OHRP has new guidelines for reporting unanticipated problems
OHRP has new guidelines for reporting unanticipated problems
AEs and UPs are separate entities
The Office for Human Research Protections (OHRP) of Rockville, MD, published, on Jan. 18, 2007, its final version of new guidelines on reporting unanticipated problems and adverse events.
Available on-line at www.hhs.gov/ohrp/policy/AdvEvntGuid.htm, the 24-page guideline, titled, "Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events," includes numerous changes from the draft guidance published in 2005. The new guidelines are effective immediately.
OHRP made the definitions more prominent and straightforward after receiving some comments about these from research institutions and others, says Michael Carome, MD, associate director — regulatory affairs of OHRP, Office of the Secretary, U.S. Department of Health and Human Services. (See chart listing public comments on UP guidance.)
"One of the key changes is in the first section on the definition of what are unanticipated problems," Carome says.
"Unanticipated problems" is shorthand for a longer phrase in the regulations of "unanticipated problems involving risk to subjects and others," Carome says.
"We tried to write a more clear definition so people will have a better understanding of what unanticipated problems means," Carome says. "So in crafting that definition, we included three specific criteria that appear repeatedly throughout the document, and we hope that brings clarity to the term."
According to the new guidance, unanticipated problems are any incident, experience, or outcome that meets all of the following criteria:
- Unexpected (in terms of nature, severity, or frequency) given a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and b) the characteristics of the subject population being studied;
- Related or possibly related to participation in the research (in this guidance document, possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
- Suggests that the research places subjects or others at greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.
Another change is that the draft version of the guidelines did not have a new definition for an adverse event, Carome notes.
"We had an appendix that provided a compilation of multiple definitions and terms from multiple different agencies," Carome explains. "We received several comments from the public that asked for more specific definitions so, in section II, we do provide a specific definition of what adverse events are."
The guidance states that the term 'adverse event,' in general, is used very broadly and includes any event that meets the following definition: "Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research (modified from the definition of adverse events in the 1996 International Conference on Harmonization E-6 Guidelines for Good Clinical Practice)."
OHRP also added language to the guidance that clearly outlines which items are required and which are recommended.
At the very beginning of the guidance, outlined by a bold black box, is a paragraph that includes this sentence, ". . .The use of the word must in OHRP guidance means that something is required under HHS regulations at 45 CFR part 46. The use of the word should in OHRP guidance means that something is recommended or suggested, but not required. An institution may use an alternative approach if the approach satisfies the requirements of the HHS regulations at 45 CFR part 46. . ."
This is the first document in which OHRP has included the boxed explanation, Carome says.
The box is in response to the growing perception that many research institutions tend to over-interpret federal guidance and create unnecessary documentation, Carome says.
"This box is our response to that," he says. "This box is typical of what the Food and Drug Administration has done for some time now, and we believe it's a good practice, and we've adopted it and will use it in future documents."
Since unanticipated problems and adverse events overlap but are not synonymous, OHRP has included in the guidance a chart that illustrates the relationship between the two terms and a flow chart that shows how to determine whether an adverse event is an unanticipated problem.
"The flow chart walks a person through three criteria, and that's new," Carome says. "It's not in the draft guidance, and as a new addition we hope it will bring clarity to the topic."
OHRP included a section on the appropriate time frame for reporting unanticipated problems in response to a request from those who commented on the draft guidelines, Carome says.
"We avoided specifying, even in the recommendations, what the time frame should be," Carome says.
"Some people who provided comments asked what the window was for being prompt in their reporting, so in section five, we added a specific time frame that ranges from one week to one month for properly reporting to various entities," Carome says.
"The time frames are just recommendations and are not mandated guidelines," Carome adds.
The Office for Human Research Protections (OHRP) of Rockville, MD, published, on Jan. 18, 2007, its final version of new guidelines on reporting unanticipated problems and adverse events.Subscribe Now for Access
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