healthy4u: NIH

Quis Custodiet Ipsos Custodes? Redux

Revised HHS Rules for Conflict of Interest Fall Short This morning NIH Director Dr. Francis Collins announced <a href="http://freepdfhosting.com/3dde31520d.pdf">revisions</a> to the existing 1995 regulations on objectivity in research that is funded by the Public Health Service. The focus is on significant financial interests (SFI) and on financial conflicts of interest (FCOI). The regulations illustrate the 3-way dance involving academic institutions (the grantees), NIH (the grantor) and academic scientists (the investigators). Thanks to Senator Grassley (R-Iowa) and his investigator Paul Thacker, headlined revelations in recent years about unacceptable management of FCOI at places like Stanford (Alan Schatzberg), Emory (Charles Nemeroff) and Harvard (Joseph Biederman) forced these revisions of the NIH regulations. The general initial reaction to the new rules has been critical – <a href="http://www.pharmalot.com/2011/08/nih-issues-new-conflict-of-interest-rules/">here</a> and <a href="http://pogoblog.typepad.com/pogo/2011/08/the-national-institutes-of-health-new-ethics-rules-a-swing-and-a-miss.html">here</a>, for instance. Many stakeholders had urged the NIH to require that institutions make the disclosed FCOI of their investigators available on a public website. Dr. Collins had intimated that we could expect to see this change, so there is consternation that it somehow became derailed by institutional lobbying in recent months. The stated concern was that institutions would feel burdened by the need to maintain these data bases. Instead, if citizens wish to inquire about FCOI involving PHS-derived research funding, they will need to write to the institution, which is obliged to respond within 5 days. That’s not exactly user friendly. POGO today made the smart <a href="http://pogoblog.typepad.com/pogo/2011/08/the-national-institutes-of-health-new-ethics-rules-a-swing-and-a-miss.html">suggestion</a> that the data could easily be attached to information about awarded funds on the <a href="http://projectreporter.nih.gov/reporter.cfm">NIH RePORTER</a> website, that already exists. A second failing is that the revised regulations do not close the regulatory loophole through which Charles Nemeroff strolled when he moved from Emory to the University of Miami. We covered that incident <a href="http://hcrenewal.blogspot.com/#uds-search-results">several times</a> on this blog last year. Though Nemeroff was under a 2-year sanction and banned from participating in NIH-funded research at Emory, his friend Thomas Insel, Director of NIMH, assured the dean of the medical school at Miami that Nemeroff was in good standing to apply for NIH funding when he moved from Emory. To underline the point, Insel displayed the bad judgment of appointing Nemeroff to 2 new NIMH review committees. Do today’s revised regulations prevent a repeat of this administrative travesty? No, they don’t. There is some mention of ensuring oversight if a sanctioned investigator wishes to transfer a grant to a new institution, but nothing to prevent the Nemeroff-Insel dance from being repeated. Here is the relevant section of today’s <a href="http://freepdfhosting.com/3dde31520d.pdf">announcement</a> (page 89): We did, however, agree with one respondent that it would be helpful to clarify, in the grants context in particular, that institutional sanctions against an Investigator can travel with the Investigator upon his or her transfer to another Institution. Specifically, we have revised 42 CFR 50.606, paragraph (a), as follows: “If the failure of an Investigator to comply with an Institution’s financial conflicts of interest policy or a financial conflict of interest management plan appears to have biased the design, conduct, or reporting of the PHS-funded research, the Institution shall promptly notify the PHS Awarding Component of the corrective action taken or to be taken. The PHS Awarding Component will consider the situation and, as necessary, take appropriate action, or refer the matter to the Institution for further action, which may include directions to the Institution on how to maintain appropriate objectivity in the PHS-funded research project. The PHS may, for example, require Institutions employing such an Investigator to enforce any applicable corrective actions prior to a PHS award or when the transfer of a PHS grant(s) involves such an Investigator.” This revision is intended to reference the range of options for the PHS Awarding Component to consider, depending on the specific circumstances at issue. For example, PHS may decide to initiate government-wide suspension or debarment of the Investigator under 2 CFR Part 376; or to use enforcement measures under 45 CFR 74.62, e.g., perhaps to make the approval of a transfer contingent upon the former Institution’s disclosure of the corrective action- including the specific sanctions against the Investigator- to the new Institution; and/or to use special award conditions under 45 CFR 74.14, e.g., perhaps to make the new Institution agree to take the same or similar action against that Investigator or explain to the PHS Awarding Component in writing why such action was not taken and what alternative measures will be used to ensure compliance. What’s wrong here? Everything is optional; everything is discretionary; everything is contextual – that is a formula for NIH and the academic institutions to just look the other way. And if a Nemeroff decides just to relocate without transferring a grant then he is free to start reapplying again right away. Miami would not be required to continue applying the Emory sanction banning him for 2 years from involvement in federal grants. The PHS Awarding Component (NIMH in this case) may or may not get involved, or it may pass the buck to the new institution. So what has changed? If it is left up to compromised federal bureaucrats like Thomas Insel, and institutional administrators like Pascal Goldschmidt at Miami, then nothing has changed. It's business as usual, folks. Dr. Collins, you have not done what you set out to do. Too bad.

Quis Custodiet Ipsos Custodes? Redux

Revised HHS Rules for Conflict of Interest Fall Short This morning NIH Director Dr. Francis Collins announced revisions to the existing 199...

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Retreat Back to Regulatory Capture: US FDA, NIH, Department of Health and Human Services All Back Off

