21% of clinical trials published in high- impact general medicine journals were motivated by marketing purposes rather than scientific objectives

http://www.tandfonline.com/doi/full/10.1080/08989621.2017.1405259
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Grave fraudulence in medical device research: a narrative review of the PIN seeding study for the Pinnacle hip system
Joan E. Steffen, Ella A. Fassler, Kevin J. Reardon & David S. Egilman
To cite this article: Joan E. Steffen, Ella A. Fassler, Kevin J. Reardon & David S. Egilman (2018) Grave fraudulence in medical device research: a narrative review of the PIN seeding study for the Pinnacle hip system, Accountability in Research, 25:1, 37-66, DOI: 10.1080/08989621.2017.1405259

ABSTRACT

In 2001, DePuy, a wholly-owned subsidiary of Johnson & Johnson (J&J/DePuy), initiated a seeding study called the “Multi-center, Prospective, Clinical Evaluation of Pinnacle Acetabular Implants in Total Hip Arthroplasty” (PIN Study). J&J/DePuy designed this study to develop new business opportunities during the launch of their Pinnacle Hip System (PHS) and generate survivorship data for marketing. This arti- cle, the first review of a seeding trial for a medical device, examines internal company documents relating to the PIN Study; the analysis herein focuses on the integrity of J&J/ DePuy’s research practices in conception, implementation, and analysis. J&J/DePuy violated the study protocol and manipulated data; consented participants in violation of stan- dards protecting human subjects; and did not secure Institutional Review Board approval for all study sites. J&J/ DePuy used PIN Study results as the “fundamental selling point” for the PHS. Medical device seeding trials are distinct from previously-documented pharmaceutical seeding trials because companies can profit directly from device sales and because these studies may be the first clinical evaluation of the device (as was the case for the PIN Study). Seeding trials are malleable marketing projects, not rigorous scientific studies. Regulatory bodies, physicians, and others should be vigilant for persuasive marketing accounts disguised as science.

Introduction

Seeding trials are clinical trials designed by pharmaceutical and medical device companies to promote the use of their products. They are typically conducted as part of a marketing strategy for products that are either under review, cleared, or recently approved by the U.S. Food and Drug Administration (FDA) (Hill et al. 2008; Krumholz, Egilman, and Ross 2011; Sox and Rennie 2008). Hill et al. recognize that “[s]eeding trials are
CONTACT David S. Egilman degilman@egilman.com Department of Family Medicine, Brown University 8 North Main St, Suite 404 Attleboro, MA 02703, USA
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/GACR.

Published with license by Taylor & Francis Group, LLC © 2017 [Joan E. Steffen, Ella A. Fassler, Kevin J. Reardon, and David S. Egilman] This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

designed to appear as if they answer a scientific question but primarily fulfill marketing objectives” (Hill et al. 2008). Seeding trials typically demonstrate four traits as follows (Hill et al. 2008; Kessler et al. 1994):

1. (1)  Marketing objectives influence study conception and design.
   
2. (2)  Marketing objectives influence data collection and analyses.
   
3. (3)  The study’s marketing goals are concealed from doctors, patients, and
   Institutional Review Boards (IRBs).
   
4. (4)  The study sponsor implements unscientific research practices.
   

In a recent descriptive study, Barbour et al. also found that seeding trials tended to recruit patients from a large number of study sites so that the average number of patients per site was very small (Barbour et al. 2016). These researchers concluded that 21% of clinical trials published in high- impact general medicine journals were motivated by marketing purposes rather than scientific objectives (Barbour et al. 2016).
There are several systematic reviews of company documents regarding the use of seeding trials to promote pharmaceuticals (Hill et al. 2008; Krumholz, Egilman, and Ross 2011). This is the first study of a seeding trial that was designed to promote the sale of a medical device.
Confidential internal documents made public as a result of recent litiga- tion against Johnson & Johnson and its subsidiary DePuy Synthes, offer an insight into a seeding trial conducted with the Pinnacle Hip System (PHS) implant. The PHS is a four-part modular artificial hip for total hip replace- ment surgeries, including metal, polyethylene, and ceramic liners (see Figure 1). The metal-on-metal (MoM) configuration of the PHS was the subject of recent litigation against J&J/DePuy alleging product liability and personal injury for this product.

This analysis focuses on J&J/DePuy’s clinical trial of the PHS: the “Multi- center, Prospective, Clinical Evaluation of Pinnacle Acetabular Implants in Total Hip Arthroplasty” (PIN Study). J&J/DePuy’s previously-confidential internal documents were systematically reviewed for characteristics of a seeding trial, and it was found to display all four features described above. Internal documents show that J&J/DePuy’s marketing department conceived of the PIN Study in 1999 and subsequently had an integral role in the design, funding, implementation, analysis, and dissemination of the findings. Document review and analysis also revealed the impact of marketing parti- cipation in the study conception, design, data collection and analysis, IRB, and informed consent. This systematic review contributes to the literature on seeding trials and litigation-generated data on corporate and regulatory behavior.

