Magnitude Of Clinical Benefit Scale Research Articles

List prices and clinical value of anticancer drugs in China, Japan, and South Korea: a retrospective comparative study

High prices of anticancer drugs have raised concerns due to their financial impact on patients and healthcare systems. This study aimed to assess the initial and latest list prices and clinical value of reimbursed anticancer drugs in China, Japan, and South Korea. We identified anticancer drugs newly approved by the National Medical Products Administration of China from January 2012 to June 2022, and by the Pharmaceuticals and Medical Devices Agency of Japan and the Ministry of Food and Drug Safety of South Korea up until June 2022. We compared initial and latest treatment prices between countries and assessed clinical value using patients' survival, quality of life (QoL), and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). We calculated Spearman rank correlation coefficients of treatment prices with clinical value for individual countries and employed regression analyses to investigate whether the relationship between prices and clinical value was modified by the country setting. Our cohort included 91 anticancer drug indications, with 60 listed for reimbursement in China, 91 in Japan, and 87 in South Korea. Median treatment prices were highest in Japan, followed by South Korea, and lowest in China, both for initial prices (US$64082 vs. US$45529 vs. US$19144, p<0.0001) and latest prices (US$50859 vs. US$31611 vs. US$18666, p<0.0001). Over time, China (β=-0.047, p<0.0001) and South Korea (β=-0.049, p<0.0001) witnessed more significant price reductions compared to Japan (β=-0.013, p=0.011). The correlations between both initial and latest treatment prices and clinical value (QoL and ESMO-MCBS) were more significant and stronger in China and South Korea than in Japan, although Japan exhibited slightly stronger correlations in terms of survival compared to China and South Korea. The relationship between clinical value and treatment prices may not be modified by the country setting. In comparison, South Korea's list prices and their correlations with clinical value appear reasonable. Policymakers in Japan could enhance efficiency by controlling prices and aligning them with clinical value, while China would need to take substantial steps to expand anticancer drug coverage. National Natural Science Foundation of China (72374149 and 72074163), and China Center for South Asian Studies, Sichuan University.

Evaluating the clinical benefit of pembrolizumab as a first-line agent in advanced solid tumors: A comprehensive review.

The study evaluates the first-line application of pembrolizumab in metastatic non-small-cell lung cancer (mNSCLC), head and neck squamous cell cancer (HNSCC), gastric cancer, and renal cell carcinoma. Utilizing the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the American Society of Clinical Oncology Value Framework (ASCO-VF), the analysis incorporates data from pivotal KEYNOTE trials. The study systematically assessed the clinical benefit of pembrolizumab in advanced solid malignancies through nine randomized controlled trials, one of which comprised two experimental arms. Data extraction from primary sources was conducted from PubMed, ASCO, and ESMO publications. Utilizing ESMO-MCBS and ASCO-VF forms, the evaluation focused on clinical benefit, toxicity, and bonus points, with discrepancies resolved through consensus discussions. Nine first-line indications for pembrolizumab received Food and Drug Administration approval for metastatic solid tumors between 2018 and 2023. Notable distinctions in ESMO-MCBS grades revealed seven trials with substantial clinical benefit (grades 5 to 4) and three with moderate to negligible benefit (grades 3 to 1). Bonus points, primarily based on the tail of the curve, were allocated to three trials for overall survival, one for progression-free survival, and one for a significant improvement in quality of life. Our evaluation of pembrolizumab across diverse cancers, especially in mNSCLC and HNSCC, revealed varied outcomes and challenges in clinical benefit interpretation. The assessment of clinical benefit, incorporating quantitative and qualitative endpoints, underscores the need to consider survivorship outcomes and patient perspectives for a comprehensive understanding.

Cost and value of cancer medicines in a single-payer public health system in Ontario, Canada: a cross-sectional study

