Evidence map›Paper›PMID 39695642›Full record

ArticleBMC medicine2024

Strength of clinical evidence supporting the United States Food and Drug Administration Accelerated Approvals from 2015 to 2022.

Xiaofang Zhang, Carl C Peck, Yaning Wang, Thomas D Szucs, Wan Sun, Xue Bai, Siyu Chen, Fengzhi Wang, Yangfeng Wu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Xiaofang ZhangPeking University First Hospital, Beijing, China.
Carl C PeckDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
Yaning WangWuhan Createrna Science and Technology Co., Ltd., Wuhan, Hubei, China.
Thomas D SzucsEuropean Center of Pharmaceutical Medicine, University of Basel, Basel, Switzerland.
Wan SunNational Biotech Group Clinical and Regulatory Sciences Joint Laboratory, Peking University Health Science- China, Beijing, China.
Xue BaiNational Biotech Group Clinical and Regulatory Sciences Joint Laboratory, Peking University Health Science- China, Beijing, China.
Siyu ChenPeking University First Hospital, Beijing, China.
Fengzhi WangNational Biotech Group Clinical and Regulatory Sciences Joint Laboratory, Peking University Health Science- China, Beijing, China.
Yangfeng WuClinical Research Institute, Institute of Advanced Clinical Medicine, Peking University, Beijing, China. wuyf@bjmu.edu.cn.ORCID 0000-0002-4451-1932

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe Food and Drug Administration (FDA)'s Accelerated Approval (AA) pathway has increasingly used to authorize market approval of new drugs amid controversy. The present study aims to inform the most recent data on the strength of clinical evidence supporting such approvals.

methodsEvidentiary characteristics of pre-approval pivotal clinical studies and regulator-required post-approval confirmatory studies supporting AAs between 2015 and 2022 were extracted from publicly available FDA documents. Descriptive analyses were conducted for each of the characteristic including study design, study phase, primary endpoint, number of participants, and magnitude of effect. Trends of these characteristics over time were documented and accounted for class of drugs, application type, novelty, orphan status, and oncology/non-oncology indications.

resultsDuring 2015-2022, 156 drug-indication pairs received AA. To support these AAs, 77% of pre-approval pivotal trials employed single-arm designs, and 22% were phase I trials, with a median of 92 participants (IQR, 45-125); 61% of post-approval confirmatory studies were required by FDA to use randomized controlled design, 25% to use clinical endpoints, and 33% specified the number of participants requirement. During the 8-year observation period, the pairs approved via AA pathway almost tripled from 20 (2015-2016) to 59 (2019-2020) and fell to 36 (2021-2022); the corresponding proportion to all new drug approvals showed the same trend. Single-arm pre-approval pivotal studies increased from 55% (2015-2016) to 91% (2019-2020) and fell to 69% (2021-2022), while the median number of participants decreased from 106 (2015-2016) to 59 (2019-2020) and rose to 106 (2021-2022). Randomized controlled post-approval confirmatory studies decreased from 75% (2015-2016) to 42% (2019-2020) and rebounded to 75% (2021-2022), while those using surrogate endpoints increased from 50% (2015-2016) to 72% (2021-2022). Analyses adjusting for drug class, application type, novelty, orphan status, and oncology/non-oncology showed similar results.

conclusionsThe number of drug-indication pairs receiving AA increased sharply during 2015-2016 to 2019-2020 but fell in 2021-2022. Meanwhile, the strength of clinical evidence supporting FDA's AAs appeared to decline from 2015 to 2020 but seems to have improved in 2021-2022. Measures should be taken to further improve the strength of evidence in Accelerated Approvals.

Indexed as

Drug ApprovalUnited States Food and Drug AdministrationClinical Trials as TopicHumansUnited StatesAccelerated approvalRegulatory scienceStrength of clinical evidenceTrend over time

Identifiers

PMID39695642
PMCPMC11657587

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.