Follow the link to the remainder of the article!  

Published with license by Taylor & Francis Group, LLC © 2017 [Joan E. Steffen, Ella A. Fassler, Kevin J. Reardon, and David S. Egilman]

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

Pelvic Surgical Mesh: "Living in Hell"

Western Australian pelvic mesh victims criticise government response to scandal

Joanne McCarthy

21 Jul 2017, 1 p.m. FiDA highlight

• Women call on WA Health Minister to order investigation into mesh surgery research

Women allege they were used as guinea pigs in pelvic mesh trials in WA public and private hospitals

SUE Turner and Jeanette McKinnon are the Western Australian women implanted with pelvic mesh devices in public hospitals who refuse to be regarded as unfortunate statistics.

They have made submissions to a Federal Parliament Senate inquiry into pelvic mesh – with a public hearing in Perth on August 25 – listing serious, permanent and life-altering consequences of their surgeries more than a decade ago.

They want answers from WA Health Minister Roger Cook about mesh research allegedly conducted in public hospitals, and whether they are included in mesh trials for which they say they did not consent.

They are scathing of Mr Cook’s commitment to “make some enquiries” about the alleged mesh research trials, in response to questions from Fairfax Media, and have called for a full investigation into whether women were used as “mesh guinea pigs” in public health facilities.  

“Something awful happened to me in 2004 and 2005 after I had mesh put into me. My world’s just so small now,” said Mrs McKinnon, who was 46 in 2004 when she was implanted with an Australian-developed pelvic mesh device at Bentley Hospital.

“It’s like living in hell. I’m dying a very slow and agonising death.”

Victorian Senator Derryn Hinch in February successfully argued for a Senate inquiry into how some pelvic mesh devices for women’s incontinence and prolapse problems after childbirth were cleared for use in Australia over the past two decades. He compared pelvic mesh products to Thalidomide, the drug that led to birth defects in babies in the 1960s.

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(Video on link.) Senator Derryn Hinch calls for a Senate inquiry into pelvic mesh.

The aggressive marketing of many mesh devices in Australia from 2003, without sufficient evidence of their safety and efficacy, led to “one of the greatest medical scandals and abuses of mothers in Australia's history,” Senator Hinch said in a speech to Parliament.

Nearly 200 Western Australian women have responded to a survey conducted by Victorian consumer health advocacy group, Health Issues Centre, for a submission to the inquiry representing the experiences of more than 2200 Australian women implanted with pelvic mesh devices.

More than 700 women are part of a current class action against major pelvic mesh manufacturer, Johnson & Johnson, in the Federal Court in Sydney.

Sue Turner, of Perth, has sought legal advice about a class action against an Australian manufacturing company, after she was implanted with an Australian-developed pelvic mesh device at Armadale Hospital in 2007.

“I was never told the device was high risk. I was never told about trials. I would never have consented to being part of a trial.

- Sue Turner, who had pelvic mesh surgery in 2007.

”

“I had a prolapse. I just trusted the doctor and our health system when he told me it would be a pretty easy fix,” Mrs Turner said.

“I was never told the device was high risk. I was never told about trials. I would never have consented to being part of a trial. If I was told there was a risk that if things went wrong I would never have a sex life again, or live a life of sometimes unendurable pain, or be left with mesh and anchors in my body that have moved and embedded into tissue very close to major blood vessels and nerves, I would never have consented. But I wasn’t told.”

In a statement to Fairfax Media Mr Cook said he would ask the Department of Health to “make some enquiries into the research undertaken, and the cases where the implants have been used”, after two senior Western Australian doctors released a series of papers from 2005 about trials in Western Australian public and private hospitals, including Armadale Hospital, using the Australian-developed pelvic mesh device.

In a statement by a WA Health Department unit, Fairfax Media was advised there are no records of research approvals for trials involving surgery on women at public hospitals using the Australian-developed pelvic mesh device.

Mrs Turner and Perth-based Australian Pelvic Mesh Support Group founder Caz Chisholm were angered by Mr Cook’s statements that the “WA Government understands the concern this has caused for some patients”, but “there have been very few complaints received by WA Health and the Health and Disability Complaints Office”.

“What are we? Guinea pigs?” Mrs Turner said.

“I want this stuff out of my body but my doctor’s told me the surgery could be life-threatening. This isn’t about numbers. It’s about how our health system allowed these devices onto the market, and how these doctors were allowed to do this surgery in public hospitals without telling us of the risks.”

Ms Chisholm said the lack of complaints was a consequence of women being told for years that their chronic problems, including often debilitating pain, repeated serious infections, and erosion of mesh into organs including the bladder and bowel, were not linked to mesh surgery, or not being told they were implanted with mesh.

“Many women who have presented to their doctors with pain and complications have been told it is not the mesh that is the cause.

- Australian Pelvic Mesh Support Group founder Caz Chisholm

”

“Many women who have presented to their doctors with pain and complications have been told it is not the mesh that is the cause. It is only because of recent media attention about stories of women's pain and complications that women are realising their own complications are identical to the media stories,” Ms Chisholm said.

“The minister says there have been very few complaints by women, but what about the doctors treating the women? Obviously doctors aren’t reporting complications either, and are they supposed to?”

Mrs McKinnon has spent more than a decade on antibiotics.

“I came out of hospital not very well in 2004 and had my first urinary tract infection shortly after that. Then it was one urinary tract infection after another. If I come off the antibiotics I get a urinary tract infection,” she said.

She had another four major surgeries over the following year to relieve the pain and address mesh erosion into organs. 

In 2009 Mrs McKinnon was diagnosed with the auto immune condition lupus, requiring steroid treatment.

“I was normal, healthy and fit before I had that surgery. I’m only 59 and I feel like a 100-year-old. I thought all these years it was just me. It’s just the nightmare that you live.”

In a statement in June the Royal Australian College of Obstetricians and Gynaecologists said the majority of women treated with mesh for incontinence or prolapse had “a good long-term result” but “in a small number of cases the complications have been very serious”.

In a submission to the Senate inquiry Victoria’s Health Issues Centre chief executive Danny Vadasz has criticised mesh debate “framed in terms of the good outcomes of the many outweighing the unfortunate experiences of a few”.

“Our health system is built on values such as equity and a universal duty of care, not on a cost/benefit analysis that accepts the unavoidability of collateral damage,” he said, in a Health Issues Centre submission arguing Australian regulators have been “asleep at the wheel” on pelvic mesh.

Do you know more? Email jmccarthy@fairfaxmedia.com.au

http://www.theherald.com.au/story/4804268/its-like-living-in-hell/

Akathisia: GSK knew Paxil could cause adult suicide?

Who is Crazy Now? Pelvic Mesh Device Failures in Australia.

Newcastle man demands hospital records

JOANNE McCARTHY

April 14, 2016, 8:33 a.m.

THEY’RE the women told they’re going crazy – that the excruciating, extraordinary pain in their groins, backs and legs is actually all in their heads.

They’re women who received pelvic mesh implants over more than a decade from 2005 when regulators failed them, and medical devices hit the market without clinical evidence of safety or efficacy.

They’re women like Jane, 66, of Newcastle, who had mesh implanted in November, 2013, to treat prolapse. Twenty months later the pain started.

“First I was getting severe pain in my left side, then it went into my right side, then it was severe back pain. I didn’t know where the pain was coming from,” she said.

She saw doctors. They prescribed painkillers, laxatives and antibiotics for the infections she kept getting, and ran tests which came back negative. By February she was in hospital and her frantic son, Paul, was pulling no punches with doctors.

“They actually told her the pain was all in her head but she’s a different person since this started. This has absolutely broken my mother. They’ve basically experimented on women by putting these things in them, and when the women come looking for help they’re put in the too-hard basket, but no-one’s got the balls to say it,” Paul said.

Jane insists she was not told what kind of mesh device would be used during her surgery.

“I was told it was a mesh but not what brand. I was told nothing else about it and I never questioned anything,” she said.

Paul is close to tears when he describes how his once vibrant mother spends her days. She struggles to leave the house.

“She’s lucky to have one good day in three months,” he said.

He is fighting to get her medical and hospital records to determine what mesh device she received and how her surgery was conducted, as a first step to having the mesh removed.

“I spend most of my time here laying on the lounge, or in bed,” said Jane.

“You’re not living.”

She gave a date in April when another test is scheduled, then gave the kind of statement that horrifies her son: “The way I feel I could be dead by then.”

Toni Shannon is 49.

Three months after she received a mesh device in April, 2014, the inexplicable excruciating pain started. It eventually stopped her from working and left her barely able to walk 50 metres at a time. It also left her devastated by the mental consequences of shockingly severe chronic pain and debilitating fatigue.  “I felt an incredible hopelessness because I could not understand why my once strong body and mind had let me down,” she said.

Before mesh surgery: Toni Shannon and husband Eric four months before pelvic mesh surgery left Mrs Shannon with devastating complications.

The pain came in waves and stabbing bursts – deep burning pain into the bones, muscles and nerves, and jolts of nerve pain “that would stop me in my tracks”.

“It was excruciating groin pain. It was like you had a knife in your vagina with super sharp burning pains that would come with a shock. Absolutely shooting pain. Completely unexpected. Terrifying. I was really thinking, am I going crazy?”

Then there was the shutdown of once normal activities. She needed help showering and dressing. The surfing she had loved for many years was out of the question. Relationships with her husband, family and friends suffered while her life was focused on managing pain and fatigue.

“I felt my life was spiralling out of control and I often thought that dying would be a better option for myself and my family,” she said.

Hospital: Toni Shannon in an American hospital after surgery to have mesh completely removed. She cannot work and has permanent complications.

There were trips to doctors, a trip to America for surgery to completely remove the mesh, and a dawning understanding of controversies about mesh devices which she was unaware of until recently.

She is outraged that her transvaginal mesh surgery – surgery through the vagina – occurred more than two years after the American Food and Drug Administration issued its first serious warnings that complications from transvaginal mesh devices were not rare, and were potentially “life-altering” for women.

She is also outraged that the Australian Therapeutic Goods Administration allowed mesh devices on the market without the clinical evidence required to make drugs available, and that as late as 2012 it reported the likelihood that unskilled doctors, rather than the mesh devices, were responsible for any complications.

Mrs Shannon cried when she spoke about her life today. She is not working, she has lost the fitness and confidence that she was once known for, and she still experiences pain after surgery to remove the mesh that had eroded into her vagina, requiring removal from muscle, nerves, tissue and bone.

She does not know when, or if, she will work again.

Overwhelmed: Caz Chisholm has more than 100 women registered on her Australian Pelvic Mesh Support Group Facebook page launched after her mesh surgery in 2014.

“It’s an unknown future. I was right at the top in my work with a lot of responsibility, but it’s like I’m stuck in a holding pattern. It’s really like a death sentence.”

Carolyn Chisholm is founder of the Australian Pelvic Mesh Support Group.

In January 2014 she was implanted with a mesh device, at almost exactly the same time an American woman was being awarded $US3.27 million in a civil suit over the same device.

The American woman’s court case was told mesh became entangled in her internal organs, eroded through her vagina, caused infections and was unable to be completely removed from her body.

Within three months of surgery Ms Chisholm was experiencing extraordinary, excruciating pain in her groin and legs, debilitating fatigue and a skin disease.

“When I complained of this unbelievable pain I was told it was ‘just healing pain’, but I was freaking out. I was told it was probably not the mesh but I knew it was,” she said.

By November 2014 she started up a Facebook page for women with mesh problems, which became the Australian Pelvic Mesh Support Group. In the past few months Ms Chisholm and 10 other women have paid more than $30,000 each to travel to America and have their mesh completely removed.

In May the women will travel to Canberra to rally against the Therapeutic Goods Administration, which registered the first transvaginal mesh devices for prolapse surgery in Australia in 2004 and 2005, with no evidence of their safety and efficacy for prolapse surgery, and with clear warnings of the need for controlled clinical trials for related mesh devices.

http://www.standard.net.au/story/3848272/sons-fears-for-mother-broken-by-mesh-surgery/?cs=2452

FDA Commissioner Dr. Califf: The Fox is in the Henhouse!

F.D.A. Asks If Faulty Blood Monitor Tainted Xarelto Approval

By KATIE THOMAS FEB. 22, 2016

The Food and Drug Administration is investigating whether a faulty blood-testing device may have compromised the results of a clinical trial that led to the approval of Xarelto, a blockbuster anticlotting drug that has been prescribed to millions of Americans since it arrived on the market in 2011.

The agency has asked the drug’s manufacturer, Johnson & Johnson, detailed questions about whether there was evidence that the device was malfunctioning while the trial was underway, according to a legal brief filed in federal court on Monday by lawyers for patients and their families who say they were injured by the drug. The lawyers also cited internal company documents that they said showed doctors were complaining to the trial leadership during the course of the study.

The clinical trial, known as Rocket AF, was led by Dr. Robert M. Califf, currently President Obama’s nominee for head of the Food and Drug Administration. It involved more than 14,000 patients worldwide and took place from 2006 to 2010.

