastatic breast cancer, particularly in younger women. Whether disparities exist in this population is unknown. Using administrative claims data between 2000 and 2011 (OptumInsight, Eden Prairie, MN) of members insured through a large national US health insurer, we identified women aged 25-64 years diagnosed with incident metastatic breast cancer diagnosed between November 1, 2000, and December 31, 2008. We examined time from diagnosis to death, with up to 3 years of follow-up. We stratified analyses by geocoded race and socio-economic status, age-at-diagnosis, morbidity score, US region of residence, urban/non-urban, and years of diagnosis. We constructed Kaplan-Meier survival plots and analyzed all-cause mortality using multivariate Cox proportional hazard models. Among 6694 women with incident metastatic breast cancer (78 % Caucasian, 4 % African American, and 18 % other), we found higher mortality rates among women residing in predominantly African American versus Caucasian neighborhoods (hazard ratio (HR) 1.84; 95 % confidence interval, CI 1.39-2.45), women with high versus lower morbidity (HR 1.30 [1.12-1.51]), and women whose incident metastatic diagnosis was during 2000-2004 versus 2005-2008 (HR 1.60 [1.39-1.83]). Caucasian (HR 0.61 [0.52-0.71]) but not African American women (HR not significant) experienced improved mortality in 2005-2008 versus 2000-2004. Despite insured status, African American women and women with multi-morbidity had poorer survival. Only Caucasian women had improved mortality over time. Modifiable risk factors for increased mortality need to be addressed in order to reduce disparities.

e19078 Background: Childhood cancer outcomes in low-middle income countries (LMICs) have not kept pace with advances in care and survival in high income countries (HICs). A contributing factor to this survival gap is unreliable access to essential cancer drugs. Lack of data on the aggregate need and cost of essential cancer drugs has hampered rational planning and acquisition in many LMICs. Methods: We created a pediatric-specific tool (FORxECAST) that estimates drug quantity and cost for 18 pediatric cancers, customizable to region, regimen, cancer stage distribution, and drug price. We used adapted treatment regimens developed by the International Society of Pediatric Oncology (SIOP), supplemented with input from disease experts, to model treatment approaches reflective of health-system capabilities. FORxECAST incorporates incidence data generated through microsimulation estimates of both diagnosed and undiagnosed (total) cases. Results: We created a pediatric-specific tool (FORxECAST) that estimates drug quantity and cost for 18 pediatric cancers, customizable to region, regimen, cancer stage distribution, and drug price. We used adapted treatment regimens developed by the International Society of Pediatric Oncology (SIOP), supplemented with input from disease experts, to model treatment approaches reflective of health-system capabilities. FORxECAST incorporates incidence data generated through microsimulation estimates of both diagnosed and undiagnosed (total) cases. Conclusions: Our results enable evidence-based forecasting of childhood cancer drug need and cost to inform health system planning in a wide range of countries. The model is adaptable to setting, diagnosis, and treatment approach, allowing decision-makers to generate results specific to their context and needs. Global estimates of essential childhood cancer drug need and cost demonstrate the comparatively small amount of aggregate resources required to treat all cases worldwide, and can help advance innovative procurement strategies with regional and international scale that drive global improvements in childhood cancer drug access.

Nearly 90% of drugs dispensed in the US are generic products. The aim of this study was to develop and implement a tool for analyzing manufacturer-level drug utilization and switching patterns within the US Food and Drug Administration’s Sentinel system. A descriptive tool was designed to analyze data in the Sentinel common data model and was tested with two case studies—metoprolol extended release (ER) and lamotrigine ER—using claims data from four Sentinel data partners. We plotted initiators of each brand and generic product over time. For metoprolol ER, we evaluated rates of switching from generics around the time of manufacturing issues. For lamotrigine ER, we examined rates of switching back to the brand among those who switched from brand to generic. We identified 1,651,285 initiators of metoprolol ER products between July 2008 and September 2015. We observed a large decrease in monthly metoprolol ER initiators (from 25,465 in December 2008 to 13,128 in February 2009), corresponding to recalls by generic manufacturers. We observed simultaneous increases in utilization of the authorized generic and brand products. We identified 4266 initiators of lamotrigine ER with an epilepsy diagnosis between January 2012 and September 2015. Among those who switched from brand to generic, the cumulative incidence of switching back was close to 20% at 2 years. Switchback rates were higher for the first available generic products. This developed tool was able to elucidate novel utilization and switching patterns in two case studies. Such information can be used to support surveillance of generic drugs and biosimilars.

BACKGROUND Providers need timely, clinically meaningful, and actionable information to improve quality of care. Payers may play an important role in providing such information in ambulatory care settings. We sought to learn about providers' use and perceptions of quality reports from insurers. METHODS We employed a mixed-methods study design. We analyzed the performance of 118 provider groups on 21 HEDIS measures included in one New England insurer's quality reporting program and evaluated how a subset of provider groups (n = 55) accessed the reports. We also conducted 14 semistructured interviews with providers and administrators to assess their perspectives about quality reports from insurers in general. RESULTS Performance on quality measures varied greatly across provider groups and by metric. Only 20% of provider groups accessed the quality reports during the study period. While providers reported that payer information on quality has the potential to be useful, respondents suggested important reasons why insurer quality reports were not widely accessed, including information overload, conflicts with other sources of information, and the significant provider effort required to make the reports actionable. CONCLUSIONS Payer-provider collaborations are needed to improve the usefulness of payers' quality measurement reports, and coordination among payers is needed to streamline reported measures.

Purpose Develop a flexible analytic tool for the Food and Drug Administration's (FDA's) Sentinel System to assess adherence to safe use recommendations with two capabilities: characterize adherence to patient monitoring recommendations for a drug, and characterize concomitant medication use before, during, and/or after drug therapy. Methods We applied the tool in the Sentinel Distributed Database to assess adherence to the labeled recommendation that patients treated with dronedarone undergo electrocardiogram (ECG) testing no less often than every 3 months. Measures of length of treatment, time to first ECG, number of ECGs, and time between ECGs were assessed. We also assessed concomitant use of contraception among female users of mycophenolate per label recommendations (concomitancy 4 weeks before through 6 weeks after discontinuation of mycophenolate). Unadjusted results were stratified by age, month-year, and sex. Results We identified 21 457 new episodes of dronedarone use of greater than or equal to 90 days (July 2009 to September 2015); 86% had greater than or equal to one ECG, and 22% met the recommendation of an ECG no less often than every 3 months. We identified 21 942 new episodes of mycophenolate use among females 12 to 55 years (January 2016 to September 2015); 16% had greater than or equal to 1 day of concomitant contraception dispensed, 12% had concomitant contraception use for greater than or equal to 50% of the 4 weeks before initiation through 6 weeks after mycophenolate; younger females had more concomitancy. These results may be underestimates as the analyses are limited to claims data. Conclusions We developed a tool for use in databases formatted to the Sentinel Common Data Model that can assess adherence to safe use recommendations involving patient monitoring and concomitant drug use over time.

Purpose High-deductible health plans (HDHPs) require substantial out-of-pocket spending and might delay crucial health services. Breast cancer treatment delays of as little as 2 months are associated with adverse outcomes. Methods We used a controlled prepost design with survival analysis to assess timing of breast cancer care events among 273,499 women age 25 to 64 years without evidence of breast cancer before inclusion. Women were included if continuously enrolled for 1 year in a low-deductible ($0 to $500) plan followed by up to 4 years in a HDHP (at least $1,000 deductible) after an employer-mandated switch. Study inclusion was on a rolling basis, and members were followed between 2003 and 2012. The comparison group comprised 2.4 million contemporaneously matched women whose employers offered only low-deductible plans. Measures were times to first diagnostic breast imaging (diagnostic mammogram, breast ultrasound, or breast magnetic resonance imaging), breast biopsy, incident early-stage breast cancer diagnosis, and breast cancer chemotherapy. Outcomes were analyzed by using Cox models and adjusted for age-group, morbidity score, poverty level, US region, index date, and employer size. Results After the index date, HDHP members experienced delays in receipt of diagnostic imaging (adjusted hazard ratio [aHR], 0.95; 95% CI, 0.94 to 0.96), biopsy (aHR, 0.92; 95% CI, 0.89 to 0.95), early-stage breast cancer diagnosis (aHR, 0.83; 0.78 to 0.90), and chemotherapy initiation (aHR, 0.79; 95% CI, 0.72 to 0.86) compared with the control group. Conclusion Women switched to HDHPs experienced delays in diagnostic breast imaging, breast biopsy, early-stage breast cancer diagnosis, and chemotherapy initiation. Additional research should determine whether such delays cause adverse health outcomes, and policymakers should consider selectively reducing out-of-pocket costs for key breast cancer services.

Low-income countries face immense challenges in enabling access to high-cost medicines, especially for chronic non-communicable diseases. In this chapter, we discuss the approach Uganda is taking to provide access to medicines with focus on high-cost antiretroviral therapies (ART) by creating a stronger, more cost effective and harmonised pharmaceutical supply system based on approaches taken to addresses challenges in providing ART, which was the first class of high-cost medicines to attract global attention and action and remains the priority high-cost medicines class in Uganda. Uganda uses a comprehensive, multi-pronged system-focused approach for capacity building at the facility, district and central levels of the pharmaceutical sectors to enable access to high-cost medicines. The approach includes strengthening supply chains and procurement processes, capacity building, increasing management effectiveness and providing sound information for shared decision-making by multiple stakeholders. This approach is producing a more efficient supply chain which is critical for all medicines and supplies but especially important for the high-cost items which is highly dependent on system improvements yielding cost savings and reducing waste of scarce financial resources, all of which are critical to improve access to medicines. The system strengthening interventions undertaken form the basis for further actions that will enable affordable, equitable access to other, even higher cost medicines for chronic non-communicable diseases.

Purpose To evaluate changes in thiazolidinedione use and quality of prescription following safety warnings for thiazolidinediones and cardiac risk in 2007, Risk Management Plan (RMP) policy for rosiglitazone in 2010, and warning for pioglitazone and bladder cancer risk in 2010 in Taiwan. Methods We obtained 2003–2011 claims data from Taiwan's National Health Insurance Research Database. Using an interrupted time series design and segmented regression, we estimated changes in monthly prescribing rates for thiazolidinediones among all and prevalent diabetes patients with and without cardiovascular disease history (CV history). We also compared time to prescription of thiazolidinediones among new diabetes patients with CV history before and after each regulatory action using survival analysis. Results Among prevalent patients with and without CV history, the prescribing rates of rosiglitazone decreased 36.88% and 28.92% after safety warnings in 2007 respectively. Pioglitazone prescriptions increased 13% among patients with CV history, but no changes were detected among patients without CV history. After rosiglitazone's RMP policy in 2010, large reductions in prescriptions were observed in patients with CV history (−101.67%) and those without CV history (−88.04%). Among new diabetes patients with CV history, cardiac safety warnings in 2007 significantly delayed the prescription of rosiglitazone, but no significant change was found for pioglitazone. Conclusions The Taiwan FDA regulatory actions for thiazolidinediones communicated possible risks of cardiac events and bladder cancer. Different safety regulatory actions had differential impacts on the use of rosiglitazone and pioglitazone and the quality use of these drugs among the high-risk patients. Copyright © 2015 John Wiley & Sons, Ltd.

In recent years drug prices have increasingly become a topic of debate for patients, providers, payers and policy makers.To place the current drug price debate into historical context, we searched the New York Times and Wall Street Journal from 1985 – 2015 and found that concerns about drug prices have commonly featured in the press over the study period with recently stronger calls for change.Price levels, types of innovations, stakeholder responses, and strategies to address high prices discussed in the media suggest that concerted efforts are required to enable affordable and high-value innovations.