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
Objectives The primary safety objective is to characterize the annual serious adverse event (SAE) rate over
The secondary safety objective is to demonstrate that there is not a worsening in seizures over time in patients treated with the RNS® System beginning at 6 to 12 months post-implant and extending to 3 years.
The primary effectiveness objective will be to estimate the median percent reduction in seizures from baseline (3 months pre-implant) to 3 years in the PAS, and evaluate if this reduction is comparable to the median percent reduction in seizures from baseline to 3 years in the controlled clinical study (51.3%).
The secondary objective will be to characterize observed battery longevity overall and in relation to total stimulation time and stimulation programming at 5 years.
Additional objectives will be to describe the demographic and clinical characteristics of treated patients, additional procedures including explants and re-implants (reasons, associated complications, and resolution), responder rate, antiepileptic drug (AED) use, discontinuations, and autopsy data.
Design An All-comer, 5-year, non-randomized open-label prospective observational study in newly implanted patients treated with the RNS System. .
Study Population Description
The study population will consist of individuals 18 years of age or older with partial
onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci, are refractory to 2 or more antiepileptic medications, and currently have frequent and disabling seizures.
Up to 375 subjects may be enrolled from up to 30 sites in order that
a minimum of 300 subjects be implanted, with no individual investigational site implanting more than 15 subjects.
Assumptions: The sample size calculation is based on the endpoint related to the secondary safety onjective (seizure worsening). Sample size calculation for a regression model with a log link and including a term for linear slope in the dependent variable indicates that 240 patients will provide over 80% power for the ability to detect a possible slope equivalent to a 20% cumulative increase in seizures over the period from pre-implant to 30 to 36 months post-implant. The sample size calculation assumes a linear regression t test of the slope with a one sided alpha of 0.05, and a standard deviation of 0.28 applicable to the term for linear slope. Conservatively assuming approximately 25% of patients do not contribute the full 3 years of data leads to selection of 300 implanted patients as the sample size.
Primary Safety Endpoint: Severe adverse event rate; Secondary Safety Endpoints: Seizure worsening Primary effectiveness endpoint: Median
percent reduction in seizures Additional endpoint: Neurostimulator batter longevity patients characteristics, all-cause mortality, antiepileptic drug (AED) use, subject disposition, RNS system explant/revision, SUDEP rate, responder rate, seizure frequency.
Followup Visits and Length of Followup
Enrollment plan: 2 patients every other month after the first site is enrolled, 12 patients
per month after all sites are enrolled.
The study consists of: (a) pre-implant criteria Informed consent process Review medical/seizure history (b) initial implant, Perform examination Review medications Review seizure data Administer Columbia suicide severity rating scale (C-SSRS) Review adverse events Perform surgery activities and (c) post-implant follow-up. Complete implant registration form Distribute Magnet/Remote Monitor Manage Neurostimulator Up to 5 years