The consent process
To obtain meaningful informed consent from study participants requires the provision of information in a manner that enhances participants’ understanding and appreciation of relevant aspects of proposed research. Having a well-written consent form does not guarantee participants’ understanding, particularly in populations with underdeveloped local languages and high levels of illiteracy which rely on verbal explanations about research. While the consent forms used for the MalariaGEN study outlined all the salient aspects of the research, the research team’s views about what information was most relevant to the intended audience determined what information was provided verbally at these three stages. Broadly speaking, during the community engagement processes and the enrolment of controls at the community level there was more space for discussions about genomic aspects of the research than during recruitment of cases in the ward.
Engaging local communities in genomic research
In KND, the NHRC has established a model of engaging local communities in research based on the traditional practices of the Kassena-Nankana community [32
]. As reported by previous studies conducted in the KND [5
], traditionally, consultation with the gatekeepers of the community (chiefs and elders) is required before any research is carried out in the community, followed by community durbars (meetings) with the wider community. The MalariaGEN study utilised these existing engagement processes.
"We first of all went to talk to the chiefs and then told them that this study is going to be conducted and people would enter the community to talk to community members and pick samples and … when a child gets sick and comes to the ward and it’s severe malaria disease this is what we are going to do [we tried] to explain the study to them. (Research Assistant)"
The MalariaGEN research team reported that this community entry process aimed to seek permission from gatekeepers of the community to conduct the study and to inform the wider community about the proposed research and its implications. The team recognised that the standard community entry process had limitations because women were infrequently involved in the process but had an important role in consenting to research involving young children in emergency situations (which frequently involve severe malaria in this context) [25
Consequently they went a step further than is usual during community engagement exercises for NHRC studies and organised meetings with women’s groups to discuss the MalariaGEN study with them. In total five large community durbars were held in addition to seven smaller meetings with women’s groups.
During community meetings discussions covered the purpose of the study, the procedures, who would be involved and the expected outcomes of the study. Great care was taken to explain scientific aspects of the research and to translate complex information about topics such as DNA and genes into lay local languages with appropriate analogies to facilitate understanding.
"…the thing in the blood that makes us different from one another and can identify people from the same family (Lay translation of genes during community engagement)"
Identifying research populations for community engagement in advance for studies recruiting patients on admission to hospital can be challenging because of the size of the catchment areas for such facilities. In such contexts community engagement strategies such as the durbar have limitations in terms of providing information to prospective participants about the research in advance. However the discussions at the end of the meetings reassured researchers that the project was broadly acceptable to the community and that aspects of genetic and genomic research could be adequately explained to the population. Moreover preparing for, and reviewing the effectiveness of the provision of information in community engagement meetings can provide a valuable means of rehearsing effective provision of complex information during individual consent processes.
"When we are doing the community meetings, that’s when we give more information, we try to explain the science aspects of these things, because you have the time to explain and explain and explain. (Researcher)"
"The experience started with the community entry when we tried to explain [the scientific terms]. The chiefs would be laughing and then they try to give [us] the appropriate word. (Fieldworker recruiting controls)"
Enrolling cases in the hospital
The consent process for recruiting cases (children with severe malaria) into the MalariaGEN study typically involved just the primary carer (usually the mother) who brought a child with severe malaria to the hospital. Discussions about the study were held at least twice. On admission to the hospital, mothers were asked if blood samples could be taken for both routine tests and potentially for research into severe malaria. A single blood draw was made for the purpose of clinical tests and DNA extraction for the research.
A more detailed discussion about the study was held subsequently if the child was eligible to participate. Subsequent to that discussion, if the child’s parent agreed, documentation for enrolment in the study would be completed. Blood for patients who did not meet the research criteria or whose primary care giver declined consent was only used for clinical purposes.
"[The nurses] can't just start taking the sample without telling the mother what we are going to do or what we are about. So from there we give some small summary ‘Excuse me I want to take some little blood from your kid and I will talk to you later… and let you know more about what is in the blood’. (Project staff recruiting cases)"
"…when I went there with my child, it was in the morning so the nurses and doctor attended to my child. At that time the VAST workers were also there so they all helped to set up the water before they came and took the blood to go and test. (Focus group with mothers of cases)"
The research team highlighted the complexities of seeking consent in hospital settings and especially in emergency situations. When children are admitted with severe malaria the priority is to provide appropriate treatment as rapidly as possible. After recruiting the initial cases researchers considered that it was practically impossible and ethically inappropriate to conduct a detailed consent process for research before collecting the samples needed for diagnosis and treatment. Consequently the research team needed to establish how to seek consent in a way that could maximize understanding and free decision-making.
The revised process in place during the rapid assessment involved project staff in charge of recruitment in the paediatric ward observing the condition of the sick child and the emotional state of the mother to ascertain an appropriate time to initiate the consent process. Consent to research was usually sought within 24 to 36 hours of admission. To protect privacy, mothers were invited to a private room for the discussion, although some preferred to discuss the research in the ward next to their child’s bed.
"When the child is brought … [with] the convulsion the child is weak, cannot open his eyes, the mother will be weeping, walking up and down, but by the time they give the drugs, and the child can even talk or respond to the mother, then she feels better, we can then do our consenting. (Project staff recruiting cases)"
There was consensus amongst the mothers interviewed that it was appropriate in the circumstances for a discussion of the project to take place after the blood samples were collected and their child’s condition had stabilised.
"They should take the blood first and when the child gets better before they come to have the discussions with [me]. (Mother of case)"
"In my case it was after my child felt better the following day before they came and had the discussions with me. If the girl [project staff] had come on the day I brought the child I could not have listened to her. (Mother of case)"
While the parents we interviewed were generally satisfied with the timing of the consent process, some mothers noted that they remained anxious about their children when discussions about the project took place.
"When she was discussing with me my attention was there but my child’s illness was also on my mind. (Mother of case)"
Although the consent form covered all the salient aspects of the research including the genetic component, the focus of the discussions during the consent process was the purpose of the study with an emphasis on the rationale for blood-taking. Discussions about malaria genetics were phrased in general terms: ‘the thing in the blood that makes your child sick and other children of the same age group not sick’.
"Then we’ll tell her that we will go to her area to take about two children of the same age and same sex, everything. Those two children must be healthy as well, then we’ll test to [confirm] whether those children are having this sickness. If it happens that they are not, then we will try to know why they’re in the same area and this one has [malaria] while that one is not having it. (Project staff recruiting cases)"
Enrolling controls in the community
Following enrolment of a case, fieldworkers visited the case’s community to enrol a matched ‘healthy’ control (a child whose parents answered ‘Yes’ to the question ‘Is your child well today?’). Enrolling controls involved a traditional multi-layered process where the permission of the head of the compound as well as the head of the household was sought before parents were approached. Fieldworkers noted that it was important for all levels of authority to understand the selection criteria for controls and appreciate why a particular child in their compound was selected.
"Traditionally, around here, before you go into somebody’s house you have to greet, so what we do is … seek permission to enter into the house from the compound head. So you tell theperson of your mission, who you are, where you are coming from and what jobs you want to do in his compound, who you are looking for, let that person understand how you got thatperson’s name. (Fieldworker recruiting controls)"
Discussions about purpose of the visit with compound heads ranged from brief to lengthy, depending on the compound head’s interest in the research. Detailed discussions about the research were then held with household heads and parents. In contrast to cases in the hospital ward, parents of controls often had more leisure to consider participation and wanted more detail about why researchers sought to enrol one of their healthy children in a study. In such circumstances fieldworkers discussed the scientific rationale of the research in further detail.
"Researchers feel that probably it is something to do with human genes because probably you have two people living in the same area… one is always sick with malaria but the other isn’t sick with malaria. When you take them to the laboratory to have a malaria test you might find out that the one that is not sick with malaria has got the malaria parasite, more than one who’s always ill. That means that it is something to do with our genes. Probably the other person's DNA or gene is different from yours, maybe it is stronger, so that fights the malaria though he has the parasite. (Fieldworker recruiting controls)"
Data from fieldworkers illustrated that an important issue when enrolling controls was explaining why blood samples from healthy children were being sought.
"What is unusual is that we go to take [blood from] the controls and not from a sick child but from a healthy child and we are taking blood samples because when your child is sick and you are taking blood you know you are coming for help but my child is not sick and you are coming for blood it is a problem! (Fieldworker recruiting controls)"
Fieldworkers explained that an extensive explanation of the rationale for taking these samples often helped to allay concerns parents might have about this process and refusals to take part in the research were rare.
Knowledge and understandings of genetic and genomic research
Findings from this study demonstrated that in addition to senior researchers and research assistants; project staff, fieldworkers and parents of cases and controls had a good level of comprehension of aspects of the MalariaGEN project relating to malaria, which is a familiar disease in KND.
In contrast, levels of understanding of the complex and unfamiliar topic of genetic research varied considerably amongst staff and participants. Fieldworkers enrolling controls, research assistants and researchers were familiar with the methods used in the study to identify genetic differences between cases and controls which may correlate to susceptibility or resistance to severe malaria. Project staff recruiting cases, and mothers of cases and controls demonstrated less understanding of the methods used in the study.
"They said if I got home, they would visit our compound to get other three children and my child, take their blood sample and my child’s blood sample to compare and see whether their malaria is the same or not. If it is not the same, they have to know why my child’s and theirs is not the same. I don’t understand that aspect of it. (Focus group with mothers of cases)"
Additionally, the research team clearly recognised the difficulty in explaining genomics in local languages and the need to identify innovative ways of explaining the 'essential characteristics' of the genomic research to participants. In general, how much of the science to communicate, given these limitations, remained a challenge at all stages of the engagement process.
"It is very challenging because, the language is pretty much undeveloped, there is no… terminology for those things, you need to explain them… if I were to write how I would explain a gene [ina local language], it is probably like a page, just for one word. (Researcher)"
"We don’t have a term, a single word that we can use to say genes, and so you talk about the blood and then you talk about the individual differences, we say that there are certain thingsin your blood that bring about our individual differences and that is what we want to extract. So with this they actually are able to understand. (Research Assistant)"
Mothers were aware that the MalariaGEN project was aimed at gaining knowledge about malaria to facilitate the discovery of effective treatment. They understood that the project method involved recruiting severely ill children at the hospital as well as healthy children in the community. Mothers understood the rationale of the MalariaGEN project in terms of looking at the children’s blood to find differences which could explain why some children got severe malaria and others did not. However, they did not engage with the scientific methods by which this would be done, and the implications of that are discussed in the following section.
"When they were recruiting us for the study they told me my child has too many parasites and that a team from VAST [NHRC] was coming to conduct a study on malaria so I can decide to be part… they said also that, they will send down some people to come to our community, recruit a child who doesn’t have the malaria and repeat the same process to find out why that child doesn’t have and my child has. (Mother of case)"
"You know there is a kind of malaria that can attack a child and make him collapse; he did not see that happen to our children so he wanted to know why that did not happen to our children. (Mother of control)"
Most mothers could understand a discussion about the genetics of malaria because they related genetics to heredity based on their experiences of diseases that run in families. However, extending this understanding to the broader concept of genomics was more challenging. It was particularly difficult to extrapolate mothers’ knowledge of heredity to explain genomics where such research involves population level sampling that does not necessarily involve families affected by the disease under study.
Sample use and data sharing
One consequence of participants’ understanding the methods of a genomic study in general terms is the difficulty of explaining potential downstream consequences of data sharing and analysis. Researchers and fieldworkers discussed the complexities of explaining the rationale for multiple uses of samples and data, a common feature of genomic research:
"The other difficulty is when you want to talk about data access. Data access in a community that does not appreciate computers…we have to have innovative ways of doing that. You know one time I was talking about data access in the durbar and then the question that came up was is it wireless, is it like TV? (Researcher)"
The MalariaGEN Network has developed a data release policy in conjunction with the ethics committees governing research in communities donating samples [17
]. This policy provides for controlled release of genomic data to legitimate external researchers for acceptable research purposes. In this study we attempted to explore issues relating to the acceptability of future uses of data. Given that the participants were not familiar with scientific methods involved in the research, discussions about future research uses could not focus on genomic data. Nonetheless some exploration of this topic was considered desirable.
During some of the FGDs and interviews questions were couched in broad terms and focussed on a more familiar and related topic of secondary sample use, such as: ‘When they use the blood for a study there may be some left over and an idea could come up for a new study. Would you say they should ask you before using the left over blood for the new study or should they continue working with it?’. Participants indicated that researchers could conduct ongoing studies with left over samples without seeking additional permission from sample donors.
"I think such an idea is not bad because they want to research into finding new solutions to solve our health problems. (Focus group with mothers of cases)"
"If they will be able to research into new solutions, it will be beneficial to us. So we have no problem with that. (Focus group with mothers of cases)"
In addition, some participants asked that they be contacted if relevant findings were generated, a topic considered further below in the discussion about boundaries between research and therapy.
"To me when there is a leftover they can use it if in future there is a study, but they should get me informed later maybe to tell me the results. (Mother of case)"
Boundaries between research and therapy
An additional factor impacting on participants’ understandings of the MalariaGEN study and their decisions about participation were beliefs about the benefits of study participation and the widespread conception that research studies are for the benefit of participants. There is a wealth of literature on this latter belief, sometimes termed ‘therapeutic misconception’ which has been demonstrated in many countries [7
] and highlighted as a concern in genomic research [36
In most clinical trials conducted by the NHRC, research participants have access to free health care services for problems unrelated to the research and medical bills of research participants are often covered by the research team. The community is familiar with this process.
"I have another child who ever participated in one of their studies; it was they who took care of the child to be healthy. I know how good it is. (Focus group with mothers of cases)"
Consequently, although in the MalariaGEN study research participants’ parents were not informed prior to consenting that their hospital costs would be met if they took part in the project, study responses revealed that participants’ unmet needs and parents’ expectations of free medical care for their children were important motivating factors for participation. Some mothers’ phrasing suggested that although they had been told research participation was optional; in practice the benefits of research participation were perceived to be so great that it would be hard to decline the study, a feature also reported in other African contexts [7
"When the [project staff member] came he did not force us; he said whoever wanted could participate in it. I saw that it was beneficial; there are so many diseases and since they came to help us (the community), you had to agree … (Mother of control)"
"She said it was not compulsory, if you did not want to participate, you could refuse; I wanted to participate that was why I thumb printed. This is one of the papers, she said it was voluntary and I knew it would be beneficial to me. (Mother of case)"
Comments from these mothers consistently suggested that they didn’t clearly distinguish between the different research projects conducted by the NHRC (or VAST as it is colloquially known), or where such distinctions are made, different types of studies are perceived to offer similar benefits, such as free healthcare for a certain period of time during the study.
"My child always falls sick and anytime I send him there he was treated free under VAST. That is why I agreed to participate in this study too. (Mother of case)"
Unlike some studies where it is not clear that participants are aware that there is a distinction between research and therapy, [34
] in KND the NHRC is well known and parents of cases clearly understood they were participating in research and could distinguish between project staff and hospital staff.
"The nurses wear white and blue; VAST workers wear mufti; that is how we know these are nurses and these are VAST workers (Focus group with mothers of cases)"
"I know where the VAST workers sit, where the nurses sit and even the doctor’s room. (Focus group with mothers of cases)."
Although clearly distinguishing between research and healthcare staff, mothers of cases and controls were generally of the view that the work of NHRC is to help them address their family’s health needs and therefore it is beneficial to participate in the research.
"I said if it was something that was not beneficial to our community, they would not have done it and since he wanted to recruit our children into the study, it would be beneficial to them. (Focus group with mothers of controls)"
"It was because malaria attacked other children around but did not attack my child; that was why I agreed so that the disease would not worry my child. (Mother of control)"
This study demonstrates that participants’ views of NHRC, and their expectations of the benefits of research (based on their previous experiences NHRC and not just information provided to them during the consent process for the MalariaGEN study) are important factors in their decision-making. Consequently, even studies that do not offer direct benefits to participants, such as the MalariaGEN study, may be perceived as offering such benefits.