Kenneth A. Getz
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Serious adverse event (SAE) reporting and to a lesser extent adverse event (AE) reporting have long been time consuming, costly,
and often perplexing tasks for investigative sites. Growing worldwide concern about patient safety in clinical trials now
seems to be unintentionally adding to the burden—with marginal to no real utility in improving subject protection.
Many sponsors have begun seeking definitive answers from investigators about whether or not an AE or SAE is related to a study
drug, an opinion that even the most astute clinician will admit comes down to guesswork. Institutional review boards (IRB)
are also asserting themselves with information requests connected to protocol deviations and Investigational New Drug (IND)
safety reports.
Growing reporting requirements for SAEs and protocol deviations are widely considered by investigative sites to be distracting
layers of bureaucracy at a time when they are expected to provide substantially higher levels of efficiency. Most sites believe
study conduct performance targets cannot be met unless the burden of safety reporting can be eased.
Sites understand the necessity of AE and SAE reporting and the federal requirements behind it. Investigative sites tacitly
submit to the volume of exchanges with study sponsors and IRBs that these requirements require. Nonetheless, safety reporting
is a very frustrating task, due in part to poor clarity around the definition of unexpected adverse events; the unpredictable
frequency of SAEs; a lack of context with which to place the observed SAEs. The time investment for investigative sites to meet safety reporting requirements is anecdotally substantial. Study coordinators
estimate that AE/SAE reporting consumes between 10% and 20% of their work effort on trials. These back-of-the-envelope estimates
vary widely by therapeutic area. Little to no data has been systematically gathered to quantify the magnitude of this burden.
But speak with any investigative site, and you'll get an ear full.
An obscure burden
Consider the case of the Alaska Clinical Research Center in Anchorage. "We're involved in a large Phase II trial that was
supposed to have few side effects and we've had two SAEs so far," says Mary Anderson, RN, study coordinator and regulatory
affairs manager. "You just never know when someone is going to have a severe allergic reaction or cardiac rhythm change."
For one of the SAEs that occurred with the current oncology trial, Anderson figures she has spent 20 hours treating and monitoring
the subject, scheduling procedures, picking up the patient's records from the hospital, and completing all the requisite paperwork,
often in triplicate. The other SAE consumed less than five hours of her time to document, she says, because the subject was
acutely ill and died of natural causes.
When an SAE occurs, an initial two to five page SAE form must be filled in and sent to the study sponsor within 24 hours,
as required by the FDA, and sites have much of the requested information on hand. But for weeks thereafter, the effected subject
requires vigilant supervision. Sponsors also ask for regular updates on the patient's status and follow-up lab work until
the SAE is resolved, as well as clarification on anything it deems inappropriate in the initial report.
Although sponsors may be loath to hear it, sites know that accurate and timely reporting isn't always possible. With AEs,
reporting is straightforward. It gets listed in a log, indicating when it started and was resolved, what action (if any) was
taken, its severity and potential association with the study drug, and the outcome. "It's no problem," says Anderson, "as
long as you know the answers. The primary issue is that patients don't always remember the precise day and time their symptoms
began."
"Recently, a female subject in a study waited until her 30-day follow-up visit to mention that she experienced hair loss during
the entire study. Other times, an AE is discovered only because the complaint was voiced to another doctor and appears as
a note on the patient's chart, often devoid of details such as date of the reported illness," she said.
Cancer patients tend to be more conscientious about recording their symptoms, but oncology trials are particularly tricky
when it comes to teasing out cause and effect. Overall, Anderson estimates that AE/SAE reporting consumes about 15% of her
work hours but nearly a quarter of her time as a study coordinator.
At Jasper Summit Research in Jasper, AL, which primarily conducts respiratory research, study coordinator Becky Thompson,
RN, CCRC, says that AE/SAE reporting consumes less than 5% of her time on most studies.
