To the Editor,

The use of residual and banked biospecimens from clinical trial enrollees in future research represents an important conduit to advance translational research in hematology/oncology and other areas of medicine [1]. Temporal, demographic, and racial/ethnic disparities observed in the consent to biobanking could impede this progress by limiting data interpretation and generalizability resulting from these secondary analyses, ultimately impacting the development of clinical practice guidelines and patient care [2]. Research on possible inequities related to consent to biobanking can help advance health equity and identify “hidden disparities” – inequalities in consenting to secondary research among individuals who have consented to clinical trial participation – in dependent data analyses.

Of concern, prior studies suggested that significant disparities in biobanking consent rates exist among racial and ethnic minorities [3, 4]. For example, in a Cancer and Leukemia Group B/Alliance Cooperative (CALGB/AC) analysis, higher socioeconomic status and non-Hispanic White race/ethnicity correlated with consent to biobanking among trial participants with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) [5]. So far, however, this association has not been examined in an independent patient cohort, and similar investigations in patients diagnosed with other hematologic malignancies have not been conducted.

Given the lack of data on temporal, demographic, and racial/ethnic trends on biobanking consenting among blood cancer patients enrolled in clinical trials, we analyzed the rates of consent to biospecimen banking among all such trial participants in the Southwest Oncology Group (SWOG) Cancer Research Network from 2000 to 2024 – to our knowledge, the largest study on racial/ethnic disparities regarding biospecimen banking consent, including patients with six different hematologic malignancies (AML, acute promyeloyctic leukemia [APL], ALL, chronic lymphocytic leukemia [CLL], chronic myeloid leukemia [CML], and myelodysplastic syndromes [MDS]). This patient cohort is ideal to study biobanking consent rates as all individuals who provide written informed consent for participation in a SWOG clinical trial must be offered the opportunity to partake in biospecimen submission for banking. If interested, patients needed to provide an additional informed consent for use of their biospecimens for future research purposes.

Collected data included demographic information, disease classification, trial eligibility, trial design, and year of registration. Fisher’s exact, Wilcoxon rank-sum, and logistic regression models were used to evaluate associations. As covariate sparsity allowed, Blinder-Oaxaca decomposition for generalized linear models was applied. All statistical analyses were performed with R (version 4.4.1). This retrospective research was conducted under a research protocol approved by the Institutional Review Board of the Fred Hutchinson Cancer Center (FHCC; #2562).

We identified 3597 adult participants of 28 SWOG trials for inclusion in our analysis. Among these, 86% (n = 3101) consented to biospecimen banking. Supplementary Table 1 and Supplementary Table 2 summarize consent rates across trials by race and ethnicity subgroups. As summarized in Table 1, most trial participants were male (n = 2068, 57%), Caucasian/White (n = 3019, 84%), and non-Hispanic (n = 2901, 81%). Biobanking consent rates were lowest for Hawaiian/Pacific Islanders (n = 8, 53%) and Asians (n = 69, 68%) and highest for Caucasian/Whites (n = 2601, 86%) and African Americans (n = 188, 93%).

Table 1 Characteristics of study population, stratified by consent status.
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Multivariable model selection was based on a priori selection of potential confounders. In a multivariable model adjusting for trial and disease characteristics (specifically, disease at time of treatment, diagnosis, trial design, and year of registration) and sociodemographic factors (specifically, age, gender, race, and ethnicity), older age, single-arm trial design, and earlier year of trial registration were associated with decreased consent to biospecimen banking (Table 2). Racial and ethnic minorities were less likely to consent, with two exceptions: African Americans were more likely to consent compared to Caucasians, and Hispanic patients were more likely to consent compared to non-Hispanic patients. In addition, patients with ALL, CML, or MDS were less likely to consent to future biospecimen use compared to those with AML. Results from Blinder-Oaxaca decomposition are summarized in Supplementary Table 3; 25% of the difference in non-consent rates may be explained by differences in age, type of trial (randomized vs. single-arm), and trial population (relapsed/refractory vs. previously untreated). Importantly, consent to biospecimen use and ethnic diversity increased over time (Table 2, Supplementary Table 4).

