ReviewJournal of the National Cancer Institute2019
Seamless Designs: Current Practice and Considerations for Early-Phase Drug Development in Oncology.
Review in Journal of the National Cancer Institute, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Expansion cohorts in phase 1 oncology trials: a systematic review of their design, implementation and outcomes.British journal of cancer · 2026Pooled it
- A Systematic Review of Adaptive Seamless Clinical Trials for Late-Phase Oncology Development.Therapeutic innovation & regulatory science · 2024Pooled it
- Systematic review of combinations of targeted or immunotherapy in advanced solid tumors.Journal for immunotherapy of cancer · 2021Pooled it
- Review
- FDA-AACR Strategies for Optimizing Dosages for Oncology Drug Products: Selecting Optimized Dosages for Registrational Trials.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Using Dose-Escalation and -Expansion Cohort Study as Pivotal Trial for Targeted Anticancer Drug Approval.JCO precision oncology · 2025Review
- Reporting quality of dose-expansion cohorts in trials of anticancer drugs could be improved: a cross-sectional study.Trials · 2025Article
- CAR T-Cell Therapy in Cancer: Balancing Efficacy with Cardiac Toxicity Concerns.Journal of cancer science and clinical therapeutics · 2025Article
- Article
- Lisocabtagene Maraleucel in Relapsed/Refractory Mantle Cell Lymphoma: Primary Analysis of the Mantle Cell Lymphoma Cohort From TRANSCEND NHL 001, a Phase I Multicenter Seamless Design Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Article
- Sensitivity Analyses of Clinical Trial Designs: Selecting Scenarios and Summarizing Operating Characteristics.The American statistician · 2024Article
- Seamless trials in oncology: A cross-sectional analysis of characteristics and reporting.PloS one · 2024Article
- US Food and Drug Administration embraces using innovation to identify optimized dosages for patients with cancer.CPT: pharmacometrics & systems pharmacology · 2023Article
- The role of clinical imaging in oncology drug development: progress and new challenges.The British journal of radiology · 2023Review
- Review
- Early phase clinical trials in oncology: Realising the potential of seamless designs.European journal of cancer (Oxford, England : 1990) · 2023Article
- Development of consensus-driven SPIRIT and CONSORT extensions for early phase dose-finding trials: the DEFINE study.BMC medicine · 2023Review
- Rare molecular subtypes of lung cancer.Nature reviews. Clinical oncology · 2023Review
- Types and progress of clinical trial design for breast cancer: a narrative review.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2023Review
- Recent innovations in adaptive trial designs: A review of design opportunities in translational research.Journal of clinical and translational science · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
Abstract
Traditionally, drug development has evaluated dose, safety, activity, and comparative benefit in a sequence of phases using trial designs and endpoints specifically devised for each phase. Innovations in drug development seek to consolidate the phases and rapidly expand accrual with "seamless" trial designs. Although consolidation and rapid accrual may yield efficiencies, widespread use of seamless first-in-human (FiH) trials without careful consideration of objectives, statistical analysis plans, or trial oversight raises concerns. A working group formed by the National Cancer Institute convened to consider and discuss opportunities and challenges for such trials as well as encourage responsible use of these designs. We reviewed all abstracts presented at American Society of Clinical Oncology annual meetings from 2010 to 2017 for FiH trials enrolling at least 100 patients. We identified 1786 early-phase trials enrolling 57 559 adult patients. Fifty-one of the trials (2.9%) investigated 50 investigational new drugs, were seamless, and accounted for 14.6% of the total patients. The seamless trials included a median of 3 (range = 1-13) expansion cohorts. The overall risk of clinically significant treatment-related adverse events (grade 3-4) was 49.1% (range = 0.0-100%), and seven studies reported at least one toxic death. Rapid expansion of FiH trials may lead to earlier drug approval and corresponding widespread patient access to active therapeutics. Nevertheless, seamless designs must adhere to established ethical, scientific, and statistical standards. Protocols should include prospectively planned analyses of efficacy in disease- or biomarker-defined cohorts of sufficient rigor to support accelerated approval.
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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.