Modeling the Progression of Illicit Substance Use Patterns from Real World Evidence


Tummala, Hari Prabhath; Bies, Robert R.; & Ramanathan, Murali (2023). Modeling the Progression of Illicit Substance Use Patterns from Real World Evidence. British Journal of Clinical Pharmacology.


Purpose: To investigate an innovative pharmacometrics approach that addresses the challenges of using real-world evidence to model the progression of illicit substance use. Methods: The modeling strategy analyzed real world data from the National Longitudinal Study of Adolescent to Adult Health (AddHealth) survey using survival analyses and differential equations. Respondents were categorized into drug-naïve, active users and non-users. The transitions between categories were modeled using interval-censored parametric survival analysis. The resulting hazard rate functions were used as time-dependent rate constants in a differential equation system. Covariate models for sex and depression status were assessed.
Results: AddHealth enrolled 6,504 American teenagers (median age: 16 years, range: 11-21 years); this cohort was followed with five interviews for 22 years (median age 38 years, range: 34-45 years). The percentages of illicit drug users at Interviews 1-5 were 7.7%, 5.9%, 15.8%, 21.4% and 0.97%, respectively. The generalized gamma distribution emerged as the preferred model for the survival functions for transitions between categories. Age-dependent prevalence was obtained from the differential equation system. Active drug use was more prevalent in males, increased in adolescence and college years, peaked at 24 years, and decreased to low levels by 35 years. Depression, which was more frequent in females, increased the drug-naïve-active user transition rates but not the active user-non-user, and non-user-active user transition rates. The evidence did not support an interaction between sex and depression. Conclusion: The model provided a satisfactory approximation for the age-dependent progression of illicit substance use from pre-adolescence to early middle age.



Substance use

Reference Type

Journal Article

Journal Title

British Journal of Clinical Pharmacology


Tummala, Hari Prabhath
Bies, Robert R.
Ramanathan, Murali

Year Published



November 23, 2023



Reference ID