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Cited by 818Health Systems, Economic Evaluations, Quality of LifeStatistical Methods in Clinical TrialsEconomic and Financial Impacts of Cancer

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)

Open access
Cherny, N.I., Sullivan, R., Dafni, U., Kerst, J.M., Sobrero, A., Zielinski, C., de Vries, E.G.E., Piccart, M.J.·2015·Annals of Oncology
DOI 10.1093/annonc/mdv249
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Abstract

The value of any new therapeutic strategy or treatment is determined by the magnitude of its clinical benefit balanced against its cost. Evidence for clinical benefit from new treatment options is derived from clinical research, in particular phase III randomised trials, which generate unbiased data regarding the efficacy, benefit and safety of new therapeutic approaches. To date, there is no standard tool for grading the magnitude of clinical benefit of cancer therapies, which may range from trivial (median progression-free survival advantage of only a few weeks) to substantial (improved long-term survival). Indeed, in the absence of a standardised approach for grading the magnitude of clinical benefit, conclusions and recommendations derived from studies are often hotly disputed and very modest incremental advances have often been presented, discussed and promoted as major advances or 'breakthroughs'. Recognising the importance of presenting clear and unbiased statements regarding the magnitude of the clinical benefit 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 magnitude of clinical benefit for cancer medicines, the ESMO Magnitude of Clinical Benefit 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 will be a dynamic tool and its criteria will be revised on a regular basis.

AI snapshot

Written from the paper’s full text.

TL;DR

ESMO developed and field-tested a standardised tool, ESMO-MCBS v1.0, to grade how much clinical benefit anticancer therapies provide in solid tumours. It uses separate forms for curative and non-curative settings, combining hazard-ratio thresholds with absolute survival gains and adjustments for quality of life and toxicity.

Key findings

  • The scale has Form 1 for curative or adjuvant treatment, graded A/B/C, where A and B indicate high benefit; Forms 2a, 2b and 2c grade non-curative treatment from 5 to 1, where 5 and 4 indicate high proven benefit. Form 2a is stratified by control median overall survival of 12 months or less versus more than 12 months, and Form 2b by control median progression-free survival of 6 months or less versus more than 6 months.
  • For non-curative therapy with overall survival as the primary outcome and control median survival of 12 months or less, the highest preliminary grade requires a hazard ratio of 0.65 or lower plus a gain of at least 3 months, or at least a 10% increase in 2-year survival. With control median survival above 12 months, it requires a hazard ratio of 0.70 or lower plus a gain of at least 5 months, or at least a 10% increase in 3-year survival.
  • When progression-free survival is the primary outcome, the maximum preliminary score is capped at 3; for control median progression-free survival of 6 months or less, the top preliminary grade requires a hazard ratio of 0.65 or lower and a gain of at least 1.5 months, while above 6 months it requires a hazard ratio of 0.65 or lower and a gain of at least 3 months.
  • Field testing across solid tumours produced scores such as 5 for T-DM1 in EMILIA, FOLFIRINOX in pancreatic cancer, and radium-223 in ALSYMPCA; 4 for erlotinib in OPTIMAL; and 1 for regorafenib in CORRECT. The scale went through 13 redrafts before v1.0 and was reviewed by 276 ESMO faculty members and 51 biostatisticians.

Methods

  • An ESMO Task Force was set up in March 2013. A first draft was developed through a snowball method from prior models and reviewed by 276 faculty members and 51 expert biostatisticians; a second-generation draft was field-tested by the Task Force, the ESMO Guidelines Committee and invited experts, with repeated modification through 13 redrafts before v1.0.
  • The grading rule uses two components: the lower bound of the 95% confidence interval for the hazard ratio compared with specified thresholds, and the observed absolute difference in treatment outcome compared with a minimum considered beneficial. Candidate thresholds were explored through simulations, and the final scale separates curative from non-curative settings and stratifies by control median overall survival or progression-free survival.
  • Field testing applied the scale to a wide range of contemporary and historical solid tumour studies. Discrepancies between graders were generally attributed to inaccurate data extraction, differing interpretation of toxicity significance or severity, or misapplication of grading criteria.

