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SC29 - Access, Value Assessments and Affordability of Novel Therapies (ID 353)
- Event: WCLC 2016
- Type: Science Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
SC29.03 - Value-based Assessments in Lung Cancer Therapy: The ESMO Perspective (ID 6723)
11:00 - 12:30 | Author(s): N. Cherny
The value of any treatment is determined by the magnitude of its clinical benefit (MCB) balanced against its cost. Whereas costs of procurement and out-of-pocket expenditures vary from country to country, the MCB, as derived from well-designed clinical trials, is a relative constant. Consequently, meaningful discussion of value and relative value are predicated on an understanding of the MCB. MCB in this context refers to the added benefit, usually compared to a control (the best current standard care). Until recently there was no standard tool for grading the MCB of cancer therapies, which may range from trivial (median progression-free survival advantage of only a few weeks) to substantial (improved long term survival). Recognising the importance of presenting clear and unbiased statements regarding the MCB from new therapeutic approaches derived from high quality clinical trials the European Society for Medical Oncology (ESMO) has developed a validated and reproducible tool to assess the MCB for cancer medicines, the ESMO MCB Scale (ESMO-MCBS). This tool uses a rational, structured and consistent approach to derive a relative ranking of the magnitude of clinically meaningful benefit that can be expected from a new anti-cancer treatment. The ESMO-MCBS is an important first step to the critical public policy issue of value in cancer care, helping to frame the appropriate use of limited public and personal resources to deliver cost effective and affordable cancer care. The ESMO-MCBS v1.0 has been developed and validated for solid cancers. The tool is presented in two parts. Form 1 is used to evaluate adjuvant and other treatments with curative intent. Form 2 (a, b or c) is used to evaluate non-curative interventions, with form 2a for studies with OS as the primary outcome, form 2b for studies with PFS or TTP as primary outcomes, 2c for studies with QoL, toxicity or response rate as primary outcomes and for non-inferiority studies. Form 2a is prognostically sub-stratified for studies where the control arm produced OS greater or less than or equal to 1 year, and form 2b is stratified for studies where the control arm PFS is <6m or >6mth. Version 1.0 can be applied to comparative outcome studies evaluating the relative benefit of treatments using outcomes of survival, QoL, surrogate outcomes for survival or QoL (DFI, EFS, TTR, PFS and TTP) or treatment toxicity in solid cancers. Eligible studies can have either a randomised or comparative cohort design or a meta- analysis which report statistically significant benefit (P>0.05, upper limit of 95[th] percentile for HR <1) from any one, or more of the evaluated outcomes. For treatments with curative intent, the scale is graded A, B or C. Grades A and B represent a high level of clinical benefit . For cancers treated without curative intent, the scale is graded 5, 4, 3, 2, 1, where grades 5 and 4 represent a high level of proven clinical benefit. The scale incorporates a “dual rule” taking into account the variability of the estimated HR from a study, the lower limit of the 95% Confidence Interval (CI) for the HR is compared to specified threshold values; and second the observed absolute difference in treatment outcomes is compared to the minimum absolute gain considered as beneficial. Different candidate threshold values for HR and absolute gains for survival, DFS and PFS, adjusted to represent as accurately as possible the expert opinion of the oncology community, have been explored through extensive simulations. In all forms HR thresholds refer to the lower extreme of the 95% CI, analogous to the convention of evaluating null effect by the upper limit of the 95%CI <1. The performance of the evaluation rule based on the lower limit of the 95% CI of HR, was compared to the simpler rule of using a cut-off for the point estimate of HR, in conjunction with the additional rule on the minimum absolute gain in treatment outcome. The simulation results under different HR values and corresponding power, favoured the proposed approach to use the lower limit of the 95% CI which takes into account the variability of the estimate. The concern that small studies generate wider confidence intervals is real and justified, however in the ESMO-MCBS v1.0 all high grading scores in a non-curative setting incorporate both HR and absolute gain to mitigate against over valuing small studies with wide HR. This structured and disciplined approach to deriving estimates of clinically meaningful benefit from published data can be used in a range of settings: it can help public policy-makers advance “accountability for reasonableness” in resource allocation deliberations, contribute to formulation of clinical guidelines , in the clinic it can help clinicians to weigh the relative merits of competing relevant therapeutic options in situations in which there is no direct comparative data and grading may also be of benefit when explaining the relative merit of therapeutic options to patients and their families. Finally ESMO-MCBS may be of use to editors, peer reviewers and commentators in considering the clinical significance of research findings from randomised clinical studies, cohort studies and meta-analyses with statistically significant positive findings. Experience accrued in evaluating trials in the management of non small-cell lung cancer have been critical in the development process of v1.0, particularly with regard to the interpretation of PFS is studies with extensive crossover on progression that precludes meaningful OS survival results. In this cohort of studies, the inclusion of QoL evaluation was able to generate confirmatory secondary evidence to support the clinical significance of the PFS findings. The proliferation of new agents targeting NSCLC with specific mutations that have been approved on the basis if Phase I-II data have challenged the working group to expand the scope of the scale to include single arm studies. This new subscale will be among the amendments in the planned revision that is under development and scheduled for publication early next year. 1. Cherny NI, Sullivan R, Dafni U et al. A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Annals of oncology 2015; 26: 1547-1573.
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