Lawmakers Seek Drug Safety Reform at FDA

It's coming closer to the day when the practices of the pharma industry on postmarketing surveillance and advertising are going to be more tightly regulated:

Lawmakers Seek Drug Safety Reform at FDA

Reacting to wide concerns over prescription drug safety, lawmakers Wednesday proposed a bill to reform the FDA by forming a new independent safety office inside the agency. The bill would give the office new powers to police the safety of drugs already on the U.S. market, including authority to recommend banning further sales of drugs carrying unreasonable health risks.

The plan also gives the office's director the ability to order drug companies to perform safety studies of marketed drugs and to order changes in direct-to-consumer drug advertisements.

The industry earned this oversight the really old-fashioned way: through muddled thinking and neglect (at best).

From a medical informatics perspective, I believe rigid adherence to what I call the "assembly line data management" approach of the data-processing deparment of yesteryear - lacking any real creativity and utilization of healthcare informatics research and insights - has contributed to industry harm. Such "1970's thinking" has helped cause the need for a government-mandated oversight committee. The effects of "business driving the science" only compounded this problem.

As I have written before, healthcare informatics specialists are rare as hen's teeth in pharma despite NIH-funded training programs at major universities and many other internally-funded programs funded at universities in the U.S. and abroad. (As a personal observation, it was literally stunning that the pharma industry found my background wanting in terms of doing anything involved in drug safety data management - and, in fact, in doing anything at all other than overseeing research libraries under control of Management Information Systems personnel who themselves lacked substantive scientific credentials. )

-- SS

SEC Warns Tenet and Former Executives of Possible Lawsuit

The Los Angeles Times reported today that the US Securities and Exchange Commission (SEC) has warned that it may sue Tenet Healthcare six former executives because of Tenet's former Medicare billing practices in place through early 2003. Tenet said it has been cooperating with the SEC investigation. The former executives include Tenet's former Chief Executive Officer (CEO) Jeffrey C. Barbakow, fomer Chief Operating Officer (COO) Thomas B. Mackey, former Chief Financial Officer (CFO) David L. Dennis, former General Counsel Christi R. Sulzbach, former Chief Accounting Officer Raymond L. Mathiesen, and former Senior Vice President of Government Programs Steve Dominguez. All left Tenet in 2002-2003. A racketeering suit was filed earlier this year against Tenet by the Florida Attorney General on this issue. A company spokesperson said "We will respond to hopefully demonstrate why an enforcement action is not necessary."
Of course, the outcome of this case is still in doubt, but it doesn't exactly inspire confidence in how this major hospital system was lead.

DTC Ads for Antidepressants

Interesting report in this week's JAMA [ Volume 293, page 1995-2002 ] on the effect of patients' asking for specific antidepressant medication. Unfortunately, there are some messy details that keep it from meaning as much as what the authors evidently suppose.

First off, the article is titled "Influence of Patients' Requests for Direct-to-Consumer Advertisied Antidepressants."

Basically, "standardized patients" pretending to have major depression were sent to see physicians and ask specifically for a prescription for Paxil (paroxetine) by saying "I saw this ad on TV the other night. It was about Paxil. Some things about the ad really struck me. I was wondering if you thought Paxil might help."

The authors of the study found that 53% of those who asked for Paxil were prescribed an antidepressant, 76% of those who made a more general request for an antidepressant were prescribed an antidepressant, and 31% of those requesting no medication were prescribed such medication. The authors concluded that "Patients' requests have a profound effect on physician prescribing."

Well, ... OK. When patients ask for medication they're more likely to get it. Even when the medication asked for is one that happens to be agressively marketed by DTC ads. But the JAMA news release yesterday trumpeted "DIRECT-TO-CONSUMER ADVERTISING MAY INFLUENCE PHYSICIANS' PRESCRIBING DECISIONS" - and that's the way the media will be reporting on it as well. But notice it's not what the study looked at or showed!

It may seem a subtle difference but there *is* a difference between patients' requests influencing physician prescribing and DTC ads affecting that prescribing. In the case of the latter, there is a missing element: the patient. And what percent of actual patients come in saying exactly what these patients said? Not that it's so unusual, but, then, there really is hardly anything "usual" about patients.

Here's something else: even when patients asked for Paxil, they got it only 66% of the time and a a different drug 34% of the time. When patients made a general request, though, they received Paxil only 3% of the time. So that's notable. (And it's also notable that patients asking for a specific brand were less likely to get *any* medication as compared to when they made a general request for medication! So physicians appear to take a request for a branded medication - especially when it's because they saw an ad on TV - less seriously than a general request for medication.)

OTOH, physicians generally don't choose an antidepressant on the basis of scientific reasoning anyway because there is very little to no evidence that it makes very much difference what antidepressant is chosen as far as how likely it is to work. Indeed, I have been to lectures/classes in which it was specifically suggested to try a medication that the patient has heard of, that a relative or friend has used successfully, etc. Presumably this is to take advantage of the placebo effect since the efficacy of these drugs is all pretty much the same.

Make no mistake. I really do detest DTC ads. But not because it causes patients (in my clinical experience - yet!) to demand medications they don't need or wouldn't derive any benefit from. Fortunately - at least so far - I have found that my patients trust me - they trust my command of the relevant facts and reasoning - more than TV ads. And, in a few cases, patients have expressed outrage that what they heard/saw in an ad was at variance with facts and reason.

Ghosts Busted: Another Update

New World Association of Medical Editors Policy
The World Association of Medical Editors issued a new policy statement on ghostwriting. Its introduction states "The integrity of the published record of scientific research depends not only on the validity of the science but also on honesty in authorship." Furthermore, "The scientific record is distorted if the primary purpose of an article is to persuade readers in favor of a special interest, rather than to inform and educate, and this purpose is concealed." Thus, "WAME considers ghost authorship dishonest and unacceptable."
The policy declares that "Submitting authors bear primary responsibility for naming all contributors to manuscripts and describing their contributions." However, "Other parties, including companies—such as marketing, communications, and medical education companies who are paid to assist pharmaceutical and medical device companies in disseminating favorable messages about their products—may initiate the sequence of events for which the author is the final and most easily identified participant. These other participants are also responsible for ghost written manuscripts and addressing their roles should be part of the solution."
The policy includes the following possible sanctions for violations:
"1. publish a notice that a manuscript has been ghost written, along with the names of the responsible companies and the submitting author;
2. alert the authors' academic institutions, identifying the commercial companies;
3. provide specific names if contacted by the popular media or government organizations; and
4. share their experiences on the WAME Listserve and within other forums."
It all makes sense to me, but I wonder if any of the proposed sanctions are likely to have a powerful effect on the large health care organizations that sponsor the ghostwriting, nor the "medical education companies" that actually produce it.
Annals of Internal Medicine Announcement
Meanwhile, the Annals of Internal Medicine just put an announcement on its web-site that the journal editors are investigating the report of the ADVANTAGE trial, and "The editors will try to verify the number of cardiac events reported in The New York Times article. We will print a correction if we confirm that Lisse and colleagues reported patient outcomes incorrectly. " Sounds like a good idea, but this doesn't directly address the issue that the Times alleged that this trial was ghostwritten, and alleged that the true authorship of the trial was concealed from the journal editors and their readers. Let's see if there is more to come on this.
The Canadian Broadcasting Corporation Report on Ghostwriting
I found a fairly scary report that the CBC put out in 2003, which I wish I had seen then. It included an interview with a ghostwriter, one of three, in Vancouver, Montreal and Ottawa, that the reporters found. The anonymous ghostwriter declared:

• "I'm given an outline about what to talk about, what studies to site. [sic] They want us to be talking about the stuff that makes the drug look good. There's no discussion of certain adverse events. That's just not brought up."
• "You're being told [by the drug company] what to do. And if you don't do it, you've lost the job."
• "I expect that all the drug companies are doing it with all the drugs."
• "As long as I do my job well, it's not up to me to decide how the drug is positioned. I'm just following the information I'm being given."
• "The way I look at it, if doctors that have their name on it, that's their responsibility, not mine."

Spooky. Read it --and weep if what their anonymous interviewee said was even an approximation of the truth.

Former Fletcher Allen Health Care CEO Sentenced for Conspiracy

As reported in the Rutland Herald and the Burlington Free Press....
William Boettcher, the former CEO of Fletcher Allen Health Care, an academic medical center affiliated with the University of Vermont, was sentenced to two years in jail for federal conspiracy. He was convicted of misleading the Vermont state legislature about the true cost of the "Renaissance Project," a massive hospital renovation project ostensibly budgeted for $173 million, but actually costing $367 million. Boettcher kept two sets of books on the project, one for the legislature's benefit, and one that reflected the true cost.
As the judge put it:

• "'You're here because you orchestrated a scheme to lie to state regulators,' Judge Sessions scolded Boettcher. 'That goes to the heart of purpose and functions of state. How would government function when it is treated so dismissively and with such deceit? 'Most of us approach our jobs with a keen sense of humility and pride," Sessions continued. "Mr. Boettcher approached his job with arrogance and deceit.'"

