A guideline for ethics in clinical trials in vulnerable populations

At a time when the need to test novel medication in HIV positive treatment naïve individuals is strong, and in which the ethical scrutiny in industrialised countries renders the conduction of such trials a complex and costly endeavour, resulting in an increased number of clinical trials in marginalized populations and resource poor countries, the EATG decided to convey its own perspective through a Position Paper on Ethics of Clinical Trials in vulnerable groups.

This Position Paper differs in several ways from other similar papers written on the subject for the reason that it intends to take a broader look at the community perspective of this complex subject. The EATG’s point of view goes beyond the trials themselves to embrace the person’s well being and treatment after the trial, his/her life conditions during the duration of the study, and the benefit of the research to the community as a whole. Below is a short overview highlighting the most important aspects.

The notion of benefit
The first focus of the position paper centres around the benefit to the community in which certain drugs are tested. In fact, before selecting a region of the world or a population in which to conduct a clinical trial, there needs to be clear commitment on how this research will benefit the community. The use of vulnerable populations as ”guinea pigs“, testing treatments that will never be available to them is entirely unethical. This is made clear in the Helsinki Declaration (October 2000), one of the pillar document of ethics of research in human subjects: ”Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research.“

Even more so, in article 8 of the research ethics guidelines elaborated by the Council of International Organisations of Medical Sciences (CIOMS), it is stated that: ”the sponsoring agency should ensure that, at the completion of successful testing, any product developed will be made reasonably available to the inhabitants of the underdeveloped community in which the research was carried out.“ In these guidelines it is also pointed out that any exception to this rule should be clearly agreed upon by both parties before the beginning of the trial. These agreements should be included in the dossier to be evaluated by ethical committees so that they can review the real ”potential benefit“ of the study for the local community.

Continuing on the same line, when pharmaceutical companies test drugs in developing countries they need to ensure the integrity of the study. For this to happen it is essential to guarantee that the area benefits from the necessary materials and equipments for the running of the study and follow-ups. If the current medical and scientific structure is not sufficient, sponsors are required to help their development through financial or in-kind assistance.

Enlarged care for the community
The second focus of the position paper is the concept of ”enlarged care“. This refers to the general conditions, such as hygienic, and nutritional, in which the participants will live during the trial. It is the duty of the trial’s sponsor to ensure that its participants have access to the best possible care, and their living conditions throughout the trial are such to ensure optimal response to treatment and resistance to study adverse events.

When conducting trials in resource-limited settings it is necessary to look at some aspects and guarantee that they are accounted for before the trial starts. One such aspect is nutrition, and water supply. It goes without saying that if participants do not have access to a sustainable diet they will not react well to a therapy. Also, the participants’ family need to be looked after in terms of treatment and livelihood to avoid sharing of medication, food or other necessities. These factors threat to lessen the benefits of study treatment to the participant but also to compromise the legitimacy of the research and the credibility of its results.

On community involvement
Lastly, the capacities of each community in regards to its ability to judge the ethics and science of trials hosted by them should be enhanced. In many resourcelimited areas local groups of activists do not possess the skills necessary to monitor the research work that is taking place in their populations. In this case they are not properly prepared to negotiate on the ethical factors of a study. On the other hand, such NGO representatives and activists are the only true experts of the local situation and hence the only bodies capable of judging the ethical dilemmas of clinical studies in their countries.

Again here the role of ensuring such increase in capacity should be the sponsor’s, who wishes to carry out research in this group. The sponsor therefore needs to involve the activist community in privileged communities to help train and educate local activists regarding the ethics and science of clinical trials. Whenever possible the results of such work should be the creation of a Community Advisory Board (CAB) which will be able to judge the benefits of future trials in their community.

Charles David McCarthy, Lital Hollander

EATN - European AIDS Treatment News, Volume 13, I – Spring 2005