What Contribution Does Investigator Bias Play in Enrollment of Diverse Research Subjects?

Disparities in child health are long-standing and persistent, despite decades of research.¹ The causes of these disparities are multi-level, complex and intersectional, yet evidence-based interventions remain elusive. It is well-documented in adult literature that racial and ethnic minorities (Black, Hispanic, Native American/Alaska Native, and Native Hawaiian/Pacific Islander) remain underrepresented in research.² While disparities in representation also exist in pediatric research, the literature is mixed.^3-5 Barriers to the inclusion of diverse populations in research have focused on participant-level factors, such as the social drivers of health. However, less well-known is the contribution that investigator bias plays in the enrollment of diverse study subjects.

This week in Pediatrics, we are early releasing an article, “Disparities by Ethnicity in Enrollment of a Clinical Trial” (10.1542/peds.2021-052595). Eric R. Coon, MD, MS at the University of Utah and colleagues conducted a secondary analysis of data from the Bronchiolitis Follow-up Intervention Trial (BeneFIT), a multi-center, unblinded, non-inferiority randomized trial of 548 participants that compared follow-up with primary care providers for hospitalized children with bronchiolitis (standard) to as needed follow-up.

The authors compared characteristics of the 42 children whom investigators deemed ineligible to participate to the 506 deemed eligible. They found that of the children included, 29% were Hispanic, compared to 52% of those excluded, while there were no racial or ethnic differences in parental acceptance of either intervention. The authors hypothesized that a potential reason for this disparity in enrollment by Hispanic ethnicity was due to provider bias.

So, what can clinicians, investigators, sponsors, and institutions do to create a more inclusive research environment? To answer that question, we invited Ronna Popkin, PhD and her colleagues from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to share their thoughts in the accompanying commentary (10.1542/peds.2021-054150). The authors recommend a layered, multi-level approach that considers the following values: (1) evidence-based training to mitigate bias, racism, and sexism; (2) increase investigator diversity; and (3) minimize bias with specific, clear inclusion and exclusion criteria for research trial participation developed through community-engagement.

Both the Research Briefs and commentary highlight how investigator bias may reduce the generalizability of research trial results and propagate disparities. Reading these articles certainly made me reflect on the biases I have that could affect care provision and research enrollment; hopefully they will encourage you to reflect on your biases as well.

Reference:

1. Flores G, The Committee on Pediatric Research. Racial and Ethnic Disparities in the Health and Health Care of Children. Pediatrics. 2010;125(4):e979-e1020.
2. Ma MA, Gutiérrez DE, Frausto JM, Al-Delaimy WK. Minority Representation in Clinical Trials in the United States. Mayo Clinic Proceedings. 2021;96(1):264-266.
3. Walsh C, Ross LF. Are Minority Children Under- or Overrepresented in Pediatric Research? Pediatrics. 2003;112(4):890-895.
4. Kelly ML, Ackerman PD, Friedman LR. The Participation of Minorities in Published Pediatric Research. J Natl Med Assoc. 2005;97(6):777-783.
5. Abdel-Rahman SM, Paul IM, Hornik C, Sullivan JE, Wade K, Delmore P, et al. Racial and Ethnic Diversity in Studies Funded Under the Best Pharmaceuticals for Children Act. Pediatrics. 2021;147(5):e2020042903.