The financial impact of cancer medicines on health systems is not well known. We describe temporal trends in expenditure on cancer medicines within the single-payer health system of Ontario, Canada, and the extent of clinical benefit these treatments offer. In this cross-sectional study, we identified cancer medicines and expenditures from formularies and costing databases (the New Drug Funding Program, Ontario Drug Benefit Program, and The High-Cost Therapy Funding Program) during 10 consecutive years (April 1, 2012, to March 31, 2022) in Ontario, Canada. For intravenous medicines, we applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) to identify expenditures associated with substantial clinical benefit. We also identified treatments associated with improved overall survival or quality of life. 69 intravenous and 98 oral or injectable medicines were funded during 2012-22. Annual expenditure on cancer medicines increased by approximately 15% per year during 2012-22; the increase was more rapid in the most recent 4 years. Total expenditure on cancer medicines in the 2021-22 financial year was CA$1·7 billion. Immune checkpoint inhibitors were the single biggest expense by class ($284 million), representing 17% of the entire cancer medicine annual budget. Drugs with the highest individual costs were lenalidomide ($178 million) and pembrolizumab ($163 million), each accounting for around 10% of the entire budget. 29 (76%) of 38 indications eligible for ESMO-MCBS scoring met the threshold for substantial clinical benefit. Eight (21%) indications had no randomised trial evidence of improved overall survival, and only four (11%) were associated with improved QOL. $346 million (67% of the expenditure on intravenous cancer medicines) was spent on drugs that improved median overall survival by more than 6 months, $82 million (16%) was spent on medicines with overall survival gains of 3-6 months, and $32 million (6%) was spent on medicines with overall survival gains of less than 3 months. $53 million (10%) was spent on medicines with no established improvement in overall survival. Costs of cancer medicines to the Canadian health system are increasing rapidly. Most funded indications met thresholds for substantial clinical benefit and two-thirds of the expenditure were for medicines that improve survival by more than 6 months. Whether this cost trajectory can be maintained in a sustainable, equitable, high-quality health system is unclear. Efforts are needed to ensure the price of medicines with substantial benefit is affordable and funding of treatments with very modest benefit might need to be re-assessed, particularly when alternative supportive and palliative therapies are available. None.

Evaluation of changes in the clinical benefits of oncology drugs over time following reimbursement using the ASCO-VF and the ESMO-MCBS

PurposeThis study aims to estimate changes in the value of oncology drugs over time from initial data of the reimbursement decisions to subsequent publications in Korea, using two value frameworks.MethodsWe retrieved primary publications assessed for reimbursement between 2007 and July 2021 from the decision documents of Health Insurance Review and Assessment and subsequent publications made available following reimbursement decision from ClinicalTrials.Gov and PubMed databases. Changes in the clinical benefit scores were assessed using the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). A paired t test was performed to test whether there was a difference in the scores between primary and subsequent publications.ResultsOf 73 anticancer product/indication pairs, 45 (61.6%) had subsequent publications, of which 62.5% were released within 1 year of reimbursement decision. The mean ESMO-MCBS and ASCO-VF Net Health Benefit scores increased from primary to subsequent publications, although the differences were not significant. The mean ASCO-VF bonus score significantly increased from 15.91 to 19.09 (p = 0.05). The ESMO-MCBS and bonus scores increased by 0.25 and 0.21, respectively, and the bonus score had a greater impact on the ESMO-MCBS score than the preliminary score did.ConclusionThe value of drugs demonstrated in subsequent publications varies considerably among oncology drugs, depending on uncertainty associated with the initial evidence and the availability of updated evidence. As decision-making in the face of uncertainty becomes more prevalent, the value frameworks can serve as simple screening tools for re-evaluation in these cases.

NCOG-29. THE NEURO-ONCOLOGY MAGNITUDE OF CLINICAL BENEFIT SCALE (NEURO-MCBS) AS A COMPREHENSIVE AND CLINICALLY RELEVANT ASSESSMENT TOOL TO DETERMINE CLINICAL BENEFIT FROM TARGETED THERAPIES IN CNS TUMORS

Abstract BACKGROUND Once first-line therapy options fail, there are no effective therapy options for most neuro-oncological conditions, including glioblastoma, gliomas, and brain metastases, thereby representing a high unmet clinical need. Novel targeted therapy options are often explored in small phase-I studies or are given as off-label therapies. Assessment of treatment efficacy in this setting is challenging and should incorporate outcome measures such as progression-free survival (PFS) or objective response rate (ORR) as well as clinical parameters. To address this, we developed the Neuro-Oncology Magnitude of Clinical Benefit Scale (Neuro-MCBS) as a comprehensive clinical tool to assess treatment efficacy in patients with CNS tumors who receive off-label targeted therapies outside of clinical trials. We prospectively evaluated the feasibility and clinical utility of the Neuro MCBS in a neuro-oncology patient cohort enrolled in MTB@ZPM. METHODS MTB@ZPM (NCT03503149) is a longitudinal observational study that provides comprehensive molecular profiling, consensus-guided and ranked targeted therapy recommendations and collection of prospective clinical outcome data. The Neuro-MCBS (grade 1 + 2=clinical benefit, grade 3=minimal benefit, grade 0=no benefit) was applied and correlated with PFS, the PFS2/PFS1 ratio, performance status (KPS, ECOG), and imaging parameters. RESULTS From February 1st, 2022 until January 31st, 2023, 70 patients were enrolled. While only a minority of n=17/36 (47%) glioblastoma and n=2/8 (25%) IDH-mutant astrocytoma patients benefited from targeted therapies, n=7/8 (88%) meningioma, n=9/10 (90%) brain metastases, and n=5/8 (63%) other tumor patients achieved a Neuro-MCBS of 1 or 2, i.e. derived clinical benefit from the molecularly based therapy. CONCLUSIONS The Neuro-MCBS is a comprehensive and clinically relevant assessment tool that incorporates clinical, imaging, and survival outcome data to determine the degree of clinical benefit from targeted therapies in patients with primary and secondary CNS tumors. Its incorporation into clinical practice provides an objective outcome measure of clinical utility vs. futility of targeted therapies.

