TABLE 2.

Common pitfalls in TBI studies and recommendations for future research.

Gaps in evidence/pitfalls	Recommendations
The use of a single biomarker is not sufficient for monitoring patients over time across the TBI spectrum	Biomarker panels are needed for better assessment of diverse clinical phenotypes of patients with TBI. Including markers from different modalities is needed for effective joint benefit.
Heterogeneity in the monitoring of brain injury biomarkers	• More research is needed to explore the optimal sampling protocol for each biomarker.
	• A protocolized algorithm that guides sampling based on the kinetics of each biomarker.
Confounding Factors	Variations could be minimized via employing stratified randomization based on possible confounders such as: • Type and severity of the injury.• Renal functions.
Lack of data from RCTs about the effect of adjuvant pharmacotherapies on different brain injury biomarkers	Exploring potential benefits of the promising agents reported in the current review, such as metformin and tetracyclines, on other emerging biomarkers.
Clinical investigation of novel therapeutic approaches	Promising agents for future clinical research • High dose vitamin D • Melatonin. • Nicotinamides.