A Female Surgical Nightmare

How a problematic medical device has escaped FDA regulation.

Lindsay Beyerstein June 13, 2012

Each year, tens of thousands of U.S. women receive mesh implants during surgery for pelvic organ prolapse.

Years of activism have made women’s health a top­ic of every­day con­ver­sa­tion. The mechan­ics of mam­mo­grams and the pros and cons of cer­vi­cal can­cer vac­cines are famil­iar, but one com­mon health prob­lem that affects mil­lions of women remains vir­tu­al­ly unknown.

When mesh works its way out through the vaginal wall and extrudes into the vagina, the woman experiences excruciating pain. During intercourse, mesh can lacerate her partner's penis.

Time, grav­i­ty and child­birth can weak­en a woman’s pelvic floor mus­cles and stretch out the lig­a­ments that hold up her uterus, blad­der and/​or bow­el, caus­ing the organs to sag and bulge into the vagi­na — or even pro­trude from it — a dis­or­der known as pelvic organ pro­lapse (POP). Up to half of all women will devel­op some degree of pro­lapse, and the diag­no­sis will become more com­mon as the Baby Boomers age. One in 10 women suf­fer­ing from pro­lapse will even­tu­al­ly need surgery to cor­rect it, and every year about 300,000 women under­go pro­lapse surgery. 

The symp­toms depend on which organs are bulging and how much. A blad­der bulging through the front wall of the vagi­na can cause incon­ti­nence, or dif­fi­cul­ty void­ing. A pro­lapsed rec­tum or small intes­tine can inter­fere with defe­ca­tion. Women with pro­lapse may report pain dur­ing sex, a vis­i­ble bulge, or a feel­ing like some­thing is about to fall out of the vagina.

The con­di­tion can be debil­i­tat­ing and demor­al­iz­ing — though rarely life-threat­en­ing. But for some patients, the cure can be worse than the disease.

Pro­lapse repair kits

In med­ical and reg­u­la­to­ry cir­cles a con­tro­ver­sy is rag­ing over the use of non-absorbable mesh for the trans­vagi­nal repair of pelvic organ pro­lapse. Use of the mesh has been linked to per­ma­nent and dis­abling com­pli­ca­tions, includ­ing chron­ic pain, nerve dam­age and infec­tion. To many health activists, syn­thet­ic trans­vagi­nal mesh is a poster child for the flaws of our med­ical device reg­u­la­tion system.

One com­mon way to repair pelvic organ pro­lapse is to shore up the sag­ging tis­sue through an inci­sion in the vagi­nal wall, a kind of surgery that has long been the pre­serve of high­ly trained pelvic recon­struc­tive sur­geons. But since the ear­ly aughts, mesh for trans­vagi­nal pro­lapse repair has been increas­ing­ly sold in kits, which typ­i­cal­ly con­tain pre-cut pieces of mesh and long nee­dles to push the mesh deep into the pelvis and anchor it to the pelvic floor. These kits have opened up POP surgery to much less expe­ri­enced surgeons.

Kits are also prof­itable for device man­u­fac­tur­ers. In 2010, 79,500 mesh kits were sold in the Unit­ed States. A sin­gle kit of ster­ile mesh and dis­pos­able instru­ments — cheap raw mate­ri­als — yields a healthy prof­it mar­gin when sold for $2,000 apiece. About 20 POP mesh prod­ucts are cleared for sale and active­ly mar­ket­ed in the Unit­ed States. 

Unfor­tu­nate­ly, the boom in trans­vagi­nal mesh kits may be based on a defec­tive sur­gi­cal the­o­ry. Tom Mar­go­lis, a Bay Area pelvic sur­geon who spe­cial­izes in remov­ing mesh, paid his own way to tes­ti­fy before an FDA meet­ing last Sep­tem­ber. He tes­ti­fied that the use of syn­thet­ic mesh for trans­vagi­nal repair of pelvic organ pro­lapse con­tra­dicts core prin­ci­ples of surgery. The vagi­na is a clean-con­t­a­m­i­nat­ed sur­gi­cal field, which means that unlike the skin of the abdomen, it can’t be ful­ly dis­in­fect­ed before surgery. Infec­tion is a risk for any type of implantable device. Pass­ing a porous mesh through a con­t­a­m­i­nat­ed field is an invi­ta­tion to infec­tion. Mar­go­lis says trans­vagi­nal mesh vio­lates the Gold­en Rule of Surgery: You shall nev­er implant a syn­thet­ic object into anyone’s body, any­where, if it’s contaminated.”

