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Editor's Note
September 2015

Informed Consent and Communicating Risk and Benefits of Research on Higher-Risk Medications

JAMA Intern Med. 2015;175(9):1568-1569. doi:10.1001/jamainternmed.2015.3555

The Belmont Report1 formally established ethical principles and guidelines in 1979 for the protection of human research subjects in the United States. Summarizing discussions among the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research from an initial 4-day meeting at the Smithsonian Institution’s Belmont Conference Center, as well as several years of subsequent deliberations, 3 core principles were identified in the Belmont Report: respect for persons, beneficence, and justice. While these principles frequently come into play in clinical research, the Belmont Report suggests that when designing a study, careful consideration should be given to informed consent, the assessment of risks and benefits, and selection of participants. To ensure that all conducted research involving human participants is aligned with these ethical principles and guidelines, institutional review boards (IRBs) have been formed across the country, both at academic medical centers and elsewhere. Considerable time and effort are invested by these IRBs, as well as by investigators and research staff, to ensure compliance with the aforementioned principles and guidelines. But how effective have we been? There are few simple ways to measure effectiveness in this area, but Bhattacharya et al2 suggest one in this issue of JAMA Internal Medicine: what proportion of applicable informed consent forms disclose black box warnings issued by the US Food and Drug Administration (FDA) for study medications?

At a single institution, Bhattacharya et al2 reviewed 4780 research protocols involving human participants approved by their IRB between January 2010 and December 2012 and determined that for 57 protocols (1.2%), a black box warning had been issued for a study medication. However, nearly two-thirds of informed consent forms for these protocols did not disclose the known safety risk. Studies of these higher-risk medications were infrequent. However, because these studies lacked disclosure of the safety risk, they can neither have ensured true informed consent nor provided a full assessment of the risks and benefits of study participation. Bhattacharya et al should be applauded for publicly examining and reporting on this problem identified at their IRB, but there is no reason to think the problem is an isolated one. Risks and benefits of study medications are difficult to quantify. However, FDA issuance of a black box warning suggests that the safety risk is clear and indisputable. Moreover, even when the FDA issues a black box warning, the agency does not make available an easily queried database to track its decisions. In fact, sometimes the published literature may provide the best summary information on these safety warnings.3 More needs to be done to ensure respect for research participants so that study participants are informed of all potential risks and benefits, particularly for higher-risk study medications.

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Article Information

Conflict of Interest Disclosures: None reported.

References
1.
US Department of Health and Human Service, Office for Human Research Protections.  The Belmont Report. http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html. Accessed June 5, 2015.
2.
Bhattacharya  T, Tice  DG, Lingam  P,  et al.  Disclosure of boxed warnings to research participants [published online July 27, 2015].  JAMA Intern Med. doi:10.1001/jamainternmed.2015.3552.Google Scholar
3.
Cheng  CM, Shin  J, Guglielmo  BJ.  Trends in boxed warnings and withdrawals for novel therapeutic drugs, 1996 through 2012.  JAMA Intern Med. 2014;174(10):1704-1705.PubMedGoogle ScholarCrossref
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