Justice Delayed - Two Device Companies Still Settling Cases from 10 Plus Years Ago

Here we go again.  After a hiatus during which the US media and perhaps parts of the government were preoccupied with such issues as the ongoing controversy over health care reform, and a government shutdown apparently arising out of this controversy, the march of legal settlements involving big health care organizations has resumed.

In alphabetical order,...


Boston Scientific

From the Minneapolis Star-Tribune on 17 October, 2013, an account of a settlement arising from alleged misbehavior that started in 2002,

A $30 million settlement between the U.S. Department of Justice and Boston Scientific will likely end a case involving the sale of defective heart devices from 2002 through 2005 by subsidiaries Guidant, Guidant Sales and Cardiac Pacemakers.

Note that the allegations were particularly egregious since they involved a company selling products they knew to be defective in ways that could prove fatal as if they were quite safe,

The settlement closes a fraudulent-claims lawsuit that alleged Guidant knowingly sold defective implantable defibrillators to health care facilities that implanted them into thousands of Medicare patients. 

In particular,

The government’s complaint said that Guidant knew as early as April 2002 that its Prizm 2 line of devices was defective and knew in November 2003 that its Renewal 1 and 2 devices were capable of short-circuiting and delivering an electric shock that 'arcs' back onto the device instead of being directed to an irregularly beating heart.

According to Boston Scientific’s website, 83 malfunctions and nine reported deaths have been connected with the Renewal devices and 40 confirmed malfunctions and five patient deaths have been associated with the Prizm devices. About 500 Renewal devices remain implanted worldwide; about 1,400 Prizm devices remain in patients, according to the website.

Although Guidant took action to fix the defects, the government alleged that the company continued to sell its remaining stock of the old, defective versions of the devices. In fact, federal officials say that as Guidant learned about the cause of the defect, it took steps to hide the problem from patients, doctors and the Food and Drug Administration.

According to the government, Guidant did not fully disclose the problem until May 2005, when two Minneapolis doctors publicly aired their concerns about one of the defibrillators after it failed to revive a 21-year-old Grand Rapids, Minn., patient. Guidant later admitted it had known for three years that the device could short-circuit, but chose not to alert doctors or the public.

This is only the latest settlement made by Boston Scientific since 2005,

Boston Scientific paid $27.5 billion to acquire Guidant in 2006. It has been paying quite a bit since in relation to Guidant’s defective defibrillators.

In 2007, Boston Scientific paid $240 million to settle claims with thousands of patients who had sued Guidant after the defective devices were recalled. Later, in February 2010, Guidant pleaded guilty to misleading the FDA about problems with the devices and paid a fine of $296 million.

In fact, the then case of the allegedly concealed implantable cardiac defibrillators (ICD) was one of the first cases of apparently unethical health care corporate management behavior leading to bad patient outcomes we discussed on Health Care Renewal.  (Look here for a more recent summary of this case.)

Yet despite the fact that this apparently deeply unethical conduct lead to patient deaths, no individual who authorized, directed or implemented the bad behavior has suffered any negative consequences for it over the eight years since the details first became public.

One physician who helped bring this case to light was also apparently concerned about the impunity of those responsible,

 Dr. Robert Hauser, one of the doctors who went public back in 2005, criticized the settlement on Thursday.

'The $30 million should have little impact on their business,' Hauser said in an e-mail. 'I find it very disturbing that such a small settlement was accepted by the DOJ in view of the magnitude of wrongdoing by Guidant management.'

Stryker Corp

This week, MLive.com reported on another settlement involving allegations of unethical behavior by a device company dating back to 2003,

 An investigation by federal authorities found that Stryker Corp. subsidiaries in five foreign countries made illicit payments and tried for several years to bribe doctors, health care professionals and government-employed officials in order to obtain or retain business.

Stryker  has agreed to pay more than $13.2 million to settle the charges.

The SEC charged the Kalamazoo-based medical technologies company with violating the Foreign Corrupt Practices Act,  alleging that its subsidiaries in Argentina, Greece, Mexico, Poland and Romania made illicit payments totaling approximately $2.2 million 'that were incorrectly described as legitimate expenses in the company’s books and records.'

The SEC said descriptions of the payments varied from a charitable donation to consulting and service contracts, travel expenses, and commissions.

The SEC states that Stryker made about $7.5 million in illicit profits as a result of the improper payments. It did not specify during what year all of the events occurred, but indicated some as far back as 2003.

Note that the payments seemed deliberately designed to corrupt health care professionals and managers, for example,

According to the SEC’s order, Stryker’s subsidiary in Greece made a purported 'donation' of nearly $200,000 in 2007 to a public university in Greece to fund a laboratory that was a pet project of a public hospital doctor. In exchange for the payment, the doctor agreed to provide business to Stryker.

Also,

The SEC stated that its investigation also found that Stryker subsidiaries bribed foreign officials by paying their expenses for trips that lacked any legitimate business purpose.

'For example, in exchange for the promise of future business from the director of a public hospital in Poland, Stryker paid travel costs for the director and her husband in May 2004,' according to the SEC. 'This included a six-night stay at a New York City hotel, attendance at two Broadway shows, and a five-day trip to Aruba.'

As in the case above, it appears that no individual who authorized, directed or implemented the questionable payments will suffer any negative consequences.  In fact, as is usual in such cases,

 The settlement does not not require Stryker to admit or deny the allegations,...

However, an SEC official did say,

 Stryker’s misconduct involved hundreds of improper payments over a number of years during which the company’s internal controls were fatally flawed. Companies that allow corruption to occur by failing to implement robust compliance programs will not be allowed to profit from their misconduct.

While Health Care Renewal has not discussed this particular case before, it is hardly the first case of bad conduct by Stryker that we have discussed.  In the past we noted
-  In 2012, a Stryker subsidiary pleaded guilty to misbranding in response to allegations that its marketers conspired to defraud physicians in order to sell a product to promote bone growth that proved harmful to patients (look here).
-  In 2010, Stryker settled a case alleging unfair and deceptive sales practices again used for bone growth accelerators (look here).  
-  In 2009, some apparently low-level Stryker employees pleaded guilty to promoting off-label use of these same products (look here). 
- In 2007, Stryker made an agreement allowing federal supervision after charges one of its units had violated anti-kickback laws when making supposed "royalty" payments, often huge, to orthopedic surgeons in connection with its production of prosthetic hips and knees.  Several other device companies signed deferred prosecution agreements, and as a result, for a time all had to make public their payments to doctors and various non-profit organizations.  (See summary here.) 

Summary

 This recent crop of settlements has some features in common.  The settlements involved multinational device companies.  The settlements occurred at least a decade after the alleged bad behavior started.  The settlements required only small payments - at least on a corporate scale -from the companies involved, but no negative consequences for anyone who authorized, directed, or implemented the bad behavior.  Finally, the settlements were made by companies who had striking past records of previous settlements of bad behavior.

The march of legal settlements demonstrates the pervasiveness of unethical behavior, often involving harm to patients or sullying of health care professionals, involving large, rich health care corporations.  It also demonstrates the impunity of the top leaders of such corporations who often make huge amounts of money despite, or perhaps because of their companies' misconduct.  Despite intermittent threats by US government officials to get tough with unethical behavior by health care corporations, this pattern has continued for years, as we have documented. 

True health care reform would hold leaders of health care organizations accountable for their organizations' behavior, and its effects on patients and health care professionals. 

Marketers' Systemic Influence over Ostensibly Scholarly, Peer-Reviewed Publications: the Medtronic Infuse BMP-2 Example

On the heels of our discussion of how one pharmaceutical company employed a "publications strategy" to commission and control randomized controlled trials to serve marketing purposes, a US Senate committee has released a report about how a device/ biotechnology company "influenced the content of articles in peer-reviewed scientific publications to present... [its product] in the best possible light."

The report was summarized by the Wall Street Journal,

A report by the Senate Finance Committee based on thousands of documents it subpoenaed from Medtronic Inc raises new questions about the integrity of the medical research underpinning one of the medical-device maker's products.

