Research where the trial is the only route to care
Where taking part in a study is the only way a person or a community can reach medical care, consent is under pressure from the setting rather than from the consent form. Such research turns on how coercion reads in those settings, whether a study should run where full protections cannot be applied, what a prevention trial owes the community it recruits from, and the human-subject protections and consent that a study placed in another country owes its participants.
Coercion when the trial is the only care
The relatively freely accessible, high-quality medical system that some countries enjoy does not exist in most of the world. In countries where taking part in a clinical study is the only way to access or afford medical care, the question of how to rate participant autonomy is a question of coercion.
A physician who ran many studies in Ethiopia had to negotiate with the village elder, whose condition for the village's participation was that the study dig six wells for fresh water. Such a condition is bribery, but its advantage to the community had to be weighed against the disadvantage of the village not taking part: no benefits of first-world health care, and no wells. So the question becomes whether to set aside the fact that it is a quid pro quo in order to secure the greater benefit, and which is in fact the greater harm: denying the village a health benefit, or paying that price to enrol enough patients. An individual may feel responsible for taking part so that the community can have the wells. If the village elder says they shall take part, they will, so the individual is under a lot of pressure to participate even when they have reservations of their own.
Offering first-world health care, a medical exam and treatment under a Western-trained physician, to people without access to a gold-standard health care system is coercive. In one practitioner's view, it is still probably in the best interest of the patient.
Consent and approval in the field
In one of the Ethiopian studies, informed consent was given in the village square, where everyone could listen in, and urine samples were taken behind the bushes, so there was no privacy at all. That was the reality of the context in which the studies were run.
In a trial in Benin, some mothers sought to have their children included in the study, because taking part at least gave them access to a physician visiting them and their family. When the team arrived, 1,500 people were waiting at the ambulatory clinic, some of them for a month. The study's ethical approval came from the mothers in the church, who constituted themselves as the ethics committee and approved it. That falls completely outside what ethics approval means to the researchers who ran the trial, but it is the real world, and in one practitioner's view adjustments have to be made to accommodate it.
Running a study without full protections
In one practitioner's view, refusing to work in such conditions denies people an opportunity that may bring them great benefit, and denies them representation in the assessment of the drugs being tested. On the same view, societies cannot always be held accountable for the best possible protections when those protections are not feasible, and insisting on them would amount to pretending that underrepresented populations, who lack the protections, the wealth and the opportunities of a gold-standard health care system, do not exist.
Conducting such a study in full compliance is, on the same view, aspirational but not always possible, and a regulator would understand that. Regulators hold that, technically, a study cannot be conducted that does not afford people outside the European Union and the other countries that subscribe to the GDPR the same protections as people inside them. In practice those protections cannot always be applied. Where they cannot, the consequence may be that the population is excluded from the benefits of participation. On the same view, any reasonable person would call that a price not worth paying, and the saying that the perfect is the enemy of the good applies.
What a prevention trial owes its community
In HIV vaccine research, local representatives should be approached early, and their involvement in the design, development, implementation and distribution of results should be sustained throughout, to ensure sound ethics, scientific quality, relevance and acceptability in the affected community. Community support on all these fronts is crucial, and local communities are often keen to be credible partners in that research.
An HIV vaccine, once developed, should be made available and affordable to the population in need. So when the research protocol is developed, it should include a scientific justification for the population selected, a balance between the risk of participation and the potential benefits to that population, and safeguards against potential medical or social harm to participants and against exploitation of the community. Factors that may increase the risk of harm to participants and hamper access to potential participants include HIV stigma; human rights discrimination against women, people who inject drugs, men who have sex with men and sex workers; limited healthcare options; limited ability to understand the study and the consent process; legal factors; and a weak regulatory framework.
The informed consent process should convey the paradoxical potential of an HIV vaccine trial to harm rather than protect, through a greater risk of infection from risky behaviour or of disease progression in those who become infected, and it should explain referral to care if seroconversion occurs. Local reviewing bodies need to know what counts as the standard of HIV prevention in their country, communities or study populations, so that they can ensure that sponsors address it in trials with stated aims, and appropriate ethical standards must also be upheld.
Placing a study in another country
For a US company, placing a study abroad raises the question of whether to run a study in an emerging or other non-US population and then apply to the Food and Drug Administration for approval, and whether such research is ethical where few social norms and human-subject protections exist in the international setting to protect individuals. One answer is regulatory: the United States has human-subject protections for research conducted there, and unless the international trial can meet those regulatory standards the agency could not approve the drug or device.
The research on which medications are predicated is increasingly conducted in the developing world, where 2 of every 5 clinical trials are held. Informed consent there is, if anything, less often observed than in the United States, and that has long been a concern. Some researchers have long regarded informed consent in the developing world as inappropriate, inefficient or inconvenient. One writer holds that dispensing with it is not ethical. What is frequently reported from there is trials without informed consent.
By law, every medication must be tested in animals first, and some group of humans is always the first to receive a drug. Increasingly, those first humans are people in the developing world. A drug's first use in humans happens all the time, it is the normal course of drug testing, and the risk has been judged acceptable. Reported as an experimental drug used only in monkeys and now being tested on West Africans, the same practice would, in one interviewer's view, provoke outrage that people were being used as guinea pigs.
Questions arise when who those first people are seems to be the product of bias, whether intentional, economic or of some other kind. What is sometimes not acceptable is the way the trials are administered and conducted. In the United States, the Code of Federal Regulations spells out that participants are told what the drug is, its known side effects, the possible results of taking it and all the options. Once researchers test drugs abroad, these rules all too often fall by the wayside, and with less oversight it is easy to cut corners. That, rather than the fact that some people are the first to receive a drug, is the problem.
People in the developing world test medications, make them possible for others to use and then end up without access to them. What is done about it will depend on how well what is happening, and the rights and needs of the various people involved, are analysed.