Introduction
Completing the institutional review board (IRB) review process is an essential component of a research study. For a novice investigator unfamiliar with the process, submission of an application to an IRB may be challenging or even intimidating. The purpose of this article is to present an overview of the purpose and process of the IRB to guide investigators in navigating the regulatory requirements of human subjects' research.
What Is an IRB?
An IRB is charged with protecting the rights of people who are involved in research as subjects. The IRB is typically a facility-based review board; IRBs exist as a result of the National Research Act, a 1974 federal government mandate enacted in an attempt to protect human research subjects from undue harm. The Food and Drug Administration (FDA) guidance describes the need for the IRB as follows: "The purpose of IRB review is to assure both in advance and by periodic review that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in research" (http://www.fda.gov/RegulatoryInformation/Guidances/ucm126420.htm).
Institutional review boards review all types of studies. Examples of studies that require IRB review and approval include patient interviews to determine the effectiveness of a treatment, chart reviews, or analysis of computer-stored clinical data to assess the prevalence of types of wounds, mailed or Web-based questionnaires or surveys to WOC nurse colleagues about their opinions about a practice reimbursement policy, as well as trials of new drugs, devices, and procedures.
Why Do We Have IRBs?
Institutional human research subject protection is a relatively modern idea. In the United States prior to 1950, there was almost no government oversight of human subjects research. In order to address this issue, the United States established the Common Rule, which is a set of core federal regulations adhered to by the FDA and all US Department of Health and Human Services and National Institutes of Health entities as found in the Code of Federal Regulations (45CFR), Part 46 Subpart A (Basic Policy for the Protection of Human Subjects): http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#subparta. The initial basic federal regulations came about as a result of several unethical research endeavors. From an international perspective, the Nuremberg trials brought to light the inhumane and unethical treatment of prisoners by the Nazi regime for research purposes. One of the most infamous and unethical US studies was the federally sponsored Tuskegee syphilis experiment in which African American men were deliberately left untreated for their syphilis infection after a cure was identified, in order to study late-stage complications of the disease. In other instances, cancer cells were injected into hospitalized patients in New York at the Brooklyn Chronic Disease Hospital without patients' knowledge and institutionalized children in Willowbrook, New York, were intentionally exposed to hepatitis in an effort to find a preventive measure for the disease that was epidemic in the institution.2 When evidence of these research trials came to light, a national commission was established by the 93rd Congress of the United States in July 1974. Referred to as the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, the commission was tasked with the responsibility to identify common ethical principles underlying human subjects' research. These principles are respect, beneficence, and justice. The informed consent contains 3 elements: information, comprehension, and voluntariness, which address the ethical principle of respect. Beneficence recognizes the obligation to protect persons from harm by maximizing benefits and minimizing possible risks. The IRB will require risk-benefit assessments in the protocol with the probabilities and risks of possible harms and anticipated benefits. Justice requires that the benefits and burdens of research be distributed fairly. For example, the selection of subjects must be the result of fair selection procedures as it relates both to the subject as an individual and to the subject as a member of social, racial, sexual, or ethnic groups.
Commission members were also asked to identify mechanisms to assure that research was conducted according to the agreed-upon principles. This commission's findings became the basis for the Code of Federal Regulations, Title 45 Public Welfare, Department of Health and Human Services, Part 46, Protection of Human Subjects known as 45 CFR 46 A (the Common Rule), which delineates the requirement for independent ethical review boards now referred to as IRBs. The Common Rule is relatively specific about the make-up of IRBs. The IRB must be composed of no less than 5 members with varying backgrounds. The membership must include a scientist, nonscientist, and someone unaffiliated with the institution. The IRB must have members professionally and experientially qualified to review the research submitted. A quorum is needed to vote on acceptance or rejection of a research protocol.3
Submitting a Protocol
In general, if you are a researcher and propose to subject people to an experimental practice or procedure, in most instances 45 CFR 46 A requires you to submit your proposal and subject consent form at minimum to an IRB for review. Some IRBs have developed an additional application with questions in which they are specifically interested that the investigator must complete. An IRB may include staff members of the institution for whom you work as well as local community members. Alternatively, the institution may delegate the process of protocol review to an independent IRB. Nearly all IRBs have Web pages and many have staff members, usually referred to as compliance coordinators, who can assist researchers in submitting their studies for review. Therefore, the first thing a new investigator can do to prepare for review by an IRB is consult the Web page of their IRB.
Most IRB Web pages include a section that enables quick startup by providing necessary forms and submission information. The researcher simply needs to follow the directions attached to the forms. If you get to a point in the process where things seem confusing, we recommend consulting the compliance coordinator. Once the protocol and consent forms have been constructed, they are then submitted to the IRB for review and recommendations (Boxes 1 and 2).
