ReviewFrontiers in neurology2023
Study design challenges and strategies in clinical trials for rare diseases: Lessons learned from pantothenate kinase-associated neurodegeneration.
Review in Frontiers in neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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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, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Pharmacological Treatment of Cerebellar Ataxia in Pediatric Ataxia-Telangiectasia: A Systematic Review.European journal of neurology · 2026Pooled it
- Feasibility and safety of sailing based rehabilitation for rare skeletal disorders using wearable sensors and patient reported outcomes.Scientific reports · 2025Trial
- A Real-World Target Trial Emulation of Eteplirsen, Casimersen, and Golodirsen to Evaluate Survival Among Patients with Duchenne Muscular Dystrophy.Advances in therapy · 2026Article
- Digital Motor Outcomes Capture Upper Limb and Mild Stage Impairment in Hereditary Spastic Paraplegia.Neurology and therapy · 2026Article
- Precision Medicine in Neurodegeneration with Brain Iron Accumulation (NBIA) Disorders: An Update on Emerging Treatments.Movement disorders clinical practice · 2026Review
- Study Designs and Crafting Endpoints for Gene Therapy Development Programs in Rare Disease: A Narrative Review.Advances in therapy · 2026Review
- Personalized Medicine for Systemic Sclerosis-Associated Interstitial Lung Disease.Current treatment options in rheumatology · 2025Article
- Mitigating the impact of study-start delays in clinical trials for rare disorders: insights and lessons from a PKAN trial.Orphanet journal of rare diseases · 2025Article
- NGLY1 as an Emerging Critical Modulator for Neurodevelopment and Pathogenesis in the Brain.International journal of molecular sciences · 2025Review
- Involvement of patient organisations in research activities: actions taken and lessons learned in a clinical research study for osteogenesis imperfecta.Orphanet journal of rare diseases · 2025Article
- Increased Survival in Patients With Molybdenum Cofactor Deficiency Type A Treated With Cyclic Pyranopterin Monophosphate.Journal of inherited metabolic disease · 2025Article
- Non-Categorical Analyses Identify Rotenone-Induced 'Parkinsonian' Rats Benefiting from Nano-Emulsified Punicic Acid (Nano-PSO) in a Phenotypically Diverse Population: Implications for Translational Neurodegenerative Therapies.International journal of molecular sciences · 2024Article
- Longitudinal natural history studies based on real-world data in rare diseases: Opportunity and a novel approach.Molecular genetics and metabolism · 2024Review
- Review
- Novel advanced patient-derivedFrontiers in neurologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 8 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substantial challenges in study design and methodology exist during clinical trial development to examine treatment response in patients with a rare disease, especially those with predominant central nervous system involvement and heterogeneity in clinical manifestations and natural history. Here we discuss crucial decisions which may significantly impact success of the study, including patient selection and recruitment, identification and selection of endpoints, determination of the study duration, consideration of control groups including natural history controls, and selection of appropriate statistical analyses. We review strategies for the successful development of a clinical trial to evaluate treatment of a rare disease with a focus on inborn errors of metabolism (IEMs) that present with movement disorders. The strategies presented using pantothenate kinase-associated neurodegeneration (PKAN) as the rare disease example can be applied to other rare diseases, particularly IEMs with movement disorders (e.g., other neurodegeneration with brain iron accumulation disorders, lysosomal storage disorders). The significant challenges associated with designing a clinical trial in rare disease can sometimes be successfully met through strategic engagement with experts in the rare disease, seeking regulatory and biostatistical guidance, and early involvement of patients and families. In addition to these strategies, we discuss the urgent need for a paradigm shift within the regulatory processes to help accelerate medical product development and bring new innovations and advances to patients with rare neurodegenerative diseases who need them earlier in disease progression and prior to clinical manifestations.
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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.