Ethicon TransVaginal Mesh Trial in Dallas – Day 2

J&J fails its Credo with Pelvic Mesh
Wednesday, March 19 marked the second day of an Ethicon TransVaginal Mesh Trial in Dallas. A 64-year-old Texas woman’s lawsuit was  brought against Johnson & Johnson’s Ethicon division. The woman underwent two revision surgeries after being implanted in 2011 with a transvaginal mesh sling – the TVT-O – made by Ethicon. She continues to experience pain and dyspareunia (pain during sex) which she attributes to the sling.  The case, Batiste vs. Johnson & Johnson, is in the 95th Judicial District Court of Judge Ken Molberg at the George L. Allen, Sr. Courts Building. – 600 Commerce Street, 6th Floor New Tower, Dallas, TX 75202. The trial began at 9:00 Tuesday, March 18.
 

After opening arguments from both sides, Dr. P (name withheld so defense can’t use it in red herring arguments)  was the first witness called by plaintiffs. Her testimony began after lunch on the first day and did not conclude until after 5:00 the next day, March 19, after she was cross examined for three hours by Ethicon defense attorney David Noteware of Dallas.

In response to questions from plaintiff’s attorney Tom Cartmell of Kansas City, Dr. P said that she had reviewed thousands of pages of documents from Ethicon, including company emails and presentations to doctors. Her review included some 25 depositions of Ethicon executives responsible for the development and promotion of the company’s TVT and TVT-O mesh.

“My opinion is that Ethicon did not act ethically in regard to warnings,” she testified. She presented documents she had prepared regarding the way a device company is required to present warnings about its products.

Dr. P said that a medical device maker should, “include an appropriate warning if there is reasonable evidence of an association of a serious hazard with the use of the device.” She said that “a causal relationship need not have been proved” in order for a company to warn doctors and patients, “because it can take too long to prove, and patients deserve to know risks now.” The company can’t depend on surgeons reading the latest literature regarding the science, safety and effectiveness of a given product, she testified, so the company has a duty to keep doctors informed.

She said that Ethicon operated on a passive system to discover adverse events; the company did not actively monitor product safety.

Dr. P presented a slide titled “Known Adverse Reactions by Ethicon at Launch.”

The list included, but was not limited to:

  • Groin pain, including chronic groin pain
  • Pelvic pain, including chronic pelvic pain
  • Complications related to shrinkage, causing contraction and scarring
  • Urinary problems
  • Voiding disfunction
  • De novo detrusor instability or urgency
  • Urinary Retention
  • Urinary Tract Infection
  • Dysuria
  • Hematuria
  • Worsening and recurrence of Incontinence
  • Irritation at wound site
  • Dyspareunia
  • Inflammation
  • Delayed healing
  • Complications requiring surgery
  • Nerve Damage
  • Blood vessel perforation
  • Bladder perforation
  • Hematoma

The IFU — Instructions for Use — must be truthful, accurate, fair and balanced, not false and misleading. A device maker cannot overemphasize benefits and downplay risks, Dr. P testified, because doctors using the product depend on getting fair and balanced presentations of medical devices from their manufacturer.

“Language that is silent on an issue can be just as damaging as language that is dishonest,” she said, and then presented a slide titled “Safety Information Missing from IFU: Adverse Reactions.” The list included but was not limited to:

  • Groin pain including chronic groin pain
  • Leg pain including chronic leg pain
  • Infection (only “may potentiate existing infection” is included)
  • Abscess
  • Venous Thrombosis
  • Chronic foreign body reaction
  • Delayed healing
  • Dyspareunia
  • Extrusions or erosions requiring mesh removal and/or reoperations
  • Pelvic pain, including chronic pelvic pain
  • Shrinkage, due to contractions and scarring
  • Vaginal perforation
  • Vaginal scarring
  • Urinary problems, including:
  • Urethral injury
  • Voiding disfunction
  • Urinary retention
  • Hematuria
  • Worsening or recurrence of incontinence

During Dr. P’s testimony, Mr. Cartmell used deposition video frames in which Ethicon Medical Director David Robinson admitted that he was aware of data related to chronic bone pain. Dr. Robinson also admitted in the deposition cuts that if, hypothetically, a company knew about chronic pain, it should have been disclosed prior to a patient’s agreeing to have that device implanted.

Mr. Cartmell raised an Ethicon study that ran from 2005-07, which was stopped early because it showed a large reaction occurring with the obturator approach in the TVT-O product. He also sounded a study of 100 women in 2004 in which many reported “persistent groin discomfort.” Two studies showed groin pain was eight times more likely to occur in women who had had the transobturator approach in comparison with the original TVT method of installation employed and taught by Ethicon.

Mr. Cartmell also referenced a study of 127 women which was stopped early due to excess leg pain in the TVT-O group compared with the TVT group. One of the researchers wrote: “We believed it was no longer ethical to randomize women to the TVT-O.”

Other studies were raised by Mr. Cartmell which showed a higher incidence of post operative groin pain with TVT-O vs. the TVT. Mr. Cartmell showed company emails which explained that with the TVT-O approach, the trocars — dramatically curved pic-like instruments which help install the mesh — pass closer to the obturator nerve and hence may contribute to the greater reports of groin pain with the TVT-O approach.

Mr. Cartmell presented internal emails which showed Ethicon employees were aware of the higher incidence of groin pain with the transobturator approach.

Ethicon’s Meng Chen on captured video frames from her deposition, said that she was aware of reports from patients in which they complained they had not been told they could have painful intercourse for the rest of their lives.

More internal Ethicon documents were shown from a Remetrix Issues — Ethicon’s databanks — meeting in which problems were recognized and listed by Ethicon:

1. tape exposure/erosion/extrusion very frequently repeated
2. patients did not feel there were adequate pre-op consent or risk-benefit assessment.
3. specific concerns: a. the three e’s (above) a.incontinence recurrence. c. post-op dispareunia. d. re-operations for tape excision removal, re-do sling procedure. e. type and intensity of the post-op complications disproportion to the warnings.

Mr. Noteware objected strongly to the next evidence raised by Mr. Cartmell, and the two of them and others on their teams huddled in a sidebar with Judge Ken Molberg to discuss. At issue was whether Mr. Cartmell was using a brochure in play in 2011 when Ms. Batiste had her surgery, and whether plaintiffs had properly introduced that brochure into evidence in pre-trial hearings and meetings.

In short, the next several pieces of evidence concerned whether Ethicon marketing was fair and balanced. Dr. P testified that in the brochures as in the IFU, Ethicon had not provided fair and balanced information, that the company overemphasized benefits and downplayed risks.

In this vein, Mr. Cartmell introduced an internal Ethicon email in which Laura Angelini, preparing for a meeting with doctors whom Ethicon hoped to interest in using the mesh, wrote, in all caps: “I WOULD LIKE THAT WE SPIN IT MORE ON THE SAFETY ASPECT RATHER THAN COMPLICATIONS.”

Internal emails also showed that Ethicon removed dyspareunia in presentations to AUGS — the American Uro-Gynecological Society — the members of which are important customers for Gynecare’s TVT and TVT-O products.

Another internal Ethicon email from Axel Arnaut to Medical Director Martin Weisberg requested that Ethicon be more “elusive” in presenting information to targeted doctors regarding vaginal erosions and fistulas.

Dr. P’s testimony returned to the proper standard of care. In this regard, much of Dr. P’s testimony concerned the product’s IFU, mostly concerning what was not in the IFU. This, according to Dr. P, included: chronic pelvic pain, chronic groin pain, dyspareunia, erosion requiring reoperation and removal, recurrence of incontinence.

Of Ethicon’s TVT-O IFU, Dr. P said, “It is not an adequate standard of care.” Among other concerns,she said the IFU carried no indication that erosions can occur and require reoperations.”

Another internal email produced by Mr. Cartmell which he used to continue demonstrating Ethicon’s propensity to over emphasize benefits and downplay the risks of TVT and TVT-O was an internal Ethicon email from Ethicon marketer Greg Slusser regarding an upcoming presentation at AUGS. Mr. Slusser’s email read in part: “Let’s make sure that when your peers talk to my peers they only have positive things to say about TVT. The only way to ensure this is to talk to your doctors. . . Let’s get them back on the TVT bandwagon prior to the meeting. . . peer to peer selling and validation that occurs at meetings is the most powerful type of promotion our marketing department puts together. To ensure this years AUGS is an overwhelming success let’s get the message straight.”

Dr. P explained to the jury that Ethicon’s correspondence and relationships with key opinion leaders – doctors in the field who can help sell Ethicon products to other doctors – is crucial to marketers.

