Post on 04-Jan-2016
DHHS / FDA / CDRHDHHS / FDA / CDRH1
DHHS / FDA / CDRHDHHS / FDA / CDRH2
CryoCath Technologies Inc.7 Fr Freezor Cryoablation
Catheter SystemP020045
FDA Circulatory System Devices Panel Meeting
March 6, 2003 Gaithersburg, MD
DHHS / FDA / CDRHDHHS / FDA / CDRH3
FDA/CDRH/ODE/CEMB PMA Review Team
James Cheng, Lead Reviewer
Lesley Ewing, M.D., Clinical and Animal Review
Lilly Yue, Ph.D., Statistical Review
Cindy Demian, Biocompatibility Review
Elaine Mayhall, Sterilization Review
Kevin Hopson, Bioresearch Monitoring Review
DHHS / FDA / CDRHDHHS / FDA / CDRH4
Sponsor Proposed Indications for Use
• The cryo-ablation of the conducting tissues of the heart in the treatment of patients with atrioventricular node reentrant tachycardia (AVNRT)
• The identification of aberrant conducting tissue responsible for supraventricular tachycardia using the reversible electrophysiological cryomapping of conducting tissue near the AV node to minimize risk of AV block
DHHS / FDA / CDRHDHHS / FDA / CDRH5
Cryoablation System Components
FreezorTM Cardiac CryoAblation Catheter
CCT.2 CryoConsole
Umbilicals and Accessories
DHHS / FDA / CDRHDHHS / FDA / CDRH6
FreezorTM Cardiac CryoAblation Catheter
• 7 French single use catheter with 4mm long gold-plated metal tip, 3 ECG ring electrodes, thermocouple sensor and a flexible, maneuverable shaft.
• Refrigerant injection tube, ECG wires, leak detection wire, and thermocouple wire are contained inside the catheter lumen.
• Catheter handle contains deflection mechanism.
DHHS / FDA / CDRHDHHS / FDA / CDRH7
CCT.2 CryoConsole
• Provides N2O refrigerant delivery & recovery.• Maintains vacuum inside catheter lumen.• Controls refrigerant pressure and flow rate to
achieve target temperature ranges.• Contains device safety systems.• Monitors integrity of umbilical connections.• Injection controller uses dedicated hardware
and has manual override.
DHHS / FDA / CDRHDHHS / FDA / CDRH8
Umbilicals and Accessories
• Coaxial umbilical – delivers liquid N2O under pressure to the catheter and evacuates N2O gas.
• Electrical umbilical – carries catheter electrical signals to Auto Connection Box.
• Auto Connection Box – connects electrical umbilical and ECG cable to console.
• ECG Cable – carries catheter ECG signals to external monitor.
DHHS / FDA / CDRHDHHS / FDA / CDRH9
Principles of Operation
• Cryogenic temperatures generated only at the catheter tip.
• Pre-cooled liquid N2O injected under pressure to the catheter tip.
• Liquid N2O expands to a gas inside the tip.
• Phase change is an endothermic reaction.
DHHS / FDA / CDRHDHHS / FDA / CDRH10
Principles of Operation
• CryoAblation – catheter tip target temperature between –68oC and -75oC maintained for up to 240 seconds.
• CryoMapping - catheter tip target temperature between –25oC and -30oC maintained for 60 seconds.
DHHS / FDA / CDRHDHHS / FDA / CDRH11
FDA Preclinical Review Goals
• Safety – ensure that the device has been appropriately designed and tested, that potential device hazards have been analyzed and mitigated, and that safety features have been qualified for use.
• Reliability – ensure that the device design and manufacture provide assurance of consistency with performance specifications.
DHHS / FDA / CDRHDHHS / FDA / CDRH12
Preclinical Qualification7F FreezorTM Catheter
Catheter Testing
• biocompatibility of catheter materials• reliability of catheter design• mechanical testing of catheter performance• electrical testing of catheter performance• qualification of sterilization procedures
DHHS / FDA / CDRHDHHS / FDA / CDRH13
Preclinical QualificationCCT.2 Console
• Software Qualification: assessment of design and development methodology, software hazards analysis, and verification and validation process.
• Hardware Qualification: assessment of N2O injection and recovery systems design, temperature controller performance, device risk analysis, and design and performance of device safety features.