Limitations

  • Stated in the paper: the scale applies only to comparative research outcomes and cannot be used when benefit evidence comes from single-arm studies; the weighting of evidence and threshold choices involve judgements open to dispute; scores are not generalisable outside the indication and context evaluated; and control-arm quality, crossover or unbalanced crossover, and later follow-up reports can skew scores.
  • Stated in the paper: ESMO-MCBS v1.0 was developed only for solid cancers, and pathological complete remission after neoadjuvant therapy was excluded because evidence for it as a consistent surrogate for survival was lacking.
  • Evident from the text: the scale is presented as a dynamic first version whose criteria will be revised, and the field-testing tables include notes about score upgrades and corrections, indicating that scoring rules and applications were still evolving.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/annonc/mdv249

Cites

149 of 149 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 52 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Simulation results under different HR values and corresponding power favoured using the lower limit of the 95% CI of HR rather than the point estimate, because it accounts for variability of the estimate.

    “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.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The expert opinion of the oncology community can be accurately represented by threshold values for HR and absolute gains.
  • Findingcitation

    Maturation of survival data increased the ESMO-MCBS score of vemurafenib in metastatic melanoma from 3 based on PFS to 4 based on OS.

    “Maturation of survival data also increased the ESMO-MCBS score of vemurafenib in the treatment of metastatic melanoma [116, 117] from ESMO-MCBS 3 based on PFS to 4, based on OS.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [116] source

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    • cites [117] source

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  • Findingcitation

    In the field testing, chemotherapy with or without trastuzumab in (neo)adjuvant HER-2-positive breast cancer was assigned ESMO-MCBS grade A.

    “Chemotherapy ± trastuzumab | HERA | (Neo)adjuvant HER-2- | DFS | 2-year DFS | 8.40% | 0.54 (0.43-0.67) | | | | | A | [ 56]”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Findingcitation

    In the field testing, ridaforolimus compared with placebo in sarcoma after response or stable disease with first-line treatment was assigned ESMO-MCBS grade 1.

    “Ridaforolimus | SUCCEED | Sarcoma after | PFS | 14.6 weeks | 3.1 weeks | 0.72 (0.61-0.85) | | | | | | 1 | [114]”
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    • cites [114] source

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  • Findingcitation

    In the field testing, T-DM1 compared with lapatinib plus capecitabine in second-line metastatic breast cancer after trastuzumab failure was assigned ESMO-MCBS grade 5.

    “T-DM1 versus lapatinib + | EMILIA | Second-line metastatic after | PFS and OS | 6.4 months | 3.2 months 0.65 (0.55-0.77) 25 months | 6.8 months 0.68 (0.55-0.85) Delayed deterioration | 5 | [57, 58]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [57] source

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    • cites [58] source

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  • May combine two claims. 15
  • Classified as probably not a substantial claim. 22
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingnone given

    For a standard treatment median survival of 6 months, an absolute gain of 3 months corresponds to an HR of 0.67, while a gain of 1.5 months corresponds to an HR of 0.8.

    “For example, for a standard treatment median survival of 6 months, an absolute gain of 3 months corresponds to an HR = 0.67, while a gain of 1.5 months corresponds to an HR = 0.8.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The expert opinion of the oncology community can be accurately represented by threshold values for HR and absolute gains.

  • May combine two claims.

    Findingnone given

    In non-curative therapies, the ASCO recommended thresholds for survival benefit correlate very closely with the thresholds for ESMO-MCBS score of 4-5 in form 2a, and the recommended thresholds for PFS correlate closely with the thresholds for ESMO-MCBS score of 3-4 in form 2b.

    “Interestingly, in non-curative therapies, the ASCO recommended thresholds for survival benefit correlate very closely to the thresholds for ESMO-MCBS score of 4-5 (in form 2a) and the recommended thresholds for PFS correlate closely with the thresholds for ESMO-MCBS score of 3-4 which is the highest attainable when the primary outcome is PFS (in form 2b).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The ESMO-MCBS can be applied to comparative outcome studies evaluating relative benefit of treatments using survival, QoL, surrogate outcomes for survival or QoL, or treatment toxicity in solid cancers.

    “The ESMO-MCBS 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.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Evidence for clinical benefit from new treatments is derived from comparative outcome studies, most commonly phase III randomised trials, which generate unbiased data.

  • May combine two claims.

    Premisecitation

    In non-curative settings, PFS and TTP provide information about biological activity and may indicate benefit for some patients.

    “In studies evaluating therapies in non-curative settings, progressionfree survival (PFS), and time to progression (TTP) provide information about biological activity and may indicate benefit for some patients [18,19]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18]

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    • cites [19]

      Not checked in the free run.

    • Rests on an assumption: Evidence for clinical benefit from new treatments is derived from comparative outcome studies, most commonly phase III randomised trials, which generate unbiased data.

  • May combine two claims.

    Premisecitation

    In the absence of a standardised grading approach, conclusions and recommendations from studies are often disputed, and modest incremental advances are often presented as major breakthroughs.

    “Indeed, in the absence of a standardised approach for grading, the magnitude of clinical benefit, conclusions and recommendations derived from studies are often hotly disputed [25] and very modest incremental advances have often been presented, discussed and promoted as major advances or 'breakthroughs' [5,[25][26][27][28][29].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25]

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    • cites [5,[25][26][27][28][29]

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  • May combine two claims.

    Interpretationcitation

    Overestimating or overstating benefits from new interventions can cause harm, including confounding public policy, undermining research credibility, harming patients, and fueling inappropriate hype.

    “Overestimating or overstating the benefits from new intervention can cause harm: it confounds public policy decision making [29], undermines the credibility of oncology research reporting [26,29,30], harms patients who choose to undertake treatments based on exaggerated expectations that may subject them to either risk of adverse effects, inconvenience or substantial personal costs [26,28] and, in”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [29] source

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    • cites [26]

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    • cites [30] source

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    • cites [28]

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    ESMO-MCBS v1.0 has been developed only for solid cancers.

    “The ESMO Magnitude of Clinical Benefit Scale version 1 (ESMO-MCBS v1.0) (Appendix 1) has been developed only for solid cancers.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Evidence for clinical benefit from new treatments is derived from comparative outcome studies, most commonly phase III randomised trials, which generate unbiased data.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisecitation

    The value of any new therapeutic strategy or treatment is determined by the magnitude of its clinical benefit balanced against its cost.

    “The value of any new therapeutic strategy or treatment is determined by the magnitude of its clinical benefit balanced against its cost [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    Hyper-mature data from studies un-blinded after compelling early results with subsequent access to the superior arm are contaminated, and late intention-to-treat follow-up data are not evaluable.

    “Hyper-mature data from studies that were un-blinded after compelling early results with subsequent access to the superior arm are contaminated, subsequently late intentionto-treat (ITT) follow-up data are not evaluable [37,38].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [37]

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    • cites [38]

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  • May combine two claims.

    Interpretationcitation

    Eligible studies for ESMO-MCBS can have a randomised or comparative cohort design or be a meta-analysis reporting statistically significant benefit from one or more evaluated outcomes.

    “Eligible studies can have either a randomised or comparative cohort design [35,36] or a meta-analysis which report statistically significant benefit from any one, or more of the evaluated outcomes.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [35] source

      Not checked in the free run.

    • cites [36]

      Not checked in the free run.

    • Rests on an assumption: Evidence for clinical benefit from new treatments is derived from comparative outcome studies, most commonly phase III randomised trials, which generate unbiased data.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The ESMO-MCBS is presented in two parts because of profound differences between curative and palliative settings.

    “Given the profound differences between the curative and palliative settings, the tool is presented in two parts.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Evidence for clinical benefit from new treatments is derived from comparative outcome studies, most commonly phase III randomised trials, which generate unbiased data.

  • May combine two claims.

    Premisecitation

    PFS and TTP are not reliable surrogates for improved survival or QoL in non-curative settings.

    “however, they are not reliable surrogates for improved survival [18,[20][21][22][23] or QoL [23,24].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [18,[20][21][22][23]

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    • cites [23]

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    • cites [24]

      Not checked in the free run.

    • Rests on an assumption: Evidence for clinical benefit from new treatments is derived from comparative outcome studies, most commonly phase III randomised trials, which generate unbiased data.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation

    While a high ESMO-MCBS score does not automatically imply high value, the scale can be used to frame value considerations and help public policy-makers advance 'accountability for reasonableness' in resource allocation.

    “While a high ESMO-MCBS score does not automatically imply high value (that depends on the price), the scale can be utilised by to frame such considerations [147] and can help public policy-makers advance 'accountability for reasonableness' in resource allocation deliberations [134,135].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [147]

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    • cites [134]

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    • cites [135]

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Statistical approaches to estimate longer term clinical outcomes despite substantial treatment crossover have been developed and applied.

    “Statistical approaches to estimate longer term clinical outcomes despite substantial treatment crossover have been developed [139, 140], and applied [141-144].”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [139]

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    • cites [140]

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    • cites [141]

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    • cites [142]

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    • cites [143]

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    • cites [144]

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  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationnone given

    The 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.

    “The 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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Consequently, the ESMO-MCBS score for a particular medication or therapeutic approach may vary depending on the indication and between studies.

    “Consequently, the ESMO-MCBS score for a particular medication or therapeutic approach may vary depending on the specifics of the indication and may vary between studies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The ESMO-MCBS incorporates a structured, rational and valid approach to data interpretation and analysis that reduces judgements affected by bias or idiosyncratic interpretation.

