Introduction
Race, ethnicity, socioeconomic status (SES), and sex are primary determinants of health.1 However, except for sex, these characteristics are generally underreported in randomized controlled trials (RCTs), and when acknowledged, patients from minority groups and/or with a poorer SES are often underrepresented.1,2 This impairs our ability to obtain knowledge exhaustively applicable to patients seen in daily care. Moreover, omitting race and ethnicity from research can conceal health disparities.
ANCA-associated vasculitis is a group of rare small vessel vasculitides, whose prevalence, clinical presentation, and outcome vary across individuals with different race and ethnicity.3 This is likely the result of complex interactions between genetics, environmental exposure, and SES. For instance, Japanese and Chinese patients have anti-myeloperoxidase-ANCA vasculitis with kidney involvement more often than Northern European patients4 and are less likely to present with ophthalmologic and ear, nose, and throat complications.4 Compared with White patients, Black patients with granulomatosis with polyangiitis have more severe neurologic involvement, subglottic stenosis, and a more relapsing disease.4
In this context, and given that a comprehensive appraisal of risk–benefit ratio of a given intervention implies the knowledge of the main patient demographics, we have investigated the adequacy of reporting sex, gender, race, ethnicity, and SES and estimated the representativeness of patients from different racial and ethnic groups in ANCA vasculitis RCTs.
Methods
We followed the PRISMA guidelines. A search of MEDLINE through PubMed and EMBASE was performed on December 19, 2022, to identify primary reports of RCTs on ANCA vasculitis published since 2000. We recorded from full-text and supplementary files which information on patient sex, gender, race, ethnicity, and SES was provided; the definitions used to identify patient's origin (race, ancestry, etc.), how it was assigned (e.g., self-reported), and the reasons for collecting it; the number of patients recruited; and subgroup analysis performed for each racial and ethnic group. This study did not require institutional review board approval because it was based on publicly available information.
Results
We included 45 RCTs, enrolling 5053 patients (median 97 patients) (Table 1). Nine studies (20%), seven of which were published after 2010, including 1445 patients, provided information on patient’s race (n=7) or racial or ethnic group (n=2). In two studies, the authors did not report patient race and ethnicity, but stated that patients were “Chinese”5 in one case or “from Japan” in the other.6 Although we can assume that participants were likely to be Asian, we considered these studies as not reporting race and ethnicity because the authors did not specify whether they were referring to place of residence, nationality, or other features. Patient's SES (education) was described in one study, and determination criteria to define ethnicity/race explained in two studies (self-reported). Race and ethnicity was more often reported after 2010 in larger, multicontinental, industry-funded studies published in high–impact factor journals. In the nine studies reporting race and ethnicity, White patients were the most represented (90%), followed by Asian (3%) and Black (2%) patients. The sex and/or gender of participants was provided in 98% studies, but the authors clearly specified if they reported the sex or gender in 36 studies (80%).
Table 1.
Characteristics of the studies included and differences between those reporting race and ethnicity and those not
| Characteristics | Whole Sample | Race and Ethnicity Reported | Race and Ethnicity Not Reported |
|---|---|---|---|
| n=45 | n=9 | n=36 | |
| Publication year | |||
| 2000–2010 | 17 | 2 | 15 |
| 2011–2022 | 28 | 7 | 21 |
| Journal impact factor, median (IQR) | 8.3 (4.0–25.4) | 51.6 (8.6–54.4) | 7.3 (3.4–14.8) |
| Funding | |||
| Non-industry funded | 22 | 0 | 22 |
| Industry funded | 23 | 9 | 14 |
| Continents | |||
| Europe | 26 | 1 | 25 |
| North America | 2 | 2 | 0 |
| Asia | 6 | 0 | 6 |
| Oceania | 1 | 0 | 1 |
| Intercontinental | 10 | 6 | 4 |
| Diseases | |||
| GPA, MPA | 20 | 7 | 13 |
| GPA, MPA±EGPA or PAN or kidney limited vasculitis | 11 | 0 | 11 |
| GPA alone | 4 | 1 | 3 |
| MPA alone | 3 | 0 | 3 |
| EGPA alone | 4 | 1 | 3 |
| Other | 3 | 0 | 3 |
| Sample size, median (IQR) | 97 (45–140) | 181 (106–197) | 78 (43–124) |
| No. of patients included | 5053 | 1445 | 3608 |
| Intervention | |||
| Pharmacologic | 44 | 9 | 35 |
| Non-pharmacologic | 1 | 0 | 1 |
| Race and ethnicity of participantsa, n (%) | |||
| American Indian or Alaskan Native | 11 (0.7) | ||
| Asian | 49 (3) | ||
| Black | 26 (2) | ||
| Hispanic or Latino | 28 (2) | ||
| Other | 46 (3) | ||
| Unknown | 8 (0.5) | ||
| White | 1306 (90) | ||
| Other reporting information | |||
| Determination criteria to define ethnicity/race explained | 2 | ||
| Reason for collecting racial/ethnic information stated | 0 | ||
| Primary outcome results reported according to race and ethnicity | 0 | ||
| Other than primary outcome results reported according to race and ethnicity | 0 |
Values are the number of studies unless indicated otherwise. EGPA, eosinophilic granulomatosis with polyangiitis; GPA, granulomatosis with polyangiitis; IQR, interquartile range; MPA, microscopic polyangiitis.
