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
The primary safety objective is to characterize the annual serious adverse event (SAE) rate over
5 years in patients treated with the RNS System.
The primary effectiveness objective is to demonstrate the median percent reduction in disabling 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 LTT controlled clinical study.
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.
Additional objectives include characterizing, describing, and evaluating:
¿ Patient characteristics
¿ Adverse events of particular relevance
¿ All-cause mortality
¿ Anti-epileptic drug (AED) use
¿ Subject disposition
¿ RNS System explant/revision
¿ Sudden unexpected death in Epilepsy (SUDEP) rate
¿ Median percentage change
¿ Responder rate
¿ Seizure frequency
in sub-populations of subjects treated with the RNS® System.
The primary safety objective is to demonstrate that there is no difference in safety in the 6-week perioperative period based on the experience of NeuroPace qualified and trained implanting physicians.
The co-primary safety objective is to demonstrate that there is no difference in safety 1 year post implant on the experinece of NeuroPace qualified and trained treating physicians and Comprehensive Epilepsy Centers.
The primary effectiveness objective is to demonstrate that the stimulation programming classes have similar effects on the overall seizure frequency.
The secondary objective is to characterize the effects of the stimulation programming classes on the overall 5 year rate of SAEs and device related non serious AEs.
A 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.
The sample size calculation is based on the endpoint related to the secondary safety objective (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.