CommonHealth

On a rainy night in early September, six women gathered for dinner at a Macaroni Grill restaurant in Gaithersburg, Maryland. They had come from around the country: Utah, Georgia, Florida, New York, Texas. But their mood wasn’t festive. All six were in town to speak publicly about their personal medical traumas in front of an advisory panel for the U.S. Food and Drug Administration.

Between them, the women figured they had undergone 45 surgical procedures to try to undo the damage resulting from vaginal surgery using synthetic mesh devices. The mesh implants were supposed to free them from the intimate discomforts that millions of women face after childbirth and as they age: pelvic organ prolapse, in which stretched, weakened tissues can allow the bladder or other organs to sag or bulge into the vagina, and stress urinary incontinence, which can lead to involuntary leakage with every laugh or cough. Once implanted, the hammock-like mesh was meant to shore up the supportive pelvic tissues and help keep sagging organs in place.

But rather than fix their problems, the mesh led to a range of far more awful complications. For some, the material eroded through the vaginal lining, causing infections and nerve damage, as well as excruciating pain, the inability to sit down or urinate without a catheter, multiple hospitalizations and a halt to their sex lives.

“I was in the most horrendous pain I’ve ever experienced,” said Amy Gezon, a 43-year-old mother of three and one of the women who testified before the FDA advisory panel. “I finally ended up in the ER after expressing a desire to end my life just to escape the pain. If I knew one-tenth of the information out there in the literature…I would have never consented to this surgery.”

A Higher-Risk Device

The FDA, which has already detailed the serious complications linked to vaginal mesh surgery in a series of public health alerts – one in 2008 and an update this summer – is now considering reclassifying some of the devices into a higher-risk category that would require more evidence of safety and effectiveness, including clinical studies. A total recall of the products is unlikely — dozens of various mesh “kits” made by numerous manufacturers are on the market.

The FDA says it will make a final decision after analyzing the testimony and documentation from its advisory panel meetings in September.

Even the mesh manufacturers say they support some kind of regulatory action. Jeff Secunda, vice president for technology and regulatory affairs for medical device industry trade group AdvaMed (The Advanced Medical Technology Association), said in a statement:

“Industry remains committed to ensuring physicians and patients have appropriate information on transvaginal mesh products…In addition to the existing body of evidence supporting current products, industry supports the collection of additional clinical evidence for new transvaginal mesh devices (premarket review) and existing transvaginal mesh devices (postmarket surveillance), specifically transvaginal mesh used to treat pelvic organ prolapse. In follow-up to the FDA advisory panel hearings in September, representatives of surgical mesh manufacturers are working to arrange a meeting with FDA to further review the group’s recommendations for collecting this additional clinical evidence.”

But whatever the federal regulators decide, the proliferation of vaginal mesh has already created a major uproar in medical and legal circles and among women simply trying to cope with the tribulations of aging.

Some doctors are accusing the gynecological surgery industry of compromising patient safety for profits. Highly trained pelvic surgeons suggest that their less-specialized gynecologist colleagues are partly to blame. At the same time, hundreds of lawsuits have been filed against the makers of vaginal mesh products charging that the devices are faulty and the risks were buried under a frenzy of marketing. And consumer advocates are calling for an end to the regulatory process that allowed these devices on the market in the first place.

Clearance vs. Approval

First, some numbers: In 2010, there were at least 100,000 pelvic organ prolapse repairs using surgical mesh, and about 75,000 of those were transvaginal procedures, according to the FDA. Additionally, the agency estimates there were about 260,000 surgeries for female stress urinary incontinence, with an estimated 206,000 of those involving a surgical mesh “sling” placed under the urethra. Most of these mesh devices are composed of non-absorbable synthetic polypropylene.

Many medical devices, including the mesh products now under scrutiny, are not required to go through the rigorous approval process that drugs must face in order to win FDA approval. The language is even different: drugs are “approved,” devices are “cleared” through what’s called the 510(k) process, which simply requires that the new device is shown to be “substantially equivalent” to a comparable device already on the market.

Under this scenario, there are generally no gold-standard safety and efficacy trials; no tests in humans. “That means it’s possible to have generations of products cleared on the basis of one predicate device that was itself never studied adequately,” Dr. Anne Weber, urogynecologist and former administrator of the Female Pelvic Floor Disorders Program at the National Institute of Child Health and Human Development wrote in a 2009 article on treating prolapse.

In a report this summer, experts at the Institute of Medicine characterized the FDA’s medical device clearance process as “flawed.”

The group Public Citizen, which petitioned the FDA to ban vaginal mesh for prolapse, wrote that the experience with these devices “provides a ‘poster-child’ example of the fundamental failure” of the current process. “Despite a complete lack of clinical data demonstrating that invasive mesh devices were reasonably safe and effective for transvaginal repair of POP [pelvic organ prolapse], these devices have been heavily promoted by industry and their highly paid physician consultants. As a result, tens of thousands of women have been seriously harmed, many permanently.”

Despite the emergence of a strong anti-mesh movement, moneyed interests, such as venture capitalists, are lobbying Congress to try to ease restrictions on all types of medical devices, according to recent reports.

A Brief History

Surgical mesh has been used to repair abdominal hernias since the 1950s, the FDA notes. In the 1970s, gynecologists started using mesh products for hernia to do abdominal repair of prolapse. Twenty year later, that practice grew to include mesh for stress urinary incontinence and ultimately, prolapse repair with mesh implanted vaginally.

At first, “surgeons would cut the mesh to the desired shape…and then place the mesh through a corresponding incision. Over time, manufacturers responded to this clinical practice by developing mesh products specifically designed for SUI and POP repair,” the FDA wrote in a overview posted in September.

Transvaginal surgery with mesh was considered a more straightforward procedure for doctors not trained in abdominal surgery, says Dr. Samantha Pulliam, associate director of the Division of Urogynecology at Massachusetts General Hospital in Boston. Also, the mesh could be implanted in women whose tissue was simply too weak to use on its own for “native” prolapse repair.

In 2004, the FDA says the first manufacturers were “cleared” to sell ready-to-use mesh “kits” for prolapse repair, which contained specialized tools, surgical instruments and pre-shaped mesh.

These kits were quickly adopted not only by urogynecologists who specialized in pelvic surgery, but also by increasing numbers of general gynecologists.

Joanne, a 77-year-old widow who lives outside Boston (and didn’t want her last name used) had severe constipation and a dropped bladder and bowel due to prolapse. In 2009, after vaginal surgery in which her doctor used one of the mesh “kits,” she says she’s had no problems, and just spent a month touring Australia.

A Recalled Product

But new questions about the FDA’s “clearance” process are now being raised. A recent Bloomberg investigation reports on a vaginal mesh device made by Johnson & Johnson (as well as mesh from other companies) “cleared” by the FDA based on its equivalence to an older product that was recalled in 1999: Boston Scientific’s ProteGen Sling. (J&J, which is facing lawsuits over vaginal mesh, told Bloomberg its mesh products are safe.)

The ProteGen “had never been implanted in a human vagina prior to its clearance,” wrote urogynecologist L. Lewis Wall, a professor at Washington University School of Medicine in St. Louis in an article published in the American Journal of Obstetrics and Gynecology.” The ProteGen, for stress urinary incontinence, was recalled due to its high complication rate; the FDA called it a “misbranded” and “adulterated” product, according to a 2002 investigation published in the New Jersey Star-Ledger. (I contacted Boston Scientific with more questions about this but they did not provide answers.)

An Implant Problem

Synthetic surgical mesh is used in many thousands of surgeries each year for prolapse and urinary incontinence, and also for hernia repair. But when mesh is permanently implanted through the vagina, it turns out, things can get complicated.

