The Role of IRBs in Human Subjects Research | Quorum Review IRB

A proposal to conduct research on human beings creates an ethical imperative: How do you perform scientific research on people while protecting each participant’s health and dignity? Researchers, ethicists, research institutions, and governments recognize that we must follow ethical guidelines when bringing humans into research; the consequences of not doing so can be inhumane and tragic. Medical and social/behavioral experiments have not always followed the most ethical routes to knowledge—consider the Nazi prison experiments, the Tuskegee syphilis study, the Milgram experiment, and coerced research on prisoners. More recently, we have seen the Gelsinger tragedy in gene therapy research, accusations of improper research on psychiatric patients, and unregulated experiments on herpes patients.

Although regulations and guidelines around the world define how research should treat human research subjects, written rules cannot resolve every ethical question. Specific situations in research require focused consideration: When (if ever) does the scientific benefit of using a placebo in a study justify a research participant not continuing accepted treatment? When does tracking a virulent disease’s spread through the population take precedence over an individual person’s right to privacy? How can we reassure a research participant that an investigator will conduct a study and analyze its results without bias or personal interest? Research ethics committees deliberate over these and other ethical challenges on a daily basis.

Research Ethics Committees (IRBs and REBs)

Most governments require some kind of ethics review—usually by a committee—to consider these questions. The term for these committees in the United States is institutional review board, or IRB; in Canada, it is research ethics board (REB). Other countries use the same or similar terms (Quorum Review IRB’s ethics boards meet requirements to operate in both the United States and Canada, and can review other international research). No matter the country, research ethics committees serve a common purpose: to ensure that research in humans follows specific regulations as well as broader ethical guidelines.

The rules for research in the United States generally fall under two sets of regulations: one that the Food and Drug Administration (FDA) enforces for approving commercial treatments and one called the Common Rule, which most government agencies follow. At the FDA, the Office of Good Clinical Practice oversees and guides human subject research policies. For research funded by the federal government, the Office for Human Research Protections (OHRP) within the Department of Health and Human Services (HHS) has the most prominent role in setting research ethics. In Canada, the Tri-Council Policy Statement (TCPS 2) sets ethics standards for conducting research on human subjects. The agencies that make up Tri-Council are the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), and the Social Sciences and Humanities Research Council of Canada (SSHRC).

In the United States and Canada, an IRB or REB must review and approve a research proposal before any human subjects enroll. In practice, the review includes ensuring that the protocol does not expose subjects to unnecessary risks, that there is an acceptable ratio of risks to benefits, that especially vulnerable populations have adequate protections, that selection of subjects is equitable, and that subjects are properly informed about what will happen in the study.

IRBs or REBs can either be associated with an existing institution, such as a university or a research hospital, or they can be independent. IRBs at institutions are often called local or institutional IRBs, while unaffiliated IRBs (such as Quorum) are known as independent IRBs.  An IRB that oversees multiple sites operating under one protocol is known as a central IRB or single IRB.  Industry-funded research often uses a central IRB model, and in the United States regulatory changes such as the 21st Century Cures Act, the National Institutes of Health (NIH) single IRB policy, and the revised Common Rule have increased the requirements for using central or single IRBs.

Issues for the IRB and REB

When reviewing research proposals, IRBs and REBs must be aware of the following:

  • The informed consent document is essential to an ethically conducted trial. IRBs and REBs review informed consent documents for appropriate description of the risks of the study, for adherence to the letter of the regulations, and for reflecting what the research protocol describes. The regulations pertaining to informed consent have many requirements, and these—combined with the drive to help the participant understand what will happen to him/her during the course of the trial—often create long, cumbersome consent forms. Reducing the size and complexity of consent forms is a constant challenge.
  • Advertisements that recruit participants into research also must have IRB/REB approval. The FDA and OHRP view advertising as the initial step of the informed consent process because advertisements can give potential subjects their first impressions of a study. While reviewing advertisements, IRBs and REBs ensure that materials provide accurate information, are not unduly influencing, and do not give a false impression that research equals treatment.
  • Other participant materials, such as patient diaries and surveys, also require IRB/REB review.
  • Translations of anything that a human subject might receive need IRB/REB approval. If any participants do not speak English, researchers must provide translated study materials, and someone who speaks the participant’s language (either a study staff member or an interpreter) must be present for any discussions about the study.
  • Privacy and confidentiality are critical topics for participants in research. Ethics committees face particular challenges now as research expands its use of internet-connected devices, large online databases, and stores of biospecimens.
  • Changes and renewals to research usually require IRB/REB approval to consider whether anything has changed that may affect a participant’s willingness to remain in the study. Examples could be new treatments that obviate continuation of the study, the discovery of new risks within the study, or additional procedures that pose unacceptable hardships to participants.
  • Conflict-of-interest questions should prompt an ethics committee’s scrutiny. Committees consider whether any possible conflicts could alter (or appear to alter) a researcher’s attitude toward participants and the results of a study. Financial incentives are the most obvious conflict of interest, but other factors, such as a researcher’s desire for prestige or the strengthening of personal relationships, may also cause ethical concerns. IRBs and REBs can impose restrictions to limit conflicts of interest and their effects.

IRBs and the FDA

The FDA requires that IRB approval remain active for the life of a study. This means that investigative sites cannot begin research until an IRB has approved the protocol and investigator for the study, that the IRB needs to know about and agree with changes to the research, and that the IRB must renew its approval of the study at least once a year.

For new pharmaceutical products, the FDA has four phases of research in human subjects. Phase I tests basic safety and dosage levels for an experimental treatment. These studies usually recruit healthy volunteers because the research focuses on safety, not effectiveness. Phase II expands into broader questions of safety, testing the possible treatment in affected participants. Phase III studies represent a crucial stage; they examine effectiveness to gauge whether this experimental treatment really works and does not have previously unnoticed side effects. Phase IV studies track long-term effects of newly approved treatments. An IRB must approve research at the start of each phase (although some Phase IV studies may not require as rigorous a review as others, depending on the risk to the participants). Device trials have a different framework, but they also require IRB/REB review. When a company requests approval for a new product, it must show the FDA that IRB approval was valid throughout the research.

After completing its Phase III research, the sponsor of the new drug submits a New Drug Application (NDA) to the FDA for approval. The NDA exhaustively describes the research and its results. A testing regimen for a new pharmaceutical treatment can take over 10 years and cost hundreds of millions—or even billions—of dollars. The FDA will review the results before deciding whether to approve the proposed treatment. Often the FDA will convene a panel of experts to review the results and recommend for or against the treatment under consideration.

The FDA does not solely oversee research conducted in the United States. It will accept research from overseas, and can approve a treatment if another country has granted approval, but generally the FDA wants to see at least some domestic research. In addition, the agency expects that international research follow both FDA requirements and the ethical guidelines of the country where the study occurs.

Dynamic Research, Dynamic Review

When IRBs and REBs review a study proposal, they must decide whether the protocol, its accompanying documents, and the facilities available for the investigative staff all meet the ethical demands of conducting research with human beings. Ethics committees must consider new developments, such as the rise in interest in biospecimens and future research, and the ever shifting regulatory framework. In addition, ethics committees must be especially conscious of how the research affects vulnerable populations, which may include children, pregnant women, people with diminished capacity for making decisions, or people who are unable to read (due to low literacy or visual impairment). Our society has real and sometimes urgent needs to learn more about the health of all people, and ethics committees can help move research forward while ensuring that human subjects are protected and respected.