Question

Conducting research projects while ensuring the protection of human subjects is necessary. What are some methods to protect personal rights of someone in one of the groups that is labeled as vulnerable? Justify your rationale. Provide References

Answer 1

The concept of vulnerability has held a central place in research ethics guidance since its introduction in the United States Belmont Report in 1979. It signals mindfulness for researchers and research ethics boards to the possibility that some participants may be at higher risk of harm or wrong. Despite its important intended purpose and widespread use, there is considerable disagreement in the scholarly literature about the meaning and delineation of vulnerability, stemming from a perceived lack of guidance within research ethics standards.

The inherited skepticism of disregard and contempt for human rights from the past has left powerful influences, making autonomy, justice and safety the citadels for current ethical research practices. Civil rights violations from the infamous Nazi and Tuskegee to radiation human experimentations have promoted sustained maturation and augmentation of clinical bioethical research environments. The lack of informed consent (IC), or coercive, guileful, forceful influences and methods that were used to obtain consent from potential participants; this associated with impaired risk-benefit scales, unjustified research population selections have prompted international regulations to stand firm on principles advocating conscientious clinical and ethical research systems. Following marketing approvals, medicinal products are conventionally utilized by pharmaceutical organizations, medical practitioners and allied bodies across a wide range of age groups, genders, special populations, nationalities and races, who unfortunately had not been satisfactorily represented in pertinent clinical studies resulting in deficient evidence-based health care.

There are several definitions available for the term “vulnerable population”, the words simply imply the disadvantaged sub-segment of the community requiring utmost care, specific ancillary considerations and augmented protections in research. The vulnerable individuals’ freedom and capability to protect one-self from intended or inherent risks is variably abbreviated, from decreased freewill to inability to make informed choices. Vulnerable communities need assiduous attention during designing studies with unique recruitment considerations and quality scrutiny measurements of overall safety and efficacy strategies ensuing research. Ethical dilemmas are widely prevalent in research involving these populations with regard to communications, data privacy and therapeutic deliberations. Non-therapeutic research participation is granted if the envisaged risks are minimal and well-being of this community is not compromised. Research with this sub-segment of population is validated if reasonable direct benefits are foreseen, in compliance with local legal regulations. The vulnerable populations refers to but not limited to children, minors, pregnant women, fetuses, human in vitro fertilization, prisoners, employees, military persons and students in hierarchical organizations, terminally ill, comatose, physically and intellectually challenged individuals, institutionalized, elderly individuals, visual or hearing impaired, ethnic minorities, refugees, international research, economically and educationally disabled and healthy volunteers. Due to their circumstances, the communities may be inclined to participate in a clinical study or be unjustifiably influenced by the expectations of predicted benefits associated with participation.

Although critically ill patients represent a vulnerable group of individuals, guidelines in research ethics assert that ethically acceptable research may proceed with such vulnerable subjects if additional safeguards are in place to minimize the risk of harm and exploitation. Such safeguards include the proper obtainment of informed consent that avoids the presence of the therapeutic misconception and the assessment of decisional capacity in critically ill patients recruited for research. Also discussed in this review are additional safeguards for such vulnerable subjects, as well as the issues involved with proxy consent. Heightened awareness to principles of ethics and provision of additional safeguards to enhance protections of vulnerable subjects would help to maintain the public trust in the research endeavor.

In 1974, after a long history of harmful research studies conducted on unwilling human subjects (such as the Tuskegee Syphilis Study initiated in the 1930s and a series of studies conducted in the 1960s at the Willowbrook State School, a New York institution for "mentally defective" children), the U.S. Congress established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Four years later, this commission issued the Belmont Report, which is the cornerstone of the ethical principals guiding federal regulations for the protection of human subjects.

There are three fundamental ethical principles, as outlined in the Belmont Report, that guide research involving human subjects: (1) respect for persons, (2) beneficence, and (3) justice. By 1991, seventeen federal departments and agencies had adopted the federal regulations known as the Common Rule (Title 45 Code of Federal Regulations Part 46 [43CFR46]).