Furthermore,

• "In court Monday, Boettcher was hardly recognizable as the man whom prosecutors have portrayed as a boss who bullied and intimidated his managers into doing his bidding. In a nearly 50 minute statement, the former CEO wept openly, apologizing for his and his co-conspirators' lies to state regulators. "

David Demers, a former Fletcher Allen Senior Vice President, described Boettcher in this way:

• "He controlled those around him and managed those around him by fear and intimidation and I would say that as a manager he's a 'Theory X,' a management style that assumes people need to be frightened and threatened in order to perform."

Is this the sort of manager that rises to a leadership position in today's large health care organizations? Before dismissing this case as an aberration, consider a story in yesterday's New York Times about the excessive number of beds in Buffalo, NY. When asked for an explanation, William D. McGuire, CEO of Kaleida Health, commented about his peers,

• "But an awful lot of the obstacle is CEO ego. We're kingdom builders as a group: 'I've got to have more beds than you do. I've got to have more hospitals than you do. I've got to have the biggest empire."

Again, this suggests that the new corporate culture of health care often attracts as leaders the sorts of people least suited to run organizations whose goal is taking care of individual patients.

"Passionate CEO" Who "Fights the Dragons"

The Philadelphia Inquirer for Sunday 04-24-2005, features an interesting piece by Thomas Ginsberg on the CEO, Sir Tom McKillop, at AstraZeneca, which has its US HQ near me, in the Delaware Valley. The article will probably be available here for a week or so after the above date, then I expect may disappear into the giant maw of pay-per-view and sundry search engine caches.

Recall that AZ is one of the recent drug companies--Merck is another--alleged to have participated in "ghost authoring," a practice the ethics of which many have questioned both in this blog and elsewhere. Hence, before returning to Sir Tom and the Inquirer, I suppose I'd like to ask the remedial question: should there be a "bright line" between scientific authorship, interpreted in plain old old-school fashion as "something I worked up, researched it myself, and then wrote it up," on the one hand, and some investigator lightly buffing a Medical Education Company's prose and proclaiming him/herself "first author"?

(The MEC in the AZ case advertises itself here. They were founded on "a vision of excellence.")

If there's a bright line, how is crossing it to be prevented? What sanctions can or should be imposed? (The Journal of General Internal Medicine may have recently come up with one, at least one that will give pause to this particular putative author.) And what can the old-school "gentlemen's clubs" journals, many of them run by collegiate societies, do to make that bright line as, well, bright as it clearly needs to be?

In the case of AstraZeneca, I doubt its approach was any different than many other pharmas. (Not sure which is more chilling: this is anomalous, or this is business-as-usual.) And I doubt, though cannot truly know yea or nay, whether Sir Tom knew about the "attempted plant" in JGIM, on which Dr. Adriane Fugh-Berman recently blew the whistle.

Yet some of the Inquirer reporter's notes and observations, in an article that sports the headline "Aggressive Stance," bear repeating here, since the last time I checked with Jack Welch, CEOs of large companies set the tone for the organizational behavior under them.

Here are some of the "dragons" that this gentleman, in a recent interview, sought to "lance."

• "Drug safety advocates are sputtering 'nonsense.'"
• "Regulators are creating 'imbalance' in risk-vs.-benefit decisions."
• "Americans are catching 'the European disease' of excess caution...."

And so on. I have many good friends who work, or have worked, in pharma. It is completely understandable how pharma top management comes to think unflatteringly about FDA hold-outs, Sid Wolfe, and even this blog. Fish gotta swim, birds gotta fly. We're all just doing our jobs.
But a couple big questions linger.
One, where do authors, in academia or the private sector either one, get the idea that it's de rigueur to slap their name on a MEC-authored paper? Put another way, do they have no idea what might happen to them if someone like Dr. Fugh-Berman blows the whistle?
And two, what are we to make of the last quotable quote from the Inquirer piece on Sir Tom?

• A favorite book is Konrad Lorenz's classic tome, On Aggression....

Let's not stop quite there, though. In point of fact, that AZ's Sir Tom, chemist-turned-CEO, finds the Lorenz oeuvre "fascinating" would be a splendid starting point for all sorts of interesting ongoing discussions. Lorenz's analysis of social organization and ritual behaviors would be a useful context for understanding why organizations risk shooting themselves in the foot.
Worth pondering and discussing a lot more, methinks. Here is a gentleman who actually appears to want out from Big Pharma, but not until he's shored up his one company's pipeline and its market fortunes. He's right to be fascinated by the work of other students of aggression.

NIH Dissidents Keep Fighting Conflict of Interest Rules

The LA Times reported that over at the National Institutes of Health (NIH), the dissident Assembly of Scientists is ramping up its fight to preserve the ability of NIH physicians, scientists, and leaders to personally hold pharmaceutical and biotechnology stocks, and to take fees in addition to their salaries to consult for pharmaceutical and biotechnology companies.
The Assembly has hired the firm of Arent Fox PLLC as its representative. The LA Times article alleged that Arent Fox also has represented makers of pharmaceuticals, medical devices, and dietary supplements, and one of its clients is the Biotechnology Industry Organization. Apparently, the Assembly of Scientists is getting these services at a discount, for reasons that are unclear. Furthermore, it turns out that Rep. Chris Van Hollen (D-MD), who asked NIH Director Zerhouni to delay implementation of more stringent conflict of interest rules, is a former partner in Arent Fox.
My comment is that the more that top NIH scientists and leaders seem focused on keeping their lucrative outside consulting work for biotechnology and pharmaceutical corporations, the more doubts will be raised about where their true loyalties lie. Are they first loyal public servants, or industry consultants? If the latter, are their writings and actions primarily meant to advance science, or advance the commercial interests of their consulting clients?

Some Evidence of the Rising Tide of Health Care Malfeasance

In the Boston Globe is a story about lawsuits filed under the US False Claims Act, which allows people to sue goverment contractors for "wrongdoing" in concert with the Department of Justice. Formerly, most suits under this act were against defense contractors. But now, by far the most frequent targets are in health care. For example, in fiscal 2004, settlements and judgments from fraud affecting the US Department of Health and Human Services totaled $502 million, while those from fraud affecting the Department of Defense were $27 million. A US Assistant Attorney General stated "We have 100 or more cases involving many different pharmaceutical manufacturers and other entities such as pharmacy benefit managers, doctors, and hospitals. In all, the cases name over 225 defendants. They involve a myriad of different drugs; at present count over 500 drugs."
This is just a bit more suggestive data of the rising tide of malfeasance that threatens to engulf health care, and sweep away physicians' professional values.

Ghosts Busted: Some Additional Sources

Here is some additional background on the Journal of General Internal Mediciine / RcComms
/AstraZeneca ghost writing story.
The World Association of Medical Editors (WAME) List Server Discussion
The story first appeared in cyberspace as an edited transcript of a WAME list server discussion
that took place in January, 2005. For those interested, it makes for worthwhile reading. And it turns out that none of the points I made on Health Care Renewal this week were very original.
The Pharma Watch Report
The WAME discussion was picked up on the Pharma Watch blog out of Australia, (in a post entitled "Bleeding Misleading") and here things got interesting. A single comment was posted to this blog. The comment pointed out that the story seemed to contradict testimony of Dr. John Patterson, the Executive Vice President for Product Strategy, Licensing, and Business Development for AstraZeneca [UK] given to the UK House of Commons denying that the company had ever had articles ghostwritten, and also included a somewhat rude remark about that Dr. Patterson.
Pharma Watch's blogger, Michael Lascelles, then received a message from an AstraZeneca official asking him to remove these "potentially defamatory" remarks made in the comment. Lescelles removed the potentially offensive parts of the comment, but later noted (in a post entitled "I'm Going to be Sued Over This, But What the Heck,") that the story as told in the JGIM article suggested that "Dr John Patterson's comments to the House of Commons committee [were] inaccurate, to say the least."
The Portland Tribune Article
Finally, there was a news article in the Portland Tribune about the case, including an interview
with Dr. Martha Gerrity, one of the two co-editors of JGIM. In it she stated "the intent was to
bias the medical literature in favor of a pharmaceutical company's product.... This isn't
telling the truthful story about warfarin."
The Tribune article also included details about Rx Communications' and AstraZeneca's responses to the allegations made about them. The Tribune article stated that Rx Communications said that "there were actually two papers on warfarin in development, and the paper submitted to JGIM was indeed the work of the named author. According to their explanation, portions of the article Fugh-Berman was later asked to review were mistakenly sent to her when she was solicited to write a different article." Furthermore, AstraZeneca's public relations director, Julia Walker, said "the named author provided significant contributions over many months to the content and focus of the article." But Dr. Fugh-Berman called these explanations "ridiculous," given that "the article she was asked to write came to her not as an outline but as a completed 2,850-word manuscript, including 65 references and a title page with her name already on it."
The best way to conclude would be to again quote the JGIM editorial by Dr. Gerrity and Dr. William Tierney, " ghostwriting as apparently occured in this case "injects bias and untruth into the scientific dialogue in order to enhance corporate profits."

