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.
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.
An Abbreviated History
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.
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 Role of the IRB
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)]
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.
Types of IRB Review
There are 3 types of IRB review categories: