Estimating dose-response for time to remission with instrumental variable adjustment: the obscuring effects of drug titration in Genome Based Therapeutic Drugs for Depression Trial (GENDEP): clinical trial data

Table 2 Observational analysis of relative dose. Regression output for dose response on time to remission under the Cox and inverse Gaussian model with and without the IV stage 1 residuals introduced as a control variable

	Cox PH model						Inverse Gaussian model
Time to remission	Log HR	95% CI	p value	With stage 1 residuals			CoEff	95% CI	p value	With stage 1 residuals
Time to remission	Log HR	95% CI	p value	Log HR	95% CI	p value	CoEff	95% CI	p value	CoEff	95% CI	p value
							Distance linear predictor
MADRS	− 0.051	− 0.079 to − 0.023	< 0.001	− 0.056	− 0.088 to − 0.024	0.001	0.026	0.018 to 0.035	< 0.001	0.028	0.014 to 0.041	< 0.001
Duration of depressive episode (weeks)	− 0.009	− 0.020 to 0.001	0.086	− 0.010	− 0.020 to 0.001	0.061	0.006	0.002 to 0.009	0.001	0.006	0.002 to 0.010	0.003
Sex (female)	− 0.153	− 0.492 to 0.187	0.378	− 0.338	− 0.747 to 0.072	0.106	0.196	0.066 to 0.325	0.003	0.240	0.063 to 0.417	0.008
							Velocity linear predictor
Age of onset (years)	− 0.007	− 0.024 to 0.009	0.378	− 0.007	− 0.024 to 0.011	0.453	− 0.002	− 0.006 to 0.003	0.457	− 0.002	− 0.00 to 0.003	0.522
BMI (kg/m²)	− 0.034	− 0.068 to − 0.001	0.050	− 0.039	− 0.076 to − 0.003	0.036	− 0.010	− 0.019 to − 0.002	0.020	− 0.012	− 0.021 to − 0.002	0.015
Relative dose	− 0.180	− 0.933 to 0.573	0.639	3.012	0.086 to 5.938	0.044	− 0.029	− 0.218 to 0.160	0.767	0.878	0.152 to 1.603	0.018
Stage 1 residuals				− 3.508	− 6.569 to − 0.447	0.025				− 1.011	− 1.774 to − 0.247	0.009

BMI body mass index, HR hazard ratio, MADRS Montgomery-Åsberg Depression Rating Scale, PH proportional hazard

ISSN: 1745-6215