Cancer Drugs Approved on the Basis of a Surrogate End Point and Subsequent Overall Survival

Kim, Chul; Prasad, Vinay

doi:10.1001/jamainternmed.2015.5868

Cited by 315 publications

(296 citation statements)

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“…Still, trial-based regulatory assessments of clinical impact may not translate to the realworld. To more precisely measure the clinical risks and benefits from treatment, future studies should extend this analysis by also incorporating post-marketing studies, 30 or using observational data or pragmatic clinical trial evidence, as it becomes available. Future academic initiatives may be able to leverage data from the National Cancer Institute's upcoming National Cancer Knowledge System-a component of the US Precision Medicine Initiative® that will integrate genomic information with clinical response data and outcomes information-to assess the real-world clinical impact from newly developed cancer drugs and to inform value-based supply-and demand-side decisions.…”

Section: Limitationsmentioning

confidence: 99%

“…For convenience, however, we take an α level of .67 or greater to indicate a high level of agreement. 30 Finally, to attempt to externally validate our results, we sought informal feedback on our analysis from 2 medical experts from the FDA. After providing their informed consent to participate anonymously, both experts were given a written description of our methods and a copy of all results.…”

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Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer Medicines

2017

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LSE has developed LSE Research Online so that users may access research output of the School. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LSE Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain. You may freely distribute the URL (http://eprints.lse.ac.uk) of the LSE Research Online website.Copyright 2016 American Medical Association. All rights reserved. Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer MedicinesSebastian Salas-Vega, MSc; Othon Iliopoulos, MD; Elias Mossialos, MD, PhD IMPORTANCE There is a dearth of evidence examining the impact of newly licensed cancer medicines on therapy. This information could otherwise support clinical practice, and promote value-based decision-making in the cancer drug market. Of these 53 drugs, 23 (43%) increased OS by 3 months or longer, 6 (11%) by less than 3 months, and 8 (15%) by an unknown magnitude; there was no evidence to suggest that the remaining 16 (30%) increased OS over best alternative treatments. Where overall survival gains could be quantified, all new cancer drugs were associated with a mean (SE) total increase in OS of 3.43 (0.63) months over the treatments that were available in 2003. Drug-related improvements in OS were, however, widely distributed across therapeutic targets-ranging between 0 (thyroid, ascites) and 8.48 months (breast cancers)-and were sometimes based on modeled data, indirect or nonactive comparisons, or nonvalidated evidence. Although 22 (42%) of 53 new medicines were associated with an increase in QoL, 24 (45%) were also associated with reduced patient safety. Of the 53 new cancer drugs, 42 (79%) were associated with at least some improvement in OS, QoL, or safety.CONCLUSIONS AND RELEVANCE Although innovation in the oncology drug market has contributed to improvements in therapy, the magnitude and dimension of clinical benefits vary widely, and there may be reasons to doubt that claims of efficacy reflect real-world effectiveness exactly. These findings raise important questions for clinical decision-making and value-based policy. JAMA Oncol. doi:10.1001/jamaoncol.2016 Published online December 29, 2016. T here are growing questions about the value gained from spending on what seem to be ever more expensive cancer medicines. Rising expenditures may make it difficult for patients to access or remain compliant with lifeextending therapies. 1,2 Yet, some have argued that high prices may be justified if new and innovative treatments offer significant benefits to patients. 2,3 Even as studies point to gains in overall survival (OS) from innovative cancer medicines, 4 efforts to examine the value from spending on new cancer drugs remain stymied by a dearth of systematic evidence on their clinical ri...

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Section: Limitationsmentioning

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Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer Medicines

2017

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“…28 29 Available data from the US show that only a small proportion of cancer treatments approved by the US Food and Drug Administration (FDA) unequivocally show benefits on survival or quality of life 30. The applicability of this evidence to the European context, however, is not clear.…”

Section: Introductionmentioning

confidence: 99%

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

Davis

Naci

Gurpinar

et al. 2017

BMJ

479

415

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Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013. Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years’ follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%). Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.

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“…Kim et al [6] reviewed the approvals issued by FDA during the 5-year period (2008)(2009)(2010)(2011)(2012) relating the path (accelerated vs. traditional) and the end points (surrogate-namely, progression-free survival and response rate vs. overall survival). All 15 drugs under the accelerated approval path used a surrogate point as the outcome measure while about half the drugs following the traditional path (21 out of 39) used that kind of measure.…”

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EMA Priority Medicines scheme (PRIME): will more paying-for-performance agreements be needed due to immature data?

2017

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Cancer Drugs Approved on the Basis of a Surrogate End Point and Subsequent Overall Survival

Cited by 315 publications

References 1 publication

Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer Medicines

Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer Medicines

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

EMA Priority Medicines scheme (PRIME): will more paying-for-performance agreements be needed due to immature data?

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