Food oral immunotherapy (FOIT) is an innovative step forward for food allergy management in both children and adults; however, major concerns have arisen regarding the applicability of clinical trial results due to racial and ethnic disparities in trial participants. Suffian et al reviewed available food immunotherapy clinical trials to quantify representation of participants from diverse racial and ethnic backgrounds. They found racial and ethnic disparities in the 26 randomized clinical trials (RCTs) that met their inclusion criteria. Suffian et al found that Black and Hispanic and/or Latinx participants were underrepresented in RCTs. This raises "concerns about the generalizability and applicability of clinical trial results among these highly burdened populations."
Clinical guidelines for managing any disease are created and practiced based on the cumulative evidence obtained through clinical trials and then systematic reviews. RCTs, therefore, must be designed with the end in mind: applicability to patients with the targeted condition. When research participants do not represent the population that the end product is intended to serve, the applications of any findings and any subsequent guidelines they inform are undermined.
Suffian et al highlight how, despite the enthusiasm for FOIT, the current base of knowledge is not representative of the US population racially or ethnically. Recruitment, retention, and racial and ethnic classification efforts related to research in the present form are fraught with issues that create roadblocks for participants, potential patients, researchers, and funders alike. The authors suggest reasonable approaches to potential short-term solutions for governmental agencies and private funding sources to encourage researchers to achieve equity in clinical trial inclusion. But are their recommendations both broad and deep enough to effect the rapid change necessary to (1) confidently apply research findings to the appropriate populations and (2) achieve true health equity that allows all patients to access life-changing food allergy therapies such as FOIT?
Although health disparities are rampant and persistent in the prevalence and morbidity of atopic disease, most suggested solutions to-date have concentrated on downstream influences. Specifically, improvements in clinical care management, inclusion reports for clinical trials, and, more recently, reclassification focus on how to define a person's race and ethnicity through governmental agencies. The problem with these approaches is that downstream influences do not change the upstream decisions that drive inequitable research studies, resulting in disparate outcomes. While we agree with Suffian et al that RCT recruitment should be equitable, focusing on RCT recruitment alone does not guarantee that studies will successfully obtain the diversity needed to confidently apply findings to diverse populations of children and adults with food allergies.
The solutions lie in multilevel interventions that address health equity and focus on the structural and social determinants of health (SDOH) driving these inequities. Addressing such issues is expensive, difficult, and requires long-term investment but avoids the piecemeal bandaging that has been done for years hoping to solve health disparities. Therefore, we must address the crux of the issue: the SDOH Healthcare Access and Quality pillar. Simply stated, children and adults do not have access to the services they need.
We also agree with Suffian et al that we need standardized definitions for races and ethnicities that are universally accepted beyond the NIH. Regardless of whether funding sources are public or private, it is in the best interest of patients and of science to know to which population a treatment may be applicable. Therefore, research bodies need to track recruitment and prioritize equitable recruitment-goal strategies. We must incorporate community-based participatory research (CBPR) into recruitment and retention. Additionally, research teams themselves must be diverse.
Parallel to these approaches, we must take a step back and comprehensively assess the issues at play that ultimately result in study outcomes that are not powered to apply to all racial and ethnic groups. We must address access to care through innovative models such as telemedicine and mobile subspecialists. Clinical reimbursement must be commensurate with the time and expertise these interventions require. Establishing protocols for the referral process can decrease bias in referrals for subspecialists and help ensure appropriate management, thereby enhancing true shared decision-making where patients have the power and capacity to make well-informed decisions with their clinicians. Systems-level health care changes are required to reduce wait times once a referral is made and ensure the health care quality provided to patients is appropriate.
When considering the upstream challenges that must be addressed to improve participant diversity and ultimately validate the findings of food immunotherapy trials for all populations, we would be remiss to ignore the downstream challenges beyond research studies -- specifically, how to feasibly apply research findings to the appropriate populations. Unfortunately, the very institutions tasked with serving the more commonly marginalized populations are often ill-equipped to provide basic standard-of-care allergy treatments. Examples include institutions that do not offer allergen immunotherapy to treat allergic rhinitis, asthma, and atopic dermatitis, as well as institutions with waiting lists over a year long for ingestion challenges, which is the criterion standard to confirm or rule out whether a patient even has a food allergy. In such inadequate circumstances, how could an advancement like FOIT begin to be offered safely and effectively? The root causes of these issues inevitably lie in the inappropriate use of funds and the lack of creative, engaged physician leadership within health care systems.
Health equity in FOIT, both in research and in clinical practice, is an unrealized dream until the many issues of research (both upstream and downstream) are thoroughly addressed. Will they be? They must be. As one of the most technologically advanced countries in health care that spends the most dollars on health care, we would expect that our population health indicators would far surpass other countries. They do not, even among White US citizens living in the top 1% and 5% wealthiest counties. Despite the poor health care outcomes within the US in comparison with other countries, the bulk of FOIT studies were performed in the US and supported by public or private US funds. Also interesting is Suffian's finding that among these studies, industry studies were more diverse than government-funded studies.
Regardless, we can and must do better. Achieving health equity in FOIT trials starts with ensuring that every child and adult with suspected IgE-mediated food allergies has access to standard-of-care diagnostics and therapeutics. By addressing this fundamental issue, we can pave the way for higher levels of care and participation in clinical trials for future therapies. To truly address racial and ethnic disparities in allergy research, we must begin where the foundation is laid: ensuring true, timely access to quality care for patients with food allergy. This will address the upstream barriers that ultimately help achieve the equitable outcomes our patients deserve.
Corresponding Author: Alice E. W. Hoyt, Hoyt Institute of Food Allergy, 123 Metairie Rd, Ste 203, Metairie, LA 70005 ([email protected]).
Conflict of Interest Disclosures: Dr Hoyt reported receiving speaker fees from Food Allergy Research and Education, Allergy & Asthma Network, and The Food Allergy Counselor, Inc and serving on the board for The Teal Schoolhouse outside the submitted work. Dr Pappalardo reported consulting work and grant funding from Food Allergy Research and Education; she reported receiving grants from American College of Allergy Asthma and Immunology, National Institutes of Health, Northwestern University AHRQ K12, Respiratory Health Association, and American Lung Association; she reported consulting work from Optum Rx/United Health Group fees for program participation with American Academy of Allergy, Asthma and Immunology; and board service with Chicago Asthma Consortium outside the submitted work. No other disclosures were reported.