Daniel Elliott, a uro­log­ic sur­geon at the Mayo Clin­ic in Rochester, Minn., who co-signed a peti­tion by Pub­lic Cit­i­zen call­ing on the FDA to take POP mesh off the mar­ket, wrote in a pub­lic let­ter last August, All too fre­quent­ly, indus­try know­ing­ly tar­gets less expe­ri­enced sur­geons, know­ing these mesh kits have not, and nev­er will be, accept­ed by more expe­ri­enced sur­geons who are ful­ly aware of their inher­ent risk with­out benefit.”

All surgery for pelvic organ pro­lapse has risks. How­ev­er, mesh has a unique risk of com­pli­ca­tions due to a phe­nom­e­non known as ero­sion.” With­in a year, in about 10 per­cent of patients, the mesh can work its way to the sur­face of the vagi­na, or into anoth­er tis­sue plane where it isn’t sup­posed to be. Mar­go­lis argues that most ero­sion is dri­ven by infec­tion. In many cas­es, the mesh is like a giant, fes­ter­ing splin­ter, attempt­ing to work its way out. 

Mar­go­lis sees patients with mesh that has become an infect­ed for­eign body ooz­ing foul-smelling dis­charge. Some have done dam­age to adja­cent organs from the mesh itself cut­ting into oth­er organs. 

He puts it this way: It’s like a slow death sentence.”

Enmeshed in pain

When mesh works its way out through the vagi­nal wall and extrudes into the vagi­na, a woman can expe­ri­ence excru­ci­at­ing pain. Exposed mesh is also a haz­ard for her male part­ner. Dur­ing inter­course, exposed mesh can lac­er­ate his penis.

It is more like a cig­a­rette burn that leaves the entire vagi­nal wall red and inflamed, and each step you take rubs the open wound against the oth­er side,” 54-year-old Janet Holt told the FDA meet­ing in 2011. It is com­plete tor­ture.” She described how her mesh shrank by a third, fold­ed in half, and abscessed at the creas­es between her legs and her groin.

An analy­sis for the Sys­tem­at­ic Review Group of the Soci­ety of Gyne­co­log­ic Sur­geons of 110 stud­ies and 11,785 women found that mesh erod­ed in about 10 per­cent of patients. Of the patients with ero­sion, 21 per­cent were suc­cess­ful­ly treat­ed with estro­gen cream, 11 per­cent had pieces of mesh cut out in a doctor’s office, and 56 per­cent had suc­cess­ful removal surg­eries the first time around. The remain­ing 23 per­cent need­ed two or three surg­eries to get the mesh out. Lana Kee­ton, the founder of the patient advo­ca­cy group Truth In Med­i­cine, notes that some women need even more surgeries.

Once in, mesh is very dif­fi­cult to remove. Mar­go­lis has per­formed more than 100 sal­vage surg­eries to remove mesh. He likens the task to get­ting rebar out of set con­crete with­out dam­ag­ing any of the sur­round­ing water mains or elec­tri­cal cables – an almost impos­si­ble task. It is painstak­ing work, and occa­sion­al­ly, he is forced to set­tle for par­tial removal, as some of the mesh is too deeply embed­ded to remove safely.

Even when mesh is suc­cess­ful­ly removed, the chron­ic pain does not nec­es­sar­i­ly go away. And one study found that some patients with mesh repairs are more like­ly to devel­op new uri­nary incontinence. 

