Background: Many pediatric studies describe the association between biological parameters (BP) and severity of sickle cell disease (SCD) using different methods to collect or to analyze BP. This article assesses the methods used for collection and subsequent statistical analysis of BP, and how these impact prognostic results in SCD children cohort studies. Methods: Firstly, we identified the collection and statistical methods used in published SCD cohort studies. Secondly, these methods were applied to our cohort of 375 SCD children, to evaluate the association of BP with cerebral vasculopathy (CV). Results: In 16 cohort studies, BP were collected either once or several times during follow-up. The identified methods in the statistical analysis were: (1) one baseline value per patient (2) last known value; (3) mean of all values; (4) modelling of all values in a two-stage approach. Applying these four different statistical methods to our cohort, the results and interpretation of the association between BP and CV were different depending on the method used. Conclusion: The BP prognostic value depends on the chosen statistical analysis method. Appropriate statistical analyses of prognostic factors in cohort studies should be considered and should enable valuable and reproducible conclusions.