Observational studyBMJ (Clinical research ed.)2021
Regulatory and clinical consequences of negative confirmatory trials of accelerated approval cancer drugs: retrospective observational study.
Observational study in BMJ (Clinical research ed.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 3 of them syntheses that pooled 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.
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.
Who cites it
55 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Comparison of treatment efficacy of targeted therapies approved in China for non-small cell lung cancer before and after the introduction of accelerated drug marketing registration procedures.International journal of clinical pharmacy · 2026Pooled it
- Regulatory and clinical outcomes of priority-reviewed innovative cancer drugs in China between 2015 and 2024: an observational study.BMC cancer · 2025Pooled it
- National Comprehensive Cancer Network Guideline Recommendations of Cancer Drugs With Accelerated Approval.JAMA network open · 2023Guideline
- A decade comparison of regulatory decision patterns for oncology products to all other non-oncology products among Swissmedic, European Medicines Agency, and US Food and Drug Administration.Clinical and translational science · 2023Trial
- Navigating the Prescription Drug Information System.Clinical pharmacology and therapeutics · 2026Review
- Article
- Clinical value and cost-effectiveness analysis of conditionally approved anticancer drugs in China from 2015 to 2023.Translational cancer research · 2026Article
- Peripheral nervous system safety signals of antibody-drug conjugates: cross-database reproducibility and labeling gaps identified using FAERS, JADER, and CVARD.Frontiers in pharmacology · 2026Article
- Do conditional marketing authorisations actually accelerate patient access? Time-to-access of conditional vs. standard marketing authorisations in Italy, Spain, and Germany.Journal of pharmaceutical policy and practice · 2026Article
- Evaluating Food and Drug Administration approved gastrointestinal cancer drugs: clinical benefit and trial endpoints over the past two decades.The oncologist · 2025Article
- Flexibility over rigor: stakeholder acceptance of the limitations of confirmatory studies following accelerated approval.Health affairs scholar · 2025Article
- Current landscape of innovative drug development and regulatory support in China.Signal transduction and targeted therapy · 2025Review
- Cancer drug applications to the EMA and the FDA: A comparison of new drugs and extension of indication in terms of approval decisions and time in review.British journal of clinical pharmacology · 2025Article
- Era of surrogate endpoints and accelerated approvals: a comprehensive review on applicability, uncertainties, and challenges from regulatory, payer, and patient perspectives.European journal of clinical pharmacology · 2025Review
- US FDA-accelerated approvals and subsequent withdrawals: influence on Japanese clinical oncology practice guidelines.Investigational new drugs · 2025Article
- The UK's Early Access to Medicines Scheme 10 years on: an evaluation using publicly available data.JRSM open · 2025Article
- Physician-Patient Communication about Novel Drugs and High-Risk Medical Devices.Medical decision making : an international journal of the Society for Medical Decision Making · 2025Article
- Financial challenges of being on long-term, high-cost medications.Neuro-oncology practice · 2025Review
- Review Mechanisms for Advanced Medical Therapies in Japan and Thailand: A Proposal for the Use of Expert Clinical Benefit Assessments at Designated Institutions.Asian bioethics review · 2025Article
- Disparities in the access to immune checkpoint inhibitors approved in the United States, the European Union and mainland China: a serial cross-sectional study.BMJ public health · 2025Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo investigate the regulatory handling of cancer drugs that were granted accelerated approval by the US Food and Drug Administration (FDA) but failed to improve the primary endpoint in post-approval trials and to evaluate the extent to which negative post-approval trials changed the recommendations in treatment guidelines.
designRetrospective observational study.
settingFDA and National Comprehensive Cancer Network (NCCN) reports. INCLUDED DRUGS: Cancer drugs that received accelerated approval from the FDA and had negative post-approval trials.
main outcome measuresRegulatory outcomes, including withdrawal, conversion to regular approval, and no action.
results18 indications for 10 cancer drugs that received accelerated approval but failed to improve the primary endpoint in post-approval trials were identified. Of these, 11 (61%) were voluntarily withdrawn by the manufacturer and one (bevacizumab for breast cancer) was revoked by the FDA. Of the 11 withdrawals, six occurred in 2021 alone. The remaining six (33%) indications remain on the label. The NCCN guidelines provide a high level of endorsement (category 1 endorsement for one and category 2A endorsement for seven) for accelerated approval drugs that have failed post-approval trials, sometimes even after the approval has been withdrawn or revoked.
conclusionCancer drug indications that received accelerated approval often remained on formal FDA approved drug labelling and continued to be recommended in clinical guidelines several years after statutorily required post-approval trials showed no improvement in the primary efficacy endpoint. Clinical guidelines should better align with the results of post-approval trials of cancer drugs that received accelerated approval.
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What OpenQuestion holds
Registered trials
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.