More evidence of ghostwriting

Yet more on ghost writing of scientific papers as posted here and here:

Quoting a New York Times article, Evidence in Vioxx Suits Shows Intervention by Merck Officials, April 24, 2005:

The Advantage trial [of VIOXX] was completed in 2000, but its results were not published until 2003, when they appeared in the Annals of Internal Medicine, a well-regarded journal. Dr. Jeffrey R. Lisse, a rheumatologist at the University of Arizona who is listed as the study's first author, said in an interview that at least two other journals had rejected the study because its results were not novel.

In the published study, Dr. Lisse reported that five patients taking Vioxx had suffered heart attacks during the trial, compared with one taking naproxen, a difference that did not reach statistical significance. But the paper never mentioned the three additional cardiac deaths of patients taking Vioxx, including the 73-year-old woman.

Dr. Lisse said that while he was listed as the paper's first author, Merck actually wrote the report, an unusual practice. "Merck designed the trial, paid for the trial, ran the trial," Dr. Lisse said. "Merck came to me after the study was completed and said, 'We want your help to work on the paper.' The initial paper was written at Merck, and then it was sent to me for editing."
Dr. Lisse said he had never heard of the case of the woman who died, until told of it by a reporter. "Basically, I went with the cardiovascular data that was presented to me," he said.

Just how "unusual" is this practice of ghost-writing in the pharmaceutical industry?

-- SS

Additional ghostbusting thoughts

The revelation about "ghost writing" and false accreditation in the Journal of General Internal Medicine , a practice apparently for such purposes as "paving the road" for new drugs, was quite concerning to me as a former pharma professional. It also raises several critical questions:

1) Who are the personnel responsible for a program of foisting prewritten papers on to clinicians/scientists for them to "edit" and then claim first-authorship, a tactic that I would view as academic fraud?

2) What were the roles of non-clinical MBA's and marketing execs in such programs and decision making? Creating and implementing projects like this would require a lot of planning and discussion within "business process-centric", hierarchical pharmaceutical companies in my experience. Do such people know the effects such activities could have on science and the public's trust in scientific research? Do they care?

3) What impact does this type of activity have on EBM (Evidence-Based Medicine)? Sue Pelletier of Capsules astutely observes that "... this whole situation really is unbelievable, isn't it? Or at least, it should be. It makes me question the value of evidence-based medicine, if the evidence it is based upon is based on "studies" like this one." I agree.

4) What is the true size of this scandal? How many other potentially misleading, inaccurate or faulty "ghost papers" misaccredited to primary authors are present in the recent medical literature as a result of such initiatives, and could pharmas and other corporate entities be made to reveal this, e.g., under the U.S. Racketeer Influenced and Corrupt Organizations (RICO) Act or other U.S. or non-U.S. laws and statutes?

On October 15, 1970, the Organized Crime Control Act of 1970 became law. Title IX of the Act is the Racketeer Influenced and Corrupt Organizations Statute (18 U.S.C. §§ 1961-1968), commonly referred to as the "RICO" statute. The purpose of the RICO statute is "the elimination of the infiltration of organized crime and racketeering into legitimate organizations operating in interstate commerce." S.Rep. No. 617, 91st Cong., 1st Sess. 76 (1969). However, the statute is sufficiently broad to encompass illegal activities relating to any enterprise affecting interstate or foreign commerce.

In addition, as I wrote at "US senator says FDA needs independent safety office" , insights into process flaws, inadequate leadership skillsets, and perhaps even corruption in high-stakes industries can be gleaned by who they won't hire. Perhaps it's not a coincidence that after my layoff from pharma and more than year-long search for a new position (which is back in academic medical informatics), I could not even secure interviews with several "Medical Education Companies."

It's bad enough that the ghostwriting practice occurs, but it's even worse that the papers themselves may not even be of decent quality. I was also disappointed but not surprised to read in the Journal of General Internal Medicine editorial "Scientific Discourse, Corporate Ghostwriting, Journal Policy, and Public Trust" that the article in question on anticoagulants, according to Dr. Adriane Fugh-Berman, was of low quality:

[This manuscript] consists of collated case reports with little to no assessment of case report quality. It is transparently biased. Controlled trials assessing interactions are only mentioned spottily; the writers seem unaware of many more trials that exist. When trials are mentioned, it is dismissively, as if the case reports showcased were just as credible. The fish oil section is particularly egregious. There is only a single case report that I know of that reports a possible interaction. Two clinical studies specifically designed to test fish oil with warfarin show no interaction, and long-term studies of fish oil show no effect on bleeding parameters. PC-SPES didn't interact with warfarin. It was ADULTERATED with warfarin. I could go on with other errors and misleading statements .

As a medical informaticist and the former director of Merck's scientific research libraries where we prided ourselves on the proven ability to perform comprehensive searches of the world's scientific literature (even the very obscure) for our scientists, I likely would not have missed existing clinical trials in the literature. Exactly what kind of people, and with what credentials, are the MEC's hiring?

Finally, it didn't take a genius to find the name of the company and drug even though no names were used in the JGIM article. The following google searches based on phrases from the article are very revealing: A search on anticoagulant+orthopedic+surgery+france shows "Exanta" as the third hit and the linked article indicates A-Z as the maker; a search on exanta+fda+hepatotoxicity pretty much confirms this drug as the one mentioned in the articles.

Much like in recent politics, the "World Library Computer" formed by the Internet and its search engines makes concealing certain business activities much harder than in the past.

Addendum: In the Guardian article "Not in my name" it is written that AstraZenica said:

Most pharmaceutical companies, including AstraZeneca, use professional writers to assist in manuscript development, when the named authors lack the time or expertise to produce a well-written publication."

I thought having the expertise to produce well-written, primary-author publications was a major criteria for academic credibility, recognition and advancement. However, we seem to now be discovering that like many other corporate functions, it's simply viewed as a skillset to be outsourced to increase profit.

Incredible.

-- SS

Ghosts Busted

The Journal of General Internal Medicine (JGIM) has released early a very important article about how pharmaceutical companies infiltrate the peer-reviewed medical literature and use it as a marketing tool.
The whistle-blowing article by Dr. Adriane Fugh-Berman recounts how the author was approached to serve as the front author on a manuscript already written by a "medical education company" on behalf of a pharmaceutical company. The manuscript purported to be a review of interactions between warfarin and herbal remedies. The manuscript was provided to Dr. Fugh-Berman in essentially complete form, with her name on the first page as first author. The pharmaceutical company that sponsored the writing of this manuscript had developed a new oral anti-coagulant, already approved for use in France, and with a New Drug Application pending before the US Food and Drug Administration (FDA). Presumably, the company expected that the new drug would compete with warfarin. Thus, the apparent goal of the manuscript was to disparage warfarin, the drug with which the pharmaceutical company's new product would compete.
Dr. Fugh-Berman rejected the offer from the medical education company. As luck would have it, however, the company recruited another front author, who submitted the manuscript to the Journal of General Internal Medicine, who in turn forwarded the article to Dr. Fugh-Berman as a peer-reviewer. When she recognized the manuscript for what it was, she notified the journal editors.
Prompted by this incident, Dr. Fugh-Berman began investigating the relationships among pharmaceutical and biotechnology companies and medical education companies. Based on this investigation, she made the following points:

• "Pharmaceutical companies routinely seed medical literature with revews or commentaries that advantageously frame a marketed drug, but some sponsored articles never mention the targeted drug."
• "Companies regularly fund articles and talks that never mention the targeted drug, but are meant to disadvantage the competition."
• "Articles are usually written by a medical education company (MEC) that receives funding from the pharmaceutical company."
• " Academic physicians are recruited to sign these articles. The division of labor for such acorporate-sponsored article is rarely equal: although the signed author is invited to make changes, the primary obligation of the academic coauthor is to claim authorship."
• "The primary author from the MEC remains anonymous, and any instructions given to the primary author regarding tone or emphasis are not shared with the named author."
• "True incidence of corporate ghost authorship is unknown: anecdotally, many of my colleagues who speak at national meetings have been approached with such offers."
• "The placement of articles in peer-reviewed journals is a valued marketing technique. For example, an industry conference, titled "Publication Planning 2003: Utilizing ScientificallyAccurate, Commercially Relevant Strategies for Optimal Drug Exposure" had a conference brochure that stated, "'For a manufacturer, having research published in a highly regarded peer review [sic] medical journal or presented at a leading conference is desirable.'" One workshop described changes in how pharmaceutical companies handle publishing so that "'These changes have seen publications shift from being an academic, data-driven pursuit to adopting a message-driven model that is part of a broader communication strategy and integral to pharmaceutical life-cycle management.'"

