Application of multiple testing procedures for identifying relevant comorbidities, from a large set, in traumatic brain injury for research applications utilizing big health-administrative data

BACKGROUND: Multiple testing procedures (MTP) are gaining increasing popularity in various fields of biostatistics, especially in statistical genetics. However, in injury surveillance research utilizing the growing amount and complexity of health-administrative data encoded in the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), few studies involve MTP and discuss their applications and challenges. OBJECTIVE: We aimed to apply MTP in the population-wide context of comorbidity preceding traumatic brain injury (TBI), one of the most disabling injuries, to find a subset of comorbidity that can be targeted in primary injury prevention. METHODS: In total, 2,600 ICD-10 codes were used to assess the associations between TBI and comorbidity, with 235,003 TBI patients, on a matched data set of patients without TBI. McNemar tests were conducted on each 2,600 ICD-10 code, and appropriate multiple testing adjustments were applied using the Benjamini-Yekutieli procedure. To study the magnitude and direction of associations, odds ratios with 95% confidence intervals were constructed. RESULTS: Benjamini-Yekutieli procedure captured 684 ICD-10 codes, out of 2,600, as codes positively associated with a TBI event, reducing the effective number of codes for subsequent analysis and comprehension. CONCLUSION: Our results illustrate the utility of MTP for data mining and dimension reduction in TBI research utilizing big health-administrative data to support injury surveillance research and generate ideas for injury prevention.