Bay Area pelvic surgeon, Michael Thomas Margolis told the FDA’s advisory panel in September that the very concept of transvaginal surgery using synthetic mesh “defies core surgical doctrines” because the vagina is defined as “clean-contaminated” due to its normal flora, including Staph and E.coli bacteria, which “can not be surgically cleansed from the operative field.” Dr. Margolis, who says he’s done scores of “salvage” operations on women with mesh complications, wrote:

“The implantation of contaminated synthetic mesh through the vagina defies basic surgical tenets because by definition it is not performed in a sterile manner. In fact so-called “mesh erosion,” the most common mesh complication, is in reality “mesh infection with chronic wound breakdown.”

And removing mesh once it’s been implanted is also problematic. Here’s how Dr. Margolis described it:

What it’s like to remove mesh from the surgeon’s perspective can perhaps be appreciated by this analogy. Extirpation of vaginal mesh is akin to taking a hammer and chisel and trying to remove the rebar from a sidewalk while leaving the cement otherwise intact and not damaging the water mains and power lines below. It is difficult if not impossible to remove all the mesh and do it safely.

In addition to erosion through the vagina, the most frequent mesh complications are “pain, infection, bleeding, pain during sexual intercourse (dyspareunia), organ perforation, and urinary problems, [as well as] reports of recurrent prolapse, neuro-muscular problems, vaginal scarring/shrinkage, and emotional problems,” the FDA reports.

The agency also describes mesh contraction as “a previously unidentified risk where the mesh shrinks in the body” [it is after all, placed in a body part that is designed to expand when needed] that can lead to “severe pelvic pain, painful sexual intercourse or an inability to engage in sexual intercourse. Also, men may experience irritation and pain to the penis during sexual intercourse when the mesh is exposed in mesh erosion.”

With all the complications, you might wonder why vaginal mesh surgery has become so popular. Some experts say that if you want to know why, you have to follow the money.

Deleting The Word ‘Experimental’ In A Bulletin

If not for a controversial shift in an influential professional group publication, vaginal mesh surgery might have had a harder time gaining popularity. And some physicians say the underlying force behind the procedure’s spread is money. Back in February 2007 — before FDA’s public health alert — the American College of Obstetricians and Gynecologists issued a clinical practice bulletin on pelvic organ prolapse.

The February bulletin warned doctors and patients to consider the vaginal mesh procedure to be “experimental.” It said: “Given the limited data and frequent changes in marketed products (particularly with regard to type of mesh material itself, which is most closely associated with several of the postoperative risks, especially mesh erosion), the procedures should be considered experimental and patients should consent to surgery with that understanding.” (Bold is mine).

Seven months later, ACOG issued another bulletin on vaginal mesh surgery. This time, the word “experimental” was gone, in favor of what some might consider a softer warning: “Given the limited data and frequent changes in marketed products for vaginal surgery for prolapse repair (particularly with regard to type of mesh material itself, which is most closely associated with several of the postoperative risks, especially mesh erosion), patients should consent to surgery with an understanding of the post-operative risks and lack of long-term outcomes data. 

Experimental procedures are often not covered by third-party insurance because evidence of their safety and efficacy is lacking. And two physicians, including one of the primary authors of the original February 2007 bulletin, have said that the threat of losing that insurance money was behind the change in wording.

Dr. Anne Weber, the urogynecologist and former head of the NIH’s pelvic organ disorder program said that as the prolapse bulletin’s lead author, she vehemently opposed the change in wording. “I think ACOG was choosing to protect its clinicians’ insurance incomes over patients’ well being,” she said in an interview.

Dr. Wall, the St. Louis urogynecologist, warned in his January 2010 article that “powerful commercial interests are reshaping the field of pelvic surgery.” The ubiquity of the vaginal mesh “kits,” he wrote, “hold out the promise of quick, easy, standardized operations; higher surgical volumes; and increased profits for both the surgeon and the device manufacturer.”