Research is defined as a systematic investigation (including development, testing, and evaluation of programs and methods) designed to discover or contribute to a body of generalizable knowledge. Not all scientific or scholarly activities qualify as research, nor does all research involve human participants. A human subject is a living individual about whom an investigator obtains either (1) data through interaction or intervention with the person, or (2) identifiable private information. Each investigator must decide if their study is to include human participants. If human participants are to be involved, the researcher is ethically obligated to become familiar with and adhere to the regulations governing the rights and safety of the human research participants.

Vulnerable Populations

Certain groups of human research participants–such as children, prisoners, individuals with questionable capacity to consent, students, or employees of the institution conducting the research–are considered to be either relatively or absolutely incapable of protecting their own interests. Because children have not legally attained an age where they can consent on their own to research or treatment, a parent or legal guardian may provide consent for a child to participate in a study. Above the age of seven, the child must also show willingness to participate by assenting to the study. Although many college students are below the age of twenty-one, they are generally treated as "emancipated adults" for the purpose of consenting to participate in research studies.

Institutional Review Boards

The National Research Act passed by Congress in 1974 that resulted in the Belmont Report also required the establishment of Institutional Review Boards (IRBs) to review all research involving human subjects funded by the Department of Health and Human Services. The regulations governing IRBs were revised in 1981.

Every institution in the United States receiving federal support for research with human subjects has to have its own IRB or access to an IRB. An IRB protects the rights, safety, and welfare of human research participants by: (1) reviewing research plans to ensure that, in its judgement, the research meets the criteria found in 45CFR46.111; (2) confirming that the research plans do not expose participants to unreasonable risks; (3) conducting continuing review of approved research at intervals commensurate with the degree of risk of the trial–but not less than once a year–to assure that human participant protections remain in force; and (4) assessing suspected or alleged protocol violations, complaints raised by research participants, or violations of institutional policies.

The IRB has the authority to approve, disapprove, or terminate all research activities that fall within its jurisdiction; require modifications in protocols, including previously approved research; require that information, in addition to that specifically mentioned in 45CFR46.116, be given to participants when the IRB deems that this information would add to the protection of their rights and welfare; and require documentation of informed consent or allow waiver of documentation, in accordance with 45CFR46.117.

IRBs must have at least five members with varied backgrounds who have no vested interest in the conduct or outcomes of the proposed research. At least one member of the IRB must not be affiliated with the institution, and the membership should be as diverse as possible. Most IRBs have many more than five members, and most are divided into subcommittees for the purpose of handling different types of studies, such as biomedical or behavioral studies.

In order to approve a research study, the IRB must assure that risks to participants are reasonable and minimized; that the selection of participants is equitable; that informed consent from each participant is sought and documented; and, when appropriate, that there are adequate provisions to protect the safety and privacy of the participants and the confidentiality of the data. Depending on the level of risk and the type of subject population, review may be done by the full IRB, or it may be expedited. Certain types of studies are exempted from IRB review and approval. Even in these exempt cases (many of which involve educational practices or tests), however, it is not the researcher but the IRB that makes this determination.

Informed Consent

Informed consent, as a legal, regulatory, and ethical concept, has become widely accepted as an integral part of research involving human subjects. A written consent document is a key part of the proposal submitted to an IRB. This is a document written to the proposed subject in a language understandable by the subject. All of the elements required by 45CFR46.116 must be included, plus any other information necessary for the prospective participant to make an informed decision. The required elements include a statement that the study involves research; an explanation of the purpose of the research, including why the individual was selected and the expected duration of the individual's participation; a description of all procedures to be followed; a description of any foreseeable risks, discomforts, and inconveniences (and what will be done to minimize or deal with them); a description of any anticipated benefits, both to the individual subject and to society; information about who to contact if there are additional questions; a statement that participation in the research is voluntary, that withdrawal may occur at any time, and that there is no penalty for withdrawal or refusal to participate; and, finally, an invitation for the participant to ask any questions about the proposed study before agreeing to participate.