Xarelto, which is also known by its scientific name, rivaroxaban, is one of a new class of drugs that are seen as a replacement for warfarin, a cumbersome 60-year-old drug used to prevent strokes in people with a heart-rhythm disorder known as atrial fibrillation. Warfarin requires careful monitoring of a patient’s diet and drug regimen, and frequent blood tests to ensure that is working. If patients receive too little of the drug, they could experience a stroke. But if they receive too much, their lives could be threatened by catastrophic bleeding.

Questions about the trial have been stirring since last fall, when Johnson & Johnson and Bayer, which sells Xarelto overseas, notified regulators that the device that was used in the trial had been recalled in 2014 because it was understating patients’ risk of bleeding. The device, the INRatio sold by Alere, was used in the trial to help doctors gauge whether patients were getting the right dose of warfarin. The trial compared the number of strokes and bleeding events experienced by patients taking Xarelto to those of patients who were given warfarin.

Regulators are looking at whether the malfunctioning device might have led doctors to give patients the wrong dose of warfarin, which could have led to additional bleeding episodes and given an unfair advantage to Xarelto.

This month, researchers with the Duke Clinical Research Institute, which oversaw the trial, published their own analysis in the New England Journal of Medicine and concluded that the faulty device did not affect the trial’s outcome. A few days later, an analysis by the European Medicines Agency, the F.D.A.’s European counterpart, came to the same conclusion.

But rather than settling the matter, the analyses have raised additional questions and have come under harsh criticism from some medical experts. The Duke researchers, for example, never mentioned the existence of central laboratory tests — taken at two points during the trial — that could have been used to assess whether the device’s readings were accurate. And the analysis released by the European drug agency, while it did include those readings, was done by the companies themselves and not by independent statisticians.

“There are so many questions that are yet unaddressed,” said Dr. Harlan M. Krumholz, a cardiologist and director of the Yale University Open Data Access Project, which has an agreement with Johnson & Johnson to make the company’s data from clinical trials available to outside researchers. He has asked the company for access to the trial data, he said, and the company has agreed — but Bayer has refused.

Dr. Krumholz called on Alere to release more information about its device. “We do not know why the device did not work well,” he said.

In a statement, a spokeswoman for the F.D.A. said that while the agency was looking into the issue, it had not changed its recommendations for the drug, which “provides an important health benefit when used as directed.”

A spokeswoman for Alere declined to comment, and a representative for Duke referred to an earlier statement detailing the results of its reanalysis.

Johnson & Johnson said the INRatio device was selected because it was F.D.A.-approved and easy to use. It said it was not informed of the device recall until last September, when it and Bayer “acted with urgency, diligence and in the best interests of patients and prescribers.” The company said that it has provided answers to the questions the F.D.A. asked and that the analysis published in the New England Journal of Medicine confirmed the safety and efficacy of the drug.

A spokesman for Bayer said the company was confident in the results of the trial and dismissed the issue as being driven by plaintiffs’ lawyers, saying, “They have cherry-picked testimony and documents divorced from any context.”

Dr. Califf is the former director of the Duke Clinical Research Institute, which conducted the trial, and served as the study’s co-chairman. He has since left Duke and is now a deputy commissioner of the F.D.A. Dr. Califf, who did not respond to an email, has no role in the inquiry into the Rocket AF trial, the F.D.A. has said. The Senate was expected to vote Tuesday on whether to confirm his nomination as head of the agency.

Just as the trial was getting underway in 2006, the INRatio was facing scrutiny by the F.D.A. In 2005 and 2006, the agency sent warning letters to HemoSense, then the manufacturer of INRatio, claiming that the devices were generating “clinically significant” erroneous values and that the company, which was later acquired by Alere, was not properly investigating the complaints.

In 2014, Alere recalled the INRatio monitors, saying that they might provide inaccurate results.

However, the connection to the Rocket trial was not made public until this past fall, when a journalist for the British Medical Journal began asking the companies about it. A spokesman for Johnson & Johnson told the journal that the company had been unaware of the recall. The revelation led to the reanalysis by the Duke researchers as well as inquiries by the European Medicines Agency and the F.D.A.

But while the European agency concluded that the trial outcome was not affected by problems with the device, the F.D.A. appears to be taking a closer look, asking pointed questions about whether the company had evidence that the device was malfunctioning during the trial and what actions it took, according to the legal document, which was filed with Judge Eldon E. Fallon in the Eastern District of Louisiana.

The legal motion filed on Monday also cited internal emails that, the lawyers said, showed that some doctors were questioning the accuracy of the device while the trial was underway. The lawyers said so many concerns were raised about the device that a special program was set up to investigate the malfunctions, but none of these details were provided to the F.D.A. when Johnson & Johnson responded to the agency this month.

