Following an overview of the consent rates and types across the two sites, we present staff and then parent perceptions of the consent process, followed by two factors influencing perceptions: parental understanding and decision-making in the trial, and factors influencing this.
Rates and Types of Consent in the Study Sites
Information on consent rates and type was collected as part of the trial procedures ().
FEAST trial consent rates and types of consent.
Across all six trial sites, 49% of parents gave full prior consent and 47% assent prior to randomisation as part of a deferred consent process. A small proportion (4%) only gave assent, with these patients dying before deferred consent could be sought. Only a tiny fraction (0.4%) of parents who initially assented or consented to participation in the trial later withdrew their children.
The number of children enrolled in the trial was higher in Soroti (n
633; contributing 20% of total trial participants) than Kilifi (n
216; contributing 6.8%). We found substantial and statistically significant differences between Kilifi and Soroti in rates of consent and in the proportion with prior assent. 87% of participants’ parents in Kilifi gave prior full consent (189/216); whereas in Soroti the equivalent proportion was 40% (257/633) (chi-squared p<0.0001). Just over half of parents in Soroti (54%) and 11% in Kilifi (p<0.0001) went through the prior assent with deferred consent. In Kilifi, a far higher proportion of screened and eligible participants refused consent (36%; 123/339) compared to Soroti (4%; 27/660) (p<0.0001).
Staff Perceptions of the Consent Process
The approach to consent developed by the trial team was generally strongly supported by all staff, with some nurses in Kilifi describing the consenting process as fostering rapport, trust and communication with patients. It was felt to be important to have prior full consent wherever possible to avoid ‘depriving the mother of the full information that she needs to make an informed decision’. Including assent for the critically ill, as opposed to a waiver or retrospective consent, was felt to be important because the research involved an intervention (fluid boluses) that was not standard of care, and therefore some information and an ability to opt out for parents was required:
I think we should [assent] because this is not standard treatment that you are giving; you are doing research and you don’t know for sure whether what you are giving is good or whether it’s bad…(Soroti\Staff\ST011).
Most staff involved in administering a deferred consent process with verbal assent were administering this form of consent for the first time and viewed it very positively. They appreciated that it allowed emergency treatments to be started without delay:
I felt that the hastened bit of it [referring to assent] was quite appropriate… because when the patient is that sick you also feel for the patient and you feel for that mother. [You think] ‘What if something happens before I start these fluids while maybe I am talking to this mother?’ (Kilifi\Staff\KL011).
Also regularly mentioned by staff was that including an option for verbal assent allowed them to continue with the research in a way that protected them from any later blame from parents for having enrolled children:
There are people who are really difficult. When you start doing something on the child and the child dies, then there you will be stuck: somebody can start saying that had it not been because of these [study procedures], my child would not have died…. (Soroti\Staff\ST012).
We have to tell them whatever is happening because if you don’t tell them and something happens, the blame will be on us (Kilifi\Staff\KL005).
Deferred consent (following initial verbal assent) was also described as ensuring that another formal step to support parents’ understanding and their ability to withdraw was introduced:
You know even you if you are in a state of shock (laughing) you may say yes to something if you are not mentally stable… you may say yes then later you say no when you came to that part of filling in the consent form… at that point it will be wise for you to withdraw that child from the study and it’s really understandable… it is very important to go back as soon as possible (Soroti\Staff\ST009).
A final argument often raised in favour of deferred consent was that it can allow some ‘buying of time’ to wait for key decision makers to arrive when children are brought to hospital by relatives other than their parents, or by a mother who does not want to make a definitive decision on her husbands’ behalf:
…depending on families there are mothers who can make decisions by themselves so those ones can accept, but there are these ones who rely on the father as the one to make decisions - majority of them go for the assent (Soroti\Staff\ST012).
This latter point was challenged by some interviewees, particularly in Kilifi, where there was some lack of clarity on whether or not there was a study-specific ‘arrangement’ to allow research to proceed in these circumstances. Some Kilifi-based interviewees were concerned that this would not be permitted in ethical practice more globally, and about how the child’s parents might later react if they heard their child had been assented by somebody else:
When it comes to relatives assenting or consenting for patients who are not their children it’s a bit tricky and because this child is not theirs… you never know how the parents will react, so I think an assent cannot…[be] for somebody who is not present (Kilifi\Staff\KL011).
Challenges and concerns shared by staff
The main challenge raised by staff was the validity of either assent or full consent when given by guardians during admission of a critically sick child:
Remember you are getting somebody in a very desperate situation and you are saying, okay I have screened this patient, and this patient is eligible now we have such and such a trial but at this stage I just need you to tell me whether you are willing or not willing to participate. Now to somebody who is desperate I think a yes answer is bigger than a no answer…the desperation here is not … to enter the trial but somebody is desperate to save the life of a very critically sick person (Soroti\Staff\MB001).
The above quote hints at parents feeling like they have to agree to ensure their children receive all emergency treatment rather than the study intervention. Other challenges highlighted by staff were parents not being able to listen given their anxiety, and – overlapping with both perceived pressure to agree and with difficulties in concentrating and understanding the information – parents believing that by agreeing to trial enrolment that all children would receive a fluid bolus (as opposed to no-bolus, the control). The bolus was reportedly seen as primarily to benefit their child.
A potential risk regarding deferred consent raised more often in Soroti than in Kilifi was that the option could be overused; introducing ‘a laziness’ in staff. In Kilifi, some staff argued that assent could ultimately lead to more late refusals, with parents having less interest in continuing to be in the study and withdrawing permission once their child had begun to improve (the point at which full consent is sought). This was difficult to explore quantitatively, given the small numbers with deferred consent in Kilifi.
In both settings staff reported that even the assent process introduces delays through encouraging questions, which introduces a dilemma in delaying initiation of treatment. Apparently unclear among staff was exactly what information they should give during assent. Although SOPs include the information, and this was covered during training, some staff reported that what to say was ‘really much more left to the prerogative of the clinician or the nurse’. Some staff were also unclear about whether or not an actual ‘yes’ was required; reportedly a major challenge in both settings where mothers often told staff to ‘just do what you want’:
These mothers come with all their anxiety, the child is sick. As much as someone would try to look brave and to say that I have actually understood go ahead - … mostly they say ‘do what you can, what I want to see is my child well’ (Kilifi\Staff\KL011).
The challenge was whether to accept such comments as a form of implicit agreement. Also unclear to staff was how to handle mothers who want to wait for a father to decide on study participation. In both settings fathers are often the main decision-makers in households but may not be present when the child is admitted. The dilemma is whether or not the mother is using the husband as a way to politely refuse; as a form of ‘silent refusal’:
It’s quite hard because often the reason you are given is that maybe ‘huyu ni mtoto wa wenyewe’ [this is the owner’s - i.e. the father’s - child]…., ‘I need the father also to give consent’ or that ‘I am waiting for the father’. So often they will not really come out and tell you that it is KEMRI [that is worrying me] but they always give other reasons (Kilifi\Staff\KL008).
One Kilifi staff member described asking the mother if she herself felt comfortable with the trial, and if so, suggesting that the child was enrolled and that the husband be fully informed on arrival. Because when fathers do later come, they ‘are usually not problematic so it’s just the fear the mothers have but the fathers are usually quite positive, quite ok to accept’. However some parents’ comments illustrate the potentially serious consequences of going against a father’s wishes:
you don’t know how they are living at their home………that [ie a woman deciding in the absence of a husband] may cause her to be slapped (laughs)… because the husband may want to know why she has done that; why she didn’t wait for her husband to come…. That may cause chaos (Kilifi/Parent/KLF 004).
The provision in the FEAST trial to waiver full consent if a child died following enrolment by parental assent, was understood and supported by most staff. They commented that it would ‘not be good’ or be ‘unethical’ to go back, given the sensitivity of the situation. Parents are typically crying, and sometimes collapsing. However, one staff member thought it was a study requirement to retrospectively obtain full consent even in the event of a death. Several felt that although it would be ‘harsh because someone has just lost their child and they are emotionally upset and all that’; it would have been better to obtain consent retrospectively to protect staff legally.
Parents’ Recall and Perceptions of the Informed Consent Process
As might be expected from staff comments and the medical condition of many children, parents’ descriptions of the admission process and information given at that stage focused on their concern for the child’s health and for their desire for treatment to proceed as fast as possible. Many parents said they ‘cannot remember’ or ‘have forgotten’ what they were told, or that they were ‘not listening to anything’. As one mother described in Soroti:
You know, you can also forget because the things [they told me] were too many and you know being only one head my heart was shaken about how the child was…that’s why [my head] didn’t grab many things (Soroti/FEAST mother/ST 010).
Others had some recollection, sometimes quite detailed, of the consent process and of the content of the discussion, but even these relatively detailed descriptions illustrate some lack of understanding or recall of the relevant trial details, and a hope or belief that inclusion in the trial is positive for the child. Two examples:
It’s a person’s freewill. If you agree to join that group, something like that, that’s when your child will be put some water but if you refuse, your child will not. That’s why she asked me before they put the water in the child and asked me whether I agree or not but I considered my child’s condition and said it’s alright. But the water is really helpful to the child. (Kilifi/Parent/KLF 011; authors’ emphasis).
They said that they are working with Makerere University and they have come to bring a study that involves treating people using fluids or something like that. They told me that it’s not only here, it is also being done in other places and countries including even some countries in Africa and others outside Africa. They are trying to treat children who are very ill using fluids. They also said that the way they have seen in some countries, it seems it is good so they also want to try it in Uganda to check if it is good so that they can see whether to continue that kind of treatment. Then they asked me that do you accept to be with us in this study? That they would treat the child and at the same time studying if I agreed. So I said that I agree, then they started treating the child from that day up to today, the child is still in their hands (Soroti/FEAST Father/ST 011; authors’ emphasis).
Many parents appreciated having been given some information before treatment began, but some felt – sometimes quite strongly - that it was pointless or even an additional worry to be given information and especially being asked ‘opinions’ (i.e. consent) at the stage:
Understanding, [is not something that can happen] until somebody sees her child is fine or recovered, but if you came to me and announce or talk, shouting to me explaining to me about KEMRI when my child is ailing... I won’t listen to you, it’s like you will be talking to the wind and the words will pass with the blowing wind. Because to me I will be looking on the condition of my child; not listening to you (Kilifi/Parent/KLF 016; authors’ emphasis).
What was not appropriate or what didn’t please me was that of being consulted first … I felt bad because you have come all the way from home because your child is not feeling well, you have brought the child and instead of them taking an urgent step of treating the child they start asking for your advice…. If it were not my decision I wouldn’t have brought the child to this place… (Kilifi/Parent/KLF007; author’s emphasis).
Another mother’s comment suggested that the way that consent was administered may not always have been ideal:
I was seated but my child was on a bed somewhere aside… she was even explaining while I had stood up to look at my child. In the end she [the nurse] asked them [the other nurses] to block me from seeing my child [so I would listen]. I cannot complain because they were in a hurry so as for the child to be put [on] the [infusion of] water (Kilifi/Parent/KLF 011).
In Kilifi, some of those who refused suggested that the consent signature indicated a handing over of the child; an absolution of blame on all sides ‘like if anything happens I don’t want us to blame each other’ which was felt to be deeply uncomfortable given the severity of the child’s illness:
You are told it is your decision. That is what is making people refuse because instead of just treating the child so that he/she is cured … It’s like you are saying in case there is anything that happens, I don’t want us to blame each other. Because you will have signed and you won’t have anything to say because you have signed yourself. So that is why people are refusing (Kilifi/Parent/KLF007).
The overwhelming recommendation from parents was for the treatment to come first and the talking and explaining later:
When a child arrives there, let him/her be treated first and then later let [the parents] be asked the questions. I even told the nurses that but they said if you have not yet decided ‘yes’ or ‘no’, we can’t start giving the child water. Now, because I want the child to recover I have to say ‘yes’ so that they can start the water (Kilifi/Parent/KLF 013).
Factors Influencing Parental Decision-making
Many of the above comments, including from staff, illustrate the difficulty of differentiating a trial related treatment intervention from standard of care. Looking across all parents’ responses to questions during our interviews, only 7/39 (18%) appeared to recall the nature of the research they were involved in, 23/39 (59%) recollected some elements of the research, and 9 (23%) simply described their whole experience as clinical care (). Those with good or some recall described a ‘project’, voluntary participation, and non-routine ‘water’ treatment. For some, simply being asked (i.e. consent) triggered their knowledge that they were in a research project.
Parents’ recall on discharge that their children were in a study.
Clearly difficult for parents and staff was explaining and understanding the concept of a trial and ‘equipoise’, leading to many parents suggesting that a decision, and particularly saying ‘no’, did not make any sense:
If you refuse what will you do in that condition and I have followed you, you cannot refuse. If I were to refuse, I couldn’t have come with him to the hospital (pause) we are grateful. (Kilifi/Parent/KLF 011; authors’ emphasis).
The above perception may have been contributed to by many of the trial staff apparently not being in equipoise at the time of this consent sub-study, with many believing that the intervention arms would prove to be life saving. As one staff member reported:
we have come to appreciate that at least that rapid infusion of fluids within the first one hour for very sick children really has some benefits so we are even trying to do it informally not only for the FEAST children but for some other children… it has helped us at least come to that conclusion even before the study has concluded (Soroti\Staff\ST009).
Others were concerned that refusal might lead to poorer quality of care, with one parent in Soroti mentioning you would have to ‘go to the other side where you have to buy things’. This might relate to the FEAST patients being relatively distinguishable from others in the ward not participating in the trial in Soroti due to their physical location and also because enrolled children did not have to buy prescribed medicines or infusion lines as often happens for paediatric patients (see ). This difference contributed to trial participants being perceived by parents as getting much better quality of care.
Once you are in that room [study room] you are given everything even the cannula, quinine, the drugs…All you do is to just look and appreciate that the child is being treated. The only expenditure is on what you have to eat and for the child because you see that even life is getting better … Even the nurses are good and the help offered is okay (Soroti/Non-FEAST mother/ST 005).
you can wish in your heart that if only you were also the one being treated like that, maybe it would be better (Soroti/Non-FEAST Mother/ST 001).
Certainly, in both settings, participants’ parents greatly appreciated the close monitoring and quick attention given to their children while at the ward, and regularly discussed being impressed and pleased by the concern and ‘tender care’ shown to children by the nurses and doctors.
Parents’ relatively low exposure to science and research was often mentioned by staff as contributing to parents’ inability to differentiate between research and standard care. In Kilifi, previous information about or personal experience with research studies in the wards or in the community sometimes led to parents automatically refusing the trial, either because they were aware that research participation is voluntary and had no interest in participating, or through a general concern about the institution’s research. The latter was sometimes based on rumours that have been extensively described in Kilifi and elsewhere 
, including misperceptions that blood samples are mixed and sold, or that staff are ‘devil-worshippers’. In other cases, past experience or information about KEMRI was much more positive, and appeared to lead to an automatic yes, regardless of understanding of study details:
I told him that I know KEMRI; one of my grandchildren is in a KEMRI malaria vaccine study so I know this organisation. When he asked me whether I was going to join or not I told him that I’m happy to and I joined (Kilifi/Parent/KLF017).