Evaluating Expected Costs and Benefits of Granting Access to New Treatments on the Basis of Progression-Free Survival in Non–Small-Cell Lung Cancer

Lakdawalla, Darius N.; Chou, Jacquelyn W; Linthicum, Mark T.; MacEwan, Joanna P.; Zhang, Jie; Goldman, Dana P.

doi:10.1001/jamaoncol.2015.0203

Cited by 21 publications

(18 citation statements)

References 24 publications

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“…Finally, a recent study suggests that approving new drugs based on surrogates (even inaccurate ones) may provide a greater benefit for society than waiting for OS data. 101 The authors found favorable societal benefits for approving non-small-cell lung cancer (NSCLC) drugs with PFS benefits of 3 months or more. This occurred despite the fact that the authors noted a poor correlation (as we also did in Table 1) between net mean PFS and OS in NSCLC cancer (r = 0.56).…”

Section: Limitationsmentioning

confidence: 99%

The Strength of Association Between Surrogate End Points and Survival in Oncology

et al. 2015

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The strength of association between surrogate end points and survival in oncology is important to understand because surrogate end points are frequently used in oncology clinical trials, supporting US Food and Drug Administration approvals and National Comprehensive Cancer Network guideline recommendations. OBJECTIVE To identify and evaluate trial-level meta-analyses of randomized clinical trials quantifying the association between a surrogate end point and overall survival in medical oncology. Trial-level correlations test whether treatments that improve the surrogate end point also improve the final end point and are widely considered the strongest evidence to validate a surrogate end point. EVIDENCE REVIEW Our literature search was built on earlier reported data sets and updated with Google Scholar and MEDLINE searches conducted on December 26, 2014. For MEDLINE, search terms included ("regression" or "correlation") and "surrogate" and "end point [or endpoint]" and ("oncology" or "cancer"). For Google scholar, search terms included ("regression" or "correlation") and "surrogate end point [or endpoint]" and "overall survival" and "trial level." A total of 108 abstracts were retrieved, and 62 articles were read in full in addition to articles identified through prior reviews. FINDINGS We found 36 articles in which 65 specific correlations between a surrogate end point and survival were identified. Surrogate end points were studied in the neoadjuvant, adjuvant, locally advanced, and metastatic settings. The most common sources for trials included in the 36 articles were systematic reviews of the published literature (10 of 36; 28%), and published literature and meeting abstracts (14 of 36; 39%). Four meta-analyses (11%) used a convenience sample, and only 5 studies (14%) attempted to include unpublished trials by surveying clinical trial registries. Among these 5 studies, only 352 of 684 eligible trials (51.1%) were included in the analyses. More than half of reported correlations (34 of 65; 52%) were of low strength (r Յ 0.7). Approximately a quarter (16 of 65; 25%) were of medium strength (r > 0.7 to r < 0.85), and 15 of 65 (23%) were highly correlated (r Ն 0.85) with survival. CONCLUSIONS AND RELEVANCE Most trial-level validation studies of surrogate end points in oncology find low correlations with survival. All validation studies use only a subset of available trials. The evidence supporting the use of surrogate end points in oncology is limited.

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Section: Limitationsmentioning

confidence: 99%

The Strength of Association Between Surrogate End Points and Survival in Oncology

et al. 2015

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“…In making drug approval decisions, the costs and benefits of granting earlier approval based on surrogate end-points must be weighed and, often (e.g. in many cancer types and LIMITATIONS OF TRADITIONAL HTA type 2 diabetes), the expected benefits outweigh the costs 15,70 . HTAs often use information on adverse events observed in clinical trials to infer real-world and long-run side-effects.…”

Section: Lack Of Long-run Evidencementioning

confidence: 99%

Limitations of traditional health technology assessment methods and implications for the evaluation of novel therapies

Doctor

MacEwan²

2017

Current Medical Research and Opinion

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“…Given the challenges in determining OS, particularly in the presence of crossover, additional efficacy end points, such as progression-free survival (PFS), are frequently used in clinical trials in oncology. There is an ongoing debate whether PFS is a useful surrogate for OS in oncology [8,9]. Although PFS may be accepted as a primary end point in oncology trials by regulatory agencies in certain settings and under certain conditions [7], reliable and unbiased OS estimates are still likely to be required for health technology assessments [10].…”

Section: Introductionmentioning

confidence: 99%

Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany

et al. 2018

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In G-BA appraisals, oncology medicines with crossover received better additional benefit ratings, but were assigned lower evidence levels, than those without. The five medicines with crossover after progression were assigned lower evidence levels than the six medicines with crossover after demonstration of superior OS, indicating that the way in which crossover is implemented may be one factor influencing the assignment of evidence levels by the G-BA.

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Evaluating Expected Costs and Benefits of Granting Access to New Treatments on the Basis of Progression-Free Survival in Non–Small-Cell Lung Cancer

Abstract: The value of providing access to new treatments on the basis of surrogate end points, and PFS in particular, likely varies considerably. Payers and clinicians should carefully consider how to use PFS data in balancing potential benefits against costs in each particular disease.

Cited by 21 publications

References 24 publications

The Strength of Association Between Surrogate End Points and Survival in Oncology

The Strength of Association Between Surrogate End Points and Survival in Oncology

Limitations of traditional health technology assessment methods and implications for the evaluation of novel therapies

Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany

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