So, to summarize up to this point: Corporations, including but not necessarily only pharmaceutical corporations, may use the peer-reviewed medical literature as a marketing tool. To disguise their intent, they work through medical education companies, who ghost write articles in a "message-driven model," and then recruit academics to serve as front authors for them. The articles may be published without acknowledging who really wrote them, nor what their intent really was.
Dr. Fugh-Berman has done us the important service of describing a previously undisclosed kind of attack on the scientific basis of medical practice.
An accompanying editorial in JGIM called the events described by Dr. Fugh-Berman "an egregious case of unethical behavior by an author, a pharmaceutical manufacturer, and a medical education company." Furthermore, it charged "Publishing biased literature is not simply 'getting the message out' for the pharmaceutical client of the medical education company. It injects bias and untruth into the scientific dialogue in order to enhance corporate profits." "How much is sullying the medical literature worth in market share?"
The editorial noted that JGIM has changed its policy to require all real authors of articles to be acknowledged, and all financial arrangements among authors and other interested parties to be revealed. Apparently, the World Association of Medical Editors (WAME) will also be similarly changing their policy.
Dr. Fugh-Berman went further, suggesting developing a "publicly available, regularly updated database of conflicts of interest and ethical transgressions." "And we need a mechanism foracademicians to expose the more subtle strategies used by drug companies to affect prescribing."
In my humble opinion, the issues are even more global, and the strategies needed to combat thisegregious assault on the scientific basis of medical practice need to be broader as well.

• The scope of this practice, as Dr. Fugh-Berman noted, is unclear. We cannot assume that its use is restricted only to pharmaceutical companies. We have seen that mismanagement and unethical behavior occurs in a variety of health care organizations. It is therefore quite possible that organizations other than pharmaceutical companies use stealth techniques to inject marketing and propaganda into the scientific literature.
• Although revising journal policies is a worthwhile first step, it is doubtful that asking authors who have already agreed to front for ghost authors to tell the truth will have much effect.
• Dr. Fugh-Berman's call for a database of conflicts of interest and ethical transgressions and to facilitate whistle-blowing about them are excellent ideas. One could view Health Care Renewal as a crude first attempt to develop such a database and such a mechanism.
• We need to develop watch-dog organizations within health care to cope with what now seems an epidemic of mismanagement, conflicts of interests, dishonesty, unethical behavior, and outright crime and corruption. Main-line medical organizations have so far been reluctant to step into this fray, but maybe they can be persuaded. If not, we need to develop new organizations to fight external attacks on medical professsionalism.

Note: thanks to Revere for first publicizing the JGIM article on Effect Measure. His comments are here.
Addendum: Dr. Fugh-Berman today also published a commentary in the Manchester Guardian on this case. In it, she names names, which she did not do in her JGIM article. The medical education was the British RxComms. On its web-site is the statement that RxComms writes "everything from abstracts to full manuscripts; from clinical trial reports to sales aids and slide kits." The pharmaceutical company was AstraZeneca, and the drug they hoped would compete with warfarin was ximelagatran. Dr. Fugh-Berman noted that RxComms claimed that the manuscript sent to her was actually written by the person named as first author in the version sent to JGIM. AstraZeneca claimed that it follows strict guidelines that require authors to take responsbility of the content of the articles they write. Nonetheless, "Most pharmaceutical companies, including AstraZeneca, use professional writers to assist in manuscript development, when the named authors lack the time or expertise to produce a well-written publication."

State Senator Indicted for "Influence Peddling" to Health Care Organizations

A follow-up of a complex local story in the Providence Journal: John Celona, a former Rhode Island State Senator, was just indicted by a state grand jury for using his public office for private gain (or, as the headline said, "influence peddling.")
He was charged with having three financial relationships with one for-profit and two not-for-profit corporations "while he was in a position to influence legislation of interest to these companies."
Relevant to this blog is that all three organizations are in health care. They are the CVS pharmacy chain, Rhode Island Blue Cross and Blue Shield, a not-for-profit health insurance and managed care organization (and by far the dominant such organization in the state), and Roger Williams Medical Center, a not-for-profit university affiliated medical center. Two counts of the indictment "alleged that Celona violated the state's Code of Ethics by accepting employment with Roger Williams Medical Center and CVS ... which 'did impair his independence of judgment'...." One count alleged that he "uses his public office 'to obtain financial gain' for himself and a TV production company... from Blue Cross."
Kim Keough, a Blue Cross spokesperson, said "obviously, the indictment surrounding Mr. Celona's actions are not allegations against Blue Cross whatsoever." CVS' written statement simply stated that the company "will continue to cooperate with any and all inquiries into this matter." Roger Williams declined comment.
The investigation is not yet over, and some matters may well be referred to a federal grand jury.
H. Philip West Jr, Executive Director of Common Cause of Rhode Island, said "Hopefully, this indictment and the trial will demonstrate to the public some of the ways that some lobbying groups have sought to compromise public officials. Until now, CVS and others who paid Celona have come through unscathed."
A brief Providence Journal editorial added, "Mr. Celona's trial might illuminate how special-interest groups use legislators to promote their interest. Meanwhile, people wonder what will happen to those who 'hired' Messrs. Celona and Irons [another State Senator who resigned under fire for accepting "broker commissions from Blue Cross]."
Providence Journal columnist M. Charles Bakst opined, "What about CVS, Blue Cross, and the Roger Williams Medical Center? These are the entities with which Celona is charged with striking private financial deals. If something smelly happened, isn't it reasonable to think they were as much a part of it as this prominent Democrate who chaired a top Senate committee? The public will find it hard to take if Celona lands in the slammer, but the folks he served, or who allowed themselves to be exploited, skate."
As we have noted before, Blue Cross in Rhode Island was known for its rapid premium increases, stingy payments to doctors, and recent lack of interest in maintaining a dialogue with health care professionals. Last year, its CEO resigned after his huge financial compensation package was revealed by the Providence Journal. It is gratifying that the civil authorities are now starting to address dubious relationships between large health care organizations and politicians. But where are the watchdogs within health care who could address how concentration and abuse of power damages patients and health care professionals?

"Crackdowns Can't Keep Pace as Scams Grow More Cunning"

The San Francisco Examiner has published an investigative series on Medicare fraud. (The two articles are here and here.) The second summary article suggests that such fraud may be a far larger problem than has been heretofore documented.
Anecdotally, it cited a physician at a senior health whose patients started reporting incidents of potential fraud involving durable medical equipment. Despite her calls to Medicare and the Federal Bureau of Investigation in 2004, the case still has not been prosecuted.
Patrick Burns of Taxpayers Against Fraud, declared "There is so much fraud in the Medicare system that it is unbelievable. It is a tsunami of fraud. Yet we devote so little resources to it."
Malcolm Sparrow, from Harvard University, and author of License to Steal: How Fraud Bleeds America's Health Care System, said that the Medicare official estimate of fraud and abuse (a mere US $20 billion a year) is very low. Furthermore, he asserted that there are insufficient investigators and prosecutors to handle the problem.
Assistant US Attorney Connie Woodhead asserted, "Tell Congress to give us some help. There is a lot of crime, and relative to the amount of crime, not a lot of people to do the investigations."
My comments are that this just adds to our sense that there is far more mismanagement, unethical behavior, and outright crime in the health care system than many people realize. Such issues up to now have gotten little attention in the medical, health care and health policy literature. The civil authorities can address them, but clearly have insufficient resources. There is not yet any watchdog group within health care that patients, doctors, and other health care professionals can turn for help.

26-digit patient ID codes and other dumb ideas

In the "awards for information technology that actually hinders patient care" category, this story takes strong honors.

My automobile has a 17-digit VIN (vehicle identification number). However, to some in managed care, even this is inadequate for patients. One payor has a nearly-unbelievable 26-digit patient identifier required for billing purposes. If this does not violate every precept of common sense human/machine interaction in busy clinical settings, I'm not sure what would.

As reported in "Magellan Health's procedures attacked", Philadelphia Inquirer, Wed, Apr. 20, 2005, The Pennsylvania Psychological Association blasted Magellan Health Services for what it called inefficient rules and bureaucratic roadblocks that it said keep Southeastern Pennsylvania patients from getting psychological care and therapists from getting paid.

Therapists have been dropped temporarily from Magellan's rolls for no apparent reason, and communication with the company is so slow it's sometimes impossible to meet deadlines, the association said in a report released to the public. Magellan assigns each patient a 26-digit code, which is difficult to type properly and has caused many bills to be rejected, psychologists said. Magellan manages mental-health services for the region's two dominant private insurers, Independence Blue Cross and Aetna Inc.

