Projected sample size calculations for various secondary stroke prevention trials. (A) In children with sickle cell anemia and silent cerebral infarcts, a hypothetical non-inferior trial of secondary cerebral infarct recurrence (stroke or silent cerebral infarct), comparing standard therapy (blood transfusion) to anticipated benefits of hydroxyurea. (B) Sample size calculation for individuals with sickle cell anemia and strokes, in a superiority trial with two arms being compared: standard therapy (blood transfusion) to a hematopoietic stem cell transplant (experimental arm). (C) In children with sickle cell anemia and silent cerebral infarcts, a superiority trial with two arms being compared: standard therapy (blood transfusion) to a hematopoietic stem cell transplant (experimental arm). *Incidence of infarct recurrence in children with preexisting SCIs receiving blood transfusion therapy.⁴  †Estimated upper boundary non-inferiority threshold is intermediate between the treatment and observation arms in the Silent Cerebral Infarct Trial (2 + 4.8 events per 100 patient-years/2). ‡Incidence of stroke recurrence (silent and overt) in children and young adults with overt stroke receiving regular blood transfusion therapy.⁷  §Incidence of stroke recurrence (silent and overt stroke) in children and young adults after an HSCT.^33,34  ||Estimated incidence of infarct recurrence (silent and overt) in children with SCIs after an HSCT (actual incidence in 10 patients was 0, but incidence estimate is not calculable).