Table 2 Logistic regression model results for declining further specimen uses among captured SWOG trials 2000–2024.
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This study differs from previous studies on biobanking consent rates in that all approached patients were already enrolled in a clinical trial; thus, all patients previously consented to participation in clinical research. This willingness itself may positively influence a participant’s perception of clinical research and affect their likelihood of consenting to biobanking. Still, we found significant disparities in the participation to biospecimen banking. First, in our cohort, African American and Hispanic patients enrolled in clinical trials were more willing to consent to biospecimen use. This finding contrasts with prior research, including the CALGB/AC study [5,6,7,8]. To directly compare our data to the latter study, we conducted a subset analysis limited to AML and ALL patients (n = 2486; Supplementary Tables 5 and 6). In this subset, older age, Asian race, Hawaiian/Pacific Islander race, Hispanic ethnicity, and single-arm trial design were associated with declining consent. In contrast to the entire cohort, African American race was not associated with increased consent among patients with AML or ALL. However, analyses like these do not allow for the assessment of causality, and whether such racial/ethnic disparities could be explained by differences in disease biology, which may result in different clinical presentations [9, 10] and/or complex beliefs around data security and genomics in biobanking, is purely speculative and will require further study. Regardless of its underlying cause(s), this finding is noteworthy given historical injustices among racial and ethnic minorities relating to lack of consent and use of genetic information within the medical research community [11, 12]. Examples include the use of genetic material from the Havasupai Tribe and Henrietta Lacks’ “HeLa” biological cell line without informed consent [11, 12]. “HeLa” cells, the first continuous human cell line, controversially aided significant advances in leukemia and hematopoietic cell transplantation research [13]. Further studies on the observed differences in consent rates by race/ethnicity are critical to achieving health equity.

Second, we found patients with ALL, CLL, CML, and MDS were less likely to consent to biobanking compared to patients with AML. To our knowledge, this is the first analysis to compare biobanking consent rates across hematologic malignancies. It is interesting to speculate that differences in disease dynamics (e.g., shorter time from diagnosis to treatment and, thus, clinical trial enrollment for patients with AML [14]) may at least partly account for this observation. Notably, however, disease presentation at time of enrollment (i.e., relapsed/refractory vs. initial presentation) did not influence consent to biobanking after multivariable adjustment.

Third, consent to biobanking and biobanking diversity increased over time in our study population (Table 2, Supplementary Table 4). While comparative studies on changes in biobanking participation rates over time are lacking, participation rates may have increased due to efforts to streamline consent processes, improve confidentiality disclosures, and acknowledge prior inequities. This study also suggests that biobanks and thus secondary data analyses are becoming more representative of our population over time given the increased ethnic diversity among consented patients.

And fourth, older adults were less likely to consent to biobanking across each disease in our cohort (Table 2). Potential explanations include logistical barriers, societal biases and the burden of the consent process itself [15]. Further research on strategies to enhance consent processes for older adults (i.e., having family or caregivers present when consenting to additional studies) may help to better understand age-related disparities in consent.

In summary, in this analysis of 3597 SWOG clinical trial participants, we found that African American and Hispanic patients and patients with AML were more likely to consent to biobanking, while older, Asian, and Hawaiian/Pacific Islander patients and patients in single-arm trials were less likely to consent – a “hidden” disparity among clinical trial participants. In contrast, sex, disease status, and trial eligibility were not significantly associated with consenting after multivariable adjustment. While causality cannot be inferred from our analyses, differences in social and cultural beliefs around clinical research may at least partially underlie racial and ethnic differences in consent rates. In addition, differences in disease severity, trial characteristics (e.g., trial stage and timing of enrollment), and variation in biobanking consent process by disease/malignancy type and institution may contribute to differences in consent by malignancy. Strengths of this study include the large cohort size, diversity of clinical trial and hematologic disease type, and the extensive SWOG clinical trial research affiliate network. Our findings must be interpreted with recognition that race and ethnicity are complex social and cultural constructs. Limitations include lack of socioeconomic variables in our data set (e.g., addresses or zip codes), which may confound or influence differences in consent rates. Limited sample size in subgroups defined by race and ethnicity subgroups precluded interaction and related analyses. Further ethnographic research is needed to understand patient decision-making processes in biobanking and advance health equity in hematological research. Research should also address gaps in understanding among epigenetic differences among various races/ethnicities in hematologic malignancies.