Show
I'm Looking for Information About OHRP considers
unanticipated problems, in general, to include any incident, experience, or outcome that meets all of the following criteria: 1. 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; 2. 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 3. Suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized. A potential harm, a type 1 ‘unanticipated problem', is an issue that must be reported to the IRB whenever something comes to an investigator's attention regarding
the research which indicates the possibility that previously unsuspected harm may occur (or may occur at a higher than expected rate) even though no one has yet experienced actual harm. It is an event, development, or information that potentially increases the likelihood of harm occurring in the future. For example, a concurrent study in animals might show that the new drug being
used in a UM study causes cancer in a fashion that seems to be relevant to people. This indicates a previously unrecognized risk—that the research participants will have an increased cancer risk, even if none have actually developed cancer. This type of unanticipated problem is usually reported using the IRB form for Other Reportable Information or Occurrences (ORIO). A type 2 ‘unanticipated problem‘ is a recognized harmful or
unfavorable outcome that has actually occurred to a research subject, a set of subjects, another individual being treated in a similar fashion in a relevant non-research setting, or another person connected to the research study (e.g. one of the researchers or the spouse of a subject). This type of unanticipated problem is an actual event(s), not a potential risk. These kinds of unanticipated problems are also adverse events (AEs). A series of AEs that signal the AEs were not just isolated occurrences and were significant to subjects' rights and welfare would be considered an unanticipated problem. An expected AE that occurs at a greater frequency or severity than expected would be an unanticipated problem. ‘Type 2' unanticipated problems should be reported to the IRB using the adverse event reporting form. Because of their unanticipated and related nature, and because of the potential risks they suggest, these AEs require a special level of attention from investigators, IRBs, institutional officials, and others. (Not all adverse events are ‘unanticipated problems' because most adverse events
are ‘expected' as it is defined above. For details on how and when to report adverse events that are not unanticipated problems, refer to the IRB's adverse event reporting guidance.) An
unanticipated problem -- because it is associated with potential risks -- is a problem that must be reported even if it is not felt to be serious. Adverse events that are unexpected and related, but not serious, would also be unanticipated problems if they suggest that the research places subjects or others at a greater risk of harm than had previously been known or recognized. Although
the primary mission of an IRB is to protect the rights and welfare of research subjects, federal regulations require investigators to report, and IRBs to evaluate, any unanticipated problem that may pose risks to people who are not the actual research subjects. The ‘others' are most often the researchers themselves or family members of the subjects,
although they can be people not associated with the research in any way. If a research subject experienced an unexpected side effect like fainting, and fainted while driving a car, causing an accident in which a stranger was injured, this would be an unanticipated problem even if the subject was unharmed. If a laboratory reagent used in the research, but not actually administered to patients or research
subjects, was found to be a potentially dangerous carcinogen, this would be an unanticipated problem posing a risk to others, namely the laboratory workers involved with the research or interacting with the research personnel in the same lab. ‘External' versus ‘UM' Unanticipated ProblemsInvestigators are required to report both internal and external unanticipated problems to the IRB. A ‘UM' unanticipated problem is one that occurs on a study that is under the direct oversight of a UM investigator or a UM IRB. The participants are UM subjects. The terms ‘Internal' or ‘Local' are sometimes used in referring to a ‘UM' event. ‘UM' includes things that happen to UM subjects anywhere, even if not on University of Michigan property. For example, a problem with a subject enrolled by a UM student conducting a study in Uganda that was approved by a UM IRB is considered a ‘UM' event. A problem that is not under the primary oversight of UM investigators or a UM IRB is referred to as an ‘External' unanticipated problem. These are events or information about which the UM investigator received a report or read a publication rather than an event the investigator handled. Other terms used include ‘Off-site' or ‘at other sites.' When an investigator receives a report of an external unanticipated problem it should be submitted to the IRB. External Adverse Event Reports and Unanticipated ProblemsUM investigators participating in multi-site trials and those using sponsored agents routinely receive a large volume of reports of external adverse events. The HHS Office of Human Research Protections (OHRP) has released guidance urging sponsors that individual adverse events should only be reported to investigators at all institutions when a determination has been made by the sponsor that the events meet the criteria for an unanticipated problem. OHRP recommends that any distributed reports include: (1) a clear explanation of why the adverse event or series of adverse events has been determined to be an unanticipated problem; and (2) a description of any proposed protocol changes or other corrective actions to be taken by the investigators in response to the unanticipated problem. Nonetheless, investigators may continue to receive reports that have not been assessed by the sponsor. When a UM investigator receives a report of an adverse event that is unexpected and related to an agent or procedure used in the UM study, the UM investigator should review the report and assess whether it meets the criteria above for an unanticipated problem. If it does, then it should be reported to the IRB. Note that many reports labeled ‘unexpected' will not meet the criteria above. It is possible for an external adverse event report from a different study, or use of the agent or procedure in a different population or route of administration to constitute an unanticipated problem for a UM study. The UM investigator should assess whether or not the information in the report indicates a problem that affects the rights and welfare of UM subjects. If in the judgment of the UM investigator it does, then the report should be submitted. If the report does not contain sufficient information for the UM investigator to make the needed assessment AND the source of the report (e.g. the sponsor) did not state the event is an “unanticipated problem” or an “unanticipated adverse device effect”, then a submission to the IRB is not required. Both FDA and the HHS Office of Human Research Protections have stated their expectation that an individual external adverse event will rarely meet these criteria for an unanticipated problem. Additional Information for Investigational Device StudiesIn addition to the general information above, studies involving FDA-regulated devices are required to follow the regulations at 21 CFR 812.
Examples of Unanticipated Problems
When and How To Report Unanticipated Problems and Unanticipated Adverse Device Effects (UADEs) to the IRBSerious unanticipated problems and UADEs must be reported within 7 calendar days of the problem (or within 7 calendar days of the study team becoming aware of the problem). Non-serious unanticipated problems must be reported within 14 calendar days of the problem (or within 14 calendar days of the study team becoming aware of the problem). If the unanticipated problem involved one or more persons experiencing actual harm , report the unanticipated problem as an adverse event. Refer to the AE Reporting page and follow the instructions provided, using the external or internal form as appropriate. If a person did not experience actual harm but an unanticipated problem entailed potential harm, and/or risk of harm to subjects or others, refer to the ORIO Reporting page and follow the instructions provided. If the IRB concurs that an event is an unanticipated problem the IRB will follow the policies and procedures outlined in the University of Michigan Human Research Protection Plan Operations Manual, part 12. (PDF) References
Posted 9/28/2007, updated 4/16/2015 PagesSee AlsoPagesRelated DocumentsIs this an example of an unanticipated problem that requires reporting to the IRB?Is this an example of an unanticipated problem that requires reporting to the IRB? No, this does not need to be reported because it was assessed by the researcher as unrelated to the research study. A researcher conducts a focus group to learn about attitudes towards hygiene and disease prevention.
What is true of inducements in research?Which is true of inducements in research? Inducements constitute an "undue influence" if they alter a potential subject's decision-making processes, such that they do not appropriately weigh the risk-benefit relationship of the research.
Which of the following lists the three principles included in the Belmont Report?Three basic principles, among those generally accepted in our cultural tradition, are particularly relevant to the ethics of research involving human subjects: the principles of respect of persons, beneficence and justice.
Which of the following studies would need IRB approval?Which of the following studies need IRB approval? Studies collecting data about living individuals. If a study intends to collect data or information about the living individual, an IRB review and approval must be obtained.
|