American Society Of Clinical Oncology Frameworks Research Articles

Choosing PD-1 Inhibitors in Oncology Setting, Left or Right?-Lessons From Value Assessment With ASCO-VF and ESMO-MCBS.

Background: Influx of innovative therapies and dramatic rise in prices have been prompting value-driven decision-making. Both the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have independently proposed value assessment frameworks. Objectives: To comprehensively examine the value of nivolumab and pembrolizumab by two value assessment frameworks with a cohort of published randomized controlled trials and offer insight into the association between these two frameworks. Methods: Trials were identified with a cutoff date of Nov 30th, 2019. Receiver operating characteristic curves were generated to establish the predictive value of ASCO-VF score to meet ESMO-MCBS grade and discriminate the agreement of these two value assessment tools. Spearman correlation was used to assess the association between monthly cost and ASCO-VF score/ESMO-MCBS grade. Results: 19 randomized controlled trials were eligible. seven (36.8%) trials were of treatment included nivolumab while 12 (63.2%) pembrolizumab. 8 (42.1%) of the trials were of treatments for non-small-cell lung cancer, 5 (26.3%) for melanoma, 2 (10.5%) were for head and neck squamous cell carcinoma, 2 (10.5%) for gastric or gastro-oesophageal junction cancer and 1 (5.3%) for urothelial cancer and renal-cell carcinoma respectively. ASCO scores ranged from 7 to 94.7 with median 40.90. 11 (57.9%) trials met the ESMO criteria for meaningful value achieved. Of 14 trials not meeting the ASCO cutoff score, only 8 did not meet the meaningful ESMO criteria. Agreement between these two frameworks thresholds was only fair (κ = 0.412, P＜0.05). A negative correlation was noted between increment monthly cost and value assessment results. Conclusion: There is only fair correlation between ASCO and ESMO value assessment frameworks. Not all treatment with nivolumab and pembrolizumab meet valuable thresholds.

Clinical Value of TTFields Treatment in Mesothelioma Using ASCO and ESMO Frameworks

The potential effectiveness and safety of TTFields in addition to pemetrexed and cisplatin or carboplatin in malignant pleural mesothelioma (MPM) was recently shown by the analysis of the phase II single arm EF-23 STELLAR trial. To account for the need of physicians and policymakers to objectively and comparably capture the clinical value of new cancer treatments the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have both developed assessment frameworks. We quantified the clinical value of the TTFields treatment in MPM by applying ASCO and ESMO frameworks to the comparison of the STELLAR data to historical controls. The EF-23 STELLAR Trial (n=80) demonstrated that adding TTFields to pemetrexed and cisplatin or carboplatin for malignant pleural mesothelioma patients resulted in overall survival of 18.2 months (95% CI 12.1-25.8) and progression free survival of 7.6 months (95% CI 6.7-8.6). The ESMO Magnitude of Clinical Benefit Scale (MCBS) and the ASCO Net Health Benefit (NHB) frameworks were applied to the EF-23 trial data using a historical control as comparator. The application of the ASCO framework to the EF-23 data resulted in a NHB score of 52. This result was at the higher end of the score range of novel cancer treatments and compares well to the results for nivolumab in advanced non-squamous NSCLC and advanced squamous NSCLC as reference points. Applying the ESMO framework resulted in MCBS scores of A/5 (adjuvant/advanced) which would be the first score reported for MPM. The MCBS scores of A/5 are the highest scores achievable in the ESMO framework, and higher than the ESMO MCBS scores reported in the literature for NSCLC treatments. Despite differences in their respective concepts, both the ASCO and ESMO frameworks suggest that adding TTFields to Pemetrexed and Cisplatin or Carboplatin in malignant pleural mesothelioma patients provides a significant clinical benefit. The high scores underline the fact that treatment with TTFields may extend progression free and overall survival without additional systemic toxicities.