DHHS / FDA / CDRHDHHS / FDA / CDRH14
System Safety Features
Primary Hazard – Gas EmbolismMitigation Features
• Catheter design and qualification (burst and leak testing)
• Catheter lumen under continuous vacuum (prevents release of refrigerant gas into bloodstream)
• Catheter safety interlock (prevents device operation until all catheter connections properly configured)
DHHS / FDA / CDRHDHHS / FDA / CDRH15
System Safety Features
Primary Hazard – Gas EmbolismMitigation Features
• Redundant blood/fluid detector systems (detects blood inside the catheter as a result of a catheter leak)
• Injectant flow profile monitoring (detects unusual catheter performance)
• Catheter pressure relief valve• Loss of vacuum detection (disables injection)
DHHS / FDA / CDRHDHHS / FDA / CDRH16
System Safety Features
Safety Hazard – ExsanguinationMitigation Features
• Redundant blood/fluid leak detectors along vacuum recovery path (disables injection and vacuum)
• Catheter design and reliability validation testing (burst and leak testing)
DHHS / FDA / CDRHDHHS / FDA / CDRH17
System Safety Features
Safety Hazard – Freezing Temperatures Along Catheter Shaft
Mitigation Features• Injectant flow profile monitoring (detects
unusual catheter performance)• Catheter qualification testing (demonstrated
refrigerant tube break did not allow external shaft temperatures to approach freezing)
DHHS / FDA / CDRHDHHS / FDA / CDRH18
System Safety Features
Safety Hazard – Software FailureMitigation Features
• Dedicated hardware-based injection controller with manual override for stopping injection delivery
• Hardware-based watchdog circuitry to monitor for software failure
DHHS / FDA / CDRHDHHS / FDA / CDRH19
Preclinical Testing Conclusions
• Preclinical testing performed by the sponsor is appropriate and acceptable.
• Specific hazards posed by the device have been appropriately analyzed and addressed by the sponsor’s device design and qualification testing.
• Overall testing shows that the device is reliable for human use.
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DHHS / FDA / CDRHDHHS / FDA / CDRH21
Clinical Summary
Lesley Ewing, M.D.
FDA, CDRH
DHHS / FDA / CDRHDHHS / FDA / CDRH22
Study purpose
• To study the safety and effectiveness of the cryoablation system to treat:– Atrioventricular re-entrant SVT due to
accessory pathways (AVRT)– Atrioventricular node re-entry SVT
(AVNRT)– Rapid ventricular response due to
atrial fibrillation (AF)
DHHS / FDA / CDRHDHHS / FDA / CDRH23
Study Design
Single arm, non-randomized, multi-center study using objective performance criteria (OPC) for comparators
The OPCs were based on the medical literature on radiofrequency ablation and designed to be used for the entire pooled study population.
The OPCs have been used in previous ablation clinical trials reviewed by the FDA.
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Objective Performance Criteria
• Guidance document issued on July 1, 2002 “Cardiac Ablation Catheters Generic Arrhythmia Indications for Use; Guidance for Industry”
• http://www.fda.gov/cdrh/ode/guidance/1382.html
• Recommendations of this guidance intended for RF ablation catheters
DHHS / FDA / CDRHDHHS / FDA / CDRH25
Table 1. Acceptable Endpoint Criteria Based on Medical Literature
STUDY ENDPOINT
TARGET VALUE
95 % CONFIDENCE
BOUND
Acute Success > 95 % >= 85 %
Chronic Success > 90 % >= 80 %
Major Complications < 2.5 % <= 7 %
DHHS / FDA / CDRHDHHS / FDA / CDRH26
Study Design
Three patient populations were included in the study:
1. Atrioventricular node re-entry tachycardia (AVNRT)
2. Atrioventricular reciprocating tachycardia (AVRT)
3. Atrial fibrillation (AF)
DHHS / FDA / CDRHDHHS / FDA / CDRH27
Inclusion Criteriapre-electrophysiology study
• Clinical history of SVT or refractory AF with rapid ventricular response documented by ECG, TTM, or holter
• EF 35% 18 years
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Inclusion Criteriapost-electrophysiology study (EPS)
• EPS documented inducible sustained AVNRT, AVRT, or AF with rapid ventricular response
DHHS / FDA / CDRHDHHS / FDA / CDRH29
Exclusion Criteria Atrial tachycardia
Sustained ventricular tachycardia
Acute MI within 2 months or unstable angina
Congenital heart defect
Clinically significant aortic, mitral or tricuspid valve disease
Severe vascular disease
History of any mitral or tricuspid valve surgery
NYHA class III or IV
Any implantable cardiac device except for pacemaker in AF patients
Any cerebral ischemic event in the preceding 3 months
Significant coagulation disorder
Pregnancy
Hyperthyroidism
Any previous cardiac ablation procedure
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Primary effectiveness endpointAcute procedural success
• AVNRT and AVRT – absence of spontaneous or inducible sustained SVT at end of procedure
• AF – absence of AV node conduction at end of the procedure
DHHS / FDA / CDRHDHHS / FDA / CDRH31
OPCs
STUDY ENDPOINT Lower or upper
95 % CONFIDENCE BOUND
Acute Success > 85 %
Chronic Success > 85 %*
Major Complications
< 7 %
DHHS / FDA / CDRHDHHS / FDA / CDRH32
Secondary Effectiveness endpoint
Long term success
• AVNRT and AVRT- no recurrence of sustained SVT by the time of the 3 month follow-up
• AF – absence of AV node conduction at 3 month follow-up
DHHS / FDA / CDRHDHHS / FDA / CDRH33
OPCs
STUDY ENDPOINT
Lower or upper95 %
CONFIDENCE BOUND
Acute Success > 85 %
Chronic Success > 85 %*
Major Complications
< 7 %
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Safety Endpoint
• The number of major complications following the use of the investigational device system should have an 95% upper bound of < 7%.
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Definition of major complications
Major Complication: Any adverse event which occurs within the first week following use of the investigational device and:
• is life-threatening; or • results in permanent impairment of a body
function or permanent damage to a body structure; or
• necessitates significant intervention, such as major surgery, to prevent permanent impairment of a body function or permanent damage to a body structure; or
DHHS / FDA / CDRHDHHS / FDA / CDRH36
Definition of major complications continued
• requires hospitalization or an extended hospital stay; or
• results in moderate transient impairment of a body function or transient damage to a body structure; or
• requires intervention such as medication or cardioversion to prevent permanent impairment of a body function or damage to a body structure.
DHHS / FDA / CDRHDHHS / FDA / CDRH37
Study Procedure
Diagnostic eps
Cryoablation
Screening and enrollment
Follow-up at 7 days, 1, 3, 6 months
Cryomapping at investigators discretion
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Study results
• 166 patients were enrolled, 164 received cryoablation lesions
• 14 total investigational sites, 11 US and 3 Canadian
DHHS / FDA / CDRHDHHS / FDA / CDRH39
EPS diagnosis
AVNRT 102/166 61%
AVRT 51/166 31%
AF 12/166 7%
AT 1/166 0.6%
DHHS / FDA / CDRHDHHS / FDA / CDRH40
Patient Accountability
166 enrolled
164 with cryoablation
157 per protocol
136 acute success 28 acute failure
120 chronic success 27 received RF ablation
25 acute RF success
6 less than full duration lesions
1 AT
12 with recurrence
2 equipment problems
2 lost to follow-up 1 death
DHHS / FDA / CDRHDHHS / FDA / CDRH41
Ablation results
Acute success (%)
AVNRT 94/103 (91)
AVRT 34/49 (69)
AF 8/12 (67)
Total 136/164 (83)
DHHS / FDA / CDRHDHHS / FDA / CDRH42
Chronic results
nLost
3 moChronic success
AVNRT 94 2 86/94 (91%)
AVRT 34 0 30/34 (88%)
AF 8 0 6/8 (75%)
Total 136 2 122/136 (90%)
DHHS / FDA / CDRHDHHS / FDA / CDRH43
Acute major complicationswithin 7 days of procedure
7 patients with 8 acute major complications
7/166 patients, 4.2% (1.7%, 8.5%)
3 patients with AVNRT procedure, 4 with AVRT
DHHS / FDA / CDRHDHHS / FDA / CDRH44
Acute major complications
Complication Rhythm RF
1 Prostatitis AVNRT No
2 Pulmonary embolus AVNRT No
3 RA thrombus AT No
4 Introducer sheared AVRT Yes
5 RA thrombus AVRT Yes
6 AMI, stent placed AVRT Yes
7 RV perforation, DVT AVRT no
DHHS / FDA / CDRHDHHS / FDA / CDRH45
Cryomapping• Mapping performed by using the
reversible cryo effects on the conduction system
• Use of cryomapping decided per case by investigator
• Criteria for effective cryomaps were predetermined per tachycardia
• Cryomapping not part of predetermined endpoints of the trial
DHHS / FDA / CDRHDHHS / FDA / CDRH46
Cryomapping
• 135 out of 164 patients had cryomap attempts
• 88/135 (65%) had effective cryomaps and 47/135 (35%) had only ineffective cryomaps
• Total # cryomap attempts was 812 with 161 (20%) of those effective cryomaps
• “negative” cryomaps may have helped the investigator determine unsuccessful cryoablation locations
DHHS / FDA / CDRHDHHS / FDA / CDRH47
Cryomapping safety
• 7 AVNRT patients had “not reversible” marked on data collection forms
• All 7 patients had successful cryoablation procedures with no adverse event reported
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DHHS / FDA / CDRHDHHS / FDA / CDRH49
Statistical Summary
Lilly Yue, Ph.D.
