Single-arm clinical trials that supported FDA accelerated approvals have modest effect sizes and were at high risk of bias
Copyright © 2022 Elsevier Inc. All rights reserved..
OBJECTIVE: To describe effect sizes of single-arm clinical trials that supported AA approvals.
STUDY DESIGN AND SETTING: We reviewed all the single-arm approvals granted by the FDA-AA pathway between June1992 to December2020. Two independent reviewers identified single-arm studies and extracted data from FDA Full-Medical Reviews. We performed a meta-analysis to estimate the effect sizes and compared it between studies that met post-approval FDA requirements for RCTs with those that did not.
RESULTS: From the total of 254 approvals, single arm clinical trials describing effects of 54 drugs for 72 clinical indications were evaluated. The effect size estimated was OR:2.22(CI95%:1.76-2.81) [relative risk (RR) = 1.63(95CI% 1.38-1.92)]; 53% of treatments had a lower 95% CI bound crossing the null effect. Effect size did not differ between the treatments that met the FDA requirement for conducting post-approval RCTs.
CONCLUSIONS AND RELEVANCE: Treatment effects observed in the FDA AA single-arm studies was modest and can be to ascribed to bias.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:148 |
|---|---|
| Enthalten in: |
Journal of clinical epidemiology - 148(2022) vom: 15. Aug., Seite 193-195 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ribeiro, Tatiane Bomfim [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Accelerated approval |
|---|
| Anmerkungen: |
Date Completed 27.10.2022 Date Revised 31.10.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jclinepi.2022.01.018 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM336278101 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM336278101 | ||
| 003 | DE-627 | ||
| 005 | 20231225231757.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jclinepi.2022.01.018 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1120.xml |
| 035 | |a (DE-627)NLM336278101 | ||
| 035 | |a (NLM)35093531 | ||
| 035 | |a (PII)S0895-4356(22)00025-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ribeiro, Tatiane Bomfim |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Single-arm clinical trials that supported FDA accelerated approvals have modest effect sizes and were at high risk of bias |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.10.2022 | ||
| 500 | |a Date Revised 31.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier Inc. All rights reserved. | ||
| 520 | |a OBJECTIVE: To describe effect sizes of single-arm clinical trials that supported AA approvals | ||
| 520 | |a STUDY DESIGN AND SETTING: We reviewed all the single-arm approvals granted by the FDA-AA pathway between June1992 to December2020. Two independent reviewers identified single-arm studies and extracted data from FDA Full-Medical Reviews. We performed a meta-analysis to estimate the effect sizes and compared it between studies that met post-approval FDA requirements for RCTs with those that did not | ||
| 520 | |a RESULTS: From the total of 254 approvals, single arm clinical trials describing effects of 54 drugs for 72 clinical indications were evaluated. The effect size estimated was OR:2.22(CI95%:1.76-2.81) [relative risk (RR) = 1.63(95CI% 1.38-1.92)]; 53% of treatments had a lower 95% CI bound crossing the null effect. Effect size did not differ between the treatments that met the FDA requirement for conducting post-approval RCTs | ||
| 520 | |a CONCLUSIONS AND RELEVANCE: Treatment effects observed in the FDA AA single-arm studies was modest and can be to ascribed to bias | ||
| 650 | 4 | |a Letter | |
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Accelerated approval | |
| 650 | 4 | |a Antineoplastic Agents | |
| 650 | 4 | |a Historical controls | |
| 650 | 4 | |a US Food and Drug Administration | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 700 | 1 | |a Colunga-Lozano, Luis Enrique |e verfasserin |4 aut | |
| 700 | 1 | |a Araujo, Ana Paula Vieira |e verfasserin |4 aut | |
| 700 | 1 | |a Bennett, Charles Lee |e verfasserin |4 aut | |
| 700 | 1 | |a Hozo, Iztok |e verfasserin |4 aut | |
| 700 | 1 | |a Djulbegovic, Benjamin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of clinical epidemiology |d 1991 |g 148(2022) vom: 15. Aug., Seite 193-195 |w (DE-627)NLM012614815 |x 1878-5921 |7 nnns |
| 773 | 1 | 8 | |g volume:148 |g year:2022 |g day:15 |g month:08 |g pages:193-195 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jclinepi.2022.01.018 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 148 |j 2022 |b 15 |c 08 |h 193-195 | ||