Laboratory parameters in prognostic sickle cell disease cohort studies in children: a systematic review and lessons for an appropriate strategy for analysis

Abstract

BACKGROUND: There is a variability of the results in the published prognostic sickle cell disease (SCD) studies. The aim of this article is to assess and demonstrate how the methods used for analysis of laboratory parameters impact the prognostic study results in children with sickle cell disease. METHODS: Firstly, a systematic review of published studies was conducted to identify the methods used in statistical analyses on laboratory parameters. Secondly, four different identified analysis were successively applied on laboratory data collected prospectively in our cohort of newborns with SCD in order to evaluate the association between laboratory parameters and cerebral vasculopathy, depending on the analysis strategy. RESULTS: Thirty-one studies were included in the systematic review in which hemoglobin and reticulocyte counts were the most frequently collected parameters. Through this review, we noted four different statistical strategies. In almost one half of the cohort studies, laboratory parameter was collected only one time per patient. When several values were available, only one statistical analysis considered the time variation. When we applied these four different statistical strategies to our cohort of SCD children, we highlighted that the conclusion on prognostic value of parameters (either as protective or as risk factor) depends on the analysis strategies applied. CONCLUSION: The laboratory parameter prognostic value depends on the analysis strategy chosen for its analysis. It raises fundamental questions about methodological approaches that concern clinician researchers. Identifying prognostic factors is currently essential for better understanding of SCD. Taking into account longitudinal data and standardization of analyses in prognostic cohort studies should allow drawing valuable and reproducible conclusions.