Ethical considerations for genetic research in low-income countries: perceptions of informed consent, data sharing, and expectations in Nicaragua

Participant demographics

A total of 43 individuals participated in this qualitative study: 36 research study participants and seven community stakeholders, representing municipalities in Chinandega (33%), León (53%), and Managua (14%). Of the 36 research participants, 20 were enrolled in the NIDDK genetics study, and 16 were originally enrolled as NIEHS cohort study participants and later consented to GWAS data sharing. All research participants were male, as this was the inclusion criteria for enrollment into both parent studies. The average research participant age was 37, ranging from 22–58 years of age. About 60% of research participants had at most a primary school level of educational attainment. Of the seven community stakeholders, three were health professionals, two were labor union leaders, and two were family members of genetic study participants. These and other demographics are listed in Table 1.

Ethical issues by domains of genetic research

Interviews highlight specific ethical issues related to the following domains of conducting genetic research: 1) knowledge and beliefs about the genetic etiology of disease, 2) informed consent, 3) data use and sharing policies, 4) benefits and risks of participation, and 5) post-study expectations. Within each domain, themes are presented along with opinions and views that differed among research participants from the two parent studies and community members.

Knowledge and beliefs about the genetic etiology of CKDnt

Participants understood basic concepts of genes and disease through their lived experiences. Nearly all study participants (94%) acknowledged associations of hereditary factors to health and disease by naming diseases that affect more than one family member; most listed were kidney disease, diabetes, heart disease, hypertension, and/or various cancers.

Two research participants expressed a deterministic and inevitable view of disease. Genetic-related causes of disease were referenced as being born with strength or insufficiency in the genes, and compared to a contagious virus:

“Genes and health go together like the links of a chain. That is where one inherits all the strength or no strength to a determined disease. One can acquire a mild flu, and another definitely does not acquire it, is immune.” (Miner, NIDDK)

“We have a bad gene in the body, so the kidneys do not work well. The bad gene causes the liquids that we normally expel through our body, to stay in the body and accumulate. Those are bad genes.” (Former sugarcane worker, NIDDK)

At least five research participants noted that CKDnt has come to affect recent generations, and was not experienced in their grandparents’ generation. They were also more likely to emphasize that exposures to environmental factors like excess sun and heat, contaminated water, and air due to nearby industries are significant causes of CKDnt.

“I think that, as it is today, it is the factories that intoxicate the air we breathe and discard waste liquids that end up in the rivers and the potable water. We do not drink it.” (Sugarcane worker, NIEHS)

The majority of research participants (78%) believed kidney disease was also caused by individual behaviors and environmental conditions, and not determined solely by genetics. Poor individual behaviors and harmful personal habits, like not drinking enough water, not wearing adequate protective gear when applying chemicals, overexertion at work, excess sun exposure, alcohol use, and poor nutrition, were often cited as at least partial causes of CKDnt. A combination of behavioral and biological factors was commonly mentioned:

“Not all bodies have the same physique or strength. Some are more vulnerable, have less capacity, and it is also due to lack of care. We take from our body and in the end, we do not put in what it needs.” (Sugarcane worker, NIEHS)

Health workers referenced genetic susceptibility as a risk factor for CKDnt, and, similar to labor leaders, were also concerned about other important environmental health influences. Both family members of the affected expressed a pre-determined view of CKDnt as reflected by this quote:

“Even if you take care of yourself, the disease already comes in the body… in one’s genes. It is part of the family DNA.” (Wife of renal patient)

Understanding of informed consent

The vast majority (97%) of research participants remembered signing the consent form; however, over half (62%) did not recall any specific information on the document. While research participants broadly understood general concepts of genetics and disease, the lack of familiarity with genetic terms seemed to be a barrier to comprehension of informed consent. When asked to explain terms in the consent form (genetics/genética, genes/gen, DNA/ADN, genetic data/datos genéticos, and ancestry/ascendencia), only five research participants (14%) provided a response. The expressions typically used to define genes and DNA were blood type (tipo de sangre), inheritance of characteristics and disease (herencia de carácter y enfermedad), descendancy (descendencia), and ancestry (ascendencia), as illustrated by these quotes:

“Genes or genetics has to do with the collection of data that comes from your father, your father’s father… well, your descendants. The lineage from where we came.”(Sugarcane worker, NIEHS)

“DNA means that you look at the blood type of one and the blood type of the other, right?” (Former sugarcane worker, NIDDK)

“DNA is a disease, right? (Brick worker, NIDDK)

Genetic data are the DNA transferred from our parents and the possible characteristics or diseases that could be inherited from my generation to another generation or vice versa.”

In the community stakeholder interviews, we provided examples of two types of consent: broad and specific. When we asked their opinions, health workers and labor leaders showed preference toward broad consent, because it was shorter and simpler. Other community members, mostly family members, preferred specific consent since they believed it would allow for the intake of information question by question, and would give the participant the opportunity to reflect. Health professionals were partial to broad consent, as it allowed for the use of information in future health studies.

Labor leaders and family members were unsure of what a ‘genetic study’ was and recommended that they also be informed of research studies, as they felt the benefits and risks apply to the whole community. Some community members thought researchers should review the consent form information with the participant’s family, while others, mainly health workers, suggested that family opinions might influence an individual’s personal decision.

Attitudes towards data use and data sharing policy

When asked their opinions about the NIH data-sharing policy, nearly all research participants and community stakeholders required additional time, repetition, and/or explanation of the policies on the consent form, and often asked the interviewer to define “genetic data”. Fewer than half of the interviewees shared any opinion about the policy. However, the majority of the participants who did express opinions believed that more researchers with shared access to information meant more people able to contribute to solutions.

Participants who underwent the original consent form process had a vague comprehension of the fate of their biological samples. Most of these participants did not recall details about the usage of leftover samples for future research purposes, although they mostly noted that their samples would be stored in Nicaragua and later sent to investigators in the U.S. They were also more likely to mention that the original consenting process was rushed, and they would have liked an opportunity to weigh in on the opinions of loved ones.

Participants who underwent the supplemental consent process retained more information on details regarding the use and storage of samples, noting that the biological samples would be analyzed, and surplus samples would be stored in the Ministry of Health (MINSA) laboratories and later sent to the U.S. for future CKD-related research. They were also more likely to mention that the study data would be stored in a computer under a confidential de-identified code.

Many issues were observed with the comprehension of the consent form. The readability assessment on the original consent form (2,418 words) and the supplemental consent form (635 words) each generated a SOL score of 8.8, suggesting a ninth-grade education level is necessary for the comprehension of the text in the consent documents.

Perceptions of benefits and risks of genetic research

Participants described several personal, community, and future benefits of research participation. For example, after blood and urine samples were collected and analyzed, the study protocol included the report-back of individual clinical results of kidney function parameters, such as serum creatinine and urinary protein, to participants during a consult with the study physician. Receiving lab results and consultations was often viewed by participants as health care they may otherwise not have access to:

“The day they came to do my medical check- up, they gave me the results right then, for free. In other places, that amount of exams would not be free, I would get only what I could afford.” (Former sugarcane worker, NIDDK)

Participants expressed understanding that the study may not lead to a cure for those currently affected by CKDnt, but they hoped that identifying the root cause of the disease might lead to a cure or prevention strategy for others in the future.

Only one participant raised concerns about the misuse or mismanagement of shared data and was worried about not knowing the intentions of the recipient:

“Today in these times, you have to know how things are done. If these files are shared with others who you do not know, then other things can happen.” (Former sugarcane worker, NIDDK)

Both groups of consented participants reported positive attitudes when asked about their experiences with the research team. They expressed gratitude for the information the team provided about CKDnt and how it helped them improve their health.

Post-study expectations

Research participants expected the genetic component of the research to reveal whether the disease is inherited. Although most participants could not articulate why the genetic results from their samples were not returned, they had diverse expectations about the information genetic research would yield. Three participants believed the genetic study would identify defects in their genes, but only one of these participants also expected the researchers to inform the individual if they had a “bad gene”. The other two did not expect the researchers to return individual results because they believed the results were confidential and would be retained by research staff for in-depth investigation.

Several participants and community members, especially health professionals, expected updates that would communicate how the research was developing over time and sought information on partnerships with national health institutions:

“Researchers need to give continuity, with a conclusion. We have to go into what this study arrived at, to see how the people are helped, through the same university or through the institutions that have to do with this, well in this case with MINSA, because it is a direct institution of the state for the care of patients.” (Health professional from León)

The main results are summarized in Table 2.