In a separate article on commercial pressures and ethics, Dr. Wall (a co-petitioner on Public Citizen’s call for a ban on vaginal mesh for prolapse) offers his analysis of ACOG’s revised practice bulletin:

“What is wrong with the new language? The experimental nature of these procedures has not changed; rather, in altering the text in this way, the ACOG Committee on Practice Bulletins shifts the responsibility for using these procedures from the surgeon (who should be acting as the patient’s fiduciary) to the patient herself, as if the signing of an “informed consent” document would be some kind of “universal disinfectant” that absolves the surgeon from any responsibility for what might happen afterwards.”

ACOG’s original response came in the form of a letter published after Wall’s article. Hal C. Lawrence III, then ACOG’s vice president of practice activities (now the group’s executive vice president) wrote, in part: “Shortly after Practice Bulletin 79 was published, the College received e-mails, letters, and phone calls from ACOG Fellows who objected to the use of the word ‘experimental’ to describe the anterior and posterior vaginal prolapse surgeries. Their concerns centered on the ambiguity of the word ‘experimental’ and their perception that ‘experimental’ did not accurately reflect the wide acceptance of these surgeries.” Lawrence rejected Wall’s argument that financial or insurance considerations were at the heart of the decision.

But Dr. Lawrence’s letter drew this published response from Dr. Weber: “In fact, the ACOG staff member at the meeting of the Committee on Practice Bulletins—Gynecology described the real reason for concern: ‘…recognition that the current wording would possibly deny payment for some physicians.’ Most of the clinicians who objected to the use of the word ‘experimental’ understood only too well exactly what meaning was intended — that the use of mesh kits as procedures for prolapse lacked sufficient evidence of risk versus benefit to adequately counsel patients as to expected outcomes. Such clinicians were concerned that insurance companies would not cover procedures labeled experimental, and they were concerned about their medicolegal risk should a complication arise in the course of procedures labeled experimental.”

I called ACOG for an updated response. A spokesperson sent me this email: “The word ‘experimental’ was interpreted differently among clinicians, and suggested to some that using surgical mesh was only permitted under the auspices of clinical trials, thus potentially affecting coding and reimbursement. Others interpreted ‘experimental’ to mean simply that its use was not standard of care. The Bulletin was revised to clarify that patients should be informed of the postoperative risks and lack of long-term outcome data.”

Weber, now a private consultant who lives in Pittsburgh, told me after ACOG published the revised bulletin, she tried to draw attention to the incident. She called a few reporters and spoke to a staffer with U.S. Sen. Herbert Kohl’s special committee on aging. The committee requested more information from ACOG, including details about financial support from the drug and medical device industry. But a spokesperson for the Senate committee said no further investigation followed.

Mesh Alerts

In 2008, a year after the revised ACOG practice bulletin was published, the FDA issued the first public health alert on the “Serious complications associated with transvaginal placement of surgical mesh in repair of pelvic organ prolapse and stress urinary incontinence.”

In July, the agency updated the 2008 alert, saying that “serious complications associated with surgical mesh for transvaginal repair of POP are not rare…Furthermore, it is not clear that transvaginal POP repair with mesh is more effective than traditional non-mesh repair in all patients with POP and it may expose patients to greater risk.”

The agency cited 3,979 reports of serious complications associated with urogynecologic surgical mesh products. These adverse event reports spanned from January 1, 2005, through December 31, 2010, with 2,874 of them in the last three years. Outside experts have said the actual number of complications is likely far higher. A 2009 review in the International Urogynecology Journal cited synthetic vaginal mesh complication rates from 7% to 25% with cigarette smoking found to increase the risk of mesh erosion by up to threefold.

Complications Rising

Last year, a clinical trial comparing vaginal mesh for prolapse to traditional surgery using women’s own ligaments for repair was stopped early due to excessive complications, with more than 15 percent of patients experiencing mesh erosion. The New York Times quoted the lead author of the report, Dr. Cheryl B. Iglesia, director of female pelvic medicine and reconstructive surgery at Washington Hospital Center in the District of Columbia, saying: “The bottom line is not only there were more complications, but the mesh didn’t prove any better than traditional surgery.”

