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Improving Diversity and Equity in Clinical Trials and Other Rare Disease Clinical Research: Kabuki Syndrome as an Example
Jacqueline Harris, Kennedy Krieger Institute, Baltimore, United States
Objective:
Patients from racial and ethnic minority patients are severely underrepresented in current clinical studies in rare diseases. Kabuki syndrome is a genetic disorder caused by heterozygous variants in either KMT2D and KDM6A. Kabuki syndrome is almost always de novo and, as such, should be equally represented in all racial and ethnic groups. However, a systematic review of literature on Kabuki syndrome revealed that black patients are disproportionately underrepresented in clinical studies in Kabuki syndrome whereas white patients are overrepresented. Limited research has been done to identify barriers to study participation. We hypothesize that access to genetic testing and therefore diagnosis is one barrier to participation in research in certain populations. Our investigation aimed to 1) determine the demographic diversity in rare disease patients (specifically Kabuki syndrome) undergoing clinical studies at a single academic medical center and 2) investigate the sociodemographic factors impacting the timeliness of initial genetic testing among a pediatric cohort with developmental delays, clinical features, dysmorphisms and/or congenital conditions seen in a single Genetics clinic.
We analyzed the database of a group conducting several large clinical research studies in Kabuki syndrome to determine the racial and ethnic composition of participants. We then conducted a retrospective medical chart review of patients seen at a Genetics clinic within an academic medical center to determine their age of initial genetic testing. We looked at all individuals in that clinic and then specifically at individuals with Kabuki syndrome to determine if the data was comparable. Information regarding patient’s sociodemographic variables were extracted. The Child Opportunity Index (COI), a multidimensional measure of neighborhood conditions at the census tract level, was also obtained for the included patients. Regression analyses were utilized to identify significant predictors of the age of initial genetic testing. Race, insurance type (commercial, medical assistance) as a proxy of socioeconomic status, and COI index scores (Education, Health and Environment, and Social and Economic domains) were included as predictors after controlling for age at appointment.
Study 1: Based on analysis of a clinical research database at a large Kabuki syndrome research center patients from minoritized groups are disproportionally underrepresented as are patients of lower socioeconomic status and COI index scores. Study 2: Regression models revealed insurance type and older age of visit as significant determinants of age of initial genetic testing. Patients on medical assistance were older than those with commercial insurance to receive genetic testing. Kabuki syndrome was representative of other genetic rare diseases as it showed similar trends to the entire group.
More research is necessary to elucidate the barriers that impact equitable representation in research of rare diseases like Kabuki syndrome and access to genetics service delivery, which in turn may result in delayed diagnosis and care management including research participation. Factors such as lack of finances and trust of medical providers, and biases from clinicians should be examined more closely, in order to improve minoritized patient inclusion in clinical trials.