SynthesisBMJ (Clinical research ed.)2015
Characteristics of efficacy evidence supporting approval of supplemental indications for prescription drugs in United States, 2005-14: systematic review.
Synthesis in BMJ (Clinical research ed.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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
15 citing papers in PubMed.
- Indication-Specific Dosing and Dose-Evaluation Strategies in New Indications for Non-Oncology Monoclonal Antibodies.Journal of clinical pharmacology · 2025Review
- Comparative Assessment of Pivotal Trials Supporting the Indication Approvals of Innovative and Modified New Anticancer Drugs in China, 2016-2022.Health data science · 2025Article
- Therapeutic value of first versus supplemental indications of drugs in US and Europe (2011-20): retrospective cohort study.BMJ (Clinical research ed.) · 2023Article
- Spending by the Centers for Medicare & Medicaid Services Before and After Confirmation of Benefit for Drugs Granted US Food and Drug Administration Accelerated Approval, 2012 to 2017.JAMA health forum · 2022Article
- Characteristics of Clinical Studies Used for US Food and Drug Administration Supplemental Indication Approvals of Drugs and Biologics, 2017 to 2019.JAMA network open · 2021Article
- A Multifaceted Perspective of Pharmaceutical Innovation: A Consideration of the Regulatory Role.Therapeutic innovation & regulatory science · 2021Article
- Weighing of Evidence by Health Technology Assessment Bodies: Retrospective Study of Reimbursement Recommendations for Conditionally Approved Drugs.Clinical pharmacology and therapeutics · 2019Article
- Completion Rate and Reporting of Mandatory Pediatric Postmarketing Studies Under the US Pediatric Research Equity Act.JAMA pediatrics · 2019Article
- Article
- Drug approval based on randomized phase 3 trials for relapsed malignancy: analysis of oncologic drugs granted accelerated approval, publications and clinical trial databases.Investigational new drugs · 2018Article
- Theory of signs and statistical approach to big data in assessing the relevance of clinical biomarkers of inflammation and oxidative stress.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Use of Health Care Databases to Support Supplemental Indications of Approved Medications.JAMA internal medicine · 2018Article
- Timing and Characteristics of Cumulative Evidence Available on Novel Therapeutic Agents Receiving Food and Drug Administration Accelerated Approval.The Milbank quarterly · 2017Article
- Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system.BMJ (Clinical research ed.) · 2017Article
- Physician-pharmacist agreement about off-label use of medications in private clinical settings in Baghdad, Iraq.Pharmacy practiceArticle
Corrections and comments
- Commented on by
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo characterize the types of comparators and endpoints used in efficacy trials for approvals of supplemental indications, compared with the data supporting these drugs' originally approved indications.
designSystematic review.
settingPublicly accessible data on supplemental indications approved by the US Food and Drug Administration from 2005 to 2014.
main outcome measuresTypes of comparators (active, placebo, historical, none) and endpoints (clinical outcomes, clinical scales, surrogate) in the efficacy trials for these drugs' supplemental and original indication approvals.
resultsThe cohort included 295 supplemental indications. Thirty per cent (41/136) of supplemental approvals for new indications were supported by efficacy trials with active comparators, compared with 51% (47/93) of modified use approvals and 11% (7/65) of approvals expanding the patient population (P<0.001), almost all of which related to pediatric patients (61/65; 94%). Trials using clinical outcome endpoints led to approval for 32% (44/137) of supplemental approvals for new indications, 30% (28/93) of modified indication approvals, and 22% (14/65) of expanded population approvals (P=0.29). Orphan drugs had supplemental approvals for 40 non-orphan indications, which were supported by similar proportions of trials using active comparators (28% (11/40) for non-orphan supplemental indications versus 24% (10/42) for original orphan indications; P=0.70) and clinical outcome endpoints (25% (10/40) versus 31% (13/42); P=0.55).
conclusionsWide variations were seen in the evidence supporting approval of supplemental indications, with the fewest active comparators and clinical outcome endpoints used in trials leading to supplemental approvals that expanded the patient population.
Indexed as
Identifiers
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.