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.

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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.

Spain Bans Bayer Essure Sterilization Coils

Spanish Ministry of Health has called Bayer to withdraw contraceptive Essure

Posted On 20 Dec 2017By : Bioethics Observatory - Institue of Life Sciences UCVComment: 0

After civil proceedings were opened against pharmaceutical company Bayer all over the world because of the higher risks of serious adverse reactions associated with its contraceptives (see HERE), now, under the authority of the Ministry of Health of Spain, has called for pharmaceutical giant Bayer to stop marketing the contraceptive Essure and to withdraw it from the market, ” as it does not have a valid CE marking certificate”. Thus, as a precautionary measure to avoid birth control implant risks, the Spanish Agency for Medicines and Medical Devices (AEMPS) has ordered health centers and professionals who have Essure to stop using it.

The AEMPS note explains that “Essure® is a permanent contraceptive system, designed to be used as a micro-insert to block the Fallopian tubes and that acts mechanically by causing a foreign body reaction that causes blockage of the tube”. It adds that “it is not advisable to remove the device or modify the follow-up guidelines of users.” Suspension of the certificate was effective from 3 August 2017 for a period of 90 days until 2 November 2017. On 4 August, the European Union took the decision to suspend the marketing of these sterilization implants for three months, after the body responsible for renewing the certification required additional elements before reaching a decision (see further information HERE)

Slow Justice: A Slap on the Wrist of J&J Corporate Perpetrators

In Second Bellwether Trial, NJ Jury Awards $15M in Ethicon Mesh Case

A Bergen County jury returned a $15 million verdict Thursday against Johnson & Johnson subsidiary Ethicon in a suit over alleged defects in its Prolift pelvic repair product.

By Charles Toutant | December 14, 2017 at 07:15 PM

Ethicon mesh

A Bergen County jury returned a $15 million verdict Thursday against Johnson & Johnson subsidiary Ethicon in a suit over alleged defects in its Prolift pelvic repair product.

The verdict, for $4 million in compensatory damages to plaintiff Elizabeth Hrymoc, $1 million in compensatory damages to her husband, Tadeusz Hrymoc, and $10 million in punitives, was awarded after a three-week trial before Superior Court Judge Rachelle Harz.

Johnson & Johnson has promised to appeal and says it stands by its pelvic mesh products.

Thursday’s verdict is the second in a bellwether pelvic mesh case in New Jersey. It follows another for $11 million that was awarded in 2014. That verdict was later upheld by the Appellate Division, and the Supreme Court declined to take up the case.

Hrymoc, 71, who suffered vaginal pain after surgery to implant the product in 2008, is unable to have sexual intercourse or undergo a pelvic exam as a result of her injuries, said plaintiffs lawyer Adam Slater of Mazie Slater Katz & Freeman in Roseland.

The jury found that the Prolift pelvic repair system was defectively designed and failed to contain adequate warnings, and that the TVT-O system for treatment of stress urinary incontinence failed to contain adequate warnings. The punitive damages were awarded based on a finding that the Prolift design and warnings demonstrated willful and wanton disregard for the health and safety of the plaintiff. The jury, including one attorney and numerous others with master’s degrees, was “very sophisticated,” Slater said.

The resolution of the Hrymoc case means that “every single important legal ruling has been made, so trying these cases going forward is going to be very streamlined,” according to Slater. Those legal issues include what evidence is admissible on particular issues, and what jury charges are allowed, he said.

“Those orders now apply in every case. It’s going to be much easier and much more efficient. That’s very, very significant,” said Slater.

Also of note is that punitive damages have been awarded in both New Jersey Prolift suits, which requires a finding, by an enhanced, clear-and-convincing evidence standard, that the defendant showed a wanton disregard for the plaintiffs’ safety and health, Slater said.

Johnson & Johnson spokeswoman Mindy Tinsley said in a statement in response to Thursday’s verdict: “Ethicon intends to appeal this verdict, as we believe the evidence showed that the company appropriately informed surgeons of the pertinent complications and that the products were properly designed and studied.”

About 2,000 pelvic mesh suits against Ethicon are still pending in Bergen County, and in 2018 the court is likely to begin trying those cases two or three at a time, according to Slater.

About 150 pelvic mesh cases against Bard are also pending in New Jersey, he said.

In September, a Philadelphia jury returned a $57.1 million verdict against Ethicon in Ebaugh v. Ethicon. That verdict was composed of $7.1 million in compensatory damages and $50 million in punitive damages.

Tinsley’s statement continued: ”All surgeries to treat pelvic organ prolapse and stress urinary incontinence have risks, including Prolift and TVT-O, and Ethicon is always concerned when a patient experiences surgical complications. The majority of surgeons around the world continue to agree that midurethral slings like TVT-O are a suitable first line surgical option to treat stress urinary incontinence. Many surgeons also continue to support the use of pelvic mesh to treat prolapse as an important treatment option for women because the vast majority of women experience improvement in their symptoms and quality of life. Ethicon stands by, and will continue to defend, our pelvic mesh products in litigation.”