Sum can exceed the total number of randomized patients because of the possibility of double ancestry or the overlap between race and ethnic definitions.
Discussion
We show that important demographic variables, such as race and ethnicity of patients with ANCA vasculitis recruited in RCTs, have been rarely reported, mainly in large international trials published after 2010 in high-impact journals. In RCTs describing race and ethnicity, nine of ten participants were White, and <5% were Asian or Black American. Sex and/or gender reporting was widespread but definition not always accurate. Even in rare cases where these demographic characteristics were provided, the studies almost never explained how data on race and ethnicity were collected, whether by patient self-report, health care professionals’ evaluation, or chart review, and the authors never reported if participating patients were representative of the underlying population (of patients) in the enrollment area. This has an effect on the inter-reliability of the use of these variables and on the estimation of study result generalizability and can conceal health disparities that may vary across different regions.
Consistent with other reports,7 our results reinforce the need to improve the reporting of main demographic characteristics and to increase diverse participation in clinical trials overall and specifically in ANCA vasculitis studies. Because the treatment of ANCA vasculitis may vary among different populations,3 it is important to address gaps in inclusion. The underrepresentation of minorities remains an issue also in other systemic autoimmune diseases. A mismatch between the expected and observed number of patients from minorities enrolled in RCTs has been, for example, observed in rheumatoid arthritis, lupus, and systemic sclerosis in different geographic areas.
The findings of this study are limited to RCTs retrieved from studies published in journals indexed in PubMed and EMBASE. The interpretation of the adequacy of main patient demographics reporting should consider that legislation on personal data protection recognizes in some countries racial or ethnic origin as sensitive data. It is, therefore, important to bear this in mind so as to be able to take account of any bias that may arise. As a strength, we analyzed for the first time the adequacy of main demographics reporting in ANCA vasculitis RCTs and addressed the issue of generalizing their results to non-White populations.
In conclusion, our observation should encourage authors and editors to improve the reporting of main demographic characteristics of patients with ANCA vasculitis recruited in RCTs, including SES, and promote more inclusive recruitment strategies in the field.
Acknowledgments
The present work was selected for presentation at the Annual American College of Rheumatology Congress held in San Diego, November 10–15, 2023.
Disclosures
X. Puéchal has been an investigator in academic studies of ANCA-associated vasculitis for which rituximab was provided by Roche Pharma. X. Puéchal has been an investigator in studies evaluating avacopan (ChemoCentryx) and vilobelimab (InflaRx) in ANCA-associated vasculitis. X. Puéchal has been an investigator in studies evaluating benralizumab (AstraZeneca) and mepolizumab (GSK) in EGPA. X. Puéchal has declared Congress inscription and/or travel (GSK and Vifor). All remaining authors have nothing to disclose.
Funding
None.
Author Contributions
Conceptualization: Michele Iudici, Xavier Puéchal.
Data curation: Michele Iudici, Juan Camilo Rueda Sanchez.
Formal analysis: Michele Iudici.
Methodology: Charlotte Girard-Guyonvarc'h, Michele Iudici, Xavier Puéchal.
Supervision: Michele Iudici, Xavier Puéchal.
Validation: Charlotte Girard-Guyonvarc'h, Michele Iudici, Xavier Puéchal, Juan Camilo Rueda Sanchez.
Writing – original draft: Michele Iudici, Xavier Puéchal.
Writing – review & editing: Charlotte Girard-Guyonvarc'h, Michele Iudici, Xavier Puéchal, Juan Camilo Rueda Sanchez.
Data Sharing Statement
Original data are available at the following repository: https://gitlab.unige.ch/Michele.Iudici1/aav_data_cjasn.git
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Original data are available at the following repository: https://gitlab.unige.ch/Michele.Iudici1/aav_data_cjasn.git