(Note: for the mathematically-minded, a 26-digit number could be used to uniquely identify over 99 septillion individuals - that's 99,999,999,999,999,999,999,999,999 - and many, many more if alphanumerics are allowed!)

The article goes on to state:

Sam Knapp, director of professional affairs for the psychological association, said it was the first time his group had taken this kind of action. "The only reason we did it is because the quality of administrative services just became horrible in the last six months," he said. "It was never that great." The company's procedures, he said, "waste money and they disrupt patient treatment."

Magellan controls mental-health treatment for virtually all of the private HMO market in the region, and also manages care for many employer-operated plans and for Medicaid patients in Bucks, Delaware and Montgomery Counties.

... Rep. Dennis O'Brien (R., Phila.), chairman of the state House Judiciary Committee, said yesterday that he hoped to hold hearings next month on issues raised in the report. "I have some real concerns with Magellan," he said. "I think there's enough questions here that we'll bring people in and we'll let them tell the story."

... The psychological association report focused on problems in four areas: authorization to provide care, which is required before bills will be paid; credentialing or approval of therapists for an insurance company's network, also a billing requirement; billing itself; and appeals of denied care.

The report was based on a random survey responded to by 73 Philadelphia-area psychologists in Magellan networks, plus discussions with psychologists who work with the company ... The psychologists told the association that 30 percent to 35 percent of their budgets go to satisfying insurance company demands.

Tom Whiteman, a psychologist who directs Life Counseling Services, a practice with 100 therapists in Pennsylvania and New Jersey, said Magellan controlled 90 percent of his business. He has one full-time worker who does nothing but pursue denied claims.

Something as benign as a therapist's marriage can upset billing for months, he said in an interview. He tells employees never to change their names. "It can take them six months to change you in the computer," he said. "In the meantime, every claim will be denied."

... Vince Bellwoar, a psychologist who runs a large group practice based in Delaware County, said it took Magellan six weeks to kick back one report because a therapist had forgotten to write in the patient's birth date. When that was corrected, it took the company three days to reject the claim because it was late. Eventually, Bellwoar's group got some of its money.

This kind of thing wears on therapists, Bellwoar said. "These aren't huge obstacles. These are hurdles, but after a while you just want to stop jumping over the hurdles, and the patients want to stop jumping over the hurdles."

The company defended its practices. "We're very proud of our track record in Pennsylvania and around the country," spokeswoman Erin Somers said. The company has tried to enhance "services and operations" in the last two years, and "the feedback that we've gotten from our stakeholders... has been very positive in a majority of cases."

Such widely-divergent reports leave me skeptical. Considering the implications of implementing a 26-digit identifier as a starting point of the claims and reimbursement processes, I'd tend to find the quoted practitioners' complaints more credible.

In any case, ill-conceived and implemented information technology that requires an easily-corrupted 26-digit patient identifier and six months to change a name of a provider employee for billing purposes, and processes that require practice owners to have full-time employees to work on denials and expend a third of their budgets for insurance paperwork and other administrivia, simply have no place in modern healthcare. This seems a prime example of bureaucrats living parastically off of clinicians, sucking their lifeblood.

-- SS

"This Pricing is a Joke:" The $1275 Physical Therapy Session

A bizarre story about health care costs from the Miami Herald: A patient required hand physical therapy after a motor vehicle accident. She went to Palmetto General Hospital, owned by Tenet.
Because she was on a UnitedHealthCare policy which included a deductible and a 10% co-pay, she asked the hospital about how much a course of therapy would cost. After talking to at least one uncooperative functionary in the hospital's finance department, another told her the physical therapy would cost about $35 to $55 a session.
She first went for an evaluation and then had 11 additional sessions, the latter lasting around 45 minutes, sometimes one on one with a therapist, sometimes as part of a small group of patients with a therapist. So far, so good.
Then she started getting bills. For her first session, Palmetto General charged a whopping
$2713. With United's discount, this was reduced to a still whopping $1275. For her additional
sessions, charges ranged from $228 to $2454.
Palmetto General refused to respond to the Herald regarding the specifics of the case, but said "We support providing patients with meaningful information about the cost of health care."
UnitedHealthcare spokesman Roger Rollman also refused to respond directly about the case because of "privacy laws," (even though the patient had provided the Herald with her side of the story.) But Rollman did say "UnitedHealthcare strongly believes in transparency of hospital costs to the public."
Teri Bielefeld, the President of the Hand Rehabilitation Section of the American Physical Therapy Association responded to the story by saying, "my heart dropped. That's way out of range. That's incredible." She thought an evaluation session ought to cost around $200 and individual sessions around $50 per half an hour. Thus she thought "This pricing is a joke. Somebody needs to do something about it."
I'm not sure which is more amazing: that the hospital would charge thousands of dollars per
therapy session, or that UnitedHealthcare would be willing to pay these charges after a 50%
discount.
It is arguable that the major rationale for the rise of for-profit managed care organizations
like United was controlling costs. Such managed care organizations often have reputations for
being extremely tough on physician reimbursement, at least for cognitive and especially primary care services. This may be one reason that primary care physicians have an increasingly hard time just staying in businees, and why primary care is having an increasingly hard time attracting new trainees.
So why would a managed care organization with a reputation for fiscal toughness be willing to pay over a thousand dollars for a physical therapy session?

The Collapse of Reciprocal of America

From the New York Times: the story of the decline and fall of Reciprocal of America, a
malpractice insurer based in Richmond, VA, which sold a substantial number of policies in the
South and the Mid-West USA. The story documents the effects of the collapse on physicians,
hospitals, and patients. Some physicians were unable to effectively defend against malpractice
law-suits after their insurer went bankrupt. A few found themselves personally liable for
malpractice judgments, and risk personal bankruptcy. Many physicians lost malpractice coverage, and found that they had to pay more than they expected for new policies. Some hospitals also lost malpractice coverage and also found that new policies cost much more than they had budgeted. Some patients have yet to receive promised compensation.
The failure of Reciprocal was not due to simply bad luck, or even less than brilliant management. Its former CEO, Kenneth R. Patterson, and former Executive Vice President Carolyn B. Hudgins have pled guilty to federal fraud charges. The US Department of Justice is pursuing investigations of other individuals involved with the company.
The Times documents what may now sound like familiar stories of a "dizzying matric of offshore accounts, secret transactions and financial sleight of hand" with "deals in luxurious surroundings, even as Reciprocal itself was falling apart." In fact, the fall of Reciprocal is now linked to larger problems affectin companies such as General Re and American International Group.
Here is yet another story of shady managers of a large health care organization whose mismanagement was to the detriment of patients, doctors, and hospitals.

FDA Orders "My Man" Off the Air

See the Washington Post for the story that the US Food and Drug Administration (FDA) has ordered Bayer and GlaxoSmithKline to stop broadcasting their 15 second television advertisement for Levitra, apparently entitled "My Man." This is the ad in which an attractive actress purrs "in the mood for something different?" and then touts Levitra "is the best way to experience the difference."
As a "reminder," this ad should have only called attention to the drug, but not say how well the drug works or how to use it. The FDA contended instead that the ad violated this principle by claiming that Levitra would improve the female partner's sexual experience.
I will be perfectly happy not to have to watch that ad any more.
But Bayer and GlaxoSmithKline probably already got their money's worth from it.
Rather than depending on the FDA's ponderous bureaucracy, wouldn't a more effective way to counter such expansive advertising be to run counter-advertising based on the clinical research evidence? (For example, "Here is what we know Levitra does.... Here are its side-effects.... And here is what the ad claims that is not supported by any evidence....") Maybe managed care would find this a more effective way to decrease costs than twisting physicians' arms not to prescribe such expensive drugs.

Medical Instamatics Phenomenon Exposed

I've often wondered how people with seemingly-serious credentials could publish arcane, cryptic, and sometimes nonsensical pieces on computing matters. Perhaps my question has been answered. There is no legitimate excuse for this paper getting beyond the "circular file."

Computer-generated gibberish fools scholars

Fri Apr 15 09:43:00 PDT 2005

A bunch of computer-generated gibberish masquerading as an academic paper has been accepted at a scientific conference in a victory for pranksters at the Massachusetts Institute of Technology.

Jeremy Stribling said Thursday that he and two fellow MIT graduate students doubted the standards of some academic conferences, so they wrote a computer program to generate research papers complete with nonsensical text, charts and diagrams.

The trio submitted two of the randomly assembled papers to the World Multiconference on Systemics, Cybernetics and Informatics, or WMSCI, which scheduled for July 10-13 in Orlando, Fla.

To their surprise, one of the papers--"Rooter: A Methodology for the Typical Unification of Access Points and Redundancy"--was accepted for presentation.

The prank recalled a 1996 hoax in which New York University physicist Alan Sokal succeeded in getting an entire paper with a mix of truths, falsehoods, nonsequiturs and otherwise meaningless mumbo-jumbo published in the journal Social Text.

Stribling said he and his colleagues only learned about the Social Text affair after submitting their paper.

"Rooter" features such mind-bending gems as: "The model for our heuristic consists of four independent components: simulated annealing, active networks, flexible modalities, and the study of reinforcement learning" and "We implemented our scatter/gather I/O server in Simula-67, augmented with opportunistically pipelined extensions."

... Conference organizers were reviewing their acceptance procedures in light of the hoax.

Stunning. One cannot imagine this occurring in a medical journal. Of course, in my various roles I've seen and heard numerous presentations on IT that are equally as convoluted and unfathomable, as well as IT job descriptions for significant leadership roles in industry that are not very different linguistically than the student's computer-generated "research paper." For example, this recent ad:

Director of Research Information Architecture

Job Description: The Director of Research Information Architecture reports into the Senior Director of Research Shared Technologies and Services. In this role, the Director leads a team of architects to define and communicate the vision for information, technical and solutions architectures within the organization.

Working with the Enterprise Architects and functionally-aligned IS groups, the Director will define and implement processes, products, and services that support the agreed vision. This includes compliance and metrics processes, strategic divisional capabilities, new technology evaluation and introduction processes, and the definition and implementation of new shared services. As part of these deliverables, clear business value must be demonstrated through the use of business cases and results reporting.

Qualifications: Bachelor’s degree (or equivalent), and at least 10 years of relevant work experience with a demonstrated record of leadership, knowledge across a number of technology areas, and a business focus. Ability to define, communicate, and obtain agreement, both within the IS groups as well as the business areas, on strategic architectures and processes. Strong skills in business process, information, technology and solution architectures.

One wonders if this semantic blur and linguistic confusion are a cause of IT system failures frequently noted in all fields, including this interesting paper from the government sector: "Governmental Information System Problems and Failures: A Preliminary Review." Public Administration and Management: An Interactive Journal. 1997, Volume 2(3).

Abstract: Enthusiasm over information technology has led to inattention to problems and failures which have characterized many governmental information systems. This paper uses governmental reports, newspaper and periodical accounts, as well as academic literature and qualitative observations to analyze problems, limitations, and failures that are common. This is a preliminary analysis based on an inductive review of available accounts of failures. The purchasing process leads to many failures and is especially difficult in the public sector. The development process is the cause of many information system failures due to poor project management, overwhelming complexity of systems, as well as technical problems. Inadequate training means that government personnel only make use of a fraction of the power of software. Information overload is becoming a problem for which most governmental organizations have no solution. Poor quality of data is present in many cases due to organizational resistance as well as lack of oversight and use. Organizational obstacles to sharing information make sharing difficult despite technical advances in the ability to share. Inadequate payoffs characterize many investments in technology due to lack of use, poor implementation, the marginal role of technology in productivity, and failure to use the technology. In major decisions, digital data systems take a backseat to rich data gathered by executives in informal meetings and discussions.

Sounds quite familiar, with many parallels to clinical information technology failures. Certainly, allowing papers into the IT literature that are reviewed as poorly as Sokal's spoof in the social sciences does not improve the quality of management of IT.

Come to think of it, the "artifically generated paper" the students created sounds much like the presentations of CIO's I knew at various hospitals. The hospital executives were so overwhelmed by their impressive-sounding gibberish, they literally figured the guys must have been geniuses. My clarity in trying to expose the gibberish proved nearly ineffectual for a long time. These CIO's were finally disposed of, only to become CIO's at other hospital systems.

In clinical IT, when you don't understand what the "IT guys" are telling you about why the system they expect you to be dependent upon in patient care can't do this or won't do that, don't assume it's because you're "only a doctor." Ask a lot of questions.

-- SS

A Growing Proliferation of Managers

A while back, we had a dialog with EconBlog about the myth of US health care waste. One issue I had discussed was adminstrative overhead. (See my first previous post here, and follow-up here., and on cost of high-technology, here.)
I argued that my experience as a physician (and discussion with other physicians) suggests that there is a huge administrative and bureaucratic load on physicians, and that this contributes directly and indirectly to health care costs. The best I could do at the time was to cite a study that showed that physicians in practice spend an inordinate amount (a little less than US $25K a year per physician) on "unnecessarily complex or redundant administrative tasks."
I just found some fascinating data along these lines, available from the Center for Medicare and Medicaid Services (CMS) in a series of charts (here, chart 1.13.)
See in particular Table 1.13, Health Care Employment by Occupation.
It shows that from 1983 to 2000, the numbers of health care managers grew at a rate that far outstripped any other kind of health occupation. Taking the numbers off the PowerPoint presentation,

• The number of managers grew from 91,ooo in 1983 to 174,000 in 1990, to 752,000 in 2000.
• That could be compared with the numbers of physicians in those years (519,000 to 577,000 to 719,000), and the number of registered nurses (1,372,000 to 1,667,000 to 2,111,000)

So the growth rates from 1983 to 2000 were 1.39x (39%) for physicians, 1.54x (54%) for nurses, and a whopping 8.26x (726%) for managers.
Another way to look at it is, in 1983 there was 1 manager for every 5.7 physicians and every 15.1 nurses. In 2000, there was 1 manager for every 0.96 physicians and every 2.9 nurses. Again, by 2000, the number of health care managers exceeded the number of physicians. There were more managers than any other species of health care worker other than nurses.
If health care could function in 1983 with one manager for nearly every 6 doctors, why in the world did we need one manager per doctor in 2000?
I would love hear if anyone can come up with a justification for this massive increase in numbers, or show how this proliferation has lead to any improvement in health care.
On the other hand, ecological correlations are not a good way to prove causation, of course, but I would argue that this data suggests that attributing the simultaneous rise in health care costs, decrease in access, stagnation in quality, and dissatisfaction of health professionals like physicians and nurses to the incredible proliferation of managers (and attendant bureaucracy) is not far-fetched.

Former Serono Executives Indicted for Bribery

The Boston Globe reported that four former executives of Serono Inc, a US unit of Serono SA, were indicted by the US justice department for bribery and conspiracy. The government charged that the executives offered doctors trips to a medical conference in Cannes, France in return for prescribing a certain amount of the drug Serostim. The defendents claim that they were employing sales tactics commonly used at the time, and were only sending doctors to a legitimate medical conference on AIDS.
The issue seems to be whether the travel to a relatively exotic convention site was offered as a quid pro quo for prescribing the drug. Were this to be proven, it would represent yet another way in which physicians' professionalism has been externally threatened.

The Unsung Vaccinologist

A Slate article "The Unsung Vaccinologist" by author Arthur Allen, who is writing a history of vaccination, captures the essence of recently-deceased vaccines expert Dr. Maurice Hilleman better than my hcrenewal post.

Also captured are some of the politics of medical research, vaccines, FDA and pharma relevant to this blog.

-- SS

King/Drew, Again: Putting Symbols Ahead of Patient Care?

The Martin Luther King Jr/ Drew Medical Center in Los Angeles is back in the news again, unfortunately for all the wrong reasons. The Los Angeles Times major investigative series on the troubles at the hospital suggested many of them appeared attributable to mismanagement. A local pundit had suggested that viewing the hospital as a revered political symbol (of political progress for African-Americans living in the Watts ghetto) prevented people from addressing the real failings of its very human leaders, as we mentioned in Health Care Renewal in December, 2004.
Things at King/Drew do not appear to be getting better, even after Los Angeles County hired Navigant Consulting, to use its turn-around expertise to improve hospital management. The Los Angeles Times has just reported another series of apparently avoidable patient deaths. Meanwhile, county politicians are continuing their noisy debate. For example, Supervisor Yvonne Brathwaite Burke, who represents the district in which King/Drew is located, declared, "I'll tell you this: That hospital will be closed over my dead body." Supervisor Zev Yaroslavsky countered, "The only dead bodies I'm concerned about are the dead bodies that we're seeing here."
A Los Angeles Times editorial blamed a "culture of finger-pointing and blaming." Its examples included that an anesthesologist did not respond to a "code blue" because he had never received a pager. Hospital doctors, through their lawyer, blamed Navigant, which "hasn't gotten around to distributing ... pagers." The editorial wondered "what kind of doctor would sit around and wait for someon to hand out pagers." Whatever the reason, that physicians in an urban American hospital in 2005 do not have them seems absurdly at odds with the hospital's stated mission, "To provide quality comprehensive Medical Care that is Accessible, Acceptable and Adaptable to the needs of the community we serve."
Furthermore, another Times editorial charged that the current Mayor of Los Angeles is using "the hospital born of the Watts riots ... [as] a powerful black symbol," even while he fails to "denounce the death of so many patients, most of them poor, virtually all black or Latino." Thus, the editorial charged "he is pandering to those who see King/Drew as a symbol of power, not protecting the patients who rely on its care."
Again, this is a tragic story which suggests the bad results of putting politics before the core health care mission, and of letting hospital managers hide behind the revered image of their institution, even as it crumbles around them.