Randomized controlled trial in gastric or gastroesophageal junction adenocarcinoma undergoing systemic therapy over two decades

IntroductionThe number of randomized controlled trials (RCTs) investigating the systemic treatment of gastric or gastroesophageal junction adenocarcinoma (GA-RCTs) is increasing. We aimed to describe the characteristics and evaluate the clinical benefit of GA-RCTs over the past 20 years. Materials and methodsWe searched for RCTs of systemic treatment in GA published in eight major journals between 2001 and 2020 in PubMed. From the included studies, the characteristics and results of GA-RCTs were extracted. Clinical benefit was assessed using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). ResultsAbout 93 RCTs with 38365 patients were included. Seventy-one (76.3%) studies received external funding, with an increase from 27.3% (2001–2005) to 94.1% (2016–2020). RCTs on targeted therapy and/or immunotherapy have also increased over time, but only 14 (41.2%) were restricted to specific biomarkers. Forty-four (47.3%) studies met their primary endpoint (defined as positive RCTs), but median overall survival has not improved over time. Moreover, only 16 (36.4%) studies met the ESMO-MCBS threshold. RCTs whose study design and results met the ESMO-MCBS thresholds has not increased over time (p = 0.827 and p = 0.733, respectively). ConclusionsGA-RCTs are increasingly focused on targeted therapy and/or immunotherapy, and are more likely to receive external funding. However, the effect size has not shown significant improvement in the past 20 years. Only a few RCTs with positive results met ESMO thresholds. Future RCTs should prioritize the clinical benefits and provide direct evidence to optimize and reform GA treatment practices.

Access to novel cancer medicines in four countries in Central and Eastern Europe in relation to clinical benefit

Almost 100 novel cancer medicines have been approved in Europe over the last decade. Limited public health care resources in countries in Central and Eastern Europe (CEE) call for a prioritization of access to effective medicines. We investigated how both reimbursement status and waiting time to reimbursement correlate with the magnitude of clinical benefit provided by novel medicines in four selected countries (Czechia, Hungary, Poland, and Slovakia). A total of 124 indications of 51 cancer medicines with marketing authorization by the European Medicines Agency in 2011-2020 were included and followed up until 2022. Data on reimbursement status and waiting time to reimbursement (i.e. time from marketing authorization to national reimbursement approval) were collected for each country. Data were analyzed in relation to clinical benefit status (i.e. substantial versus nonsubstantial clinical benefit) of indications according to the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). The degree of reimbursement differed between countries with 64% of indications with reimbursement in Czechia, 40% in Hungary, 51% in Poland, and 19% in Slovakia. In all countries, a significantly greater proportion of indications with a substantial clinical benefit was reimbursed (P < 0.05). The median waiting time to reimbursement ranged from 27 months in Poland to 37 months in Hungary. No significant differences in waiting time in relation to clinical benefit were observed in any country (P= 0.25-0.84). Cancer medicines with a substantial clinical benefit are more likely to be reimbursed in all four CEE countries. Waiting times to reimbursement are equally long for medicines with or without a substantial clinical benefit, indicating a lack of prioritization of fast access to medicines delivering a substantial benefit. Incorporation of the ESMO-MCBS in reimbursement assessments and decisions could aid in better utilization of limited resources to deliver more effective cancer care.

HTA and Reimbursement Status of Metastatic Hormone‑Sensitive Prostate Cancer, Non-Metastatic Castration-Resistant Prostate Cancer, and Metastatic Castration-Resistant Prostate Cancer Treatments in Europe: A Patient Access Landscape Review