Slater was joined at trial by his firm’s David Mazie, David Freeman, Cheryll Calderon, Karen Kelsen and David Estes.

Ethicon’s lawyers included William Gage of Butler Snow in Ridgeland, Mississippi; Judith Wahrenberger of Ruprecht Hart Weeks Ricciardulli in Westfield; Kelly Crawford of Riker Danzig Scherer Hyland & Perretti in Morristown; and Philip Combs of Thomas Combs & Spann in Charleston, West Virginia.

Why Jury Trials/Verdicts Do Not Stop Medical Device Harm-for-Profit

Listen to this link: J&J defense lawyers attempt to void a $502 federal trial verdict by disassociating the 'parent' company from toxic metal-on-metal DePuy Pinnacle hips

This took place on December 7 at the New Orleans 5th District Federal Court of Appeals.

J&J Tramples on Basic Civil Rights to Jury Trial Verdict

J&J Faces High-Stakes Appeal to Toss Pinnacle Hips Judgment

By Jef Feeley

December 7, 2017, 10:16 AM CST  Bloomberg  FiDA highlight

• Challenge to $151 million judgment affects 10,000 other cases 
• Former Solicitor General Clement squares off against Ken Starr 

The stakes are high as Johnson & Johnson seeks an appeals-court ruling tossing out a $151 million judgment over its Pinnacle artificial hips in a case could foreshadow the outcome for thousands of lawsuits over the devices.

J&J and its DePuy unit, which makes the artificial hips, will have former Solicitor General Paul Clement arguing Thursday that the verdict should be reversed because there was insufficient evidence that the hips were defectively designed and deceptively marketed. The companies will also attack “highly inflammatory comments” at the trial by prominent plaintiffs’ lawyer Mark Lanier.

Kenneth Starr, the Clinton-era independent counsel, will defend the verdict in favor of five hip patients who won a $502 million verdict last year, only to see it slashed to $151 million by the trial judge. Starr will argue that there was enough evidence to support the verdict, including proof that J&J knew the metal-on-metal hips were flawed and would prematurely fail but concealed its knowledge to preserve billions in sales.

J&J, winner of only one of the four Pinnacle cases that have gone to trial since 2014, faces more than 10,000 patient suits blaming the company for selling faulty hips. The argument is scheduled for Thursday afternoon in the U.S. Circuit Court in New Orleans.

Juries in federal court in Dallas have ordered the company to pay a total of more than $1.7 billion in damages over the hips, but several of the awards were later cut by U.S. District Judge Ed Kinkeade, who is overseeing a consolidation of suits over the devices. One verdict was for more than $1 billion.

J&J Ordered to Pay $502 Million Over Pinnacle Hip Failures

J&J welcomes the court’s “review of the multiple legal issues presented by our appeal, many of which have implications for’’ the remaining Pinnacle cases, said John Beisner, a Washington-based lawyer for the company.

A central issue on appeal is whether Pinnacle’s hips were defectively designed and doomed to fail, forcing costly and painful follow-up surgeries. J&J argues that plaintiffs failed to meet a legal standard that the product was unreasonably dangerous, a safer alternative design existed, and the defect caused the injuries.

J&J also vigorously protests Kinkeade’s decision to let Lanier tell jurors at the trial about a litany of J&J’s bad acts that the company contends had nothing to do with the hips.

The judge allowed Lanier to “inflame the jury’s passions’’ by referring to almost $80 million in settlements J&J agreed to in 2011, amid claims that overseas officials bribed European doctors to implant the company’s hips and knees, the company says. Lanier should have also been barred from telling jurors that J&J paid kickbacks to “henchmen’’ of former Iraqi dictator Saddam Hussein under a United Nations program, the company argues.

The Dallas jury hit J&J with $360 million in punitive damages, which the judge reduced to $9.6 million under a Texas law limiting such awards.

Chamber Brief

The U.S. Chamber of Commerce filed a brief supporting J&J, which also argues on appeal that the plaintiffs failed to prove the company hid the risks from patients and that the trial court lacked jurisdiction.

The hip recipients say they proved a safer alternative design existed and the company’s warnings to patients were inadequate. They note that Lanier mentioned the J&J bribery scandal at the trial only after DePuy’s lawyers “opened the door’’ by hyping the company’s good works.

The plaintiffs are challenging Kinkeade’s decision to apply the punitive-damages cap, saying the measure unconstitutionally tramples on their equal-protection rights. The award was supported by the evidence, they say.

The case is Christopher v. DePuy Orthopedics, No. 16-11051, U.S. Fifth Circuit Court of Appeals (New Orleans).

— With assistance by Christie Smythe

https://www.bloomberg.com/news/articles/2017-12-07/j-j-faces-high-stakes-appeal-to-toss-pinnacle-hips-judgment