FDA, CDRH
Division of Biostatistics
DHHS / FDA / CDRHDHHS / FDA / CDRH50
Study Design
• Effectiveness and safety outcomes
– Primary: • Acute procedure success
• Major complication occurrence
– Secondary: • Long-term clinical success at 3-month
conditional on acute success
• Evaluated for the entire SVT patient population
DHHS / FDA / CDRHDHHS / FDA / CDRH51
Study Design
• Study success criteria
a.Acute procedure success
The lower 95% two-sided confidence
bound of the acute success rate for all ITT
patients should be greater than 85%.
ITT: Cryoablation catheter activated
DHHS / FDA / CDRHDHHS / FDA / CDRH52
Study Design
b. Major complication occurrence
The upper 95% two-sided confidence bound of the major complication incidence
rate for all safety patients should be less than 7%.
Safety patients: Cryoablation catheter
inserted
DHHS / FDA / CDRHDHHS / FDA / CDRH53
Study Design
c. Conditional Long-term clinical success
The lower 95% two-sided confidence
bound of the conditional long term success rate for all ITT patients should be greater than 85%*.
DHHS / FDA / CDRHDHHS / FDA / CDRH54
Study Results
Acute Success ITT, OPC:85%
n 164
# Success 136
Rate 83% (< 85%)
95% C.I. (76%, 88%)
DHHS / FDA / CDRHDHHS / FDA / CDRH55
Incidence of Major complications
OPC: 7%
n 166
# Patients with major complications
7
Incidence Rate 4.2%
95% C.I. (1.7%, 8.5%)
DHHS / FDA / CDRHDHHS / FDA / CDRH56
Conditional Long-term SuccessOPC: 85%*
Protocol-specified Exact C.I.
ITT Excluding L F/U
n 136 136 134
# Success 122 122
#Failure 12 12
#Lost to F/ U 2 2 0
Rate 90%: 122/136 91%: 122/134
95% C.I. (83%, 94%) (85%, 95%)
DHHS / FDA / CDRHDHHS / FDA / CDRH57
Post-hoc Subgroup Analyses
• Subgroup analysis on the ablation safety and effectiveness endpoints for the three patient subpopulations
AVNRT AVRT AF
• Subgroup analysis on the impact of effective cryomapping on ablation acute success --- “cryomapping utility”
DHHS / FDA / CDRHDHHS / FDA / CDRH58
Post-hoc Claims• The cryoablation of the conducting tissues of
the heart in the treatment of patients with atrioventricular node reentrant tachycardia (AVNRT)
• The identification of aberrant conducting tissue responsible for supraventricular tachycardia using the reversible electrophysiological cryomapping of conducting tissue near the AV node to minimize risk of AV block
DHHS / FDA / CDRHDHHS / FDA / CDRH59
Post-hoc Subgroup Analysis
• When should we perform subgroup analysis?
– When the study has succeeded in pre-specified overall analysis, may do subgroup analysis
– When the study has failed in pre-specified overall analysis, generally do not perform subgroup analysis because the risk of false positive results increases
DHHS / FDA / CDRHDHHS / FDA / CDRH60
Post-hoc Subgroup Analysis
• Some criteria to judge the validity of subgroup analysis:
– Prospectively defined hypotheses?– Biologically plausible subgroup classification? – Significant treatment effect in overall
analysis?– Significant interaction of treatment with
subgroup variable?
DHHS / FDA / CDRHDHHS / FDA / CDRH61
Subgroup Analysis on Ablation• Is there justification to examine the post-
hoc subgroup analysis?
– Prospectively defined hypotheses? ... NO– Biologically plausible subgroup classification?
…YES– Significant treatment effect in overall
analysis? ... NO– Significant interaction of treatment with
subgroup variable? ... ???