The Rocket trial has previously come under criticism. In 2011, the F.D.A.’s medical reviewers recommended against approval of Xarelto, citing concerns that the patients receiving warfarin during the trial were being poorly managed, which could give an unfair advantage to Xarelto.

An outside advisory committee later voted to approve the drug — although several members cited reservations — and the agency allowed it to go on the market. It has since become the best-selling drug in its class, bringing in $1.9 billion in the United States in 2015, according to Johnson & Johnson.

Some said the fact that Xarelto has been on the market since 2011 gave them faith in the safety of the product. “The real world has already made the case for this drug,” said Dr. Jürgen vom Dahl, a German cardiologist who served as an investigator in the trial, who said he did not recall encountering any problems with the device.

Dr. vom Dahl also said that he and his German colleagues have wondered whether Dr. Califf’s F.D.A. nomination was playing a role in the renewed questions about the trial. “We don’t know what is real science, and what is more politics,” he said.

But others say that plenty of questions remain, and that they are disheartened by a seeming reluctance by Duke, Johnson & Johnson and Bayer to be forthright about the problem.

“It depends on where you put the flashlight,” said Robert Powell, a clinical pharmacologist who has worked in the drug industry, as well as for six years at the F.D.A. “I think they were directing people away from the problem.”

Sabrina Tavernise contributed reporting.

Bayer Essure 'birth control' device had a WARRANTY!

 

Conceptus(R) Introduces the Only Patient Reliance Warranty for Permanent Birth Control

Essurance Promise (TM) Program Confidently Demonstrates the Essure(R) Procedure's Unprecedented Performance

  0   0   0   209

May 02, 2011 09:00 ET | Source:  Conceptus, Inc.

MOUNTAIN VIEW, Calif., May 2, 2011 (GLOBE NEWSWIRE) -- Conceptus, Inc. (Nasdaq:CPTS), developer of the Essure^® procedure, the most effective permanent birth control method available, today introduced the Essurance Promise^™ Program, the industry's first-ever patient reliance warranty program, at the American College of Obstetricians and Gynecologists 59th Annual Clinical Meeting.

The Essurance Promise^™ Program is an exclusive "out-of-pocket" payment assistance program for the Essure Confirmation Test. After a patient has had the Essure procedure and both inserts are successfully placed, she returns for her Essure Confirmation Test three months later. If she is told by her physician that the Essure procedure requires more time to be effective or she cannot rely on Essure for permanent birth for any reason at that time, the Company will pay her uncovered costs for the Essure Confirmation Test, up to a maximum of $150 per test, and in accordance with certain conditions. 

Conceptus is uniquely able to offer such a warranty program because the Essure procedure's clinical and real-world commercial performance is unsurpassed among all other permanent birth control options, including tubal ligation, vasectomy and the only other competing hysteroscopic sterilization product. For nearly a decade of clinical trial follow-up, there have been zero reported pregnancies with the Essure inserts when properly placed. Results in the commercial setting over this same time period are equally compelling and continue to reflect the Essure procedure's superb clinical performance. 

No other method of permanent birth control works better than the Essure procedure and no company other than Conceptus backs up their procedure with a reliance warranty, which gives women full confidence in this birth control choice.

"The Essurance Promise^™ Program is an innovative solution demonstrating our conviction that patients can rely upon Essure for permanent birth control. The warranty supports both physicians and patients by giving them peace of mind when they choose the Essure procedure, while emphasizing the importance of the Essure Confirmation Test," said Mark Sieczkarek, president and chief executive officer of Conceptus. "This program further advances our leadership role in the hysteroscopic permanent birth control market that we pioneered more than a decade ago."

The Essure procedure is the market leader between two competing hysteroscopic sterilization procedures and has been trusted by more than half a million women since 2002.  Following the introduction of the competitor's product last year, the market may have experienced confusion and lack of clarity regarding the differences between the two products. The Essurance Promise Program underscores Essure's unparalleled performance, including the fact that the competitor product's failure rate is 10 times higher than Essure's failure rate, based on three-year clinical data. In addition, Essure clinical trial patients have experienced zero reported pregnancies, while the competitor's product has resulted in 12 pregnancies in patients followed for five years. The Essure procedure has a proven clinical and commercial track record, but the competitor's product has yet to establish and report its long-term clinical and real-world, commercial safety and effectiveness.

A key competitive advantage of the Essure insert is its stainless steel/Nitinol inner/outer coil design, which is radiopaque and allows for visual confirmation of each insert's proper placement both during the procedure and during the Essure Confirmation Test. The competitor's insert is neither visible during the procedure nor during the confirmation test.  

