February 1, 2013~ As the plaintiff’s case wraps up in the Linda Gross v. Ethicon trial, the deposition of the Medical Affairs Director of Ethicon (Johnson & Johnson) Europe appeared to jurors via his taped deposition. Dr. Axel Arnaud seemed dismissive of the questions asked by plaintiff attorney Adam Slater.
At times his thick French accent was difficult to understand and there were a few words between the men lost in translation. Otherwise his powerful testimony showed just how much Ethicon understood before and after the launch of Prolift and what little the company did in the name of patient safety. Thanks as always to Courtroom View Network.
Day 15 in Ms. Gross product liability lawsuit against Ethicon, a division of Johnson & Johnson, produced a mountain of documents, many generated from the European team in development both before the controversial new prolapse mesh device, Prolift was launched and after.
Dr. Axel Arnaud, the Paris-based Medical Affairs Director for Ethicon since 1992, was primarily focused on developing the Prolift, polypropylene mesh that would be delivered to doctors in a pre-cut kit. It was made of the Gynemesh PS, another Ethicon product, and now considered the leading product to market to treat women suffering from pelvic organ prolapse (POP). Not that there was any real suffering.
The company noted in a Power Point presentation that POP is a “functional disorder not a life-threatening disease.”
Still with the proper marketing, products for the aging Baby Boomer market were forecast to be a winner. Marketing was an important ingredient. At every product development or clinical data meeting was at least one marketing manager, either U.S.-based or European.
Plaintiff attorney Adam Slater asked Dr. Arnaud: ” We learn marketing people weigh in heavily on clinical data on what they need to successfully market the product?
Dr. Arnaud: “I want to disagree with that. The marketing did not have input. It was essentially medically driven.”
Later in their exchange, the doctor was careful to call Ophelie Berthier, the French marketing team member, the “European Product Manager in Charge of the Commercialization of Prolift.”
Slater asked, “Marketing?” “Yes,” said Dr. Arnaud.
There Is No Gold Standard
Documents show the developers of the new mesh product knew there was no “Gold Standard” developed yet to place transvaginal mesh. Dr. Arnaud and the French team working for Ethicon wanted to develop a “simple, safe, reproducible, logical and effective method that attract non-experts,” that is surgeons who may not have the top skills.
The first meeting of Group TVM, made up of six gynecologist and experts in pelvic floor surgeries, was held in Nice, France on June 5, 2000. The group would work with hospital centers,universities, non-profit hospitals and private clinics to coordinate logistics in France. Later three additional experts were added with expertise in gynecology. Dr. Arnaud coordinated the group.
Group TVM was focused on the novel procedure tools and technique. In September 2003, along with three U.S. doctors, they would conduct a study on the TVM procedure with three month follow-up.
An earlier study showed a post-complication rate of mesh exposure of 12.3% using the TVM technique of mesh implant using trocars or hook like devices to thread the implant into the pelvis.
Prolift had a March 2005 day of launch set in company stone.
From the two people present at the meeting from marketing, “this will be sufficient data to launch the product.”
Adverse events that were “manageable” was the goal. Dr. Arnaud said an erosion rate of 30% would be high. Generally it was between 5 to 10% but 20% would still be acceptable.
Slater: “Acceptable to who?
Arnaud: “You know 5% is great 10% is the average, 20% is the upper limit”.
Ophelie Bertier, the European marketer said in an email that shrinkage which leads to dyspareunia was an ongoing problem. Slater asked Dr. Arnaud if he thought complications could be figured out by a woman’s surgeon after the fact?
A: “If you are a device manufacturer, it’s not necessarily your role to find a solution for the complications of surgical complication. So if there is a retraction, what can the manufacturer do? Nothing. It’s the surgeon. What can the manufacturer say? There is nothing we can do.”
“When you design a product, are an inventor, you don’t know what will happen in 20 years, you don’t have a crystal ball.”
Slater asked, so Ethicon launched the product anyway?
Dr. Arnaud: ” Very frankly I can say erosion, we knew; retraction, we knew. I don’t think we hid anything to anyone. there are a lot who are benefiting from those procedures.”
“Now you are telling me I’m a very bad boy I should never have done that but I do not feel bad because we offered the world a procedure; maybe things have not gone perfectly well, but we are not hiding anything we tried to do our best; not to make money; as TVM doctors are absolutely not interested in the money.”
Before Prolift Launch
Working for Gynecare in the Netherlands, Wessel Van Dijk wrote to company officials in an email. “Gynemesh was over designed for the pelvic floor.” He asked for a substitute product, one that was as “light” as possible to reduce foreign body reaction to avoid the formation of scar tissue.
Eight months before the launch of Prolift an e-mail from Professor Jacquetin of the French TVM team knew there was still a problem with the stiffness of the Prolift material. Mesh that is stiff and had shrinkage would not be compatible in a sexually active women.
But improvements in the material would be the “next frontier.” With American Medical Systems (AMS) right on their tail with a new product launch – Launch the Prolift anyway- was the goal. On target – March 2005.
“But continue to improve and be proactive and not reactive about that.
Slater: “Did your company ever make an effort to identify how many women would experience the serious complications that would cause permanent impairment? Did you ever make an effort to quantify that?
Arnaud: “I don’t know.”
Slater: “Are you aware their erosion rate at the TVM study that counted all exposures of mesh into vagina was 20.7%?”
Arnaud: “I’m aware of that.”
Slater: “Is it your testimony to this jury that is acceptable? Yes or no?
A couple of months before the launch of Prolift, Dr. Arnaud sent an email to Ophelie Berthier, marketing for Ethicon. It requested to add a Warning to the Prolift IFU, (Instructions for use), the technical language that would go to doctors.
Dr. Aaraud had just been informed by TVM group of researches about the correlation between the removal of a uterus (hysterectomy) and an increased rate of mesh erosion and retraction that can lead to anatomical distortion of the vagina. “This must be taken into consideration in a sexually active woman.”
But the additional warning never made it into the IFU because the product insert had already been printed in time for the March 2005 launch and the launch team didn’t believe the data was strong enough to put the information in the IFU.
Doctors did not have the advantage of that warning in recommending Prolift mesh to women following a hysterectomy.
First Do No Harm
At a Gynecare presentation now two months before the March 2005 launch a “Graft or No Graft” power point presentation was given about Prolift.
Slater: “You had no long-term data regarding Prolift when you launched it?
Arnaud:” No we had no long term data when you launch a product. We had long term data about the material used,” he said.
Slater:”Did you talk to doctors who were removing mesh to determine the difficulty of removing the mesh. Did you look into that issue?”
Arnaud: “We did not specifically do that.”
Showing Dr. Arnaud pieces of mesh that were removed from a woman at the Mayo Clinic, Slater asked if Ethicon knew at the time of launch that there would be complications that would require cutting the mesh out of a woman’s body. Those complications are very rare, said Dr. Arnaud.
Slater then read his questions.
Arnaud: “We knew implanting a mesh in the human body inguinal area, abdominal wall, vaginal wall may result in the need to remove it, I can say yes we knew because its obvious when you implant something when something goes wrong you must excise it.”
Slater: ‘You knew it would take surgical skill to remove it?”
Slater showed Dr. Arnaud a report he authored in May 2005, two months after the launch of Prolift. It says:
“In summary, our conclusions in placing UlraPro within in pelvic floor as a direct substitute in sub for Gynecare PS is very reasonable.”
Slater: “That’s the conclusion in this document correct?” “Yes.”
French TVM Group
The French TVM group meanwhile continued to conduct studies on the TVM procedure itself. In one study that spanned from March 2005 to August 2006 at locations around France involving 107 patients, there was 15-25% mesh shrinkage in 60% of the cases. Among women who reported symptoms of tenderness or pain as a result, there were 21 patients or 19.6%. Dr. Arnaud said that was a significant number.
Dr. Arnaud told Slater he didn’t remember if he saw this data or not.
Mesh Is Not Bad
The message to prioritize for the new Prolift transvaginal mesh would be “Mesh is not Bad” though out 2007 said Ethicons Worldwide Marketing Director Allison London Brown. That message would echo through educational efforts and public announcements to “continue to drive sales of Prolift and Gynemesh PS.”
Two Years After the Launch of Prolift
In 2007, two years after Prolift was launched, some at the Ethicon TVM group were still not happy with the complications of mesh shrinkage and erosion. A pore size less than 1 mm led to excessive scar bridging and excessive fibrosis, both known to cause chronic pain and dyspareunia.
UltraPro mesh would be the solution in the next generation of Prolift, the Prolift+M. But increasingly the thought was that polypropylene mesh might be part of the problem.
“Polypropylene meshes might not be improvable in terms of shrinkage, we
said Dr. Peter Meier, of Ethicon Women’s
Health & Urology in an email.
Along with the conclusion by Peter Meier was
Jonathan Meek, another in the Ethicon,
Dr. Arnaud called him a “dreamer.”
“Graphs that mimic human tissue mechanical property are a dream,” he said.
“There are two kinds of people, those who dream about an ideal material and marketers, so this is fine but these people are not in the real life regarding this,” he said.”Anyone not having knowledge in this area can dream that way.”
Slater reminded him the Michel Cosson who was a French expert in pelvic organ repair and part of the French TVM group also felt polypropylene “might not be improvable in terms of shrinkage.” Arnaud said Cosson was an expert in POP repair, not in biomaterials.