“You are a research fellow working on a clinical trial for cryptococcal meningitis (CM) in Ugandan AIDS patients. If a patient is diagnosed with CM and enrolled in this trial, they receive free care for treatment duration and reimbursement for non-medical expenses. Seventy-five percent of this population lives on less than two dollars per day and cannot afford these costs otherwise. A woman presents with CM symptoms, but after testing her cerebrospinal fluid, she is instead diagnosed with deadly bacterial meningitis. She cannot be enrolled in the trial and is too poor to buy antibiotics. ”
I recently presented this case at a classroom discussion about global health research ethics. When this dying woman’s mother pulled on my lab coat and pleaded for help one day at the government-run Mbarara Regional Referral Hospital (MRRH), where I worked as a clinical research fellow for nearly a year, I did not know what to do, and neither did my peers.
Like many global health-oriented physicians, my career began with short-term medical mission trips as a pre-medical student. However, I found these trips to be self-serving and unsustainable; indeed, the ethical shortcomings of these trips have long been argued because often participants’ benefits outweigh those receiving of their “help.“ Thinking research might be a way to develop an ethical global health career, I completed a summer clinical research project in India, which I found more productive and substantial than short-term mission trips. Galvanized by the belief I could change the world through ethical research, I applied for the clinical research fellowship in Uganda.
Ultimately, I found my experience as ethically fraught as the short-term missions I swore to avoid. I am not alone in these sentiments: others have noted that AIDS in Africa has paradoxically been both a source of significant tragedy and significant academic opportunity. Unfortunately, these opportunities are distributed unevenly, producing fresh inequalities. In their efforts to reduce suffering in Africa, some global health researchers have inadvertently capitalized on the intellectual opportunities provided by those same African sufferers.
At MRRH, where the shortages of gloves, saline, and basic medications reflect the hospital’s poverty and its patients, research-based medical care is often the only care people receive. Academic collaborations between western and sub-Saharan African institutions enable African researchers to publish in journals viewed by western audiences. As of 2017, patients presenting to MRRH with tuberculous meningitis or CM were enrolled in American-run clinical trials and treated without charge by experts with effective medications. Western-based surgical teams have improved MRRH’s surgical capacity, where sophisticated procedures are now performed with modern equipment. In 2004, after multinational research programs dedicated to tackling AIDS, tuberculosis, and malaria (ATM) worldwide were launched in the late 1990s, clinics started supplying HIV-positive Ugandans with free antiretrovirals and other services, causing a significant decline in HIV-related mortality.
However, inequities in patient care are apparent in the areas of MRRH that have not yet benefitted from foreign research dollars, particularly the intensive care unit and the emergency department. The two working ventilators in the hospital are usually occupied by neurosurgical patients. Deaths due to trauma and road traffic accidents in Africa cause the loss of more life-years than AIDS and malaria combined , which is also true at MRRH. Like the woman in the case above, patients suffering from other non-ATM infectious diseases are sometimes victims of these inequalities at MRRH.
This unequal distribution of research wealth in a resource-limited setting such as MRRH troubles me. At MRRH, often, patient care follows research dollars; when the money runs out, so does the patient care. The Declaration of Helsinki requires control groups to receive the ‘best’ current treatment, not the local one – and while in developed countries the difference between ‘best’ and ‘local’ may be small, in settings like MRRH this difference is profound and may result in severe ethical consequences.
In March of 2018, I watched a presentation by researchers who conducted a CM clinical trial in eastern Uganda, similar to ours at MRRH. A conference attendee voiced concern that the trial had violated the Helsinki Declaration, since many participants in the control group had not received any treatment. The presenter responded that the standard of care treatment for CM at this hospital was often no treatment, because the hospital had nothing to treat its patients. And, in late 2017 when the CM clinical trial at MRRH ended, CM patients there no longer received free treatment.
Uganda is often cited as the success story in sub-Saharan Africa in its efforts to reduce its HIV burden, largely due to funding from large international research programs. But perhaps these trials reveal that acceptance of this ethical relativism in clinical research could result in the exploitation of underserved populations abroad for research programs that could not be performed in the sponsoring country. Researchers must first be aware that conducting clinical research in resource-limited settings may create as many inequalities as it alleviates, particularly where the minimal standard of care for certain conditions is lacking. Secondly, research is often the conduit for medical care for impoverished people, which in turn creates unique ethical issues.
How can we global health researchers mitigate some of these ethical quandaries? I suggest that before embarking on clinical research (particularly in underserved areas), researchers assess their site’s health care needs and risk of patient exploitation, and that teams include medical anthropologists and epidemiologists well-versed in the local population’s health care needs and their receptiveness to clinical research. At MRRH, this was not a requirement of institutional review board approval for studies, so research teams must take this responsibility onto themselves.
Billions of people worldwide have benefitted from the discoveries that clinical research provides. Unfortunately, historically in our quest for valuable intellectual resources, those benefits have sometimes come at the cost of human exploitation. To maximize the benefit of clinical research for all involved, global health researchers must ensure this exciting and evolving field grows in an ethically sound manner.
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