Wednesday, March 18, 2009

Should expected clinical outcomes of the disease under study, which are efficacy endpoints, be reported as AEs/SAEs?

The paragraphs below are from the following website:

Some protocols instruct investigators to record and report all untoward events that occur
during a study as AEs/SAEs, which could include common symptoms of the disease under
study and/or other expected clinical outcomes. This approach enables frequency
comparisons of all events between treatment groups, but can make event recording in the
CRF burdensome, result in more expedited reports from investigators to sponsors, and fill
safety databases with many untoward events that most likely have no relationship to study
treatment and that could obscure signal identification.
In some clinical trials, disease symptoms and/or other expected clinical outcomes
associated with the disease under study, which might technically meet the ICH definition of
an AE or SAE, are collected and assessed as efficacy parameters rather than safety
parameters. An example might be severity scoring of prospectively defined disease
symptoms at each clinic visit during a rheumatoid arthritis study. The hypothesis underlying
this approach is that the study treatment will have a positive impact on disease symptoms.
If prospectively defined clinical outcomes, such as symptoms of a studied chronic disease or
death due to disease progression in an oncology trial, are to be assessed as efficacy
endpoints and not as AEs/SAEs, the methods for recording and analyzing these data should
be clearly described in the protocol. In addition, sponsors are advised to consult with
applicable regulatory authorities to ensure that safety reporting instructions in protocols are
acceptable, especially if certain clinical outcomes are to be excluded from traditional AE/SAE
In high morbidity/mortality trials, independent data monitoring committees (IDMC)
generally monitor all acquired AE/SAE and clinical outcomes data to assess benefit and risk
on an ongoing basis. A reviewing IDMC could halt a trial if there was significant
improvement in pre-specified clinical outcomes in the treatment group compared to the
control group. It is also possible that a study treatment might unexpectedly worsen prespecific
disease symptoms and/or other clinical outcomes that are being assessed as
efficacy parameters.1

1. “Good Clinical Practice: A Question & Answer Reference Guide”, Barnett International,
2007, #9.10 p. 215

“Good Clinical Practice: A Question & Answer Reference Guide 2007,” is available for $39.95

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