Use of historical controls to assess emerging interventions in cystic fibrosis: a comparison of methods and a look forward

• Activity Number: 570 - Addressing the Unique Analytic Challenges of Drug Development in Rare Diseases with the Use of Innovative Designs and Real World Evidence in Clinical Trials
• Type: Topic Contributed
• Date/Time: Thursday, August 6, 2020 : 3:00 PM to 4:50 PM
• Sponsor: ENAR
• Author(s): Amalia Magaret*
• Companies: University of Washington
• Keywords: historical controls; inverse probability weighting; real-world evidence

Abstract

We will present a new challenge and some solutions affecting study design in a rare disease setting. The cystic fibrosis community is currently celebrating the recent approval of the most broadly applicable and effective therapy to date, which is indicated to benefit persons with 90% of disease-causing mutations. The quality of life improvements for persons receiving these therapies are radical for some, permitting full-time employment, parenthood, and a long and vibrant adulthood. Non-traditional designs are needed to develop alternative therapies, as persons receiving effective therapy cannot ethically be randomized to unproven alternatives for long periods of time, and persons not receiving effective therapy are few in number. We demonstrate, using a real data example, several approaches to increase power through the use of historical controls: inverse probability weighting and meta-analytic predictive