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.
Major depressive disorder (MDD) is a highly prevalent, under-treated, and disabling condition in the United States (US) and worldwide, with an estimated 17.3 million adults in the US experiencing 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 in much shorter timeframes within MDD treatment trials. To address this unmet measurement need in drug development, the overall objective of this project is to develop a Qualification Plan to support the qualification of the Symptoms of Major Depressive Disorder Momentary Assessment (SMDDMA) with the resulting impact of this work being the advancement of a publicly available, psychometrically sound, fit-for- purpose patient-reported outcome measure of depression symptom severity to facilitate the assessment of faster onset of symptom relief in patients with MDD.