Abstract LB-161: Application of the ASCO and ESMO frameworks to TTFields treatment of mesothelioma

Abstract Objective: To assess the clinical value of tumor treating fields (TTFields) in malignant pleural mesothelioma (MPM) by means of the ASCO and ESMO frameworks. Background: The potential effectiveness and safety of TTFields in addition to pemetrexed and cisplatin or carboplatin in MPM was recently shown by the analysis of the Phase II single arm EF-23 STELLAR trial. To account for the need of physicians and policymakers to objectively and comparably capture the clinical value of new cancer treatments the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have both developed assessment frameworks. We quantified the clinical value of the TTFields treatment in MPM by applying ASCO and ESMO frameworks to the comparison of the STELLAR data to historical controls. Materials/Methods: The EF-23 STELLAR Trial (n=80) demonstrated that adding TTFields to pemetrexed and cisplatin or carboplatin for malignant pleural mesothelioma patients resulted in overall survival of 18.2 months (95% CI 12.1-25.8) and progression free survival of 7.6 months (95% CI 6.7-8.6). The ESMO Magnitude of Clinical Benefit Scale (MCBS) and the ASCO Net Health Benefit (NHB) frameworks were applied to the EF-23 trial data using a historical control as comparator. Results: The application of the ASCO framework to the EF-23 data resulted in a NHB score of 52. This result was at the higher end of the score range of novel cancer treatments and compares well to the results for nivolumab in advanced non-squamous NSCLC and advanced squamous NSCLC as reference points. Applying the ESMO framework resulted in MCBS scores of A/5 (adjuvant/advanced) which would be the first score reported for MPM. The MCBS scores of A/5 are the highest scores achievable in the ESMO framework, and higher then the ESMO MCBS scores reported in the literature for NSCLC treatments. Conclusions: Despite differences in their respective concepts, both the ASCO and ESMO frameworks suggest that adding TTFields to Pemetrexed and Cisplatin or Carboplatin in malignant pleural mesothelioma patients may provide a significant clinical benefit. The high scores underline the fact that treatment with TTFields may extended progression free and overall survival without additional systemic toxicities. Citation Format: Justin Kelly, Uri Weinberg, Christina Proescholdt. Application of the ASCO and ESMO frameworks to TTFields treatment of mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-161.

Current Value Frameworks—What's New?

Current Value Frameworks—What's New?

Evaluating the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) value frameworks for Food and Drug Administration (FDA) approved checkpoint inhibitors (CIs).

6624 Background: Although the development of CIs has led to a dramatic change in the oncology landscape, these agents are associated with significant costs and toxicity. ASCO and ESMO have developed separate frameworks to define the value of emerging cancer treatments in order to encourage cost-effective therapies. We apply these frameworks to trials supporting FDA approvals of CIs and explore the correlation between these two scoring systems. Methods: We searched the FDA database for CIs and indications approved between January 1, 2011 and January 1, 2019. Only randomized phase II/III trials for solid tumors were included. Data on survival, toxicity and quality of life were extracted from the most recent publications by two reviewers independently. A trial showing a substantial benefit was defined as an ASCO score of ≥ 45, or ESMO Grade 4-5 (palliative setting) or Grade A/B (curative setting). Concordance for substantial benefit was assessed using Cohen’s Kappa while Spearman coefficients were used to determine the degree of correlation in individual scores. Results: We identified 40 FDA indications for 7 CIs. Of these, 18 indications based on Phase I/II single-arm trials were excluded. The remaining 22 indications were based on 21 randomized phase II/III trials (3 adjuvant, 18 metastatic). In the palliative setting, 73% and 86% trials showed substantial benefit based on ASCO and ESMO frameworks respectively [median ASCO score: 54.8, interquartile range (IQR) 46.2-64.0; median ESMO score: 5, IQR: 4-5]. 27% of trials were scored intermediate or low benefit by ASCO, while 9% were ineligible for ESMO scoring. Weighted kappa was 0.719 between the two frameworks. Spearman rho was 0.84. All 3 adjuvant trials were assigned ESMO grade A but low benefit with ASCO (median 37.7, IQR 20.5-40.9). Conclusions: In the palliative setting, the majority of trials supporting FDA approved CI indications demonstrated substantial benefit using both ASCO and ESMO frameworks. There was a strong correlation between the two frameworks. However, in the curative setting scores were discordant. The ASCO framework may require further refinement for adjuvant trials.