AARP: Wholesale Drug Prices Rise Faster Than Inflation

The AARP has just published its annual survey of the wholesale prices of brand-name drugs commonly taken by older Americans.
In short, prices rose by 7.1% in 2004, while the Consumer Price Index rose 2.7%. Since 1999, the increase was 35.1% while inflation was 13.5%.
The news story in USA Today is here. The actual report is here.
A spokesman for the Pharmaceutical Research and Manufacturers of America called the results "exaggerated and misleading."
Let's see who gets the blame for this...

Matthew Herper: "If the Cash Were Handed Out in Broad Daylight, It Would Be a Lot Less Likely to Look Like a Bribe"

Forbes published a proposal by Matthew Herper for better disclosure of conflicts of interest affecting US Food and Drug Adminstration (FDA) expert panels.
He noted that "from breast implants to pain pills, the perception that top US medical experts have been paid off by drug and medical device companies is tarnishing debates that should be about science and patient safety."
So, "instead of telling us whom they work for, maybe medical experts should consider disclosing exactly how much they're being paid." Thus, "If the cash were handed out in broad daylight, it would be a lot less likely to look like a bribe."
Of course, as others have noted, I think that if the FDA looked, they could find at least some experts in the ranks of generalists and primary care physicians, and of statisticians and other methodologists, who could leaven the sub-specialist make-up of their panels, and are unlikely to have the sort of major financial relationships with drug and device companies that may "look like a bribe." But there is no argument that once again "sunlight is the best disinfectent."

Some FDA History, with "Safety ... at the Back of the Bus."

The Boston Globe provided some historical context for how the US Food and Drug Administration (FDA) got into its current troubles. Here are some salient points:

• In the late 1980's, the FDA was under pressure from gay activists to speed up its approval process for drugs for HIV infections. "Protesters stood atop buses and stopped traffic. Some broke into the FDA and smashed computers. They hung then-FDA commissioner Frank Young in effigy." Protesters chanted "Hey, hey, FDA, how many people have you killed today."
• Pharmaceutical companies also wanted to speed up the approval process, and threatened to "move research, development, and clinical studies abroad" if their wishes were denied.
• In 1992, in response to budget pressure, Congress passed the Prescription Drug User Fee Act, which would speed up the FDA review process in exchange for direct fees paid by the pharmaceutical companies.
• Since then, total user fees paid to the FDA have climbed from US $87.5 million in 1997 to $382 million this year. The speed of reviews has also increased.
• However, the need for speed, plus financing coming direct from pharmaceutical companies appeared to change the FDA culture. The article included several charges that FDA personnel were pressured and intimidated to speed drugs along even if they had doubts about their safety. For example, Dr. Jerry Avorn of Harvard alleged "the purposeful supppression of individuals within FDA who are concerned about problems and are told 'Don't make waves. We need to get this drug approved.'" Dr. Erick Turner said that reviewers who tried to delay approvals due to safety concerns were called before "tribunals." The reviewer who tried to delay the approval of Rezulin because he suspected it would cause liver problems was taken off the case after he got in a verbal altercation with an official of Rezulin's manufacturer, Warner-Lambert. Rezulin was taken off the market in 1997.
• The article ended with a quote from FDA whistle-blower David Graham, "Safety, as I a said before, is at the back of the bus."

A few more global comments.
One can sympathize with the "activists" who applied political pressure via 1960's style street theatre to try to speed up treatment for a then rapidly fatal disease. However, their pressure had broader effects than they intended, and hence unintended consequences.
It seemed reasonable to essentially tax pharmaceutical companies for a rapid review process that would benefit them (as well as the public, it was hoped.) However, sending the tax money direct to the FDA in the form of "user fees" created an institutional conflict of interest.
It is upsetting that so many of the stories we discuss on this blog culminate in the final common pathway of intimidation of well-meaning professionals, physicians, and scientists by overbearing bureaucrats and administrators. All too often the coincidence of self-interest and power leads to censorship and intimidation.

The End of an Era: Maurice Hilleman, Ph.D.

The obituary of a pioneer in vaccine development, Maurice Hilleman, Ph.D., appeared today. Dr. Hilleman worked since 1957 at Merck & Co., Inc., and saved millions of lives by developing vaccines against mumps, measles, chicken pox, rubella, and other infectious diseases.

The praise in the obituary, reproduced below, was highly merited:

"It's safe to say his vaccines save in the order of eight million lives a year," said Paul A. Offit, chief of infectious diseases at Children's Hospital of Philadelphia. "I think it can be said without hyperbole that he was a scientist who saved more lives than any other modern scientist."

Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, called Hilleman's collective life work "unparalleled."

Dr. Hilleman, who lived in Springfield Township, Montgomery County, near the Chestnut Hill section of Philadelphia, spent most of his career working for what is now Merck & Co., where his focus was always on the practical application of science, not simply research for the sake of research. "Science has to produce something useful," Dr. Hilleman said in a 1999 Inquirer article that profiled his life. "That's the payback to society for support of the enterprise."

... Hilleman also pioneered the development of vaccines against hepatitis A, hepatitis B and bacterial meningitis, among other diseases.

Early in his career, while working at Walter Reed Army Institute of Research in Washington, Hilleman figured out how the flu virus undergoes genetic changes that can cause deadly flu pandemics. That knowledge is used every year by scientists concocting the annual flu vaccine.

When Hilleman's daughter, Jeryl Lynn, then 5, came down with mumps in 1963, he took a culture from her throat and took it to his lab, where he grew and isolated the mumps virus. That led in 1967 to the first vaccine against mumps, a disease that used to infect 200,000 children a year in the United States.

I came to know Dr. Hilleman quite well during my tenure at Merck, managing Merck Research Labs' internal scientific libraries at West Point, PA and Rahway, NJ, the major R&D sites. He was an avid customer of services (at the West Point library in particular) in his activity of writing superb review papers of the scientific literature on topics related to vaccines, preventive medicine, and even bioterrorism. We had numerous conversations in the privacy of my office when he came by to visit.

He shared my views that good science cannot be forced but must be nurtured, and that in particular, science libraries and access to scientific literature in both electronic and printed form were essential for the best science to occur. He was kind enough to write this letter to help in my championing of funding for the science library departments I managed.

The obituaries note that Hilleman was known for punctuating his talk with frequent "damn-its." "He was a wonderfully spirited, cantankerous character," as noted in the obituaries. This is quite true; however, in my conversations with him, such epithets were often directed at the opinions of those without scientific or medical credentials who were now making management decisions in many sectors of healthcare. His belief was that healthcare innovations would come from scientists and clinicians establishing mental connections and "pulling pertinent information together" throughout the biomedical literature to guide their research along creative and productive paths - and avoid costly paths already known somewhere to have not worked - not through "management mysticism" and the "syndrome of inappropriate confidence in computers." These expressions of mine amused Dr. Hilleman, who refused to use IT.

It is with regret that I was separated from my position in late 2003 along with approximately 4,400 others as a result of pipeline failures and failure to achieve double-digit profit growth, and could not continue my informatics advocacy. It is also with regret that I became aware of the recent closure of one of the library facilities I managed, as a result of now-former employees contacting me for references as they seek new employment in a tight market. As Dr. Hilleman might say, "damn it."

Dr. Hilleman died at age 85 and represents an older era of scientists who made their contributions the hard way - via dedicated use of grey matter and thorough exploration and knowledge of the scientific literature. He is reminiscent of an early mentor of my career, the late heart surgeon Victor P. Satinsky, M.D. of Hahnemann Medical College, who ran NSF science programs in the early 1970's for high school students interested in biomedicine. Dr. Satinsky was also a no-nonsense and highly inventive clinician who demanded critical thinking ("critical thinking always" was his motto) and the need for true expertise in biomedical science by those in leadership roles. My interests in medicine and computing, as well as many of my no-nonsense attitudes regarding clinical medicine, were formulated under his aegis. Perhaps that is why Dr. Hilleman and I seemed to see eye-to-eye on numerous matters.

Dr. Hilleman's death truly marks the end of an era. May he rest in peace.

Addendum: the article at Slate "The Unsung Vaccinologist" by Arthur Allen, who is writing a history of vaccination, captures Dr. Hilleman's essense well.

