Stakeholder Perspectives on Research Consent and Reconsent for Procedures Involving Biological Samples and Biobanking of Children and Adolescents Living With HIV in Kenya

Abstract

Objective

To explore the perspectives of stakeholders on consenting and reconsenting children and adolescents living with HIV (CALWH) to participate in research involving biological sampling and biobanking. Stakeholders included CALWH, their caregivers, subject matter experts (SMEs) such as Institutional Review Board (IRB) members, Community Advisory Board (CAB) members, Healthcare Providers, researchers, and community leaders.

Study design

This qualitative study was conducted at the Academic Model Providing Access to Healthcare (AMPATH) in Kenya. Semi-structured interviews were conducted with CALWH, their caregivers, and SMEs. Audio recordings were transcribed, thematically analyzed, and emerging themes derived.

Results

In total, 99 participants were interviewed, of which the majority (52%) were female; 50% of CALWH were female with a median age of 17.5 years (range 11-24); 70% of caregivers and 44% of SMEs were female. All SMEs, CALWH, and caregivers emphasized that recontacting and reconsenting were their strong preferences for the use of biospecimens and also an essential procedure to address legal and ethical considerations and confidentiality. All CALWH wanted consent to detail how they will be informed about research findings and emphasized making their results available to them. Caregivers highlighted the importance of trust in the use of the stored samples to be maintained as per the consents.

Conclusion

Our findings revealed that CALWH and their caregivers want researchers to go beyond the typical information provided about biospecimen storage and use. They desire to be recontacted and reconsented as well as maintain ongoing communication with the research team about the research findings.

Plain Language Summary

Bioethics of reconsenting biospecimen samples of adolescents and children living with HIV from the perspective of stakeholders

The study explores the bioethics surrounding re-consent for children and adolescents living with HIV from a stakeholder perspective. Stakeholders include children and adolescents living with HIV (CALWH), their caregivers, Institutional Review Board (IRB) members, Community Advisory Board (CAB) members, healthcare providers, researchers, and community leaders. Results found that repeat contacting and reconsenting is an essential procedure to ensure legal and ethical considerations and confidentiality are upheld. The findings suggest researchers should provide comprehensive information on the purpose of biospecimen storage to participants.

Introduction

Globally there are an estimated 1.7 million children and adolescents living with HIV (CALWH) aged 10 to 19 years, with 88% living in African countries. ¹ Human Immunodeficiency syndrome infection (HIV) incidence remains a concern in Kenya with about 83, 000 children aged 0 to 14 years living with HIV with 59% on antiretroviral treatment (ART). ² Despite the advent and availability of combined ARTs, which has significantly reduced morbidity and mortality among children perinatally infected with HIV, HIV remains a public health problem in African countries. ²

CALWH are a complex and vulnerable population; they experience interrelated clinical, behavioral, and social challenges as they transition from childhood into adolescence and young adulthood. ³ Early initiation of ART and associated treatment fatigue make CALWH vulnerable to negative clinical outcomes, with adolescents having particularly poor treatment adherence, high treatment failure, and an accumulation of drug resistance.^4,5 In order to address the unique needs of this population, it is critical that children and adolescents participate in research to investigate challenges and identify evidence-based interventions to improve care for this vulnerable population. One such area of research involves the longitudinal collection of blood specimens.

Biospecimen research and biobanking have significantly increased in the past few decades, ⁶ including for diagnostics, clinical care, and research. ⁷ In resource-limited settings, including many African countries, advanced research and testing of biospecimens has often been done by multinational research teams and involved the transfer of specimens to research laboratories in high-income countries. However, increasingly, biospecimens are now being analyzed and stored at local laboratories and biobanks in Africa. ⁸

