Beyond Mistrust: Diverse Biobanking Preferences Among Parents and Adolescents with Sickle Cell Disease

Abstract

Purpose

To examine biobanking preferences among adolescents with sickle cell disease (SCD) and parents of children with SCD, to inform best practices for promoting informed consent.

Methods

A purposeful sample of caregivers of patients with SCD (any genotype) (n=200) and adolescents aged 13–18 years (n=100) completed a written survey that included five questions about biobanking, and a subset participated in follow-up interviews.

Results

Adolescents (82.0%) were significantly more willing than parents (69.0%) to grant permission for long-term sample storage (p=0.0237). Both groups expressed support for allowing their samples to be used in research beyond SCD (parents: 75.0%; adolescents: 79.0%; p=0.532). In contrast, support for the use of samples by researchers outside the home institution, conditional on appropriate privacy protections, was more limited (parents: 57.0%; adolescents: 58.0%; p = 0.967). Altruism (78%) supporting participation and mistrust (62%) constraining participation were the most frequent themes shaping participants’ views. Perspectives varied widely regarding sample use, biobanking intentions, permission processes, perceived burden, storage duration, ownership, motivation, reciprocity, trust, potential harm, and privacy considerations.

Conclusion

Substantial diversity in biobanking preferences exist. Teams should consider offering a flexible range of consent options to respect participant autonomy and accommodate the broad spectrum of views revealed in this study.

INTRODUCTION

Patients with sickle cell disease (SCD) are historically under-represented in biobanks,¹ often attributed to a limited willingness to consent to biobanking among African American parents.^2,3 The lack of inclusion of racially minoritized patients with SCD in biobanking has tended toward a monolithic assumption that this is due to medical mistrust.^4,5 Biobanking is a foundational infrastructure that supports modern genetics and genomic medicine. It acts as the bridge between patient samples and the data-driven discoveries relevant to precision medicine. Disparate inclusion in biobanks risks increasing disparities, limiting generalizability, and further marginalizing communities from access to advances in personalized medicine.⁶ The purpose of this study was to learn about biobanking preferences from adolescents with SCD and parents (non-dyadic) of children with SCD to inform best practices for promoting informed consent in biobanks. Learning from this specific study cohort with an existing high participation in biobanking has potential to help inform inclusivity in biobanking.

METHODS

As previously described,⁷ this mixed-method study included a convenience sample of caregivers of patients with SCD (any genotype) and adolescents aged 13–18 during their routine hematology appointments. All participants had previously been approached for participation in the SCCRIP cohort study (Sickle Cell Research and Intervention Program) which has a biobank and clinical data repository.⁸ Participants on this SCDGEN study (Clinical Trial: NCT04416178) completed a written survey which include five questions about biobanking (Table 1). While biobanking was not part of SCDGEN, the cohort had been previously approached for participation in the SCCRIP biobank protocol.⁸ A subset of parental participants participated in follow-up interviews. During the interviews, parents were asked to reflect and conversationally expand upon their previous answers to the survey questions. Interviews were balanced to achieve representation across our age-based clinics (infant/toddler, school age, and teen) to ensure a diversity of illness experiences and continued until thematic saturation was achieved.

Table 1:

Participant Demographics and Survey Responses

Characteristics	Parent Survey	Patient Survey
	n (% or SDa)	n (% or SDa)
Total Participants, n (%)	200 (67)	100 (33)
Age at enrollment
Mean (SD)	NA	15.9 (1.7)a
Race, n (%)b		p value 1
Other	1 (0.5)	1 (1.0)
Black Or African American	199 (99.5)	99 (99.0)
SCD genotype, n (%)		p value 0.931
Hb SB0	5 (2.5)	3 (3.0)
Hb SS	123 (61.5)	59 (59.0)
Hb SC	60 (30.0)	31 (31.0)
Hb SB+	12 (6.0)	7 (7.0)
Education, n (%)
Less than a high school degree	15 (8)	5 (6)
GED or high school diploma	57 (30)	30 (34)
Some college	64 (34)	26 (30)
College graduate	46 (24)	23 (26)
Post-college degree	5 (3)	2 (2)
Prefer not to answer	1 (1)	1 (1)
Annual household income
<$20,000	19 (10)	15 (17)
$20,000 – $39,999	25 (13)	14 (16)
$40,000 – $59,999	17 (9)	9 (10)
$60,000 – $94,999	9 (5)	2 (2)
$95,000 and over	5 (3)	1 (1)
Don’t Know	77 (41)	25 (29)
Prefer Not to Answer	36 (19)	21 (24)
Perceived enrolled in a biobank, n (%)
Yes	188 (94)	87 (87)
No	12 (6)	13 (13)
The hospital keeps a biobank with blood or tissue samples from children with SCD.		p value 0.473
True	180 (91.4)	88 (88.0)
False	17 (8.6)	12 (12.0)
I have been asked if I wanted to store my extra blood or tissue in a biobank for future research.		p value 0.000702
Yes	113 (56.5)	35 (35.0)
No	87 (43.5)	65 (65.0)
I would give my permission for the hospital to store my samples for future research		p value 0.0237
Yes	138 (69.0)	82 (82.0)
No	62 (31.0)	18 (18.0)
I would be okay if researchers used my samples to study diseases other than SCD.		p value 0.532
Yes	150 (75.0)	79 (79.0)
No	50 (25.0)	21 (21.0)
I would be okay if researchers outside of the hospital used my samples for research if my personal health information was protected.		p value 0.967
Yes	114 (57.0)	58 (58.0)
No	86 (43.0)	42 (42.0)

^aChi-square or Fisher’s exact test was used to test the relationship between parents and patients’ responses.

^bIdentified by electronic medical record.

Factual inaccuracies were operationalized as statements made by participants that contradicted verifiable information. A fact-checking guide was created prior to coding. Interview transcripts were segmented into discrete meaning units (i.e., clauses or sentences) that expressed a single factual claim. Each meaning unit was treated as an independent analyzable item. Each factual statement was coded using a two-category scheme: factually inaccurate or accurate. The number of inaccurate statements was held as the numerator and the total number of factual statements was treated as the denominator to calculate the proportion of inaccurate statements (reported as a percentage).

Descriptive statistics were used to summarize the demographic characteristics of parents and patients, as well as their responses to the bio-banking survey. Chi-square or Fisher's exact test was used to test the relationship between parents and patients' responses. For the interviews, three trained coders applied constant comparative methods for inductive thematic transcript analysis using MAXQDA©.⁹ The coders were masters and/or doctoral-level clinical researchers who have completed qualitative research methodology training. Consensus discussion resolved discrepancies.¹⁰ This study was reviewed and approved by the local institutional review board. Informed consent was obtained from all participants (age of legal majority) with informed assent obtained from all minors.

RESULTS

One hundred adolescents with SCD and two hundred parents participated (94% response rate). While 94% of parents and 87% of adolescents perceived participating in a biobank, 95.5% of parents and 93% of adolescents had enrolled via the SCRIPP study. Adolescents and parents (Table 1) demonstrated a high level of awareness regarding the existence of the institutional biobank (91.4% and 88.0%, respectively), with no statistically significant difference observed (p=0.473). However, a significant disparity emerged in participants’ recollection of whether they had previously been asked about storing extra clinical samples for future research. More than half of parents (56.5%) reported remembering such discussions, compared with only 35.0% of adolescents (p < 0.001). Notably, adolescents (82.0%) were also more willing to grant permission for sample storage than parents (69.0%), (p = 0.0237). Both groups supported the use of samples in research beyond SCD (parents: 75.0%, adolescents: 79.0%), (p = 0.532), while support for the use of samples by researchers outside of the institution, contingent upon privacy protections, was more limited (parents: 57.0%, adolescents: 58%), (p = 0.967).

