ETHICAL ASPECTS OF VULNERABLE GROUPS OF PATIENTS IN CLINICAL TRIALS

Definition of Vulnerable Subjects

According to ICH E6 (R1) Guidelines definition for vulnerable groups.

Individuals whose desire to volunteer in clinical studies may be improperly influenced by the expectation, whether justified or not, of benefits associated with involvement or of a reciprocal response from senior members of a hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, secondary hospital and laboratory employees, employees of the pharmaceutical industry, members of the armed forces, and persons kept in custody. Other vulnerable subjects include patients with eternal diseases, persons in nursing homes, unemployed or needy persons, patients in emergency situations, ethnic minority groups, homeless persons, travelers, immigrants, juveniles, and those incapable of giving consent.

Determine Vulnerability.

Researchers are encouraged to consider all potentially relevant factors to determine the vulnerability

  • Willingness can be influenced by the expectation of benefits or retaliation

  • Intrinsic and extrinsic factors

  • Intrinsic: race, gender, Income, educational attainment, low literacy, health status, housing, legal status

  • Extrinsic: what does the study require, where does it take place, who is conducting it, could there be a risk of retaliation.


 Different approaches to define vulnerable populations


Determining which individuals or groups should be considered vulnerable and in need of additional protection as research participants is an ongoing challenge for researchers and IRBS. There are different approaches to defining vulnerable populations that might be appropriate in different contexts. These include:


  1. Categorical approach

  2. Contextual approach


Categorical vulnerability.

The categorical (or sub-group) approach defines vulnerable populations as those groups in society whose members share features that might make them vulnerable. For example, the U.S. Code of Federal Regulations lists "children, prisoners, pregnant women, mentally disabled persons, and economically and educationally disadvantaged persons" as a vulnerable group.


Contextual vulnerability.

In its 2001 report, Ethical and Policy Issues in Human Subjects Study, the National Bioethics Advisory Commission (NBAC) suggested an alternative to the categorical description of the vulnerability, underlining the extent to which vulnerability in research subjects is delicate to context. NBAC described six types of vulnerability that could apply to research participants in different situations:

  • Cognitive and communicative vulnerability: the incapability to understand information and make decisions, either due to capacity (e.g., young children), or circumstances (e.g., a stressful emergency or language barrier).

  •  Institutional vulnerability: being subject to an authority association in a formal hierarchal structure (e.g., prisoners or military personnel).

  • Deferential vulnerability: being subject to the authority of others (e.g., children or military personnel).

  • Medical vulnerability: having a serious health condition for which there is no satisfactory standard treatment.

  • Economic vulnerability: being deprived in the distribution of social goods and services such as income, housing, or health care.

Principles of Ethics.

  1. Respect-autonomy, decisions are made free of Influence.

  2. Beneficence-do no harm: benefits versus risk

  3. Justice protection from exploitation for access to participate

  • Wrong to target poor populations because the least will be spent

  • Recruit all those who might benefit even it is hard to recruit, engage and retain.


Ethical Considerations.

  • Voluntary participation-Consenting process

  • Benefits and risks

  • Compensation: Use of Incentives benefit to motivate action!

  • Retention strategies.

  • Handling unanticipated events-any experience of this? threats, crime, high expectations

  • Withdrawal

  • Post research obligations-

  • Provision of related knowledge, capacity building income generating activities

  • Sensitization, dissemination of results, follow up

  • Strategy

  • Interventions.


Informed Consent & Vulnerable Populations.


  • When seeking consent from participants in vulnerable populations, researchers should confirm that the participants will not be exploited, including being placed in conditions which compromise their safety or dignity and which place them in a position of even greater powerlessness.

  • Researchers may need to make extra allowance to ensure that the consent is genuine and does not place extra risk or stress on the participant.


Informed Consent of Special Population

  • When a clinical trial (therapeutic or non- therapeutic) includes subjects who can only be enrolled in the trial with the consent of the subject's legally acceptable representative (e.g., minors, or patients with severe dementia), the subject should be informed about the trial to the extent compatible with the subject's understanding and, if capable, the subject should sign and personally date the written informed consent

Special Considerations For Children

  • Regulations that protect the children, so as to prevent their exploitation are:

  • OHRP 45 CFR 46 Subpart D

  • FDA 21 CFR 50 Subpart DSP

  • If the parents of the children are died, or not known then the legal guardian must give consent.

  • Stepparents, grandparents, adult siblings, adult aunts and uncles may not consent a child to research.

  • In case of life-threatening events only consent from parents would be adequate, as there is the expectation of direct benefit. The trial details should be explained completely to the child.


Special Considerations For Women

  • Regulations that protect women, so as to prevent their exploitation are: OHRP 45 CFR 46 Subpart B

  • Research studies involving pregnant women and fetuses should accomplish the following requirements to obtain IRB agreement:  Preclinical studies should include pregnant animals and clinical studies should include non-pregnant women to deliver data for assessing potential risks to pregnant women and fetuses

  • Risk of the fetus is mainly produced by interventions or procedures which hold direct benefit for the women or the fetus.


REFERENCES:

  1. https://youtu.be/fYEyTsH8vGk

  2. https://gsdrc.org/topic-guides/social-protection-2/vulnerable-groups-needs-and-challenges/

  3. https://www.slideshare.net/mahmoudShakria/vulnerability-238803409

  4. https://www.sciencedirect.com/science/article/pii/S2212420920313285

  5. https://pallipedia.org/vulnerable-groups/



 

Written by: Ruhina Tabassum

Pharm D

Student ID: 172/0922



 




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