2026-04-13T04:01:09Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/131262025-06-14T04:13:44Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Tibau Martorell, Ariadna
author
Hwang, Thomas
author
Romano Cardozo, Alejandra
author
Borrell, Maria
author
Molto Valiente, Consolacion
author
Gich, Ignasi
2025-06-14T04:13:44Z
2025-06-14T04:13:44Z
2025-05-23T10:09:10Z2025-05-23T10:09:10Z2025-03
http://hdl.handle.net/11351/13126
Approval anticancer medicines; Accelerated approvalAprobación de medicamentos anticancerígenos; Aprobación aceleradaAprovació de medicaments anticancerígens; Aprovació acceleradaImportance The accelerated approval pathway was developed to expedite US Food and Drug Administration (FDA) drug approval for life-threatening conditions based on changes to unvalidated surrogate measures, with conversion to regular approval then based on a required confirmatory trial. However, confirmatory trials may not be completed in a timely fashion.
Objective To analyze factors associated with time to conversion to regular approval.
Design, setting, and participants This cohort study of cancer drugs FDA-approved from 1992 to 2022 extracted pivotal and confirmatory trial characteristics, outcomes, safety data, and confirmatory study status at approval from drug labels and published reports. Clinical benefit was assessed using the European Society of Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) for pivotal and confirmatory studies. High benefit was defined as grade A or B (for trials of curative intent) and 4 or 5 (palliative intent) and low benefit as grade C and 2 or below. Data were analyzed between August 2023 and August 2024.
Main Outcome and Measure Time to full approval or withdrawal.
Results This cohort study analyzed 102 cancer drug indications granted accelerated approval by the FDA between 1992 and 2022 and converted to regular approval by August 31, 2024. The median (IQR) time to conversion was 3.1 (1.9-4.8) years. Of these, 83 (81%) received priority review, and 27 (26%) carried boxed warnings. On the ESMO-MCBS scale, 12 of 101 pivotal trials that were scorable showed high benefit (12%), 27 intermediate benefit (27%), and 62 low benefit (61%). Twenty-one confirmatory trials (21%) were initiated after accelerated approval. Factors at the time of accelerated approval that were associated with shorter times to full approval included priority review designation, absence of boxed warnings, initiation of confirmatory studies before approval, and pivotal trials showing intermediate or high benefit on the ESMO-MCBS framework. Among the 102 confirmatory trials, 34 (33%) demonstrated significant improvements in overall survival, and 14 of 35 trials (40%) reporting on quality of life showed significant benefits. The ESMO-MCBS scale was applicable to 98 trials, with 46 (47%) scoring high clinical benefit, 29 (30%) intermediate, and 23 (23%) low. Indications with benefits in overall survival (median [IQR], 2.15 [1.40-3.38] vs 3.70 [2.33-5.78] years), quality of life (median [IQR], 2.29 [1.85-3.53] vs 4.22 [2.52-5.72] years), and high clinical benefit in confirmatory trials (median [IQR], 2.34 [1.52-3.39] vs 3.91 [2.59-6.42] years) were associated with faster conversion to full approval.
Conclusions and Relevance In this cohort study, drugs with low clinical benefit or safety concerns at accelerated approval were linked to delayed confirmatory studies, while high clinical benefit in confirmatory trials correlated with faster conversion. These associations can help guide patient decision-making around accelerated approval drugs.Funded by the Kaiser Permanente Institute for Health Policy. Authors were supported by grants from Arnold Ventures and Commonwealth Fund (Kesselheim) and Alfonso Martín Escudero Foundation (Tibau).
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
Medicaments antineoplàstics - Ús terapèutic
Càncer - Tractament
Medicaments - Desenvolupament
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Drug Development::Drug Approval
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::/therapeutic use
PHENOMENA AND PROCESSES::Physical Phenomena::Time::Time Factors
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::desarrollo de medicamentos::autorización de medicamentos
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::/uso terapéutico
FENÓMENOS Y PROCESOS::fenómenos físicos::tiempo::factores de tiempo
Factors in Time to Full Approval or Withdrawal for Anticancer Medicines Granted Accelerated Approval by the FDA
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion