Motivation to participate in research
All the women who were invited agreed to participate in the study. Table 1 shows the socio-demographic and clinical profiles of respondents. All these had severe obstetric complications that constituted the severe morbidity, which included severe obstructed labor, eclampsia and obstetric hemorrhage. All except two had completed at least primary level of education, three had participated prior in clinical trials for prevention of Mother-to-Child HIV transmission, and only 2 were primipara, indicating that they had prior experiences with the healthcare system before the index pregnancy or delivery where they developed obstetric complications.
Many survivors of pregnancy complications had the view that research about the cause of illness was necessary to obtain answers to many questions about pregnancy-related complications so as to develop new medications, to improve on existing medications, to examine the causes of illnesses or to identify how to improve the health of women during pregnancy, as exemplified by two respondents:
Respondent 7: “There is always a lot that is not known about illness in pregnancy. And sometimes emergencies occur suddenly. On one day you are fine, the next day you are very sick. Even doctors cannot explain why the diseases occur. It is necessary to find answers to those questions.”
Respondent 2: “Finding out better ways of treating disease is good. Investigations provide answers to many questions about the disease. They are therefore necessary even when you know that gathering the evidence requires many pregnant women to be involved, even if it may lead to some dangers to pregnant women, with all the risks that (it) entails.”
Some respondents, especially when asked about whether it is acceptable for them to be involved in those investigations, were of the view that in such emergency situations, investigations were not the priority. Rather, it was providing the necessary emergency care that was a priority, but acceptance would depend on how the information was communicated and on whether the mothers understood, as exemplified by two of the respondents.
Respondent 1: “There is often so much happening when you come in with a sick child. Moreover, this may occur when you have gone through a difficult pregnancy. You are worried about your baby. What you need then is treatment for both of you. There is no need to waste time on being involved in those investigations. Your health and that of the child take priority. Taking part in other activities is the last thing on your mind.”
Respondent 2: “I wouldn’t accept to take part. You should not go beyond your limits. If you (?) are already sick or your child is in danger, there is no reason to add on to that danger, unless there is hope of getting something better for you or your baby... I cannot even recommend what I do not support. Why would you take a risk if you don’t have to, or if there is nothing to gain? But if they tell you more about what is involved, so that they explain carefully, … then I can accept.”
Preferences regarding consent process
Regarding how invitation to participate should be communicated, most respondents were of the view that this should be when they or the unborn babies were out of danger, and therefore when they could understand without what was referred to as “pressure”, “stress” or “anxiety.” The respondents preferred that the information would need to be simplified and brief, if they were to consider participating, as exemplified by two respondents:
Respondent 3: “You doctors have your difficult language. We don’t understand it. At that time what I need is help and care. I have no time to listen or understand those “heavy” medical terms. What they tell me should be short and simple, so that if I have to ask my friends for opinion, I would be able to tell them exactly what they (research team) ask me to do.”
Respondent 5: “They should give me time. They may come and give me information, but should give me a written summary to read on my own. If I can understand, then I may accept.”
Most respondents were of the view that they needed time to understand the information given about research participation, and that researchers should assess whether they have understood the basics about the study, as demonstrated by two respondents:
Respondent 2: “You tell me about a new study that you want to do. If you want me to take part, I may mess your study. You need to test me to check if I have understood. Ask me a few questions about what I need to do and what you are going to do for me. If I answer correctly, then you guess that I have understood. If answers are wrong, then you repeat the information till I understand.”
Respondent 5: “They should ask me, that okay, if you have understood, what is your role? What are you going to do? What do you understand? Remember, at that time, your brain is not ‘steady’ and you may be tired. They need to check if you will do the right thing that they want. If it is taking the medicine correctly, they ask how many tablets, at what time, and what else you will be doing.”
Other respondents were of the view that the information about the research should be given privately or individually, rather than to everyone present, and participation should be confidential. Privacy and confidentiality were highly valued, as exemplified by one respondent:
Respondent 5: “They need to come to you and then ask, are you going to take part. That should concern only me. I may not want other people, even my relatives to know that I am involved.”
Interviews explored whether randomization to different study groups, may influence trial acceptability. Most participants did not understand the reason or benefit of randomization. While seemingly in conflict with the concept of randomization, most respondents were of the view that the investigators would decide what was best for them, and therefore they would not mind the randomization procedures. Thus, to most participants, it was okay for the investigators to decide for them, and they trusted them to make the correct decisions for them. This misunderstanding signals trust in clinical researchers to do what is best for individual clinical trial participants regardless of methodological constraints such as the need for randomization, and is exemplified by two respondents:
Respondent 7: “I do not understand why doctors would let me belong to one or other group just by chance. But they know better what they need to find out. I believe they would do the right thing. If what they do makes me belong to a particular group, I have no objection.”
Respondent 5: “I think even when doctors say you should belong to this or that group, they know the best. For me what would matter is that they do the right thing. I believe they are called to serve. I have a feeling most doctors still know what is right and that is what they do for patients. Much as I do not understand how they would do it or why, I would believe that is the right thing if they did it.”
Solidarity and communal consent
The community played an integral role in the uptake and acceptability of clinical trials amongst respondents. Patient decision-making was intimately tied to the relationship with others in their local community, whose advice was considered important for the decision whether or not to participate. This is exemplified by three respondents:
Respondent 1: “I have ever looked after a mother who was involved in something like that (participated in an HIV drugs trial during pregnancy). Before joining, we discussed the ideas and thought it would be a good thing. So we advised her to participate. At least even if there was not much good or benefit, there was nothing she would lose. So even for me, I would participate if invited, but I may need to consult my friends first.”
Respondents 3: “I would ask myself, is this a good thing for me? If I am convinced, I would go ahead. If I have doubts, I would ask my friends or family members. Depending on their opinion, I would make a decision to join or not.”
Respondent 4: “It depends on how they convince me as to what I may benefit. Where I am not sure, I would ask for more time while I consult my friends or other patients. I may even call some nurses or family doctor. If they know better, what they advise to do is what I may take as the right decision. I think even if they were in my position, that is what they would do…If they asked me for advice, I would give it”.
Most respondents considered the advice of family members and friends as very crucial in decision-making, especially in emergency situations. A number of participants reported that the benefits of the trial should be available to everyone involved, including other patients and community members, so because of that, their advice regarding participation was necessary. This would place the need for high standard of health care to be extended towards the patients in the investigation and that other community members would guarantee that the correct things are done. Members in the community, not only those involved in the study, would share the blame rather than the individual alone if something went wrong, as exemplified by one respondent.
Respondent 3: “If the purpose if generating information to help science, then it should not be a personal responsibility but a responsibility of everybody. This means that even the community members, the health facility managers and local political leaders should have a say about which investigations are acceptable… If they gave a green light prior, then that makes it easy for me to accept invitation to participate. Because then I know the major concerns that I may also have would have been addressed.”
The local political leaders and other trusted members in the community were thought to have a significant influence on clinical trial acceptability. When the local leader or influential person (such as a nurse or doctor) is trusted by the community members and this individual approves the trial, the potential study participants will be much more comfortable with the invitation and (making own) decision to participate in the clinical trial. The prior acceptance by the community, especially the influential members, that such investigations should be conducted is a guarantee for easier acceptance and motivation to participate in the clinical trial. Similarly, this prior acceptance reduces the likelihood of declining further participation or default by participants (such as loss to follow up) from the clinical trial requirements as exemplified by other respondents:
Respondent 6: “Our leaders are sometimes good and consider what is important for us. …I believe they all have the best interests of patients on their mind as they deliberate about accepting such a study to be done.”
Respondent 9: “You can ask other nurses or doctors first for their opinion. If they are not sure about the study, you may decline immediately. If they are somehow positive, you may consider whether you can join. It all depending (sic) on how they approach you and what you think is important for you.”
Respondent 5: “If you have an opportunity to ask those already in the study, this can help you to make a decision. They can explain what is going on and what is involved (what participation involve. But you have to consider and make your own decision. If there is positive advice from your doctor or nurses, then there is no need for many questions.”
Benefits, risks and compensation for research-related harms
Most participants were of the view that participation should involve possibility of personal benefit for them, their unborn baby or the newborn at birth. Regarding potential benefits, the respondents suggested that they expect individualized care, better care or some medications if they agreed to participate, as exemplified by two respondents:
Respondent 1: “They have to convince me that it is a good idea. They need to talk to me in a language I understand best, not English. I expect that they would provide me with better care. For instance, get me the drugs I need, or give me better attention.”
Respondent 7: “At least they should contribute to some of my expenses like on drugs or food. They have to assure me that there is something to gain for me or my baby…I need to later be able to say, yes, taking part was a good idea. I want a higher standard of care if I participate. This can only be if I am better off than those who do not take part.”
For many respondents, hope for benefit was a significant motivation for clinical trial participation. This is exemplified by the following respondents:
Respondent 1: “I had to buy most of the drugs. If you are very sick, they (doctors and nurses) tell you buy this and that medicine, that it will make you get better. Before the research study, when you visit the government hospital, you pay for the tests, you buy the medicines and sometimes you do not have the money. If they can provide the drugs I need, then I would take part. That may save me some of the expenses.”
Respondent 6: “I would not hesitate to participate if they offer me help. That may be my only chance. The (study) nurses may provide some drugs that I could not afford. I am grateful that both my child and I are okay now. Some friends lost their babies. If taking part in the study solves the medical problem, then why not?”
While most participants could be motivated by the need to help other mothers (without possibility of personal benefit), they were not willing to accept the invitation unless their newborns were to benefit, that is, they were unwilling to participate in research for the sake of generating information to help other newborns. This is demonstrated by the respondents below:
Respondent 6: “Maybe for myself I can accept participation even if I may not benefit, as long as my participation could benefit other women so that they do not suffer like me. However, where my baby is involved, I cannot do anything like that. I can’t participate for the sake of helping others.”
Respondent 14: “Sometimes you hear rumors that those involved in research are given free drugs and they pay for the laboratory tests and other investigations. If they invited me and I knew they offered these, then I would not hesitate to join.”
Respondent 11: “I would not have a problem making the decision (to participate in research). But many times, you take part but you never know what has come out of the blood and other samples they take. If I were to know the results, then I would take part…Even if I may not personally benefit, I would need to know the results…If it is for my baby to take part, I would not accept, unless my child is to benefit.”
Other respondents suggested that participation would depend on how they were approached and how the invitation to participate was presented. A prior positive relationship cultivated with them by health workers would make it easier for them to make the decision to participate. This is exemplified by two respondents below:
Respondent 16: “It depends on how they approach me. If they are helpful with good manners, then I can accept. At times, you may go to the hospital and they ignore you, mistreat you or don’t help even when you call for help. Why should I join their studies? But If joining is my hope for getting help, I cannot hesitate to join
Respondent 15: “Some health workers are good, they are kind, they are supportive. If they could tell you to do something, you just accept because of their approach. ”
Regarding potential burdens or risks, respondents suggested that participation may lead to spending a longer period of time in the health facility as researchers complete the study, or due to some unexpected harm. Where there may be a possibility of significant harm, most respondents would either hesitate to participate, or would decline the invitation to continue participation, as exemplified by two respondents:
Respondent 8: “You never know what happens. If they give you medication that is not fully tested, the baby may be affected. Even me I may get complications. In that case I will have to decline or may leave their study.”
Respondent 6: “They may keep you longer in hospital because they still want you to do this or that procedure, taking off more blood, doing more checks on you. If what they tell me involves any of that, then I would not join. I would not want unnecessary delays.”
Respondents were highly influenced whether or not to participate by whether there would be risks for their baby. Risks to the mother herself were secondary, in comparison. The main reason for giving the baby priority was that the baby needs to be able to grow optimally and survive the pregnancy. Most respondents reported that they would tolerate more risk than they would tolerate for the baby, as exemplified by several respondents:
Respondent 6: “As a mother I would accept quite a lot for that myself. Unless the risks are really dangerous. For my baby, there are a lot of things that I will not accept under all circumstances. However, if the danger is on my baby, then I will not accept. I would hesitate.”
Respondent 8: “I have no reason to refuse. At least if they assure me that what the study involves will not hurt my baby… They have to convince me that I will benefit. The information they tell me should be clear to me…Whatever procedures they will do (should be) safe for me and my baby. If am convinced, I can then be involved.”
Respondent 4: “There is never an acceptable risk for my pregnancy. Never. I cannot accept to participate just to satisfy someone’s interests. A pregnant woman and her baby should be very much protected in our society. After all, a pregnancy is like an illness itself…I can understand that that the results may help me or others. But my interests and my concerns are more important.”
For research that involved invasive research procedures, women were willing to accept procedures that included blood draws or caesarean section among the study procedures, provided they were assured of safety for them or their unborn baby. However, they needed guarantees that these procedures have a clear medical indication and would be similar to procedures that are undertaken in case of obstetric emergencies. This is exemplified by three respondents:
Respondent 1: “I am sure many women suffer the same problem I had. If (taking part in research) can put my baby in danger, I cannot accept. I would not accept anything that they are just trying out…May be some risk for me is acceptable, but for my baby, the danger should be zero if I am to accept for the sake of benefitting others. ..I cannot accept treatment chosen by chance or lottery. It should be medicine that works…I think many would also do the same (accept to take part in research) to help other women”.
Respondent 6: “When I remember what I went through, I think it is important to help others in that critical period to also have this joy, to be able to appreciate my happiness that I went through this period well…There may be some danger. But if there is hope, then I would accept and go through it... May be this is God’s way of using me to help others… But I would leave immediately if I suspect some serious danger to my baby,”
Respondent 3: “I had to buy most of the medications. Even many investigations (like the ultrasound scan) were not free. If the participation may provide you a chance to have someone else meet these costs, then I would willingly participate.”
On the issue of whether there should be compensation for adverse events or harms that may arise during the research, most respondents were of the view that it is the responsibility of investigators to plan and provide compensation, regardless of whether harms that eventuate were foreseeable. Participants were more concerned about harms or injuries that may cause death or disability (either serious or permanent). Respondents perceived that the responsibility of compensation should be guaranteed by the community or health facilities and should be enforceable. Monetary compensation, provision of treatment for the adverse event, or both, were thought necessary and the type of response was thought to depend on the circumstances and nature of the complication. In the absence of an appropriate response, respondents believe that researchers should be held responsible and could even be sued to obtain the compensation. This is exemplified by two respondents:
Respondent 1: “If the investigators suspect that my life may be put in danger, they should be ready for compensation by treating me or my baby, and even pay me some money for the trouble caused to me. …The society should guarantee that this happens and should put the investigators to task if they fail.”
Respondent 7: “They find me with my illness and want me to get involved. They should compensate me in case of problems. If not, they should leave me alone. They should not add to my trouble, or else we end up in court.”