Semi-structured qualitative interviews with parents revealed critical findings regarding caregiver perceptions of biobanking. Most interview transcripts (78%) included factual inaccuracies about biobanking, including therapeutic misestimation (the belief that donating samples would translate into immediate clinical care improvements), confusion about how samples are anonymized, and perception that the sample use is time-limited. As depicted in Table 2, eleven biobank-related topical themes were raised by interviewees as considerations for informed consent (use, intention, permission, burden, duration, ownership, motivation, reciprocity, trust, harm, and privacy). Altruism (78%) supporting participation and mistrust (62%) constraining participation were the most frequent themes shaping participants’ views.

Table 2.

Diverse Preferences: Focus Group Themes and Counter-Themes

Preferences	Theme	Exemplar Quote	Counter-Theme	Exemplar Quote
Use	Disease Expansive	“There’s other diseases as well out there, so if my son can contribute to making things better or help find a solution to some of these diseases, then I’m okay with it.” “Because there’s a lot of disease out there that they don’t have like a lot of resources to. So if they can use some of our samples to help with another disease, if someone has, they need help, I would not, that it wouldn’t be a problem.”	Diagnosis Specific	“My child is a sickle cell patient, so using his blood to study things that are not sickle cell related, it will not be an accurate research because my son is not a child of this category, or my child does not deal with those issues that you are researching.” “I just wouldn’t allow it, like I said, because I don’t know what their intentions is. Even if they explain to me what’s going on, I still wouldn’t allow it because he’s only should be having research done towards sickle cell and nothing else.”
Intention	Convenience and Control Sample	“If other studies are like come about at a later time and they need certain samples for certain diseases, then they’re already there versus going out and recollecting them.” “Biobanking is great because it’s a great asset because it allows you to have samples at hand without having to, okay, let me go try to find another control group or let me go or let me try to pan up an entire new survey of people to give samples.”	Current and Child Sample	“If it’s helpful for her health and benefit for her and others, then maybe yes, or it just depends what else it will be about and how much it would help her.”
Permission	Blanket Consent	“I’m not against it because at the end of the day, I gave my child’s blood and I also signed something and y’all have a small little area where I find saying that y’all still can do what y’all need and want and research this blood the way y’all want to.”	Permission Limited	“If you had my permission, it would be okay… everything should, you know, have someone’s set permission for that next something if you’re going to keep using their blood and their tissue.”
Burden	Low	“It’s not like he has to give a kidney. He produces new blood every day, so a small sample could save someone life.” “I don’t see it causing any harm to my child for you to use blood sitting in your lab already. You aren’t hurting my child to do that.”	High	“He already goes through so much more for his sickle and it is a lot. A whole lot. Then you want more blood here and more blood there. The blood adds up. It’s another thing done to him because of sickle.”
Duration	Longitudinal	“I think that with biobanking and being able to hold those samples and keep them for long periods of time, it just allows you to see what will happen over time and or happen to whatever that sample is over time.” “The thing is that science has future needs so this is helping the future because they store the blood forever.”	Immediate	“My focus in this is today and using it to make better for these kids now.” “They can keep it for now not for forever.”
Ownership	Transition of Specimen Ownership	“Well, it is your blood now. We gave it to you all.”	Maintain Sense of Child’s Ownership	“My child is now almost 14. So, at this age, you would have to ask my child [to continue to use stored specimen]. It’s his blood.”
Motivation	Altruism	“For one, it can help the next person out. I would like to help the next person getting help for my kids themself. So, for me, if I or my kids can help out on getting something done for the next person or the next organization, I’m fine with that.”	Limit Benefit to Sickle Cell Community	“Because it’s like I’m already iffy about the sickle cell research, so anything that’s not pertaining to finding a cure for something she actually has, then I don’t think I’ll be.” “In a selfish manner I would want them to find other stuff, but my purpose in doing it is specifically for research for sickle cell.”
Reciprocity	Mutual Dependence	“I mean, sickle cell disease is just one disease, but it also affects other things. It just, I mean, it affects brain development, it affects organ development, organ functions. So, I mean, it doesn’t necessarily it doesn’t just stop with sickle cell disease because once again the body works together.” “It could be also used for something else other than the actual sickle cell that can help my child or other children. Because as we know, life with hydroxyurea, that is something that’s actually a cancer medicine, but it actually helps for sickle cell.”	Depends on Utility	“It just depends what else it [research] will be about and for who and for why.” “Depends on what that other project is doing.”
Trust	Intact Trust	“I trust the doctors. I trust the team.”	Mistrust	“So, if, if you are completely honest and transparent with the patients, then maybe they’ll be willing to participate, but a lot of times when you ask those questions, you receive a blank answer. So, you know, that that leads to mistrust.” “I mean like you really – I’m not – sometimes I’d be questioning whether or not they actually using it for what they say they’re going to use it for. I have no evidence that’s what they’re doing, but that is pretty much all I really think about. Like if they really using it towards sickle cell or are they actually and putting it into something else?”
Harm	Freedom from Perception of Causing Harm	“I don’t see it causing any harm. So, that’s primarily it. I mean, there’s other diseases as well out there, so if my son can contribute to making things better or help find a solution to some of these diseases, then I’m okay with it. No harm to him or them.”	Fear of Causing Harm	“I feel, but it can be harming to someone else’s child or especially if they’re trying to use my child’s blood to research for someone else’s child. It could become harming because what my child’s blood does, another person’s blood might not do.”
Privacy	Privacy Confidence	“That’s anonymous. So I’m not afraid of anybody giving her information or anything to that nature.”	Privacy Concern	“Could your information be leaked?” “Because you can always go back and if, because these are labeled. Are they labeled or...? It seemed like when I talked to one lady and she told me, I can’t really remember, once the samples were taken, are these samples still labeled to the specific person that the sample came from?”

