Related Experiment Video
Updated: Feb 23, 2026
In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
Published on: December 20, 2017
Clinical Trial Design for Alpha-1 Antitrypsin Deficiency: A Model for Rare Diseases
Adam Wanner1, Stephen C Groft1, J Russell Teagarden1
1Division of Pulmonary and Critical Care Medicine, University of Miami and Alpha-1 Foundation, Miami, Florida.
Abstract:
Clinical research in rare diseases, including alpha-1 antitrypsin deficiency (AATD), faces challenges not shared by common disease research. These challenges may include the limited number of patient volunteers available for research, lack of natural history studies on which to base many clinical trial interventions, an urgency for the development of drug therapies given the often poor prognosis of rare diseases and uncertainties about appropriate biomarkers and clinical outcomes critical to clinical trial design. To address these challenges and initiate formal discussions among key stakeholders-patients, researchers, industry, federal regulators-the Alpha-1 Foundation hosted the Clinical Trial Design for Alpha-1 Antitrypsin Deficiency: A Model for Rare Diseases conference February 3-4, 2014 in Bethesda, Maryland. Discussions at the conference led to the conclusions that 1) adaptive designs should be considered for rare disease clinical trials yet more dialogue and study is needed to make these designs feasible for smaller trials and to address current limitations; 2) natural history studies, including the identification of appropriate biomarkers are critically needed and precompetitive collaborations may offer a means of creating these costly studies; and 3) patient registries and databases within the rare disease community need to be more publicly available and integrated, particularly for AATD. This report summarizes the discussions leading to these conclusions.
Insights
Clinical trials for rare diseases like alpha-1 antitrypsin deficiency (AATD) need adaptive designs and better natural history studies. Integrating patient registries is crucial for AATD research progress.
Area of Science:
- Rare disease clinical research
- Alpha-1 antitrypsin deficiency (AATD) research
Background:
- Rare diseases present unique research challenges, including limited patient populations and lack of natural history data.
- Urgent need for drug therapies and clear biomarkers for rare diseases like AATD, which often have poor prognoses.
Purpose of the Study:
- To address challenges in rare disease clinical trial design.
- To foster discussion among stakeholders including patients, researchers, industry, and regulators.
- To establish a model for rare disease clinical trial design using AATD as a case study.
Main Methods:
- Convened the 'Clinical Trial Design for Alpha-1 Antitrypsin Deficiency: A Model for Rare Diseases' conference.
- Facilitated discussions among key stakeholders: patients, researchers, industry, and federal regulators.
- Summarized conference discussions and conclusions regarding rare disease clinical trial design.
Main Results:
- Adaptive designs are promising for rare disease trials but require further study for feasibility in small populations.
- Natural history studies and biomarker identification are critical needs, potentially addressed through precompetitive collaborations.
- Enhanced public accessibility and integration of patient registries and databases are essential, particularly for AATD.
Conclusions:
- Further research is needed to implement adaptive trial designs effectively in rare diseases.
- Development of natural history studies and biomarkers through collaboration is vital for rare disease therapeutic advancement.
- Improved integration and public access to patient registries will accelerate rare disease research, especially for AATD.
Related Concept Videos
01:11Clinical Trials: Overview
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:15Bioavailability Study Design: Healthy Subjects Versus Patients