On 21 November, a judge in Australia’s Federal Court, Anna Katzmann, ruled that Ethicon and its subsidiary Johnson & Johnson had been deceptive, misleading, and negligent in rushing transvaginal products onto the market before conducting proper testing. A further ruling is scheduled in February to consider damages for more than 1350 women involved in the case.
Widely reported in the media, the court ruling is worth further scrutiny, as it raises serious questions about the approval of mesh; inherent problems with the design of mesh; the lack of information and consequently lack of informed consent; and the judge’s damning verdict on the manufacturer’s approach to regulatory approval.
At 1487 pages, the ruling (you can access it here) takes time to wade through. Given the vital contribution it makes to understanding the problems with mesh, I have tried to summarise some of the critical points. I have numbered the paragraphs (§) in the document if you want to search for the relevant texts.
The case centred on three women: Kathryn Gill, Diane Dawson, and Ann Sanders, the applicants, who between them received nine mesh devices (§1) related to the Tension-free Vaginal Tape System (for gaps in the evidence see §3068) for the treatment of stress urinary incontinence, and the Gynecare Gynemesh Prolift (§3099) and Prosima (§3106) devices for the treatment of Pelvic Organ Prolapse (POP).
In the case proceedings, “there was no dispute that all of the complications could be caused by implantation of the Ethicon Devices” (§191), and that each was clinically significant. The case primarily focussed on the magnitude of the risks, and whether they had been appropriately disclosed to the applicants (§195).
The credibility of the expert witnesses is covered in §301. Katzman was not impressed with a number of the manufacturer’s witnesses (§303), who were seen as “too eager to please the respondents” (§305). For example, Prolift erosion rates were reported to be 20.4% in a series of 917 consecutive cases. Professor Alan Lam, who was an author of the report, “tried to distance himself from this evidence” (§271); Judge Katzman found that “his attempts to resile from the higher erosion rate were quite unconvincing.” However, among the experts, there was an acceptance that so long as a “foreign body (such as a mesh implant) is present in the human body, there is likely to be an ongoing or chronic inflammatory response” (§353).
Judge Katzman also voiced concerns over the lack of testing of mesh in vaginal tissue in a wide selection of patients before market release (§340). Mechanically cut mesh was “particularly problematic,” as “it frayed and pieces of polypropylene could break off during implantation” (§351).
The size of mesh pores proved contentious: meshes with smaller pores have higher risks of infection, cause less ingrowth of tissue, and lead to more chronic pain and foreign body sensations (§479).
There was “no place for mesh with pores of less than 1 mm,” said expert witness Dr Boris Batke (§481). But pore sizes reduce after implantation: the pores can collapse altogether, and mechanical stresses can further reduce their size (§500). Under minimal strain, the Prolift mesh arms could curl, with further reduction in pore size (§510). Even a mild load of one newton has a dramatic impact on pore size. A confidential Ethicon memorandum (§484) revealed that “under this loading, the initial pore size of between 3–4 mm decreases to values down to 0.3 mm” (see page 147 for an image of this effect in the UltraPro Mesh). The pore size of the mesh before implantation will therefore not be the pore size of the mesh after implantation (§516), which the judge described as an “unacceptable design failure of the Prolift” (§519).
Another witness, Professor Klosterhalfen, stated that “polypropylene mesh products are incompatible with the female pelvis because, while the meshes are flexible, they are not elastic” (§611). He also said that “flexible structures like polypropylene meshes are only able to elongate in one direction but an elastic structure like the vagina can stretch in all directions.” This mechanical mismatch between the mesh and the pelvis can cause severe damage, including infection, erosion, and chronic pain.
