(32) Characterizing Extension Studies in Interventional Research: Twenty Year Trends

Publication Number: 706

Background: Interventional extension studies, including long-term extensions (LTE) and open label extensions (OLE), can provide robust information on the safety and tolerability and efficacy of medicinal products or devices. However, open label extension studies have come under criticism for selection bias and lack of control data. Furthermore, although extension studies are not uncommon, in the authors’ experiences there is a clustering in products for the treatment of neurological and endocrine/metabolic diseases.

Objectives: This research aims to characterize trends in extension studies in interventional research over the last 20 years using metadata from a large clinical trial registry.

Methods: Clinicaltrials.gov was searched for interventional studies containing the terms "long-term extension" or "open-label extension" posted from 01-Jan-2002 to 31-Dec-2021. 1,737 studies were returned and 728 were excluded as they were determined not to be stand-alone extension studies. 1009 studies included in the analysis were mapped to ICD-11 taxonomy based on study indication and divided into 2 time periods: P1: first posted between 2002 and 2011, and P2: first posted date between 2012 and 2021. Studies were further analyzed by study phase, design characteristics and therapeutic area.

Results: There was a 37.4% increase in the number of studies in P2 compared to P1, mainly attributable to studies in early development (phase 1 to phase 2), which increased by75.6%. 12.7% of studies were randomized and 8.0% where OLEs. 19.0% had a parallel groups design and 13.7% were OLEs. 5.9% of studies included masking, with 3.5% of LTEs including masking of both participant and investigator. There were no notable differences between the 2 time periods. Studies were most frequently conducted in diseases of the nervous system (22.9%) followed by endocrine, nutritional or metabolic diseases (12.4%).

Conclusions: These findings point to a trend towards initiating extension studies earlier in development over the last 10 years. We identified a sizable number of OLEs that included control groups and randomization and LTEs that included masking, which serves to generate more scientifically robust results. The finding that extension studies were most frequent in neurological and endocrine/metabolic indications confirmed the authors own experience and may be related to high proportions of rare disease and high disease burden in these areas, which would require further investigation.