Ms. Batiste’s attorney Tom Cartmell returned to a slide Dr. P had prepared, titled: “Safety Information Missing from IFU: Warnings and Precautions.”

●  Mesh extrusion or erosion may occur and be recurrent and it has been reported to occur years after the mesh has been implanted. Some will require surgery, and multiple surgeries may be necessary including removal of the mesh.

● The TVT-O mesh will cause a chronic foreign body reaction, and may cause chronic inflammation and/or scarring and contraction of the mesh. Contracture of the mesh may cause pain that can be chronic and may require surgery to remove the mesh.

● Surgery to remove the mesh, if necessary, may be difficult and morbidity associaed with explant of the mesh may be significant.

●  Dyspareunia may occur and may be chronic.

● Groin pain, which may be persistent has been reported in a significant number of women treated with TVT-O. Neuropathy resulting in gait difficulties. . .

● Groin pain, which may be persistent, has been reported in a significant number of women treated with TVT-O.  Neuropathy, resulting in gait difficulties. . .

Dr. Pence also testified that Johnson & Johnson did not investigate mesh fraying so didn’t know the consequences.

Mr. Cartmell showed an  internal Ethicon email which stated: “Fraying is inherent in the design and construction of the product. The application of tension exacerbates this issue.” (The word ‘tension’ refers to the pulling of the mesh during installation.)

One research paper comparing “Tensile properties of five commonly used mid-urethral slings” stated that TVT deforms as a result of its low stiffness. It easily “deforms when tensioning under the urethra” and there is “irreversible deformation with very low force applied.” The conclusion of this comparison was not conclusive, as the authors pondered on paper what type of mesh was best – Soft or hard tape? Elastic or very stiff?  Can all be used for same application?

Ethicon inter-department Emails from as far back as 1998 when the TVT first hit the market raised concerns about fabric memory problems, product curling, fibers crumbling and being released from the knitted structure. Ethicon determined that there was a reduction in mesh width due to roping or deconstruction of the knit when it was placed by doctors, and Ethicon’s own researchers determined that TVT released more particles than any of its competitors.

A Dr. Hilton of the UK wrote that, “Thinner meshes such as Volpene (also made by Ethicon) would be an improvement over Prolene mesh” (used in the TVT products.)

Laser cut vs. Machine Cut Mesh

Mr. Cartmell also asked Dr. P several questions regarding laser cut vs. machine cut prolene mesh. Emails from Ethicon’s Gene Kammerer read that, “Overall, surgeons preffered laser cut mesh.”

Several internal Ethicon email exchanges seemed to suggest that laser cut mesh was superior to machine cut mesh, as the machine cut type (still in use today) left a jagged edge and tended to rope more than laser cut mesh.

An internal Ethicon document from Jan. 18, 2005 compared laser cut or ultra sonic mesh to machine cut mesh, the type given the plaintiff, Ms. Batiste in 2011, and found the laser cut to be superior on several important counts.

● Particle loss is significantly reduced through the ultrasonic (US, or laser cutting) process
● US creates beaded, dull edges, not sharpened edges [as with MCM] ● US significantly reduces the “roping” effect by maintaining integrity of the knit stretching produces

Mr. Cartmell asked Dr. P why Ethicon did not switch from machine cut mesh to laser cut mesh when their own data showed laser cut to be superior. Dr. Pence said she believed that Ethicon wanted to keep giving women the machine cut mesh because the company did not want to lose its seven-year safety data. If Dr. Pence is correct, the irony is profound, if  safety is the primary concern of any medical device study.

An internal document from April 25, 2006 (five years before Ms. Batiste was implanted with machine cut mesh) received email comment from Gene Kammerer of Ethicon’s Research & Development department. Mr. Kammerer emailed several Ethicon decision makers that, “Overall, surgeons preferred laser cut mesh.”  One concern was that machine cut mesh naps/hairs on the edge.  “It scratches like Scotch Brite pads. . . ” wrote Mr. Kammerer.

In a 2003 email, Ethicon’s Axel Arnaut raises the issue that erosions (through the vagina) from machine cut  TVT mesh are due to its sharp edges.

“Ethicon knew they had a product they had improved with laser cuts,” said Dr. P. “But they decided they would not lose their data.”

