At Iowa, safety's first when human beings are under the microscope

Patricia Feldick (right), research assistant in the Preventive Intervention Center, checks the blood pressure of UI staff member Gay Mikelson. Mikelson is a volunteer participant in a study on the effects of low-dose estrogen on osteoporosis, one of the many studies conducted at Iowa that involve human subjects. Photo by David Pedersen.

Able because she’s in good health. Willing because she is one of a number of UI faculty and staff who participate in human research studies on campus.

Mikelson, a secretary in the Department of Management and Organizations in the Henry B. Tippie College of Business, is enrolled in ULTRA, a study of postmenopausal women to determine whether a very low dose of estrogen can help prevent osteoporosis, or brittle bones.

Mikelson, who began participating in the study a year ago, wears a clear patch on her stomach, although she does not know whether she is actually receiving estrogen or whether the patch is a placebo. She changes the patch weekly. As part of the study protocol, she also takes a multivitamin daily as well as calcium supplements twice a day. She also sends in a monthly written report of her health status and visits the Preventive Intervention Center at University of Iowa Hospitals and Clinics (UIHC) for a checkup every three months.

She is not compensated for her participation in the study.

“That’s not why I do it anyway,” Mikelson says. “I do it because what they learn may help others someday.”

From testing new medical devices to looking at the effect of medications on driving performance to surveying political and social viewpoints, studies involving human subjects are integral to the University’s research mission.

And it is the work of the Institutional Review Boards (IRBs), with support from the UI Human Subjects Office (HSO), to approve and oversee these studies and ensure that participants are not exploited or harmed.

IRBs are the committees that review all studies that involve human subjects, ensuring that the studies comply with federal regulations regarding research using human subjects. Two IRBs composed of UI faculty and staff, as well as members from the public, assume this responsibility.

IRB-01 reviews research conducted in the Colleges of Dentistry, Medicine, Pharmacy, or Public Health or research that involves patients at UIHC.

IRB-02 reviews and approves projects involving human subjects that are conducted in the Colleges of Business, Education, Engineering, Law, Liberal Arts and Sciences, and Nursing.

The HSO provides administrative support for the IRBs. It keeps files on all human subjects research at the University, maintains a database for tracking all research proposals submitted to the IRB, serves as a resource for investigators on regulatory information, and provides guidance with forms and submission procedures. The office is big on the “little things,” says Trish Wasek, director of the HSO.

“The University’s ability to attract external funding for research, and even its research reputation, is tied to its ability to keep good records and to comply with governmental regulations,” Wasek says. “So we pay very close attention to the details when it comes to the IRBs and studies that require human participation.”

All studies involving human subjects must have IRB approval. The first step for an investigator is completing a new project application. When completed, the application will contain funding sources, proper documentation from the Food and Drug Administration (if the study involves a medication or medical device), a detailed research plan (including risks/benefits to study participants), recruitment materials, as well as the consent form that participants must sign.

The HSO reviews the completed application. If the study involves any drug, a special pharmacy committee also reviews it. The same goes if the study involves diagnostic or therapeutic radiation—a medical radiation protection committee reviews additional documentation. There is also an institutional biosafety committee that reviews studies involving gene therapy.

Once the application is ready, the IRB chair determines whether it needs full board review. Some studies can be classified as exempt or expedited review status if they are minimal-risk studies; however, expedited status does not mean that the study is being rushed through the approval process.

For studies that require full IRB review, the chair assigns an IRB member to be the study’s primary reviewer. This person scrutinizes the application materials and presents the study to the full committee. The committee then discusses the risks and benefits of the study. Sometimes the principal investigator is asked to be present at the IRB meeting to provide additional information.

If there are no questions to the study’s design, and any revisions to the consent document (or any other changes) are straightforward, a motion is made to approve the study once the requested revisions are made. The vote is then taken. The principal investigator has two months to respond to the requested revisions.

“It’s a very thorough process,” Wasek says. “Ask any investigator who has required IRB approval for a research study and he or she will tell you there are no shortcuts.”

In some cases, a decision on a study application may be tabled to give the investigator an opportunity to alleviate IRB concerns. The application is then reconsidered at a future IRB meeting. But if a study is disapproved, no one on campus can overrule that decision.

Both the Food and Drug Administration (FDA) and the Office of Human Research Protection (OHRP), a regulatory unit within the U.S. Department of Health and Human Services (HHS), have oversight authority related to University IRB operations.

For years the University has filed a Multiple Project Assurance with HHS. This document underscores the University’s commitment to complying with federal regulations concerning all human subjects research done at the institution or at the Iowa City Veterans Affairs Medical Center. It also gives the OHRP the authority to review all UI research records related to human subjects and, if the University is not in compliance with federal guidelines, put “on hold” any study involving human participants.

Altruism aside, Mikelson also sees volunteering for ULTRA as a way to monitor her own health.

“At my yearly checkup, I had a mammogram, a Pap smear, and other general health tests, which was good,” she says. “So you could say that I’ve benefited from the study, too.”

Article by David Pedersen