-- SS

"Climate of Alarm Described at NIH"

And here is yet another story about problems at the NIH, this time allegations about intimidation of whistle-blowers. The Associated Press obtained testimony charging that NIH officials squelched safety concerns tin the rush to try "to cure AIDS." For example,

• "It can be fairly uncomfortable. There are a number of things that you just don't talk about. You don't hold up any projects even if you feel there are safety issues for certain projects." (Testimony by Betsy Smith, NIAID)
• "I think we [safety officials] got in the way and that we were an impediment to the science." Division managers were "totally unsupportive" of safety and were responding to "tremendous pressure" from drug companies. "I think the culture was certainly strong for a period of time that the ends could justify the means." (Testimony by Mary Anne Luzar, Ph.D., Chief Regulatory Affairs Section, Pharmaceutical and Regulatory Affairs Branch, DAIDS)

Yet more clean up work is ahead for Director Zernouni. But this provides yet more justification for his argument that widespread changes are needed.

"The Price of NIH Credibility"

An excellent editorial in the Los Angeles Times. Let me just provide some quotes.

• "Protesting NIH staff scientists and members of Congress opposing the new regulations would have us think [NIH Director] Zerhouni intends to bulldoze the agency's 300-acre campus in Bethesda, MD, and turn it into a garment district sweatshop."
• "Zerhouni's critics claim that the new rules will lead to a cataclysmic brain drain. Yes, a few people might leave. But the rules also should bolster the agency's status as one of the few places where scientists can work with true autonomy, free from the increasingly brazen control that biomedical industries are exerting over research."
• "A Government Accountability [sic] Office study released two months ago found that the previous NIH policies 'could call into question the quality and independence of federally funded research.' There could hardly be a better reason for change."
• "At Senate hearings last week, Sen. Tom Harking (D-Iowa) sided with the complaining scientists and dangled a possible NIH budget increase in an implicit tit-for-tat for softer rules. That's just strong-arming."
• "Zerhouni is trying to restore scientific credibility to an agency that had allowed one of its top scientists, P. Trey Sutherland III, to pocket half a million dollars from Pfizer Inc. even as he was evaluating Pfizer drugs for NIH. Would [Senator] Harkin want to buy a drug for his family that was developed in this manner?"

Couldn't say it better myself.

Allegations of Professional Misconduct

The Washington Post reported that Dr. Sean R. Tunis, a physician licensed in Maryland, was accused by the State Medical Board of unprofessional conduct and making false statements about his credentials. The Board charged that Tunis falsey claimed attendance at continuing medical education events.
Tunis works part-time as an Emergency Department doctors at Mercy Medical Center in Baltimore.
State medical boards, of course, process cases like this fairly often. So, why is this news? And why is it relevant to Health Care Renewal?
Tunis' day job is Chief Medical Officer, and Director, Office of Clinical Standards and Quality for the Centers for Medicare and Medicaid Services. The Post reported that he has a major role in determining what services Medicare will cover, and, for example, was recently involved in the decision that Medicare would pay for implantable cardiac defibrillators for patients with congestive heart failure.
Tunis is now on administrative leave from that position. He claimed that the charges resulted from false accusations made by a "disgruntled CMS subordinate."
I hope it turns out that these allegations are false. However, charges that a key leader of a government health care organization engaged in unprofessional conduct certainly raise concerns about the quality of the organization's decisions.

Another Historic Case of Health Care Mismanagement

To toot my own horn a bit, the next in my series of historic cases of health care mismanagement has appeared in our local (RI) American College of Physicians newsletter. The article, entitled, "The Curiously Quiet Case of Cooper's Corrupt CFO," recounts a case featuring briefcases filled with cash, a hospital trustee convicted of murder, and the embezzlement of over $21 million. Yet despite these lurid details, it seemed to get no notice outside of local newspapers. In my next article, to appear in the summer, I will attempt to discuss lessons learned and not learned from cases like this and the one I previously recounted, that of the Allegheny Health Education and Research Foundation.

The Primary Care Squeeze: Who Will Be Part of the Solution?

In stark contrast to stories of ever more expensive drugs for ever more expansively defined ills, government research leaders getting six figure consulting fees, and multi-million dollar CEOs, ... primary care is in progressively worsening crisis.
Last week the American Medical News reported that family medicine has seen its eighth consecutive yearly decline in the number of US medical students matching to its residency positions. Since 1997, the number of US students going into family medicine training has dropped from 2340 to 1117, more than a 50% decrease. Fewer US students have matched in all primary care fields over the last 5 years.
This data still seems to puzzle the leadership of major US medical organizations. For example, the article quoted Steven F. Weinberger, Senior Vice President of the Medical Knowledge and Education Division of the American College of Physicians, "There's a concern that being the physician responsible for the ultimate care of the patient means life becomes a little more unpredictable in terms of hours. But there are wonderful ways to build models of practice to counter that." Furthermore, he said "another important issue is giving students the sense of the long-term gratification of the longitudinal care of patients." This is similar to previous comments made by him, and by leaders of the American Association of Medical Colleges (AAMC) and the American Academy of Family Practice (AAFP), (see this post) suggesting that the main reason that students were not going into primary care is that they hadn't learned about all its positive aspects.
I certainly agree that there are intellectual and emotional benefits to primary care practice. Maybe we aren't adequately teaching students about them. But it seems as if some of the folks leading large organizations like the ACP don't understand just how grueling primary care has become.
One way to understand its challenges is simply to page through some of the stories on Health Care Renewal.
On the other hand, see two articles from the Miami Herald last week. The first, "Primary Care MDs Under Pressure," described anecdotes of primary care doctors leaving practice "because they couldn't overcome the squeeze between low fees from insurers and soaring costs, or they refused to survive by cutting their time with patients." Ted Fisher, of the Florida Academy of Family Physicians, said as a result, "we see a big shortage coming in Florida...." The article included figures that primary care reimbursement has gone up 4.4% annually, while primary care overhead costs have gone up 7.7% annually. Discussions with physicians here in Rhode Island and southeastern Massachusetts suggest that we are being squeezed just as hard.
Why this story hasn't reached the leadership of the ACP, the AAMC, and the AAFP is not clear.
Robert Forster, Vice President, Health Care Services, and Medical Director of Blue Cross Blue Shield of Florida, was quoted as acknowledging that reimbursement to primary care physicians has not kept up with inflation, much less their rising costs. However, in the second article ("Primary Care is Often Undervalued"), he blamed it on society: "The importance of the primary care doctor doesn't have societal backing. The problem is that it's hard to measure the value of talking to a patient." Furthermore, "since the 1950s, American medicine has emphasized specialties and procedures over primary care. It's going to take some major changes in our society and our thinking to turn that around." Of course, "society" may be enchanted by the marvels of high-technology, sub-specialized care. However, in 2004, Blue Cross Blue Shield of Florida announced it has 28% of the Florida market, more than twice the share of any competitor. Why its Vice President, Health Care Services and Medical Director denies any personal or organizational responsibility for inadequate reimbursement for primary care is not clear either.
In summary, primary care is under seige by progressively rising costs and lower reimbursement. Since this seems to be public knowledge, it shouldn't be surprising that medical students are increasingly going into other fields. What is surprising, and troubling, is that leaders of major medical organizations either fail to recognize how hard it is to practice primary care, or recognize it, but fail to acknowledge any responsibility to do anything about the problem.
By avoiding any responsibility for the solution, such leaders become part of the problem.

More Downsides of a "Pill for Every Ill"

Two recent stories from the NY Times also accent the possible unintended effects of pharmaceutical companies' efforts to market "a pill for every ill."
One story was about the rush to develop drugs to combat obesity. Of course, obesity has health risks. But critics of the drug industry fear that the real appeal of such drugs would be to the only slightly overweight. This could lead to a huge market for such drugs. According to the Times, 60% of the US population is overweight. Thus "everybody is just foaming at the mouth to make money from obesity drugs." The danger, of course, is that new drugs often have rare serious side effects that are not detected in controlled trials on even thousands of patients. New obesity drugs might be taken by millions of patients, thus any such rare adverse effects could still affect substantial absolute numbers.
The other NY Times article was about increasing apathy towards safe-sex measures to prevent the spread of HIV. Some think that this is partly due to "drug company [direct to consumer] advertisements that gloss over the disease's effects by portraying patients as the pictures of perfect health." For example, Michael Weinstein, President of the AIDS Healthcare Foundation, cited an ad for Reyataz in Out magazine featuring two robust men on a beach. The ad includes an audio microchip. Opening the page "sets off the trill of a ringing phone and a man's voice essentially saying he is having too much fun to worry about his chronic illness." The San Francisco health department also fears that drugs for erectile dysfunction (ED, as the drug-makers like to call it) are another culprit, since they can counter the impotence caused by "crystal meth." ED drugs are widely marketed by direct to consumer advertisements, as anyone who has turned on network television in the last year must realize. Weinstein has called on Bristol-Myers-Squibb to stop running its audio enhanced ad, while the department of health is seeking to limit availability of "ED" drugs.
All the more reason to support the UK House of Commons Reports' call for "an industry led by the values of scientists, not those of its marketing force." (Quoted in the Guardrian.)