Under further questioning from Mr. Cartmell, Dr. P explained that Ethicon implanted prolene mesh in two dozen beagle dogs in what was meant to be a 10-year TVT safety study, but found the degradation of the prolene mesh continued to increase after five and seven years and so halted the study after just seven years.

Mr. Cartmell then played a short video of Ethicon’s Dr. Thomas Barbolt in which Dr. Barbolt was asked if Ethicon knew the prolene material was subject to surface degredation.

“Yes,” said Dr. Barbolt.

Under more questioning by Mr. Cartmell, Dr. P said the degradation increases the risk of infection, inflammation; therefore Ethicon violated the standard of care by claiming elsewhere that there was no degradation of prolene.

Cross Examination of Dr. Pence

Attorney David Noteware of Dallas then cross examined Dr. P for defense. Mr. Noteware through questioning revisited Dr. P’s education, that she majored in microbiology and had a Ph. D in toxicology but had no medical training and had never been in an operating room to see the mesh implanted, though she had admittedly seen video of the procedure.

Mr. Noteware reminded Dr. P that she had said the IFU was not adequate, or “honest” because it did not show all the adverse events. Mr. Noteware then pointed out through questioning  that Dr. P had failed to state the authors’ conclusion in a study which Mr. Cartmell had referenced which showed 22/100 responders reported groin pain. The authors’ conclusion, Mr. Noteware read to her on the monitor facing jurors, was that, “The TVT-O is a safe and effective procedure, alternative to other treatments.” Did Dr. Pence not agree with the authors’ conclusion?

Dr. P explained that she had not broached the conclusion because she was talking about labeling. She said she could not answer whether or not she agreed with the authors. She said she would need to look and understand all the data they were looking at before she could determine whether or not she agreed with their conclusion.

Mr. Noteware then revisited a study comparing the TVT to the TVT-O found there was a 26.4% to 1.7% difference in reports of leg pain. Dr. P had used this as an example of why, in her opinion, leg pain should have been included in the IFU. Mr. Noteware disputed whether it should have been included in the IFU. He asked Dr. Pence if she had read a report from a nearby University which said there was a “high level of satisfaction” with the TVT.

She could not recall the particular report. Mr. Noteware then asked Dr. P again if she was a medical doctor, a nurse, or a biomedical engineer. Dr. P agreed that she was none of those things.

Had Dr. P ever been to any ACOG (American College of Gynecologists) or ACS (American Continence Society) or AUGS (American Uro-Gynecological Society) meetings? No, she had not, she said.

Mr. Noteware asked her how many hours she had worked on transvaginal mesh litigation and how much had she made at it. She had worked 450 hours, she said, at $500 per hour. Mr. Noteware calculated that she had then made $220,000 so far.

Mr. Noteware then asked Dr. P if she could give him a document that says all adverse events and all reasonably common side effects have to be recorded in the IFU.

“Yes,” said Dr. P. She could produce that. Mr. Noteware asked if she could produce it now. She could not but said she could bring it tomorrow if she were called back, though she had been hoping to return to her home (in California) after trial on this day.

Mr. Noteware then asked if she agreed that all surgical procedures – for the conditions of which TVT mesh is one option – present some risks. Did all these surgical procedures include risks of injury to blood vessels of the pelvis, difficulty urinating, pain, scarring, pain with intercourse, bladder and bowel injury.

“Yes,” said Dr. P. All have such risks.

Mr. Noteware then showed video captions of Ethicon’s Dr. Hart, who he said had some 5,000 operations installing the TVT mesh. Dr. Hart was asked if he thought dyspareunia needed to be put into the IFU. Dr. Hart responded that every gynecological surgeon knew that dyspareunia was a possible problem with any operation on the female pelvic floor and therefore it was not necessary to put that information as a warning in the IFU. Did Dr. P not agree with Dr. Hart on that point?

Dr. P responded, “His (Dr. Hart’s) statement is in conflict with the standard of care.”

Mr. Noteware then raised another study which Mr. Cartmell had pointed out said that animal studies showed that what Ethicon had called a transitory reaction to the mesh was not transitory. Mr. Noteworthy noted that Dr. P had neglected to read the rest of that statement, which he now read himself on the monitor: “It decreases over time to a minimal level.”

Mr. Noteworthy asked Dr. P whether she agreed with that statement. Dr. Pence responded that she would have to look at the entire study, all of its data and how it was reported and recorded before she could properly answer that question.

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