"The Essurance Promise Program is unprecedented for a permanent birth control procedure. Essure is backed by a growing body of scientific data validating the optimal design characteristics and clinical performance of Essure's Nitinol coil insert, both in the FDA trials and the clinical evidence reported in the literature over the past decade," said Barbara Levy, M.D., Medical Director for Conceptus.  "I highly recommend that OBGYNs talk to their patients about the Essure procedure and the Essurance Promise Program."

Additional information on the Essurance Promise^™ Program

Federal Law prohibits any company from offering this kind of program to Medicaid or Medicare patients and is also restricted where prohibited by law. Complete program details can be found on the Conceptus physician website www.essuremd.com.

About the Essure^® Procedure

The Essure procedure, FDA approved since 2002, is the first permanent birth control method that can be performed in the comfort of a physician's office in less than 10 minutes (average hysteroscopic time) without hormones, cutting, burning or the risks associated with general anesthesia or tubal ligation. Soft, flexible inserts are placed in a woman's fallopian tubes through the cervix without incisions. Over the next three months, the body forms a natural barrier around and through the inserts to prevent sperm from reaching the egg. Three months after the Essure procedure, a doctor is able to perform an Essure Confirmation Test to confirm that the inserts are properly placed and the fallopian tubes are fully blocked, giving the patient reliance on Essure for permanent birth control.

The Essure procedure is 99.95% effective based on one year of follow up with zero pregnancies reported in clinical trials, making it the most effective form of permanent birth control on the market. The procedure is covered by most insurance plans, and when it is performed in a doctor's office the cost to the patient may be as low as a simple co-pay. Essure has been proven and trusted by physicians since 2002, with more than 500,000 women worldwide having undergone the Essure procedure.

About Conceptus, Inc.

Conceptus, Inc. is a leader in the design, development, and marketing of innovative solutions in women's healthcare. The Company manufactures and markets the Essure procedure. The Essure procedure is available in the United States, Europe, Australia, New Zealand, Canada, Mexico, Central and South America and the Middle East. The Company also promotes the GYNECARE THERMACHOICE^® Uterine Balloon Therapy System by ETHICON^™ Women's Health & Urology, a division of Ethicon, Inc., in U.S. OB/GYN physician offices.

The Conceptus, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=7961

Please visit www.essure.com for more information on the Essure procedure. Patients may call the Essure Information Center at 1-877-ESSURE-1 with questions or to find a physician in their area.

© 2011 Conceptus, Inc-- All rights reserved. Conceptus, Essure, Essurance Promise and Your Family is Complete. Your Choice is Clear are registered trademarks and service marks of Conceptus, Inc.                                                                                                                    

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Investor Relations and Public Relations Contact:
Cindy Klimstra
(650) 962-4032

- See more at: http://globenewswire.com/news-release/2011/05/02/445842/220416/en/Conceptus-R-Introduces-the-Only-Patient-Reliance-Warranty-for-Permanent-Birth-Control.html#sthash.GdM5APMu.dpuf

Medical device warranty: an antidote to industry entitlements? Congress is selling out!

The 21st Century Cures Act — Will It Take Us Back in Time?

Jerry Avorn, M.D., and Aaron S. Kesselheim, M.D., J.D., M.P.H.

June 3, 2015   (FiDA highlight)

In May 2015, the 21st Century Cures Act was introduced in the U.S. House of Representatives, with the goal of promoting the development and speeding the approval of new drugs and devices.1 Championed by the pharmaceutical, biotechnology, and device industries, the bill was approved unanimously (51 to 0) in committee and continues to be debated. If enacted into law, some of its provisions could have a profound effect on what is known about the safety and efficacy of medical products, as well as which ones become available for use.

Some aspects of the bill could indeed enhance the development of and access to new drugs. The legislation calls for annual increases in the stagnating budget for the National Institutes of Health (NIH) amounting to about 3% per year for 3 years when adjusted for inflation. It would also provide an additional $2 billion per year for 5 years to create an “NIH Innovation Fund.” Together, this support would help counteract the effects of sequestration and budget cuts that have reduced the purchasing power of the NIH to its lowest level in years. Given the crucial role that NIH-funded research plays in generating the findings on which so many new drugs are based,2 this boost would be a welcome development. Another useful provision could make deidentified data from NIH-funded clinical trials more available to researchers.

Other proposed changes could lead to less salutary outcomes for patients and the health care system. An underlying premise of the bill is the need to accelerate approval for new products, but this process is already quite efficient. A third of new drugs are currently approved on the basis of a single pivotal trial; the median size for all pivotal trials is just 760 patients. More than two thirds of new drugs are approved on the basis of studies lasting 6 months or less3 — a potential problem for medications designed to be taken for a lifetime. Once the Food and Drug Administration (FDA) starts its review, it approves new medications about as quickly as any regulatory agency in the world, evaluating nearly all new drug applications within 6 to 10 months, an impressive turnaround for such complex assessments.