Background: Prostate cancer is the second most common cancer in men, with up to one-third of men being diagnosed in their lifetime. Recently, novel therapies have received regulatory approval with significant improvement in overall survival for metastatic castration-resistant prostate cancer, metastatic hormone-sensitive prostate cancer, and nonmetastatic castration-resistant prostate cancer. To improve decision-making regarding the value of anticancer therapies and support standardized assessment for use by health technology assessment (HTA) agencies, the European Society for Medical Oncology (ESMO) has developed a Magnitude of Clinical Benefit Scale (MCBS). Objective: This review aimed to map HTA status, reimbursement restrictions, and patient access for 3 advanced prostate cancer indications across 23 European countries during 2011-2021. Methods: HTA, country reimbursement lists, and ESMO-MCBS scorecards were reviewed for evidence and data across 26 European countries. Results: The analysis demonstrated that only in Greece, Germany, and Sweden was there full access across all included prostate cancer treatments. Treatments available for metastatic castration-resistant prostate cancer were widely reimbursed, with both abiraterone and enzalutamide accessible in all countries. In 3 countries (Hungary, the Netherlands, and Switzerland), there was a statistically significant difference (P&lt;.05) between status of reimbursement and ESMO-MCBS “substantial benefit” (score of 4 or 5) vs “no substantial benefit” (score &lt;4). Conclusion: Overall, the impact of the ESMO-MCBS on reimbursement decisions in Europe is unclear, with significant variation across the countries included in this review.

HTA and Reimbursement Status of Metastatic Hormone‑Sensitive Prostate Cancer, Non-Metastatic Castration-Resistant Prostate Cancer, and Metastatic Castration-Resistant Prostate Cancer Treatments in Europe: A Patient Access Landscape Review.

Background: Prostate cancer is the second most common cancer in men, with up to one-third of men being diagnosed in their lifetime. Recently, novel therapies have received regulatory approval with significant improvement in overall survival for metastatic castration-resistant prostate cancer, metastatic hormone-sensitive prostate cancer, and nonmetastatic castration-resistant prostate cancer. To improve decision-making regarding the value of anticancer therapies and support standardized assessment for use by health technology assessment (HTA) agencies, the European Society for Medical Oncology (ESMO) has developed a Magnitude of Clinical Benefit Scale (MCBS). Objective: This review aimed to map HTA status, reimbursement restrictions, and patient access for 3 advanced prostate cancer indications across 23 European countries during 2011-2021. Methods: HTA, country reimbursement lists, and ESMO-MCBS scorecards were reviewed for evidence and data across 26 European countries. Results: The analysis demonstrated that only in Greece, Germany, and Sweden was there full access across all included prostate cancer treatments. Treatments available for metastatic castration-resistant prostate cancer were widely reimbursed, with both abiraterone and enzalutamide accessible in all countries. In 3 countries (Hungary, the Netherlands, and Switzerland), there was a statistically significant difference (P<.05) between status of reimbursement and ESMO-MCBS "substantial benefit" (score of 4 or 5) vs "no substantial benefit" (score <4). Conclusion: Overall, the impact of the ESMO-MCBS on reimbursement decisions in Europe is unclear, with significant variation across the countries included in this review.

ESMO-Magnitude of Clinical Benefit Scale for haematological malignancies (ESMO-MCBS:H) version 1.0

The European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) has been accepted as a robust tool to evaluate the magnitude of clinical benefit reported in trials for oncological therapies. However, the ESMO-MCBS hitherto has only been validated for solid tumours. With the rapid development of novel therapies for haematological malignancies, we aimed to develop an ESMO-MCBS version that is specifically designed and validated for haematological malignancies. ESMO and the European Hematology Association (EHA) initiated a collaboration to develop a version for haematological malignancies (ESMO-MCBS:H). The process incorporated five landmarks: field testing of the ESMO-MCBS version 1.1 (v1.1) to identify shortcomings specific to haematological diseases, drafting of the ESMO-MCBS:H forms, peer review and revision of the draft based on re-scoring (resulting in a second draft), assessment of reasonableness of the scores generated, final review and approval by ESMO and EHA including executive boards. Based on the field testing results of 80 haematological trials and extensive review for feasibility and reasonableness, five amendments to ESMO-MCBS were incorporated in the ESMO-MCBS:H addressing the identified shortcomings. These concerned mainly clinical trial endpoints that differ in haematology versus solid oncology and the very indolent nature of nevertheless incurable diseases such as follicular lymphoma, which hampers presentation of mature data. In addition, general changes incorporated in the draft version of the ESMO-MCBS v2 were included, and specific forms for haematological malignancies generated. Here we present the final approved forms of the ESMO-MCBS:H, including instructions. The haematology-specific version ESMO-MCBS:H allows now full applicability of the scale for evaluating the magnitude of clinical benefit derived from clinical studies in haematological malignancies.

Health technology assessment for cancer medicines across the G7 countries and Oceania: an international, cross-sectional study.

