Purpose Whether the ASCO Value Framework and the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (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 United Kingdom and Canada. Methods Randomized clinical trials of oncology drug approvals by the US Food and Drug Administration, European Medicines Agency, and Health Canada between 2006 and August 2015 were identified and scored using the ASCO version 1 (v1) framework, ASCO version 2 (v2) framework, and ESMO-MCBS by at least two independent reviewers. Spearman correlation coefficients were calculated to assess construct (between frameworks) and criterion validity (against QALYs from the National Institute for Health and Care Excellence NICE and the pan-Canadian Oncology Drug Review pCODR). Associations between scores and NICE/pCODR recommendations were examined. Inter-rater reliability was assessed using intraclass correlation coefficients. Results From 109 included randomized clinical trials, 108 ASCOv1, 111 ASCOv2, and 83 ESMO scores were determined. Correlation coefficients for ASCOv1 versus ESMO, ASCOv2 versus ESMO, and ASCOv1 versus ASCOv2 were 0.36 (95% CI, 0.15 to 0.54), 0.17 (95% CI, -0.06 to 0.37), and 0.50 (95% CI, 0.35 to 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. Conclusion The weak-to-moderate correlations of the ASCO frameworks with the ESMO-MCBS, as well as their correlations with QALYs and with NICE/pCODR funding recommendations, suggest different constructs of clinical benefit measured. Construct convergent validity with the ESMO-MCBS did not increase with the updated ASCO framework.
Abstract
Background
older patients are commonly believed to derive less benefit from cancer drugs, even if they fulfil clinical trial eligibility Talarico et al. (2004, J Clin Oncol, 22(22):4626–31). ...We aim to examine if novel oncology drugs provide differential age-based treatment outcomes for patients on clinical trials.
Methods
a systematic review of randomised control trials (RCTs) cited for clinical efficacy evidence in novel oncology drug approvals by the Food and Drug Administration, European Medicines Agency and Health Canada between 2006 and 2017 was conducted. Studies reporting age-based subgroup analyses for overall or progression-free survival (OS/PFS) were included. Hazard ratios (HRs) and confidence intervals (CIs) for age-based subgroups were extracted. Meta-analyses with random effects were conducted, examining patient subgroups <65 and ≥65 years separately and pooled HRs of studies primary endpoints (OS or PFS) compared to examine if differences existed between age-based subgroups. Sensitivity analyses were conducted for cancer type, primary endpoint and systemic treatment.
Results
one-hundred-two RCTs, including 65,122 patients, met the inclusion criteria. One study reported age-based toxicity and none reported age-based quality of life (QOL) results. Pooled HRs 95% CIs for patients <65 and ≥65 years were 0.61 0.57–0.65 and 0.65 0.61–0.70, respectively, with no difference between them (P = 0.14). Sensitivity analyses revealed similar results.
Conclusion
our results suggest that older and young patients, who fulfil clinical trial eligibility, may derive similar relative survival benefits from novel oncology drugs. There is, however, a need to report age-based toxicity and QOL results to support patient discussions regarding the balance of treatment benefit and harm, to encourage informed decision-making.
The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration was established to develop a framework for generating and using real-world evidence (RWE) to inform the ...reassessment of cancer drugs following initial health technology assessment (HTA). The Reassessment and Uptake Working Group (RWG) is one of the five established CanREValue Working Groups. The RWG aims to develop considerations for incorporating RWE for HTA reassessment and strategies for using RWE to reassess drug funding decisions. Between February 2018 and December 2019, the RWG attended four teleconferences (with follow-up surveys) and two in-person meetings to discuss recommendations for the development of a reassessment process and potential barriers and facilitators. Modified Delphi methods were used to gather input. A draft report of recommendations (to December 2018) was shared for public consultation (December 2019 to January 2020). Initial considerations for developing a reassessment process were proposed. Specifically, reassessment can be initiated by diverse stakeholders, including decision makers from public drug plans or industry stakeholders. The reassessment process should be modelled after existing deliberation and recommendation frameworks used by HTA agencies. Proposed reassessment outcome categories include maintaining status quo, revisiting funding criteria, renegotiating price, or disinvesting. Overall, these initial considerations will serve as the basis for future advancements by the Collaboration.
Purpose
The National Institutes of Health’s policy for the inclusion of females in clinical research was a pivotal step towards the consideration of sex as a biological variable, which is of ...particular importance in oncology, given differential incidence and outcomes of cancer between the sexes, and known pharmacodynamic, pharmacokinetic, and immunological differences. Therefore, we aim to investigate if such biological sex-based differences translate to clinically meaningful outcome differences from recently approved systemic oncology therapies.
