DRAFT FDA
Questions for the Circulatory System Devices Panel
March 6, 2003
P020045
CryoCath
Technologies, Inc.
7F Freezor
Cardiac Cryoablation Catheter and
CCT.2
Cryoablation Console System
Results of this clinical trial were compared to
objective performance criteria (OPCs) established for the study for both safety
and effectiveness. The OPCs were
determined from the radiofrequency ablation medical literature.
Safety
1. The safety endpoint was the occurrence
of major complications, as defined in the study protocol. The FDA interprets the definition of major
complications to include all adverse events requiring treatment which occurred
within 7 days of the procedure. The upper bound 95% confidence bound forinterval of the major study complication
rate wasof of 4.8% (2.1%, 8.59.3%. This%) exceeded the safety OPC, which specified an upper 95% confidence boundinterval safety OPC of 2.5% upper bound of of less
than 7% or less. The FDA interprets the
definition of major complications to
include all adverse events requiring treatment which occurred within 7 days of
the procedure. Please
comment on the following:
a. Please discuss whether the results of the clinical
study provide a reasonable assurance of device safety for the intended patient
population.
b. Please discuss the applicability of a safety OPC
for cryoablation which was based on reported clinical experience with
radiofrequency ablation.
Effectiveness
- Ablation
21. The primary
effectiveness endpoint was defined for patients with AVNRT and AVRT as the
absence of recurrence and non-inducibility of sustained SVT at the end of the
procedure. For patients with AF, it was
defined as the absence of AV node conduction at the end of the procedure. Study results were compared to effectiveness
objective performance criteria (OPCs) established
for the study. TResults
showed that the device did not meet the effectiveness OPC
for the overall study population or for eachany patient subgroup. The lower bound 95% confidence intervaboundl for aacute
success forof the entire study population was 83% (76%, 88%). The
OPC for acute success specified a was
lower 95% confidence bound equal to or greater >≥ than 85%.
a.
Please discuss whether the results of the clinical study provide a
reasonable assurance of effectiveness in (a) the overall patient population or
(b) in any individual patient subgroup.
b.
If the clinical trial does not provide enough
evidence of effectiveness please discuss what would be needed.
Safety
2. The primary safety endpoint was the occurrence
of major complications, as defined in the study protocol. Results were compared to the safety OPC
established for the study and showed that the study complication rate
exceeded the safety OPC. Please comment
on the following
a. The safety OPC for this study was based on clinical experience with
radiofrequency ablation for the treatment of supraventricular tachycardias
(SVT). Please
discuss the applicability of this safety OPC on the evaluation of safety of
cryoablation for the treatment of SVT.
b. Please discuss whether the results of the clinical study provide a
reasonable assurance of device safety for the intended patient population.
Effectiveness
- Cryomapping
3. The submission describes the use of cryomapping technology
and effectiveness resultsevaluation. of the effectiveness of this
technology are described in the submission. Please comment ondiscuss whether the
study results demonstrateshow that the cryomapping technology is reasonably effective
for use in the intended patient population.
Training/Learning
Curve
4. The applicant suggestsAcute success rate
varied per institution in this study.
Acute success rate per institution ranged between 0 and 100%. CryoCath
reports that the study resultshows an
institutional learning curve, with improvement after the fifth procedure per
investigational site. The total
number of participating physicians and site were 34 and 13,
respectively. Please comment on the
following:
a. Please discuss the concept of site-based and physician-based
learning curves.
b. All
new devices inherently involve a learning curve in their evaluation. Please discuss whether the concept of a learning curve,
either per site or per physician, may be considered in the evaluation of device
safety and effectiveness.
c. If you
decide that a learning curve may be considered in device safety and
effectiveness, please discuss conclusions that may be made from the data
submitted in this PMA and its impact on safety and effectiveness of the device.
d. Please discuss whether and/or
what type of physician training should be required for this device if approved.
User Skill
5. Success of ablation procedures depends both on device performance
and user skill. Please discuss clinical
trial designs that would help FDA assess and/or reduce this source of bias in the
trial.
Labeling
65. Labeling for a new device should
indicate which patients are appropriate for treatment, should identify
potential device-related adverse events, and should explain how the device
should be used to optimize its risk/benefit profile. If you recommend device approval, please address the following:
a. Please discuss whether the proposed warnings, precautions,
and contraindications are acceptable, based on the study results.
b. Please discuss whether the instructions for use adequately
describe how the device should be used.
Post-Market
Study
76. If you recommend approval, please
discuss whether a post-market study should be performed to address any issues
that are unresolved, but not essential to the premarket approval of the device.
prepared EMallis, 01/15/03As of 0123/032627/03