ALBERT

Description: Background: Factors influencing participation in clinical trials have been reported, but few studies analyze the combination of issues which affect overall patient accrual. When designing clinical trials, investigators are aware that some potential subjects may not be candidates for research participation and other subjects will decline. Total sample size is further affected by protocol-defined eligibility. BABY HUG (NCT00006400) is a randomized, double-blind, placebo-controlled Phase III clinical trial of hydroxyurea (HU), which had an enrollment goal of 200 infants, age 9–17 mo, with Hb SS or Sβ0-thalassemia. A number of screening tests (spleen scan, 99mTc-DTPA renal clearance, abdominal sonogram, transcranial Doppler ultrasound, neuropsychological testing, blood analyses) were required prior to study entry and at exit, with at least monthly follow-up visits during the 2-year study period. To enhance recruitment, an anonymized registry of potential subjects was created to identify factors affecting enrollment. Methods: BABY HUG study coordinators considered all infants with an FS/SS diagnosis on newborn screening who were less than age 17 mo. The coordinators developed an IRB-approved spreadsheet to record the number of potentially eligible subjects; whether parents were approached and, if not, why not; and reasons of those approached for participating or declining. Most of these reasons could be categorized into one of several common themes. Results: Of 1107 potential participants (23–132/center) identified between October 2003 and June 2007, 239 (22%) entered the screening process and 193 (17%) were randomized. More than 25% were not approached for various reasons, including poor adherence to standard clinical care or failing to meet eligibility criteria. Factors influencing enrollment decisions are shown in the figure. The willingness to contribute to medical knowledge, the hope of being randomized to receive the investigational drug (HU), and the desire for closer clinical care were the most common reasons for participating in BABY HUG. Conversely, fear of research, transportation problems, parental work schedules and the demanding nature of the study (with frequent blood samples and clinic visits) were the primary reasons for parents declining. Disease severity had less impact on decision-making, perhaps reflecting the often asymptomatic history of potential subjects. Conclusion: The time and effort required by multiple screening tests and frequent visits impact the willingness of eligible subjects to participate in a study. Similar trials may require a larger pool of potential participants than expected to meet accrual goals. Factors that influence subject availability and the decision-making process of participating families must be considered for successful recruitment. Figure Figure

Description: Abstract 174FN2 Introduction: Neurocognitive deficits by school age in children with sickle cell disease (SCD), with and without a history of stroke, has been well established. However, little is understood with respect to the onset and course of these deficits in early childhood and how these may relate to SES and disease status. We are undertaking a 4-year mixed cross-sectional longitudinal study of early neurodevelopmental status in children younger than 4 years of age with SCD. The primary aims are to: (1) characterize the prevalence and nature of the developmental deficits in infants and toddlers while controlling for socio-economic status (SES); (2) examine the moderating effects of sickle cell phenotype, hematologic severity, and parent characteristics on developmental outcome. The current presentation is based on the first 80 baseline neurodevelopmental evaluations. Patients and Methods: Children 3 ½ years of age or younger with SCD of any phenotype were eligible to participate. Comprehensive neurodevelopmental evaluations using the Bayley Scales of Infant Development were conducted when the child reached specific age levels (9, 15, 21, 30, and 40 months), with an ultimate planned sample size of a minimum of 45 children with SCD at each of the five age levels. Demographics and data regarding phenotype, hematologic variables, and occurrence of pain crises were obtained separately. Results: To date, 199 children have been enrolled in the study. We have conducted 205 evaluations and completed data analysis of the baseline data for 80 patients. Of those 80, phenotype distribution was representative of the sickle cell population (HbSS=56%, HbSC=31%). Gender was balanced (51% female). As expected, race/ethnicity of most children was African/African American (95%), about 5% Hispanic/Biracial. Maternal education attainment was high, as almost half of the mothers (48%) were college graduates. Mean Mental Index was 84.2 (sd=13.5) and Motor Index was 89.1 (sd=14.4) (compared to published norm means of 100, sd=15). Fourteen children (17.5%) had a significant delay (Index score 〉 2 sd below the mean) on either the Mental or Motor Index, with 7 children significantly delayed on both. Lower SES, based on maternal education attainment, was not sufficient to explain developmental delay. Poor performance was present in 10% of children whose mothers were college graduates. Male children were at significantly greater risk for delays, controlling for SES, pain crisis, pneumonia/ACS, and %hemoglobin. Odds ratio of significant developmental delay was 〉9 times more likely among those who had vaso-occlusive pain episode, controlling for SES, gender, pneumonia/ACS, and hemoglobin concentration. Of note, none of the children had been identified as delayed by their primary care physician or sickle cell provider. Conclusions: Early cognitive and motor delays are present in SCD and not sufficiently explained by lower SES. Increased vulnerability of male gender is consistent with other at-risk populations, but has not been previously addressed in SCD research. Significant developmental delay in children with chronic illness may go unrecognized by primary care practices, medical specialty clinics, or parents. The importance of routine neurodevelopmental assessment for children with chronic medical disease, and SCD in particular, is clear. This study was funded by the NHLBI as a Patient Services Project within the Washington Area Comprehensive Sickle Cell Center. Disclosures: No relevant conflicts of interest to declare.