Criticisms have emerged that cancer medicines offer modest benefits at increasingly high prices. Reimbursement decisions made by health technology assessment (HTA) agencies have become a complex endeavour for cancer medicines. Most high-income countries (HICs) use HTA criteria to identify high-value medicines for reimbursement under public drug coverage plans. We compared HTA criteria specific for cancer medicines in economically similar HICs, to understand how these criteria contribute to reimbursement decisions. We did an international, cross-sectional analysis in collaboration with author investigators across eight HICs, from the Group of Seven (known as G7; Canada, England, France, Germany, Italy, and Japan) and Oceania (Australia and New Zealand). Publicly available data from HTA agency reports and official documentation were extracted and analysed between Aug 15, 2021, and July 31, 2022. We collected data pertaining to the decision-making criteria used by the national HTA agency; HTA reimbursement status for 34 medicine-indication pairs corresponding to 15 unique US top-selling cancer medicines; and HTA reimbursement status for 18 cancer medicine-indication pairs (13 unique medicines) with minimal clinical benefit (score of 1 on the European Society of Medical Oncology Magnitude of Clinical Benefit Scale). Descriptive statistics were used to compare HTA decision criteria and drug reimbursement recommendations (or for Germany and Japan, final reimbursement status) across the eight countries. Therapeutic impact related to clinical outcomes of the new medicine was a uniform criterion across the eight countries, whereas quality of evidence (under the remit of therapeutic impact assessment) and equity were infrequently cited criteria. Only the German HTA agency mandated that surrogate endpoints be validated in therapeutic impact assessment. All countries except Germany included formal cost-effectiveness analyses within HTA reports. England and Japan were the only countries that specified a cost-effectiveness threshold. Of the 34 medicine-indication pairs corresponding to US top-selling cancer medicines, Germany reimbursed the maximum (34 [100%]), followed by Italy (32 [94%] recommended for reimbursement), Japan (28 [82%] reimbursed), Australia, Canada, England, and France (27 [79%] recommended for reimbursement), and New Zealand (12 [35%] recommended for reimbursement). Of the 18 cancer medicine-indication pairs with marginal clinical benefit, Germany reimbursed 15 (83%) and Japan reimbursed 12 (67%). France recommended nine (50%) for reimbursement, followed by Italy (seven [39%]), Canada (five [28%]), and Australia and England (three [17%] each). New Zealand did not recommend any medicine-indications with marginal clinical benefit for reimbursement. Considering the overall cumulative proportion across the eight countries, 58 (21%) of 272 indications for the US top-selling medicines and 90 (63%) of 144 marginally beneficial medicine-indications were not recommended for reimbursement or reimbursed. Our findings indicate discordance in public reimbursement decisions across economically similar countries, despite overlapping HTA decision criteria. This suggests a need for improved transparency around the nuances of the criteria to ensure improved access to high-value cancer medicines, and deprioritisation of low-value cancer medicines. Health systems have opportunities to improve their HTA decision-making processes by learning from the systems in other countries. None.

Single-arm trials supporting the approval of anticancer medicinal products in the European Union: contextualization of trial results and observed clinical benefit

Single-arm trials (SATs) can sometimes be used to support marketing authorization of anticancer medicinal products in the European Union. The level and durability of antitumor activity of the product as well as context are important aspects to determine the relevance of trial results. The aim of this study is to provide details on the contextualization of trial results and to evaluate the magnitude of benefit of medicinal products approved based on SATs. We focused on anticancer medicinal products for solid tumors approved on the basis of SAT results (2012-2021). Data were retrieved from European public assessment reports and/or published literature. The benefit of these medicinal products was evaluated via the European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS). Eighteen medicinal products were approved based on 21 SATs-few medicinal products were supported by >1 SAT. For the majority of clinical trials, a clinically relevant treatment effect was (pre)specified (71.4%) and most often an accompanying sample size calculation was provided. For 10 studies, each testing a different medicinal product, a justification for the threshold for a clinically relevant treatment effect could be identified. At least 12 out of 18 applications included information to facilitate the contextualization of trial results, including six supportive studies. Of the pivotal SATs analyzed (n= 21), three were assigned an ESMO-MCBS score of 4, which corresponds to 'substantial' benefit. The clinical relevance of the treatment effects shown by medicinal products for solid tumors tested in SATs is dependent on the effect size and context. To better facilitate regulatory decision making, prespecifying and motivating a clinically relevant effect and aligning the sample size to that effect is important. External controls may facilitate in the contextualization process, but the associated limitations must be addressed.

Analysis of oncological drugs authorised in Spain in the last decade: association between clinical benefit and reimbursement.

Our study aimed to assess whether there was a relationship between clinical benefits and reimbursement decisions as well as the inclusion of economic evaluations in therapeutic positioning reports (IPTs) and to explore factors influencing reimbursement decisions. We analysed all anti-cancer drugs approved in Spain from 2010 to September 2022. The clinical benefit of each drug were evaluated using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) 1.1. The characteristics of these drugs were obtained from the Spanish Agency of Medicines and Medical Devices. Reimbursement status information was obtained using BIFIMED, a web resource available in Spanish and consulted the agreements of the Interministerial Committee on Pricing of Medicines (CIPM). In total, 73 drugs were included involving 197 indications. Almost half of the indications had substantial clinical benefit (49.8% yes vs. 50.3% no). Of the 153 indications with a reimbursement decision, 61 (56.5%) reimbursed indications had substantial clinical benefit compared to 14 (31.1%) of the non-reimbursed (p < 0.01). The median gain of overall survival was 4.9months (2.8-11.2) for reimbursed indications and 2.9months (1.7-5) in non-reimbursed (p < 0.05). Only six (3%) indications had an economic evaluation in the IPT. Our study revealed that there is a relationship between substantial clinical benefit and the reimbursement decision in Spain. However, we also found that the overall survival gain was modest, and a significant proportion of the reimbursed indications had no substantial clinical benefit. Economic evaluations in IPTs are infrequent and cost-effectiveness analysis is not provided by CIPM.

Value assessment of NMPA-approved new cancer drugs for solid cancer in China, 2016-2020.

Whether the high cost of cancer drugs is commensurate with their value to patients, which has become the focus of public concern. We aimed to assess the value of new cancer drugs approved for solid cancer in China and to explore the association between price and value of drugs. We identified all new drugs for solid tumor that approved by the China's National Medical Products Administration (NMPA) between 2016 and 2020. The value of these drugs was assessed according to the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). We calculated Cohen's κ statistic to describe agreement between the two frameworks. Spearman's correlation coefficient was used to evaluate the correlation between price and value of drugs. Between 2016 and 2020, 37 new drugs were approved by the NMPA for solid tumor and we could evaluate the value of 28 drugs (76%). Eight (29%) of drugs were approved for non-small-cell lung cancer and 6 (21%) for breast cancer. ASCO-VF scores had a range of -20 to 110.1, and the median score was 43.3 (inter-quartile range 27.1-58.35). Only seven drugs (25%) met the ASCO-VF cutoff score. By the ESMO-MCBS, 13 drugs showed a meaningful value. Agreement between these two frameworks thresholds was only fair (κ = 0.515, P < 0.05). We found no statistically significant correlation between launch price of drugs and clinical benefit according to both frameworks. Not all NMPA-approved new cancer drugs had meaningful value as measured by ASCO-VF or ESMO-MCBS. There was no significant correlation between drug price and the level of clinical benefit.

The correlation between the costs and clinical benefits of PD-1/PD-L1 inhibitors in malignant tumors: An evaluation based on ASCO and ESMO frameworks.

Background: Life expectancy for patients with malignant tumors has been significantly improved since the presence of the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors in 2014, but they impose heavy financial burdens for patients, the healthcare system and the nations. The objective of this study was to determine the survival benefits, toxicities, and monetary of programmed cell death protein-1/programmed cell death protein ligand-1 inhibitors and quantify their values. Methods: Randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitors for malignant tumors were identified and clinical benefits were quantified by American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). The drug price in Micromedex REDBOOK was used to estimate monthly incremental drug costs (IDCs) and the correlation between clinical benefits and incremental drug costs of experimental and control groups in each randomized controlled trial, and the agreement between two frameworks were calculated. Results: Up to December 2022, 52 randomized controlled trials were included in the quantitative synthesis. All the randomized controlled trials were evaluated by American society of clinical oncology value framework, and 26 (50%) met the American society of clinical oncology value framework "clinical meaningful value." 49 of 52 randomized controlled trials were graded by European society for medical oncology magnitude of clinical benefit scale, and 30 (61.2%) randomized controlled trials achieved European Society for Medical Oncology criteria of meaningful value. p-values of Spearman correlation analyses between monthly incremental drug costs and American society of clinical oncology value framework/European society for medical oncology magnitude of clinical benefit scale scores were 0.9695 and 0.3013, respectively. In addition, agreement between two framework thresholds was fair (κ = 0.417, p = 0.00354). Conclusion: This study suggests that there might be no correlation between the cost and clinical benefit of programmed cell death protein-1/programmed cell death protein ligand-1 inhibitors in malignancy, and the same results were observed in subgroups stratified by drug or indication. The results should be a wake-up call for oncologists, pharmaceutical enterprises and policymakers, and meanwhile advocate the refining of American Society of Clinical Oncology and European Society for Medical Oncology frameworks.

Application of Value Framework to Phase III Trials of Immune Checkpoint Inhibitors in Esophageal and Gastric Cancer.

