Randomization is not associated with socio-economic and demographic factors in a multi-center clinical trial of children with sickle cell anemia

Abstract

Background: Few studies have investigated factors influencing participation rates for minority children with a chronic disease in clinical trials. The Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial provides an opportunity to study the impact of demographic and socio-economic factors on randomization in a clinical trial among Black children. Our primary objective was to characterize the factors associated with successful randomization of children with sickle cell disease (SCD) and silent cerebral infarct (SCI) in the SIT Trial after initial consent.

Procedure: Differences in socio-economic and demographic variables, family history and disease-related variables were determined between eligible participants who were successfully randomized and those who were not randomized following initial consent. Head of household educational level and family income were examined separately for US versus non-US sites.

Results: Of 1,176 children enrolled in the SIT Trial, 1,016 (86%) completed screening. Of 208 (20%) children with qualifying SCI on pre-randomization MRI, 196 (94%) were successfully randomized. There were no differences in socio-economic, demographic, or disease-related variables between children who were or were not randomized. Participants from non-US sites were more likely to be randomized (22% vs. 12%, P = 0.011); although, randomization by country was associated with neither head of household education nor family income.

Conclusion: In the SIT Trial, acceptance of random allocation was not associated with socio-economic or demographic factors. Although these factors may represent barriers for some participants, they should not bias investigators caring for children with SCD in their approach to recruitment for clinical trial participation.

Keywords: clinical trials; randomization; research participation; sickle cell disease; study recruitment.

Figure 1. Study Participation and Withdrawal in the SIT Trial

Participants in the SIT Trial underwent both an initial screening and pre-randomization MRI. Those with SCI on screening MRI but no progression of disease on pre-randomization MRI or transcranial Doppler were subsequently randomized to transfusions or observation. Groups were defined as: 1) consented participants who missed initial screening MRI, 2) consented participants who had a positive screening MRI but missed pre-randomization MRI, 3) consented participants who were involuntarily dismissed from the study due to abnormal transcranial Doppler ultrasound or progression of disease on pre-randomization MRI and those with MRI failures, 4) consented participants who screened negative on initial MRI, 5) all participants who successfully completed screening MRI, pre-randomization MRI and were eligible for randomization; 6) participants who were eligible for randomization but either declined randomization or were dismissed from the study due to non-adherence, lost to follow-up, etc., and 7) consented participants who were successfully randomized.