One of the key problems in the entire mesh controversy, says pelvic surgeon Samantha Pulliam, of MGH, is the criteria for selecting patients. She says in the rush to use what many thought would be a promising new device for prolapse repair, some doctors may have chosen inappropriate patients. For instance, she said, younger, fairly active women, who are still having sex and could have had alternative types of non-vaginal surgery or other treatments, were instead treated with vaginal mesh and experienced complications. “There are rare but acceptable times to use vaginal mesh,” Dr. Pulliam said. “Choosing the right patient is critical.” For instance, an older, less sexually active woman who can not have abdominal surgery or who has had recurrent prolapse after past surgeries might be a better candidate, she said.

Still, the American Urogynecologic Association put out a statement after its annual meeting Sept. 15 that the group “supports the judicious use of transvaginal mesh for [pelvic organ prolapse] repair performed only by surgeons with appropriate training on patients who have been fully informed of the risks and benefits of all available treatment options.” And a group of pelvic surgeons wrote a letter to the FDA this summer suggesting that the agency is overstating the problems with vaginal mesh. In the hands of adequately trained physicians, they wrote, and among carefully selected patients, vaginal mesh can be a useful tool.

Dr. Peter Rosenblatt, Director of Urogynecology and Reconstructive Pelvic Surgery at Mt. Auburn Hospital, a teaching hospital of Harvard Medical School in Cambridge, MA, was one of the surgeons who signed the letter. He says mesh erosion can be a “nuisance” but adds that for a minority of patients it is a serious complication. “The overwhelming majority of my patients are happy,” said Rosenblatt, who is also paid by Boston Scientific, one of the mesh manufacturers, to teach other doctors how to use the devices.

Not A Half-Court Shot, A Lay-Up

But some women with mesh complications say they simply weren’t clearly informed of the risks. Linda, a 44-year-old mother of three from South Hampton, PA is in the midst of litigation with one of the mesh makers and didn’t want her last name used. She said she went in for surgery after her bladder had dropped and was bulging into her vagina. The doctor made the procedure sound “uneventful,” she said. “He said, ‘It’s not a half-court shot, it’s a lay-up,’” she told me in an interview. Instead, Linda came out of surgery in excruciating pain, she says, with blood in her urine. She was rushed back into surgery to repair a punctured bladder. More problems followed, she said, among them: long-term self-catheterization, mesh contraction, hemorrhaging, blood clots, blood transfusions, more surgery to remove the mesh which had eroded to the point that her husband could feel it when they had sex.

Since her last surgery Linda says: “I’m leaking all the time, now I’m a pants-wetter. It’s been a nightmare.” She adds: “I’m not dying, I don’t have a terminal illness…but the last doctor I went to said ‘You’re going to be my patient for life… So, if I can get one person to not get this surgery it will be worth it.”

Kathleen, 52, of Collegeville, PA, also in the midst of litigation over mesh complications, told me she agreed to surgery on the cusp of a significant birthday. She didn’t have bladder problems, she said, but the bulge in her vagina made her feel particularly old. “I was turning 50,” she said. “I just wanted to be a better 50.”

If there’s one takeaway here, it’s this: patients must be their own most aggressive medical advocates. If you are considering this surgery, read the FDA’s suggested list of questions and take them with you to the doctor.

Amy Gezon, the Utah mom who spoke before the FDA panel, considers herself lucky. She spent about $50,000 in medical expenses and travel to get her mesh removed, and though she still has permanent scarring and recurrent pain, she says most of the mesh is now gone. She told the FDA that what has happened to aging women suffering from mesh complications is, in her opinion, “among the most egregious social injustices concerning women’s health.”

(A 2011 Favorite)