The clinical trial is a study in which a new drug is tested in humans to determine its safety and efficacy. In the context of clinical trial, according to ICH Guidelines (E6-R1), ‘Vulnerable Population’ means “individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.”

Examples of vulnerable populations or groups

Vulnerability can be situational or individual-

• Economically/socially disadvantaged people like unemployed, orphans, abandoned individuals, persons below the poverty line, ethnic minorities, sexual minorities (LGBTQ), etc.

• Children (up to 18 years) 

• Women in special conditions like pregnant, lactating mothers, or those having poor decision-making abilities/poor access to healthcare

• Female fetuses 

• Tribals/marginalized communities

• Refugees, migrants, homeless, populations in conflict/war zones, riot areas, or disaster zones. 

• Cognitively impaired, mentally/physically disabled

• Terminally ill or comatose patients

• Patient suffering from rare a disease

• Decreased self-reliance due to dependency or being under a hierarchical network. For example- students, employees, subordinates, defense service personnel, healthcare workers, institutional individuals, under trial, and prisoners.

What are they vulnerable to?

• Physical control

• Coercion

• Undue Influence

• Manipulation

Why are they vulnerable?

These populations/groups are vulnerable because they lack decision-making ability or due to some situational/personal limitations they are unable to provide voluntary, informed consent.

These vulnerable populations are always at risk of exploitation during clinical trials. In the past, such incidents happened. For example:

• Tuskegee Trial (1932-1972): Poor Afro-American men were deceived and observed for untreated syphilis. This study was conducted without patients’ informed consent. 

• Nuremberg Experiment (1932-1948): Nazi doctors used prisoners in Nazi concentration camps for medical experimentation. Researchers placed victims in Vacuum Chambers that duplicated the lack of oxygen at high altitudes. Wounds were inflicted (gunshot, stab, amputation) and then treated by various techniques. Many were forced to drink poisonous water or breathe noxious gases. Some victims were immersed for hours; unclothed in tubs of ice-cold water. Others were fed nothing but salt water. All this torture caused unnecessary pain, suffering, and death of people. This study was conducted without the consent of the participants.

These shocking incidents gave rise to several international guidelines to protect human participants in clinical trials:

1. The Declaration of Helsinki (2009)

2. The Belmont Report (1979)

3. Guidelines of The Council of International Organization of Medical Sciences (CIOMS)

4. WHO GCP (World Health Organization Good Clinical Practice) guidelines (1995)

5. ICH GCP (International Conference on Harmonization Good Clinical Practice) guidelines (1996)

The above reports and guidelines set some principles to protect vulnerable populations from exploitation. Some of those principles are:

• Vulnerable populations have an equal right to participate in research study and acquire the benefits arising out of it.

• All the required information should be provided to them so that they can give assent for participation without any doubt. 

• If vulnerable participants lack the ability to give consent then a Legally Authorised Representative (LAR) should be involved in the consent process. Special attention must be given to ensure participants’ privacy and confidentiality. If the trial includes only vulnerable populations then their health needs must be taken care of. 

Women in special situations:

Women have equal rights to participate in the trial. Researchers must provide the ethical committee with proper justification for the inclusion of pregnant and lactating women in clinical trials designed to address the health needs of such women or their fetuses/ nursing infants.

Children:

Parents are the major decision makers for their minor children.  A child’s agreement to participate in research is called an ‘Assent’.

Assent-

0-7 yrs: No assent. Parental/LAR consent required

>7-12 yrs: Oral assent + Parental/LAR consent

>12-18 yrs: Written assent + Parental/LAR consent

Vulnerability needs to be considered to offer better protection and not to stop research on the vulnerable. Vulnerable groups should not be denied their right to participate in relevant clinical trials. 

^(MSM)