The ABCs of IRBs: A Brief Overview

At some point in their careers, most oncologists will need to submit a research proposal to their hospital’s Institutional Review Board (IRB). Too many physicians view the IRB process as an additional bureaucratic burden in their already overloaded daily schedules. In reality, these boards serve an extremely important purpose: protecting human subjects who choose to participate in research.

An Abbreviated History

Since most medical schools do not provide information regarding IRBs in their curriculum, many oncology fellows may not have a basic understanding of IRBs or what they do. This article provides a brief overview of IRBs and outlines pertinent resources for fellows who conduct or may contribute to human research studies.The mandate for IRBs in the United States is a result of notorious human experiments performed over the last century. The horrific Nazi experiments during World War II involved physicians overseeing research on: the effects of drinking sea water; human experiments with spreading diseases such as hepatitis, typhus, and malaria; cold immersion studies; and, human sterilization experiments. Sadly, irresponsible studies were carried out in the United States as well, including the Willowbrook Hepatitis Studies, Milgram Studies of Obedience, and the Tuskegee Syphilis Study.

The Role of the IRB

In short, these types of research prompted the current US system of protection in human subject research. The ethical standards for the conduct of human subject research are codified in several federal regulations, including 45CFR46 and 21 CFR Parts 50 & 56. The IRB serves an integral part in the system of protection by upholding these standards.The IRB has the authority to approve, require modifications to, or disapprove a research activity. Each IRB is composed of at least 5 members from various disciplines, at least one of whom is a non-scientist. Some institutions have multiple IRBs, depending on the number of research proposals to be reviewed.

According to 45CFR46.111, in order to approve a research proposal the IRB must determine that each of the following requirements is satisfied:

• Risks to subjects are minimized: By using procedures that are consistent with sound research design and do not unnecessarily expose subjects to risk. Whenever appropriate, by using procedures already being performed on subjects for diagnostic or treatment purposes.
• Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB considers only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research).
• Selection of subjects is equitable. In making this assessment the IRB takes into account the purposes of the research and the setting in which the research will be conducted.
• Informed consent will be sought from each prospective subject or the subject’s legally authorized representative.

• Informed consent will be appropriately documented, typically with a signed consent form.
• When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
• When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
• When some or all of the subjects are likely to be vulnerable to coercion or undue influence, additional safeguards are included in the study.

Is This Project Human Research?

This is a question often asked by clinicians and investigators. At times there is an affirmative and straightforward answer, such as in the case of drug trials designed to determine the effectiveness of a new pharmaceutical formulation in treating a certain illness. But at other times, the answer is not as immediately apparent.

The federal regulations define research as “a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.”[45CFR46.102(d)] A human subject is defined as “a living individual about whom an investigator (whether professional or student) conducting research obtains data through intervention or interaction with the individual, or identifiable private information.” [45CFR46.102(f)]

Types of IRB Review

There are a lot of grey areas here. If you have any questions regarding whether a project you are planning to implement is considered human research, you should address them to your local IRB office. They will likely require some written documentation from you to consider the question. The details vary by site, but you may be asked to submit a written protocol and/ or an application; this varies by site.There are 3 types of IRB review categories:

• Full Board Review This type of review is conducted for studies that entail greater than minimal risk to subjects. It is carried out by a fully convened IRB committee. According to federal regulation, minimal risk means that “The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.” [45CFR26.102(f)]
• Expedited Review This type of review is for studies that involve minimal risk to subjects. The review is performed by the IRB chair or an experienced designee. One example is a project that collects biological specimens for research purposes via noninvasive means (such as hair and nail clippings in a non-disfiguring manner). The Department of Health and Human Services (DHHS) Office for Human Research Protections (OHRP) has a list of activities that fall under the category of minimal risk. Please note that use of the term “expedited” does not necessarily translate into a speedier review by the IRB.
• Exempt Review Regulations specify several research activities that are considered exempt from review (45CFR46.101b). An example would be a minimal risk survey that cannot be linked to subjects through any form of identifiers. Due to the potential for conflict of interest, it is important to note that someone other than the investigator must make the determination of whether or not a study meets the criteria for exemption. Typically, this determination should be made by an IRB member. Contact your IRB office to determine the local procedures for exemption in your institution.