Evaluating the value of checkpoint inhibitor therapy using the ASCO and ESMO frameworks.

17 Background: The advent of checkpoint inhibitor therapy (CIT) has dramatically changed the oncology landscape, but is associated with significant costs. A positive randomized clinical trial (RCT) may not translate to meaningful outcomes for patients. The American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) have developed frameworks to quantify the value of cancer treatment. We applied these frameworks to RCTs involving CIT in order to explore the relationship between trial outcomes and magnitude of clinical benefit. Methods: A literature search was conducted to identify CIT RCTs. Data extracted included study characteristics, pre-specified estimated hazard ratios (eHR) and observed HR (oHR). ASCO Value Framework version 2016 and ESMO Magnitude of Clinical Benefit (MCB) scale v1.1 were applied to each publication by 2 authors independently. Results: 30 RCTs (3 adjuvant, and 27 advanced setting) using CIT were identified between January 2010- October 2018. The majority of trials were in lung cancer (37%) and melanoma (36%). The eHR was 0.71±0.06 (range: 0.55-0.78), and oHR was 0.76±0.15 (range: 0.49 – 1.11). 54% RCTs did not achieve eHR, with a difference of 0.16±0.12 (range: 0.01 – 0.41). ASCO framework scores ranged -24.0 to 71.3, far below the maximum potential score of 180. 18 RCTs formed the basis for FDA approvals. The mean ASCO framework score was 45.6 ± 16.6 (range: 14.4 - 71.3) for FDA approved indications, and 14.0 ± 18.4 (range: -24 – 49) for non-FDA approvals (p < 0.001). All FDA approvals scored grade 4 or 5 on the ESMO MCB scale, indicating a meaningful clinical benefit. Many non-FDA approved RCTs did not receive an MCB grade as they were negative trials. There was no difference in the ASCO framework scores between MCB grade 4 and 5 RCTs. 3 adjuvant RCTs had an ASCO framework score ranging from 20.5 to 38.7 despite an MCB Grade A. Conclusions: Many trials did not meet the pre-specified eHR. FDA approval had statistically significantly higher NHB scores than non-FDA approvals, and they were deemed to have a meaningful clinical benefit according to the ESMO MCB scale. ASCO framework scores may require re-calibration since the highest score achieved in CIT RCTs was only 40% of the maximum score.

PCN26 - ASSESSING THE POTENTIAL VALUE OF AN INNOVATIVE ONCOLOGY THERAPY FROM THE HEALTH TECHNOLOGY ASSESSMENT (HTA) PERSPECTIVE: MARRYING CLINICAL VALUE FRAMEWORKS WITH ECONOMIC ASSESSMENT METHODOLOGY

This study assessed the clinical benefit of oncology regimens for an ultra-rare tumor using concepts from European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) frameworks. It also enhanced clinical assessment of these frameworks by accounting for potential long-term benefits of a novel treatment. An enhanced value framework (EVF) was developed by combining ESMO and ASCO frameworks with well-validated approaches for projecting long-term survival. Published single-arm data for chemotherapies and patient-level data from recently approved immuno-oncology (IO) agent for treating aggressive ultra-rare tumor in metastatic setting was used. Under the ESMO Magnitude of Clinical Benefit Scale (MCBS), form 2a was selected due to lack of sufficient follow-up data on potential curative benefits in terms of overall survival (OS) at the time of approval. Along with OS benefit (1 to 4, indicating increasing OS benefit), MCBS also valued improvements in toxicity and/or quality of life (QoL) (1 for significant improvement in either). The ASCO value framework calculated incremental net health benefit (NHB) by combining scores attributable to clinical benefit, toxicity, and bonus benefits. The projected mean OS over life-time for IO was 42.5 months in the base case compared with 4.2 months for chemotherapies, driven mostly by improvements in progression-free survival (35.0 vs 2.5 months). Under ESMO MCBS version 1.1, IO scored 3 points higher than chemotherapies for efficacy (4 over 1) as well as 1 for improvement in both toxicity and QoL. Under the ASCO framework, the NHB of IO vs chemotherapies ranged from 212-218, with 193 attributable to clinical benefit, 0-5 to toxicity, and 20 bonus points. From HTA perspective, the IO agent for ultra-rare tumor in this case study was determined to provide considerable clinical benefit, irrespective of value framework used to assess benefits associated with the product.