DISCUSSION

Factual misinformation and not remembering whether biobanking consent was provided were prevalent in our study, as in other biobanking consent studies.¹¹ This gap may reflect normal variation in memory over time or may indicate a communication gap in how biobanking and research use are addressed with adolescents during assent discussions. Study participants identified eleven considerations parallel to existing consensus on essential knowledge needs for understanding biobanking consent.¹² Of key note was the wide range of values and priorities within diverse preferences for each of these eleven topics. Opinions on use, intention, permission, burden, duration, ownership, motivation, reciprocity, trust, harm, and privacy differ considerably within the SCD cohort (Table 2). Awareness of this diversity of perspectives is key to community engagement, tailored communication, and participatory consent processes.¹³ The diverse preferences of this cohort compel creative considerations for biobanking education and consent. Values inform attitudes, which by extension inform educational needs. The goal of informed biobanking consent should be to ensure patient-caregiver understanding sufficient to make an ongoing values-informed choice.

Some parents depicted a “handing over” of the specimen to research in a language that implied a sense of finality in the transfer of the specimen to science, while others described a sense of continued proprietorship. Many parents depicted their fiduciary responsibility as temporary and recognized their child as the specimen owner. As pediatric and adolescent patients are increasingly enrolled in biobanks by their parents, it is important to honor decisional agency through reapproach efforts. Given the diversity of perspectives on biobanking ownership and duration preferences, sensitivity and transparency should guide when and how reapproach occurs (including at timepoints even before the legal age of majority).

Although over 90% of adolescents were aware of biobanks, only one-third of adolescents (35%) recalled conversations about storing extra samples for future research. This may be due to the time lapse between the actual assent (as long as a decade prior) and now being asked about their assent experience. Participatory engagement with adolescents could help layer information about biobanking so that baseline knowledge of its existence translates into tailored awareness of participation options. Engaging communication tools such as interactive websites or videos can help improve adolescent assent experiences.¹⁴ Incorporating creative approaches through engaging informational guides might lead to trustworthy consent options translating over time into more inclusive biobanks. Notably, adolescents were more willing to endorse permission for sample storage than parents. Tailoring communication early on could help guide assent and consent discussions toward values-aligned participation or declination decisions and recall of those decisions.