Research utilizing the collection and analysis of biospecimens and their storage in biobanks presents a myriad of bioethical issues and challenges. For example, research participants should understand why and how their biospecimens are being used and stored; there should be adequate consent and assent processes for participation (including details on re-consenting, and short and long-term specimen storage, and their future use, if necessary). There is also a need for researchers to observe the privacy and confidentiality of participants across the research process and have consistent regulatory oversight and policies understood and communicated, especially if biospecimens are being transferred or shared with other institutions in or outside of the country. In many settings and populations, there are often social contexts that impact how research involving biospecimen use and storage should be done, including religious beliefs. Other studies have described barriers to providing consent for participation in research where biobanking is involved, including lack of availability and dissemination of results to participants and their concerns about the use of the samples taken.^9,10

Additional bioethical considerations emerge when research involves children and adolescents, who require additional protections, ¹¹ including assent and consent for those who are enrolled as children but reach adulthood during study follow-up, and those living with HIV who often face additional stigma and marginalization. Moreover, the challenges of participants not fully understanding the current and future use of their biospecimens may be heightened for younger populations who are still developing cognitively. Despite these important challenges, there are few empirical investigations on the perspectives of children and adolescent research participants, without and particularly with HIV, concerning research processes such as consenting, recontacting, and reconsenting for research involving biological sampling and biobanking. To address this gap and better understand these challenges, we conducted a qualitative study with CALWH, their caregivers, IRB members,—community advisory board members, healthcare providers, researchers, and community leaders participating in longitudinal clinical research involving biospecimens and biobanking in western Kenya.

Methods

Study Setting

This qualitative study was performed at the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya. AMPATH was established in 2001 and grew to be one of the largest and most effective HIV treatment programs in Sub-Saharan Africa (SSA).^12,13 AMPATH is led by Moi University and Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya, and a consortium of North American universities led by Indiana University School of Medicine, in partnership with national and county governments across western Kenya. AMPATH has enrolled over 200,000 people in HIV care. ¹⁴

This study was nested within a longitudinal cohort (NIH: NIAID R01AI147333) of perinatally infected CALWH to address existing drug resistance research gaps. The original recruitment of this cohort was between 2010 and 2014 for children aged 0 to ≤14 years, with documented perinatal HIV infection and on ART. The parent study conducted adherence assessments, and collected blood for CD4, HIV viral load, and ART concentrations. The research-experienced CALWH were recruited from within those enrolled in this parent study and attending the AMPATH Rafiki Centre of Excellence in Adolescent Health for their HIV care (specific inclusion criteria follows). The research-naïve CALWH were also recruited from within the AMPATH Rafiki Centre. The parent study included repeated collection of biospecimens from those participants, many of which were archived for long periods and shipped to Brown University (an AMPATH partner institution) in Providence, Rhode Island, USA for advanced HIV drug resistance testing phenotyping and genotyping, as well as continued ongoing banking of biospecimens in Kenya.^15–18

Study Design

We conducted qualitative interviews to explore perceptions on bioethical considerations for research participation of CALWH in four different categories of participants: (1) CALWH currently enrolled in the parent study (research-experienced); aware of their HIV status; (2) CALWH not in the parent study and research-naïve; aware of their HIV status; (3) Caregivers of CALWH enrolled in the parent study; and (4) subject matter experts (SMEs) (IRB members, CAB members, healthcare providers, researchers, and community leaders). The interviews focused on the participants’ perspectives on consenting and reconsenting processes for biospecimen collection and storage practices, privacy and confidentiality issues related to stored specimens, the use of samples for future research studies, accessibility of the test results done as part of the research study, and sharing of samples with other researchers outside of the original research team through biobanking.

