Joint longitudinal model-based meta-analysis of FEV1 and exacerbation rate in randomized COPD trials

Figures

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  Fig. 1. Goodness-of-fit plots for the MBMA published model using the combined dataset and published MBMA estimates a Observed FEV1 vs. population predictions; b Observed FEV1 vs. individual predictions; c Absolute individual weighted residuals vs. individual predictions; and d Conditional weighted residuals vs. time

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  Fig. 2. Goodness-of-fit plots for the post-2013 MBMA model using the combined dataset and including new drugs a Observed FEV1 vs. population predictions; b Observed FEV1 vs. individual predictions; c Absolute individual weighted residuals vs. individual predictions; and d Conditional weighted residuals vs. time

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  Fig. 3. Dose-response relationship for fourteen compounds (given as mono-therapy). Reference doses (black dotted line); estimated ED50 (vertical blue dotted line) and Emax (horizontal blue dotted line) parameters and FEV1 response reported in studies between 1996 and 2013 (pink) and between 2013 and 2020 (blue) are shown

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  Fig. 4. Goodness-of-fit plots for the exacerbation rate model using the combined dataset and published model. a Mean annual exacerbation rate vs. population predictions, b Mean annual exacerbation rate vs. individual predictions, c Absolute individual weighted residuals vs. individual predictions and d Conditional weighted residuals vs. arm

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  Fig. 5. Goodness-of-fit plots for the post-2013 exacerbation rate model using the combined dataset. a Mean annual exacerbation rate vs. population predictions, b Mean annual exacerbation rate vs. individual predictions, c Absolute individual weighted residuals vs. individual predictions and d Conditional weighted residuals vs. arms

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  Fig. 6. Relationship between predicted mean annual exacerbation rate and placebo adjusted drug effect on FEV1 for different study year in patients with moderate and severe disease. For predictions, it was assumed a predicted %FEV1 (ppFEV1) of 70 and 40 for moderate and severe patients, respectively; and 61% of patients required to wash out from ICS (Eq. 16). Dots are observed data for moderate (left panel) and severe (right panel) patients; lines are the median annual exacerbation rate for a given year; ribbon represents the continuous interval for studies from 1992 and 2016; ΔΔFEV1 is the placebo adjusted change from baseline in FEV1. ISV and IAV are not included in the predictions

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  Fig. 7. Comparative effectiveness of anti-inflammatory drugs. Point estimate and 95% CI for the relative obtained using the llp option in PsN is displayed for all drugs. Plot is stratified by drug 2

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  Fig. 8. Comparative effectiveness of bronchodilator drugs. Point estimate and 95% CI for the relative obtained using the llp option in PsN is displayed for all drugs. Plot is stratified by drug 2