Parents citing positive attitudes towards biobanking often linked their reasoning to altruism. While some parents preferred to limit any future sample use to assurance of direct benefit to their own child, most parents cited the importance of utilizing samples to advance scientific knowledge to help other children impacted by SCD. A range of receptivity existed regarding the contribution of additional disease knowledge beyond SCD. When discussing the extension of specimen and data use to other diseases and diagnoses, many parents mentioned reciprocity and acknowledged the multi-organ involvement of SCD, with the hope that these extended medical insights could still help patients with SCD. While altruism was a unifying theme, the interviews revealed a range of perceptions on the relevance, lacking a clear connection to the child, and divergent opinions on allowances for use beyond SCD.

Tension arose from the idea of sharing specimens outside the institution where the child receives hematologic care. Hesitancy regarding specimen sharing beyond the immediate care setting was described as concerning due to unfamiliar personnel, questionable intentions, and lack of existing or established trust. The finding that many participants did not want their specimens used outside of the hospital, where relationships exist, reflected not only mistrust but also privacy concerns, re-identification risks, and hesitancy about the logistical safeguarding of specimens across settings. Notably, respondents were not presented with potential benefits of broader sharing of their samples, Prior breast cancer cohort biobank research suggested that framing the question as, “Would you be willing to allow this if it led to faster discovery of new treatments?” increased approval.¹⁵ The layers of benefit may be an additional consideration in interpreting the results of this study and for future exploration of contextual preferences.

Existing literature tends to equate the under-representation of minoritized communities in biobanks through a monolithic lens of mistrust, translating into biobank refusal. Biobanking consent is consistently presented as binary: either participants agree to participate under the stated research terms or decline. This approach may foster barriers to consent and may perpetuate power imbalances.¹⁶ Limiting biobanking consent to yes/no removes nuance, eliminates negotiation, and doesn’t account for partial or conditional agreement. This raises consideration of the ethical permissibility of broad consent models. Broad consent is most convenient for research teams, and yet broad consent may not fully attend to the specific concerns of biobank participants in a way that actualizes preferences or maximizes self-determination.^2,17,18 Clarifying patient ownership and/or considering sharing revenues from downstream discoveries could be a way to further improve the power balance in favor of participants.¹⁵

Proactive trustworthiness in biobanking includes empowering a range of options to honor diverse preferences. Tiered consent processes and flexible consent models may be strategies to improve values-aligned participation.¹⁹ Participation options could include a range: open research or restricting research to SCD disease; mandatory re-assent at various developmental ages or only at the age of majority for continued specimen use; and data management contained to a single institution (local use only) or specific recontact requirements to share specimens/data outside of the institution. Additionally, transparency surrounding consent conversations should also include who does or does not obtain economic gains from potential commercial success from such biobanking endeavors.²⁰ Leaders within the African American community have suggested offering remuneration for commercial success from biobanking samples, which may increase interest in participation.²¹ From an ethics perspective, this would require thoughtful protections from undue influence.

Limitations of this study include that it was conducted at a single site and that adolescents were not interviewed to provide further insight into their biobanking perceptions. All participants had been offered biobank participation. The study includes relatively few individuals who did not participate in the biobank, whose perspectives are arguably more informative about barriers to participation than those of patients who already participate. Despite being a single-site study, the large sample size and representative population yield relevant insights. Inclusion of patients with SCD in biobanks is essential for more widely relevant research outcomes and for equitable treatment advances. The next steps should include intentional, participatory approaches to explore what consent options would be most preferred by the community most impacted by SCD. Flexible consent models may foster trust and help address mistrust. Collaborative and creative approaches would be warranted to ensure the feasibility of each dynamic consent option. The practical potential of offering a diverse range of consent options should be pursued to ensure biobanks are maximally inclusive.

Data Availability:

Individual participant data will not be shared. For deidentified summation format of original data, please contact Dr Meaghan Weaver – Meaghann.Weaver2@stjude.org