    “The ESMO-MCBS incorporates a structured, rational and valid approach to data interpretation and analysis that reduces the tendency to have judgements affected by bias or uninformed and/or idiosyncratic data interpretation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    For cancer therapies, the ESMO-MCBS provides a clear, well-structured and validated mechanism to indicate the magnitude of benefit in addition to the level of evidence that can inform national and international guidelines.

    “For cancer therapies, the ESMO-MCBS scale provides a clear, well-structured and validated mechanism to indicate the magnitude of benefit in addition to the level of evidence that can inform both national and international (e.g.ESMO) guidelines.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationnone given

    The grading may be of benefit in explaining the relative merit of therapeutic options to patients and their families.

    “The grading may also be of benefit in explaining the relative merit of therapeutic options to patients and their families.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The final levels of evidence and grades of recommendation were agreed without significant disagreement among panel members, except where openly noted in the text.

    “Final given levels of evidence and grades of recommendation in this manuscript were consented without significant divergence between the different panel members if not otherwise openly specified in the text (Table 1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    The validity of results may be influenced by the quality and design of the study.

    “The validity of the results may be influenced by the quality and design of the study.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    In studies that allow crossover on subsequent therapy, this may be the best available evidence of activity since subsequent therapies may reduce the likelihood of observing survival benefit.

    “In studies that allow crossover on subsequent therapy, this may be the best available evidence of activity since subsequent therapies may reduce the likelihood of observing survival benefit.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The writing group conducted a detailed literature review for the manuscript, which was extended to all other Panel Members after the preliminary paper was circulated.

    “A detailed literature review was done by the writing group for this manuscript and was extended after sending out the preliminary paper to all other Panel Members (see Appendix).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The ESMO-MCBS can only be applied to comparative research outcomes and is not applicable when evidence of benefit derives from single-arm studies.

    “The ESMO-MCBS can only be applied to comparative research outcomes; it is therefore not applicable when evidence of benefit derives from single-arm studies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationnone given

    This information may be especially helpful when treatments incorporate substantial out-of-pocket costs and the real value of treatment needs to be candidly addressed to avoid over-investment or sacrifice of limited financial resources for treatments with only limited benefit.

    “This information may be especially helpful when treatments incorporate substantial out of pocket costs and the real 'value' of the treatment needs to be candidly addressed to avoid over investment or sacrifice of limited financial resources to pay for treatments that have only limited magnitude of benefit.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Study design and conductnone given

    The validity of the ESMO-MCBS is derived from statistical validity.

    “(iv) statistical validity”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    The ESMO-MCBS v1.0 represents a first version of a well-validated tool to stratify the magnitude of clinical benefit for new anti-cancer treatments and is applicable over a full range of solid tumours.

    “It represents a first version of a well-validated tool to stratify the magnitude of clinical benefit for new anti-cancer treatments and is applicable over a full range of solid tumours.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The process of relative weighting of evidence and thresholds for HR and absolute gains involves judgements and subjective considerations that are amenable to dispute and challenge.

    “The process of relative weighting of evidence and the thresholds for HR and absolute gains involves judgements and subjective considerations which are amenable to dispute and challenge and indeed, this is invited as part of the dynamic process of peer review and further development.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Grading derived from the ESMO-MCBS provides a backbone for value evaluations for cancer medicines.

    “Grading derived from the ESMO-MCBS provides a backbone for value evaluations for cancer medicines.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The GRADE Working Group emphasised that a particular quality of evidence does not necessarily imply a particular strength of recommendation.

    “The GRADE working group emphasised that a particular quality of evidence does not necessarily imply a particular strength of recommendation [149, 150].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [149] source

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    • cites [150] source

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  • Classified as probably not a substantial claim.

    Interpretationnone given

    The data encapsulated in ESMO-MCBS scoring can help clinicians weigh the relative merits of competing therapeutic options when no direct comparative data exist.

    “The data encapsulated in ESMO-MCBS scoring can help clinicians to weigh the relative merits of competing relevant therapeutic options in situations in which there is no direct comparative data comparing the available therapeutic options.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    While these approaches are encouraging, they incorporate a range of assumptions and are not universally accepted.

    “While these approaches are encouraging, they incorporate a range of assumptions and are not universally accepted [145].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [145]

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The level-of-evidence and grade-of-recommendation scores were proposed and fully agreed within the writing committee that convened at the Lugano Consensus Conference.

    “The scores for level of evidence and grade of recommendation were proposed and fully consented within the writing committee that met at the Consensus Conference in Lugano.”
    Quote in the paperNot a substantial claim
33 of 33

  • The paper relies on this without support.

