Bleeding and mortality outcomes in ITP clinical trials: a review of thrombopoietin mimetics data.
Patients with ITP may have severe thrombocytopenia, putting them at risk for serious bleeding. ITP trials of new treatments must allow use of standard-of-care therapies to prevent serious bleeding. Thrombopoietin mimetic trials used platelet counts and rescue/concomitant medication use as endpoints. These trials were of insufficient size and duration to measure mortality or serious bleeding, which are infrequent with appropriate treatment. A recent Cochrane review criticized the thrombopoietin mimetic registrational trials for inadequately assessing bleeding and survival. We discuss how these endpoints are difficult to measure in clinical trials designed to improve platelet counts and minimize bleeding, in accordance with ethical trial design.
Division of Hematology-Oncology, Duke University Medical Center, Durham, NC, USA. ivy.altomare@duke.edu
Ivy
I
Altomare
Jeffrey
J
Wasser
Vinod
V
Pullarkat
D001565:Benzoates / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use*; D015994:Incidence; D010976:Platelet Count; D016016:Proportional Hazards Models; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D011720:Pyrazoles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D011961:Receptors, Fc / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012107:Research Design; D059039:Standard of Care; D013926:Thrombopoietin / Q000819:agonists* / Q000627:therapeutic use; D016896:Treatment Outcome
D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag