January 26, 2013 ~ It was Day 11 in the Linda Gross v. Ethicon trial that brought Dr. Charlotte Owens, Worldwide Medical Affairs Director for Ethicon to the stand via videotaped deposition. Her story was remarkable for the safety and efficacy information that did not make it into the Clinical Expert Report. It was her responsibility to sign off on the new mesh, Prolift, that Ethicon, a division of Johnson & Johnson was preparing to launch.
Thanks to Courtroom View Network for access to this trial!
The Clinical Expert Report would be the final word and was designed to have all adverse events included so physicians would have a full understanding of the product they were about to permanently implant in their female patients. That was especially important since Prolift was a novel medical device – the first mesh to come in a kit with pre-cut Gynemesh PS, a brand name for a Johnson & Johnson soft Prolene mesh, and the hook-like implantation tools.
Attorney Adam Slater showed the jury a videotaped deposition of Owens who worked at Ethicon from 2003 until August 2005. Owens, an Ob-Gyn, had a meteoric rise from Kissimmee, Florida where she worked as a generalist in women’s care to WorldWide Medical Director for a global medical device company Ethicon in Somerville, New Jersey.
When she began her job, Dr. Owens had done native tissue and some mesh pelvic floor repair. She would consult with a urogynecologist on cases of a complicated nature.
In July 2006, 16 months after the Prolift launch, plaintiff Linda Gross, 41 of Watertown, South Dakota would have the Prolift permanently implanted to shore up a pelvic prolapse. The jury has been shown evidence that Gross has existed in chronic debilitating pain ever since.
Owens and the team behind the March 2005 launch decided a review of the existing literature would form the basis of the report. Dr. Owens would gather all relevant information for inclusion.
On Day 11 of Linda Gross v Ethicon, attorney Adam Slater presented the Prolift Clinical Expert Report which bore striking similarities to the Gynemesh report from 2002. The first sentence was the same. A sentence containing the misspelled word “prolaspe” appeared in both versions.
Another sentence had a misplaced word “are” in both reports.
“A recent development of using polypropylene mesh placed as a mid-urethral sling in a tension-free manner has demonstrated a high clinical success rate are and with a low complication rate.”
“A recent development of utilizing a PROLENE mesh placed as a mid-urethral sling in a tension-free manner has demonstrated a high clinical success rate are and with a low complication rate.”
Later in her deposition, Slater suggested what may have happened.
Dr. Owens was shown a December 2004 email from Sean O’Bryan the Regulatory Affairs head who suggested the Clinical Expert Report needed to be rewritten to include several bullet points. Seven seconds later in the email chain, R&D’s Scott Ciarrocca volunteered to draft the report and give it to Owens to “polish off.” It was the polished off report that contained the typos.
Slater asked if Owens had copied the report verbatim
“I was not copying it,” said Owens. “I used the relevant information for the previously document in the Prolift Clinical Expert Report” she said.
French TVM Scientists
Slater didn’t stop there. To continue to point out the similarities, he listed a number of things that didn’t make it into the Clinical Expert Report for the Prolift.
Mesh contraction never made it in the report he said and neither did the work of the French scientists working on the novel TVM (transvaginal mesh) implant procedure using the tools they were developing. In 2004 the scientists had discussed serious mesh contraction when using Gynemesh through the vagina.
Q:”You didn’t talk about that in the Clinical Expert Report correct? “No,” she said.
Q: “Despite what you say is thorough review of the literature you didn’t refer to article by very doctors who developed the Prolift?
The jury was shown a study by the French researchers developing the Prolift published in November 2004 that warned of the potential of infection, mesh exposure, hematoma and mesh contraction. That never made it into the Clinical Expert Report.
The final Clinical Report said, “tissue contraction has been used for tissue report in hernia repair, instances are rare… ..There were no instances of tissue contraction reported in the Gynecare Gynemesh clinical evaluation.”
Dr. Owens told Slater contraction was not in the Clinical Expert report she said because there was none, but “I talked about it in the IFU (Instructions for Use).”
Instructions for Use (IFU)
The French team in an email produced by Slater dating January 11, 2005, two months before the launch of Prolift, wanted a change to the IFU. The Instructions for Use, a product insert, are supposed to contain all relevant warnings, precautions, adverse events and contraindications to inform doctors about the use of the product.
Slater showed Dr. Owens an email from team member Dr. Axel Arnaud to Ophelie Berthier, Marketing Director Worldwide at Ethicon:
Subject IFU Prolift: “Ophelie: I suggest we change this to add to IFU from Axel Arnaud, “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.”
The information never made it to the IFU. The IFU product label had already been printed said R&D‘s Scott Ciarrocca In writing. “This would be a next revision addition but they want it in there ASAP.”