After some brave words about transparency, integrity and all that, US government officials seem to be running back to the arms of the health care corporate CEOs. Weakening FDA Conflict of Interest Rules As <a href="http://www.reuters.com/article/2011/08/01/us-fda-bias-idUSTRE7703R320110801">reported</a> by Reuters, <blockquote>U.S. lawmakers likely will change the criteria for advisers reviewing new medicines next year because of complaints that the rules meant to prevent conflicts of interest make it harder to find real experts. Congressional lawmakers may require the Food and Drug Administration to relax the rules that bar advisers from reviewing a drug if they have even indirect financial ties to related manufacturers, as part of an FDA funding bill.</blockquote> This was not purely an initiative of legislators, but was egged on by a top FDA administrator <blockquote>The agency often must delay panel meetings while it searches for experts without conflicts, lawmakers and FDA officials say. Top doctors are usually the ones drugmakers hire as speakers or consultants. 'We have had difficulty in recruiting highly qualified people. And we've had delays in having panels because of this,' Dr. Janet Woodcock, head of the FDA's drugs center, told a House of Representatives hearing earlier this month. The result is that 23 percent of FDA advisory panels have vacancies, more than double the agency's stated goal, according to the FDA's quarterly report at the end of May.</blockquote> The rationale was that those paid by drug and device companies are the most expert: <blockquote>The FDA tightened guidelines in 2007 to minimize industry ties that could sway a panelist's view, partly inspired by the scandal with Merck's pain reliever Vioxx. Ten of the 32 panelists advising the FDA on the drug consulted for drugmakers. Nine of the 10 recommended putting the drug back on the market after it was pulled in 2004 over concerns about heart risk. The restrictions go too far, say lawmakers who want the FDA to approve more new medicines, in part because they promote American jobs. 'No longer can we deny experts simply because they have ties to industry,' said Georgia Representative Phil Gingrey during a House of Representative hearing on FDA funding last month. The committee's chairman, Fred Upton from Michigan, called the conflict of interest rules 'rigid and unrealistic.' Industry executives, who want the FDA to speed drug approvals, also support relaxing the rules. Biogen Idec CEO George Scangos said the guidelines 'exclude a lot of people who would be the best qualified.'</blockquote> Of course, the drug and device companies have been touting their paid "key opinion leaders" as the best and the brightest for a long time. There is plenty of evidence, however, that they are mainly those whom those companies find the most compliant, and in many cases, those who are willing to be stealth marketers on those companies' payrolls. (See this <a href="http://hcrenewal.blogspot.com/2008/06/key-opinion-leaders-were-sales-people.html">post</a> about those who recruit KOLs regarding them as salesmen, and more <a href="http://hcrenewal.blogspot.com/search/label/key%20opinion%20leaders">here</a>.)  "Key opinion leaders" supported by commercial grant funding may seem like experts to academic medical institutions' leadership who now value outside funding more than teaching and research excellence (see this <a href="http://hcrenewal.blogspot.com/2010/12/american-medical-schools-are-only-in-it.html">post</a>). Furthermore, as <a href="http://www.politico.com/news/stories/0811/60522.html">reported</a> by Politco, the Project on Government Oversight, a watchdog group, chastised FDA leadership for exaggerating the difficulty of finding unconflicted experts, concluding in their letter to the FDA Commissioner, "to gain the public trust, we must ensure that the FDA relies on the best available information for its policies, rather than personal opinions and biases." So far, government officials seem to be more worried about the opinions of corporate leaders than the public trust. Weakening NIH Conflict of Interest As <a href="http://http//www.nature.com/news/2011/110801/full/476017a.html">discussed</a> in Nature, <blockquote>Francis Collins hailed it as a 'new era of clarity and transparency in the management of financial conflicts of interest' (S. J. Rockey and F. S. Collins J. Am. Med. Assoc. 303, 2400–2402; 2010). But the director of the US National Institutes of Health (NIH) may have spoken too soon when he described a new rule, proposed last year, that would require universities and medical schools to publicly disclose online any financial arrangements that they believe could unduly influence the work of their NIH-funded researchers. Nature has learned that a cornerstone of that transparency drive — a series of publicly accessible websites detailing such financial conflicts — has now been dropped.</blockquote> In more detail, <blockquote>The NIH's parent agency, the Department of Health and Human Services (DHHS), proposed the new rule in May 2010, after congressional and media investigations revealed that prominent NIH grant recipients had failed to tell their universities or medical schools about lucrative payments from companies that may have influenced their government-funded research. The DHHS called the proposed websites 'an important and significant new requirement to … underscore our commitment to fostering transparency, accountability, and public trust'. Under the proposal, institutions with NIH-funded researchers would determine, grant by grant, if any financial conflicts existed for senior scientists on the grant. For example, these would include receiving consultancy fees, or holding shares in a company, 'that could directly and significantly affect the design, conduct, or reporting' of the research. The institutions would post the details online, where they would stay for at least five years. </blockquote> But of course the medical schools decided that it would just be too much trouble to do all this: <blockquote>'The websites don't appear out of nowhere,' says Heather Pierce, senior director of science policy at the Association of American Medical Colleges (AAMC) in Washington DC. They would 'require employees to not only create the website but to pull the information, review it, and make sure it is up to date and accurate'. That is not the only objection from the powerful academic lobbies. During the public comment period last summer, the Association of American Universities and the AAMC submitted a joint statement saying: 'There are serious and reasonable concerns among our members that the Web posting will be of little practical value to the public and, without context for the information, could lead to confusion rather than clarity regarding financial conflicts of interest and how they are managed.'</blockquote> Given how academic medical institutions have expanded their administrations and bureaucracy, the enormous amounts they spend on management, and the huge <a href="http://hcrenewal.blogspot.com/search/label/executive%20compensation">compensation</a> they give their executives, and further given how much of their revenues come from government sources (Medicare, Medicaid money for patient care, Veterans Administration money supporting many faculty members, Medicare money funding graduate medical education, and NIH and other government research grants), the notion that getting a few staffers to process disclosures would be administratively or financially burdensome is just laughable. At least Iowa's Republican Senator Charles Grassley, seemingly one of the last politicians in Washington who cares about the integrity of government programs and spending, is upset. As <a href="http://blogs.nature.com/news/2011/08/senator_urges_white_house_not.html">reported</a> again by Nature, <blockquote>The US Senate's leading advocate for government transparency wrote today to the White House's budget office, demanding that it protect a proposed rule that would obligate universities to post their publicly-funded biomedical researchers' financial conflicts on a publicly accessible website. 'The public's business should be public... I urge OMB to follow through and approve a rule that includes a publicly available website,' Senator Charles Grassley, Republican of Iowa ..., wrote in in <a href="http://blogs.nature.com/news/Grassley.omb.pdf">this letter </a>to Jacob Lew, the director of the White House's Office of Management and Budget (OMB).</blockquote> Furthermore, he wrote: <blockquote>I am troubled that taxpayers cannot learn about the outside income of the researchers whom the taxpayers are funding, and this flies in the face of President Obama's call for more transparency in the government.</blockquote> We will see if his protest does any good, but again it appears that government officials are more worried about the revenues of big health care organizations than the needs of the public. Retreating from Threats to Disbar Forest Laboratories CEO We previously <a href="http://hcrenewal.blogspot.com/2011/05/logical-fallacies-to-defend-ceos-from.html">posted</a> about how the US Department of Health and Human Services threatened to disbar the CEO of Forrest Laboratories from dealings with the government after his company pleaded guilty to obstruction of justice and misbranding, and paid a $313 million fine. Now, <a href="http://online.wsj.com/article/SB10001424053111903885604576490631294926432.html">per</a> Alicia Mundy writing for the Wall Street Journal, things have changed: <blockquote>The U.S. government dropped efforts to force the resignation of a prominent pharmaceutical-company chief executive, reversing course after protests from the company and major business groups. The about-face on Forest Laboratories's longtime leader, Howard Solomon, represents a significant retreat by the Department of Health and Human Services, which has said it wants to step up punishments against drug-company executives when wrongdoing happens on their watch. Forest agreed last year to plead guilty to misdemeanors involving marketing of its drugs including the antidepressant Celexa, and it paid $313 million to resolve the matter. Mr. Solomon wasn't personally accused of any wrongdoing. Nonetheless, the government notified him in April that it was considering excluding him from jobs at health-care companies that sell to the U.S. government. It invoked a little-used clause in the Social Security Act that allows such an action against corporate leaders of companies found guilty of criminal misconduct, even if the leaders had no knowledge of the misconduct. The exclusion move would have effectively forced Forest to remove Mr. Solomon from office, because Forest and other drug companies rely on business from U.S. government agencies such as Medicare and the Veterans Administration. In a letter to Mr. Solomon on Friday, the office of the inspector general of the Department of Health and Human Services said, 'Based on a review of information in our file, and consideration of the information your attorneys provided to us both in writing and in an in-person meeting, we have decided to close this case.'</blockquote> We have <a href="http://hcrenewal.blogspot.com/search/label/legal%20settlements">discussed</a> - some might say endlessly - how despite numerous publicly reported cases of wrongdoing by health care organizations, hardly any individual who authorized, directed or implemented the bad behavior has ever faced any negative consequences. There have been recent fulminations by some government officials that this is going to change. The case of the Forest Laboratories CEO appeared to be an example of such change, but no more. The Wall Street Journal went on to discuss why the government may have changed course: <blockquote>The government's retreat came after a barrage of complaints from Forest and business groups including the U.S. Chamber of Commerce and the Pharmaceutical Research and Manufacturers of America, the drug industry's leading trade group. In July, Forest spent $80,000 to hire former Louisiana Sen. John Breaux to lobby the government regarding exclusion, according to Senate records. Mr. Breaux didn't return a call requesting comment. Forest said earlier that it was just trying to make its case that this was a highly unusual action by the U.S. government.</blockquote> Of course it was unusual. That is the whole problem. In any case, it looked like the government was much more concerned about the coddling of corporate CEOs and their lobbyists' and cronies' opinions than about deterring bad behavior by large health care organizations. Summary After a bit of blustering by the current US administration about transparency and integrity it appears to be back to business as usual in the US capital. Over the last 20 years, government has increasingly answered to corporate CEOs instead of "we, the people." Protecting patients' and the public's health has given way to protecting the financial health of large health care organizations, and the compensation of rich CEOs. Federalism is giving way to corporatism. As long as this continues, expect our health care system to continue its slow collapse. Eventually, expect the CEOs to get in their private jets and escape while the rest of us picks up the pieces. Until we dispel the fog of corporatism that has spread over the government that was once supposed to be of the people, by the people, and for the people, expect no real health care reform, and expect continuing rising costs, declining access, and worsening patient care. Obviously, true health care reform would start with the government and its officials putting patients' and the public's health first, way ahead of the financial comfort of corporate CEOs. See also <a href="http://alison-bass.blogspot.com/2011/07/tougher-nih-rules-about-financial.html">comments</a> by Alison Bass.

Retreat Back to Regulatory Capture: US FDA, NIH, Department of Health and Human Services All Back Off

After some brave words about transparency, integrity and all that, US government officials seem to be running back to the arms of the health...

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Former NIH Director Spins Through Revolving Door, Ends Up at Sanofi-Aventis

A bit of news that got little attention this month was a new job for the former head of the US National Institutes of Health (NIH).  Dr Elias Zerhouni had <a href="http://www.nature.com/news/2008/081001/full/455570a.html">left the NIH</a> in October, 2008.  Here is the <a href="http://www.reuters.com/article/idUSLDE6BD08Q20101214">Reuters version</a> of the story of his hew career: <blockquote>French drugmaker <a href="http://hcrenewal.blogspot.com/search/label/Sanofi-Aventis">Sanofi-Aventis</a> (SASY.PA) replaced its head of research and development with a leading academic and former top U.S. health official on Tuesday to raise its game in medical innovations. The company said Elias Zerhouni would lead R&D of drugs and bring R&D for vaccines under his control too as Sanofi reshapes its portfolio and looks to vaccines as one area for growth to offset sales losses from mounting generic competition. The appointment of Zerhouni, a professor of radiology and biomedical engineering, comes as Sanofi battles to buy U.S. rare disease specialist Genzyme. Chief executive Chris Viehbacher brought in Zerhouni in February 2009 as his scientific adviser, shortly after taking charge of the group which he has been transforming to include the development of drugs based on biotechnology.</blockquote> Zerhouni's Embrace of Corporate Health Care Although Zerhouni ostensibly left the NIH to return to academia at Johns Hopkins University, note that by February, 2009, four months after his resignation was announced, Zerhouni was already advising the Sanofi CEO.  Soon after he joined the corporate health care world in earnest.  In April, 2009, he was <a href="http://www1.actelion.com/en/our-company/news-and-events/index.page?newsId=1301120">proposed </a>for membership on the board of directors of Actelion Ltd, a <a href="http://www1.actelion.com/en/our-company/index.page?">Swiss biotechnology company</a>.  On December 8, 2009, he was <a href="http://www.implu.com/releases/2009/20091211/33777/implu_viewer">elected</a> to the board of Danaher Corp, a diversified technology corporation which makes <a href="http://www.danaher.com/business/strategic_detail.asp?key=17">medical devices</a>.  At some time he had become <a href="http://www.zerhounigroup.com/about/index.php">President</a> of the Zerhouni Group, which <a href="http://www.zerhounigroup.com/expertise/index.php">advertised itself</a> as a resource to "pharmaceutical and biotechnology companies, trade organizations, sovereign wealth funds, government agencies, and research entities around the globe." Zerhouni at the NIH: His Response to the Conflict of Interest Scandal There is more than a little irony inspired by Zerhouni's quick circuit through the revolving door. Zerhouni became director of the NIH in 2002, and announced his departure <a href="http://www.nature.com/news/2008/081001/full/455570a.html">in October, 2008</a>. In December, 2003, David Willman published his <a href="http://articles.latimes.com/2003/dec/07/nation/na-nih7">landmark article</a> in the Los Angeles Times on severe conflicts of interest affecting NIH scientists and leaders.  It revealed that formerly stringent conflict of interest policies at the Institutes were rescinded by then director Dr Harold Varmus in 1995, during the Clinton administration, and increasingly since 1998, disclosure of NIH personnel's conflicts of interest had been reduced.  Thus, in 2002, Zerhouni had taken charge of an agency already deeply affected by conflicts of interest affecting many of its leaders, even though that was not yet public.  He initially did nothing about the situation.  Willman published another <a href="http://www.latimes.com/news/nationworld/nation/la-na-nih22dec22,0,7519657.story?coll=la-home-headlines">series of articles</a> revealing even more breathtaking conflicts of interest in December, 2004.  (See our post <a href="http://hcrenewal.blogspot.com/2004/12/anechoic-effect-and-conflicts-of.html">here</a>.)   By then, a Los Angeles Times editorial said there was the "appearance of corruption" at the NIH, and called for Dr Zerhouni's resignation.  Only after the second series of articles did Dr Zerhouni swing into action (see post <a href="http://hcrenewal.blogspot.com/2004/12/few-echoes-from-allegations-of-nih.html">here</a>).  In February, 2005, he announced that he would now hold the NIH to a "<a href="http://hcrenewal.blogspot.com/2005/02/nih-seeks-higher-standard-better-late.html">higher standard</a>."  Yet new conflict of interest stories kept surfacing and their handling kept provoking concern (e.g., see this <a href="http://hcrenewal.blogspot.com/2007/07/ongoing-nih-conflicts-of-interest-story.html">post</a> from 2007, and this <a href="http://hcrenewal.blogspot.com/2008/10/nih-management-reprimanded-scientific.html">post</a> from 2008), and concerns about how NIH deals with conflicts of interest affecting the extramural researchers it funds persist to this day (e.g., see this <a href="http://hcrenewal.blogspot.com/2010/07/ethics-turnaround-sort-of-by-nih.html">post</a>).  By the late 1990s, the NIH, like many other government agencies, seemed to have become extremely cozy with the world of big corporations.  Dr Zerhouni did nothing to obvious to reduce the local version of this coziness until it had become a public scandal.  His actions let questions about the relationships of the NIH, once a pristine example of a government run biomedical research agency, with big health care business persist to this day.  So it should perhaps be no surprise that he so quickly transitioned from the government that is supposed to be"of the people, by the people, for the people" to top leadership positions in corporate health care. Other US Government Health Care Agency Leaders Transit the Revolving Door Meanwhile, the previous commissioner of the US Food and Drug Administration, Dr Andrew von Eschenbach, is <a href="http://www.healthtransformation.net/cs/andrew_c_von_eschenbach_md">Senior Director for Strategic Initiatives</a> at the Center for Health Transformation, a group whose <a href="http://www.healthtransformation.net/cs/our_members">membership</a> includes some of the biggest health care organizations, many of which have had their own moments in the sun on Health Care Renewal.  For example, see Charter Members, <a href="http://hcrenewal.blogspot.com/search/label/AstraZeneca">AstraZeneca</a>, <a href="http://hcrenewal.blogspot.com/search/label/Sutter%20Health">Sutter Health</a>, and <a href="http://hcrenewal.blogspot.com/search/label/WellPoint">Wellpoint</a>; and Platinum Members, <a href="http://hcrenewal.blogspot.com/search/label/GlaxoSmithKline">GlaxoSmithKline</a> and <a href="http://hcrenewal.blogspot.com/search/label/Merck">Merck</a>.  Dr Eschenbach is also on the <a href="http://www.esplp.com/von-eschenbach-joins-histosonics-board.aspx">board of directors</a> of Histosonics Inc.  Also, the previous director of the Centers for Disease Control, Dr Julie Geberding, became <a href="http://www.merck.com/newsroom/news-release-archive/corporate/2009_1221.html">President</a> of Merck Vaccines in late 2009.  Conclusions So the revolving door just keeps spinning, its revolutions suggesting how closely tied together big government and big corporations have become in what is now the health care business.  Whatever the motivations of Doctors Zerhouni, von Eschenbach, and Geberding were, the message to every person in a leadership position in health care in the US government has to still be: you too can earn big corporate compensation soon after you leave here.  Who knows how much that siren song will lead current government leaders to avoid antagonizing the leaders of big health care corporations during their government "service."  That is, of course, not what we want them to be thinking about if government agencies ae to serve the people, not the CEOs of big corporations.  I am sure that the career transitions of Doctors Zerhouni, von Eschenbach, and Geberding were perfectly legal.  If we want government health care agencies to put the peoples' interests ahead of those of the CEOs of big health care corporations, should not, however, the law be changed to at least slow down the revolving door?

Former NIH Director Spins Through Revolving Door, Ends Up at Sanofi-Aventis

A bit of news that got little attention this month was a new job for the former head of the US National Institutes of Health (NIH). Dr Elia...

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ETHICS TURNAROUND (sort of) by NIH INSTITUTE DIRECTOR

ETHICS TURNAROUND (sort of) by NIH INSTITUTE DIRECTOR What a difference a month makes. When I went on vacation in June the Director of NIMH, Thomas Insel, was stonewalling about his relationship with Charles Nemeroff. Insel wanted to put distance between himself and the poster boy for conflict of interest in academic medicine. The heat was on Insel because of revelations that he helped Nemeroff get a new position at Miami after his fall from grace at Emory. Insel also gave a green light for Nemeroff to reapply for NIMH grant funding, and he appointed Nemeroff to new research review committees. These actions were widely seen as efforts to help Nemeroff get back into circulation. It didn’t help that people called attention to past favors and lobbying by Nemeroff on behalf of Insel. Things continued to unravel, and on about June 29 Insel placed a <a href="http://www.nimh.nih.gov/about/director/2010/more-on-public-trust-and-conflict-of-interest.shtml">disclaimer</a> on his official blog. Insel here allowed that his earlier official statements “may be viewed as misleading.” This softening of Insel’s position was picked up June 29 by the <a href="http://chronicle.com/blogPost/NIH-Official-Softens-Denial-of/25174">Chronicle of Higher Education</a>. Not only was Insel’s disclaimer on his official weblog undated, it is mealy mouthed and it was widely criticized – <a href="http://hcrenewal.blogspot.com/2010/06/insel-admits-his-statements-may-be.html">here</a> and <a href="http://1boringoldman.com/index.php/2010/06/29/plausible-deniability-is-neither-a-medical-nor-scientific-standard/">here</a>, for instance – as further evidence of Insel’s disingenuousness. By July 7 we learned of further revisions to Insel’s position. In response to pressure from Senator Charles Grassley (R-Iowa), Insel <a href="http://freepdfhosting.com/2e0f575924.pdf">issued</a> a mea culpa in which he agreed that Nemeroff’s actions constituted “an egregious violation of NIH policy and University rules.” Insel also acknowledged that his willingness to help Nemeroff “may have created the appearance of favoritism. In retrospect, I regret that my actions… appear inappropriate for a Federal research official given my past association with Dr. Nemeroff.” This new statement also was raked over as further evidence of Insel’s dissembling – see <a href="http://www.pharmalot.com/2010/07/nimhs-insel-on-nemeroff-i-regret-my-actions/">here</a> and <a href="http://1boringoldman.com/index.php/2010/07/08/a-start/">here</a> and <a href="http://www.margaretsoltan.com/?p=24272">here</a>. Nowhere in Insel’s new self serving statements is there any apology for his ill advised appointment of Nemeroff to new Federal research review panels. This signals once again that Insel just doesn’t get it when it comes to his crony Nemeroff. It is not in the job description of an NIH Institute Director to taint research review panels with compromised and sanctioned scientists. Keep in mind that the appearance of malfeasance and impropriety most often occurs in the presence of malfeasance and impropriety. That is a standard Bayesian proposition that Insel seems not to grasp. In light of these developments, who can take seriously the work Dr. Insel says he has done to develop a new NIH initiative on ethics? The leadership of NIH tacitly acknowledged this problem when they recently <a href="http://blogs.nature.com/news/thegreatbeyond/2010/07/nih_extends_public_comment_per.html">extended</a> the period of comment on the new ethics proposals. This was done specifically to mend the regulatory hole that Insel and his crony Nemeroff walked through when Insel assured Pascal Goldschmidt at Miami that Nemeroff could go right ahead to apply for new NIMH funding. Left to his own initiative, Insel kept the hole wide open. His July 7 statement to Senator Grassley that "I do not condone the gap in our policy that allowed (Nemeroff) to avoid the penalty implemented by Emory by moving to another university…” rings hollow: actions speak louder than words, and Insel had many months in which he could have closed the gap before the present scandal surfaced. How much longer can NIH tolerate an ethical prevaricator as an Institute Director? Bernard Carroll

ETHICS TURNAROUND (sort of) by NIH INSTITUTE DIRECTOR

ETHICS TURNAROUND (sort of) by NIH INSTITUTE DIRECTOR What a difference a month makes. When I went on vacation in June the Director of NIMH,...

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Open Letter to Dr. Josephine Briggs

