DOI: 10.1148/radiol.2372031637
(Radiology 2005;237:383-384.)
© RSNA, 2005
Responsible Conduct of Radiology Research Part IV. The Boundary of Research and Practice1
Jeffrey A. Cooper, MD, MMM
1 From the Association for the Accreditation of Human Research Protection Programs, 915 15th St NW, Suite 900, Washington, DC 20005-2315, and the Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa. Received October 8, 2003; revision requested January 5, 2004; revision received May 6; accepted June 14.
Address correspondence to the author (e-mail: jcooper{at}aahrpp.org).
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ABSTRACT
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The purpose of this series of articles is to explain the ethical and legal basis for responsible conduct of radiology research and the rules that an investigator must follow. Part four of this series explains special situations that commonly arise during human research in radiology. The boundaries of research and innovative care or quality improvement often are not clear. When human research activities are or become subject to regulation, they must be reviewed and approved by an institutional review board. Therefore, physicians performing innovative care or conducting quality improvement should have a low threshold for seeking institutional review board guidance. Physicians performing innovative care should also consider their ethical obligation to future patients to conduct research to prove the validity of such innovative care.
© RSNA, 2005
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INNOVATIVE CARE AND RESEARCH
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When the Food and Drug Administration (FDA) approves a drug or device, they also approve labeling, which is commonly referred to as a package insert. The package insert provides information about the indications, contraindications, and method of use. Use of a drug or a device in a manner that is inconsistent with the package insert is called off-label use. Examples of off-label use include use of an intracoronary stent in the peripheral vasculature and use of technetium 99m sulfur colloid in the detection of aspiration.
The FDA regulates the sale and marketing of drugs and devices by manufacturers, not their use by physicians. Therefore, physicians are allowed to use approved products as they wish (1,2). The regulations that cover emergency use of a test article do not apply (see part three of this series) (3).
Physicians may desire institutional review board (IRB) approval of off-label use. The IRB has no regulatory authority to convey such approval, however, and should not exert oversight of medical practice by reviewing and approving clinical procedures. Radiologists who seek approval for the off-label use of products should discuss their situation with their chief of service or medical director. These individuals, rather than the IRB, are responsible for medical practice.
Radiologists commonly find themselves using imaging techniques or agents in novel or off-label ways to provide the best care for their patients. Although there is no intent to conduct research at the outset, radiologists may subsequently desire to retrospectively review their data. Radiologists need to be certain whether their sole intent is clinical or whether they have both clinical and research intent. If there is any prospective collection of data or establishment of databases beyond those required for clinical care, discussion of research in the clinical informed consent form, or any research intent, IRB review is required at the outset. If the initial intent is solely to provide the best patient care and a subsequent decision is made to conduct a retrospective review, IRB approval must be obtained before collecting, organizing, or analyzing data. In this case, publications, including abstracts, should clearly indicate that the study was retrospective and that patients were selected and treated on the basis of clinical criteria.
Although a radiologist has the option to use a product for off-label purposes and retrospectively evaluate the data, he or she should ask the question, "If there were no possibility of ever publishing the results of this off-label use, would I still conduct the off-label use?" This is a way of asking, "Is my primary intent doing what is in the best interest of the patient or conducting research?" If the answer to the first question is no, the off-label use should be performed as part of a research protocol (4).
Physicians are provided latitude to practice medicine with innovative techniques. Provided that a physician's sole intent is to enhance the well-being of his or her patient, such practice generally does not fall under the Department of Health and Human Services regulatory definition of research. Although the regulations distinguish between activities that are or are not research, they do not identify activities that are not research but ought to be evaluated in a research study. Since research forms the basis of evidence-based medicine and since physicians ought to practice evidence-based medicine whenever possible, research ought to be conducted to prevent the proliferation of untested practices. Therefore, when physicians undertake innovative medical practice, they should evaluate those procedures at an early stage with a research protocol to determine whether they are safe and effective (5).
