OHRP cites lack of safety reporting in hip study

IRBs told to create plans to report back to subjects, improve reporting on future studies

Researchers studying whether specially padded underwear protected elderly wearers from hip fractures came up with a one-sided garment design that allowed them to compare the results of a padded hip and an unprotected hip on the same person.

However, when the study unexpectedly revealed more falls and fractures on participants' protected sides, the investigators failed to notify IRBs of the development and did not inform continuing and new participants about the potential risks of the study, according to a determination letter released by the Office for Human Research Protections (OHRP).

The June 23 OHRP letter (http://www.hs.gov/ohrp/detrm_letrs/YR11/june11a.pdf) cited letters and emails among the investigators to show that they had identified a problem with increased falls and fractures, but "failed to report unanticipated problems, i.e., increased falling to the pocketed (protected) side and the associated risk of possible fractures, to their respective IRBs, institutional officials, the funding agencies and OHRP, in contravention of the requirements of HHS regulations…"

In addition, emails quoted in the OHRP letter suggest that the data safety monitoring board (DSMB) that was monitoring the study was not told of the significance of the data involving falls.

The letter notes that had the new risk associated with the study been disclosed to subjects, "it is reasonable to conclude that such information might have significantly affected their willingness to continue to participate."

Plans for contacting subjects

The three institutions involved in the study – Hebrew Rehabilitation Center for Aged in Roslindale, MA; the University of Maryland Baltimore School of Medicine; and Washington University School of Medicine in St. Louis — all have been instructed by OHRP to provide plans for contacting subjects enrolled in this study to provide them with the previously undisclosed risk information.

The institutions also have been required to come up with corrective plans to ensure that researchers:

— disclose "reasonably foreseeable risks to the subjects;"

—whenever appropriate, give the IRB and subjects new information developed during the study that may affect subjects' willingness to continue participating;

—and report unanticipated problems to IRBs, institutional officials, funding agencies and OHRP.

How can an institution make such assurances if researchers do not give them the necessary information? Representatives from the three institutions involved in the study all declined to comment to IRB Advisor about the matter, citing continuing efforts to evaluate the situation and formulate their responses to OHRP.

Creating a culture'

But Mark S. Schreiner, MD, chairman of the Committee for the Protection of Human Subjects at The Children's Hospital of Philadelphia and a member of the editorial advisory board for IRB Advisor, says IRBs' options are limited in this type of situation.

"This is exactly the sort of information that IRBs should get," Schreiner says. "This was an important safety signal that affected the likely willingness of subjects to enroll and of subjects already enrolled to continue with the study.

"If people don't report this type of thing, there's nothing the IRB can do."

He does note that the larger institution has the obligation to educate investigators about what information they need to report to IRBs and about the importance of doing so.

"This is a matter of creating a culture where investigators understand their responsibility," Schreiner says.

Dale E. Hammerschmidt, MD, an associate professor of medicine at the University of Minnesota in Minneapolis who served on IRBs for 25 years, agrees that there is little IRBs can do to uncover safety problems that occur within a study, particularly in cases where the DSMB is not getting the proper information, either.

However, he says the IRB can examine at the outset of a study how the safety reporting is supposed to be handled. It can require that safety monitoring reports from the DSMB or other oversight body be provided on a regular basis.

"The IRB can look at the DSMB charter for a study and can look at the monitoring plan," he says. "They usually cannot serve a police function at a remote site. What they can do is examine the infrastructure, and make a judgment as to whether it would suffice if conscientiously implemented."