Day two of Linda Gross v Ethicon trial in an Atlantic City court brought an Ethicon engineer to the stand who was presented with a mountain of internal company documents intended to show how safety and efficacy of the Prolift transvaginal mesh took the back seat to bringing it to market ahead of the competition.
Linda Gross is a 47-year-old woman from South Dakota who had the Prolift implant in 2006. Today Gross is unable to work, sit and is in chronic pain even after 18 corrective surgeries, according to her lawyer. Hers is the first of more than 1,974 lawsuits that have been filed in the Superior Court of New Jersey (here).
Plaintiff attorney Adam Slater questioned Scott Ciarrocca, head of Research & Development for Ethicon, (a division of Johnson & Johnson) and the team leader in charge of bringing what would be known as the Gynecare Prolift mesh to market.
Ciarrocca worked with a French team of nine doctors called Groupe TVM to test the feasibility of transvaginal mesh (TVM) Dr. Michel Cosson was part of the TVM team who, according to an article published in 2011 (here), is on the speaker’s bureau of Ethicon and a paid consultant for Ethicon Women’s Health and Urology and “performs sponsored educational activities for Ethicon Women’s Health and Urology, Olympus and Ipsen.”
Also working with Groupe TVM was Professor Bernard Jacquetin who would later file a patent for the TVM which he would sell to Ethicon.
When asked during the afternoon session by an Ethicon attorney if the French doctors were being paid, Ciarrocca said he didn’t believe they were.
Research & Development of Prolift
The development of TVM was prompted by the 20-30 percent recurrence rate associated with conventional repairs using sutures. The French TVM Group chose Gynemesh PS because the Prolene Soft mesh made of polypropylene (PP) a petroleum-based byproduct, was thought to be safe, “well tolerated” and “inert” in the body according to the company.
Besides Ethicon was spearheading the research which it wanted to fast-track it to market ahead of any competitors.
The French TVM team chose to work with cadavers to train on TVM procedure. Even a skilled surgeon would have to learn how to avoid puncturing the nearby bladder, vessels, nerves or the urethra which could cause a woman to bleed internally or suffer nerve injury.
TVM was considered a new procedure so mastering the fundamentals was important before gaining proficiency.
The Prolift would later be developing using Gynemesh PS as the first TVM to come pre-cut in a box with an insertion device called a cannulas and a retrieval device to capture one end and pass it through her groin.
Plaintiff attorney Adam Slater provided internal J&J documents that showed the schedule the Prolift must complete before a March 2005 marketing date. First there was the FDA approval to sell, predicted to be granted in January 2004.
On this day Slater did not raise the point that Ethicon never sought FDA approval before marketing Prolift. It was marketed for three years without FDA approval before the FDA caught the lapse and later approved Prolift under a 510(k) application. In 2008, the company had to claim it was “substantially equivalent” to a mesh already on the market, in this case the Gynemesh PS.
*Product Features Will Justify a Premium Price As Compared to GYNEMESH PS Sheets.
*Multiple Kits Will Be Required To Fully Exploit Market.
*Adoption of Synthetic Mesh Procedure in US Will Meet Expectations.
It was assumed the clinical trial of implants with six month follow-up would be sufficient to support the Prolift launch.
Other Critical Assumptions about the project stated, “No major competitive offerings with similar features/advantages enter the market ahead of us. No significant technology development is required for this project.”
On the stand Ciarrocca confirmed if the team found problems with the mesh it would have to be brought back to development stage. It was agreed that the Clinical Study would include a minimum of 40 cases a with a six-month follow-up. The failure rate upper limit was set at 20 percent.”
“Acceptable results from the series are a condition of approval” the team agreed and would be necessary before commercial release.
EROSION AND RETRACTION
Gynemesh PS would replace defective pelvic tissue and the TVM team was doing the TVM procedures to discover whether or not the Prolift was even feasible. The Gynemesh would be held in place by passing cannulas through the obturator fascia (anterior wall) of the sacrospinous ligament to attach the arms of the mesh, then capturing the end of the mesh with a retrieval device.
Since the Prolift kit had not been developed yet, neither had the implant devices. The French doctors would improvise using whatever they could to implant the mesh into place.
Even doctors with a high skill set were having trouble placing the mesh in the blind procedure in the area of a woman’s body fraught with a high probability of hemorrhage and nerve, ligament damage. Doctors practiced placement using cadavers.
Pelvic pain after placement would not be a criteria for success.
It was shown that a key part of the training would be having the doctors feel the needle passage to ensure they pass in the right place through the right structures. The team reported, “Cadavers may not give this full experience and where possible the training surgeons need to get hands on in live surgery by either “scrubbing in” where allowed…”
“The TVM represents a MAJOR mind shift on several key aspects of prolapse surgery that may require a greater shift in thinking,” said the report. “No suturing of the mesh to the vagina or lateral structures: Passage THROUGH the sacrospinal ligaments: –All of these are new concepts and will require good back up during the education process to explain why they are essential to good results.”
The Prolift, as it would later be called, was never tested on a live human, said Ciarrocca.
