Trial reportAnnals of translational medicine2022
Novel clinical trial design and analytic methods to tackle challenges in therapeutic development in rare diseases.
Trial report in Annals of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 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
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Ultra-Orphan drug development for GNE Myopathy: A synthetic literature review and meta-analysis.Journal of neuromuscular diseases · 2025Pooled it
- Unlocking the Potential: A Systematic Review of Master Protocol in Pediatrics.Therapeutic innovation & regulatory science · 2024Pooled it
- Bayesian Dynamic Borrowing to Enhance Evidence for New Therapies.PharmacoEconomics · 2026Review
- Review
- Artificial Intelligence in Inherited Epidermolysis Bullosa: Current Evidence, Challenges, and Future Directions.Diagnostics (Basel, Switzerland) · 2026Review
- Areas of research priorities in epilepsy: A position paper of the European Reference Network for Rare and Complex Epilepsies, EpiCARE.Epilepsia open · 2026Article
- An updated review of the SMA clinical trial landscape in the United States: Findings from analysis of recruitment targets on ClinicalTrials.gov and a survey of SMA clinical trial sites on factors affecting site capacity and readiness.Contemporary clinical trials communications · 2026Article
- Consensus for the most suitable trial design to assess therapy for rare vascular malformations: a Delphi study.Scientific reports · 2026Article
- BPED: A Bayesian basket design for pediatric trials with external data.Journal of biopharmaceutical statistics · 2025Article
- The complexity of finding fit-for-purpose real-world data for oncology patients with rareESMO real world data and digital oncology · 2025Article
- Increased Survival in Patients With Molybdenum Cofactor Deficiency Type A Treated With Cyclic Pyranopterin Monophosphate.Journal of inherited metabolic disease · 2025Article
- Single-arm clinical trials: design, ethics, principles.BMJ supportive & palliative care · 2024Review
- Charting a course for global progress in PIDs by 2030 - proceedings from the IPOPI global multi-stakeholders' summit (September 2023).Frontiers in immunology · 2024Article
- Advancing the pipeline of cystic fibrosis clinical trials: a new roadmap with a global trial network perspective.The Lancet. Respiratory medicine · 2023Review
- Treatable traits: a comprehensive precision medicine approach in interstitial lung disease.The European respiratory journal · 2023Article
- Reading Between the Lines: Navigating Nuance in Medical Literature to Optimize Clinical Decision-Making and Health Care Outcomes.Advances in medical education and practice · 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
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While only a fraction of the worldwide population may have a particular rare disorder, millions of people worldwide are affected across the over 6,000 rare disorders and do not have a safe and effective approved therapy to help them live or manage complications from the disorder. Challenges to clinical development of new therapies in rare disorders include difficulty in powering and recruiting into a study in small and often heterogenous population, scarcity of natural history data informing critical design elements such as endpoint selection and study duration, and ethical and recruitment challenges in randomizing patients to a placebo arm. In this review, we describe some existing and novel strategies to tackle these challenges, by efficient utilization of available resources. We discuss the role of natural history studies and endpoint selection as they remain critical features that apply across designs and disorders. We also review some novel clinical trial designs including incorporating external control and/or longitudinal measures, master protocol designs, and adaptive designs. Additionally, we review some analytic strategies that are often associated with these designs, such as the use of causal inference methods, and Bayesian methods. We hope this review will raise awareness of these novel approaches and encourage their use in studies of rare diseases.
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.