Kenneth Getz1, Zachary Smith2, Laura Shafner3, Adam Hanina3. 1. Tufts Center for the Study of Drug Development, Tufts University School of Medicine, 75 Kneeland Street, Suite 1100, Boston, MA, 02111, USA. Kenneth.getz@tufts.edu. 2. Tufts Center for the Study of Drug Development, Tufts University School of Medicine, 75 Kneeland Street, Suite 1100, Boston, MA, 02111, USA. 3. AiCure, 19 West 24th Street, 11th Floor, New York, NY, 10010, USA.
Abstract
BACKGROUND: Although there is broad agreement that the accurate estimation of non-adherence rates in clinical trials is essential to determining the dose-response relationship, treatment safety and efficacy effects, no accurate estimates have ever been produced. METHODS: This study used a novel platform combining artificial intelligence and virtual patient monitoring to identify and quantify the scope of unreported intentional non-adherence in clinical trials of new medical therapies. Nearly 260,000 observations were drawn from a convenience sample of 2976 study volunteers participating in 23 clinical trials of psychiatric, neurological and neuromuscular diseases. RESULTS: The results indicate that 4% of all confirmed doses were intentionally non-adherent, 48% of all study volunteers had at least one intentionally non-adherent dose and 5% of study volunteers were intentionally non-adherent for more than one-third of all doses required. CONCLUSIONS: Several factors were associated with, and predictive of, unreported intentional non-adherence including clinical trial phase; clinical trial duration; geographic location where the study was conducted; and investigative site enrollment volume. The findings also show that although the overall rate of intentional non-adherence does not change over the course of a clinical trial, study volunteers who deliberately chose not to take their first dose had a mean intentional non-adherence rate five times higher than that observed among those who were first dose adherent. Implications of the study results are discussed.
BACKGROUND: Although there is broad agreement that the accurate estimation of non-adherence rates in clinical trials is essential to determining the dose-response relationship, treatment safety and efficacy effects, no accurate estimates have ever been produced. METHODS: This study used a novel platform combining artificial intelligence and virtual patient monitoring to identify and quantify the scope of unreported intentional non-adherence in clinical trials of new medical therapies. Nearly 260,000 observations were drawn from a convenience sample of 2976 study volunteers participating in 23 clinical trials of psychiatric, neurological and neuromuscular diseases. RESULTS: The results indicate that 4% of all confirmed doses were intentionally non-adherent, 48% of all study volunteers had at least one intentionally non-adherent dose and 5% of study volunteers were intentionally non-adherent for more than one-third of all doses required. CONCLUSIONS: Several factors were associated with, and predictive of, unreported intentional non-adherence including clinical trial phase; clinical trial duration; geographic location where the study was conducted; and investigative site enrollment volume. The findings also show that although the overall rate of intentional non-adherence does not change over the course of a clinical trial, study volunteers who deliberately chose not to take their first dose had a mean intentional non-adherence rate five times higher than that observed among those who were first dose adherent. Implications of the study results are discussed.
Entities:
Keywords:
Data quality; Dose adherence; Dose response; Investigational drug safety; Modeling behavior; Non-adherence; Treatment effect size