Introduction: Various statistical approaches can be used to deal with unmeasured confounding when estimating treatment effects in observational studies, each with its own pros and cons. This study... Show moreIntroduction: Various statistical approaches can be used to deal with unmeasured confounding when estimating treatment effects in observational studies, each with its own pros and cons. This study aimed to compare treatment effects as estimated by different statistical approaches for two interventions in observational stroke care data. Patients and methods: We used prospectively collected data from the MR CLEAN registry including all patients (n = 3279) with ischemic stroke who underwent endovascular treatment (EVT) from 2014 to 2017 in 17 Dutch hospitals. Treatment effects of two interventions - i.e., receiving an intravenous thrombolytic (IVT) and undergoing general anesthesia (GA) before EVT- on good functional outcome (modified Rankin Scale <= 2) were estimated. We used three statistical regression-based approaches that vary in assumptions regarding the source of unmeasured confounding: individual-level (two subtypes), ecological, and instrumental variable analyses. In the latter, the preference for using the interventions in each hospital was used as an instrument. Results: Use of IVT (range 66-87%) and GA (range 0-93%) varied substantially between hospitals. For IVT, the individual-level (OR similar to 1.33) resulted in significant positive effect estimates whereas in instrumental variable analysis no significant treatment effect was found (OR 1.11; 95% CI 0.58-1.56). The ecological analysis indicated no statistically significant different likelihood (beta = - 0.002%; P=0.99) of good functional outcome at hospitals using IVT 1% more frequently. For GA, we found non-significant opposite directions of points estimates the treatment effect in the individual-level (ORs similar to 0.60) versus the instrumental variable approach (OR =1.04).The ecological analysis also resulted in a non-significant negative association (0.03% lower probability). Discussion and conclusion: Both magnitude and direction of the estimated treatment effects for both interventions depend strongly on the statistical approach and thus on the source of (unmeasured) confounding.These issues should be understood concerning the specific characteristics of data, before applying an approach and interpreting the results. Instrumental variable analysis might be considered when unobserved confounding and practice variation is expected in observational multicenter studies. Show less
Smit, R.A.J.; Trompet, S.; Dekkers, O.M.; Jukema, J.W.; Cessie, S. le 2019
This thesis investigates the validity and usefulness of physician's preference-based instrumental variable analysis in clinical epidemiological studies. Chapter 2 describes a survey amongst general... Show moreThis thesis investigates the validity and usefulness of physician's preference-based instrumental variable analysis in clinical epidemiological studies. Chapter 2 describes a survey amongst general practitioners, showing substantial variation in prescribing preference and showing prescribing patterns which suggest the stochastic monotonicity assumption may be plausible for physician's preference as an instrumental variable. Chapter 3 describes an application of physician's preference-based instrumental variable analysis in a moderate-sized study, showing uninformatively wide confidence intervals which limit the usefulness of instrumental variable analysis in this setting. Chapter 4 focuses on the bias-variance trade-off of instrumental variable analysis in comparison to conventional analyses, using simulations and theoretical derivations. Chapter 5 compares instrumental variable and conventional estimates of the effect of third versus second generation oral contraceptives on occurrence of venous thromboembolism. The similarity of these estimates under different sets of assumptions suggests major confounding is unlikely. Chapter 6 contains a suggestion for an additional step for reporting of instrumental variable analyses. The focus shifts to Mendelian randomisation in the second part of the thesis. Chapter 7 reviews the methodological approaches used in Mendelian randomisation studies and the quality of reporting. Chapter 8 shows that collider-stratification bias may exist in Mendelian randomisation studies in elderly populations. Show less
Boef, A.G.C.; Dekkers, O.M.; Vandenbroucke, J.P.; Cessie, S. le 2014
