Whitney Palmer

Protecting Patients

Published in the Summer 2011 Summa Magazine

The Role of Summa Health System’s Institutional Review Board in Advancing Medicine

By Whitney L.J. Howell

New drugs. New medical devices. New therapeutic protocols. Summa Health System tests them all through research and each has the potential to improve the health of different patients in different ways. But they do have one thing in common – Summa’s Institutional Review Board.

Most patients who agree to participate in clinical trials have likely never heard of an institutional review board (IRB). IRBs serve as objective third parties in all discussions about medical research involving human subjects. In addition to safeguarding patient safety, these committees ensure the nature and manner in which proposed research will be conducted are both ethically and scientifically sound. Think of them as the safety net for clinical investigations.

Formal, regulated IRBs are a relatively recent directive. The National Institutes of Health’s Policies for the Protection of Human Subjects, first issued in 1966, achieved regulatory status on May 30, 1974. Promulgated by the Department of Health, Education and Welfare (now the Department of Health and Human Services), the regulations established the IRB as one mechanism through which human subjects would be protected.

Despite being mandated by the Department of Health and Human Services, these committees – of which Summa has two – operate largely in the background. And their charge is more than merely greenlighting research, said Jessica Conrad, Summa’s IRB manager.

“Our IRB is here to minimize the risks associated with a study and to make sure our patients know exactly what to expect if they participate,” Conrad said. “We catch problems and ask questions about research projects that could affect human health – it’s something we take very seriously.”

Monitoring studies conducted at Summa keeps the IRB committees busy. In 2010, both groups completed approximately 1,600 reviews and approved 150 protocols. Proposals come from pharmaceutical companies and device manufacturers, as well as from Summa’s physicians, nurses and other clinical staff.

Who Serves?

As a federal requirement, all IRBs share some characteristics. Every committee must have at least five members, both male and female, and they must come from varied professions. Specifically, IRBs must include at least one individual from these areas: a scientific concentration, a non-science field, and sectors wholly unaffiliated with the reviewing institution.

Summa takes extra steps, however, to guarantee that it analyzes study proposals from all angles, Conrad said. To delineate between which investigations were conceived outside the health system and which are borne of the institution, Summa operates two committees – IRB1 and IRB2. IRB1 tackles submissions from pharmaceutical companies and device manufacturers. Summa investigator-initiated study protocols fall under IRB2’s jurisdiction.

Members appointed to serve on both committees reflect the nature of the studies reviewed. While both bodies have a medical librarian, a lab technician, and a nurse, that is where they part ways. IRB1 also relies on two infectious disease specialists, two oncologists, and an emergency room physician. IRB2 is rounded out with a psychologist, an obstetrician, a surgeon, an ICU doctor, a family practitioner, and a cardio-pulmonary statistician. The remaining members, such as retired nurses, school teachers, and lawyers, are recruited from the community. All members are selected based on their levels of expertise and how their knowledge can strengthen submitted protocols. They do receive instructions on how to work within the IRB framework, however.

“Once members accept the appointment to the IRB committee, we review the process and educate them so they know what IRB participation calls for,” Conrad said. “Every new member is paired with an experienced member who can mentor and train them.”

At Summa, simply agreeing to become a member of an IRB isn’t enough. Appointees must make the time commitment to read protocols and attend monthly meetings. According to Conrad, Summa experts must attend 70 percent of the IRB meetings, and community members are expected to be present at 50 percent.

Why Community Members?

Although all research submitted for IRB approval has a solid foundation in science, not everyone who participates as a study subject has the same levelof scientific understanding. This reality makes it necessary to incorporate community members – most of whom are from outside the hard sciences – to analyze proposals through a lay person’s eyes.

“Many times the medical people involved with the IRB wouldn’t see any problems with a proposal, and from their perspective, they were right,” said Richard Haas, a former Goodyear attorney who served on Summa’s IRB committee until 1997. “But, coming from a lay person’s perspective, I could see how some people could be confused about why they would be asked to participate and what they could and could not do if they did get involved.”

Community members are an excellent second set of eyes – outsiders who can step into a discussion and ask for greater clarity. It is also helpful, Conrad said, to include community members from a variety of ethnic and racial groups.

“Having board members of Hispanic or other ethnic descent will definitely give you a different perspective in your approach to conducting research,” she said. “You have a clearer view of what types of research will be accepted and what will positively impact your community.”

In fact, the U.S. Food and Drug Administration regulations require that, as part of being qualified as an IRB, the IRB must have “… diversity of members, including consideration of race, gender, cultural backgrounds and sensitivity to such issues as community attitudes ….”

How It Works

On the surface, the IRB committee’s job is relatively simple. It approves, disapproves, and modifies research. Through a continual review, it monitors changes and keeps a close eye on the informed consent process, as well as the methods used to move the research forward. If members don’t like what they see, they can, as a group, suspend or terminate any previous IRB approval.

Giving protocols the go-ahead, however, is more involved than that, and the step-by-step process depends on whether the proposed protocol comes from a company or Summa itself.

Pharmaceutical companies and device manufacturers often handle much of the process before Conrad’s office sees the proposal. They reach out directly to the physician or other investigator to gauge his or her interest in assuming the principal investigator role. If, after reading the protocol, the principal investigator chooses to move forward, a study coordinator begins working on the informed consent paperwork. For the most part, companies already have existing consent forms, and experienced coordinators will edit the documents based on the small changes Summa requires to protect its patients.