Josephine P. Briggs, M.D. Director, National Center for Complementary and Alternative Medicine Dear Dr. Briggs, As you know, we've met twice. The first time was at the <a href="http://www.sciencebasedmedicine.org/?p=4100" mce_href="http://www.sciencebasedmedicine.org/?p=4100">Yale "Integrative Medicine"</a> Symposium in March. The second was in April, when Drs. Novella, Gorski and I <a href="http://www.sciencebasedmedicine.org/?p=4575" mce_href="http://www.sciencebasedmedicine.org/?p=4575">met with you</a> for an hour at the NCCAM in Bethesda. At the time I concluded that you favor science-based medicine, although you are in the awkward position of <a href="http://www.sciencebasedmedicine.org/?p=4671" mce_href="http://www.sciencebasedmedicine.org/?p=4671">having to appear 'open-minded'</a> about nonsense. More about that below, but first let me address the principal reason for this letter: it is disturbing that you will shortly appear at the <a href="http://www.naturopathic.org/content.asp?admin=Y&contentid=363" mce_href="http://www.naturopathic.org/content.asp?admin=Y&contentid=363">25th Anniversary Convention</a> of the American Association of Naturopathic Physicians (AANP). It is disturbing for two reasons: first, it suggests that you know little about the tenets and methods of the group that you'll be addressing; second, your presence will be interpreted as an endorsement of those methods and of that group---whether or not that is your intention. If you read nothing more of this letter or its links, please read the following articles (they're "part of your education," as my 91 y.o. mother used to say to me): <a href="http://www.medscape.com/viewarticle/465994" mce_href="http://www.medscape.com/viewarticle/465994">Naturopathy: A Critical Appraisal</a> <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140750/?tool=pubmed" mce_href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140750/?tool=pubmed"></a> <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140750/?tool=pubmed" mce_href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140750/?tool=pubmed">Naturopathy, Pseudoscience, and Medicine: Myths and Fallacies vs Truth</a> The first article is an introduction to the group to which you will be speaking; the second is my response to complaints, from that group and a few of its apologists, about the first article. It was a surprise to me that the editor, George Lundberg, preferred that I make my response a comprehensive one. Thus the second article inevitably became the crash course---call it CAM for Smarties---that your predecessors never offered you, replete with examples of useless and dangerous pseudoscientific methods, real science being brought to bear in evaluating such methods, proponents' inaccurate or cherry-picked citations of biomedical literature, bits of pertinent but little-known history, the standard logical fallacies, embarrassing socio-political machinations, wasteful and dangerous 'research' (funded---unwittingly, I'm sure---by the NCCAM), bait-and-switch labeling of rational methods as "CAM," vacuous assertions about 'toxins' and "curing the underlying cause, not just suppressing the symptoms," anti-vaccination hysteria, misleading language, the obligatory recycling of psychokinesis claims, and more. Please excuse me if this sounds preachy; I admit that it does, but understand that I'm writing in good faith. My own views of "CAM" did not dawn on me overnight, but were the result of years of research. My 'internship,' as it were, consisted of <a href="http://www.sciencebasedmedicine.org/?p=115" mce_href="http://www.sciencebasedmedicine.org/?p=115">sitting on a state commission</a> from the fall of 2000 until the spring of 2002, listening to AANP members (including at least <a href="http://www.naturopathic.org/content.asp?admin=Y&contentid=363#shiva" mce_href="http://www.naturopathic.org/content.asp?admin=Y&contentid=363#shiva">one </a>with whom you will share the podium), reading about 'naturopathic medicine,' and attempting (unsuccessfully) to engage its advocates in rational discussion. I began that task open to forming opinions based on whatever information became available; by its end it had become abundantly clear that the group is best characterized as a pseudoscientific cult, and nothing since has altered that opinion. Regarding your presence at the convention being tantamount to an endorsement of 'naturopathic medicine,' this is so obviously true that it ought not be necessary to mention it. Previous experience, however, has taught me to expect an air of---please don't take this personally---<a href="http://www.sciencebasedmedicine.org/?p=438" mce_href="http://www.sciencebasedmedicine.org/?p=438">utter cluelessness </a>whenever I've raised such an issue. If you've read the second naturopathy article linked above, you already know that according to proponents, <blockquote>The validity of naturopathic medicine is demonstrated by its support in government (including accreditation of its schools and NIH-funded research), on medical school Web sites, and in other parts of the public domain.</blockquote> An appearance at their annual convention by the most important "CAM" administrator at the NIH surely has the <a href="http://www.naturopathic.org/content.asp?contentid=62" mce_href="http://www.naturopathic.org/content.asp?contentid=62">political arm</a> of the AANP licking its chops. NDs, as they call themselves, are currently licensed in 14 or 15 states and a couple of provinces, and aggressively seek licensure throughout the U.S. and Canada. They appear to wield political clout well out of proportion to their numbers, no doubt thanks in part to the <a href="http://nccam.nih.gov/about/naccam/charter.htm#jump4" mce_href="http://nccam.nih.gov/about/naccam/charter.htm#jump4">legislative language</a> that created the NCCAM's National Advisory Council for Complementary and Alternative Medicine (NACCAM): <blockquote>Of the 18 appointed members...Nine...shall be practitioners licensed in one or more of the major systems with which the Center is involved. Six of the members shall be appointed by the Secretary from the general public and shall include leaders in the fields of public policy, law, health policy, economics, and management. Three of the six shall represent the interests of individual consumers of complementary and alternative medicine. </blockquote>Thus there have been 1-3 NDs on the NACCAM since its inception in 1999, although their numbers in general are, by any measure, miniscule: I reckoned there were about 2500 in the U.S. in 2003; the AANP now places that number at 6000. By comparison, there are about 800,000 MDs and 50,000 DOs in the U.S. NDs <a href="http://www.naturopathic.org/content.asp?pl=16&sl=60&contentid=60" mce_href="http://www.naturopathic.org/content.asp?pl=16&sl=60&contentid=60">claim to be well trained</a> to practice what most people think of as family medicine or primary care medicine, although their version of training is chock full of pseudoscientific nonsense and lacks a true residency program. They began by purporting to use only "natural medicines," but in regions where they've become politically connected they've sought, and been granted, the license to <a href="http://www.oregon.gov/OBNM/rules/850-060-0225.-0226_1.pdf" mce_href="http://www.oregon.gov/OBNM/rules/850-060-0225.-0226_1.pdf">prescribe numerous drugs</a>. Predictably, they've recently begun to <a href="http://www.sciencebasedmedicine.org/?p=143" mce_href="http://www.sciencebasedmedicine.org/?p=143">bump people off</a> with such exotic choices as intravenous colchicine and disodium ethylenediaminetetraacetic acid (that pesky <a href="http://www.ncbi.nlm.nih.gov/pubmed/18596934?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" mce_href="http://www.ncbi.nlm.nih.gov/pubmed/18596934?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum">TACT </a>drug), in addition to more folksy nostrums such as acupuncture, vitamin B12, and an "herbal tincture" for a teenage girl who would shortly <a href="http://www.seattleweekly.com/2005-06-08/news/death-by-natural-causes.php" mce_href="http://www.seattleweekly.com/2005-06-08/news/death-by-natural-causes.php">die of asthma</a>. I see that your talk is titled "Complementary and Alternative Medicine: Promising Ideas from Outside the Mainstream." I imagine that it will cover some of the material that you covered at the Yale Symposium, where you used the similar phrase, “Quirky Ideas from Outside the Mainstream.” Without reading more into that word substitution than is warranted, let me assure you that there are no promising ideas emanating from naturopathy, even if there are plenty of quirky ones, e.g., <a href="http://www.sciencebasedmedicine.org/?p=62" mce_href="http://www.sciencebasedmedicine.org/?p=62">inflating balloons in the nasopharynx</a> to effect a “controlled release of the connective tissue tension to unwind the body and return it toward to its original design." Regarding the implicit requirement of your office that you appear open-minded even to medical absurdities, you made that clear in <a href="http://nccam.nih.gov/about/offices/od/2010-04.htm" mce_href="http://nccam.nih.gov/about/offices/od/2010-04.htm">your own account</a> of our NCCAM meeting and of <a href="http://theintegratorblog.com/site/index.php?option=com_content&task=view&id=650&Itemid=189" mce_href="http://theintegratorblog.com/site/index.php?option=com_content&task=view&id=650&Itemid=189">another </a>that you'd had a few weeks earlier, involving a group of <a href="http://www.theness.com/neurologicablog/?p=41" mce_href="http://www.theness.com/neurologicablog/?p=41">homeopaths</a> and associated <a href="http://www.theness.com/neurologicablog/?p=40" mce_href="http://www.theness.com/neurologicablog/?p=40">crackpots</a> who called themselves "the leading scientists in the field": <blockquote>Recently, I hosted two meetings with groups that represent disparate views of CAM research. These meetings have given me a renewed appreciation for the value of listening to differing voices and perspectives about the work we do. My NCCAM colleagues and I know there are differing views of the value of doing CAM research. On one side, we have stakeholders who are staunch CAM advocates, and on the other side, we have CAM skeptics. Each group has its own beliefs and opinions on the direction, importance, and value of the work that NCCAM funds. The advocates would like to see more research dollars supporting various CAM approaches while the skeptics see our research investment as giving undue credibility to unfeasible CAM modalities and want less research funding. As I've stated before, our position is that science must remain neutral, and we should be strictly objective. There are compelling reasons to explore many CAM modalities, and the science should speak for itself. (emphasis yours) </blockquote> Certainly science must remain neutral in the face of not-yet-seen data from rigorous studies, but that is different from what you, in your dual roles as "CAM" Explicator-in-Chief and Steward of Public Funds, must remain. You typically face questions that are, for all purposes relevant to the NIH, to modern medicine, and to the American citizenry, already settled---whether by basic science, clinical studies, rational thinking, or all three. I've offered several examples in the two naturopathy articles linked above. Consider homeopathy, a <a href="http://www.homeowatch.org/policy/aanp.html" mce_href="http://www.homeowatch.org/policy/aanp.html">core claim</a> of "naturopathic medicine" and the subject of your meeting with the "staunch CAM advocates." It makes no more sense for you to remain neutral on that topic than it would for the NIMH Director to remain neutral on exorcisms, or for the NCI Director to remain neutral on Krebiozen. Edzard Ernst, a one-time homeopath whose own portfolio of <a href="http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ernst%20E%22%5BAuthor%5D" mce_href="http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ernst%20E%22%5BAuthor%5D">"CAM" investigations</a> dwarfs the entire output of the NCCAM, puts it <a href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TDC-4XHJVNN-2&_user=6396456&_coverDate=11%2F30%2F2009&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000069771&_version=1&_urlVersion=0&_userid=6396456&md5=30c4f7ae24e5f3dc1403ca0972baf838" mce_href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TDC-4XHJVNN-2&_user=6396456&_coverDate=11%2F30%2F2009&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000069771&_version=1&_urlVersion=0&_userid=6396456&md5=30c4f7ae24e5f3dc1403ca0972baf838">this way</a>: <blockquote>Should we keep an open mind about astrology, perpetual motion, alchemy, alien abduction, and sightings of Elvis Presley? No, and we are happy to confess that our minds have closed down on homeopathy in the same way. </blockquote> Science and skepticism, moreover, are not distinct. Good science involves, first and foremost, skepticism. This is true for the design of any experiment, in which the primary goal is to attempt to falsify the hypothesis, and also for scientific thinking in general. Bruce Alberts, the editor of Science, <a href="http://www.sciencemag.org/cgi/content/full/319/5870/1589" mce_href="http://www.sciencemag.org/cgi/content/full/319/5870/1589">discussed this</a> in a 2008 editorial titled "Considering Science Education": <blockquote>...society may less appreciate the advantage of having everyone acquire, as part of their formal education, the ways of thinking and behaving that are central to the practice of successful science: scientific habits of mind. These habits include a skeptical attitude toward dogmatic claims and a strong desire for logic and evidence. As famed astronomer Carl Sagan put it, science is our best "bunk" detector. Individuals and societies clearly need a means to logically test the onslaught of constant clever attempts to manipulate our purchasing and political decisions. (emphasis added) </blockquote> I believe that you know all this at some level, but that your current job demands that you bend over backward to frame skeptics as extreme---distinguishing them from "neutral" scientists. Thus you, like many <a href="http://www.sciencebasedmedicine.org/?p=150" mce_href="http://www.sciencebasedmedicine.org/?p=150">reporters</a>, have placed skeptics of homeopathy or naturopathy at one end of a contrived belief spectrum, and "staunch CAM advocates" at the other. Please indulge me while I compare this <a href="http://www.sciencebasedmedicine.org/?p=319" mce_href="http://www.sciencebasedmedicine.org/?p=319">version of 'neutrality'</a> with others that exist in the popular domain: <ul><li>Some people feel strongly that the moon landings were a collective hoax. Others feel just as strongly that they really happened.</li><li>Some people believe that the Holocaust didn't happen. Others believe that it did.</li><li>Some people believe that the variety of species on earth is a product of Intelligent Design (ID). Others believe in the theory of evolution by variation and natural selection. </li></ul>This could go on and on, but you probably get the point. The last bullet is more pertinent to your tacit endorsement of the AANP than you might imagine. What follows is a representative <a href="http://web.archive.org/web/20030518030621/http:/www.scnm.edu/news/uploads/ms.pdf" mce_href="http://web.archive.org/web/20030518030621/http:/www.scnm.edu/news/uploads/ms.pdf ">view of herbalism</a> offered by Thomas Kruzel, with whom you will also <a href="http://www.naturopathic.org/content.asp?admin=Y&contentid=363#thomas_kruzel" mce_href="http://www.naturopathic.org/content.asp?admin=Y&contentid=363#thomas_kruzel">share the podium</a> at the convention (he will discuss "Emunctorology"; don't ask). Kruzel is <a href="http://www.aznma.com/viewbulletin.php?id=115" mce_href="http://www.aznma.com/viewbulletin.php?id=115">Past President of the AANP</a> and the former Vice President of Clinical Affairs and Chief Medical Officer at the Southwest College of Naturopathic Medicine. He was selected Physician of the Year by the AANP in 2000, and Physician of the Year by the Arizona Naturopathic Medical Association in 2003: <blockquote>Herbal Medicine: Naturopathic physicians have been trained in the art and science of prescribing medications derived from plant sources. The majority of prescription drugs are derived as well from plants but are often altered and used as single constituents. What makes herbal medicine unique is that plants have evolved along with human beings and have been used as non-toxic medications for centuries.If there is any problem with herbal medicines it is that unless one knows how to prescribe them, they may not be effective. Herbal medications should be prescribed based on the symptoms that the person presents rather than for the name of the disease. Herbal medications are much more effective at relieving the patients symptoms when prescribed in this manner. When prescribed the medicines act with the body’s own innate healing mechanism to restore balance and ultimately allows healing to occur.What’s nice about plant or herbal medicines is that because they are derived from the whole plant they are considerably less toxic to the body. The plant medicine has evolved to work in harmony with the normal body processes rather than taking over its function as many drug therapies do. Because of this herbal medicines may be taken for longer periods of time without the side effects so often experienced with drugs. </blockquote>You are particularly impressed, I hope, by the magical, ID-like claim that "plant medicine has evolved to work in harmony with the normal body processes." Other curious assertions include the conflation of herbal medicine with the core claims of either homeopathy or the non-existent 'allopathy' (we can't tell which)---"...should be prescribed based on the symptoms..."---demonstrating that the author doesn't know much about even the fanciful methods for which he claims expertise; and the dangerously false statement that medicines "derived from the whole plant are considerably less toxic" (than are well-researched and precisely dosed "prescription drugs").Dr. Briggs, please consider the possibility that you no longer must hide your considerable <a href="http://nccam.nih.gov/about/offices/od/briggsCV.pdf" mce_href="http://nccam.nih.gov/about/offices/od/briggsCV.pdf">scientific prowess</a> in order to be a good NCCAM Director. Your 'stakeholders' include not only very small numbers of naturopaths, homeopaths, and other fringe practitioners, but also far larger numbers of citizens who wonder about the validity of what those practitioners are peddling. It is to those citizens that you should be directing your efforts, which ought to begin with sober, objective, skeptical, scientific considerations of the various claims, the vast majority of which can, like balloons in the nasopharynx, be deflated in milliseconds by anyone with even a modest understanding of nature. They don't require clinical trials.Things are changing elsewhere. My colleague Steve Novella has <a href="http://www.sciencebasedmedicine.org/?p=6146" mce_href="http://www.sciencebasedmedicine.org/?p=6146">just written</a> about substantial efforts to deny insurance coverage for homeopathy in the land of its birth, Germany. In the UK, homeopathy has been far more popular than it is here, even to the point of its being funded by the National Health Service. One of the "staunch CAM advocates" who reportedly attended your meeting by teleconference was <a href="http://www.homeopathyworldcommunity.com/video/everyday-homeopathy-lectures" mce_href="http://www.homeopathyworldcommunity.com/video/everyday-homeopathy-lectures">Peter Fisher</a>, Homeopath to the Queen. Yet both the British Medical Association and the House of Commons Science and Technology Committee have seen through the ruse of pseudoscience that is homeopathy, the former declaring it "<a href="http://www.telegraph.co.uk/health/alternativemedicine/7728281/Homeopathy-is-witchcraft-say-doctors.html" mce_href="http://www.telegraph.co.uk/health/alternativemedicine/7728281/Homeopathy-is-witchcraft-say-doctors.html">witchcraft</a>" and latter making this <a href="http://www.parliament.uk/business/committees/committees-archive/science-technology/s-t-homeopathy-inquiry/" mce_href="http://www.parliament.uk/business/committees/committees-archive/science-technology/s-t-homeopathy-inquiry/">statement</a>:<blockquote>The Committee concurred with the Government that the evidence base shows that homeopathy is not efficacious (that is, it does not work beyond the placebo effect) and that explanations for why homeopathy would work are scientifically implausible.</blockquote>American citizens want and deserve, for their tax money, exactly that sort of definitive evaluation of such claims. Your first responsibility, Dr. Briggs, is to them---it is not to the AANP, other "CAM stakeholders," Tom Harkin, Orrin Hatch, or Dan Burton, and certainly not to the members of the NACCAM. Yes, we "skeptics see [the NCCAM] research investment as giving undue credibility to unfeasible CAM modalities," because the <a href="http://www.csicop.org/si/show/ongoing_problem_with_the_national_center" mce_href="http://www.csicop.org/si/show/ongoing_problem_with_the_national_center">evidence is overwhelming</a> that this is the case. We also see your appearing at conventions of <a href="http://www.sciencebasedmedicine.org/?p=247" mce_href="http://www.sciencebasedmedicine.org/?p=247">pseudomedical pseudoprofessional organizations </a>as giving undue credibility to unfeasible and dangerous claims.Sincerely yours,Kimball C. Atwood, M.D. SkepticThis letter has been cross-posted on <a href="http://www.sciencebasedmedicine.org/">Science-Based Medicine</a>.

Open Letter to Dr. Josephine Briggs

Josephine P. Briggs, M.D. Director, National Center for Complementary and Alternative Medicine Dear Dr. Briggs, As you know, we've met t...

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INSEL and NEMEROFF - WHAT SANCTIONS?

INSEL and NEMEROFF – WHAT SANCTIONS? Thomas Insel, Director of NIMH, has another <a href="http://www.nimh.nih.gov/about/director/2010/more-on-public-trust-and-conflict-of-interest.shtml">posting</a> in his own defense on his official blog today. He has been widely <a href="http://http//hcrenewal.blogspot.com/2010/06/public-trust-at-nimh.html">criticized</a> lately for the appearance of cronyism in his relationship with Charles Nemeroff. For the past three months, Insel has been trying to put some distance between himself and Nemeroff, but the public isn’t buying it. I have called his statements disingenuous <a href="http://hcrenewal.blogspot.com/2010/04/quis-custodiet-ipsos-custodes.html">here</a> and <a href="http://www.miamiherald.com/2010/06/10/1672327/senator-tells-um-hes-troubled.html">here</a>. Dr. Insel’s statements today are equally disingenuous. <a href="http://1boringoldman.com/index.php/2010/06/15/de-barred-not-a-bad-idea/">Negative reactions</a> are already appearing from those familiar with Nemeroff’s history. There is no argument that Nemeroff was instrumental in Insel’s move to Emory in 1994, that Nemeroff was Insel’s department chairman at Emory, that Nemeroff helped Insel again when Insel’s initial term as director of the Yerkes laboratory at Emory was not renewed in 1999, or that Nemeroff lobbied for Insel’s appointment as NIMH Director in 2002. There is no argument that Insel and Nemeroff have given <a href="http://hcrenewal.blogspot.com/2010/04/quis-custodiet-ipsos-custodes.html">glowing public recommendations </a>of each other, or that they have a record of <a href="http://www.pharmalot.com/2010/06/can-the-nih-really-monitor-conflicts-of-interest/">cozy personal communications</a>. There is no doubt that Pascal Goldschmidt at Miami sought and received a recommendation from Insel before hiring Nemeroff last year or that Insel went out of his way to put a personal gloss on the official NIH position regarding Nemeroff’s eligibility for grant funding if he left Emory. These are matters about which Dr. Insel prevaricates today in his blog. Continuing his prevarication, Dr. Insel today also avoids confronting the issue of Nemeroff’s continuing service on NIMH review committees under Insel’s watch during the period that he was under sanction by Emory University, and banned from participating in NIH grants – before he relocated to Miami. Nemeroff’s curriculum vitae on the U Miami website states that he is a member of the NIMH Review Group, Interventions Committee for Adult Mood and Anxiety Disorders (ITAV), 7/1/2006 - 6/30/2010. This means Insel allowed Nemeroff to continue in that peer review role even though he was banned by Emory from association with NIH grants. The question is why? And what does that tell us about Insel's judgement? It gets worse. During the period that Nemeroff was at Emory and under sanction vis à vis NIH grants, he continued to function as operational director of a NIMH-funded program administered by the American Psychiatric Association (APA). It is inconceivable that Insel was not aware of this arrangement. The APA program is known as Research Colloquium for Junior Investigators, and it is funded through NIMH project # 5R13MH064074-10. For the past few years Nemeroff, as Chair of the APA Committee on Research Training, has directed this program. The nominal Principal Investigator is Darrel Regier, who is the Executive Director of the American Psychiatric Institute for Research and Education (APIRE). At the session in New Orleans during the annual APA meeting last month, one of the featured speakers was Bruce Cuthbert, PhD, one of Insel’s principal lieutenants. In God’s name, why is the APA fronting the compromised Nemeroff as a role model to junior investigators, and why does NIMH/Insel allow this unsavory arrangement to continue? Could it be that Nemeroff’s crony <a href="http://hcrenewal.blogspot.com/2008/08/follow-money-part-ii.html">Alan Schatzberg</a>, the outgoing president of the APA, ran interference for his friend? And what will the new APA president Carol A. Bernstein do about it? And then there is the issue of Nemeroff’s appointment to two new NIMH review committees just recently. Dr. Insel prevaricates again about his awareness or approval of those actions. As reported by Paul Basken in the <a href="http://chronicle.com/article/While-Revising-Ethics-Rules/65800">Chronicle of Higher Education</a>, “An NIH spokesman, John T. Burklow, answering written questions about the matter, confirmed Dr. Nemeroff's full eligibility for agency activities and said he will begin serving this coming week on two scientific panels that review NIH grant applications.” Here again, Dr. Insel seems to be trying to help his crony Nemeroff to get back into circulation after his fall from grace at Emory. Emory University went through the wringer to discipline Nemeroff, at long last, in 2008. The actions of Insel in running interference for Nemeroff’s rehabilitation must leave Emory perplexed. Are Dr. Insel’s statements today disingenuous? You bet. Isn’t it time for the adults at NIH to step in and end this farce?

INSEL and NEMEROFF - WHAT SANCTIONS?

INSEL and NEMEROFF – WHAT SANCTIONS? Thomas Insel, Director of NIMH, has another posting in his own defense on his official blog today. He ...

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Public Trust at NIMH?

Public Trust at NIMH? The NIMH Director, Thomas Insel, MD, is under siege for his problematic relationship with Charles Nemeroff. In his own defense, Insel placed a remarkable new <a href="http://www.nimh.nih.gov/about/director/2010/nimh-reducing-conflict-of-interest-ensuring-public-trust.shtml">post</a> today on his official blog. It signals that Insel and NIMH just don’t understand the current controversy. Since the story appeared in <a href="http://chronicle.com/article/While-Revising-Ethics-Rules/65800">The Chronicle of Higher Education</a> 2 days ago, it has reverberated on <a href="http://hcrenewal.blogspot.com/2010/06/happy-times-at-nimh-part-iii.html">Health Care Renewal</a>, on <a href="http://www.pharmalot.com/2010/06/can-the-nih-really-monitor-conflicts-of-interest/">Pharmalot</a>, on <a href="http://www.margaretsoltan.com/?p=23664">University Diaries</a>, on the <a href="http://blogs.nature.com/news/thegreatbeyond/2010/06/another_conflict_brouhaha_for_1.html">Nature blog</a>, on the <a href="http://news.sciencemag.org/scienceinsider/2010/06/nih-conflicts-overhaul-bumps-up-.html">Science blog</a>, and on <a href="http://scienceblogs.com/drugmonkey/2010/06/more_evidence_that_the_nih_has.php?utm_source=networkbanner&utm_medium=link">Drug Monkey</a>, to name just a few. The authors on these sites have been uniformly critical of Insel and of NIMH, as have almost all the comments. What does Dr. Insel say in his defense today? Mainly, he demonstrates that he doesn’t get it. The very way in which he frames the issue tells us that. First he says it is about financial conflicts of interest. It isn’t. It is about the corruption of academic psychiatry. Financial conflicts of interest are just a part of that problem. Second, he says it is about whether the bad boys and girls in psychiatry were badder than those in other medical specialties. It isn’t. It never was. Third, he says he is surprised by criticism that he and NIMH have not taken firm action against the bad boys and girls, then he spends the rest of his column evading that issue. This degree of sophisticated indirection is achieved only in the highest echelons of bureaucracies. Instead of a frank discussion of the real issues, we get a self serving description of the ways in which NIMH has taken steps to preserve the integrity of the research that it funds (starting after the scandal about the bad boys and girls broke within the Senate Finance Committee in 2008 – a detail not included by Dr. Insel. Where were they before?). By the time one makes it through this glossed-up history and the new promissory notes, it is easy to lose sight of what provoked the controversy this week. It’s about the appearance of hypocrisy, with Insel assisting the compromised Nemeroff to land a new job at Miami while he is co-chairing a NIH effort to revise ethics guidelines. It’s about consistency of discipline. After Emory University went through the wringer to discipline Nemeroff, at long last, and to ban him from involvement with NIH grants for 2 years, doesn’t NIH have a responsibility to make the discipline stick? After all, NIH deferred to Emory in the investigation of Nemeroff to begin with. What message does it send for Insel, a well known crony of Nemeroff, to blithely assure Pascal Goldschmidt at Miami that Nemeroff is “absolutely in fine standing” with NIH and that he “not only could begin applying for NIH grants as soon as he arrived in Coral Gables, but that he could also continue to serve on the NIH's expert panels that help decide on which grant applications win federal financing?” As Drug Monkey said, “It’s about optics, NIH. This doesn’t look good.” It looks instead like cronies exploiting the gaps and inconsistencies in administrative oversight between academic centers and NIH. It’s also about common sense and administrative propriety. Let us perhaps grant that Insel could not prevent or discriminate against Nemeroff in applying for new NIMH funding. There is weasel wording to cover Insel if he chose to take such a position. But does that mean Insel has no discretion over whether Nemeroff is invited onto two new NIMH review panels? Nemeroff has no entitlement to claim a place on these peer review panels. Whatever possessed Insel to extend this privilege to a compromised individual like Nemeroff? The answer plainly is that Insel doesn’t recognize the compromise and corruption of his crony Nemeroff. The appearance is that Insel is setting out to help Nemeroff get back into circulation after his fall from grace at Emory. By his own blog posting today Insel tells us that he lacks the grasp of nuanced issues that his position requires. He doesn’t get the big picture in this controversy or, if he does, he wants to evade it. Either way, NIMH deserves better. Bernard Carroll.

Public Trust at NIMH?

Public Trust at NIMH? The NIMH Director, Thomas Insel, MD, is under siege for his problematic relationship with Charles Nemeroff. In his own...

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Quis Custodiet Ipsos Custodes?

HAPPY TIMES AT NIMH Two weeks ago I <a href="http://hcrenewal.blogspot.com/2010/03/dr-pangloss-as-nih-institute-director.html">discussed</a> a Commentary in JAMA by Dr. Thomas Insel, Director of the National Institute of Mental Health. Over on <a href="http://carlatpsychiatry.blogspot.com/2010/03/dr-tom-insel-nimh-chief-scolds.html">Danny Carlat’s blog</a>, Dr. Insel took exception to my linking him with Charles Nemeroff, and appeared to be putting distance between himself and Dr. Nemeroff. So, I did some checking, and a correction to one of my statements is in order. I had said, “ … that Insel appointed Nemeroff as an advisor soon after he (Insel) moved to NIMH.” That was my recollection. It turns out what I recalled was instead Insel showcasing Nemeroff in the NIMH Director’s 7th Annual Research Roundtable June 10, 2003, a few months after Insel moved from Emory University to NIMH. Let the record stand corrected. At that gala meeting, held at the National Press Club in Washington, DC, Dr. Insel characterized Nemeroff as one of the “real stars of NIMH’s research community…” Nemeroff used the occasion to pimp GlaxoSmithKline’s drug paroxetine (Paxil), showing data on change in platelet stickiness after Paxil in patients with heart disease and depression. This highlighting of Paxil by Nemeroff focused on the surrogate outcome of platelet function, and contained no evidence that Paxil modified any important clinical endpoints. Nevertheless, Nemeroff speculated liberally about the place of antidepressant drugs in managing heart disease. This is the sort of stuff Insel described at the Roundtable as “ … an excellent sampling of the Institute’s exciting research endeavors.” My general point two weeks ago was that Dr. Insel, the Director of an NIH Institute, downplayed the seriousness of the ethics issues surrounding the seven academic psychiatrists he mentioned in his Commentary in JAMA. Though he spoke in platitudes about the need for transparency, the spirit of transparency did not move him to disclose his own close ties with Dr. Nemeroff, who is one of the seven. Lest there be any remaining doubt about those ties, here is Dr. Nemeroff lauding Dr. Insel at the 201st meeting of the National Advisory Mental Health Council September 13, 2002 in the presence of the NIH Director, Elias Zerhouni, MD. From the Minutes: Dr. Charles Nemeroff, Reunette W. Harris Professor and Chair, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, commended Dr. Zerhouni’s selection of Dr. Insel as the next NIMH Director and added that Dr. Insel is the epitome of courage defined as grace under pressure. Dr. Nemeroff added that Dr. Insel will leave his current position as a most beloved professor, a respected scientist, and a great person. In the comments on Danny Carlat’s blog I called Dr. Insel’s objections to my linking him with Nemeroff disingenuous. I still think that. Dr. Insel and Dr. Nemeroff are closer than Insel now seems comfortable acknowledging. Their record of talking up each other is hard to ignore. The irregularities identified by Senator Grassley involving Nemeroff’s reporting to NIH, his conflict of interest, and his conflict of commitment occurred on Insel’s watch. Considering the appearance of cronyism in their relationship, is it even possible for Dr. Insel to investigate Dr. Nemeroff’s performance in areas like the Emory-GlaxoSmithKline-NIMH Collaborative Mood Disorders Initiative? Bernard Carroll

Quis Custodiet Ipsos Custodes?

HAPPY TIMES AT NIMH Two weeks ago I discussed a Commentary in JAMA by Dr. Thomas Insel, Director of the National Institute of Mental Health...

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DR. PANGLOSS AS NIH INSTITUTE DIRECTOR

DR. PANGLOSS AS NIH INSTITUTE DIRECTOR JAMA is out today with a <a href="http://jama.ama-assn.org/cgi/content/extract/303/12/1192">Commentary</a> by Dr. Thomas Insel, Director of the National Institute of Mental Health. Using indirection, Dr. Insel has risen to the defense of seven academic psychiatrists on whom an ethical searchlight has been trained for the past several years by Senator Grassley and others. With ludicrous optimism and a series of straw man discussions, Dr. Insel makes the case that things are not really as bad as they seemed to be or, if they were, then other specialty physicians were doing much the same things. Dr. Insel needs to recalibrate his ethical compass. Why is an NIH Institute Director issuing this apologia for the corruption of academic psychiatry? Does he not have better things to do, such as ensuring that longstanding NIH regulations on conflict of interest are enforced? Why does an NIH Institute Director presume to speak for academic psychiatry? Where are the leaders of the major professional and scientific organizations like the American Psychiatric Association, the American College of Psychiatrists, the American College of Neuropsychopharmacology, and the Society of Biological Psychiatry? Why are they not stepping up publicly to the plate? Perhaps they are confounded by the awkward fact that some of the seven individuals are current and past presidents of these very organizations. Even the Institute of Medicine of the National Academy of Sciences has not sanctioned those of the seven who are Institute members. Why is an NIH Institute Director downplaying the gravity of the ethical controversies surrounding these compromised individuals like Charles Nemeroff at Emory (now at Miami), and Alan Schatzberg at Stanford? To hear Dr. Insel tell it, all they did was fail to disclose income from pharmaceutical companies. That is not the half of it. Readers can look <a href="http://hcrenewal.blogspot.com/search?q=Nemeroff">here</a> and <a href="http://hcrenewal.blogspot.com/search?q=Schatzberg">here</a> for much more detail on the activities of Nemeroff and Schatzberg. If Dr. Insel chose to remain ignorant of or to overlook the history of false claims on behalf of pharmaceutical corporations or the concealment of consulting relationships or the complaisance with ghostwriting or the patently misleading “educational” presentations or the cashing in through stock sales or the editorial self dealing, then Dr. Insel’s fitness to serve as an NIH Institute Director needs to be reviewed. Surely Dr. Insel knows that Nemeroff and the others worked mainly with the marketing personnel within pharmaceutical companies. Nemeroff’s staggering schedule of promotional talks for GlaxoSmithKline, released by Senator Grassley, is testament to that. So is Nemeroff’s record of priming the pump for himself with GSK by giving the corporation unpublished research data from NIMH-funded projects at Emory. In turn, GSK and its medical education communications company, Scientific Therapeutics Information, Inc., incorporated Nemeroff’s privileged material in the training manual for PsychNet – a speaker program designed to build advocacy for GSK’s antidepressant drug Paxil. These issues go well beyond just failing to report income. They signify the corruption of academic psychiatry. Doesn’t Dr. Insel understand that? In his Commentary, Dr. Insel reported no financial disclosures. This is a good example of the problem that Dr. Insel doesn’t see. Many readers will interpret this Commentary from the Director of NIMH as the opening move in the attempted rehabilitation of Charles Nemeroff by his friends and cronies. Though Dr. Insel spoke in platitudes about the need for transparency as a solution, the spirit of transparency did not move him to disclose that Nemeroff is his former boss at Emory; that Nemeroff found a position for him when Insel was departing the intramural research program at NIMH; that Nemeroff lobbied for Insel’s appointment as NIMH Director; and that Insel appointed Nemeroff as an advisor soon after he moved to NIMH. These are pertinent conflicts of interest that readers of JAMA deserve to know about. Quis custodiet ipsos custodes? Maybe Dr. Insel should stick to his knitting and resist the impulse to speak for academic psychiatry as a whole. A good place for him to start looking hard would be at the productivity and accounting of the once vaunted Emory-GSK-NIMH Collaborative Mood Disorders Initiative (Principal Investigator Charles B. Nemeroff; 5U19MH069056). One never knows what one will find when the rocks are turned over.

