Critics worry new rules may encourage under-reporting of side effects
By Trevor Stokes | January 13, 2006
The public commentary period ended Friday (January 13) for the new draft guidelines from the Office for Human Research Protections (OHRP) on reporting adverse events during clinical trials -- with some critics expressing concern that the new rules, if passed, may discourage researchers from reporting side effects.
Under the new guidelines, researchers do not need to report some expected adverse events as long as they have consent from their institutional review boards IRBs. The purpose of the change is to reduce data overload, a common complaint from many IRBs.
Reducing workload is a good goal, but not if it means cutting important corners, critics say. ?Any filter that you put up runs the risk of filtering out valuable data,? Eric M. Meslin, director of Indiana University Center of Bioethics, told The Scientist. ?This is the challenge whenever you put a semi permeable membrane into this stream of data.?
The problem of data overload arose after reports of expected side effects from hundreds of researchers and dozens of centers in massive multicenter studies flooded IRBs with little facility to analyze the data. ?The ultimate goal is to ensure reporting and analysis of adverse events in a timely and meaningful way to avoid human subject harm,? the draft?s main author, Michael Carome, associate director for regulatory affairs at OHPR, told The Scientist. He added that the organization hopes to finalize the guidelines by June, 2006.
To minimize side effect reporting, the draft distinguishes common side effects from unanticipated problems, and establishes three categories of reportable side effects: an unexpected death or life threatening condition related to the research; an expected adverse event that happens more frequently than expected; or an unexpected adverse event is so severe that it changes the study?s risk benefit ratio.
?I think with the emphasis on the three reportable categories, it may result in underreporting of situations,? Quincy Byrdsong, manager of the clinical research center at Meharry Medical College in Nashville, Tennessee, told The Scientist. For instance, Byrdsong noted that researchers may hesitate to report events ranging from ?dizziness, vertigo, headaches, rashes, shortness of breath, loss of short-term memory,? because they are not life threatening.
?If death happens and it?s expected, then it?s not an adverse reaction? Well, that?s absurd,? said Vera Hassner Sharav, president of The Alliance for Human Research Protection (AHRP), a national network that advocates responsible and ethical medical research practices.
?There?s no excuse to narrow down the reporting, we need to broaden the reporting,? Adil Shamoo, co-founder of the advocacy group Citizens for Responsible Care and Research (CIRCARE) and editor-in-chief of Accountability in Research, told The Scientist. ?It could make the adverse reporting not only biased, but also not capture important events.?
The OHRP guideline leaves it up to individual investigators to interpret what new side effects beyond an IRB?s scope are worth reporting?another potential problem, critics say. ?Once you open those interpretations up, we can not be sure how the investigator will interpret insignificant or significant,? said Tom Ball, executive director of The National Association of IRB Managers, an independent human research management organization.
But not all scientists agreed that filtering data is a potential problem. George Gasparis, Columbia University?s IRB executive director, told The Scientist that he believed reporting fewer side effects helps patients more than it has the potential to hurt. ?To dilute IRBs with reports of many unrelated adverse events compromises an IRB?s mission of protecting human subjects,? said Gasparis, former director of the Division of Assurances and Quality Improvement at OHRP. ?It?s a false sense of security that we?re protecting.?
The guidelines are not mandatory for investigators or IRBs. ?The key is whether IRBs will make use of this guidance. The response will rest with them as the gate keeper and the protector of patient welfare,? Meslin noted. ?The guideline is solving one problem, and we don?t know if it will create others.?
Links within this article
Guidance on Reporting and Reviewing Adverse Events and Unanticipated Problems Involving Risks to Subjects or Others, OHRP
Using a Centralized IRB Review Process in Multicenter Clinical Trials, Food and Drug Administration, March 25, 2005
The Alliance for Human Research Protection (AHRP)
The National Association of IRB Managers
B. Roehr, ?Institutional review boards in crisis,? The Scientist, May 9, 2005.
Eric M. Meslin, director of the Indiana University Center for Bioethics