1 – Vulnerability

A vulnerable group can be part of the population of a high-income country, or of a middle or low-income country. The notion of vulnerability can also be applied to the entire population of a low or very low income country, or to a country where democracy is lacking and civil society under-represented. We define a group or a country as being vulnerable considering:

• The level of the proposed community’s economic power;
• The state of access to care, and treatment standards in that specific group / population, in comparison to other, less vulnerable groups
• The experience or understanding of scientific research in the group/country as a whole;
• Local infrastructure, human resources, and technical capacity for providing health care and treatment options;
• Experience and capacity in conducting ethical and scientific review;
• The ability of individuals in the community to provide informed, pressure-free consent.

Clinical research in vulnerable groups and /or populations conceivably involves particularly high risks to research subjects, represented by a range of reasons, including poverty, mal-nutrition, accompanying pathologies, logistic and economical difficulties, education levels, freedom of choice. All of the above might interfere with the person’s ability to freely and effectively decide upon participation in a trial, and on the probability of retention in the trial, and increase the risk and danger of adverse events.

In low income countries, in which access to treatment is lacking, clinical trials sponsored by pharmaceutical companies from high income countries may represent a valid source for early access to treatment. On the other hand, such trials are invariably complicated by the risk of lacking and insufficient healthcare infrastructure and personnel, by economical constraints, and by uncertain ethical standards. Most importantly, the individual consent for participation in drug development trials cannot be considered pressure-free, given that subjects in the study have no other alternative to access lifesaving treatments.

A particular source of concern is that research sponsors may be attracted to conduct studies in vulnerable populations due to the ease of enrolling large numbers of treatment naïve individuals, to the laxity of ethics standard and control, and to the ability to offer trial participants inadequate treatment and insurance standards with significant reductions in costs.

For this reason, trials conducted in vulnerable populations require an additional set of rules and regulations to defend the rights of individuals taking part in research, and to avoid exploitation of vulnerable groups as subjects to unethical studies based on substandard treatment and care.

In this setting, the role of ethics committees, and the quality of information given to the participants are also of particular importance.

As a general rule, phase II and III drug-development trials should be conducted simultaneously in the host community and the sponsoring country, and the aims and methods of the trials should be equal. This is an important control mechanism to ensure that collateral trials involving unnecessary risks to subjects are not conducted in vulnerable populations, and that competent ethics committees judge all trials applying uniform measures. A parallel conduction in the sponsoring country may be omitted only on condition that the drug is designed to treat or prevent a disease or other condition that rarely or never occurs in the sponsoring country. [1]

Trials may be conducted in a given country only when investigators have good reason for testing the intervention in that particular population and only when it is expected that the intervention will be accessible to that population.