FAILURE RATE EXCEEDED EXPECTATIONS
In an email dated July 19, 2003, Dr. Cosson was asked if he is seeing slippage of the arms of mesh.
Principal investigator, Dr. Cosson says about the implants,“the problem are more erosion, retraction it is possible to have a recurrence but it is usually due to a retraction of the mesh and the arms of the mesh are still in place even in those cases, sincerely Michel.
The TVM studies yielded mixed results. In the final report by Cosson, dated June 27, 2006, the conclusion was the recurrence rate at six months was 12.6%, over 20%. The failure rate at 12 months of 18.4% represented a failure rate of 26.6%.
Slater reminded the witness that the company’s own Risk Assessment said if Erosion or Recurrences of a medium impact (M) were more than 20%, the team would need to “go back into Concept Stage,” delay the launch and increase resources, according to the Gynecare Risk Assessment.
But instead the team said, “In conclusion, while this study did not meet the stringent predefined statistical criteria in terms of demonstrating an incidence of prolapse recurrence as 12 months below 20%, the absolute rate of 18.4%.. demonstrates the invaluable role of TVM in treating patients with vaginal prolapse in terms of reasonable success rates and a lower rate of recurrence/re-operation compared to other published studies.”
Slater asked Ciarrocca,” One of the leaders of this group of doctors is telling you it’s a problem and you as a responsible R&D leader said we should do something here, right?”
Ciarrocca – “No, we did not stop the problem.”
In an email by French team member Axel Arnaud, he strongly suggested that the following warning be added to the Surgical Technique Guide:
“WARNING: Early clinical experience has shown that the use of mesh through a vaginal approach can occasionally/uncommonly lead to complications such as vaginal erosion and retraction which can result in an anatomical distortion of the vaginal cavity that can interfere with sexual intercourse. Clinical data suggest the risk of such a complication is increased in case of associated hysterectomy. This must be taken in consideration when the procedure is planned in a sexually active woman. Regards Axel”
Since his email was issued in January 2005, two months before Prolift was put in the market, the IFU stock had already been “launched” said Ciarrocca. The team agreed to put it in the next IFU but the warning was not added in the 2005 or when the instructions were rewritten in 2007.
Within Johnson & Johnson many departments were involved with bringing Prolift to market. Besides Research & Development and the French medical team, Regulatory Affairs, and U.S. and worldwide marketing were involved in an exchange of emails.
It would be up to the Medical Affairs Director, Charlotte Owens to write the Clinical Expert Report to assure the safety and efficacy of the new Prolift product prior to its launch.
Medical Affairs could rely on clinical data or existing literature. It chose the literature pathway.
Ciarrocca admitted on the stand he provided Owens with a template for the Prolift Clinical Expert Report by copying the 2002 Gynemesh Clinical Expert report. Slater pointed to the similarities which even included the misspelled word “prolaspse” that appeared in both the Gynemesh report from 2002 and in the Prolift report of 2005.
By way of explanation Ciarrocca said “I copied from the Gynemesh PS as a starting point for her evaluation.”
The Product Device Design Safety Assessment (DDSA) was the responsibility of the Medical Affairs department. The design defect analysis was supposed to fully assess the risks of the product to act as a patient safety net.
Slater asked Ciarrocca: “However in Device Design Safety Assessment, chronic pain is not evaluated?
Ciarrocca: “I don’t believe chronic pain appears there.”
Slater: “You did not evaluate mesh contraction causing pain, dyspareunia or need for further surgery right?
Ciarrocca: “Those are not there.”
Ciarrocca added that dyspareunia (painful sex) would be included as “tissue trauma.” Despite multiple surgeries a woman might need to treat mesh erosion, mesh removal was never evaluated either.
The final Clinical Expert Report needed to sell the Prolift mesh based on available clinical data was signed off on by Medical Director Charlotte Owens on January 14, 2005.
The Definition of Clinical Need said that native tissue repair recurrence remained at 20% and that interviews with experienced surgeons had indicated the mesh repair was multi-directionally stretchable, with a “minimum foreign body mass, minimum foreign body reaction, and good tissue incorporation with little retraction.”
It added that within the human body: “In vivo forces and exerted strains on pelvic floor repairs during the post operative period are not known.”
Slater asked Ciarrocca, “When your company put the Prolift on the market and said it was safe and effective your company didn’t know those forces right?
Ciarrocca: “But we had clinical experience and the Gynemesh PS showed it worked well for that procedure.”
Slater: “You didn’t understand the forces on the pelvis?”
Ciarrocca: “We understood enough to know Gynemesh PS was good enough to complete that repair.”
Slater: “Did you know the forces in the pelvis?”
Ciarrocca: “To a numeric value, I guess no.”
During a brief afternoon cross examination by the attorney for Ethicon the emphasis was placed on what Ethicon did include in the Instructions for Use (IFU) included the potential for infection, inflammation, adhesion formation, fistula formation, erosion, extrusion and scarring…” and the warning, “The risk of mesh exposure may be higher when performing tvm procedure with concurrent hysterectomy.”
The IFU warned doctors to read carefully, “Training on use of Gynecare Prolift is recommended and available. Contact your company sales representative to arrange for training.”