Delivery of meaningful cancer care: a retrospective cohort study assessing cost and benefit with the ASCO and ESMO frameworks

The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have developed frameworks that quantify survival gains in light of toxicity and quality of life to assess the benefits of cancer therapies. We applied these frameworks to a cohort of contemporary randomised controlled trials to explore agreement between the two approaches and to assess the relation between treatment benefit and cost. We identified all randomised controlled trials of systemic therapies in non-small-cell lung cancer, breast cancer, colorectal cancer, and pancreatic cancer published between Jan 1, 2011, and Dec 31, 2015, and assessed their abstracts and methods. Trials were eligible for inclusion in our cohort if significant differences favouring the experimental group in a prespecified primary or secondary outcome were reported (secondary outcomes were assessed only if primary outcomes were not significant). We assessed trial endpoints with the ASCO and ESMO frameworks at two timepoints 3 months apart to confirm intra-rater reliability. Cohen's κ statistic was calculated to establish agreement between the two frameworks on the basis of the median ASCO score, which was used as an arbitrary threshold of benefit, and the framework-recommended ESMO threshold. Differences in monthly drug cost between the experimental and control groups of each randomised controlled trial (ie, incremental drug cost) were derived from 2016 average wholesale prices. 109 randomised controlled trials were eligible for inclusion, 42 (39%) in non-small-cell lung cancer, 36 (33%) in breast cancer, 25 (23%) in colorectal cancer, and six (6%) in pancreatic cancer. ASCO scores ranged from 2 to 77; median score was 25 (IQR 16-35). 41 (38%) trials met the benefit thresholds in the ESMO framework. Agreement between the two frameworks was fair (κ=0·326). Among the 100 randomised controlled trials for which drug costing data were available, ASCO benefit score and monthly incremental drug costs were negatively correlated (ρ=-0·207; p=0·039). Treatments that met ESMO benefit thresholds had a lower median incremental drug cost than did those that did not meet benefit thresholds (US$2981 [IQR 320-9059] vs $8621 [1174-13 930]; p=0·018). There is only fair correlation between these two major value care frameworks, and negative correlations between framework outputs and drug costs. Delivery of optimal cancer care in a sustainable health system will necessitate future oncologists, investigators, and policy makers to reconcile the disconnect between drug cost and clinical benefit. None.

Measuring the Value of New Drugs: Validity and Reliability of 4 Value Assessment Frameworks in the Oncology Setting.