Data Collection and Analysis

Eligible research experienced CALWH were randomly selected for an invitation to participate if they were enrolled in the parent study, aware of their HIV status, and between the ages of 10 to 24 years. This was done using their scheduled study and clinic visits for the parent study. Eligible research-naïve CALWH were randomly selected during their routine clinic at the Rafiki Center of Excellence in Adolescent Health. They were eligible to participate if they had never participated in a research study, were aware of their HIV status, were between 10 and 24 years, and receiving HIV care at the AMPATH Rafiki Centre . All CALWH included in the study were both perinatally HIV-infected and knew their own HIV status. Caregivers of CALWH were also randomly selected from scheduled visits and were eligible if they were parents/guardians ofCALWH enrolled in the parent study, above 18 years, aware of the child's HIV status, and had knowledge of the child's care and research participation. SMEs were identified by the research team, a multinational group of researchers and academics from Moi University, College of Health Sciences, AMPATH, and Moi Teaching and Referral Hospital, who have been conducting HIV research with children and adolescents in western Kenya for more than a decade. Subject matter experts were identified as experts in community leadership, healthcare provision, research, ethics, and policy. A list was generated by the multinational group of researchers and academics and the facilitators reached out to them for availability for the interviews. SMEs were eligible if they were above 18 years old and included members of adolescent or community advisory boards, community leaders such as village elders and chiefs, healthcare providers, clinical and social researchers within the AMPATH Research Network, AMPATH laboratory leadership, and ethics review board representatives. All the SMEs were Kenyans and lived in Kenya full-time.

The interviews were carried out by trained facilitators from the AMPATH qualitative research core (AQRC) with extensive experience in qualitative interview methods, and fluency in English and Swahili. AQRC is a department at AMPATH consisting of full-time, trained qualitative researchers who provide technical expertise to AMPATH researchers conducting qualitative research in Kenya.

These facilitators had no prior engagement with the study participants. However, the authorship team consists of research staff and co-investigators who had previously participated in the parent R01 of this study and also similar research involving a similar population. A pilot test of the interview guide was conducted with one research-naïve adolescent, one research-experienced adolescent and their caregivers who are accessing care at AMPATH but who had not participated in the parent study and one healthcare worker in the pilot to assess if the questions were comprehensible and appropriate to the study population. The interviews were guided by semi-structured questions in interview guides for the 3 categories of stakeholders: CALWH, caregivers, and SMEs. The research assistants elaborated the meaning of key concepts in a simple language that could be understood by the participants in each category during each section of the guide. “Biospecimen” was described as any biological material obtained from participants such as blood, hair, urine, and body tissue for research purposes. “Future use” was explained as any other use of biospecimens after the initial purpose is completed. The term “broad consent” was described as “participants giving the researchers permission to use their biospecimen in the future for a wide range of research areas without further re-consenting. The research could be the same one or totally different from the original research.” Research assistants were trained to use culturally appropriate probing methods within this context that both ensured that the terms and question items were clear to the participants (assessing understandability), as well as more traditional probing techniques in which they continued to ask participants follow-up questions or more questions about the theme or topic until the issue was addressed thoroughly.

The interviews were conducted in private rooms and participants were interviewed separately. AQRC facilitators determined the thematic saturation after noticing that there were no new surprising results discussed by participants as compared to the initial interviews. Thematic saturation was reached after completing 30 interviews in each category. Some of the SMEs (especially the researchers and ethics review board members) were interviewed via virtual online platforms. De-identified interviews were audio-recorded, transcribed, translated, and verified. This study adopted a thematic analysis approach. Text data were coded using both deductive (theory driven) and inductive (data driven) content analysis and a framework approach. An initial codebook was developed and organized in line with the key research questions; transcripts were reviewed by team members. Initial coding was done by HK and EG and reviewed by JA and AC. Major themes were identified, synthesized, and summarized by HK and EG using NVivo Version 12. A narrative review was used to extract emblematic quotes.

Ethical Review and Approval of the Study

The study was approved by the Icahn School of Medicine at Mount Sinai Institutional Review Board in New York, NY, USA (study number 20-01177); the Institutional Research Ethics Committee at the Moi University School of Medicine/Moi Teaching and Referral Hospital in Eldoret, Kenya (approval number 0003689); and the National Commission for Science, Technology and Innovation (NACOSTI), a Kenyan government research regulatory body (reference number NACOSTI/HW/3/1/16). All participants over the age of 18 years and caregivers provided informed consent. Assent was obtained from participants who were 17 years and below, in addition to informed consent from their parent or guardian. A detailed, standardized informed consent/assent form written in either Kiswahili or English was read aloud with adequate time for questions and clarifications, and written consent/assent was obtained by trained, bilingual research assistants with experience in recruiting children for research.

Results

The Results Presented Below With Illustrative Quotes in Supplemental Tables

Participant Demographics

We enrolled 99 participants in the study, consistent with best practices for thematic saturation; 40 CALWH (20 research experienced and 20 research naïve), 20 caregivers, and 39 SMEs, including 5 community advisory board (CAB) members, 10 health care providers, 5 village chiefs, 5 village elders (community leaders), 5 IRB experts, 5 clinical researchers, 3 social science researchers, and 1 laboratory lead. A slight majority (52%) of all participants were female; 50% of CALWH were female, median age of 17.5 years, (range 11-24), 70% of caregivers were female, and 44% of SMEs were female. During analysis, the participants were categorized into 3 groups: CALWH, caregivers, and SMEs.

Consenting and minimum Levels of Understanding Related to Biospecimen Use, Storage, and Sharing

All participants were asked to consider the consent processes and understanding of biospecimen use and storage for research with this population (Supplemental Table 1). The SMEs emphasized most strongly the need for CALWH to better understand from the consent process why samples were needed, what they were used for, and how they were to be stored and used in the future. This theme was generally supported by the caregivers and CALWH as well, but while most research-naïve adolescents stressed the need to understand the purpose for specimen storage and use, the research-experienced adolescents often expressed trust in the research team once the initial consent was given. Participants across the 3 groups highlighted that consent forms sometimes lacked clarity related to the term “future use,” that study participants in this setting may not understand what is meant or implied by “future use,” and that researchers may not provide enough information for what that would entail. All participants stressed the importance of including these details, particularly what will be done with the biospecimens, where they will be stored, and who will use them, in the original consent documentation. Several research-experienced adolescents emphasized that they trusted the researchers and the institutions involved to make decisions regarding sample storage and specimen use and that this trust was an important factor in whether or not to participate. “Having trust” assured them that their stored samples would be used by professionals and used for the correct purpose, as well as that their information would be kept private to avoid disclosure, as per the consent content. Most caregivers, but only one adolescent (research-naïve female) highlighted the inherent power imbalances that occur after a participant provides a sample, meaning that once the sample is with the researcher, the participant has no control over what is done with and to it. One SME participant also expressed concerns that they did not feel as though adequate informed consent could be obtained if the details surrounding sample use were not clearly discussed and understood as part of the consent process.

Broad Consent and Reconsenting Requirements for Future Use of Biospecimens

Participants discussed the use of broad consent in the research process and the requirements for reconsenting for future use of biospecimens that are held in biobanks (Supplemental Table 2). Broad consent can be used as an alternative to study-specific consent, whereby it allows an investigator to collect data or specimens for a current study, and subsequently use those data in future research without having to obtain additional consent, or reconsent. Broad consent was viewed both positively and with concern. The majority of caregivers cited that broad consent isessential for future use of specimens in order to make the specimens readily available whenever needs for further tests. Moreover, some participants thought that the use of broad consent, including using general, overarching statements regarding the future use of specimens in the original consent form, was sufficient for participants enrolled in research studies. Some participants offered examples of how best to communicate future use in broad consent documents. Participant age was also discussed as an important consideration in the use of broad consent, with many SMEs, IRB members, and community leaders agreeing that adolescents who originally engaged in the research study at less than age 18 should have to reconsent to the future use of specimens when the adolescent turns 18 years. Participants from all categories felt reconsenting would be appropriate due to potential changes in adolescent perspectives with aging and the need for an opportunity to reevaluate their willingness as young adults to have their own biospecimens stored or used in future studies. While all participant categories highlighted concerns related to the use of broad consent, SMEs expressed the most concern, including the unclear future use of samples and the need to ensure that test results and other benefits are returned to sample donors. Both genders of research-naïve and -experienced adolescents raised concerns about potential misuse of stored samples. Examples of misuse include using it for exposing private health issues of individuals, personal benefits, and social practices such as cults.

Participants were also asked to consider whether research participants should be recontacted and reconsented for different uses of biospecimens outside of the original study aims. There was a strong agreement among all CALWH that researchers should recontact participants for consent to use their biological samples in additional research. This was especially true if the samples were going to be used in research studies or analyses unrelated to the original research question; participants gave examples of samples being used for clinical questions unrelated to HIV or sharing samples with another researcher. However, one male participant in the research-naïve, above 18 years group had a different view than the rest; he maintained that initial consent is sufficient for further uses of the specimens. SMEs from across the categories also primarily emphasized that participants must be contacted to reconsent, except one male community lead, a chief who expressed that after the initial consent, ownership of the specimen changes, and there is no need to reconsent for its use. Similarly, some female caregivers thought that reconsenting was not required for future use of biological samples, citing that the original sample was provided for research purposes and that was sufficient; once samples were provided, they were viewed as the researcher's responsibility and that it involves a lot of work to contact a participant to reconsent. Confidentiality was highlighted as a reason for reconsenting for future use of samples, noting that participants have an agreement with the researcher to maintain their privacy. All participants across the 3 categories viewed confidentiality as essential, particularly the SME participants.

Discussion

Participants in this study discussed the consent process and requirements for research collecting and storing biospecimens, as well as the consent-related considerations for studies that propose future use of biospecimens. Our study highlights participants’ interest in knowing more about the reasons for collecting, storing, and using biological samples in future projects. This is consistent with other studies, in which participants indicated that they would like to know what their samples would be used for. ¹⁹ Comprehension of consent by study participants is critical and investigators should ensure that consents include language that fits with not only the participants’ literacy level, but also with the cultural context. This may be difficult in many settings, especially in multinational research in which language from one country's Institutional Review Board may not be clear or understandable in another setting.

Reconsenting for different uses for samples was the most striking theme. Research studies conducted mostly in high-income countries with adults who have used healthcare in the last 10 years have reported that individuals want to be able to decide whether their samples are used for future research. ²⁰ The majority of participants though, say that their willingness to donate specimens is not affected by the specific details of the future research, such as the disease in question, technology being used, or the methodology of the study. In contrast, studies have found that only a minority, spanning from 4% to 40% of participants, would not provide consent for future unspecified research with their biospecimens. ²¹ Taken together, these findings suggest that, after initial consent, many individuals are not concerned about the various studies for which their samples might be used, with key exceptions, including studies related to cloning and research with vulnerable groups provided that they are informed. It is also important for research teams and biobanks to maintain contact information and protocols to ensure participants with banked specimens are reconsented once they turn 18 years of age. This is to give them the opportunity to exercise their autonomy and to express their values in research participation. This is consistent with research conducted in Canada indicating that minors should be reconsented upon obtaining capacity. ²² However, in this study, while the use of broad consent was recommended by some participants, many also expressed concerns were associated with it. Those who expressed preference for broad consent also maintained that the researcher takes full responsibility for the stored specimen after its initial collection; however, substantial groups of participants in each stakeholder group wanted to have some input on the sample use. These findings concur with those of another study in the United States, where most participants preferred broad consent, citing that “the research would help others,” “I would only have to sign the paper or be asked about the research once,” and “broad consent allows for research in the future that might not have been considered yet.” These findings suggest that individuals are willing to provide broad consent for future research with their biospecimens, but this increases when given consideration of those exceptions. ²⁰

Studies in low and middle-income countries have presented similar findings. In a malaria clinical trial in Uganda, Wendler et al ²³ reported that most participants were willing to permit sample export and storage and waive additional consent for future research, provided the study was approved by an ethics review committee and they were informed about the types of studies stored samples would be used for. Two qualitative studies conducted in Nigeria and South Africa to explore the perspectives of researchers on biobanking reported community support for sample storage and reuse, but on the condition that the appropriate structures were in place to protect the interests of participants, including confidentiality measures. ²⁴ In Egypt, a study on patients’ attitudes regarding their participation in research and with the collection, storage, and future use of blood samples for research purposes reported that adult participants thought that future use of biospecimens should be limited to the original illness being studied. ²⁵ Less is understood about the considerations for future use of biospecimens with children and adolescent participants, particularly those living with HIV in low and middle-income countries.

It is important to note that there are many practical challenges to the feasibility of reconsenting participants who turn age 18 years after they have exited a study, particularly in resource-limited settings. Specifically, during a time of life when adolescents and young adults often relocate for education or work opportunities. Youth frequently change their addresses and phone numbers, and they often move during late adolescence and young adulthood. All of these factors make the potential process of reconsenting very difficult, and in many settings, these challenges are thought to only be solved by the use of a broad consent. In our setting in Kenya, we have had some advantage in being able to reconsent youth participants when the research participants mostly receive HIV care from the same health system (in part because there are a limited number of facilities providing HIV care), and we have been able to maintain systems of robust unique identifiers in the electronic medical record systems for clinical patient identifiers and linking to study identifiers with ethics board approval. This allows research teams to identify changing contact information more readily. In the AMPATH Kenya health system, and its closely embedded research network, we also have robust retention and outreach programs where the patients are followed up closely in the community and through collaboration between the research team and clinical team. For example, in our previously concluded longitudinal studies on treatment failure and drug resistance with the same cohort, ²⁶ we mostly relied on the AMPATH outreach department who routinely traced patients lost to follow-up which included them traveling to the children's last known address and contact families and friends. Additionally, we have used updates clinical contacts data and leveraged our ongoing relationships with families and this has given us confidence in follow-up and reconsenting the majority of participants. Thus, we are may be more able to reach study participants years later than would be feasible in other settings. However, we recognize the challenges of weighing the pros and cons of “broad consent” practices with the many challenges to successfully reconsenting participants out of sheer feasibility.

Strengths and Limitations of the Study

This study has a few limitations. First, the perceptions gathered in this study are from a specific population from Western Kenya and may not be generalized to other populations or regions globally. However, this group was chosen to provide a fairly heterogeneous set of perspectives, and the clinical cohort has been shown to resemble other clinical cohorts of patients living with HIV in African countries. Second, the data were collected qualitatively and we do not have quantitative data to augment the findings. Nonetheless, qualitative inquiry provides rich context and understanding for the cultural and age-specific concerns these populations may experience, and these in-depth data were critical to our objective. Finally, an important strength of this study is the inclusion of different categories of participants (CALWH, their caregivers, and SMEs), particularly those who have participated in research for multiple years provided unique and highly relevant insights as it allows exploration of reconsenting and recontacting participants for research involving biobanking from the perspective of participants, family members, healthcare providers, and research investigators, which further shapes our understanding of this complex topic. However, in past research where longitudinal follow-up of participants has required recontacting, we experienced challenges with finding updated contact information such as phone numbers and home addresses.

Conclusions

CALWH, their caregivers, and other SMEs (IRB members, CAB members, healthcare providers, researchers, and community leaders) want researchers to go beyond the typical information provided about biospecimen storage and use. They desire to be recontacted and reconsented as well as maintain ongoing communication with the research team about the research findings. The challenges of cross-cultural and age-appropriate communications must be carefully met.

Supplemental Material

sj-docx-1-jia-10.1177_23259582241305424 - Supplemental material for Stakeholder Perspectives on Research Consent and Reconsent for Procedures Involving Biological Samples and Biobanking of Children and Adolescents Living With HIV in Kenya

Supplemental material, sj-docx-1-jia-10.1177_23259582241305424 for Stakeholder Perspectives on Research Consent and Reconsent for Procedures Involving Biological Samples and Biobanking of Children and Adolescents Living With HIV in Kenya by Josephine Aluoch, Ashley Chory and Michael Scanlon, Emma Gillette, Hillary Koros, Dennis Munyoro, Celestine Ashimosi, Whitney Beigon, Janet Lidweye, Jack Nyagaya, Allison DeLong, Rami Kantor, Rachel Christine Vreeman, Violet Naanyu, Winstone M. Nyandiko in Journal of the International Association of Providers of AIDS Care (JIAPAC)