Medtronic was 'heavily involved in drafting, editing and shaping the content of medical journal articles' about the product—a bone-growth protein used in spine surgery called Infuse—even as it was paying the physicians who wrote those articles a total of $210 million for unrelated work, the Senate report alleges.

In one instance, a Medtronic employee recommended to one of the physicians not publishing a list of side effects associated with Infuse in a 2005 journal article, company emails show. Medtronic marketing officials also urged inserting language into other journal articles touting the use of Infuse as better for patients than using bone harvested from their pelvises because of the pain associated with the latter, other company documents show.

Medtronic's influence extended to preparing a physician's 2002 speech to a panel advising the Food and Drug Administration on whether to approve the drug, the report alleges. The physician's disclosure to the panel at the time suggested his testimony was independent, but the company had in fact helped him draft it and paid him as a consultant the previous year, company documents show. Medtronic later hired the physician as an executive.

In response to the Senate report, Medtronic issued a statement saying it 'vigorously' disagreed with any suggestion that 'it improperly influenced or authored any of the peer-reviewed published manuscripts.' The company also denied that it 'intended to under-report adverse events' associated with Infuse.

The Extent of the Problem

The report itself is available here. It is worth discussing some of its sections about how the company is alleged to have influenced the peer-reviewed, scholarly clinical literature in more detail.

First, it asserted that "Medtronic employees, including employees working for its marketing department, collaborated with physician authors, many of whom had significant financial relationships with Medtronic, to draft" 11 specific articles in the literature published between 2002 and 2009.

Obfuscating Adverse Effects

The report provided detail about specific instances in which Medtronic employees appeared to influence publication to further marketing objectives.  The first was apparently to cloud discussion of adverse effects of its product [italics added for emphasis]:

documents indicate that a Medtronic employee involved in editing a draft of the 2005 Journal of Bone and Joint Surgery (JBJS) article by Burkus, et al. about a similar InFuse procedure involving allograft bone (a cage made from donated bone rather than the FDA-approved titanium), recommended that 'significant detail' concerning adverse event  data should not be published.

On June 16, 2004, Dr. Julie Bearcroft, Director of Technology Management in Medtronic’s Biologics Marketing Department, wrote an e-mail to other Medtronic employees, commenting on a draft of the study, 'I have made some significant changes to this document (some at the request of Dr. Burkus) both in format and content.  In this e-mail, she asked: 'How much information should we provide relative to adverse events? . . . You will see my [note] in the attached document but I don’t think significant detail on this section is warranted.'  The referenced note in the draft article stated: 'I don’t believe we want to report in the same manner as we do in IDE studies. I personally think it is appropriate to simply report the adverse events were equivalent in the two groups without the detail.' According to an internal e-mail, the adverse events were observed in the trial and formatted in a detailed table. But following the advice of Bearcroft, this table of adverse events was not included in the published paper.

On July 3, 2004, after Medtronic edited the paper, Dr. Burkus sent a draft to his co-authors writing that 'this manuscript documents the superiority in clinical and radiographic outcomes with the use of rhBMP2 in a study population of only 133 patients.'

According to the Carragee et al. Spine Journal article published in 2011, the 2005 JBJS article 'reported no complications, such as end-plate fracture, collapse, and implant migration associated with rhBMP–2 despite the clear radiographic findings in at least the one presented case.  The e-mail exchange indicates that, in addition to Medtronic editing the manuscript without attribution, the company was recommending that the article omit a complete accounting of adverse event data, including serious adverse event data that were already considered a documented concern by FDA in similar application.
 
These types of adverse events were disclosed in Table V of a 2009 follow-up article concerning the original IDE study. Studies published in 2007 revealed that InFuse is associated with 'a clinically important early inflammatory and osteoclastic effect of the rhBMP–2 in soft tissue and bone, respectively.  In other words, Medtronic recommended against including information in the study that was ultimately revealed to have an association between In-Fuse and weakening that could lead to collapse of the bone and implant and required that patients undergo additional surgery.

Note that in this example, someone explicitly associated with marketing apparently edited a draft of a scholarly article, suggested that detail about adverse effects of the company's product be omitted, and that the published article in fact omitted such detail.

The report also included an example in which another Medtronic employee apparently tried to "tone down" the discussion of adverse effects of the product, but did so too late to influence the published version. 

Emphasizing the Adverse Effects of an Alternative to Using the Company's Product

On the other hand, the report also included an example in which it alleged that a company employee suggested adding emphasis to the drawbacks of using a management strategy that did not include use of the company's product.

Documents show that Medtronic edited draft publications to stress the pain patients experienced from undergoing a bone graft procedure instead of receiving InFuse. Medtronic markets InFuse as a less painful alternative to bone graft procedures for patients undergoing spinal fusion surgery.

In particular,

After receiving a draft of an early InFuse study 52 to review in October 2001, Medtronic’s Neil Beals, whose 'primary job responsibility was to manage Biologics marketing programs and initiatives,'  recommended that the physician authors of the study emphasize pain experienced by patients who received the bone graft. The patients were divided into an investigative group that received InFuse and a control group that received a bone graft obtained from the iliac crest of their pelvis.  An October 31, 2001 e-mail shows that Beals suggested to Dr. Burkus that 'a bigger deal should be made of elimination of donor site pain with INFUSE . . . so that ‘equivalent’ results aren’t received as a let down.'   Again, after reviewing a later draft of the study, Beals asked Dr. Burkus on March 8, 2002, 'would it be appropriate to make a bigger deal out of donor site pain and include more discussion and references?  Subsequently, a sentence was inserted at the end of a later draft, and included in the published version of the article, that read, 'The use of rhBMP–2 is associated with high fusion rates without the need for harvesting bone graft from the iliac crest and exposing the patient to the adverse effects associated with that procedure.'

Medtronic also sought to include discussion of long-term pain in the Baskin, et. al. 2003 paper on InFuse in the cervical spine. In a draft of the publication that was being circulated on August 30, 2002, the authors wrote, '[b]y 12 months after surgery, the patients [sic] graft-site pain had resolved . . . and no patients complained about the graft-site appearance.'  Beals inserted comments after this sentence stating, 'ALTHOUGH THE PATIENTS DID NOT COMPLAIN ABOUT APPEARANCE DIDN’T SOME STILL EXPERIENCE PAIN AT THE DONOR SITE? SEEMS LIKE RESIDUAL EFFECTS OF DONOR SITE SHOULD BE NOTED.  [sic] [emphasis in original]. In an e-mail to his colleague, Beals wrote, 'I would also add in more discussion on donor site pain and need for osteogenetic graft material (plant seed of doubt for just using allograft by itself ).  A review of the final published article reveals that, after Beals made the suggestion to emphasize pain at the bone graft site, a sentence was added in the final version of the article that read,  '. . . even at the 24-month follow-up assessment, some patients continued to experience residual pain at the donor site, and rated the appearance of the site as only fair.'

Note that in these two examples, another marketing employee edited drafts of two scholarly articles, suggested that more emphasis be put on supposed adverse effects of the procedure that the articles compared to the procedure which used the company's product, and that the two articles included such emphasis. 

Deceptive Response to Peer Reviewers' Criticisms of Apparent Bias 

Finally, the report included an instance in which a company employee managed correspondence between an article's ostensible first author and journal editors to try to defend wording which reviewers had criticized for bias in favor of the company's product.

In summary,

E-mail exchanges between Dr. Burkus and Medtronic employees regarding a study of InFuse utilizing the posterior lumbar interbody fusion (PLIF) technique and published in The Spine Journal in 2004 demonstrates that Medtronic employees not only edited the draft manuscript to include comments supportive of InFuse,  they also covertly participated in the peer-review process by drafting responses to peer-reviewers on behalf of the physician authors named on the paper.

In particular, one employee, Rick Treharne, previously identified as "Senior Vice President of Clinical and Regulatory Affairs," wrote a very positive summary statement for the article's discussion section:

In a January 10, 2003, e-mail to Dr. Burkus, Rick Treharne wrote, 'In looking over the data, I was impressed with how well the BMP patients actually did. So much so that I added a few paragraphs at the end that you may not agree with.' 

However, the reviewers were skeptical,

One reviewer wrote: 'Unless the authors can discuss the results of this study in an unbiased manner, which they have been unable to do in its present form, this data should not be published.'  Another reviewer wrote: 'The manuscript is full of biased statements that are a reflection of the data evaluators—the company that markets the product.'  That reviewer recommended a discussion of potential bias in the text of the paper writing,  'As it stands it is an advertisement for a specific product without significant scientific merit.'

Then, Medtronic employees then took over the process of responding to this review, to wit,

E-mail correspondence on May 28, 2003, indicates that Medtronic’s Rick Treharne wrote and sent Dr. Burkus a draft letter to Dr. Tom Mayer, Editor-in-Chief of The Spine Journal, to address concerns raised by orthopedic surgeons tasked with peer-reviewing the submitted PLIF paper. A subsequent e-mail by Julie Bearcroft notes that she and Dr. Burkus collaborated further on the response to the peer-reviewers of this study during a Lumbar Spine Study Group event.

In response to the peer-reviewers’ concerns about bias in the manuscript, the response letter seemingly misled The Spine Journal by stating that 'To help eliminate any potential bias, only one of the co-authors was a clinical investigator—the other three were independent reviewers of all the data. Since these data are taken from a clinical IDE study sponsored by a company, only the company would have all the data in its database—data that is reviewed by FDA auditors. We don’t believe any discussion of bias is needed for the text.'  By the end of 2003, 'independent reviewers' Dr. Haid and Dr. Burkus would have received $7,793,000 and $722,000 from Medtronic, respectively. This draft letter, written at least in part by Medtronic on behalf of Dr. Burkus, did not disclose the company’s role in directly editing the paper nor did it disclose the magnitude of financial payments made to the supposed 'independent reviewers.'

Thus, in this case, a marketing employee apparently edited a draft of a scholarly article to exaggerate benefits of the company's product, directly adding text to the article, and when peer-reviewers suggested that the article showed bias towards the company's product, apparently two employees ghost-wrote a response letter that claimed that certain authors were "independent reviewers," obfuscating that they had previously received large payments from the company.

Summary

In 2010, we noted reporting that suggested Medtronic had paid huge amounts, millions of dollars, to spine surgeons for reasons that were not clear.  Later that year, we noted further reporting that surgeons who were getting amounts sometimes exceeding one million dollars from Medtronic were not disclosing these payments in scholarly articles about the company's BMP-2 product.

Now there appears a US Senate committee report alleging that Medtronic marketing employees systematically influenced the writing, editing, and publication of multiple ostensibly scholarly articles, ostensibly written by doctors, to favor the Medtronic In-Fuse BMP-2 product.  This adds to previous case studies suggesting that pharmaceutical, biotechnology, device and probably other kinds of company marketers may try to systematically manipulate the design, implementation, analysis, and dissemination of supposedly scholarly and unbiased clinical research to more effectively market their products and services.  

This is discouraging to a former full-time academic physician who now realizes that the difficulties I encountered getting my manuscripts published, given that they written entirely by academic investigators and uninfluenced by marketers, may have been due to the cacophony of competition from marketing influenced texts professionally promoted to journals to serve vested interests.

This is more discouraging to a proponent of evidence-based medicine who believes that medical decisions ought to be informed by critical review of clinical research obtained by systematic search in order to weigh the benefits and harms of management options,accounting for patients' values.  When that clinical research was being deliberately influenced and biased by people selling goods and services, it is not clear that even rigorous critical review will distill the truth from the injected bias.  Yet if physicians cannot depend on published research to guide their decision making for individual patients, what can they depend on?

I conclude as I did my last post,...   Thus health care professionals, policy makers, researchers, and the interested public need to be even more skeptical about arguments made to promote innovative treatments and other clinical interventions.  However, it is not clear that even rigorous skepticism can defend the integrity of evidence based medicine from marketing disguised as clinical research.

Going forward, we must consider erecting an impregnable barrier between clinical research and those whose primary interest is to make money by selling health care goods and services.  If we do not do that, we will forever need to worry that we really have no idea what "works in medicine," and whether any particular test, treatment, or program provides benefits that outweigh its harms.