Slater asked if Owens thought the warning by the French doctor was appropriate given the quality of life issues a woman could suffer. Owens said “I think the warning that ended up in the IFU was appropriate.”
Mesh Removal Not Discussed
Dr. Owens said there was no study on how to remove mesh that was causing complications. Gynecare had not addressed finding a safe and effective way to remove some or all of the Prolift mesh if necessary.
Slater: “You were aware some women would suffer severe complications and could be left with lifelong pain and disability. You knew that would happen in some patients?
Owens: “We knew there would be some patients with complications with the product, yes.
Q: “Did you understand the IFU is considered under FDA regulations to be the primary label for a medical device?
Q: “Did you understand it was important to put in all adverse events and contraindications in the IFU?”
Q: “You understood at launch it could lead to dyspareunia, that patient could suffer complications that would be permanent and compromise their quality of life?
A:”Yes, we knew that may have long term complications.”
Slater showed Dr. Owens a published study of 684 patients following and how their fared following a transvaginal mesh implant. It was one of the sources of data Dr. Owens did use to show the Prolift was safe and effective and could be marketed?
In “Safety of transvaginal mesh procedure retrospective study of 684 patients” patients were followed at six weeks, three and six months after surgery, a relatively short time to give any long-term indication of success. However even at the six month review the post-surgical complication rate was 33.6%.
Slater: “When you signed off that Prolift would be a safe and effective product did you know the six month complication rate was 33.6%?”
Owens: “I don’t remember what the complication rate was at the interim analysis.”
The study also included 77 granulomas or exposures at a rate of 11.3%, 80 mesh contractions, prolapse recurrence and new stress urinary incontinence.
Researchers concluded in the report, “This preliminary study should be completed by a longer-term survey of our documents.”
Slater: “Were you aware when you said the Prolift was a safe and effective product that should be placed in patient’s bodies that one of the studies you were relying on the authors had a found relative high incidence of late post surgical complication? Did you know that yes or no?
Owens: “I was aware of several factors but can’t say I was aware of late post-surgical complications alone, but I was aware of several factors related to this study.”
Slater: “Mesh contraction and causing symptoms listed like pelvic pain, dyspareunia, dyschesia, were you aware when you used this study as a basis to say Prolift was safe, patients would suffer dyspareunia and dyschesia?
Owens: “ We were aware this was a potential with the mesh implant yes.”
Slater: “You knew it could lead to difficulty defecating?
Slater: “If you as Worldwide Medical Director had not signed off on safety and efficacy it would not have been launched correct?
Owens: “I’m one of the signators. If we didn’t feel it was safe and effective we would not have launched.
Slater: “You were Worldwide Medical director so the company was relying on you for your opinion.
Owens: “The company was relying on the entire team.”
As part of the launch of a new medical device, a Device Design Safety Assessment (DDSA) must be completed. It has to identify all potential failure modes. Owens’ job was to access and score all of the possible complications depending on severity and frequency. That way a potential device failure could be averted through warnings or design changes to the Prolift.
Dr. Owens met with a quality engineer and marketer on this project but she provided the sole medical oversight. A score of 180 or higher would be addressed in the education program.
The jurors were told the passage of the mesh guides or trocars could strike nerves and cause damage and harm urinary retention.
Slater: Please show me where on this is evaluated the harm of urinary retention? Pleases show me?”
A:”There is no specific nerve mentioned in this document.”
Q: Show me where chronic pain is mentioned? Show me where hazards are scored for dyspareunia?
A- “The term dyspareunia doesn’t appear in this document”
Q- “Is there any evaluation of vaginal distortion in this document?
Owens: “It doesn’t appear in this document
Slater: “Mesh can contract right? That hazard could lead to chronic pain.
Owens: “It can.”
Slater: “It can lead to recurrence of prolapse, dyspareunia.”
Owens: “It can.”
Slater: “It can lead to additional operations to remove the contracted mesh?”
Owens: “It can.”
Slater: “It can lead to new injuries to the woman?
Owens: “It can.”
Slater: “None have a score attached to them, those results of contraction?”
Owens: “We don’t have a score for words not in the document.”
Change to UltraPro
Just two months before the launch of Prolift, Dr. Owens was shown an email from Gene Kammerer, a principal scientist at Gynecare. His message would have brought the entire product launch to a halt. Directed to Dr. Dieter Engel, Research & Development the email said:
“I wanted to discuss with you the possibility of using the UltraPro repair in place of the Gynemesh. Without going into too much detail here, this mesh could reduce the scar contraction, formation and lower the density of the scar formation resulting in fewer cases of reoccurance of prolapse and erosion.”
Dr. Owens said she didn’t remember being informed of Gene Kammerer’s viewpoint and if a risk was reduced by using UltraPro would she wait?
“Ultimately anyone on the team would have the same feeling,” she said.