In one of her most damning conclusions (§4445), Judge Katzman, referring to the certification mark that indicates conformity with health, safety, and environmental protection standards, said that Ethicon was negligent in its evaluations for market approval: “they did not justify CE marking either before Prolift was taken to market or afterwards. In other words, they were not entitled to apply the CE mark.” She also provided a stark warning for all manufacturers (§4440): “even if the literature route is followed, the manufacturer is obliged to critically review the literature and ‘duly’ justify reliance on existing clinical data. As with all the other devices, in the case of Prolift, that obligation was not discharged.”
Mrs Sanders referred to inadequate consent procedures; “I assumed, because no one told me otherwise, that it was going to be safe to be inside me for the rest of my life” (§4524).
Likewise, Kathryn Gill (§4462) highlighted that at the time she decided to have mesh inserted, there had been an absence of information on the risks of chronic severe pain and pain on intercourse; the risk of vaginal shortening or narrowing; the fact that an erosion could require multiple operations; that it might be impossible to remove the mesh; and that the mesh might be unsuitable for her because of her psoriasis. She deposed (§4465) that she would not have consented to the operation if she had been told of the following matters (reproduced in full):
(1) that erosions did not occur only in a small percentage of cases or that they were often difficult to treat and might require multiple operations;
(2) the risk of erosion was in the order of 1 in 10 or more patients experiencing the problem;
(3) there was a risk of chronic and severe pain that might not be able to be treated effectively because the mesh might not be able to be removed;
(4) there was a risk of chronic pain with intercourse which might not be able to be remedied because the mesh might not be able to be removed;
(5) the mesh was unsuitable for younger women like her who wished to remain sexually and physically active;
(6) the mesh was unsuitable for patients with an autoimmune disease like psoriasis;
(7) there was a risk of recurrence of the prolapse which would be more difficult to treat because of the presence of the mesh;
(8) there were risks of vaginal narrowing and shortening;
(9) there was a risk of contraction of the mesh, which could cause chronic pain and pain with intercourse, and which might be difficult to treat because the mesh might be unable to be removed.
There are important issues that I haven’t covered, which others might want to discuss: the role of key opinion leaders, such as the TVM group (§148); the placement of mesh (§180), the mechanism of mesh erosion (§218), pain (§229), the role of tension (§263), and the significance of the immune response and those with preexisting immune conditions (§278).
You can also read about problems with biocompatibility and lack of understanding of what constitutes an “appropriate host response” (§330); a host of issues with the instructions for use (§2836); and misclassification of the risks as rare (§4491).
Finally, achieving only the minimum requirements for regulatory approval of devices will be judged harshly in a court of law. Johnson & Johnson, have until the 20th of December to appeal the decision.
This judgment should make regulators, policymakers, health professionals, and manufacturers urgently rethink the methods for approving transvaginal mesh products.
To all those involved with mesh or affected by mesh, the judgment makes for sobering reading.
BMJ Evidence-Based Medicine publishes original evidence based research, insights and opinions on what matters for health care. (Instructions for authors)
Carl Heneghan is the editor in Chief BMJ EBM, Professor of EBM, University of Oxford and will be speaking at EBM Live, Getting Better with Evidence, on the 10th December in New Zealand on the implications of the mesh judgment.
Acknowledgement: I would like to thank Jeff Aronson for helpful comments and edits.
Competing interests: CH has received expenses and fees for his media work. He holds grant funding from the NIHR, the NIHR School of Primary Care Research and the NIHR Oxford BRC. He has received financial remuneration from an asbestos case and given free legal advice on mesh cases, and received income from the publication of a series of toolkit books published by Blackwells. On occasion, he receives expenses for teaching EBM and is also paid for his GP work in NHS out of hours. He is Editor in Chief of BMJ Evidence-Based Medicine, clinical advisor to the APPG on Surgical Mesh and an NIHR Senior Investigator. CH is also Director of CEBM and Programs in EBHC CEBM jointly runs the EvidenceLive Conference with the BMJ and the Overdiagnosis Conference with some international partners based on a non-profit model.
FEDERAL COURT OF AUSTRALIA
Gill v Ethicon Sàrl (No 5)  FCA 1905