Recent trials testing immune-checkpoint inhibitors in esophago-gastric malignancies have shown mixed results. We aim to assess key subgroups using the ASCO Net Health Benefit Score (NHBS) and ESMO Magnitude of Clinical Benefit Scale (MCBS). A search for phase III trials of FDA-approved anti-PD-1 or anti-PD-L1 drugs in esophago-gastric cancer trials was identified using www.clinicaltrials.gov. These published studies were scored using the ASCO NHBS and ESMO MCBS. The ASCO NHBS scores were compared by primary site of cancer (esophageal vs gastric) and PD-L1 expression using the Mann-Whitney test and the ESMO-MCBS grading, by Fisher's Exact test. Fifteen of 45 clinical trials were included. Of them, 6 were primarily esophageal cancer trials, and 9 were primarily gastric cancer trials. Ten stratified their analysis based on PD-L1 expression. The ASCO NHBS score was higher (mean 40, range 20 to 56.6 vs. mean 12, range -1.1 to 18.4, P < .01) for esophageal cancer than gastric cancer. No difference was observed in survival and response endpoints between the 2 groups. Similarly, the ESMO MCBS scored higher for esophageal cancer group than gastric cancer (P < .05). Additionally, the scores were higher in those with high PD-L1 expression vs. low PD-L1 (mean 36, range 11.2-66.6 vs. mean 14, range -19.5 to 43.6, P < .05). The ASCO NHB and ESMO scores were consistently higher among esophageal cancer trials than gastric cancer trials and in those with high PD-L1 expression than low expression. Histology and PD-L1 expression should be considered when discussing value of immunotherapy to patients.

Application of value framework to phase III trials of immune checkpoint inhibitors in esophageal and gastric cancer.

e18817 Background: Recent clinical trials testing use of immune-checkpoint inhibitors in esophageal and gastric carcinomas have shown both positive and negative results. Given these mixed signals, we aimed to assess outcomes and tolerability of key subgroups using the ASCO Net Health Benefit Score (NHBS) and ESMO Magnitude of Clinical Benefit Scale (MCBS). Methods: A detailed search for phase III trials investigating use of FDA-approved anti PD-1 or anti PD-L1 drugs in esophageal and gastric cancer trials was completed using www.clinicaltrials.gov followed by primary literature identification on PubMed. These studies were then independently selected, reviewed, and scored using the ASCO NHBS and ESMO MCBS by two investigators, and any discrepancy was mutually resolved. The ASCO NGBS scores were compared by primary site of cancer (esophageal vs gastric) and PD-L1 expression using the Mann-Whitney test. The ESMO-MCBS grading were compared using Fisher's Exact test. Results: Of the 45 records identified, 15 clinical trials were included. Of them, six were primarily esophageal cancer trials, and nine were primarily gastric cancer trials. Of all 15, 10 stratified their analysis based on PD-L1 expression. The ASCO NHBS score was significantly higher for esophageal cancer than gastric cancer (mean 40, range 20 – 56.6 vs. mean 12, range -1.1 – 18.4, p &lt; .01). No difference, however, was observed in survival and response rate outcome endpoints between the two groups. Similarly, the ESMO MCBS was also higher for esophageal cancer group than gastric cancer (p &lt; .05). Additionally, the median scores were higher in the patients with high PD-L1 expression vs low PD-L1 expression (mean 37, range 11.2 – 66.6 vs. mean 14, range -19.5 – 43.6, p &lt; .05). Conclusions: In this cohort of drug registration trials of immune checkpoint inhibitors for upper GI cancers, we showed the ASCO NHB scores and ESMO scores were consistently higher among esophageal cancer trials than gastric cancer trials and in those with high PD-L1 expression than those with low PD-L1 expression. Oncologists should carefully discuss overall clinical value and expectations of immunotherapy benefit with their patients per cancer histology and PDL1 expression, exercising caution in cases of gastric adenocarcinoma with low PD-L1 expression.[Table: see text]

Association between control group therapy and magnitude of clinical benefit of cancer drugs.

e18604 Background: Oncology societies have developed tools to quantify the magnitude of clinical benefit. These include the American Society of Clinical Oncology Value Framework (ASCO-VF) version 2, the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) version 1.1, the National Comprehensive Cancer Network (NCCN) Evidence Blocks and the ASCO Cancer Research Committee criteria (ASCO-CRC). Associations between the characteristics of approved drugs and magnitude of clinical benefit have been explored in depth. Here, we assess the association between characteristics of control group therapy and magnitude of clinical benefit. Methods: We searched Drugs@FDA to identify new solid tumor cancer drugs approved based on randomized trials (RCTs) between January 2012 and December 2021. Substantial clinical benefit was defined as: overall survival gain ≥ 2.5 months and progression-free survival gain ≥ 3 months for the ASCO-CRC (palliative setting only); ASCO-VF threshold score ≥45 (palliative and curative setting); NCCN Evidence Blocks threshold score ≥16 (palliative and curative setting); and grade A or B for trials of curative intent and 4 or 5 for those of non-curative intent using ESMO-MCBS. Associations between characteristics of control group therapy (e.g. type of active therapy, use of matched placebo and overlap between experimental and control therapy) and substantial clinical benefit scores were explored using logistic regression. Results: We identified 174 RCTs supporting the approval of 76 drugs for 164 indications. Of these, 47% (82/174) were placebo-controlled trials among which 42% (34/82) comprised active treatment with a matched placebo. Substantial clinical benefit was observed in 45%, 46%, 72% and 73% using the ESMO-MCBS, ASCO-VF, NCCN Evidence Blocks and ASCO-CRC, respectively. These low proportions resulted in an inability to fit multivariable models adequately. RCTs with a control group comprising of active treatment with a matched placebo were associated with significantly lower odds of substantial benefit with ESMO-MCBS (OR 0.27, P = .003) and ASCO-VF (OR 0.30, P = .008) but not with NCCN Evidence Blocks (OR 0.74, P = .55) or ASCO-CRC criteria (OR 1.36, P = .54). Similar results were observed when excluding trials in the curative setting. There was a non-significant association with higher odds of substantial benefit with ESMO-MCBS with trials in which the control group was chemotherapy (OR 1.97, P = .07). For ASCO-CRC a non-significant association in the opposite direction was observed (OR 0.40, P = .06). Conclusions: Clinical benefit scales can be sensitive to the type of control group therapy. RCTs with an active treatment and matched placebo in the control group were less likely to be scored as providing substantial clinical benefit using the ESMO-MCBS and the ASCO-VF scales. Control group therapy did not influence NCCN Evidence Blocks or ASCO-CRC scores.

Building a Healthcare Alliance for Resourceful Medicine Offensive Against Neoplasms in Hematology Added Value Framework for Hematologic Malignancies: A Comparative Analysis of Existing Tools

ObjectivesThe Innovative Medicines Initiative–funded, multistakeholders project Healthcare Alliance for Resourceful Medicine Offensive Against Neoplasms in Hematology (HARMONY) created a task force involving patient organizations, medical associations, pharmaceutical companies, and health technology assessment/regulator agencies’ representatives to evaluate the suitability of previously established value frameworks (VFs) for assessing the clinical and societal impact of new interventions for hematologic malignancies (HMs). MethodsSince the HARMONY stakeholders identified the inclusion of patients’ points of view on evaluating VFs as a priority, surveys were conducted with the patient organizations active in HMs and part of the HARMONY network, together with key opinion leaders, pharmaceutical companies, and regulators, to establish which outcomes were important for each HM. Next, to evaluate VFs against the sources of information taken into account (randomized clinical trials, registries, real-world data), structured questionnaires were created and filled by HARMONY health professionals to specify preferred data sources per malignancy. Finally, a framework evaluation module was built to analyze existing clinical VFs (American Society of Clinical Oncology, European Society of Medical Oncology, Magnitude of Clinical Benefit Scale, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, Institute for Clinical and Economic Review, National Comprehensive Cancer Network Evidence Blocks, and patient-perspective VF). ResultsThe comparative analysis describes challenges and opportunities for the use of each framework in the context of HMs and drafts possible lines of action for creating or integrating a more specific, patient-focused clinical VF for HMs. ConclusionsNone of the frameworks meets the HARMONY goals for a tool that applies to HMs and assesses in a transparent, reproducible, and systematic way the therapeutic value of innovative health technologies versus available alternatives, taking a patient-centered approach and using real-world evidence.

Clinical Benefit Scales and Trial Design: Some Statistical Issues.

Recently developed clinical-benefit outcome scales by the European Society for Medical Oncology and the American Society of Clinical Oncology allow standardized objective evaluation of outcomes of randomized clinical trials. However, incorporation of clinical-benefit outcome scales into trial designs highlights a number of statistical issues: the relationship between minimal clinical benefit and the target treatment-effect alternative used in the trial design, designing trials to assess long-term benefit, potential problems with using a trial endpoint that is not overall survival, and how to incorporate subgroup analyses into the trial design. Using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale as a basis for discussion, we review what these issues are and how they can guide the choice of trial-design target effects, appropriate endpoints, and prespecified subgroup analyses to increase the chances that the resulting trial outcomes can be appropriately evaluated for clinical benefit.