Institutional review boards are committed to providing service while following federal regulations. If they too freely interpret or fail to properly interpret regulations, subjects may be harmed and an institution's entire research program may be shut down by a federal office with research oversight, either OHRP (Office for Human Research Protections) or the FDA. For example, a healthy volunteer died after participating in an asthma study conducted at Johns Hopkins University in 2001. The IRB and the researcher were faulted by OHRP for failing to provide adequate consent and oversight and the institution's research mission was temporarily halted.5
IRB Responsibilities and Your Research
The responsibilities of the IRB fall into 2 main categories: initial and continuing review.4 The purpose of the initial review is to ensure that any risks encountered by research participants are necessary in order to conduct the research and that the benefit to the subject balances-associated risk. This is often referred to as the risk-benefit ratio. For example, a WOC nurse may desire to complete a clinical trial looking at a new type of silver dressing. The IRB will want to know whether there are any potential benefits or risks to the patient for participating in this clinical trial. For example, an example question about a benefit may be "Will the wound heal faster?" Example questions about risks may be "Will there be a risk of the wound deteriorating with the new dressing?" or "What is the risk for infection from the new dressing?" The IRB must be assured that risks as well as possible benefits are stated on the consent form and the risk of participation is ethically justified. Continuing review involves ongoing yearly assessment of the risks and benefits and ethical conduct once the study is under way.
Your study may have to be reviewed by an entire IRB committee (generally 8-10 people) or, if the study poses minimal or no risk, then it may be eligible to be reviewed by an exempt or expedited process (Box 3). For example, mailing out a questionnaire to ostomy patients usually poses minimal risk and this type of study may be expedited. The expedited process is generally less complicated and requires less time as it involves having 1 or 2 people of the IRB committee reviewing the study as opposed to the full committee.
Use of an IRB is mandated only for federally funded studies or by the FDA for studies that involve new drugs or devices. Even so, many institutions sign an assurance known as a Federal Wide Assurance, which states that they will require all research to be conducted according to federal regulations. However, if an institution is private and does not receive federal research funding, they may not create an IRB. If you work in a facility without an IRB, you will need to engage the services of an independent IRB when completing a trial that is funded by a source that requires such approval (such as the WOCN Center for Clinical Investigation). An example of an independent review board is Western IRB. The Western IRB has predetermined charges for all aspects of study review and this information is available at its Web site: http://www.wirb.com.
A common question about the need for review by and IRB concerns surveying WOC nurse colleagues. Even though those being surveyed are professional colleagues, if the survey is for a research study, then the WOC nurses are considered research participants. In this case, the study would require review by an IRB. A simple telephone call or e-mail to the IRB can answer whether a review is needed and if so, the appropriate type of review is required.
Multisite and International Studies
You might participate in a collaborative study, one that is being conducted at multiple sites and involves a number of WOC nurses. The method of the IRB review in this instance will depend upon your institution's policy. The Common Rule allows for there to be an agreement between the participating centers that allows one IRB to be the IRB of record. However, the individual institutions must determine if this is acceptable or not. It is more common that each site will conduct its own review mostly due to anxiety over accountability if something has been done in error.
In the case of international studies, there are equivalent foreign groups or boards that provide research oversight. Often the ministry of health for a country will give approval for research to be conducted by foreign research groups. US researchers should first consult their local IRBs when developing an international research proposal. Typically the local IRB will require the foreign countries' IRB equivalent to send a letter approving the research. In most cases, there is a collaborator who is a native of the country where the research is being conducted.
Quality Improvement Projects Versus Research
Clinicians often voice confusion when trying to distinguish between quality improvement (QI) and research projects, and the distinction between these activities is frequently not straightforward. If the intent is to implement what is already known to be "best clinical practice," the project can probably be categorized as QI. The problem comes when there is an attempt to compare practices. According to Grady6 of the National Institutes of Health, "The guiding principle should be that activities whose goals extend beyond the immediate interests of patients should undergo independent review to ensure that patient interests are protected."6 Given this standard, any project that is not clearly directed toward immediate patient benefit should be categorized as a research study. Nevertheless, there is ongoing debate about this distinction and we recommend consulting your IRB when determining whether your project should be categorized as a research study or QI project.
Conclusion
The IRB approval process may seem overwhelming to a novice investigator. However, this anxiety may be relieved by bearing in mind that the IRB exists to protect research participants from undue harm rather than obstructing the research process. With the help of the IRB, the principal investigator will have peace of mind that the study is ethical and that subjects will not be exposed to unnecessary risk. Many IRBs have staff committed to assisting researchers in complying with complex government regulations and prevent disruption of institutional research through effective oversight. Investigators are encouraged to consult their local IRB Web site and communicate with the IRB if online directions need further clarification. Early communication in the process will enable timely start of a study and ethical research.
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