ABSTRACT
Major depressive disorder (MDD) is a highly prevalent, under-treated, and disabling condition in
the United States (US) and worldwide. An estimated 17.3 million adults in the US experienced
at least one major depressive episode in 2017, representing 7.1% of the adult population. With
the emergence of antidepressant agents with faster onsets of action, there is a need for new
clinical outcome assessments capable of detecting clinical benefit within much shorter
timeframes. However, a psychometrically sound, publicly available measure of depression
symptom severity at shorter time intervals after drug administration has not been recognized by
FDA as fit-for-purpose for use in drug development. We propose the preparation of a
Qualification Plan to support the qualification of the Symptoms of Major Depressive Disorder
Momentary Assessment (SMDDMA) as a patient-reported outcome measure for the momentary
assessment (i.e., “at this moment”) of depression symptom severity in individuals with MDD.
The SMDDMA was accepted into the Center for Drug Evaluation and Research’s (CDER’s)
COA Qualification Program under DDT #000109 on February 4, 2019. As supported by FDA in
response to the Letter of Intent, a cognitive interview study was recently completed to generate
qualitative evidence for the content validity of the SMDDMA. The resulting cognitive interview
report was submitted to FDA on March 5, 2020, as an interim submission with a request for
preliminary feedback on the qualitative findings. After receiving FDA feedback on the qualitative
results, the next step in the qualification process will be to submit a Qualification Plan to FDA to
address the Depression Working Group 2.0’s research plan for obtaining the quantitative
evidence necessary to support qualification of the SMDDMA for use in MDD drug development.
Our approach includes two aims. For Aim 1, we will develop (1) a protocol for a quantitative pilot
study for the SMDDMA to assess its cross-sectional measurement properties, (2) a statistical
analysis plan for analysis of the data to be derived from the quantitative pilot study, and (3) a
user manual for the SMDDMA, including an item definition table for the SMDDMA to support
translations and cross-cultural adaptations. These documents will provide the foundation for Aim
2, in which we will finalize and submit a Qualification Plan for the SMDDMA using the CDER
COA Qualification Plan content outline. The long-term result of this project will be a publicly
available PRO measure for assessing depression symptom severity in MDD clinical trials of
rapid-acting antidepressants. As such, qualifying the SMDDMA will fill a critical gap in the
assessment of symptom severity in MDD treatment trials for emerging innovative therapies.