DHHS / FDA / CDRHDHHS / FDA / CDRH62
Subgroup Analysis on Ablation
• OPCs developed for entire patient population may be wrong for subpopulations, so can’t applied to subpopulations.
• If the subgroup analysis had been planned in the design stage, a multiplicity adjustment, such as Bonferroni, for significance level should have been performed.
DHHS / FDA / CDRHDHHS / FDA / CDRH63
Subgroup Analysis on Ablation
Acute Success (OPC:85%)AVNRT AVRT AF
Success
Rate
91%
(94/103)
69%
(34/49)
67%
(8/12)
95%
C.I.
(84%,
96%)
(55%,
82%)
(35%,
90%)
Adjusted
C.I.
(82%,
97%)
(52%,
84%)
(30%,
93%)
DHHS / FDA / CDRHDHHS / FDA / CDRH64
Subgroup Analysis on Ablation
Major Complications (OPC:7%)AVNRT AVRT AF
Incidence
Rate
2.9%
(3/103)
7.8%
(4/51)
0%
(0/12)
95%
C.I.
(0.6%,
8.3%)
(2.2%,
18.9%)
(0%,
24.5%)
Adjusted
C.I.
(0.4%,
9.6%)
(1.6%,
21.5%)
(0%,
32.8%)
DHHS / FDA / CDRHDHHS / FDA / CDRH65
Subgroup Analysis on Ablation
Conditional Long-term Success (OPC:85%)AVNRT AVRT AF AVNRT*
Success
Rate
91%
(86/94)
88%
(30/34)
75%
(6/8)
93%
(86/92)
95%
C.I.
(84%,
96%)
(73%,
97%)
(35%,
97%)
(86%,
98%)
Adjusted
C.I.
(82%,
97%)
(69%,
98%)
(28%,
98%)
(85%,
98%)
* Excluding 2 lost to follow-up subjects
DHHS / FDA / CDRHDHHS / FDA / CDRH66
Subgroup Analysis on Ablation
• Results
Suppose that the OPCs were appropriate for the subgroups. For any patient subgroup,
– With or without multiplicity adjustment, the study has failed to meet the primary safety and effectiveness OPCs
• Conclusion
– None of the three subgroups met the OPCs for either primary safety or primary effectiveness.
DHHS / FDA / CDRHDHHS / FDA / CDRH67
Subgroup Analysis on Cryomap
Patient accountability:
• Of 164 patients who got cryoablations, 135 patients had cryomapping attempts, and 29 did not.
• Of the 135 patients who had cryomapping attempts, there were 87 patients with effective cryomappings and 48 patients with ineffective cryomappings
• Effective cryomapping rate: 64%, (87/135)
• Reversibility rate: 92% (80/87)
DHHS / FDA / CDRHDHHS / FDA / CDRH68
Subgroup Analysis on CryomapAblation acute success
n
#Ablation
Acute
Success
Ablation
Success
Rate
“Effective” 87 82 94%
“Ineffective” 48 31 65%
“No attempts” 29 23 79%
DHHS / FDA / CDRHDHHS / FDA / CDRH69
Subgroup Analysis on Cryomap
• Sponsor: Grouped “ineffective” & “no attempts” and formed “without effective”
• “W/o effective”: n=77, acute success: 54, failure: 23
• Compared “effective” with “without effective”
• Concluded that “effective” was significantly better than “without effective” in ablation acute success
DHHS / FDA / CDRHDHHS / FDA / CDRH70
Subgroup Analysis on Cryomap
Ablation Acute Success Group “Effective” “W/o effe.” p-value
AVNRT(n=102)
94% (62/66)
89% (32/36)
0.45
AVRT(n=49)
94% (17/18)
55% (17/31)
0.004
AF(n=12)
100%(3/3)
56%(5/9)
0.49
Overall 94% (82/87) 70% (54/77) <0.0001
DHHS / FDA / CDRHDHHS / FDA / CDRH71
Subgroup Analysis on Cryomap
However,
• The significant result was driven by 49 AVRT patients.
• There is no significant difference detected in ablation acute success between “effective” and “w/o effective” patients for AVNRT and AF subgroups.
DHHS / FDA / CDRHDHHS / FDA / CDRH72
Subgroup Analysis on Cryomap
Question:
1. What is the meaning of the comparison?
2. Why grouping “Ineffective” with “no
attempts”?
3. Is the subgroup classification, "effective”
vs. “without effective” biologically
plausible?
