January 22, 2013 ~ Much thanks to Courtroom View Network for access to the live court proceedings and graphics shown to the jury.
The Prolift surgical mesh did not undergo any FDA approval before it was marketed in March 2005. Last June Ethicon, a division of Johnson & Johnson announced it was removing Prolift and three other transvaginal meshes from the market. But for the 1,984 cases pending in Superior Court of New Jersey specifically blaming Prolift for life-altering injuries, the removal was too late.
Until Day 8 of the Linda Gross v Ethicon trial there had been no mention, outside of opening arguments, of the 800 pound gorilla in the room.
Ethicon launched its new Prolift pelvic floor repair system in March 2005 hoping to beat out other competitors with a “premium price” as previous documents have shown. But it did so without notifying the U.S Food and Drug Administration (FDA), which today’s expert witness said allowed Ethicon to evade the risks it was supposed to address under agency regulations.
Depending on which side you listen to that move either flew in the face of the regulatory agency or was business as usual.
Qualified as an expert in the workings of the FDA was Dr. Peggy Pence. She has consulted medical device and drug manufacturers for 20 years on how to bring products to market clearing FDA rules and regulations while making sure the products are safe and effective. Her lengthy resume spans 40 years and includes stints at large pharmaceutical companies, device giants and small start ups.
Dr. Pence reviewed tens of thousands of pages in this case going through clinical trials, internal e-mails and company documents as well as reviewing regulations that applied to specific questions in this case. She combed the MAUDE database, a little known and incomplete registry of adverse events or side effects that health facilities are supposed to submit to the FDA. It is the only way the agency has to keep track of complications.
FDA relies on manufacturer to provide relevant information in the initial submission. But it is an honor system when it comes to medical devices. The FDA would not know if information was not submitted.
In morning testimony, plaintiff attorney David Mazie showed Dr. Pence and the jury that Ethicon had plans to file for 510(k) approval that went back as far as June 2003.
That would mean it would have to name a “predicate device” and pay a few thousand dollars while the FDA looked over the notification paperwork before Prolift could be sold. By filing a 510(k), the company could avoid hundreds of thousands of dollars in clinical trials to assure safety and efficacy and the years it would take to do so.
But a new and unique medical device cannot undergo 510(k). A new device has no “predicate” and therefore cannot claim “substantial equivalency” to a similar device, the basis for the fast-track 510(k) approval.
Shown to the jury was a document dated October 7, 2004, more a year before the launch of Prolift showing Ethicon knew Prolift represented a “Major Mindshift” on several key aspects of pelvic organ prolapse surgery, “which may require a greater shift of thinking.”
Top surgeons who would be employed to train new recruits in the use of Prolift might take anywhere from 5 to 30 cases before understanding how to use this particular procedure.
That’s because as compared to the previous generation, the Gynemesh PS, the Prolift was pre-cut and sold in a kit. It represented a larger volume of mesh, said Dr. Pence which could lead to a greater inflammatory reaction. The “arms” of the mesh were put in locations where, if there were any complications, were difficult and dangerous to remove. The surgical technique required an incision through the vagina and buttocks to implant the mesh opening up the opportunity for nerve and blood vessel damage. And there were specific tools to implant the mesh that were part of the Prolift kit.
Technically, said Dr. Pence, there was no similar device on the market therefore 510(k) was not the appropriate pathway to the market.
With a novel device the manufacturer needs to ask the FDA to classify the device or to submit the time consuming and expensive PMA premarket application to assure patient safety and efficacy.
“All potential risks are supposed to be evaluated,” said Dr. Pence, and Ethicon failed to do so. “In my opinion it was not reasonable.”
In an excerpt of a taped deposition, a company representative said, “The reason we didn’t feel the need to was become the changes were not significant enough to warrant a 510(k).”
Prolift was launched in March 2005 out of any regulatory oversight. It was only when the FDA was notified about the new generation of mesh, the Prolift +M that Ethicon wanted to launch did the FDA even realize the Prolift was sold. By that time it had been marketed for three years. When the FDA discovered the omission, it granted approval for Prolift and the Prolift +M in 2008.
After all this was a brand new product never before used and never tested in humans.
Product precautions are supposed to be included in the product warning label or IFU (Instructions for Use). That way the end user- the doctor – can determine if a medical device is appropriate for that patient, especially important when the implant is a permanent one.
Defective product litigation can mean the product was defective in its manufacture, in its design and in its instructions and descriptions.
As expert witness Dr Pence said, “Labeling is the cornerstone of risk management and that’s why it’s so critically important.”
Attorney Mazie pointed out the IFU (Instructions for Use) or patient brochure failed to warn of dyspareunia, mesh removal, the danger of pudendal neuralgia, the lack of long term studies, what mesh will do in your body, chronic pain, that it should not be used in sexually active women. There was nothing in the patient brochure or IFU that said doctors needed specialty training.
Q- Mazie: “A patient brochure is considered labeling? “Yes.
Q-“Did the patient brochure meet the regulations and standards?
Dr Pence: “No it did not. It did not list all of the potential adverse events that should have been warned about.”
During the trial it has been repeatedly shown the important role that marketing played in bringing Prolift to market including its involvement in setting a launch date and making important decisions about adverse event warnings.
When Mazie asked if it was appropriate to have people smiling and hugging in a warning brochure, the Ethicon team objected to the question being outside of the scope.
The patient brochure also said there was a “small risk of the mesh being exposed into the vaginal canal.” Dr. Pence says she would not consider a 20% risk a small risk.
What is the downside of an incomplete patient brochure?
“If patient brochure is incomplete and is a starting point for discus with physician. If patient brochure is incomplete and IFU is as well the physician has incomplete info to discuss with the patient,” said Dr. Pence
Ethicon attorney William Gage asked Dr. Pence if she understood Linda Gross was a nurse, implying she would know enough to ask important questions. And she was asked what Dr. Benson, who implanted the mesh in Linda Gross knew or didn’t know.
A-“My responsibility was to make a decision what Ethicon’s regulatory responsibilities were and whether or not they fulfilled those.”
William Gage, the attorney for Ethicon, tried to show that under FDA rules, it is the device maker who is in the best position to determine when changes to the device could affect safety and effectiveness. Therefore it was up to Ethicon to determine whether or not to go to the FDA for clearance of the Prolift.
Gage continued insisting that Ethicon did not even have any requirements to put out a patient brochure or IFU (Instructions for use) at all. His point backfired.
Gage: “Did FDA require patient brochures? Ethicon supplied them at time of launch didn’t it?”
Pence: “FDA did not require patient brochure because FDA did not know they were marketing it.”
Showing the patient brochure to the jurors, Mr. Gage who said the IFU warned users “should be familiar with pelvic floor mesh before employing the Gynecare Prolift Pelvic Floor Repair System.” He went on that the information warned in the IFU:
“Potential adverse reactions are those typically associated with surgically implanted materials including potentiation inflammation, adhesion formation, fistula formation, erosions, extrusion, scarring that results in implant contraction. Punctures or lacerations of vessels, nerves, bladder, urethra or bowel may occur during Gynecare Prolift Guide passage and may require surgical repair.”
According to Dr. Pence says the brochure needed to be in an easily read for laymen, and didn’t go far enough to even begin a conversation between physician and patient.
As occurred with Dr. Anne Weber, Ethicon wanted the jury to know how much money Dr. Pence made as an expert witness. She answered that her company had received in excess of $200,000 in reviewing documents for the plaintiff attorneys. In addition, it was pointed out that she was also an expert in denture cream, pain pump as well as mesh litigation, contracting and consulting jobs that had supplied her with at least one-third of her income for 2012.
Mr. Gage established that a Class II medical device such as mesh may not always have to submit a 510(k) clearance notification. In some special circumstances granted under the 1976 FDA regulations, when medical devices were first grandfathered into FDA law. The decision whether cutting up the Gynemesh and include it in a kit required FDA notification was a decision for the company to make he said.
Dr. Pence reminded the jury the FDA relies on the manufacturer to weigh all of the information to make an appropriate decision.
“Because the FDA believes the manufacturer is in the best position to do that? asked Mr. Gage. “Because it is their responsibility,” answered Dr. Pence. #