In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
Transit. Adolescent B (as adults) : 18-21 yrs,
Detailed Study Protocol Parameters
Study Design Description
This is a 5-year, prospective, observational, multi-center
patient outcome registry to follow the clinical course and
outcome of patients with treatment-resistant depression (TRD) who are currently in a major depressive episode (MDE) treated with and without VNS Therapy. The study is a new enrollment study.
Study Population Description
The registry will enroll a minimum of 500 Treatment-Resistant Depression (TRD) patients treated with adjunctive
VNS Therapy and a minimum of 300 TRD patients who are not treated with VNS Therapy.
500 TRD patients treated with adjunctive VNS Therapy and a minimum of 300 TRD patients
who are not treated with VNS Therapy.
Response based on MADRS Assessment: Defined as ¡Ý 50% improvement from baseline in Montgomery
Asberg Depression Rating Scale (MADRS) score at visit month assessment post-baseline across the 60 months of follow-up.
Secondary endpoints are separated into two groups: Group 1 includes clinically important prospectively defined endpoints that if found statistically significant (P < 0.05) will be submitted for consideration for label claim. Group 2 will include other supportive secondary endpoints.
Group 1: Secondary Endpoints for Label Claim:
(a) Response based on Clinical Global Impression (CGI): The Clinical Global Impressions is a clinicianrated scale used to assess the level of severity and improvement in depressive symptoms over time. For the analysis, a response is defined as achievement of CGI rating ¡°1¡± or ¡°2¡± (¡°Very much improved¡± or ¡°Much improved¡±) at visit month assessment post-baseline.
(b) Duration (or maintenance) of response based on MADRS: Defined as the difference between the first recorded date post-baseline that response is achieved (MADRS ¡Ý 50%) and the first date at which maintenance of the MADRS reduction decreases to 40% or less. Sackeim et al. (2007) suggested using a criterion of maintenance of response at follow-up visit months assessments post-response to
40% in order to avoid characterizing a minor decrease (e.g., from 51% to 49%) as a loss of benefit. Only a subpopulation that achieved response will be included in the summary.
(c) Remission based on MADRS: Defined as MADRS total score ¡Ü9 at visit month assessment postbaseline.
(d) Duration of remission based on MADRS: Defined as the recorded post-baseline date of first recurrence/relapse (¡Ý 20 MADRS score) minus the recorded date of first achieved remission (MADRS
score ¡Ü 9). Only a subpopulation that achieved remission will be included in the summary.
Group 2: Supportive Exploratory Secondary Endpoints:
(a) Response based on Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR)
(b) Remission based on SLICE-C Psychiatric Status Rating and QIDS-SR.
(e) Predictors of suicide attempts and suicidal ideation
(f) Quality of Life, Health Outcomes and Depression
(g) Safety Endpoints: (i) Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER); and (ii) MDR reportable events on VNS treated patients.
Followup Visits and Length of Followup
All of the patients are planned to be followed for 60 months after enrollment. Visits
include a screening and a baseline visit, and follow up visits at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after baseline.