FDA validation of surrogate endpoints in oncology: 2005–2022

Walia, Anushka; Haslam, Alyson; Prasad, Vinay

doi:10.1016/j.jcpo.2022.100364

Cited by 32 publications

(25 citation statements)

References 7 publications

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“…Finally, although the US Food and Drug Administration (FDA) conducted a round-table meeting on the use of PROs in 2020, in their Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics statement from 2018, their list of commonly used efficacy endpoints in oncology clinical trials does not even mention QoL or PROs (30). Therefore, it is not astonishing that the list of endpoints in oncological trials shows frequent surrogate outcomes without strong correlation to relevant clinical endpoints and only limited clinical benefit rates, but that QoL and PROs are rare (31).…”

Section: Findings From the Recent Systematic Review By Fabian Et Almentioning

confidence: 99%

The value of patient reported outcomes in palliative radiotherapy: A discussion in light of current findings

Gaertner¹,

Zimmermann²,

Simone³

2023

Ann Palliat Med

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Section: Findings From the Recent Systematic Review By Fabian Et Almentioning

confidence: 99%

The value of patient reported outcomes in palliative radiotherapy: A discussion in light of current findings

Gaertner¹,

Zimmermann²,

Simone³

2023

Ann Palliat Med

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“…Although the latter is vital, it is not clear if it is necessary for regulatory decision making. Meanwhile, the United States Food and Drug Administration (FDA) itself has stated that trial level validity is the standard to which they aspire and has conducted several papers assessing that 10 . Progression‐free survival (PFS) has been accepted by regulatory authorities as a valid end‐point for registrational clinical trials in MM.…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, the United States Food and Drug Administration (FDA) itself has stated that trial level validity is the standard to which they aspire and has conducted several papers assessing that. 10 Progression-free survival (PFS) has been accepted by regulatory authorities as a valid end-point for registrational clinical trials in MM. Previous analysis of surrogacy of PFS for OS conducted by industry, as well as an older independently conducted analysis, has shown a positive association between treatment effects on PFS and OS.…”

mentioning

confidence: 99%

Time‐to‐event surrogate end‐points in multiple myeloma randomised trials from 2005 to 2019: A surrogacy analysis

et al. 2022

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The use of end-points other than overall survival (OS) in oncological randomised controlled trials (RCTs) can, under some conditions, reduce the cost and duration of studies. 1 However, the validity of these alternative end-points is not consistently proven in most malignancies, including multiple myeloma (MM), and therefore their widespread use is of concern. 2 Drugs approved by regulatory authorities for MM on the basis of surrogate end-points in Europe and the United States over the last 15 years include carfilzomib, ixazomib, thalidomide, lenalidomide, pomalidomide, liposomal doxorubicin, panobinostat, daratumumab, isatuximab, elotuzumab, 3 selinexor, belantamab mafodotin, ciltacabtagene autoleucel, and idecabtagene vicleucel. 4-6 Some of these agents have gone on to demonstrate an OS benefit in confirmatory registration trials. 7,8

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“…progression, are the most common surrogate endpoints used. 1 Prior work has shown that the US Food and Drug Administration (FDA) has steadily expanded surrogate categories for drug approval over the last two decades. 2 Moreover, surrogates are used for both accelerated approval, where there is a further post-marketing efficacy commitment, and regular approval, where there is not.…”

mentioning

confidence: 99%

An empirical analysis of overall survival in drug approvals by the US FDA (2006–2023)

Elbaz,

Haslam,

Prasad

2024

Cancer Medicine

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BackgroundThe US Food and Drug Administration (FDA) has expanded the use of surrogate markers in drugs approved for oncology/hematology indications. This has likely resulted in a greater number of approvals and possibly drugs coming to market faster, but it is unknown whether these drugs also improve overall survival (OS) for patients taking them.MethodsWe sought to estimate the percentage of oncology drugs that have shown to improve OS in a cross‐sectional analysis of US FDA oncology drug approvals (2006–2023). We searched for OS data in registration trials and the peer‐reviewed literature.ResultsWe found 392 oncology drug approvals. Eighty‐seven (22%) drug approvals were based on OS, 147 drug approvals were later tested for OS benefit (38% of all approvals and 48% of drugs approved on a surrogate), and 130 (33%) have yet to be tested for OS benefit. Of the 147 drug approvals later tested for OS, 109 (28% of all approvals and 74% of drugs later tested for OS) have yet to show OS benefit, whereas 38 (10% of all approvals and 26% of drugs later tested for OS benefit) were later shown to have OS benefit. In total, 125 out of 392 (32%) drugs approved for any indication have been shown to improve OS benefit at some point, and 267 (68%) have yet to show approval.ConclusionAbout 32% of all oncology drug approvals have evidence for an improvement in OS. Higher standards are needed in drug regulation to ensure that approved drugs are delivering better patient outcomes, specifically in regards to survival.

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FDA validation of surrogate endpoints in oncology: 2005–2022

Cited by 32 publications

References 7 publications

The value of patient reported outcomes in palliative radiotherapy: A discussion in light of current findings

The value of patient reported outcomes in palliative radiotherapy: A discussion in light of current findings

Time‐to‐event surrogate end‐points in multiple myeloma randomised trials from 2005 to 2019: A surrogacy analysis

An empirical analysis of overall survival in drug approvals by the US FDA (2006–2023)

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