Abstract
Purpose
Given the historical use of limited confounders in multiple sclerosis (MS) studies utilizing administrative health data, this brief report evaluates the impact of incorporating high-dimensional proxy information on confounder adjustment in MS research. We have implemented high-dimensional propensity score (hdPS) and high-dimensional disease risk score (hdDRS) methods to assess changes in effect estimates for the association between disease-modifying drugs (DMDs) and all-cause mortality in an MS cohort from British Columbia (BC), Canada.
Methods
We conducted a population-based retrospective study using linked administrative databases from BC, including health insurance registries, demographics, physician visits, hospitalizations, prescriptions, and vital statistics. The cohort comprised 19 360 individuals with MS, followed from January 1, 1996, to December 31, 2017. DMD exposure was defined as at least 180 days of use for beta-interferon or glatiramer acetate, or at least 90 days for other DMDs. The outcome was time to all-cause mortality. We compared Cox proportional hazards models adjusting for investigator-specified covariates with those incorporating additional empirical covariates using hdPS and hdDRS methods.
Results
In the unadjusted analysis, DMD exposure was associated with a 69% lower risk of mortality (HR 0.31; 95% CI: 0.27–0.36). Adjusting for investigator-specified covariates, the adjusted hazard ratio (aHR) was 0.76 (95% CI: 0.65–0.89). HdPS analyses showed a 20%–23% lower mortality risk (aHRs: 0.77 to 0.80), while hdDRS analyses indicated a 19%–21% reduction (aHRs: 0.79 to 0.81).
Conclusions
Incorporating high-dimensional proxy information resulted in minor variations in effect estimates compared to traditional covariate adjustment. These findings suggest that the impact of residual confounding in the question under consideration may be modest. Further research should explore additional data dimensions and replicate these findings across different datasets.
Given the historical use of limited confounders in multiple sclerosis (MS) studies utilizing administrative health data, this brief report evaluates the impact of incorporating high-dimensional proxy information on confounder adjustment in MS research. We have implemented high-dimensional propensity score (hdPS) and high-dimensional disease risk score (hdDRS) methods to assess changes in effect estimates for the association between disease-modifying drugs (DMDs) and all-cause mortality in an MS cohort from British Columbia (BC), Canada.
Methods
We conducted a population-based retrospective study using linked administrative databases from BC, including health insurance registries, demographics, physician visits, hospitalizations, prescriptions, and vital statistics. The cohort comprised 19 360 individuals with MS, followed from January 1, 1996, to December 31, 2017. DMD exposure was defined as at least 180 days of use for beta-interferon or glatiramer acetate, or at least 90 days for other DMDs. The outcome was time to all-cause mortality. We compared Cox proportional hazards models adjusting for investigator-specified covariates with those incorporating additional empirical covariates using hdPS and hdDRS methods.
Results
In the unadjusted analysis, DMD exposure was associated with a 69% lower risk of mortality (HR 0.31; 95% CI: 0.27–0.36). Adjusting for investigator-specified covariates, the adjusted hazard ratio (aHR) was 0.76 (95% CI: 0.65–0.89). HdPS analyses showed a 20%–23% lower mortality risk (aHRs: 0.77 to 0.80), while hdDRS analyses indicated a 19%–21% reduction (aHRs: 0.79 to 0.81).
Conclusions
Incorporating high-dimensional proxy information resulted in minor variations in effect estimates compared to traditional covariate adjustment. These findings suggest that the impact of residual confounding in the question under consideration may be modest. Further research should explore additional data dimensions and replicate these findings across different datasets.
| Original language | English |
|---|---|
| Article number | e70112 |
| Number of pages | 6 |
| Journal | Pharmacoepidemiology and Drug Safety |
| Volume | 34 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2025 |
Keywords
- administrative health data
- confounder adjustment
- disease risk score
- high-dimensional data
- multiple sclerosis
- propensity score
- residual confounding