By MICHELLE L. BRANDTKeith Humphreys, PhD, knew at the start of his multicenter trial on substance abuse treatment that dealing with institutional review boards — the groups that oversee research involving human subjects at universities and hospitals — would be a challenge. But he didn’t realize how much of a challenge it would be. His experience was so eye-opening that he decided to examine the issue more carefully and conduct an economic analysis of IRB activities.
"The economic study came out of frustration over what we went through," said Humphreys, associate professor of psychiatry and behavioral sciences at the School of Medicine and the Veterans Affairs Palo Alto Health Care System. "We tried to make lemonade out of lemons."
Humphreys’ economic analysis found that nearly 18 months and 17 percent of the total research budget for his multicenter observational study were spent on IRB activities. He also found that the IRB procedures — despite being costly and time-consuming — had no discernible impact on human subject protection.
"The essential procedures of the study never changed substantially, despite exchanges of more than 15,000 pages of material among the nine IRB sites," Humphreys wrote in a letter published last month in the Annals of Internal Medicine. He referred to the IRB activities as "$50,000 of paper shuffling" and said he hopes this economic analysis will lead to further examination of IRB procedures.
Federal Food and Drug Administration regulations give IRBs the authority to approve or require modifications in human research. In a multicenter trial, the IRB at the coordinating center (the "home IRB") must approve the research protocol in order for the study to continue. IRBs at each participating site have discretion in how intensively they re-review an approved protocol, and IRBs may be less compelled to review the protocols of observational (non-experimental) studies, which pose minimal risk to participants.
The home IRB approved the research protocol for Humphrey’s observational study on treatment for heroin addiction, yet the IRBs at participating sites chose to conduct independent, full-board reviews — sometimes by multiple local committees. The IRBs also expected final say on the protocol, meaning they conducted new reviews each time there was a change in study documents.
Humphreys reported that the IRBs requested numerous revisions to the formatting and wording of consent procedures and patient survey forms and had difficulty agreeing with each other on the details of the protocol. Disagreement involved changes as trivial as saying "study description" rather than "description of study," he said. The IRBs would not directly communicate with one another, and Humphreys and his team at the coordinating center did numerous back-and-forths until a consensus was reached. In the end, when each IRB signed off on the study protocol, little of substance had changed.
"We spent thousands of dollars doing things like changing the font from Helvetica to Times New Roman and making sure the border of the forms were the right color," said Humphreys. "I couldn’t believe how much time and money the process was taking."
The researchers’ economic analysis found that these IRB activities, including initial reviews, continuing reviews and amendments reports, cost more than $56,000 or just less than 17 percent of the total research grant budget for the first 18 months of the study. Most of these costs ($29,824) reflected the IRBs’ expenditures for supplemental actions (activities that occurred after the home IRB had already approved the protocol). The researchers also found that the protocol did not significantly change after all the reviews.
"This was essentially a public-private sector collaboration to lose money," said Humphreys.
While agreeing that oversight of human research is crucial, Humphreys said it is important for people to realize that there are problems with the procedures. "If costs such as those identified in this project continue to grow without consideration of the benefits of facilitating scientific projects, we worry that future research may be unjustly affected," he wrote in the letter.
Humphreys’ hope is that researchers and policymakers engage in a dialogue on IRB procedures and begin to weigh the cost and benefits of multi-center review for minimal-risk studies, such as his initial observational study. Given the budgetary pressures that hospitals and research facilities now face, he said this is a particularly timely issue.
Humphreys’ collaborators on the economic study include Jodie Trafton, PhD, health science specialist and voluntary clinical instructor of psychiatry at the VA Palo Alto Health Care System, and Todd H. Wagner, PhD, consulting assistant professor of medicine and health economist, also with the VA. The study was funded by the Department of Veterans Affairs Health Services Research and Development Service.
Stanford Report, August 6, 2003