Are You Ready for Some (Political) Football? - the NFL, Concussion Research, the NIH, and the Revolving Door

conflicts of interest NIH Partners Healthcare revolving doors

Are You Ready for Some (Political) Football? - the NFL, Concussion Research, the NIH, and the Revolving Door

Unknown 5/27/2016 Komentar

Probably because it involved the favorite American sport, the controversy about the risk of concussions to professional National Football League (NFL) players, and how the NFL has handled the issue is very well known.  A recent article in Stat, however, suggested that one less well known aspect of the story overlaps some issues to concern to Health Care Renewal.

Allegations that a Prominent Physician and NFL Official Tried to Influence the NIH Grant Review Process

The article began,

Dr. Elizabeth Nabel, president of Boston’s Brigham and Women’s Hospital [BWH] and one of the nation’s most prominent medical executives, was part of a National Football League effort to 'steer funding' for a landmark concussion study away from a group of respected brain researchers, according to a congressional committee report that was sharply critical of the league.

The report found that the NFL 'inappropriately attempted to influence' the National Institutes of Health’s [NIH] grant selection process.

Dr Nabel, in fact, not only runs the BWH, a renowned teaching hospital and major component of Partners Healthcare, but also serves as the "chief health and medical advisor" to the NFL. Anyone who has followed even a bit of the media coverage about the NFL and concussions affecting football players knows that the NFL could be negatively affected by any more research that associates playing professional football, concussions, and the adverse effects of concussions. 

The Stat article chronicled the intricate communications between Dr Nabel and the NIH as documented by a report from the Democratic staff of the House Committee on Energy and Commerce.

 It cited a series of communications between NFL representatives, including Nabel, and officials of the NIH, and a foundation that accepts gifts from private donors to support NIH research. The discussions began after the NIH decided last year to award a $16 million grant to a research team led by Dr. Robert Stern of Boston University — but before the award was publicly announced.

The money for the grant was to come from a donation pledged by the NFL to the Foundation for the National Institutes of Health, and league officials say they were concerned about aspects of Stern’s group and the proposed study.

Research by Stern’s team and BU colleagues has helped establish a link between football and chronic traumatic encephalopathy, long-term brain damage that’s been observed in a growing number of athletes, including former NFL players, who suffered repeated head injuries.

The implication seems to be that this research group might be counted on to fearlessly pursue research even if the outcomes suggested that playing football might lead to adverse medical effects, which might not be so good for the NFL's interests.  So,

Nabel, who knows the NIH well from her 10 years working as a high-level manager in the agency, sent two emails to Dr. Walter Koroshetz, director of the National Institute of Neurological Disorders and Stroke [NINDS], according to the report. That’s the NIH branch that was awarding the grant.

In one email on June 23, 2015, she wrote, 'I am taking a neutral stance here,' while noting a concern about a potential conflict of interest: members of the NIH grant review panel had coauthored papers with two researchers that she had heard might be receiving the grant — Dr. Ann McKee and Dr. Robert Cantu of BU.

Later that day, she wrote Koroshetz that 'a Dr. Stern, who may also be with this group, has filed independent testimony in the NFL/Players Association settlement.'

Indeed, Stern was critical of how the settlement would be administered, pointing out flaws with the neuropsychological tests that the league proposed using to determine how to compensate injured players.

 Notwithstanding that Dr Nabel had an obvious conflict of interest herself: she worked for the NFL.  In any case,  

'I hope this group is able to approach their research in an unbiased manner,' Nabel’s email continued, the report says.

Nabel sent Stern’s testimony to Koroshetz, according to the report.

'My sole objective,' Nabel said in her statement, was to ask her former NIH colleagues to 'ensure there were no conflicts of interest among grant applicants.'

The NIH found no conflicts involving the grant review panel and stuck with its decision to award the grant to the Stern group. It ended up using internal funds, not the NFL money, to pay for the grant.

The NIH told STAT it agrees with the 'characterization of events in the report.'

An Affront to the Sanctity of the Grant Review Process?

Although Dr Nabel and the NFL asserted that they acted appropriately at all times, neither the committee staff nor one very prominent ethicist agreed,

The committee report said that Koroshetz disagreed ..., and said he was aware of no other instance where a donor raised objections to a grantee prior to the issuance of a notice of grant award.'

'The NFL’s characterization of the appropriateness of its actions suggests a lack of understanding of the importance of the NIH’s independent peer review process,' the committee report states.

Nabel’s spokeswoman said Koroshetz never told Nabel her actions were inappropriate. 'In fact, all of their interactions were very collegial and cordial,' she said.

I will interject that the question was not whether Dr Nabel was hostile or bullying, but was whether she tried to inappropriately influence the grant review process.  So also,

Arthur Caplan, a professor of bioethics at New York University, said Nabel’s actions, as described in the report, risk harming Nabel’s reputation and that of the Brigham. 'When she did anything to try to shape the selection of investigators or challenge the objectivity' of the grant selection process, he said, 'she had to know that that was 100 percent inappropriate, 100 percent unacceptable.'

Having served on numerous NIH and Agency for Healthcare Research and Quality (AHRQ) review committees (known as "study sections"),  let me add some context at this point.  Study section members must meet rigorous standards for freedom from conflicts of interest.  They also fiercely guard their independence.  The grant reviews they construct are supposed to be entirely about the scientific, clinical and public health merit of the proposals, and the scores they give proposals are the most important determinants of whether it gets funding.  Funding decisions are actually made by agency staff and advisory boards, but are supposed to depend only on the reviews and the general priority of the proposals' topics.  Nobody - I repeat, nobody - outside of this process is supposed to influence the funding decisions.

So the notion that big wigs from big outside organizations with vested interests in how a particular research project might turn out were communicating with top NIH officials about grant proposals, and that the officials allowed them to continue to communicate, and allowed even the chance they would be influenced by their communication strikes this old reviewer, to quote Dr Caplan, as "100 inappropriate, 100 percent unacceptable."

Did the Revolving Door Enable the Attempt to Influence NIH Grant Review?

Not directly discussed in the Stat article, however, was why Dr Koroshetz, director of NINDS, was willing to accept, if not agree with Dr Nabel's communications.  The article did note that Dr Nabel was a former "high-level manager" at the NIH.  In fact, according to her official Brigham and Womens' Hospital biography, Dr Nabel was director of the US National Heart, Lung and Blood Institute from 2005-2009.  She became CEO of the BWH in 2010.  Thus, she was a former top NIH leader who once held a rank commensurate with that held by Dr Koroshetz.

But wait, there is more.  Also according to her official BWH biography, Dr Nabel's husband is one  Gary Nabel, now the chief scientific officer at Sanofi.  Dr Gary Nabel, in turn, was Director of the Vaccine Research Center at the National Institute for Allergy and Infectious Diseases (NIAID), another NIH institute, through 2012, but then according to Science, became chief scientific officer at Sanofi. So Dr Nabel's husband was also a high-ranking NIH leader, although apparently not as high-ranking as his spouse and the NINDS director with whom she communicated. 

Thus it appears that maybe Dr Nabel had outsized influence at the NIH and on the NINDS director because she was a former NHLBI director, and the spouse of a former high-ranking NIAID leader.  Her attempts to influence the NIH grant application process therefore appear to be a possible manifestation, albeit delayed, and partially at one spousal remove, of the revolving door pheonomenon.

We have noted that the revolving door is a species of conflict of interest. Worse, some experts have suggested that the revolving door is in fact corruption.  As we noted here, the experts from the distinguished European anti-corruption group U4 wrote,

The literature makes clear that the revolving door process is a source of valuable political connections for private firms. But it generates corruption risks and has strong distortionary effects on the economy, especially when this power is concentrated within a few firms.

  This case suggests how the revolving door may enable certain of those with private vested interests to have excess influence, way beyond that of ordinary citizens, on how the government works.

Worse, this case also suggests how it seems that the country is increasingly run by a cozy group of insiders with ties to both government and industry.  In fact, just a little more digging reveals that a key player in this case has even more ties to big private health care organizations.  According to ProPublica, in the last three months of 2014, Dr Elizabeth Nabel received $26,070 from Medtronic, mainly for food, travel and lodging, but which included $8572 for "promotional speaking/ other."  In 2015, she was appointed to the board of directors of Medtronic, despite not having previously owned any Medtronic stock, according to the company's 2015 proxy statement.  Also in 2015, she was appointed to the board of directors of Moderna Therapeutics.    Her husband, as noted above, now works as chief scientific officer for Sanofi.

So, as we have said before.... The continuing egregiousness of the revolving door in health care shows how health care leadership can play mutually beneficial games, regardless of the their effects on patients' and the public's health.  Once again, true health care reform would cut the ties between government and corporate leaders and their cronies that have lead to government of, for and by corporate executives rather than the people at large.

Video addendum: the beginning of "League of Denial" from PBS Frontline



ADDENDUM (29 May, 2016) - This post was republished on the Naked Capitalism blog.

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There They Go Again - the New England Medical Journal Publishes another Rant, this Time about Power Morcellation

cancer FDA logical fallacies New England Journal of Medicine Partners Healthcare

There They Go Again - the New England Medical Journal Publishes another Rant, this Time about Power Morcellation

Unknown 3/21/2016 Komentar

In 2015, we noted (here and here) that the New England Journal of Medicine seemed to have been reduced to publishing rants about "pharmascolds" who are paranoid about conflicts of interest. Now there they go again....

Background

The sad story about the risks of power morcellation for the treatment of fibroids has received considerable media attention.  The state of play through July, 2014 was described in a series of articles in the Cancer Letter of July 4, 2014. (Look here.)

Uterine fibroids are a common affliction of women.  Their preferred surgical management had changed from open surgery to minimally invasive surgery, sometimes robotically performed, and often incorporating a device called a power morcellator to pulverize the fibroids, allowing the use of small incision.  However, after a patient at the Brigham and Womens' Hospital (BWH) in Boston, part of the Partners Healthcare system, was found to have disseminated sarcoma post power morcellation, most likely because the machine spread tumor cells throughout her abdomen, the US Food and Drug Administration (FDA) issued an advisory against using the procedure morcellation, and despite some controversy, the procedure is now uncommonly used.

The patient so severely affected was Dr Amy Reed, an anesthesiologist at the BWH.  Her husband, a cardiothoracic surgeon at BWH, launched a campaign to reduce the use of power morcellation.  His pursuit of this campaign underlined an important part of the history, 

The use of power morcellation was effectively allowed by the FDA in the absence of any controlled trials meant to assess its safety or efficacy in this context.  The device was deemed moderate risk and approved through the 510(k) process because it appeared similar to previously allowed devices, even though older devices were not used to remove fibroids.  The Cancer Letter quoted Dr David Challoner, who was on a relevant Institute of Medicine (IOM) committee, saying allowing the device on the market was 

one more example of the clearance of a device for a use, not approval, based on predicates already in the market, that is, prior morcellators for other uses

The New England Journal of Medicine Weighs In - with a Special Pleading

Once again, NEJM national correspondent Dr Lisa Rosenbaum had a contrarian view(1).  As we discussed here and here, last year Dr Rosenbaum wrote three commentaries suggesting the importance of conflicts of interest in health care had been overblown, especially with respect to medical journals.

