Sickle cell disease affects upwards of 100,000 Americans and is most commonly diagnosed in populations of African or Mediterranean ancestry (Stevens, Patterson, Li, Smith-Whitley, & Barakat, 2016). Sickle cell disease research and therapeutic clinical trials has been impeded by disparities in participation due in part to mistrust of research among racial/ethnic minorities (Stevens et al., 2016). Additionally, there is a lack of funding and availability of new therapeutics or research opportunities for sickle cell disease, generally (Smith, Oyeku, Homer, & Zuckerman, 2006). Finally, sickle cell disease often presents clinically with marked symptoms within the first several months of life, therefore is often associated with diseases of childhood. Previous research has demonstrated that there are pervasive barriers to having clinical trials targeted towards children due to safety concerns and fear of lack of enrollment (Tsukamoto et al., 2016). Even within under-represented pediatric populations, very young children (under the age of three) are further excluded from clinical trial opportunities (Wynn et al., 2010). Given these contextual features, very little is known about clinical trial characteristics that promote or inhibit participants from enrolling. Additionally, very little is known about the rate of early termination of clinical trials (often due to lack of enrollment) or scientific success (defined as dissemination through publication, not necessarily validating a hypothesis) among trials targeting those with sickle cell disease. Thus, the purpose of our overall study was to assess factors related to inclusion and representation in sickle cell disease research. This specific analysis focuses on the relationship between inclusion of very young children (under 3) on study completion, early termination of the study, and publication of study results.
Method.
We conducted a retrospective analysis using existing data from ClinicalTrials.gov, a publically-accessible database. The ClinicalTrials.gov web site was issued in 2000 following the Food and Drug Administration Modernization Act of 1997 that required the National Institutes of Health to create a public information resource on trials regulated by the Food and Drug Administration (ClinicalTrials.gov, 2017). The law expanded in 2007 to require more types of trials to be registered, additional trial information, submission of summary results (including adverse events) and associated penalties for non-compliance (ClinicalTrials.gov, 2017). Submission of all therapeutic clinical trials to ClinicalTrials.gov with expanded fields of inquiry was required from 2007 to present. Over a four week period in June 2016, ClinicalTrials.gov was searched for the keywords “sickle cell” which identified all therapeutic, behavioral, and observational clinical trials that were registered in the database ranging from 1997 to present. Trials were included in the analysis if they pertained to the sickle cell population and had a “status” (completed, terminated, recruiting) outcome present for abstraction. No further inclusion/exclusion criteria were necessary. Key clinical trial variable characteristics were abstracted. Our main independent predictor variable was inclusion criteria of the clinical trial related to pediatric age ranges (defined here as 0 to 18, yes/no) which was further dichotomized into “inclusion of children under 3” (yes/no). Descriptive statistics were calculated to describe clinical trial characteristics, and logistic regressions were calculated to determine the relationship of key predictor variables on our outcomes of interest (study completion, early termination and publication of study findings).
Findings.
526 clinical trials met initial inclusion criteria where data was abstracted, which included clinical trials recruiting for both adult and pediatric age ranges. Of those, 338 clinical trials were pediatric only studies. Of the pediatric studies, 141 (41.7%) included those who had inclusion open to children under 3. Among pediatric studies, the average minimum age range of inclusion was 5.8 years old. Among the pediatric clinical trial sample (n=338), 138 (40.8%) of the studies were completed, 39 (11.5%) of the studies were terminated early, and 110 (32.5%) presented publications that were linked to the clinical trial. In our univariate analysis, there was no statistically significant relationship between eligibility criteria of children under 3 to the outcomes study completion, early termination, or publication of study findings.
Conclusions.
The production of knowledge focused on very young children is limited due to unequal rates of participation in clinical trials. We were interested in assessment of structural (clinical trial features) related to eligibility of young children and the relationship to study outcomes and scientific success. Less than half of the sickle cell disease pediatric clinical trials included children under 3, which alone is a significant study finding. Even within a clinical population that already has limited participation in clinical trials, there may be sub-samples within this group that are at even greater risk for unequal representation in clinical trials and access to advances in drugs, devices, behavioral interventions, and general knowledge about the disease. Nurses often play a key role in clinical trial design and recruitment. There are significant areas related to advocacy and clinical trial design that nurses must play a role in to ensure production of knowledge pertaining to vulnerable populations.
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