TITLE:
Pharmacological Treatment of Adult Attention-Deficit/Hyperactivity Disorder (ADHD) in a Longitudinal Observational Study: Estimated Treatment Effect Strengthened by Improved Covariate Balance
AUTHORS:
Ole Klungsøyr, Mats Fredriksen
KEYWORDS:
Covariate Balance, Propensity Score, Marginal Structural Model, Causal Treatment Effect, ADHD
JOURNAL NAME:
Open Journal of Statistics,
Vol.7 No.6,
December
13,
2017
ABSTRACT: An improved method for estimation of causal effects from observational
data is demonstrated. Applications in medicine have been few, and the purpose
of the present study is to contribute new clinical insight by means of this new
and more sophisticated analysis. Long term effect of medication for adult ADHD
patients is not resolved. A model with causal parameters to represent effect of
medication was formulated, which accounts for time-varying confounding and
selection-bias from loss to follow-up. The popular marginal structural model
(MSM) for causal inference, of Robins et
al., adjusts for time-varying confounding, but suffers from lack of robustness
for misspecification in the weights. Recent work by Imai and Ratkovic[1][2] achieves robustness in the MSM, through improved covariate balance
(CBMSM). The CBMSM (freely available software) was compared with a standard fit
of a MSM and a naive regression model, to give a robust estimate of the true
treatment effect in 250 previously non-medicated adults, treated for one year,
in a specialized ADHD outpatient clinic in Norway. Covariate balance was
greatly improved, resulting in a stronger treatment effect than without this
improvement. In terms of treatment effect per week, early stages seemed to have
the strongest influence. An estimated average reduction of 4 units on the
symptom scale assessed at 12 weeks, for hypothetical medication in the 9 - 12
weeks period compared to no medication in this period, was found. The
treatment effect persisted throughout the whole year, with an estimated average
reduction of 0.7 units per week on symptoms assessed at one year, for
hypothetical medication in the last 13 weeks of the year, compared to no
medication in this period. The present findings support a strong and causal
direct and indirect effect of pharmacological treatment of adults with ADHD on
improvement in symptoms, and with a stronger treatment effect than has been
reported.