This time, she argued that the FDA overreacted to the tragic case of  Dr Amy Reed. In particular, she was afraid that the risks of power morcellation were exaggerated, and based on poor quality data,

Several experts argued that these risk estimates were too high and that it was riskier to expose 100,000 or so women per year to open procedures rather than laparoscopic ones. Since the rarity of LMS precludes a randomized trial, however, risk estimates had to be based primarily on retrospective case series of varying rigor. Some studies were poorly stratified for risk factors such as age, and others spanned decades during which diagnostic criteria for LMS had changed.

Dr Rosenbaum failed to mention that the lack of good data about the risks of power morcellation stemmed from the lack of any large, well designed randomized controlled trials done to assess its benefits and harms. Of course, since the device's use was allowed by the FDA 510(k) process without any requirement for trial data, there was no incentive for device companies, at least, to do such trials.

Nonetheless, Dr Rosenbaum also argued the benefits of power morcellation were downplayed. 

the benefits of morcellation are largely invisible and thus 'unavailable.' Who sees the women who undergo a minimally invasive procedure, recover quickly, and avoid losing income? What does a pulmonary embolus, a wound infection, or a hemorrhage that didn’t happen look like? You can’t post pictures of these nonevents on social media. But their nonoccurrence is why we ought to be celebrating.

A March 18, 2016 article asked my opinion about Dr Rosenbaum's use of the clinical evidence.

'She talks about the data concerning the possible harms of power morcellation and argues that that data comes from relatively low-quality studies, not randomized, controlled trials, and that it is hard to tell the actual rate of harms, in particular, the dissemination of cancer. On the other hand, Dr. Rosenbaum implies that the benefits of power morcellation are well known.'

'She writes initially that power morcellation allows the treatment of fibroids to be ‘done more efficiently and effectively,’ she later implies that power morcellation is less invasive, leads to quicker recovery, avoids income loss, and furthermore, reduces the likelihood of pulmonary embolus, wound infection, or hemorrhage.'

'However, she doesn’t provide any data about these ostensible benefits. A quick search suggested that there are no good randomized, controlled trials that assessed benefits. Her argument that we have abandoned a beneficial treatment based on poor quality and perhaps exaggerated the data about its harms—that does not seem to be supported by any clear data about its benefits.'

I rendered that opinion on March 18 before I read a Cochrane Collaboration review of minimally invasive surgery versus open surgery for fibroids(2).  However, that review does not seem to contradict my statements above.  The review included some patients who were treated using power morcellation, but apparently did not find any studies that assessed patients treated only with power morcellation with those treated only with an alternative.  Even so, it only included nine studies that enrolled a total of 808 patients.  Thus, I think it is reasonable to say that there have not been any large, well-done randomized controlled trials of power morcellation versus other treatments of fibroids.  Even so, while the review found some advantages for minimally invasive surgery versus open surgery in terms of short-term post-operative pain and length of hospital stay, it did not address pulmonary embolus, wound infection, or hemorrhage directly.  So while Dr Rosenbaum was right to say that the evidence from clinical research about the magnitude and nature of harms of power morcellation was relatively weak, the evidence about its benefits is also weak. Thus, Dr Rosenbaum's argument that the harms have been exaggerated while the benefits were overlooked was based on a logical fallacy, special pleading. 

This special pleading seemed the basis for her claim that

women may suffer more from its [power morcellation's] disuse.

So, as I was quoted by the Cancer Letter,

'The NEJM is perhaps the most prestigious, most highly regarded English-language medical journal in the world,' Poses said. 'It is, in many cases, viewed as the standard for scholarly medical journals. I am a bit surprised that it published a commentary by its own national correspondent that appears to make an argument—about benefits and harms of treatment and policymaking about treatment—that does not have a clear discussion of the data that support or fail to support either the benefits or the harms of the treatment.'

More Arguments, Less Justification

Dr Rosenbaum insisted that her concerns were about the question,

How do you use data to clarify tough trade-offs when the most compelling narratives paint evidence-based reasoning itself as an anathema?

However, she did not demonstrate an approach to policy making on power morcellation that was more evidence-based than what has transpired so far.

In addition, Dr Rosenbaum decried challenges to health care innovation from "the power of tragic stories," and the title of her commentary ("N-of-1 policymaking") suggested that the the FDA approach to power morcellation was based on a single tragic story.  Yet an FDA spokesperson insisted in the March 18, 2016 Cancer Letter article,

The FDA evaluated the available data at the time and determined that it was of sufficient quality and reliability to support our November 14, 2014 decision.

Furthermore, Dr Rosenbaum expressed concerns that power morcellation met its "demise" because of unwarranted concerns about the "greedy corporation," "medicine's corruption," and "industry greed."   Yet she ignored arguments that these concerns were not unreasonable.    

First, the commentary ignored claims that power morcellation procedures were very lucrative, e.g., those in the 2014 Cancer Letter article

'This is a very lucrative procedure.'  [Dr] Noorchashm, [Dr Reed's husband] said.  'The procedure itself bills $30,000 to $50,000, depending on the center.'

Nor did she argue against the assertion in the same article that device companies used political influence to promote their very expensive product,

There is a very strong pressure from the device industry to get into the market quickly.

The device companies have been able to make [the 510(k) process that allowed power morcellation] survive politically over the ensuing 40 years.

Also, Dr Rosenbaum's NEJM commentary failed to counter the assertion by Dr Noorchashm that the device manufacturers concealed the risks of power morcellation.

Device manufacturers clearly knew of the cancer risk.  You can see warnings about malignant tumors in the Ethicon and Karl Storz user manuals.  Clearly, their lawyers had warned them to put them there to avoid liability.  The bottom line is that these manufacturers knew of this hazard, but neither reported it back to the FDA, as would have been the safe and responsible thing to do.(3) 

Finally, according to the March 18, 2016 Cancer Letter article, while Dr Reed has apparently sued the BWH, and Dr Rosenbaum admitted she is on "faculty" at the BWH, neither she, the NEJM, nor the BWH will say whether she is currently being paid by the BWH.  Particularly,

the hospital declined to provide information on Rosenbaum's title and whether she is a full-time faculty member, citing personnel policies.

My response (in the Cancer Letter article) was

'I can see that the hospital would not want to reveal her salary, if in fact she has one, and that has privacy implications,' Poses said. 'But I don’t understand why the hospital would not be able to simply tell you whether or not she is employed there and in what capacity.'

Thus, the latest commentary in the New England Journal of Medicine by National Correspondent Dr Lisa Rosenbaum used special pleading to argue for an expensive medical device with dubious benefits but which no more dubious evidence suggests may cause cancer.  The commentary also decried the device's critics as unreasonably concerned about "greed" and "corruption," even though the device is clearly expensive, there are at least creditable allegations that the device makers used political influence to promote it and concealed its risks, and ironically the commentary itself obfuscated whether Dr Rosenbaum has a major financial relationship to the hospital that is being sued in connection with use of that device there.

Thus, this latest New England Journal of Medicinearticle, like those by the same author in the same journal which we have discussed before (here and here), seems more like a rant in a political blog than a scholarly article in the US' and perhaps the world's most prestigious scholarly medical journal.  What is going on at the NEJM? What has happened to its editorial standards?  Why should it continue to inspire such trust?    

ADDENDUM (22 March, 2016) - See also comments in the 1BoringOldMan blog. 


References

1.  Rosenbaum L.  N-of-1 policymaking - tragedy, trade-offs, and the demise of morcellation.  N Engl J Med 2016; 374: 986-990.  Link here.
2.  Chittawar PB, Franik S, Pouwer AW et al.  Minimally invasive surgical techniques versus open myomectomy for uterine fibroids. Cochrane Library 2014. Link here.
3.  Dyer O. US surgeon who campaigned against potentially dangerous device receives legal threat.  Brit Med J 2014; 349: g5577.  

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