Many women will have good out­comes with or with­out mesh. Pro­po­nents of mesh say that the grafts cre­ate more durable repairs than non-mesh surg­eries, and that non-mesh repairs have a high fail­ure rate. A large ret­ro­spec­tive study from the pre-mesh-kit era found that 29 per­cent of women who had surgery for pelvic organ pro­lapse or incon­ti­nence had to have at least one re-oper­a­tion. Mesh advo­cates also say that try­ing to rearrange pro­lapsed pelvic organs using only native con­nec­tive tis­sue, which tends to be weak­er in women with pro­lapse to begin with, can be an exer­cise in futil­i­ty. (Skep­tics like Elliott insist skilled sur­geons can treat any can­di­date for surgery with­out mesh, and there­by elim­i­nate the risks of mesh-induced com­pli­ca­tions.) Jeff Secun­da, a vice pres­i­dent at AdvaMed, a trade asso­ci­a­tion rep­re­sent­ing med­ical device man­u­fac­tur­ers, says mesh is an impor­tant treat­ment option” with an estab­lished track record.” He adds that in recent years col­lab­o­ra­tion between the device man­u­fac­tur­ers, doc­tors and reg­u­la­to­ry bod­ies has sup­port­ed and sus­tained patient safe­ty and innovation.”

FDA begins to stir

Mesh repairs are sup­posed to be more durable, but in the last few years, the FDA has become increas­ing­ly con­cerned that may not be the case. In 2011, the FDA ana­lyzed the Medicare data­base and found that of the 212,113 patients who under­went trans­vagi­nal repair for pro­lapse, those who got mesh were 2.26 times more like­ly to need repeat surgery than those who didn’t. How­ev­er, since the study wasn’t ran­dom­ized, it’s pos­si­ble that women already at a greater risk of relapse were more like­ly to get mesh.

In 2008, the FDA warned patients and doc­tors that its post-mar­ket sur­veil­lance was pick­ing up a trou­bling pat­tern of adverse events. By 2011, the agency warned that com­pli­ca­tions from mesh were not rare, and could be seri­ous. In Sep­tem­ber 2011, the FDA held a pub­lic meet­ing to hear opin­ions about mesh reg­u­la­tion. In ear­ly 2012, the FDA ordered mesh man­u­fac­tur­ers to test the safe­ty and effi­ca­cy of their prod­ucts and report back. Mesh prod­ucts that don’t pass the tests could be tak­en off the market.

Reg­u­la­to­ry lapses

So why was mesh approved for use in POP surg­eries in the first place?

The FDA is respon­si­ble for reg­u­lat­ing all med­ical devices on the U.S. mar­ket, from the low-tech tongue depres­sor to the state-of-the-art heart valve. Drugs and med­ical devices are reg­u­lat­ed dif­fer­ent­ly, based on cer­tain assump­tions: Com­pared to drugs, devices tend to have a short­er prod­uct life cycle, may be used by rel­a­tive­ly few peo­ple, and are expect­ed to under­go incre­men­tal changes from one mod­el to the next. 

This kind of think­ing makes sense for tra­di­tion­al med­ical devices like pow­er scoot­ers and heart rate mon­i­tors. It’s more prob­lem­at­ic for per­ma­nent­ly implantable devices like pelvic mesh or arti­fi­cial hips — very few of which were on the mar­ket when Con­gress set up the cur­rent reg­u­la­to­ry frame­work for med­ical devices in 1976. A drug might wear off in a few hours, but trans­vagi­nal mesh is sup­posed to last a lifetime.

Mod­er­ate-risk (Class II) and high-risk (Class III) devices must pass an FDA review before they go on the mar­ket, which can be accom­plished by one of two ways: The man­u­fac­tur­er may sub­mit evi­dence that the device is safe and effec­tive, or it may sub­mit evi­dence that the device is sub­stan­tial­ly equiv­a­lent to anoth­er prod­uct (known in the busi­ness as a pred­i­cate”) that is already on the mar­ket. The lat­ter approach, referred to as 510(k), is much quick­er and cheap­er than the for­mer, and accounts for more than 90 per­cent of med­ical devices cleared for market. 

The 510(k) process was orig­i­nal­ly intend­ed for low­er-risk prod­ucts like sur­gi­cal gloves and hear­ing aids. It was not designed to eval­u­ate safe­ty and effec­tive­ness because it was sup­posed to be for minor upgrades to low-risk devices that had already been shown to be safe.