    Evidence for clinical benefit from new treatments is derived from comparative outcome studies, most commonly phase III randomised trials, which generate unbiased data.

    “Evidence for clinical benefit from new treatment approaches is derived from comparative outcome studies, most commonly phase III randomised clinical trials, which generate ostensibly unbiased data regarding the efficacy, benefit and safety of new therapeutic approaches.”

  • The paper relies on this without support.

    The magnitude of clinical benefit derived from well-designed clinical trials is a relative constant across countries.

    “Whereas costs of procurement and out of pocket expenditures vary from country to country, the magnitude of clinical benefit, as derived from well-designed clinical trials, is a relative constant.”

  • The paper relies on this without support.

    The expert opinion of the oncology community can be accurately represented by threshold values for HR and absolute gains.

    “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.”

  • The paper relies on this without support.

    Current guideline practice of major oncology organizations grades level of evidence but not magnitude of benefit.

    “The prevailing current practice of the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), ESMO and the National Cancer Institute (NCI) in their guidelines is to grade the 'level of evidence' supporting the efficacy of therapeutic interventions”

  • The paper relies on this without support.

    ASCO has undertaken two initiatives to promote value in cancer care.

    “ASCO has undertaken two initiatives to help promote the value in cancer care.”

  • The paper relies on this without support.

    ASCO has not yet described their proposed approach to evaluate the magnitude of clinical benefit.

    “ASCO has not yet described their proposed approach to evaluate the magnitude of clinical benefit.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting grade-A disease-free-survival thresholds

    Major

    Table 2 gives an HR threshold below 0.60 for the highest curative-treatment grade, while the grading form uses below 0.65. A study with an HR between those values would receive different grades under the two rules.

  • OPTIMAL trial cites a different study

    Minor

    The OPTIMAL trial row cites reference 43, which the bibliography identifies as a study of pathological complete response in breast cancer. The bibliography lists the OPTIMAL erlotinib trial as reference 44.

  • Reported hazard ratio falls outside its confidence interval

    Minor

    The sunitinib row reports a hazard ratio of 0.42, but its stated confidence interval ends at 0.054-below both the estimate and the stated lower bound of 0.32.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Emanuel, 2005, The cost of marginal medicine is too high, MedGenMed, 7, 67
  2. Davis, 2014, Drugs, cancer and end-of-life care: a case study of pharmaceuticalization?, Soc Sci Med
  3. Gruskin, 2008, Process is the point: justice and human rights: priority setting and fair deliberative process, Am J Public Health, 98, 1573, 10.2105/AJPH.2007.123182 · DOI · Paper page
  4. Stintzing, 2013, Analysis of KRAS/NRAS and BRAF mutations in FIRE- 3: a randomized phase III study of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS (exon 2) metastatic colorectal cancer patients, 2013 European Cancer Congress, 1693

Cited by

Sorted by citations

Authors
Cherny, N. I., Sullivan, R., Dafni, U., Kerst, J. M., Sobrero, A., Zielinski, C., de Vries, E. G. E., & Piccart, M. J.
Affiliations
  • Shaare Zedek Medical Center (IL)
  • King's College London (GB)
  • National and Kapodistrian University of Athens (GR)
  • The Netherlands Cancer Institute (NL)
  • Ospedale Policlinico San Martino (IT)
  • Medical University of Vienna (AT)
  • Université Libre de Bruxelles (BE)
Corresponding author
Cherny, N.I.
ORCID
Venue
Annals of Oncology
Publisher
Elsevier BV
Published
2015-08
Volume
26
Issue
8
Pages
1547-1573
ISSN
0923-7534 (ISSN-L)
DOI
10.1093/annonc/mdv249
OpenAlex
W2134119471
Cited by
818
References
149
Citations by year
2026: 37 · 2025: 40 · 2024: 57 · 2023: 59 · 2022: 57 · 2021: 76 · 2020: 66 · 2019: 83 · 2018: 93 · 2017: 113 · 2016: 112 · 2015: 23
FWCI
274.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Annals of Oncology (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, other-oa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders
ESMO
Topics
  • Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Health Systems, Economic Evaluations, Quality of Life
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Economic and Financial Impacts of Cancer
Keywords
ESMO Magnitude of Clinical Benefit Scale, cancer therapy, oncology, cost-effectiveness, progression-free survival, survival benefit
MeSH terms
Cost-Benefit Analysis, Europe, Humans, Neoplasms, Societies, Medical, Treatment Outcome, Outcome Assessment, Health Care, Advisory Committees

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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