Methods
A systematic review of randomized control trials (RCTs) cited in Food and Drug Administration, European Medicines Agency, and Health Canada approvals was conducted. Chemotherapy, targeted agents, and immunotherapy RCTs reporting sex-based sub-group analyses for overall/progression-free survival (OS/PFS) were considered. Hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized. Sensitivity analyses for survival endpoints, drug type, and cancer site were conducted.
Results
Ninety-nine RCTs were included, representing 62,384 patients (23,574 (38%) female). Pooled OS HRs 95% CIs were 0.77 0.72–0.81 and 0.76 0.72–0.79 for females and males, respectively (
P
= 0.73), and 0.51 0.47–0.56 and 0.57 0.53–0.61 (
P
= 0.08) for PFS. Sensitivity analyses yielded similar results. No RCTs reported sex-based toxicity or quality-of-life (QOL) data.
Conclusion
Female and male patients appear to derive comparable benefits from recently approved systemic oncology therapies. Future RCTs are encouraged to report sex-based toxicity and QOL data.
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Introduction
The American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) have been developed to ...quantify clinical benefit and establish value of anticancer therapies. While ASCO-VF is indifferent to the cancer type, ESMO-MCBS does not endorse their framework for scoring hematologic malignancies. The reason for this exclusion and whether ESMO-MCBS can be applied in the hematologic setting is still unclear. The purpose of this study was to determine whether measurement characteristics of ESMO-MCBS are similar to ASCO-VF when evaluating hematologic malignancies.
Methods
Phase III randomized controlled trials (RCTs) of hematological malignancy drugs approved by the US Food and Drug Administration, European Medicines Agency and Health Canada between 2006 to 2017 were identified and scored using ASCO-VF (version 2) and ESMO-MCBS (version 1.1) by two independent reviewers. We assessed the convergent construct validity of the two frameworks to determine the degree to which these two theoretically similar measures assess the same construct of clinical benefit. Spearman correlation coefficients were calculated for the preliminary framework scores (using only the survival efficacy components of the scores) and the final framework scores (following adjustment of the preliminary scores with toxicity and quality of life (QoL) data). Correlation coefficients were also calculated for each subtype of blood cancer separately. The inter-rater reliability of the frameworks was assessed using intra-class correlation coefficients (ICC).
Results
In total, 48 studies were included and scored using the ASCO-VF (median score: 34.38; IQR: 22.26 - 51.69) and ESMO-MCBS (median score: 3; IQR: 2.75 - 4). Out of the 48 RCTs, 16 (33%) evaluated novel anticancer treatments for leukemia, 23 (48%) for myeloma, 8 (17%) for lymphoma and 1 (2%) for myelodysplastic syndromes. Spearman correlation coefficients between both frameworks for preliminary and final scores were 0.01 (95% CI, -0.23 to 0.25) and -0.02 (95% CI, -0.28 to 0.24), respectively. When stratified by indication, the correlation coefficients for the preliminary scores were -0.01 (95% CI, -0.50 to 0.49), -0.06 (95% CI, -0.46 to 0.29), and 0.58 (95% CI, -0.21 to 0.91) for leukemia, myeloma, and lymphoma, respectively. The correlation coefficients for the final scores by cancer indications were -0.09 (95% CI, -0.56 to 0.42), 0.15 (95% CI, -0.22 to 0.49), and -0.29 (95% CI, -0.86 to 0.52) for leukemia, myeloma, and lymphoma, respectively (Table 1). For both preliminary and final scores, ASCO-VF showed excellent and ESMO-MCBS showed good inter-rater reliability (Table 2).
Conclusions
Our results suggest divergent validity of ESMO-MCBS and ASCO-VF when assessing hematologic malignancies, indicating that these frameworks likely measure different constructs of clinical benefit in this setting. Furthermore, the ASCO-VF demonstrated improved inter-rater reliability compared to ESMO-MCBS. It remains unclear which framework is correctly assessing the clinical benefit of hematologic drugs. To better understand if one framework is more accurate in its evaluation, future research that compares these frameworks to other established measures of clinical benefit (such as quality adjusted life years) in the hematologic setting is warranted. Due to the lack of construct validity and ESMO's endorsement of their framework solely for solid cancers, the ASCO-VF should currently be considered for use in the hematologic setting.
No relevant conflicts of interest to declare.
Introduction
The 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.
Methods
We 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.
Results
Twenty-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).
Conclusions
Current 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.
No relevant conflicts of interest to declare.
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