Polypropy­lene mesh has been used since the 1950s for her­nia repairs. In the 1970s, gyne­col­o­gists began exper­i­ment­ing with mesh for POP repairs. In 2001, the FDA — with­out review­ing clin­i­cal data or proof of safe­ty and effi­ca­cy – deter­mined that sur­gi­cal mesh intend­ed for POP repair was sub­stan­tial­ly equiv­a­lent to sur­gi­cal mesh for her­nia repair. Two years lat­er, the FDA approved the first syn­thet­ic mesh kit for POP.

510(k) is an out­ra­geous choice for any kind of implant­ed med­ical device,” says Diana M. Zuck­er­man, pres­i­dent of the Nation­al Research Cen­ter for Women & Fam­i­lies, an advo­ca­cy group that has been urg­ing the FDA to get trans­vagi­nal mesh off the market.

The stan­dard for 510(k) clear­ance is sub­stan­tial equiv­a­lence. The rea­son­ing goes some­thing like this: If Device A is safe and effec­tive, and you can show that Device B is a lot like Device A, then it may be safe to assume that B is safe and effec­tive as well.

That sounds rea­son­able until you con­sid­er that Device A may nev­er have been shown to be safe or effec­tive in the first place. Some devices were on the mar­ket before 1976 and were grand­fa­thered into the new sys­tem of regulation. 

A device can even serve as a pred­i­cate even though it has been shown to be unsafe. Under cur­rent law, the FDA must accept Device A as a valid pred­i­cate even after it has been recalled for defects that endan­ger patient health and safe­ty. As long as the intend­ed use and tech­no­log­i­cal char­ac­ter­is­tics are the same, the FDA can’t refuse to grant sub­stan­tial equiv­a­lence to B based on defects in A’s design.

The prob­lems of the sys­tem are obvi­ous. For exam­ple, mesh prod­ucts are on the mar­ket today (such as Ethicon’s Gynecare TVT) that were cleared based on their sub­stan­tial equiv­a­lence to the Pro­te­Gen blad­der sling — which was with­drawn in 1999 after hun­dreds of women report­ed severe pain, life-threat­en­ing infec­tions and neu­ro­log­i­cal com­pli­ca­tions. The Pro­te­Gen sling had orig­i­nal­ly been approved in 1996 when it was deemed sub­stan­tial­ly equiv­a­lent to an ear­li­er mesh prod­uct used for car­dio­vas­cu­lar surgery.

All sur­gi­cal mesh is cat­e­go­rized as Class II (mod­er­ate-risk). Pre-amend­ment devices in Class I (low-risk) and Class II — like her­nia mesh­es — were nev­er com­pre­hen­sive­ly eval­u­at­ed by the FDA for safe­ty and effectiveness. 

The FDA is cur­rent­ly con­sid­er­ing whether to reclas­si­fy trans­vagi­nal POP mesh as a Class III device. FDA spokesper­son Michelle Bolek explained that if this mesh is reclas­si­fied, all mesh prod­ucts, includ­ing those already on the mar­ket, will have to apply for pre­mar­ket approval. Pre­dictably, the indus­try is resist­ing the move, insist­ing that the exist­ing con­trols on Class II devices are suf­fi­cient to pro­tect the public.

The Oba­ma FDA deserves praise for tak­ing action on trans­vagi­nal mesh, but the strug­gle illus­trates why the reg­u­la­to­ry frame­work for med­ical devices needs to change. If trans­vagi­nal mesh­es had to demon­strate their safe­ty and effec­tive­ness before going on the mar­ket, the FDA wouldn’t be play­ing catch-up to rein in a prod­uct that has already hurt tens of thou­sands of women.

Lind­say Bey­er­stein is an award-win­ning inves­tiga­tive jour­nal­ist and In These Times staff writer who writes the blog Duly Not­ed. Her sto­ries have appeared in Newsweek, Salon, Slate, The Nation, Ms. Mag­a­zine, and oth­er pub­li­ca­tions. Her pho­tographs have been pub­lished in the Wall Street Jour­nal and the New York Times’ City Room. She also blogs at The Hill­man Blog (http://​www​.hill​man​foun​da​tion​.org/​h​i​l​l​m​a​nblog), a pub­li­ca­tion of the Sid­ney Hill­man Foun­da­tion, a non-prof­it that hon­ors jour­nal­ism in the pub­lic interest.
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