Malaya Pimentel-Santos, MD
I JUST gave up my precious weekend to attend a two-day workshop on research ethics. But truthfully, I have no regrets.
Just last September at the European Congress for Tropical Medicine and Hygiene, I attended a riveting presentation on the experience of conducting a drug trial during the 2014 West Africa Ebola outbreak.
In the midst of no less than a public health catastrophe in one of the poorest regions in the world; involving a disease for which there is currently no specific treatment, and which claimed over 11,000 lives in at least five countries, they took up the challenge of generating scientifically sound, and potentially lifesaving knowledge.
Current standards call for patients to be randomly assigned to either receive the treatment or the study control (placebo/no treatment). We must understand that their study population consisted of critically ill patients. Thus, deliberately allocating subjects came with the possibility either withholding a lifesaving treatment (should the drug eventually be proven effective) or causing more complications (should the drug be shown to have side effects). In the course of their work, they had to hurdle this, and several other major ethical dilemmas, such as whether to include special populations such as pregnant patients and children – who are normally excluded from drug trials – but who also stood to potentially benefit (or suffer complications) from the experimental drug. Although this is a bit of an extreme example, it serves to illustrate the need for principles and standards to guide the conduct of biomedical research. And this was the subject of the workshop I just attended.
Pitfalls from the past
Historically, major medical breakthroughs emerged from activities that by today’s standards are highly questionably both from an ethical and even a moralperspective. In 1796, Dr. Edward Jenner “discovered” the small pox vaccine after injecting an eight-year-old boy with cowpox. Fortunately, this is no longer within the realm of acceptable practice. No longer can researchers expect to be absolved when the end (research findings leading to medical benefit) justifies the means (indirectly or unintentionally violating the rights of vulnerable subjects).
In order to avoid the pitfalls of the past, there are regulations that are now in place to guide us, which are largely the result of the mistakes of the past. The Nuremberg code emerged from the dark shadows of Nazi research in the 1940s. The Belmont Report on the protection of human subjects in research emerged in the aftermath of the infamous Tuskegee study on syphilis, which was conducted by the United States National Health Service from 1932-1972, purportedly to document the natural history of syphilis; but which also effectively withheld treatment – and cure – from its 600 African-American subjects even after penicillin became standard treatment for the disease.
At present, the conduct of biomedical research involving human subjects is guided by three basic ethical principles: Respect, beneficence, and justice.
Respect for persons
A milestone in the development of researchethics was the recognition of the existence “vulnerable subjects”, such as the young, the elderly, poor, and indigenous populations, and those who are – for whatever reason – unable to protect their own rights as research subjects. Central to this concept is the requirement for informed consent, prior to becoming part of any study. In short, should vulnerable populations be a necessary part of the research, there must be an additional layer of safeguards and protective mechanisms, to prevent possible harm or abuse.
Beneficence (and non-maleficence)
Primumnon nocere (first, do no harm) is a basic tenet in medicine, and a phrase often attributed to Hippocrates. Ideally, no harm should ever come to the subjects of research. Unfortunately, the exact outcomes are unknown, and we cannot absolutely ensure that no harm will result. In a broader sense, no research is completely free from “harm”; in a poorly designed study at the very least there will be wasted resources and unnecessary inconvenience caused to the subjects who devoted their time to the study. Thus, for practical purposes, it is the researcher’s responsibility to ensure that the benefit to the subjects must far outweigh the risks.
There is an ethical obligation to ensure equitable distribution of both the benefits and the risks that are inherent to research. This, again, is related to the protection of vulnerable persons. Relevant to our situation is the practice of conducting studies in developing and low-resource countries, where we must be on guard against practices that may directly or indirectly lead to a worsening of the inequity that is already a part of the socioeconomic system. Similarly, we must guard against abuses of our own populations, which may be considered to be doubly vulnerable in part because of economic disadvantage and a lack of information and education.
Today, we continue to do research because we hope to generate new medical knowledge that will ultimately benefit humanity. Unfortunately the answers only become clear after the research data is collected and analyzed (otherwise there would be no need to do the research). Even with the most diligent literature review, we cannot always ensure a positive outcome. One message that stands out in my mind is that during the study of ethics, difficult questions are sometimes raised, for which there are no easy or straight answers. Nonetheless we must hurdle on, and always refer back to the guiding principles of respect for persons, beneficence and justice
My sincerest thanks to Dr. Marita Reyes (my former dean at the UP College of Medicine), Prof. Edlyn Jimenez and Dr. Sally Vios for sharing your knowledge, experience and insights, and even more importantly for your dedication to raising the bar forethical standards in local research. This truly was a weekend well spent.
Vital Signs Issue 83 Vol. 4, January 1-31 2016