different statistical tools for data analysis

Other common permanent sequelae of SCD that significantly impair patients’ educational attainment, employment status and quality of life include vaso-occlusive crises (VOCs), severe acute and chronic pain, silent cerebral infarcts (silent strokes), increased susceptibility to infections, cognitive morbidity and end-organ damage that occur across lifespan. 1 2 This disorder is currently recognised as a global public health concern, being the leading cause of paediatric stroke (around 11% of unscreened and untreated children and adolescents with SCD will have at least one stroke by the age of 17 years). Sickle cell disease (SCD), a group of inherited blood disorders characterised by mutations in the beta-globin chain of haemoglobin that led to chronic haemolytic anaemia, affects over 3 million people worldwide, with an estimated 300 000 children born with SCD annually-of which 80% are in sub-Saharan Africa. The methodological quality of the trials will be evaluated using the Risk of Bias 2.0 tool, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach.

Dichotomous outcomes will be reported as OR, risk ratio or HR, while continuous data will be reported as standard mean differences, both with 95% CI/credibility interval. Different statistical methods and models will be tested. We will provide a narrative synthesis of the findings, and whenever possible, results will be pooled by means of pairwise or Bayesian network meta-analyses with surface under the cumulative ranking curve analyses. Outcomes of interest will include: vaso-occlusive crisis, haemoglobin levels, chest syndrome, stroke, overall survival and adverse events.

We will include randomised controlled trials comparing the effects of disease-modifying agents in patients with SCD under 18 years old. Searches will be conducted in PubMed, Scopus and Web of Science (no language nor time restrictions) (first pilot searches performed in May 2022). We will follow international recommendations on conduction and report of systematic reviews and meta-analyses. Methods and analysis This systematic review protocol is available at Open Science Framework (doi:10.17605/OSF.IO/CWAE9).

Different statistical tools for data analysis