Being Human and Considering the Role of Human Trials

Being Human and Considering the Role of Human Trials

ThmitosisSmalle use of an experimental drug to treat a handful of health care and ministry workers infected with the Ebola virus may have attracted more press attention than the outbreak itself. One interesting aspect of this coverage is the platform that it provides for a discussion of the ethics of human subject research.

Ebola virus has been known for nearly 40 years, and while the total number of reported cases over that period has been relatively low, at least in comparison to other infectious diseases, the mortality rate has remained exceptionally high.

From a practical standpoint, the most effective way to manage an outbreak is to reduce the number of new cases through containment. While a proven treatment may be part of a containment protocol for other diseases, that has not been the case for the Ebola virus. The experimental drug ZMapp that has attracted so much attention has not been tested in human subjects, and the limited quantity produced for laboratory testing would not be sufficient to control an outbreak, much less provide hope of relief to more than a handful of patients.

This raises some questions:

  • What is the best use of the limited supply?
  • How should that use be governed?

The World Health Organization issued a statement on August 12, 2014:

There was unanimous agreement that there is a moral duty to also evaluate these interventions (for treatment or prevention) in the best possible clinical trials under the circumstances in order to definitively prove their safety and efficacy or provide evidence to stop their utilization.

Ongoing evaluation should guide future interventions.

In other words, while the use of an experimental drug may be warranted, the most ethical response is not explicitly focused on short term care of individual patients, but rather controlled use to determine potential benefits, as well as potential dangers of the treatment. The population that needs to be protected includes not only the patients suffering in the current outbreak, but the potential patients in the next one.

Dr. Ross Upshur, professor at the Dalla Lana School of Public Health at the University of Toronto provided a more colloquial expression:

Trust me, I am no fan of Ebola, but taking whatever might be out in however many labs around the world and starting to stick them into people without a good clear (study) protocol, without informed consent, without regulatory oversight would be foolish.

The World Medical Association held its 64th General Assembly in Fortaleza, Brazil last year, and updated the Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects:

Informed Consent

27.       When seeking informed consent for participation in a research study the physician must be particularly cautious if the potential subject is in a dependent relationship with the physician or may consent under duress. In such situations the informed consent must be sought by an appropriately qualified individual who is completely independent of this relationship.

Unproven Interventions in Clinical Practice

37.       In the treatment of an individual patient, where proven interventions do not exist or other known interventions have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorised representative, may use an unproven intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering. This intervention should subsequently be made the object of research, designed to evaluate its safety and efficacy. In all cases, new information must be recorded and, where appropriate, made publicly available.

It is easy to understand why patients, facing a disease with a 50 – 90% mortality rate, might be willing to try anything that offers hope. That is when we need to remember history, and why some of the current practices regarding human research were developed. We need to remember that a desperate patient does not provide an open license to unregulated experimentation.

The Office of Laboratory Animal Welfare (OLAW) has guidelines for developing protocols, to reduce the number of animals used in experiments, and ensure that the animals subjected to experimental conditions are for the purpose of providing beneficial information.

Our patients are human.

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