“Once the application and consent form have been prepared, the companies and principal investigator submit them to the IRB,” Conrad said. “Generally, we don’t ask companies to make changes to the protocols because the study could be ongoing at 600 sites. We do focus, however, on making sure the consent forms are as clear as possible.”

IRB1 receives the documents via an electronic system and reviews the protocol to catch anything problematic that might remain.

This is where Summa has a unique and beneficial agreement with other hospitals and universities in the areas surrounding Akron and even some in other states. Under the agreement, Summa and other institutions involved in the same project can rely on each other’s protocol review instead of conducting an additional one. Such a relationship exists between Summa and all institutions associated with the Austen BioInnovation Institute in Akron, as well as Kent State University, The Ohio State University and Duke University in North Carolina.

“This type of connection makes it easier to talk with each institution first,” Conrad said. “It’s easier to get things through the IRB process – it’s easier to get agreement.”

The process for investigator-initiated ideas, however, is frequently more involved and can take up to six months to complete. Sometimes, investigators bring Conrad a yet-to-be fleshed-out idea, giving her the opportunity to offer significant guidance before too much of the study outline is in place. Others submit what they deem to be finished proposals for the committee to read and dissect.

The Approval Process

First and foremost, the committee’s main concern is mitigating risk to study participants. And, that comes in two forms – ensuring the study’s potential benefits outweigh the associated risks and requiring and verifying that study coordinators secure written consent from each subject.

“Keeping track of informed consent is an important detail,” said Deborah Barnbaum, Ph.D., philosophy professor at Kent State University and Summa IRB community member, “because the majority of Summa’s research investigations are multi-site clinical trials in either Phase II or Phase III. With that many people involved in a study, proper documentation, and getting it done correctly, is a necessity,” she said.

“In light of the Belmont Report that looked at medical ethics after the Tuskegee Syphilis Study, those of us who are involved with the IRB process hold it as our first priority to make sure people who volunteer for research studies know what they’re getting into,” said Barnbaum, who also chairs Kent State’s IRB committee. “Are the documents detailing the study’s purpose clear enough so anyone can understand it and ask the right questions?”

“Effective informed consent procedures are equally important for the community at large,” said Marguerite Erme, D.O., M.P.H., Summit County Health Department medical director and member of Summa’s IRB1. “Frequently, the public has a negative perception of medical research and an uninformed view about the people who choose to participate in studies.”

“The people who participate in research are performing a wonderful service that may provide a benefit they’ll never see,” said Erme. “But they are certainly aware of the study’s intent and what they have volunteered to do.”

Beyond perfecting the informed consent process, IRB committees check to see if the projected study sample will be adequately varied. They also look for provisions, such as a data safety monitoring board, that will monitor data accuracy and protect patient safety and privacy throughout the investigation.

For researchers trying to determine whether to submit a protocol, Conrad offers specific advice. Make sure the proposal either furthers an existing area of research or is uncharted territory. Outline the study clearly, and include as much detail as possible.

“When, as an investigator, you think you’ve added enough detail, add more,” Conrad said. “We want to know how your study will play out step-by-step. Tell us the dosages of drugs, the medications that exclude patients from participating, and tell us how long things are going to take. We want – and need – to know it all.”

The IRB chair receives all submitted protocols and then assigns two reviewers – one scientific and one nonscientific – to each study. The research also falls into one of three categories: exempt, expedited, or full-board review.

The IRB chair can deem a study exempt from further review if there is no way to identify participants based on the data collected for research. For example, a protocol using a retrospective chart review would be exempt. Research can be expedited if it calls for minimal risk to any participants and if reviewers require only minor changes to the proposal.

Investigators must submit their study outlines for full-board review if they suggest research that puts participants at more than minimal risk and involves any protected groups, such as children, pregnant women, the elderly, psychiatric patients, or prisoners. These studies are intensely scrutinized, and occasionally they give committee members pause.

Red Flags   

“We wouldn’t be a good IRB board if we didn’t sometimes have questions about whether some parts of a proposal are ethical,” Erme said. “We’ve sent some protocols back for significant revisions, and we’ve denied approval to some.”

Conrad agrees there have been occasions when parts of a study outline made the IRB committee uncomfortable. For example, any proposals that would deceive participants about the study’s intent are circumspect. Investigators must not only prove it would be impossible to achieve their goals without deception, but they must also clearly outline their plans for revealing the truth to participants.

“Problems also arise when protocols aren’t sufficiently balanced,” Barnbaum said. Investigators testing a new drug or medical device must design the study to test the unverified product against a well-understood, standard-of-care therapy. Otherwise, it is impossible to determine if the proposed treatments produce better results with less risk.

“Identifying pitfalls is a large part of why IRBs exist,” she said. “Ninety-five percent of the research we see has no problems. We’re here for the five percent that make it through the drafting process and still raise questions.”

To read the article in the original publication: http://www.thesummafoundation.org/media/11058/18979.pdf pg. 6

September 14, 2011 - Posted by wjpalmer | Healthcare | Austen Bioinnovation Institute in Akron, Belmont Report, Deborah Barnbaum, Institutional Review Board, Jessica Conrad, Marguerite Erme, Richard Haas, Summa Health System Institutional Review Board, using community members in Institutional Review Boards, what makes an Institutional Review Board submission unacceptable