Several organizations have developed frameworks to systematically assess the value of new drugs. To evaluate the convergent validity and interrater reliability of 4 value frameworks to understand the extent to which these tools can facilitate value-based treatment decisions in oncology. Eight panelists used the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), Institute for Clinical and Economic Review (ICER), and National Comprehensive Cancer Network (NCCN) frameworks to conduct value assessments of 15 drugs for advanced lung and breast cancers and castration-refractory prostate cancer. Panelists received instructions and published clinical data required to complete the assessments, assigning each drug a numeric or letter score. Kendall's Coefficient of Concordance for Ranks (Kendall's W) was used to measure convergent validity by cancer type among the 4 frameworks. Intraclass correlation coefficients (ICCs) were used to measure interrater reliability for each framework across cancers. Panelists were surveyed on their experiences. Kendall's W across all 4 frameworks for breast, lung, and prostate cancer drugs was 0.560 (P= 0.010), 0.562 (P = 0.010), and 0.920 (P < 0.001), respectively. Pairwise, Kendall's W for breast cancer drugs was highest for ESMO-ICER and ICER-NCCN (W = 0.950, P = 0.019 for both pairs) and lowest for ASCO-NCCN (W = 0.300, P = 0.748). For lung cancer drugs, W was highest pairwise for ESMO-ICER (W = 0.974, P = 0.007) and lowest for ASCO-NCCN (W = 0.218, P = 0.839); for prostate cancer drugs, pairwise W was highest for ICER-NCCN (W = 1.000, P < 0.001) and lowest for ESMO-ICER and ESMO-NCCN (W = 0.900, P = 0.052 for both pairs). When ranking drugs on distinct framework subdomains, Kendall's W among breast cancer drugs was highest for certainty (ICER, NCCN: W = 0.908, P = 0.046) and lowest for clinical benefit (ASCO, ESMO, NCCN: W = 0.345, P = 0.436). Among lung cancer drugs, W was highest for toxicity (ASCO, ESMO, NCCN: W = 0. 944, P < 0.001) and lowest for certainty (ICER, NCCN: W = 0.230, P = 0.827); and among prostate cancer drugs, it was highest for quality of life (ASCO, ESMO: W = 0.986, P = 0.003) and lowest for toxicity (ASCO, ESMO, NCCN: W = 0.200, P = 0.711). ICC (95% CI) for ASCO, ESMO, ICER, and NCCN were 0.800 (0.660-0.913), 0.818 (0.686-0.921), 0.652 (0.466-0.834), and 0.153 (0.045-0.371), respectively. When scores were rescaled to 0-100, NCCN provided the narrowest band of scores. When asked about their experiences using the ASCO, ESMO, ICER, and NCCN frameworks, panelists generally agreed that the frameworks were logically organized and reasonably easy to use, with NCCN rated somewhat easier. Convergent validity among the ASCO, ESMO, ICER, and NCCN frameworks was fair to excellent, increasing with clinical benefit subdomain concordance and simplicity of drug trial data. Interrater reliability, highest for ASCO and ESMO, improved with clarity of instructions and specificity of score definitions. Continued use, analyses, and refinements of these frameworks will bring us closer to the ultimate goal of using value-based treatment decisions to improve patient care and outcomes. This work was funded by Eisai Inc. Copher and Knoth are employees of Eisai Inc. Bentley, Lee, Zambrano, and Broder are employees of Partnership for Health Analytic Research, a health services research company paid by Eisai Inc. to conduct this research. For this study, Cohen, Huynh, and Neville report fees from Partnership for Health Analytic Research. Outside of this study, Cohen receives grants and direct consulting fees from various companies that manufacture and market pharmaceuticals. Mei reports a grant from Eisai Inc. during this study. The other authors have no disclosures to report. Study concept and design were contributed by Bentley and Broder, with assistance from Elkin and Cohen. Bentley took the lead in data collection, along with Elkin, Huynh, Mukherjea, Neville, Mei, Popescu, Lee, and Zambrano. Data interpretation was performed by Bentley and Broder, along with Elkin, Cohen, Copher, and Knoth. The manuscript was written primarily by Bentley, along with Elkin and Broder, and revised by Bentley, Broder, Elkin, Cohen, Copher, and Knoth. Select components of this work's methods were presented at ISPOR 19th Annual European Congress held in Vienna, Austria, October 29-November 2, 2016, and Society for Medical Decision Making 38th Annual North American Meeting held in Vancouver, Canada, October 23-26, 2016.

Do the American Society of Clinical Oncology (ASCO) Value Framework and the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale measure the same construct of clinical benefit?

6509 Background: Whether the American Society of Clinical Oncology (ASCO) Value Framework and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) measure similar constructs of clinical benefit is unclear. It is also unclear how they relate to quality-adjusted life-years (QALYs) and funding recommendations in the UK and Canada. Methods: Randomized clinical trials (RCTs) of oncology drug approvals by the Food and Drug Administration, European Medicines Agency and Health Canada between January 2006 and August 2015 were identified and scored using the ASCO version 1 (v1) framework (August 10, 2015), ASCO version 2 (v2) framework (May 31, 2016) and ESMO-MCBS (May 30, 2015) by at least two independent reviewers. Spearman correlation coefficients were calculated to assess construct (between frameworks) and criterion validity (against incremental QALYs from the National Institute of Clinical Excellence (NICE) and the pan-Canadian Oncology Drug Review (pCODR)). Associations between scores and NICE/pCODR recommendations were examined by logistic regression models. Inter-rater reliability was assessed using intra-class correlation coefficients. Results: From 109 included RCTs, 108 ASCOv1, 111 ASCOv2 and 83 ESMO scores were determined. Correlation coefficients for ASCOv1 vs. ESMO, ASCOv2 vs. ESMO, and ASCOv1 vs. ASCOv2 were 0.36 (95% CI 0.15-0.54), 0.17 (95% CI -0.06-0.37) and 0.50 (95% CI 0.35-0.63), respectively. Compared with NICE QALYs, correlation coefficients were 0.45 (ASCOv1), 0.53 (ASCOv2) and 0.46 (ESMO); with pCODR QALYs, coefficients were 0.19 (ASCOv1), 0.20 (ASCOv2) and 0.36 (ESMO). None of the frameworks were significantly associated with NICE/pCODR recommendations. Inter-rater reliability was good for all frameworks. Conclusions: The weak-to-moderate correlations between the ASCO frameworks and ESMO-MCBS, with QALYs, and with NICE/pCODR funding recommendations suggest different constructs of clinical benefit measured. Construct convergent validity with the ESMO-MCBS in fact did not increase with the updated ASCO framework.

Validity and Reliability of Value Assessment Frameworks for New Cancer Drugs.

Several organizations have developed frameworks to systematically assess the value of new drugs. These organizations include the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the Institute for Clinical and Economic Review (ICER), and the National Comprehensive Cancer Network (NCCN). To understand the extent to which these four tools can facilitate value-based treatment decisions in oncology. In this pilot study, eight panelists conducted value assessments of five advanced lung cancer drugs using the ASCO, ESMO, and ICER frameworks. The panelists received instructions and published clinical data required to complete the assessments. Published NCCN framework scores were abstracted. The Kendall's W coefficient was used to measure convergent validity among the four frameworks. Intraclass correlation coefficients were used to measure inter-rater reliability among the ASCO, ESMO, and ICER frameworks. Sensitivity analyses were conducted. Drugs were ranked similarly by the four frameworks, with Kendall's W of 0.703 (P = 0.006) across all the four frameworks. Pairwise, Kendall's W was the highest for ESMO-ICER (W = 0.974; P = 0.007) and ASCO-NCCN (W = 0.944; P = 0.022) and the lowest for ICER-NCCN (W = 0.647; P = 0.315) and ESMO-NCCN (W = 0.611; P = 0.360). Intraclass correlation coefficients (confidence interval [CI]) for the ASCO, ESMO, and ICER frameworks were 0.786 (95% CI 0.517-0.970), 0.804 (95% CI 0.545-0.973), and 0.281 (95% CI 0.055-0.799), respectively. When scores were rescaled to 0 to 100, the ICER framework provided the narrowest band of scores. The ASCO, ESMO, ICER, and NCCN frameworks demonstrated convergent validity, despite differences in conceptual approaches used. The ASCO inter-rater reliability was high, although potentially at the cost of user burden. The ICER inter-rater reliability was poor, possibly because of its failure to distinguish differential value among the sample of drugs tested. Refinements of all frameworks should continue on the basis of further testing and stakeholder feedback.

Assessment of Value Using the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) Frameworks for Novel Therapies for the Hematologic Malignancies

