ArticleOrphanet journal of rare diseases2016
Directions for new developments on statistical design and analysis of small population group trials.
Article in Orphanet journal of rare diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05072288 (A Remote Physical Activity Program Via the PACE Tool to Counter the Physical Impairments, Accentuated by the Pandemic, in the Population Suffering from Type 1 Myotonic Dystrophy), which is not on this map. Cited by 29 papers, 5 of them syntheses that pooled it.
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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.
A Remote Physical Activity Program Via the PACE Tool to Counter the Physical Impairments, Accentuated by the Pandemic, in the Population Suffering from Type 1 Myotonic Dystrophy
Who cites it
29 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- In Silico Clinical Trials in Drug Development: A Systematic Review.Therapeutic innovation & regulatory science · 2026Pooled it
- Keratin-associated epidermolysis bullosa simplex: phenotypes and challenges in clinical trials - a narrative review and systematic update.Orphanet journal of rare diseases · 2025Pooled it
- Bayesian Approaches for Confirmatory Trials in Rare Diseases: Opportunities and Challenges.International journal of environmental research and public health · 2021Pooled it
- Pooled it
- Physical Therapy and Exercise Interventions in Huntington's Disease: A Mixed Methods Systematic Review.Journal of Huntington's disease · 2017Pooled it
- Trial
- Overview of Regulatory Guidelines Related to Methods and Models for Small Populations.Clinical pharmacology and therapeutics · 2026Review
- Does randomization matter in rare disease clinical trials.PloS one · 2026Article
- A Pharmacometrics-Informed Trial Simulation Framework for Optimizing Study Designs for Disease-Modifying Treatments in Rare Neurological Disorders.CPT: pharmacometrics & systems pharmacology · 2025Article
- Innovative methodologies for rare diseases clinical trials.Orphanet journal of rare diseases · 2024Article
- Translational perspectives to treat Epidermolysis bullosa-Where do we stand?Experimental dermatology · 2020Article
- Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor.Blood · 2020Article
- Profiling trial burden and patients' attitudes to improve clinical research in epidermolysis bullosa.Orphanet journal of rare diseases · 2020Article
- Recommendations for the design of therapeutic trials for neonatal seizures.Pediatric research · 2019Article
- Integrating molecular nuclear imaging in clinical research to improve anticancer therapy.Nature reviews. Clinical oncology · 2019Review
- Regulatory strategies for rare diseases under current global regulatory statutes: a discussion with stakeholders.Orphanet journal of rare diseases · 2019Article
- The patient's view on rare disease trial design - a qualitative study.Orphanet journal of rare diseases · 2019Article
- Evidence supporting regulatory-decision making on orphan medicinal products authorisation in Europe: methodological uncertainties.Orphanet journal of rare diseases · 2018Article
- Recommendations for the design of small population clinical trials.Orphanet journal of rare diseases · 2018Article
- Recent advances in methodology for clinical trials in small populations: the InSPiRe project.Orphanet journal of rare diseases · 2018Review
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4 authors.
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Abstract
backgroundMost statistical design and analysis methods for clinical trials have been developed and evaluated where at least several hundreds of patients could be recruited. These methods may not be suitable to evaluate therapies if the sample size is unavoidably small, which is usually termed by small populations. The specific sample size cut off, where the standard methods fail, needs to be investigated. In this paper, the authors present their view on new developments for design and analysis of clinical trials in small population groups, where conventional statistical methods may be inappropriate, e.g., because of lack of power or poor adherence to asymptotic approximations due to sample size restrictions.
methodFollowing the EMA/CHMP guideline on clinical trials in small populations, we consider directions for new developments in the area of statistical methodology for design and analysis of small population clinical trials. We relate the findings to the research activities of three projects, Asterix, IDeAl, and InSPiRe, which have received funding since 2013 within the FP7-HEALTH-2013-INNOVATION-1 framework of the EU. As not all aspects of the wide research area of small population clinical trials can be addressed, we focus on areas where we feel advances are needed and feasible.
resultsThe general framework of the EMA/CHMP guideline on small population clinical trials stimulates a number of research areas. These serve as the basis for the three projects, Asterix, IDeAl, and InSPiRe, which use various approaches to develop new statistical methodology for design and analysis of small population clinical trials. Small population clinical trials refer to trials with a limited number of patients. Small populations may result form rare diseases or specific subtypes of more common diseases. New statistical methodology needs to be tailored to these specific situations.
conclusionThe main results from the three projects will constitute a useful toolbox for improved design and analysis of small population clinical trials. They address various challenges presented by the EMA/CHMP guideline as well as recent discussions about extrapolation. There is a need for involvement of the patients' perspective in the planning and conduct of small population clinical trials for a successful therapy evaluation.
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