Human-Subject Research Laws: Do Companies Need To Comply?

Human-subject research laws are influenced by the Belmont Report, which outlines the basic ethical principles in research involving human subjects. These principles include respect for persons, beneficence, and justice. While thesection 45 CFR 46 of the Federal Policy for the Protection of Human Subjects, or the Common Rule, applies to federally funded programs, Food and Drug Administration (FDA) rules apply to any company research on drugs or devices that are regulated by the FDA, regardless of funding. FDA rules are similar to the Common Rule and are designed to protect public health and advance public health. The FDA protects human subjects by ensuring the safety and efficacy of drugs, biological products, and medical devices. While some research may not fall under the Common Rule, many institutions voluntarily apply the protections laid out in it.

The Common Rule and its application to companies

The Common Rule is a set of ethical guidelines for research involving human subjects in the United States. It was published in 1991 and outlines the basic provisions for Institutional Review Boards (IRBs), informed consent, and assurances of compliance. The Common Rule is codified in the regulations of 15 federal departments and agencies, including the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA).

The Common Rule establishes the ethical principles of respect for persons, beneficence, and justice as the foundation for human subject research. It includes requirements for assuring compliance by research institutions, obtaining and documenting informed consent from research participants, and IRBs' membership, functions, operations, review of research, and record-keeping. The Common Rule also provides additional protections for vulnerable research subjects, including pregnant women, human fetuses, prisoners, and children.

While the Common Rule primarily applies to government-funded research, many academic institutions also adhere to these ethical standards regardless of funding. The Common Rule serves as the baseline for ethical conduct in human subject research and ensures that the rights and welfare of participants are protected.

Companies conducting human subject research must comply with the Common Rule if their research is conducted, supported, or otherwise regulated by a federal department or agency that has adopted it. This includes research in the biomedical and behavioral fields. Pharmaceutical companies, for example, must follow the FDA's rules, which are similar to the Common Rule, when researching new drugs intended for sale in the US market.

Additionally, companies may voluntarily apply the protections outlined in the Common Rule, even if their research falls outside the scope of federal oversight. This demonstrates a commitment to ethical research practices and the protection of human subjects.

FDA rules and their application to companies

The FDA's mission is to enforce laws enacted by the U.S. Congress and regulations established by the Agency to protect the consumer's health, safety, and pocketbook. The Federal Food, Drug, and Cosmetic Act is the basic food and drug law of the U.S. and is intended to assure the consumer that foods are safe to eat and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; and that all labelling and packaging is truthful, informative, and not deceptive.

The FDA's rules are very similar to the Common Rule, which is the current U.S. system of protection for human research subjects. The Common Rule was published in 1991 and is codified in separate regulations by 15 Federal departments and agencies. The FDA is not considered a Common Rule agency because its regulations differ, however, it is required to harmonize with the Common Rule whenever permitted by law.

The FDA's regulations for the protection of human subjects (21 C.F.R. § 50) include four subparts, while the FDA regulations for institutional review boards include five subparts (21 C.F.R. § 56). FDA regulations apply to all clinical investigations regulated by the FDA under sections 505(i) and 520(g) of the Federal Food, Drug, and Cosmetic Act, as well as clinical investigations that support applications for research or marketing permits for products regulated by the FDA.

The FDA's rules apply to companies in the following ways:

• Companies that do research on new drugs that they plan to sell in the U.S. must comply with the FDA's rules to protect humans in research.
• Companies that are developing products for rare diseases and conditions can be promoted by the FDA.
• Companies must pay user fees, import programs, and more.
• Companies must follow the FDA's electronic submissions program for the device, radiological health, and blood-regulated industries.

Informed consent and its implementation in companies

Informed consent is a cornerstone of clinical research ethics, and its implementation in companies is essential to protect the rights and welfare of human subjects involved in research. The process of obtaining informed consent involves providing potential participants with essential information about the research, including its purpose, expected duration, procedures, risks, benefits, and alternatives. This information enables individuals to make a voluntary and informed decision about their participation.

In the context of companies, informed consent is particularly relevant in the field of human-subject research, where companies conduct studies or trials involving human participants. The implementation of informed consent in companies is guided by federal regulations, institutional review boards (IRBs), and ethical principles. Here are some key aspects of informed consent and its implementation in companies:

Federal Regulations:

• The Common Rule, also known as the Federal Policy for the Protection of Human Subjects, provides a set of standards for conducting human-subject research. It defines the requirements for obtaining informed consent, including the elements that must be included in the consent form and the process.
• The Common Rule is applicable to research conducted or supported by federal departments and agencies. However, it's important to note that not all human-subject research falls under the purview of the Common Rule, as some studies may be funded by private companies or other sources.
• The U.S. Food and Drug Administration (FDA) also has its own set of regulations for human subject protection, which are similar to the Common Rule but not identical. Companies conducting clinical trials or drug development must comply with FDA rules to protect human subjects.

Institutional Review Boards (IRBs):

• IRBs play a crucial role in reviewing and approving research protocols, including informed consent forms. They ensure that the rights and welfare of human subjects are protected.
• IRBs may provide consent templates, guidance, and training to research staff to help them develop informed consent forms that comply with the applicable regulations.
• The IRB panel reviews each study submission, including the consent form, and may suggest revisions to ensure all required elements are included and written in understandable language for potential participants.