Nonetheless, as introduced, the 21st Century Cures Act instructs the FDA to consider nontraditional study designs and methods of data analysis to further speed approvals. Adaptive trial designs and the use of Bayesian methods hold promise in some kinds of evaluations, particularly in oncology. However, more problematic proposals include encouraging the use of “shorter or smaller clinical trials” for devices and the request that the FDA develop criteria for relying on “evidence from clinical experience,” including “observational studies, registries, and therapeutic use” instead of randomized, controlled trials for approving new uses for existing drugs. Although such data can provide important information about drug utilization and safety once a medication is in use, there is considerable evidence that these approaches are not as rigorous or valid as randomized trials in assessing efficacy.

The bill would also encourage the FDA to rely more on biomarkers and other surrogate measures rather than actual clinical end points in assessing the efficacy of both drugs and devices. The FDA already uses surrogate end points in about half of new drug approvals.3 Some biomarkers are accurate predictors of disease risk and can be useful measures of the efficacy of a new drug (such as low-density lipoprotein cholesterol for statins). But though a drug's effect on a biomarker can make approval quicker and less costly, especially if the comparator is placebo, it may not always predict the drug's capacity to improve patient outcomes. Bevacizumab (Avastin) delayed tumor progression in advanced breast cancer but was shown not to benefit patients. Similarly, rosiglitazone (Avandia) lowered glycated hemoglobin levels in patients with diabetes even as it increased their risk of myocardial infarction. In 2013, patients began to receive a new drug for tuberculosis approved on the basis of a randomized trial relying on a surrogate measure of bacterial counts in the sputum — even though patients given the drug in that trial had a death rate four times that in the comparison group, mostly from tuberculosis.4 These provisions in the legislation would not immediately change FDA approval standards, but they would give the agency greater discretion, backed by congressional support, to approve drugs on the basis of less rigorous data.

The proposed legislation would make immediate changes with respect to new antibiotics and antifungals by enabling their approval without conventional clinical trials, if needed to treat a “serious or life-threatening infection” in patients with an “unmet medical need.” In place of proof that the antimicrobial actually decreases morbidity or mortality, the FDA would be empowered to accept nontraditional efficacy measures drawn from small studies as well as “preclinical, pharmacologic, or pathophysiologic evidence; nonclinical susceptibility and pharmacokinetic data, data from phase 2 clinical trials; and such other confirmatory evidence as the secretary [of health and human services] determines appropriate to approve the drug.” Antimicrobials approved in this manner would carry disclaimers on their labeling, but there is no evidence that such a precaution would restrict prescribing to only the most appropriate patients. If passed in its current form, the bill would also provide hospitals with a financial bonus for administering costly new but unproven antibiotics, which could encourage their more widespread use. The bill gives the secretary of health and human services the authority to expand this nontraditional approval pathway to other drug categories as well, if “the public health would benefit from expansion.”

The 21st Century Cures Act goes still further in altering the requirements for approving medical devices — an area long criticized for lack of rigor as compared with drug evaluations,5 though regulatory oversight has improved in recent years. As proposed, the new law would redefine the evidence on which high-risk devices can be approved to include case studies, registries, and articles in the medical literature, rather than more rigorous clinical trials. Another section would allow device makers to pay a third-party organization to determine whether the manufacturer can be relied on to assess the safety and effectiveness of changes it makes to its devices, in place of submitting an application to the FDA. Thus certified by the external company, a device maker would be authorized to continue to assess its own products on an ongoing basis.

Informed consent by patients in drug trials has traditionally been sacrosanct, with exceptions made only when consent is impossible to obtain or contrary to a patient's best interests. But another clause in the proposed law adds a new kind of exception: studies in which “the proposed clinical testing poses no more than minimal risk” — a major departure from current human subject protections. It is not clear who gets to determine whether a given trial of a new drug poses “minimal risk.”

Embedded in the language of the 21st Century Cures Act are some good ideas that could streamline the development and evaluation of new drugs and devices; its call for increased NIH funding may prove to be its most useful component. But political forces have also introduced other provisions that could lead to the approval of drugs and devices that are less safe or effective than existing criteria would permit.

Over the past 80 years, this country's regulatory approach has embraced steadily improving criteria for accurately assessing therapeutic efficacy and risk. Patients and physicians would not benefit from legislation that instead of catapulting us into the future, could actually bring back some of the problems we thought we had left behind in the 20th century.

http://www.nejm.org/doi/full/10.1056/NEJMp1506964?query=TOC&