When Context Is Hard to Come By: External Comparators and How to Use Them

Christian, Jennifer; Brinkley, Emma; Warren, Edward J.; Hall, Marni; Dreyer, Nancy A

doi:10.1007/s43441-019-00108-z

Cited by 20 publications

(25 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The use of historical controls in particular is well established. 24 An oftcited example is the original marketing application approval of blinatumomab for ALL in 2014. 8 The single-arm trial was supported by a historical control group of data derived from chart review of 694 patients from US and European study sites.…”

Section: Discussionmentioning

confidence: 99%

Use of Real-World Evidence to Support FDA Approval of Oncology Drugs

et al. 2020

View full text Add to dashboard Cite

Objectives: Real-world evidence (RWE) has gained increased attention in recent years as a complement to traditional clinical trials. The use of RWE to establish the efficacy of oncology drugs for Food and Drug Administration (FDA) approval has not been described. In this paper, we review 5 recent examples where RWE was submitted in support of the FDA approvals of original or supplementary indications for oncology drugs.Methods: To identify cases where RWE was used, we reviewed drug approval packages available at Drugs@FDA for oncology drugs approved between 2017 and 2019. Five cases were selected to present a broad overview of different types of RWE, different circumstances under which RWE has been used for regulatory approvals, and how FDA evaluated the data in each case. The type of RWE submitted, the indication, limitations identified by FDA reviewers, and the outcome of the submission are discussed.Results: RWE, particularly historical controls for rare or orphan indications, has been used to support both original and supplementary oncology drug approvals. Types of RWE included data from electronic health records, claims, post-marketing safety reports, retrospective medical record reviews, and expanded access studies. Small sample sizes, data quality, and methodological issues were among concerns cited by FDA reviewers. Conclusion:By bridging the gap between the constraints of the trial setting and the realities of clinical practice, RWE can add value to a regulatory submission. These early examples provide insight into how regulators evaluated RWE submitted as evidence of efficacy for oncology drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Use of Real-World Evidence to Support FDA Approval of Oncology Drugs

et al. 2020

View full text Add to dashboard Cite

show abstract

“…To understand the outcomes at individual HTA level, we reviewed comparator types and outcomes for the following key decision-making bodies: HAS, France (69); PBAC, Australia (37); G-BA, Germany (32); NICE, England (24); and pCODR/CADTH, Canada (33).…”

Section: Outcomes For Sat Hta Submissions For Key Hta Bodiesmentioning

confidence: 99%

“…Here patient selection criteria from the index study protocol are applied to the external data source (to the extent possible) so that the comparator population looks as similar as possible to the index study population. 12,24 This type of supplementary dataset can be used for naive (unadjusted comparison) or adjusted indirect treatment comparison using STC or MAIC approaches.…”

Section: Introductionmentioning

confidence: 99%

Use of External Comparators for Health Technology Assessment Submissions Based on Single-Arm Trials

et al. 2021

View full text Add to dashboard Cite

Background: Single-arm trial (SAT) data is increasingly reviewed for drug approvals by regulators and Health Technology Assessment (HTA) bodies. Supplementary data in the form of external comparators (ECs) can be used to provide clinical context to support these drug evaluations. In this study we characterized HTAs for SAT-based submissions, the use of supplementary EC data and outcomes from HTA review.Methods: HTA Accelerator database was used to describe SAT-based HTA submissions with decisions (2011-2019).Results: A total of 433 SAT-based HTA submissions were identified between 2011 and 2019 with a 13-fold increase during this period. Around 65%(283/433) were in oncology or hem-oncology. Around 52%(226/433) of submissions contained some type of EC data, including prior clinical trials (24%, 104) and real-world data (RWD) (20%, 87), but 40%(175) contained no EC data. The overall acceptance rate for SAT-based submissions was 48% and with RWD EC data acceptance was 59%. In the latest 5year period (2015-2019), use of RWD ECs increased 22% as a proportion of submissions per year, whereas, prior trial ECs decreased (-14%) and use of no EC remained stable (-2%). Between 2015 to 2017 and 2018 to 2019, acceptance rate for RWD ECs increased by 20% (41% in 2015-2017 to 61% in 2018-2019) whereas prior trial EC use decreased by 10% and no EC submissions decreased 16%. Of 226 submissions using ECs, only 29%(66) used an adjusted indirect treatment comparison method.Conclusions: SAT-based submissions to HTA bodies are rapidly evolving in terms of composition and acceptance. Types of EC and methodological approach used are important determinants of positive outcomes.

show abstract

“…The value of RWE is attributed to the fact that data collection is undertaken for routine care and practice, making RWD creation essentially free of charge with the added benefit of being representative of typical patients, events and outcomes. In contrast to 5–7 years ago, RWE is now being perceived as more than just a solution for post-approval safety commitments, with a wealth of submissions now bringing RWE complemented RCTs (with RWE endpoints) to the frontline of drug approvals and market access [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Bridging the Gap Between RCTs and RWE Through Endpoint Selection

LoCasale

Pashos

Gutierrez

et al. 2020

Ther Innov Regul Sci

View full text Add to dashboard Cite

This commentary is authored by several industry real-world evidence (RWE) experts, with support from IQVIA, as part of the 'RWE Leadership Forum': a group of Industry Leaders who have come together as non-competitive partners to understand and respond to RWD/E challenges and opportunities with a single expert voice. Here, the forum discusses the value in bridging the industry disconnect between RTCs and RWE, with a view to promoting the use of RWE in the RCT environment. RCT endpoints are explored along several axes including their clinical relevance and their measure of direct patient benefit, and then compared with their real-world counterparts to identify suitable paths, or gaps, for assimilating RWE endpoints into the RCT environment.

show abstract

When Context Is Hard to Come By: External Comparators and How to Use Them

Cited by 20 publications

References 0 publications

Use of Real-World Evidence to Support FDA Approval of Oncology Drugs

Use of Real-World Evidence to Support FDA Approval of Oncology Drugs

Use of External Comparators for Health Technology Assessment Submissions Based on Single-Arm Trials

Bridging the Gap Between RCTs and RWE Through Endpoint Selection

Contact Info

Product

Resources

About