Ethical Principles:

• The Belmont Report, published in 1979, established three core ethical principles for human-subject research: Respect for Persons, Beneficence, and Justice. These principles form the foundation for the Common Rule and FDA regulations.
• Respect for Persons emphasizes treating individuals as autonomous and protecting those with diminished autonomy.
• Beneficence focuses on maximizing benefits and minimizing potential harm to research participants.
• Justice refers to the equitable distribution of burdens and benefits associated with the research study.

Implementation in Companies:

• Companies conducting human-subject research should have a Human Research Protection Program (HRPP) to ensure an institution-wide approach to protecting human research participants.
• Clinical research coordinators, under the supervision of investigators, are responsible for ensuring that research consent forms comply with federal regulations and institutional requirements.
• Companies should provide training and resources to research staff to help them understand and implement the requirements for informed consent effectively.
• The use of simple language, visual aids, and alternative formats can improve the comprehension of consent forms by potential participants, especially those with limited literacy or diverse sociocultural backgrounds.

In summary, informed consent is a critical aspect of human-subject research conducted by companies. By adhering to federal regulations, collaborating with IRBs, and upholding ethical principles, companies can ensure that participants are adequately informed and protected, making informed consent a collaborative and ethical process.

Ethical considerations in human-subject research

Human research is a broad field that involves significant risks and ethical considerations. The ethical principles and guidelines for human-subject research are based on the Belmont Report, which outlines three core principles: respect for persons, beneficence, and justice. These principles form the foundation of the Department of Health and Human Services (HHS) Common Rule regulations and the United States Food and Drug Administration's (FDA) human subject protection regulations.

The principle of respect for persons acknowledges individuals as autonomous agents and protects those with diminished autonomy. This requires treating individuals as self-governing agents, obtaining their voluntary and informed consent, and protecting them from harm.

Beneficence, the second principle, is an obligation to treat individuals ethically by maximizing benefits and minimizing potential harm. This includes conducting research with the intention to benefit individuals and society, while also being mindful of risks and ensuring the safety of participants.

The third principle, justice, refers to fairness in the distribution of burdens and benefits. It emphasizes equitable selection of research subjects, ensuring that vulnerable populations are not exploited, and considering the impact of research on society as a whole.

In addition to these principles, there are further ethical considerations in human-subject research:

• Informed consent: Participants must be provided with sufficient information about the research, including its purpose, risks, benefits, alternatives, and their right to withdraw. This process should be free from coercion or undue influence.
• Risk/benefit assessment: A careful evaluation of the risks and benefits associated with the research is essential. Risks should be minimized, and the potential benefits should outweigh them.
• Selection of subjects: The selection of research subjects must be fair and avoid exploiting vulnerable populations. It should not be based on convenience or the easy availability of certain groups.
• Institutional Review Boards (IRBs): IRBs play a crucial role in reviewing and approving research protocols, ensuring compliance with ethical standards, and providing ongoing oversight to protect the rights and welfare of human subjects.
• Confidentiality and privacy: The protection of participants' personal information and confidentiality of research records is critical. This includes adhering to medical privacy requirements and obtaining consent for the use of identifiable data or specimens.
• Additional protections for vulnerable populations: Special considerations are necessary for certain vulnerable groups, such as pregnant women, prisoners, and children, to ensure their rights and welfare are protected.
• Compliance and oversight: Human-subject research is governed by federal regulations, state laws, institutional policies, and accreditation standards. Compliance with these regulations is essential to protect the rights and welfare of research participants.

These ethical considerations are essential to ensure that human-subject research is conducted responsibly and ethically, protecting the rights and welfare of participants while also advancing knowledge and contributing to societal benefits.

Institutional Review Boards (IRBs) and their role in companies

Institutional Review Boards (IRBs), also known as Independent Ethics Committees (IECs), Ethical Review Boards (ERBs), or Research Ethics Boards (REBs), are committees that ensure the ethical treatment of human subjects in research. IRBs are most commonly used for studies in health and the social sciences, including anthropology, sociology, and psychology.

IRBs are governed by Title 45 Code of Federal Regulations Part 46 in the United States. These regulations define the rules and responsibilities for institutional review, which is required for all research that receives support, directly or indirectly, from the US federal government. Specifically, research on human subjects conducted by any institution must be reviewed by that institution's review board if it involves:

• The federal government
• Any type of federal funding (e.g. a research grant)
• Testing an FDA-regulated product

IRBs are composed of a group of people independent of the specific research being conducted. They review proposed research plans and related documents before a study can begin and then periodically (usually annually) for the study's duration. The goal of IRB review is to ensure that the rights and welfare of participating research subjects are protected. To do this, IRBs evaluate whether:

• Risks to subjects are minimized and reasonable in relation to the importance of the expected knowledge
• The process and outcomes of subject selection are fair, including delineated inclusion and exclusion criteria
• There are adequate plans for obtaining informed consent

IRBs have the authority to approve, require modifications to, or disapprove research. While most of the heavy lifting occurs during research initiation, an IRB will continue to monitor trial activities as long as there are interactions between researchers and participants.

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