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