As IRBs debate and consider how to assess risks and benefits in research, here are a couple of examples of cases where IRBs made controversial and sometimes opposing decisions:
• Smallpox vaccine trials: After Sept. 11, 2001, some worried about terrorists developing bioweapons such as smallpox, says Ernest Prentice, PhD, associate vice chancellor for academic affairs at the University of Nebraska Medical Center in Omaha. Prentice is the former chair of SACHRP.
“There was concern about whether or not we’d be exposed to smallpox,” Prentice explains. “There was a limited stock of the vaccine, which was not enough to inoculate everyone, so the idea was to dilute the vaccine and give it to kids to see if produced an immunological response.”
The federal government pulled Dryvax, the smallpox vaccine used previously, from freeze-dried storage stockpiles. The National Institutes of Health (NIH) coordinated a multisite trial of diluting the vaccine in adults and wanted to develop a study at three institutions for dilution vaccine in children. The goal was to inoculate young children, ages two to five, to assess its safety.1,2
IRBs had to assess the potential risk of a terrorist getting hold of smallpox, which had been eradicated worldwide but was available in a handful of laboratories. Then they had to determine the risk to individual children receiving the vaccine and weigh that against the potential societal and individual benefit provided by a vaccine to a dangerous disease that no longer exists, yet could possibly appear again.
Two IRBs that reviewed the pediatric smallpox vaccine protocols approved them. A third IRB voted against it, and the study had to go to the Office for Human Research Protections (OHRP) for review.1
“This shows that IRBs can come to different conclusions,” Prentice notes.
A panel of 10 reviewers considered risks and benefits of the vaccine. Before the smallpox vaccine was discontinued in 1971, it was routinely given to children from ages 1 and up. It also was considered to be the vaccine with the most severe adverse side effects, including the common side effect of fever and pain and less common reactions of vaccinia rash and widespread blotchy macular rashes. Some children had rare adverse effects, such as Stevens Johnson Syndrome, encephalitis, and death.1,2
The panel of 10 reviewers was concerned that the risk was understated and not reflected in the consent form or protocol. They also felt the potential benefit to the individuals was overstated.1
Reviewers also questioned the adequacy of the safety monitoring plan and said there was not an adequate discussion of alternatives to families.1
The reviewers rejected the research under 45 CFR 46.405, but felt it could be approved under 45 CFR 46.407, which “finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children.”1
After the panel’s review, the U.S. Department of Health and Human Services (HHS) canceled the trials, saying that bioterrorism preparedness plans had evolved to the point that the vaccine trials were unnecessary.1
• Transplants using animal organs: In 1984, an infant with a congenital heart defect called Baby Fae died from transplantation rejection complications 20 days after receiving the heart of a baboon. The infant was the first infant to receive an organ from an animal, and her surgery was considered an experiment.3
“An IRB had approved it,” Prentice says.
In 1992, surgeons and researchers transplanted a baboon liver into an adult man, who also died soon after the procedure.4
Despite these early failures, researchers continued to move forward with transplants involving animals because of the potential benefit to society, Prentice says.
Medical researchers are interested in xenotransplants because of the very limited supply of human organs for transplant and the much greater demand, he notes.
- Resnik D, Halsey N, Berkelman R. Assessing pediatric research: considering individual risk and societal benefit. Transcript of meeting held Aug. 2, 2012, Washington, D.C. Available online: http://bioethics.gov/node/744.
- Sharava VH. Comment on FDA Docket Number 02N-0466, re: Proposed smallpox vaccine trail to test the safety of Dryvax administration to children 2 to 5 years of age. 2003. Available online: http://www.ahrp.org/ahrpspeaks/smallpox1202.php.
- Altman LK. Baby Fae, who received a heart from baboon, dies after 20 days. The New York Times. Nov. 16, 1984. Available online: http://nyti.ms/1M10Xyi.
- Hoke F. Undaunted by death of first baboon liver recipient, interdisciplinary transplant team looks to the future. The Scientist. Sept. 28, 1992. Available online: http://bit.ly/1KK738V.