DHHS / FDA / CDRHDHHS / FDA / CDRH73
Subgroup Analysis on Cryomap
• If we try to test the impact of effective cryomapping on ablation acute success, we could compare “effective” group with “ineffective” group, and use “no attempts” as a control.
• Ablation acute success: 94%, 65%, 79%
• Effective cryomapping rate: 64%
DHHS / FDA / CDRHDHHS / FDA / CDRH74
Subgroup Analysis on Cryomap
• If we try to test the impact of attempted cryomapping on ablation acute success, we could compare “attempted” with “no attempts”.
• “Attempted” includes “effective” and “ineffective”.
DHHS / FDA / CDRHDHHS / FDA / CDRH75
Subgroup Analysis on Cryomap
• Compare “attempted” with “no attempts”
• There is no significant difference detected in ablation acute success between “attempted” and “no attempts” groups.
Ablation Acute SuccessAttempted W/o attempts
Succ. Rate 84% (113/135) 79% (23/29)
Exact test p-value = 0.59
DHHS / FDA / CDRHDHHS / FDA / CDRH76
Subgroup Analysis on Cryomap• Is there justification to examine the post-
hoc subgroup analysis?
– Prospectively defined hypothesis? ... NO– Biologically plausible subgroup
classification? ... ???– Significant treatment effect in overall
analysis? ... NO– Significant interaction of treatment with
subgroup variable? ... ???
DHHS / FDA / CDRHDHHS / FDA / CDRH77
DHHS / FDA / CDRHDHHS / FDA / CDRH78
Clinical and Statistical Conclusions
• The device did not meet the primary effectiveness and safety OPCs for either the overall study population or any patient subgroup.
• No patient had unintentional permanent AV node block at the end of the procedure or during follow-up.
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Clinical and Statistical Conclusions
• There were a low number of recurrences after successful cryoablation. Cryoablation lesions appear to have a durable effect.
DHHS / FDA / CDRHDHHS / FDA / CDRH80
Clinical and Statistical Conclusions
• The post-hoc assessment of cryomapping effectiveness is questionable. There was no significant association detected between effective cryomapping and ablation acute success for the AVNRT subgroup.
• There was no adverse event reported due to cryomapping.
DHHS / FDA / CDRHDHHS / FDA / CDRH81
DHHS / FDA / CDRHDHHS / FDA / CDRH82
DRAFT FDA Questions for the Circulatory System
Devices Panel
DHHS / FDA / CDRHDHHS / FDA / CDRH83
FDA Draft Panel Questions
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.
DHHS / FDA / CDRHDHHS / FDA / CDRH84
Question 1: Safety
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 95% confidence bound for the major complication rate was 8.5%.
DHHS / FDA / CDRHDHHS / FDA / CDRH85
Question 1: continued
This exceeded the safety OPC, which specified an upper 95% confidence bound of less than 7%. 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.
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Question 1: continued
b. Please discuss the applicability of a safety OPC for cryoablation which was based on reported clinical experience with radiofrequency ablation.
DHHS / FDA / CDRHDHHS / FDA / CDRH87
Question 2: Effectiveness - Ablation
The device did not meet the effectiveness OPC for the overall study population or for any patient subgroup. The lower 95% confidence bound for acute success for the entire study population was 76%. The OPC for acute success specified a lower 95% confidence bound > 85%.
DHHS / FDA / CDRHDHHS / FDA / CDRH88
Question 2: continued
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.
DHHS / FDA / CDRHDHHS / FDA / CDRH89
Question 3: Effectiveness - Cryomapping
The submission describes the use of cryomapping technology and effectiveness evaluation. Please discuss whether the study results show that the cryomapping technology is effective for use in the intended patient population.
DHHS / FDA / CDRHDHHS / FDA / CDRH90
Question 4: Training/Learning Curve
Acute success rate varied per institution in this study. Acute success rate per institution ranged between 0 and 100%.
a. Please discuss the concept of site-based and physician-based learning curves.
DHHS / FDA / CDRHDHHS / FDA / CDRH91
Question 4: continued
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. Please discuss whether and/or what type of physician training should be required for this device if approved.
DHHS / FDA / CDRHDHHS / FDA / CDRH92
Question 5: Labeling
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:
DHHS / FDA / CDRHDHHS / FDA / CDRH93
Question 5: continued
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.
DHHS / FDA / CDRHDHHS / FDA / CDRH94
Question 6: Post-Market Study
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.