IntroductionThe cost of cancer care is rising to unsustainable levels, predominantly driven by an increase in expenditures for novel therapies. In the era of biologic therapies, these excessive costs are disproportionately borne by patients with hematologic malignancies. Although the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) have both developed frameworks to determine the relative value associated with new solid tumor therapies (and specifically with ESMO, to the exclusion of therapies in hematology), it is unclear if they can be applied in the assessment of value of treatments for blood cancers.MethodsWe evaluated the value of new therapies for hematologic malignancies using the ASCO (version 1 from August 10, 2015 and version 2 from May 31, 2016) and ESMO (version 1 or v1) frameworks. All US Food and Drug Administration, European Medicinal Agency, or Health Canada approved parenteral therapies for hematologic malignancies from 2006-2015 were identified. A systematic review of randomized controlled trials (RCTs) for these therapies was conducted. Two reviewers independently scored the trials using the ASCO value framework v1 (range of scores -20 to 130), v2 (lower range undefined to 180) and ESMO Magnitude of Clinical Benefit Scale (range 1-5). Disagreements were descriptively presented and resolved by consensus. The concurrent validity between the ASCO and ESMO scores was measured by the Spearman correlation coefficient.ResultsTwenty-three RCTs in malignant hematology were identified and scored. Seven of 23 studies reported primary outcomes unique to hematologic malignancies (for example, time-to-progression in myeloma, cytogenetic response in chronic myeloid leukemia, and symptomatic response in multicentric Castleman's), other than the main outcomes used to derive ASCO/ESMO scores (overall and progression-free survival). The median ASCO v1 score for the trials was 24 (IQR 22-40, min 6 and max 53). The median ASCO v2 score was 26.7 (IQR 17.4-37.6, min -33.3 and max 116.3). The median ESMO score was 2 (IQR 2-3, min 1 and max 4). Using the ASCO v1 framework, 10 studies resulted in disagreements in scoring, predominantly due to variable interpretations of the scoring system. Two studies could not be scored. One study did not report toxicity grades and another study of maintenance rituximab in lymphoma did not report on conventional oncology outcomes that could fit into the ASCO model. Using the ASCO v2 framework, 14 studies resulted in disagreements, predominantly due to differences in scoring toxicities. With the ESMO Scale, 12 studies resulted in disagreements, most occurring due to variable interpretations in scoring survival or progression-free survival outcomes when median values were not provided in the study publication. Two studies could not be scored with the ESMO Scale. One study did not report hazard ratios and another study's reported outcomes did not fit the ESMO scoring options. The correlation coefficient between ASCO v1 and ESMO scores was 0.10 (95% CI: -0.37 to 0.53), suggesting that the correlation was not significantly different from chance only. The coefficient between ASCO v2 and ESMO was -0.21 (95% CI: -0.59 to 0.24) and between ASCO v1 and ASCO v2 was 0.30 (95% CI: -0.15 to 0.65).ConclusionsCurrent value frameworks are challenging to apply to therapies for hematologic malignancies. When studies could be scored, the correlations between ASCO (v1 and v2) and ESMO results were poor, suggesting that these frameworks may not reliably identify the value of therapies in hematology. Consideration for the unique outcomes and toxicities in this population is warranted. The ASCO and ESMO frameworks continue to evolve, and a partnership with societies representing hematologists and their patients would be fruitful. DisclosuresNo relevant conflicts of interest to declare.

BI3 - Assessing Prescription Drug Value In The United States: A Hypothetical Example Comparing Asco And Icer Framework Outcomes

Increasing oncology drug prices have led to several value-based framework initiatives in the US. To understand the key determinants impacting decision-making, a hypothetical oncology treatment was evaluated using the American Society of Clinical Oncology (ASCO) and Institute for Clinical and Economic Review (ICER) frameworks. The ASCO adjuvant setting value framework estimates the net health benefit (NHB) of an oncology drug using trial-based clinical benefit and toxicity. ICER’s framework evaluates the “Care Value” in the context of clinical effectiveness, incremental cost, benefits/disadvantages, and other contextual factors. Care value is then benchmarked to determine value to a health system. A hypothetical treatment was compared to best standard care (BSC) for a population with 0.5% disease prevalence. Treatment was assumed to reduce risk by 5% (overall survival [OS]) and 10% (progression-free survival [PFS]), cost 10% more than BSC, improve tolerability, and reduce administration burden. NHB was calculated using the ASCO framework. Incremental cost/quality-adjusted life-year (QALY) was determined using a partitioned survival model; budget impact was estimated separately using drug, administration and adverse event costs. Costs were assessed within ICER’s value-based framework using these models. Various scenarios were utilized to compare and contrast outcomes of the frameworks. NHB, cost/QALY gained, and budget impact were 58/100, $318,274, and ~$11 million, respectively. Changes in OS impact assessed drug value within both frameworks. The ASCO framework is sensitive to changes in tolerability while this effect was modest in the ICER framework. Substantial drug price reductions may be necessary in order to meet ICER thresholds even when maximum NHBs are present as assessed within the ASCO framework. Overall budget impact is considered in the ICER framework, but is unlikely to impact decision-making for low-prevalence diseases. The ASCO and ICER value frameworks may favor different types of drugs depending upon their clinical and economic profile.