DR. PANGLOSS AS NIH INSTITUTE DIRECTOR

DR. PANGLOSS AS NIH INSTITUTE DIRECTOR JAMA is out today with a Commentary by Dr. Thomas Insel, Director of the National Institute of Menta...

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Seeking NIH to fund studies on medical ethics, conflicts of interest in medicine and research, and prescribing behavior

Adriane Fugh-Berman MD is principal investigator (PI) of the <a href="http://pharmedout.org/">PharmedOut</a> project. PharmedOut is an independent, <a href="http://pharmedout.org/aboutus.htm">publicly funded</a> Georgetown University Medical Center project that educates physicians about industry influence on prescribing. project that empowers physicians to identify and counter inappropriate pharmaceutical promotion practices. PharmedOut promotes evidence-based medicine by providing news, resources, and links to pharma-free CME courses. PharmedOut is requesting that the U.S. NIH (National Institutes of Health) fund more research into ethics, conflicts of interest, and prescribing behavior. One hundred researchers, clinicians, and ethicists have signed a letter sponsored by PharmedOut asking NIH to fund research on medical ethics, conflicts of interest, and industry influence on prescribing behavior. Stimulus funds have increased the NIH budget by ten billion dollars, but NIH has no mechanism for funding research on how commercial interests affect the choice of medical therapeutics. Signers include Virginia Barbour MD, Chief Editor of PLoS Medicine, Jerome Kassirer, MD, former editor in chief of the New England Journal of Medicine, Jerry Avorn MD, the Harvard physician who invented academic detailing, Kay Dickersin PhD, Director of the U.S. Cochrane Center, and Susan Wood, PhD, former head of the FDA Office of Women’s Health Research, who resigned over political influence regarding FDA decisions on the emergency contraceptive Plan B. Institutional signers include the Public Library of Science, the American Medical Student Association, the National Physicians Alliance, Consumers Union, the Center for Science in the Public Interest, and the National Women’s Health Network. The letter, sent to NIH today, is available at <a href="http://www.pharmedout.org/NIHLetter.pdf">http://www.pharmedout.org/NIHLetter.pdf</a> (PDF) and below: <blockquote>Nov. 17, 2009 From: Adriane Fugh-Berman MD Department of Physiology and Biophysics Georgetown University Medical Center Box 571460 Washington DC 20057-1460 Phone: (202) 687-7845 Fax: (202) 687-7407 ajf29 AT georgetown DOT edu To: Francis S. Collins, MD, PhD Director National Institutes of Health 9000 Rockville Pike Bethesda, MD 20892 Dear Dr. Collins, We are writing to ask NIH to fund studies on medical ethics, conflicts of interest in medicine and research, and prescribing behavior. NIH funds a substantial portion of the generation and dissemination of evidence, but the uptake of that evidence and its translation into clinical practice is strongly affected by the complex web of relationships that exists among industry, academicians, medical educators and clinicians. There is growing evidence that each strand of this web is compromised by ethical lapses and financial conflicts of interest. The recent disclosure of ghostwritten articles, physician payoffs, and the use of academic opinion leaders to increase markets for FDA-regulated products indicate that ethical lapses may permeate biomedical research. A PLoS Medicine editorial in September called ghostwriting “The dirty little secret of medical publishing” and notes “the systematic manipulation and abuse of scholarly publishing by the pharmaceutical industry and its commercial partners in their attempt to influence the health care decisions of physicians and the general public.” [1] An October 1 editorial in the Boston Globe called for a ban on industry speaker fees to physicians. [2] Last month, a commentary in JAMA called for physicians to pay for continuing medical education (CME), [3] citing a recent Institute of Medicine report [4] that criticized physicians’ reliance on industry-funded education. A stated goal of the NIH is to “exemplify and promote the highest level of scientific integrity, public accountability, and social responsibility in the conduct of science.” Could the muted effect that large, definitive NIH studies, including the WHI, ALLHAT, and CATIE, have had on clinical practice be due to commercial influences? To what extent have ghostwritten articles corrupted the medical and scientific literature? The extent to which industry influences the interpretation of science is unknown. Dr. Elias Zerhouni, in the September 17th issue of Nature, commenting on Senator Grassley’s investigation of academic medical centers, said “People flouted the rules, didn’t disclose, and did it for years on end, repeatedly.” [5] In your role as the director of “the steward of medical and behavioral research for the Nation,” we ask that you acknowledge the research gap on the effect of conflicts of interest and commercial influence on medical decisionmaking and set in motion a process that leads to recognition of the importance of funding studies on research ethics, the beliefs and behaviors of researchers and clinicians, and the effects of industry-academic relationships on the generation and dissemination of medical knowledge. Between bench and bedside lies a path treacherous with ethical quandaries. NIH is the best place to launch and support a scientifically rigorous inquiry into the state of research ethics, industry-academic relationships, and the effect of these relationships on human health. There is currently no identifiable mechanism through which NIH would fund this research. Your leadership regarding the importance of this issue as one the NIH needs to direct resources towards is essential. We hope to discuss these issues in a face-to-face meeting. Sincerely, Adriane Fugh-Berman, MD Associate Professor, Georgetown University Medical Center Director, PharmedOut ajf29 AT georgetown DOT edu http://pharmedout.org [and others whose signatures can be seen at the PDF - ed.] [1] Ghostwriting: The Dirty Little Secret of Medical Publishing That Just Got Bigger. PLoS Medicine, September 8, 2009. <a href="http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000156">http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000156</a> [2] Keep Doctors Independent; Ban Fees From Drug Makers. Boston Globe, October 1, 2009. <a href="http://www.boston.com/bostonglobe/editorial_opinion/editorials/articles/2009/10/01/keep_doctors_independent_ban_fees_from_drug_makers/">http://www.boston.com/bostonglobe/editorial_opinion/editorials/articles/2009/10/01/keep_doctors_independent_ban_fees_from_drug_makers/</a> [3] Campbell EG, Rosenthal M. Reform of Continuing Medical Education: Investments in Physician Human Capital. JAMA. 2009;302(16):1807-1808. <a href="http://jama.ama-assn.org/cgi/content/full/302/16/1807?home">http://jama.ama-assn.org/cgi/content/full/302/16/1807?home</a> [4] Institute of Medicine. Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: National Academies Press; April 28, 2009. <a href="http://www.iom.edu/CMS/3740/47464/65721.aspx">http://www.iom.edu/CMS/3740/47464/65721.aspx</a> [5] Wadman M. The Senator’s sleuth. Nature. 2009 Sept;461(17):330-4. </blockquote>This letter caught my eye, and I expressed support as follows, adding an additional angle to Dr. Fugh-Berman's letter: <blockquote>Dear Dr. Fugh-Berman, As a blogger at Healthcare Renewal, I will enthusiastically sign on to and endorse your letter calling on NIH to fund more research into ethics, conflicts of interest, and prescribing. I also wish to add an extended point: The issues of ethics and conflict of interest also affect healthcare information technology (HIT), and ultimately physician practice. HIT applications are experimental medical devices now being pushed upon physicians via the Office of the National Coordinator and HHS. These medical devices are soon to undergo regulation as such in the EU (pdf report from the Swedish Medical Products Agency <a href="http://www.lakemedelsverket.se/upload/foretag/medicinteknik/en/Medical-Information-Systems-Report_2009-06-18.pdf">here</a>), <a href="http://www.hc-sc.gc.ca/dhp-mps/md-im/activit/announce-annonce/md_notice_software_im_avis_logicels-eng.php">Canada</a>, the <a href="http://www.genomeweb.com/dxpgx/electronic-health-record-systems-will-require-some-form-oversight-government-adv">U.S.</a> and other countries as well. They are used in patient care without patient consent. Their use holds significant potential to monitor and enforce practices deemed appropriate by whomever has the most influence on the bodies controlling the use of these technologies and the data they generate. From that perspective, and from the perspective of the 2009 National Research Council report that calls for accelerating interdisciplinary research in biomedical informatics, computer science, social science [i.e., the social and ethical implications of health IT], and health care engineering as a sine qua non of health IT success, I believe it is time for NIH to take a leadership role in regulating these devices, conflicts of interest in the health IT industry, and the ethics of their use.</blockquote> I perhaps should have written "I believe it is time for NIH to take a leadership role in sponsoring research on regulating these devices, conflicts of interest in the health IT industry, and the ethics of their use", rather than calling on NIH to be a regulator. However, until the regulatory affairs concerning health IT are in order, I felt the stronger statement appropriate. -- SS

Seeking NIH to fund studies on medical ethics, conflicts of interest in medicine and research, and prescribing behavior

Adriane Fugh-Berman MD is principal investigator (PI) of the PharmedOut project. PharmedOut is an independent, publicly funded Georgetown...

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Who Investigated the Case of the Deadly Contaminated Heparin?

A year and a half ago, we posted quite a bit about the case of the deadly contaminated heparin. In retrospect, what is most amazing is how quickly this case fell off the radar screen. Summary of the Case of the Deadly Contaminated Heparin Here is a summary: - We have posted several times, recently <a href="http://hcrenewal.blogspot.com/2008/03/heparin-in-era-of-hogwash.html">here</a> and <a href="http://hcrenewal.blogspot.com/2008/03/fake-heparin-then-sick-and-dead.html">here</a>, about the tragic case of suddenly allergenic heparin. Although heparin, an intravenous biologic anti-coagulant, has been in use for over 70 years, serious allergic reactions to it had heretofore been rare. Starting late last year, hundreds of such reactions, and now 21 deaths were reported in the US after intravenous heparin infusions.All the heparin related to these events in the US was made by <a href="http://www.baxter.com/">Baxter International</a>. - We then learned that although the heparin carried the Baxter label, it was not really made by Baxter. The company had outsourced production of the active ingredient to a long, and ultimately mysterious supply chain. Baxter got the active ingredient from a US company, <a href="http://www.spl-pharma.com/">Scientific Protein Laboratories LLC</a>, which in turn obtained it from a factory in China operated by <a href="http://www.spl-pharma.com/changzhou.htm">Changzhou SPL</a>, which in turn was owned by Scientific Protein Laboratories and by <a href="http://www.techpool.com.cn/english/index.asp">Changzhou Techpool Pharmaceutical </a>Co. Changzhou SPL, in turn, got it from several consolidators or wholesalers, who in turn got it from numerous small, unidentified "workshops," which seemed to produce the product in often primitive and unsanitary conditions. None of the stops in the Chinese supply chain had apparently been inspected by the US Food and Drug Administration nor its Chinese counterpart. - Most recently, we found out that the Baxter International labelled heparin was contaminated with over-sulfated chondroitin sulfate, a substance not found in nature, but which mimics heparin according to the simple laboratory tests used in the Chinese facilities to check incoming heparin. (See post <a href="http://hcrenewal.blogspot.com/2008/03/fake-heparin-then-sick-and-dead.html">here</a>.) Further testing revealed that the contamination seemed to have taken place in China prior to the provision of the heparin to Changzhou SPL. (See post <a href="http://hcrenewal.blogspot.com/2008/03/who-was-responsible-for-purity-of.html">here</a>.) It is not clear whether Baxter International or Scientific Protein Laboratories had inspected most of the steps in the supply chain, or even knew what went on there. - The Baxter and Scientific Protein Laboratories CEOs did not seem aware of where they got the heparin on which the Baxter International label was eventually affixed. But one report in the New York Times alleged that Scientific Protein Laboratories would not pay enough for heparin to satisfy any sources other than the small "workshops." - Leaders of all organizations involved, Baxter International, Scientific Protein Laboratories, Changzhou SPL, the Chinese government, and the US Food and Drug Administration, and the US Congress assigned blame to each other, but none took individual or organizational responsibility. (See post <a href="http://hcrenewal.blogspot.com/2008/05/blaming-some-dude-for-contaminated.html">here</a>.) Since we last posted about the case, three prominent articles by one research group appeared that addressed how contamination of the heparin with oversulfated chondroitin sulfate lead to adverse reactions, some fatal (1-3). An editorial in the New England Journal of Medicine congratulated all the scientists on quickly figuring out the nature of the problem, "allowing heparin to come clean," but did not comment on what the case might mean for drug regulation, or the leadership of health care organizations.(4) The case was used to illustrate the difficulties of national regulation of an increasingly out-sourced pharmaceutical industry.(5) Dr Jerry Avorn did call for more effective, better funded and up to date pharmaceutical regulation.(6) At the time, I thought that the most striking feature of this case, beyond the deaths of many real patients, was how every leader involved tried to dodge accountability for it. Now, in August, 2009, I have been unable to discover whether any of them subsequently took accountability for it. And in this post global financial collapse world, I would now add that the case also exemplifies the adverse effects of the single-minded pursuit of short-term profit and economic efficiency. However, in retrospect, the most distressing aspect of this case is its lack of repercussions, specifically, the lack of any inquiry into how the oversulfated chondroitin sulfate got into the supposedly pure heparin given to patients, and how such adulteration of pharmaceuticals could be prevented in the future. Allegations of Conflicts of Interest Affecting the Scientific Investigation of the Case This week, however, the case has an eerie echo. The Wall Street Journal just <a href="http://online.wsj.com/article/SB125003545637224263.html">reported</a> allegations that the US FDA official involved in the case has conflicts of interest. <blockquote>The investigation of Janet Woodcock, the director of the FDA's Center for Drug Evaluation and Research, stems from an ethics complaint filed by Amphastar Pharmaceuticals Inc., a California company that says it has been delayed in its six-year effort to win approval for a generic version of Lovenox, a multi-billion-dollar blood thinner. In its complaint, Amphastar alleges that its competitor had special access to Dr. Woodcock at critical times in the prolonged approval process, which is ongoing. Amphastar points out that Dr. Woodcock co-authored a scientific paper with scientists at Momenta Pharmaceuticals Inc. while both companies were battling to win FDA approval of their generic blood thinners. Amphastar contends that Dr. Woodcock's collaboration with Momenta is a conflict of interest and has asked that she recuse herself from the entire matter at the FDA. Both Amphastar and Momenta, which is based in Cambridge, Mass., submitted applications seeking FDA approval of their generic versions of Lovenox heparin sold by Sanofi-Aventis SA. Amphastar applied in 2003, two years before Momenta. Lovenox, a low-molecular-weight heparin, is a blockbuster biologic drug that brought in $3.5 billion in world-wide sales last year. </blockquote>The specific allegations were: <blockquote>Amphastar, in letters sent to the FDA in April and June, cited some public contacts and email between Dr. Woodcock and one of Momenta's founders, Massachusetts Institute of Technology biological engineering professor Ram Sasisekharan, beginning in February 2007. Among those contacts were their attendance at an international medical conference in Thailand in November 2007. Mainly, however, Amphastar points to Dr. Sasisekharan's appointment to lead an FDA task force in early 2008, which put him and Momenta in regular contact with the agency. That task force was investigating tainted Chinese-made heparin, a crisis that led to nearly 100 deaths. Drs. Woodcock and Sasisekharan, along with other Momenta scientists, then co-authored two medical journal articles last year identifying the cause of the contaminated Chinese heparin imports, a finding that won scientific -- as well as Wall Street -- kudos for Momenta. It is unusual for FDA officials to co-author journal articles with industry researchers.... In April 2008, after the tainted-heparin article was published, an investment report from Morgan Stanley cited Momenta's FDA connection as a 'game-changer,' and Momenta's stock jumped 17% in a day. </blockquote>So, Dr Woodstock arranged for the scientific investigation of the contaminated heparin to be carried out mainly by people employed by or with financial relationships with <a href="http://www.momentapharma.com/">Momenta Pharmaceuticals</a>. The (actually three) articles published as a result of this investigation (1-3), disclosed most of these relationships, but seemed to minimize the relationship of the senior author of all three articles, Dr Ram Sasiskekharan, to the company. Although he was actually a co-founder of the company, and has been on the <a href="http://ir.momentapharma.com/directors.cfm">board of directors </a>of the company since 2001, none of the articles mentioned the former relationship, and only one specifically mentioned the latter. Although the two New England Journal of Medicine articles referred to Momenta Pharmaceuticals' abilities to analyze "complex mixtures, including heparin," none mentioned that the company is developing two anticoagulant products, M-enoxaparin and M118, which could compete with heparin (as described in the company's <a href="http://ir.momentapharma.com/index.cfm">investor relationships web-page</a>). On the other hand, the Nature Biotech article(3) noted that Dr Sasiskekharan and one other author have "served as scientific advisors to Scientific Protein Laboratories," and a third author was a scientific advisor to Baxter International. The relationship between Dr Sasiskekharan and SPL was noted by two of the New England Journal articles(1-2). Questions Raised So the complaint about Dr Woodcock by Amphastar raises multiple questions about the investigation of the case of the deadly contaminated heparin. <ul><li>Why did the FDA put the scientific investigation of Baxter International/ Scientific Protein Laboratories / Changzhou SPL contaminated heparin in the hands of multiple employees, and the co-founder and board member of Momenta Pharmaceuticals, a company that applied to market a product to compete with heparin?</li><li>Was the nature of this apparent conflict clear to the federal agencies that also funded the investigation, which included the National Institutes of Health (NIH) and the Centers for Disease Control (CDC)?</li><li>Did the federal agencies involved also realize that several of the investigators, including the apparent senior investigator, also had ties to two companies (Baxter International and Scientific Protein Laboratories) involved in the production of the contaminated heparin?</li><li>If the federal agencies did not know of the conflicts, why not? And what will they do about them now?</li><li>If the federal agencies did know of all the conflicts, why did they allow such a conflicted group of scientists to investigate one of the most important cases of drug adulteration of the new century?</li></ul>Although there has now been a scientific investigation into the nature of the contamination of the deadly heparin, there has not been any formal inquiry of which I am aware into the actions, decisions and events that allowed the case to unfold. Now that the case seems to involve not only questionable business management decisions, but also a conflicted scientific investigation, maybe someone in authority will see to it that such an investigation occurs. Finally, the case of the deadly contaminated heparin now becomes another illustration of how the complex web of conflicts of interest that pervades our health care system may muddle efforts to protect the public from adulterated medicines, one of the more fundamental public health responsibilities of the government. Hat tip to and see further <a href="http://www.margaretsoltan.com/?p=16272">comments</a> by Prof Margaret Soltan in the University Diaries blog. References 1. Kishimoto TK, Viswanathan K, Ganguly T, Elankumaran S, Smith S, Pelzer K et al. Contaminated heparin associated with adverse clinical events and activation of the contact system. N Engl J Med 2008; 358: 2457-67. [Link <a href="http://content.nejm.org/cgi/content/abstract/NEJMoa0803200v2">here</a>.] 2. Blossom DB, Kallen AJ, Patel PR, Elward A, Robinson L, Gao G et al. Outbreak of adverse reactions associated with contaminated heparin. N Engl J Med 2008; 359: 2674-84. [Link <a href="http://content.nejm.org/cgi/content/full/359/25/2674">here</a>.] 3. Guerrini M, Becaati D, Shriver Z, Naggi A, Viswanathan K, Bisio A et al. Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Nature Biotech 2008; 26: 669-675. [Link <a href="http://www.nature.com/nbt/journal/v26/n6/full/nbt1407.html">here</a>.] 4. Schwartz LB. Heparin comes clean. N Engl J Med 2008; 358: 2505-9. [Link <a href="http://content.nejm.org/cgi/content/full/358/23/2505">here</a>.] 5. Schweitzer SO. Trying times at the FDA - the challenge of ensuring the safety of imported pharmaceuticals. N Engl J Med 2008; 358: 1773-7. [Link <a href="http://content.nejm.org/cgi/content/full/358/17/1773">here</a>.] 6. Avorn J. Coagulation and adulteration - building on science and policy lessons from 1905. N Engl J Med 2008; 358: 2429-31. [Link <a href="http://content.nejm.org/cgi/content/full/358/23/2429">here</a>.]

Who Investigated the Case of the Deadly Contaminated Heparin?

A year and a half ago, we posted quite a bit about the case of the deadly contaminated heparin. In retrospect, what is most amazing is how q...

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