Contains Nonbinding Recommendations
2. Aggregate Reports
An IND safety report based on data in the aggregate must be in a narrative format (§
312.32(c)(1)(v)). Sponsors should use judgment in deciding what to include in the
narrative report. The report should include a description of the suspected adverse
reaction, along with all relevant information, such as summary information about
symptoms, concomitant medications, demographics, comorbid conditions, past history,
pertinent laboratory test results, timing of events (onset and duration), and duration of
treatment. Data from previously submitted individual case IND safety reports should be
included, if applicable. Finally, the narrative report should describe the characteristics
and results of the analysis, including a description of the databases, how the conclusion
was reached, who reviewed the analysis, any planned changes in monitoring or to study
documents (e.g., informed consent, investigator brochure), and any planned further
analyses.
To evaluate the aggregated data in narrative format, FDA and participating investigators
need the information on the individual cases that are summarized in the report.
Therefore, at the same time that the narrative format IND safety report is submitted, the
individual cases that were analyzed should also be submitted (e.g., a completed FDA
Form 3500A for each case). If some individual cases were previously submitted as IND
safety reports, they should be resubmitted and clearly identified as duplicates. Before
submission, each individual case report should generally be unblinded. If a sponsor has
concerns that unblinding will compromise the integrity of the study, the sponsor should
discuss this in advance with the review division (see section VI.C).
If a sponsor is monitoring and evaluating the occurrence of a serious event in the
aggregate (rather than submitting each case individually), FDA expects that records of
each case will be complete (e.g., a completed FDA Form 3500A for each case), including
a description of the suspected adverse reaction and any other relevant information, and
that each case will be followed up for additional information, if necessary.
The sponsor should determine an appropriate approach for reporting subsequent
occurrences of the same event to FDA and all participating investigators, and the sponsor
should include a description of this approach in the initial expedited narrative IND safety
report. For example, each subsequent occurrence of an infrequent event with immediate
health implications or an event that is uncommon in a specific study population (e.g.,
stroke in young adults) should be reported in an expedited report. For an event that is
known to occur independent of drug exposure in the study population, the sponsor may
specifically describe an approach for reporting to FDA and all participating investigators
(e.g., an updated aggregate narrative once a certain number of additional cases are
identified or after a specified period of time, as appropriate).
3. Other Reports
For reports of overall findings or pooled analyses from published and unpublished in
vitro, animal, epidemiological, or clinical studies, a narrative format must be used (21
22