Documents Needed for IRB Review

In assessing the type of review your research project may require, a useful tool to have on hand is a group of decision charts published by the DHHS. This will guide you through a list of questions to determine which review category is appropriate for your particular study (see sidebar for resources). Also, communicating with the IRB office to confirm that you are completing the correct forms for submission can save you time later.Typically, IRBs include a list of documents required for review submissions on their website. The documents may vary according to the type of research involved. The website will also have a template consent form containing standard language.

Examples of documents that may be required to be submitted with each new full-board review submission include an IRB application, detailed study protocol, subject consent form, data collection tools, grant/contract application, Investigator Brochure, recruitment advertisements, subject questionnaires, and Financial Interest Disclosure forms.

The Full Board IRB Review Process

In addition, funding and accreditation agencies have adopted policies that mandate human research protection education for all study personnel. Many institutions utilize the Collaborative Institutional Training Initiative (CITI) course for this purpose. This contains various training modules and a certificate is issued upon successful completion of the course. Most IRBs will not issue final approval of a project until they have verified that all study personnel have completed this training.For full IRB review, the board will need all of the required documentation to assess that the study meets the federal criteria for approval. Many IRBs operate on a primary reviewer system whereby 1 or more IRB members are assigned a protocol based on the member’s education, background, and expertise. If no member has the appropriate expertise, an outside consultant is usually called upon. Some IRBs invite the investigator to the convened meeting to present their new protocols and answer any questions that might arise.

Much of the committee’s discussion is typically focused on weighing the risks involved with the study versus the potential for benefit to subjects. Risks include not only physical risks but also psychological and social risks. Recommended changes to the consent form are also discussed. If significant concerns are raised by the IRB, the protocol may be tabled or disapproved.

During the meeting, the IRB will determine the length of approval. This is based on the risks associated with the study and cannot exceed 1 year. The IRB may shorten the approval period for higher- risk protocols.

IRB Approval Timeline

At the conclusion of the discussion, an IRB member makes a motion, it is seconded by another member, and then all members vote for or against approval or may abstain from voting. Members with a conflict of interest are required to leave the meeting room during the discussion and cannot participate in the vote.Oncology fellows need to be aware that once an application is submitted to the IRB it may take up to a month to be reviewed, although the time frame depends on the particular institution. Ask your local IRB for its average turn around time. This may vary according to review category and deadlines for submission. Since projects cannot be initiated until IRB approval is received, it is imperative to take this interval into consideration when developing a timeline for the implementation of any given research project.

Conclusion

Another issue to consider in scheduling planning is that project approval will likely not be granted outright. Upon review, the IRB may determine that certain changes are required in order to obtain approval. These could include recommended changes to the protocol, consent document, data collection sheet, etc. The investigator will need to respond to the IRB’s suggested revisions in writing and resubmit the materials for review by the IRB.It is the responsibility of the investigator to maintain IRB approval at all times. This means that continuing reviews must be submitted in a timely manner to avoid a lapse in approval. All study amendments must be submitted for approval prior to their implementation. Protocol deviations or violations and adverse reactions must be reported.

It is important for oncology fellows to communicate with their local IRB office. The IRB staff can review materials (such as study protocols, consent forms, etc) prior to the formal submission to the full IRB committee and can provide answers to many questions. This can save investigators valuable time and avoid aggravation in the long run.

Breaches in compliance can lead not only to bad headlines in newspapers, but also a suspension of all federally funded research at the institution. The ultimate responsibility for the protection of human subjects in research rests with the investigator and is congruent with the declaration in the Hippocratic Oath to “Do no harm.”

The primary mission of the IRB is to protect human subjects. But it is important to note that in so doing, they can serve as a resource and can also protect investigators who are conducting the studies.

Nancy Fell Hill, MPH, is a New Jersey— based research administrator and freelance author. She has more than 10 years of experience working with IRBs in both a hospital setting and a large university.