The General and Plastic Surgery Devices Panel met on February 28, 2003 in Salons A, B, & C at the Gaithersburg Hilton Hotel at 620 Perry Parkway Gaithersburg, Maryland to provide advice and recommendations to the Agency for a premarket application submission and for two clinical issues.
The meeting began at 8:00 am with Mr. Stephen Rhodes updating the committee on events related to panel activities that had occurred since the panel last met in July of 2002. In his update, Mr. Rhodes indicated that on December 19, 2002, FDA released a Class II Special Controls Guidance Document for surgical sutures and that on February 11, 2003, the agency released an updated guidance document, entitled, “Guidance for Saline, Silicone Gel, and Alternative Breast Implants.”
The morning session of the panel meeting concerned a PMA (P020012) for Artes Medical USA, Inc.’s Artecoll. Artecoll is a suspension of polymethylmethacrylate (PMMA) microspheres (30-42 microns in size) in 3.5% collagen. Artecoll also contains the drug lidocaine HCl at 0.3% and various buffers in distilled water. The focus of the discussion was on the preclinical and clinical data submitted by Artes Medical USA, Inc. in the PMA. The panel was asked to provide recommendations and advice to the agency for this PMA.
Artes presented data from their randomized, controlled, multicenter (8) trial designed to determine the safety and effectiveness of Artecoll compared to a collagen implant. Artecoll or the collagen control was injected into 1-4 of the following areas in the patient’s face; glabellar folds, nasolabial folds, upper lip lines and mouth corners. Two Hundred Eighty Five (285) patients were enrolled (141 Artecoll and 144 control) into the study. Of those enrolled, 251 (128 Artecoll and 123 control) were treated. Of those treated, 233 (114 Artecoll and 119 control) were evaluated. The primary effectiveness endpoint was the mean change in the 6-point Facial Fold Assessment (FFA) Scale at 6 months following injection. The only statistically significant (p = <0.001) improvement in FFA score at 6 months was observed for nasolabial folds, where the improvement for Artecoll was 0.77 while the control change was 0. For glabellar folds, upper lip lines and mouth corners, Artecoll and control improvement in FFA scores were 0.34 and 0.32, 0.08 and 0.22 and 0.26 and 0.09, respectively. No statistically significant differences were observed for these. The total number of patients exhibiting adverse events in the Artecoll population was 21 (out of 128 treated, 16.4%) while only 16 (out of 123, 13%) of the control patients were observed to have adverse events. However, the total number of adverse events was 26 in Artecoll patients and 36 in control patients.
Following panel deliberations, the panel voted 4 (Dr. Newburger, Dr. Boykin, Dr. Miller and Dr. McGrath) for approvable with conditions to 1 (Dr. Blumenstein) against. The conditions of approval included a post approval study for safety of not less than 5 years, a contraindication for lip augmentation, physician training, and a patient educational brochure.
In the afternoon, the panel discussed clinical trial issues associated with devices intended to treat emphysema and clinical trial issues for devices intended to ablate lung tumors.
During the discussion for the clinical issues related to emphysema treatment devices, the panel recommended that the trials include only patients who are candidates for no other procedures or those that have refused other treatments. All patients should have received optimized medical treatment for 3 to 6 months before enrollment. The panel members agreed that lung volume reduction surgical patients were not the appropriate control group, but that comparisons should be made to optimized medical treatment and studies should be multicentered. Safety analyses should include an assessment of deaths, air leaks, hospital days, reoperations, decreases in FEV1, 3, 6, 9, and 12 month assessments of device positioning, ease of device removal, COPD exacerbations, intubations, bleeding, and a tabulation of patients that were discontinued due to a lack of benefit. Effectiveness determinations should include exercise capacity (increase of 10 Watts), 6 minute walk test, St George’s Quality of Life Assessment, spirometry (FEV1 increase of 12 to 15%), decrease in oxygen consumption, and increase in length of life. The panel consensus was that follow up should continue for at least 6 months for effectiveness and at least 1 year for safety.
The consensus of panel opinion for the lung tumor ablative devices was that patients with inoperable, stage 1 or stage 2, isolated tumors less than 3.5 cm in size could be included. The panel recommended that effectiveness be assessed by measuring survival, quality of life, reduction in tumor size, increase or maintenance of breathing capacity by assessment of FEV1, time to treatment failure (tumor return), pain and fever. The majority of panel members felt that CT scanning and biopsy were the best measures of measuring tumor size over time. Recommendations for follow up were at least 30-days for acute safety follow-up, 3-6 months for FEV1, a minimum of 1-year for treatment complications (with 3 to 5 preferable), 2 years for survival and all patients should be followed until time of death. The panel recommended that, radiation therapy, chemotherapy, surgical and other ablative technique patients would make appropriate controls.
Contact: David Krause, Ph.D., Executive Secretary
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