The IRB, as a regulatory body, can make a determination whether an activity is human research according to the regulations. Once the IRB has determined that an activity is not human research, however, the IRB should not be in the position of having to decide whether that activity ought to be evaluated in a research study. Instead, a body that oversees medical practice should make such decisions (5). When investigators need guidance to determine whether innovative medical practice should be performed as part of a research study, they should consult with their medical staff committee or medical director.
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QUALITY IMPROVEMENT VERSUS RESEARCH
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A common controversy is whether an activity designed for quality improvement is research according to the definition of research in the Department of Health and Human Services regulations (6). The reason for this controversy is clear, as both quality improvement and research activities are systematic and use the scientific method. Quality improvement uses the scientific method to improve patient care, whereas research uses the scientific method to obtain knowledge that can be generalized. Some quality improvement activities are not designed to develop knowledge that can be generalized from one radiology department to another. For example, measuring patient satisfaction to determine the optimal staffing for the outpatient registration process will probably not result in knowledge that can be generalized. On the other hand, a comparison of the diagnostic accuracy of two magnetic resonance imaging sequences in the detection of ligament injuries of the knee will probably result in knowledge that can be generalized. Some knowledge does not clearly fit in either category, such as the comparative use of resources among several conscious sedation protocols.
When quality improvement activities might have a design that will generate knowledge that can be generalized, consultation with an IRB is recommended. In response to this consultation, IRBs should provide a rapid and responsive approach to such consultation, so as to not hamper quality improvement activities. If the quality improvement activity falls under the regulatory definition of research, it must be reviewed by an IRB or determined to be exempt from the regulations. In some cases, activities that are both quality improvement and research become impracticable to complete if informed consent becomes a requirement. When these activities involve minimal risk and the absence of informed consent does not affect the rights and welfare of the participants, investigators should request a waiver of informed consent. The IRB should grant a waiver of informed consent if it determines that the situation meets the regulatory criteria.
Quality improvement activities without any design to obtain knowledge that can be generalized may, at a future point, reveal knowledge that can be generalized. IRB review should be sought when this knowledge is discovered. IRBs should understand that such situations occur without any intent of the investigator to circumvent IRB regulations. Investigators should understand that use of this mechanism to circumvent IRB approval is inappropriate. Commonly existing data can be reviewed and reported as exempt research. Future activities can be reviewed as prospective research.
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CONCLUSION
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Since the boundaries of research and innovative care or quality improvement often are not clear, when activities are or become human research, thus becoming subject to Department of Health and Human Services or FDA regulations, they must be reviewed and approved by an IRB. Therefore, physicians performing innovative care or conducting quality improvement should have a low threshold for seeking IRB guidance. Physicians performing innovative care should also consider their ethical obligation to future patients to conduct research to prove the validity of such innovative care.
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FOOTNOTES
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Abbreviations: FDA = Food and Drug Administration • IRB = institutional review board
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References
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- Investigational new drug application: applicability. 21 CFR
312.2 (2002).
- Investigational device exemptions: applicability. 21 CFR 812.2 (2002).
- Cooper JA. Responsible conduct of radiology research. III. Exemptions from the regulatory requirements for human research. Radiology 2005;237(1):3–7.[Abstract/Free Full Text]
- Amdur RJ, Speers MA. Identifying research intent. In: Amdur RJ, Bankert E, eds. Institutional review board: management and function. Sudbury, Mass: Jones & Bartlett, 2002.
- Office of the Secretary. The Belmont report: ethical principles and guidelines for the protection of human subjects of research. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. http://ohrp.osophs.dhhs.gov/humansubjects/guidance/belmont.htm. Published 1979. Accessed September 15, 2003.
- Casarett D, Karlawish JH, Sugarman J. Determining when quality improvement initiatives should be considered research: proposed criteria and potential implications. JAMA 2000;283(17):2275–2280. [Abstract/Free Full Text]
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