Estimating Treatment Effectiveness of Intracranial Pressure Monitoring in Traumatic Brain Injury.

To the Editor: With great interest, we read the study by Yuan et al (1) in a recent issue of Critical Care Medicine. In this retrospective observational multicenter study, the authors aimed to assess the effectiveness of intracranial pressure (ICP) monitoring in patients with moderate and severe traumatic brain injury (TBI). They found a favorable effect of ICP monitoring on mortality in three subgroups. There are two drawbacks that we would like to address concerning this study. First, multiple subgroups were tested, without prespecification. Testing multiple subgroups within the same patient population is not recommended, as there is a high risk of spurious findings, especially when the subgroup effects are not clinically plausible and prespecified, when the overall treatment effect is neutral, and when the subgroup effects are inconsistent for different (correlated) outcomes (2). Which all is the case in this study. The subgroup results should therefore be interpreted as explorative. Further confirmation in large-scale observational studies is required before drawing more definitive conclusions. Second, the adjustment for confounding by indication has likely been incomplete. As expected, patients with ICP monitoring differed from those not monitored in several aspects. The authors aimed to adjust for confounding by indication by estimating propensity scores of receiving treatment and corrected their analyses accordingly. Propensity scores can however only correct for observed confounders (3) while treatment decisions may also be based on factors that are not captured in the data. As an alternative approach, we would suggest instrumental variable (IV) analyses to estimate treatment effects in observational studies in TBI. IV analysis is a relatively new method that can adjust for unobserved confounders. The instrument should be highly correlated with the treatment under study but not with the observed and unobserved confounders. Since between-center variation in treatment is large in TBI, center might be a suitable instrument. To our knowledge, two studies estimated effectiveness of ICP monitoring using this IV-like approach (4, 5). In both studies, patients treated in centers that more often performed ICP monitoring, had a lower mortality, and had a more favorable outcome. This approach is expected to provide a less biased estimate of treatment effects. In summary, the results of Yuan et al (1) should be interpreted with caution. We recommend future studies with IVlike methods to validate their subgroups findings. Supported, in part, by the European Union FP 7th Framework program (grant 602150). All authors and institutions have received funding from the European Union FP 7th Framework program (CENTER TBI, grant 602150). Dr. David Menon received support for article research from the National Institute for Health Research, United Kingdom. Maryse C. Cnossen, MSc, Hester F. Lingsma, PhD, Center for Medical Decision Making, Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands; Andrew I. R. Maas, MD, PhD, Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium; David K. Menon, MD, PhD, Division of Anaesthesia, University of Cambridge/ Addenbrooke’s Hospital, Cambridge, United Kingdom; and Ewout W. Steyerberg, PhD, Center for Medical Decision Making, Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands