On swearing versus thuggery: a statistical analysis

A few bloggers commented on the (referenced) use of a bad word (F***) in my previous post (1, 2), and a few more commented below the post itself. I received a large number of comments by E-mail. The post was about suppression of data from Zetia or ezetimibe clinical trials, and the harm to both science and patients that results from such actions. I hypothesized that I would get some very negative responses to the linguistics, but that was not the case (n=13, all either positive or neutral). Sadly, for purposes of this discussion, it was therefore not possible to disprove the null hypothesis of no-offence.

I thought I would use this to discuss two rather different topics of relevance to medicine in general.

1. The statistical relevance of non-occurrence of an event
2. The problem of decorum versus thuggery

The statistical relevance of non-occurrence of an event

In this case there were no negative responses amongst 13 events. This problem has general relevance in medicine. Commonly, in clinical studies there are no observed events in a large number of patients. Forgetting for the moment that study patients might not reflect real-world patients, and that results of studies are often manipulated, it is interesting to examine the statistical meaning of non-occurrence. For example, if there are no deaths following liver biopsy in 200 consecutive patients in a particular hospital, how confident can we be about the mortality rate? If no patients (of 13) die in a Phase I study of an experimental drug, what does this mean? If the public relations officer of a bisphosphonate manufacturer claims that there were no cases of Osteonecrosis of the Jaw (ONJ) in formal clinical trials (n=3000) what are the confidence limits for the rate of ONJ within the population (assuming no-cheating, proper followup, and real-world similarity of trial patients)?

If the true rate of occurrence of an event in the population is R, then the probability P of non-occurrence in n consecutive patients is:

P = (1 - R)ⁿ

We can solve this for n as follows:

n = (log P)/log(1 - R)

This enables calculation of the number of consecutive non-occurrences needed to infer a low rate of occurrence R at a chosen P value. To the naive, the resulting numbers may seem surprising. If there are no deaths in 13 patients in a Phase I trial, then all we can say is that the likely death rate is less than 20% (at P=0.05). To infer a death rate in our Phase I study of not more than 1% we need to observe 299 cases with no death. I wonder whether patients in Phase II trials are provided with such information, either numerically or in spirit?

On the problem of decorum and swearing

I was interested in some of the responses I received. In the words of David Kern:

When you're in an argument with a thug, there are things much more important than civility. I do not like incivility. Yet, I like thugs even less.

My feeling is that our profession cares a great deal more about decorum and a sort of "pseudo-politeness" than we do about actions that are truly immoral, anti-science, and damaging to patients. Patients seem to care rather more about scientific honesty than we imagine. I have written previously of the quotation by the Irish priest Steve Gilhooley about the relation between decorum and thuggery. The quotation was delivered as part of a sermon on El Salvador. Gilhooley spoke passionately from the pulpit:

"I said to them, '70,000 people have been butchered and none of you gave a shit.'"

There was silence. A priest had sworn in the pulpit.

"And the reason I know none of you gave a shit," he continued, "was because none of you fell off your seat when I said '70,000 had been butchered', but nearly all of you fell off your seats when I said 'shit'."

Much of Gilhooley's feelings about the church would apply to the current sad state of medicine. Says Gilhooley [of the church]

"There are those who would rather hide the truth. Those whose priorities have become so skewed that they would protect [sexually] abusive priests before they would protect those who fight for justice and transparency. These are the people who are really in control in the Church. Well, let them get on with it. Let them bury it in the ground, and then we'll all start something else."

The offense caused by words depends on the priority we ascribe to various things. According to the "Hitchhiker's Guide to the Galaxy," the most offensive word in the universe is "Belgium." A journalist in the Melbourne Sunday Age (29.6.2003) provided an eloquent example of the significance of words following Greg Rusedski's Wimbledon soliloquy during his tennis match with Andy Roddick:

"As this is a family paper, both major and minor obscenities have been replaced by the names of birds. The result should be informative and educational."

"I can't do anything if the crowd albatross calls it. Absolutely vulture ridiculous. At least replay the point. Robin ridiculous, falcon ridiculous, budgie ridiculous. Some lesser-crested grebe in the crowd changes the whole match and you allow it to happen. Well done, well done, well done. Absolutely muttonbird..."

Here are some varied educational links:

1. Stupendous BBC/Advertising Standards Authority report on swearing - an impact analysis listing all the bad words (complete with graphs and statistical analysis)
2. Great piece on the evolution of swearing by a Geoffrey Nunberg (a linguist at UC Berkeley)
3. Why we curse. What the F***? by Steven Pinker, Harvard (fantastic, a must read).
4. Clin Psych blog on the Pinker article
5. How stuff works: Swearing
6. Swearing in other languages
7. West Side woman faces jail time for swearing at toilet: Pennsylvania Times-Tribune. Dawn Herb was facing jail for swearing at her overflowing toilet in her own home. She was overheard by an off duty police officer who heard her yell: "Are you f***ing retarded? Get me the f***ing mop." Patrolman Gilman said he then yelled, "Watch your mouth", to which the person replied: "F*** off.". She was later acquitted.
8. College Teacher fired for saying F___ in class: Inside Higher Education
9. Devil's Kitchen: On swearblogging (an excellent, intelligent UK political blog which includes a great deal of swearing).
10. Ben Goldacre: Sweary Mary

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More problems with Ezetimibe (Zetia, Vytorin): Let there be light

Yet more problems with Zetia (ezetimibe) clinical trials are now being reported in the New York Times (see background to the Enhance trial of ezetimibe Ezetimibe (Zetia, Vytorin): the smell of bad science). This has to do with hidden data in other studies of the drug.

Part of the problem here is the redefinition of what we mean by scientific fraud, and a redefinition of science itself. If I (as an individual scientist) were to study 20 rats, and then plot a graph showing only the results from those rats "I liked", or those rats I "considered important enough" then I would be guilty of scientific fraud.

Somehow when the stakes are higher we confuse power with honesty, and the deception is tolerated. It's an oddly familiar pattern of deception.

From 2000 to 2003, Merck and Schering-Plough conducted eight long-term safety studies of Zetia in combination with statins. Only three of those studies were published. Now some questions are being asked about what those studies showed, and why prescribers and patients were not given a full view of the evidence.

A Schering executive, Dr. Robert J. Spiegel, said "the companies had not considered the studies scientifically important enough to publish their findings. Some may eventually be published".

Well fuck you Dr. Spiegel, it's not your decision. When patients might die it's always "scientifically important". You might personally think that other scientists and even patients don't need to know what the evidence is, but it really isn't your call. If you want to sell your product under the banner of science you have to behave like a scientist. Science which cannot be scrutinized is not science at all. If you disable doctors and patients from making rational (and scientific) decisions about the use of your product, then you cannot claim to be a science based-enterprise. There are many other serious problems with suppressing clinical data. Patients in these trials exposed themselves to unknown risks in the interests of all of us. Suppression or distortion of that data is an affront to their dignity as human beings.

Science is, as Carl Sagan put it, a candle in the dark. It shines a light on the world around us and allows us to see beyond our superstitions and fears, beyond our ignorance and delusions, and beyond the magical thinking of our ancestors, who rightfully fought for their survival by fearing and trying to master occult and supernatural powers.

Let there be light.

From other blogs:

1. Brody, Howard (2007-12-21). New Cholesterol Controversies: Regaining Perspective. Hooked: Ethics, Medicine, and Pharma.
2. Aberegg, Scott (2007-12-22). Patients and Physicians should BOYCOTT Zetia and Vytorin: Forcing MRK and SGP to come clean with the data. Medical Evidence Blog.
3. Aberegg, Scott (2007-12-20). Are Merck and Schering-Plough "enhancing" the ENHANCE data?. Medical Evidence Blog.

From the NY Times, By ALEX BERENSON, Published: December 21, 2007:

The discovery of the unpublished research comes as Merck and Schering are already under criticism for not yet releasing data from an important Zetia study, called Enhance, that they completed early last year.

"The unpublished Zetia studies, devised as safety tests, would not prove the drug’s effectiveness. But they would give the public more information about Zetia’s potential risks. All the unpublished studies covered periods at least one year in length and were intended to show whether long-term use of Zetia might pose dangers that short-term use did not.

Most of the studies about Zetia in which Merck and Schering have published the results covered periods of only 12 weeks — not enough time for liver problems to develop in most patients.

The unpublished studies, conducted from 2000 to 2003 according to the F.D.A. documents, were not listed on the industry Web sites where companies are supposed to register the results of all drug trials that were ongoing after October 2002. The New York Times discovered references to the studies in briefing papers on the F.D.A. Web site.

“We keep telling people we want to practice evidence-based medicine, and what we keep finding out is that much of the evidence is obscured,” said Dr. Harlan Krumholz, a cardiologist at Yale, when told about the previously undisclosed studies. “There is important evidence, but it’s not in public view. It’s hidden from investigators.”"

“You don’t want to have data missing,” said Dr. Bruce Psaty, a professor of medicine and epidemiology at the University of Washington. “When there have been adverse effects, when the benefits don’t look impressive, those are the trials that historically don’t make it to press.”

A Schering executive, when asked by a reporter about the unpublished studies, confirmed their existence. But the executive, Dr. Robert J. Spiegel, said the companies had not considered the studies scientifically important enough to publish their findings. Some may eventually be published, he said.

“We’re pretty comfortable that people don’t have trouble tolerating Zetia,” said Dr. Spiegel.

Dr. Eric J. Topol, a cardiologist and director of the Scripps Translational Science Institute in La Jolla, Calif., said that he had asked Merck and Schering more than four years ago to conduct a large, long-term trial to prove that Zetia could reduce heart attacks and strokes. But the companies had little interest, he said.

“They looked at me like I was an alien,” Dr. Topol said.

Dr. Mark Stolk, a gastroenterologist in the Netherlands, last year reported two cases of patients who had developed hepatitis, a liver disease, after taking Zetia alongside Lipitor. One of the patients has since died.

But Dr. Beatrice A. Golomb, an associate professor at the University of California, San Diego, said doctors have lost sight of the purpose of prescribing drugs like Zetia.

The goal of prescribing cholesterol-lowering drugs is not reducing cholesterol, Dr. Golomb said. It is reducing the number of deaths and heart attacks in patients, he said. And without data to prove that Zetia actually reduces heart attacks, doctors cannot be sure they are helping patients when they prescribe the drug, she said.

See post followup: On swearing versus thuggery: a statistical analysis
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A ray of light - well done Dr John P. Kastelein

A note of congratulations to Dr John Kastelein for saying the right thing out loud. I would imagine this is only the first step in the tortuous path that might lead to honest reporting of the ENHANCE trial of ezetimibe. For background see Ezetimibe (Zetia, Vytorin): the smell of bad science.



From the Wall Street Journal

The lead researcher of a long-delayed drug study says he regrets not standing up to Merck & Co. and Schering-Plough Corp. when they first told him last month that they planned to alter the statistical analysis of their jointly sponsored trial.

Under mounting criticism, the companies last week reversed the earlier decision to change the primary measure to evaluate the drug.

John P. Kastelein, a cardiologist at Academic Medical Center, Amsterdam, and principal investigator of the study, said he breathed a 'sigh of relief' when the companies told him last week they were reversing course.

'It's never, ever right to change the primary endpoint of a study,' especially after all the data are in, he says. 'It is statistically not good and it gives the wrong impression to the outside world.' He says he initially went along with the plan but now regrets not firmly resisting it from the outset.

He says the episode was the culmination of a long-running battle over the conduct of the trial and the companies' worries that some deficiencies in the data would jeopardize a good result.

From Health care Renewal: Manipulation of ENHANCE Reversed:

"So this case is unusual, in that an early public outcry resulted in at least some of the clinical research manipulation being reversed. There may be hope yet."

Indeed. The problem is that with so much deception in clinical trials, and with so much at stake it is hard to know when data can be believed. Nevertheless this is a first step. However it still appears that the companies involved had control over the study database in this trial - a crucial problem.

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Christmas gifts for the MHRA and GMC

Quite liked this cover. A new book by John O'Farrell. Gifts for my totally non-corrupted friends at the MHRA (the UK drug regulator) and my totally non-corrupted and non-racist and honest friends at the General Medical Council. All as pure as the driven slush. Merry Christmas to all.

Synopsis
Here at last is a chance to have a good laugh and learn all that stuff you feel you really ought to know by now...you can read how Anglo-Saxon liberals struggled to be positive about immigration; 'Look I think we have to try and respect the religious customs of our new Viking friends - oi, he's nicked my bloody ox!' Discover how England's peculiar class system was established by some snobby French nobles whose posh descendants still have wine cellars and second homes in the Dordogne today. And explore the complex socio-economic reasons why Britain's kings were the first in Europe to be brought to heel; (because the Stuarts were such a useless bunch of untalented, incompetent, arrogant, upper-class thickoes that Parliament didn't have much choice.) A book about then that is also incisive and illuminating about now, "2000 Years of Upper Class Idiots in Charge" is an informative and cantankerous journey through Britain' fascinating and bizarre history. It is as entertaining as a witch burning, and a lot more laughs. Even more laughs than GlaxoSmithKline's study 329 and all those children who died.

Perhaps a copy too for the UK Panel for Research "integrity". I recall an immensely productive and useful meeting with them exactly a year ago.

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Contemptible response of the week - from Health Canada

The prize for the most ludicrous letter of the week goes to Health Canada (the Canadian equivalent of the American FDA or the UK MHRA).

This letter could serve as a model template for all regulators. It is as timely as it is informative. I am sure that the writer is not personally responsible but perhaps she needs to consider the part she plays in the farce. The letter no doubt reflects with some honesty the spirit of the actual procedures used to deal with a serious complaint. Below the letter are details of the complaint (of 2005) that precipitated the response received last week. It is truly amazing how hilarious these "regulatory" bodies are - and how little they care that actual human beings die as a result of their actions.

This letter was the sole response to a formal complaint made by four Canadian health policy researchers about illegal and misleading direct to consumer advertising of the drug Diane-35 (cyproterone and estradiol) during 2005. The complaint mentioned that the advertisements were in contravention of the Food & Drugs Act. Diane-35 increases the risk of venous thromboembolism compared to other similar hormone combinations, and there were at that stage at least six reported deaths in Canada. Diane-35 was the subject of two safety advisories in Canada which warned doctors not to use Diane-35 for two unapproved (off-label) uses: for birth control or mild acne. Diane-35 was only approved for a restricted indication in Canada: treatment of a subgroup of patients with endocrine disorders and very severe acne who have failed to respond to all treatments. Nevertheless the DTC advertisements promoted Diane-35 for unapproved uses, and targeted a vulnerable population: adolescent girls. The ads conveyed scientifically false information. Risks were also not mentioned.

Mild acne was promoted as an indication through the use of images of young girls with flawless skin preening in the mirror and the message to 'Ask your doctor or your dermatologist' at the end of the ad. The addition of dermatologist was a clear hint of the indication. Anyone who had severe acne that had failed to respond to previous treatment would not have the flawless skin of these models, either before or following treatment. There is also no indication for the use of Diane as a contraceptive. Three to 10 extra cases of venous thromboembolism occur per 10,000 women taking Diane-35 per year, as compared to the rate of venous thromboembolism in users of other oral contraceptives. Several other illegal aspects of the advertisements were noted.

Of course it is possible that the "satisfactory" actions taken by Health Canada might have included prison sentences for those implicated (the usual sanction in a sane society when individuals recklessly break laws and endanger real people). Readers might wish to contact Saveen Kamarn at (604)666-8516 or Saveen_Kamarn@hc-sc.gc.ca to find out what happened. As usual my profession remains silent.

Onwards and upwards for honest science.

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Memory Hole (7 December): A case study in ethical medical leadership

Scientific Misconduct Blog Memory Hole: Events of December 7th

9 years ago today: A critical commentary on the role of leadership in medicine

On 7 December 1998 Professor Manuel Buchwald wrote a letter which has become a case study in medical ethics.

In that year Professor Brenda Gallie held the position as leader of the Research Division of Cancer and Blood at the Hospital for Sick Children at the University of Toronto. Her line manager was Professor Manuel Buchwald (OC, PhD FRSC, and Lombard Insurance Chair of Pediatric Research, Hospital for Sick Kids Chief of Research). Buchwald is one of the co-discoverers of the Cystic Fibrosis gene. He is listed in the Canadian Who's Who.

In May 1998 Gallie learned that Dr. Nancy Olivieri, a member of her Division had failed to persuade Buchwald or the hospital administration to assist honestly with a critical ethical crisis involving clinical research funded by the Canadian Pharmaceutical Company Apotex.

Gallie wrote to Buchwald and the hospital President suggesting that the matter required urgent action. They responded by telling her that she "did not know the whole story", and should not become involved. It later became known that Apotex were involved in granting tens of millions of dollars to the University, and that the University were about to attempt to whitewash the embarrassing affair. The funding from Apotex was promised to increase to $55million, and university leaders were encouraged to act according to the wishes of Apotex. As part of a widespread campaign of bullying, the leadership of University of Toronto began to attack a series of academics who had attempted to stand up for honesty in science. On the 7th of December 1998 Buchwald wrote the below letter to Gallie. It is self explanatory. It includes a wonderful series of comments on integrity in medical leadership. Moral duty, our duty to patients and our duty to colleagues are, according to Buchwald, inconsistent with being a leader. Moral integrity is apparently incompatible with the overriding duty of a leader to the institution.


For the complete letter see here - Manuel Buchwald to Brenda Gallie, 7 December 1998

This letter is derived from the morality of Auschwitz. It would seem to me to disqualify someone from being a respected scientist involved in human research. The University of Toronto did nothing to discipline Buchwald. Gallie was appalled, and resigned her leadership position. She moved her research program to the Ontario Cancer Institute.

Great intellect implies neither humanity nor ethical insight. It's all in the ventromedial prefrontal cortex several inches behind the brow. Buchwald, as a younger scientist had held himself as an advocate for human rights.

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Perceptions of probity

I found this picture interesting.

Take a look at look at the two images from your seat. Note which face is angry, and which is calm (Mr Left or Mr Right). Now get up and move back at least 10 feet.

I had the same feeling when speaking about ghostwriting and scientific misconduct at recent meetings of the International Society of Medical Publication Professionals (ISMPP). Different people, apparently looking at the same world, do not see the same thing.

Although "ghostwriters" are ostensibly the key enemy, I had a different view after these meetings. Most honestly believe that what they do is important and good. Most are very nice people, well intended, and with genuine concerns about integrity. Most are shocked when shown examples of what has happened - and the consequences.

This is in contrast to academic medical leadership who have acquiesced with deception, and have passed their sense of integrity to the next generation. Medical writers do facilitate deception, but are not generally responsible for it. Some ghostwriters have however been participants in outright scientific fraud.

There are problems with overemphasising only one facet of a very large problem, and pretending that it is the whole problem.

Work of Phillippe G. Schyns and Aude Oliva at MIT

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Ezetimibe (Zetia, Vytorin): the smell of bad science

Concerns are brewing over strange events, quack science and possible scientific misconduct during reporting of the "Enhance" trial of the cholesterol-lowering drug Ezetimibe[1][2][3][4][8]. Ezetimibe is sold by Merck and Schering-Plough (trade names Zetia and Vytorin with annual sales of $4billion). No trials have shown that Ezetimibe reduces cardiovascular events (the main endpoint). No such trials were required prior to FDA approval. The drug does however lower the bad form of cholesterol (LDL).

I personally have no problems with drug approval in the absense of evidence of efficacy, so long as customers (doctors and patients) are not misled. Its a free world. I guess all patients have been told that a) the relationship between LDL lowering and actual clinical disease is not straightforward, b) that some drugs lower LDL but increase risk, c) that the relevant science prescribers have been permitted to see is a sack of potatoes.

The "Enhance" study of Ezetimibe was supposed to look at a surrogate endpoint that is one step closer to actual cardiovascular events - namely the development of atherosclerotic arterial plaques. So what happened?

• Oddly the reporting of "Enhance" was put off by a year, and it is now planned to remove the shroud of secrecy sometime in 2008 (possibly.....). Cardiologists expected to see results at a medical meeting in November 2006, then at another in March 2007, then at another this month. But none materialized [8].
• It turns out the companies have decided to change the study's primary endpoint in retrospect. To convince everyone that this is the right thing to do, they brought in an "outside" expert advisory "panel" who concluded that the wrong thing is the right thing (presumably for a fee). They then refused to state who these supposed experts were.
• It turns out that the company has had full control over all of the study data and that the lead "author" has not yet seen any of it.
• Lead investigator of the study, Dr John Kastelein (Academic Medical Center, Amsterdam, the Netherlands)stated that "The suggestion that the results are being suppressed because they are negative is simply wrong. People are assuming that anyone can take a peek at the data, but how can they do that if it hasn't even been unblinded and there are 40 000 images to analyze?"

With respect Dr Kastelein, the assertion that altering endpoints before unblinding cannot cause bias is obvious and utter nonsense.

1. Firstly, we have no confidence (P=0.3) that the study has not in fact been secretly unblinded. This lack of confidence is the logical assumption following numerous odd events and data alterations which have taken place in the past (random examples here[5][6]). Unblinding codes are presumably held by the same entity holding the raw data (I guess). That same entity has a huge financial stake in the outcome. That entity is not yourself Dr Kastelein. Nor is that entity a secure impartial honest third party (a complete guess).
2. Secondly, as an experienced scientist you will be fully aware it is perfectly easy to fiddle the results of a randomized trial given a "blinded" study database even without the un-blinding codes. Ezetimibe has many side "effects" that distinguish it from placebo apart from it's intended clinical benefit (LDL lowering is itself such a "side effect"). It would be easy for an individual "exploring" the data to examine the relationship between LDL lowering and various "primary endpoints" without unblinding to get a pretty good idea of the "primary" endpoints to reject, exclusion criteria to be applied, or even the variables that might require a little "recoding".

There is no certainty here, but strange events have taken place on a sufficiently regular basis for the confidence limits to be wide (P=0.3). The smell is not one of science Dr Kastelein. I'm glad you expressed unease with the process, and queried the mysterious need to alter the endpoints. Word is that you are one of the honest people. I believe you should go the whole way, and stand up for honest science and integrity. You might also make some comment about the need for company statisticians to be involved with the data at all.

Others [4] have pointed out some of the key problems with this research, and I have added a few more:

1. Seek to get your drug on the market before we know whether it actually makes us live any longer or prevents real disease.
2. Keep all the data under your strict control; don't even let the (so-called) lead investigator see it.
3. Change the primary study endpoint in the middle of the trial.
4. Pretend that this is science.
5. Keep all the processes as secret as possible at each step of the way.
6. Conduct studies that focus on patients who are not at all representative of the intended target customer for the drug.
7. Pretend that you are a company based on science, but at the same time pretend out loud that altering data or endpoints in a still-blinded study cannot possibly be a means to induce bias.

If you are a patient taking one of these drugs, go ask your prescriber for a summary of the scientific evidence. Alternatively pay a visit to your nearest homeopath (an Ouija board may also prove useful).

References:

1. Hughes, Sue (2007-11-23). Concerns Raised on Delay of Ezetimibe Data. Medscape/Heartwire.
2. Merck/Schering-Plough Update on ENHANCE Trial. Merck Website.
3. Berenson, A (2007-11-21). After a trial, silence Page C1. New York Times.
4. Brody, Howard (2007-11-24). Here We Go Again: Everything That's Wrong with Industry Sponsored Trials. Hooked: Ethics, Medicine, and Pharma.
5. Blumsohn, Aubrey (2007-10-21). Vioxx and a quacking duck. Scientific Misconduct Blog.
6. Blumsohn, Aubrey (2007-05-19). On the redefinition of research misconduct. Scientific Misconduct Blog.
7. Berenson, Alex (2007-11-24). Cardiologists Question Delay of Data on 2 Drugs. New York Times.
8. Herper, Matthew (2007-11-19). Drug Trials: The Vytorin Question. Forbes. Retrieved on 2007-11-27.

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Procter and Gamble and the rigmarole of integrity

It is obvious to several people that I have been extremely lazy the past week. I have been struggling to catch up with the memory hole feature after attending (and presenting at) a few great meetings.

The excellent picture of Sisyphus sleeping is with kind permission of artist Michael Bergt. Sisyphus is condemned to roll a large rock up a hill. Upon reaching the top the rock rolls back, and the task has to be repeated - endlessly. The story appears to be one of eternal and pointless labor.

I haven't said much about recent progress with the first of the three shonky Procter and Gamble publications. I felt it best to allow time for the excuses to be finalized, and to allow others to comment first. A few examples of those comments are referenced.[1][2][3][4][5][6] I don't necessarily agree with all commentary, but generally people are not morons.[7]

I am finding the "Memory Hole feature" quite useful myself as a way of understanding how we got where we are. To catch up I am going to skip the dates 13-20 November. I'll get back to filling in the blanks over the next few weeks.

References:

1. Colquhoun, Professor David (2007-11-06). Universities Inc. in the UK, Corporate Corruption of Higher Education: part 2.
2. Baty, Phil. "Expert admits he did not have full access to data", Times Higher Education Supplement, 2007-10-12.
3. Silverman, Ed. Boning Up: Journal Tightens Disclosure Policy. Pharmalot.
4. Woodhead, Michael (2007-10-28). A double dose of dodgy data.
5. Saunders, Professor Peter (2007-11-01). Actonel, Dog that Did Not Bark in the Night. Institute of Science in Society.
6. Poses, Roy (2007-10-12). Journal Changes Policy After Blumsohn Case.
7. Moron - n. a person whose actions are explained by motives one is not smart enough to understand. See also * Dullard, Idiot, Ignoramus (Author: S.R. Brubaker, Devil's Dictionary Defiled)

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Memory Hole (12 November): Corruption of medicines "regulation"

Scientific Misconduct Blog Memory Hole: Events of November 12th

Quote of the day

"We could make no greater mistake than to be lulled into a sense of false security by believing that some disembodied force called the government will act like a beneficent big brother and make certain that the special interests will not predominate. If the general welfare is to be protected, it will be protected by the actions of people, not the government."
-Dr. A. DALE CONSOLE, former medical director for drug giant ER Squibb (as quoted in Peretz Glazer and Migdal Glazer, ISBN 0465-09173-3)

3 years ago today: FDA shows "respect for the scientific process" by intimidating scientist

On 12 November 2004 a Food and Drug Administration (FDA) official called the Lancet in an attempt to prevent publication of a study that raised concerns about the drug Vioxx. The article would have embarrassed the FDA

The author, David Graham pulled the paper at the last minute because he feared for his job. The study was due to be posted on the Lancet website on Nov 17th 2004. FDA Acting Commissioner (and convicted criminal) Lester Crawford said that Galson contacted Lancet editor Richard Horton "out of respect for the scientific review process."

Horton responded: "You will not be surprised if I say that I was a little taken aback to get your call on Friday (Nov. 12). It is very unusual indeed for a member of the employing institution of an author to contact us in the middle of the review and publication process of a manuscript."

On November 18th Graham told a Senate panel that the FDA is "virtually defenseless" against another "terrible tragedy and a profound regulatory failure". Excess deaths resulting from the use of Vioxx have been estimated at 100,000.

USA TODAY Scientist says FDA called journal to block Vioxx article 28 Nov 2004

3 years ago today: FDA: Being honest is a conflict of interest

On 12 November 2004 the FDA removed Dr. Curt Furberg from an FDA advisory committee for alleged "intellectual conflict of interest" (but more likely to protect Pfizer). Furberg had previously analyzed the data relating to Bextra and had concluded that Bextra carried cardiovascular risk (similar to Vioxx).

Sandra Kweder, acting director of the FDA's office of new drugs, said "If he's already expressed a particular point of view, and especially written a paper on it, would be difficult to expect him to come to such a meeting and be objective about the subject".

What a corrupt muddle. Apparently (but not always) being a scientist and taking a scientific approach is a conflict of interest. FDA's action against Dr. Furberg contrasts sharply with the agency's infinite tolerance of overt and extensive financial conflicts of interest of its advisory panel members.

Sources:

1. WALL STREET JOURNAL, FDA Removes Panel Member From Drug Review, Nov 12 2004
2. http://www.ahrp.org/infomail/04/11/15.php
3. http://www.gooznews.com/archives/000091.html
4. http://www.ahrp.org/infomail/04/11/12a.php

3 years ago today: Sharper teeth for the UK Medicines "Watchdog"

On 12 November 2004 it was reported that the UK government announced sweeping changes to the "independent" and "transparent" medicines watchdog body after years of criticism and pressure, banning those who sit on its central licensing committee from having any personal or financial interests in pharmaceutical companies [Sharper teeth for medicines watchdog, The Guardian, November 12 2004].
(Duh!)

In March 2003 a review committee of the UK Medicines regulator tasked with looking at the safety of GSK's drug Seroxat had to be disbanded when it was revealed that half the members had share holdings in GlaxoSmithKline. Here are some later and ongoing members of the MHRA and their personal interests in just this one company:

Professor A Breckenridge - GSK Fees
Professor H Dargie - GlaxoSmithKline Consultancy
Dr M Donaghy - GSK Shares
Dr J C Forfar - GSK Shares
Dr R Leonard - GSK Fees/ Publicity work
Prof D J Nutt - GSK Consultancy Psychotropics and 300 shares (1)
Professor J F Smyth - GSK Consultancy
Professor Christopher Bucke - SKB Shares
Prof Nicholas Mitchison - GSK Shares
Dr Brian J Clark - GSK PHD student funding
Professor Robert Booy - GSK Consultancy
Professor S M Cobbe - GSK Research grant
Professor J E Compston - GSK Consultancy
Dr A Glasier - GSK Shares (£10,000)
Dr Andrew A Grace - GSK Consultancy
Dr P Hindmarsh - GSK Consultancy on growth, probably lapsed by now
Professor P D Home - GSK Consultancy - Ex-employee of GSK
Dr R F A Logan - GSK Shares
Professor R MacSween - SmithKline Beecham Shares
Professor J O’D McGee - SmithKline Beecham Shares
Professor David R Matthews - GSK Honorarium for advice
Dr A Smyth - GSK Conference expenses
Professor A D Struthers - GSK Shares
Professor J C E Underwood - GSK Shares
Dr A Gerard Wilson - GSK Consultancy
Dr Rosemary Leonard - GSK Fees/ Publicity work
Mr David P S Dickinson - GSK Fee paid work
Dr Charlotte C D Williamson - GSK Shares
Professor Anthony H Barnett - GSK Advisory work and lectures diabetes related products
Professor V Krishna K Chatterjee - GSK Consultancy on preclinical research
Professor Albert - GSK Shares

Professor Alistair Breckenridge [Link][Link][Link][Link] and Dr Ian Hudson [Link][Link][Link] are both former employees/advisors of GlaxoSmithKline, having been involved with GSK's drug Seroxat. Both now work for the MHRA.

The very definition of independence. If any of the above named have ever made any statement about selective reporting in GSK clinical trials, or GSK's study 329, or disputes their GSK funding, I would be pleased to hear from them to correct the record.

"Following the path of least resistance
is what makes rivers and men crooked."

2 years ago today: Scott Gottlieb - what is the half-life of a conflict of interest?

On 12 November 2004 further concerns were raised in the press over the circumstances that led to the appointment of Dr. Scott Gottlieb to the position of deputy commissioner at the Food and Drug Administration. Gottlieb's absurd anti-science and anti-transparency stance, his conflicts of interest, and attempts to interfere with FDA decisions were causing anxiety. He was heavily criticised for attempting to intimidate staff behind the scenes in relation to a Pfizer osteoporosis drug. Gottlieb had also been appointed by one Lester Crawford (who was convicted of criminal offenses relating to his role as FDA Commissioner).

Upon taking his post Gottlieb recused himself for up to a year from any deliberations involving nine companies that are regulated by the FDA, including Eli Lilly, Roche and Proctor & Gamble. (In analogy with radioactive decay, one year is the well recognized decay time for the effect of a conflict of interest after switching off a current income stream).

"He came to this job with no regulatory experience, directly from Wall Street, where he served as a biotech analyst and stock promoter. Between them, Drs. Von Eschenbach and Gottlieb have whined incessantly about the need to speed drug development."

"When asked about his industry connections, Gottlieb said that he complied with all legal requirements".

For some depressing reason the British Medical Journal (a scientific journal?) decided to employ Gottlieb as a staff writer from 1997-2005.

Source:
Henderson, Diedtra. "FDA official recused in flu fight - His ties to drug firms spark questions over agency hiring policies", Boston Globe, 2005-11-12.

Read further:

1. The Scott Gottlieb example - The Carpetbagger Report (2005-09-26).
2. Corporate Crime Reporter: Zheng Xiaoyu Meet Lester Crawford.
3. Henderson, Diedtra. "FDA official recused in flu fight - His ties to drug firms spark questions over agency hiring policies", Boston Globe, 2005-11-12.
4. Mundy, Alicia. "Wall Street biotech insider gets No. 2 job at the FDA", The Seattle Times, 2004-08-24.
5. Blumsohn, Aubrey (2007-09-01). Gottlieb pronounces on pharmaceutical research integrity. Scientific Misconduct Blog.
6. Poses, Roy (2007-08-31). Conflicted View on the Pitfalls of Government-Sponsored Comparative Effectiveness Research. Health Care Renewal.

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Memory Hole (11 November): What else happened?

Scientific Misconduct Blog Memory Hole: Events of November 11th

9 years ago today: New laws and missing raw data

On 11 November 1998 new congressional laws were enacted to deal with access to raw scientific data. This followed refusal by Harvard to release raw data based on a spurious excuse of participant "confidentiality".

"When tax dollars pay for a scientific study, should the public be allowed to see the results? Of course. And now it can, thanks to a provision in the new federal budget law". Read on....

That's good law, but why should it apply only to publicly funded research? Withholding of raw data means that the work is not science in any conventional sense, and should not be published or publicized as science. Science that cannot be scrutinized is not science at all.

3 years ago today: The MHRA: "Shake-up" vs "inaction and cover-up"

On 11 November 2004 the following item appeared on BBC News about the UK drug "regulator". It is reproduced in full.

BBC NEWS: [Link] Shake-up for drug licensing body, November 11, 2004

A reform of the way drugs are regulated has been outlined by ministers to make the system more independent. A new code of conduct has been drawn up for the Medicines and Healthcare products Regulatory Authority (MHRA) body responsible for licensing. It proposes not allowing the members of the body, the Commission for the Safety of Medicines (CSM), to hold interests in the pharmaceutical industry. It also calls for more patient involvement in the process. Two lay representatives will sit on the CSM, the new name for the Committee for the Safety of Medicines, as well as patient representatives on every expert advisory group under the plans. The MHRA has also written to pharmaceutical companies to demand more action on their agreement to publish their clinical trial data. The move comes after heavy criticism at the way the MHRA operates. On Wednesday in a Westminster Hall debate Dr Ian Gibson, chairman of the Commons science and technology select committee, said the MHRA had an image problem. He said it was "gaining a reputation for not giving out information". "I think it is time the culture of secrecy was addressed.

"The damage done by the public believing they have been lied to or defrauded is difficult to repair. "It is the only regulatory agency that is fully industry funded. "It is a difficult task to convince people that a regulatory body entirely funded by the industry is impartial." Last month BBC's Panorama programme criticised the MHRA over its handling of anti-depressant drug Seroxat. The Panorama investigation claimed vital information relating to Seroxat was overlooked.

It suggested the drug could be addictive and increase suicidal feelings in young adults. Health Minister Lord Warner said it was important the MHRA was "open and transparent". He said the changes meant that "everyone can be confident in the impartial and independent expert advice given on the safety of medicines". Professor Sir Alasdair Breckenridge said: "Proposals for the new commission incorporating strengthening of patient and lay involvement, tightening of the rules of interest and increased transparency will move the MHRA forward in its aims of improving public health." And Harry Cayton, the government's patients tzar, welcomed the increased involvement of patients, saying it would increase the agency's "expertise and strengthen its ability to take account of the public interest". "I hope that following these reforms the MHRA will be more active in communicating with the public about its processes and decisions."

No shake-up ever took place. See also:
The MHRA : Why is the government not acting?
1463 days to nothing - the GlaxoSmithKline Criminal Investigation

1 year ago today: Medical Leadership in action

On 11 November 2006 Elizabeth Paice, Chair of the medical forum charged with delivering MMC (Modernising Medical Careers) in the UK stated "MMC is going to be really, really good". (From BMA News 11 Nov 2006)

And it was good, really good.

Read on:

• Fiasco over doctors’ jobs
• Pick a doctor by computer 'fiasco'
• Dr Elizabeth Paice in Article 10 Human Rights Act 1998 Shock
• On Elizabeth Paice

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Memory Hole (11 November): UK Government hides clinically relevant science

Scientific Misconduct Blog Memory Hole: Events of November 11th

7 years ago today: UK government hides clinically relevant science

On 11 November 2000 a BBC report indicated a deliberate attempt by the UK Department of Health to hide science and to mislead the public and doctors - a case of scientific misconduct perpetrated by government.

If there was scientific evidence relating to potential transfer of mad cow disease (vCJD) through improperly cleaned surgical instruments would you want your doctor to know? According to a report by BBC Panorama the UK government tried to hide a scientific report that it didn't like. The report suggested that there is a real risk of spreading vCJD via surgical instruments. The report also revealed serious flaws in hospitals' equipment cleaning procedures.

Kate Priestley, Chief Executive of NHS Estates NHS Estates (an executive agency of the Department of Health) ordered microbiologist David Hurrell to destroy all copies of the report "It asked me to destroy or return all the copies of the reports and draft reports and data that I had got and to delete all electronic files." Here is a letter:



BBC Panorama stated "A senior expert on hospital decontamination methods has told Panorama how he was asked to destroy all evidence of a government-commissioned study into standards of decontamination in English hospitals."

The letter read: "In light of the somewhat negative outcome... there is a need to ensure, at the express request of ministers, that the final version and earlier draft reports remain strictly confidential." The benefits of the study "may be compromised if the findings of the report were to enter the public domain in an inappropriate or unauthorised fashion".

Professor Michael Banner who led the team of experts was not allowed to see part of the decontamination report either. Banner says, "It's really quite absurd and unbelievable that the document has not been made available... It's astonishing that anyone would wish to hold back information from the public about the state of hospitals."

Panorama asked the Department of Health three questions:

1. Why has Michael Banner, Chair of the Incident Panel, been refused sight of the report?
2. Why, if this was only an interim piece of work not considered for publication, was consideration given to which photos might be used for the cover of the final report last summer?
3. Why was it decided, in the light of the somewhat negative outcome of the report and at the express request of Ministers, that the final version and earlier draft reports remain strictly confidential?

The Department of Health replied saying only that this line of questioning was "silly". Panorama then asked why "if they were so silly, were many of the people involved in the report being telephoned on Friday and asked not to talk to Panorama?" This is a disgrace. Alan Milburn was the Secretary of State for Health at the time.

See also: BBC: Ministers sought to bury vCJD report; http://darrendixon.supanet.com/cjdreport.htm

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Memory Hole (10 November): What else happened

Scientific Misconduct Blog Memory Hole: Events of November 10th

1 years ago today: Statins decrease cholesterol by 0.13mmol/L

On 10 November 2006 a paper in the Journal of Internal Medicine (260; 551) reported that average cholesterol levels had fallen considerably in Swedish men between 1986 and 2006 - from 6.32 to 5.51 mmol/L. Almost none of this decrease was due to statins. Fewer than 10% of people were a lipid lowering drug, and these accounted for only 0.13 mmol/L of the population decrease.

2 years ago today: GSK: Our product is.......

On 10 November 2005 Chris Viehbacher, head of U.S. operations at GlaxoSmithKline Plc, was quoted as saying "In the long term Glaxo would like to spend a lot more on researching new medicines and a lot less on selling them".."So far we haven't found a more effective way of educating physicians."

The product is science.

Chris Viehbacher is an accountant. I have seen no comment from Viehbacher on any possible deception in GSK drug trials, or those trials that disappeared. Perhaps Silence is part of the "education".

Source: Hirschler, Ben. "Drug giants wary on cutting sales forces", Reuters, 2005-11-10.

3 years ago today: Pfizer and Bextra - optional truthfulness

On 10 November 2004 Pfizer entered the scientific debate over their hidden Bextra data - by abusing critics.

Cardiologist Garret FitzGerald reported a pooled analysis of clinical trial results showed patients taking Pfizer's arthritis drug Bextra were twice as likely to have a heart attack or stroke as those taking a placebo. When reports appeared in the New York Times, instead of addressing the science Pfizer attacked back. The report they said "draws unsubstantiated conclusions about the cardiovascular safety of" Bextra and "is based on information that has not been published in a medical journal or subject to independent scientific review."

Their product is science but there was no science in the response. Five months later on April 7, 2005, Pfizer withdrew Bextra from the U.S. market.

Pfizer has since disclosed that, at the time of those statements, it did indeed have studies that demonstrated heart problems among patients taking Celebrex or Bextra. When a Pfizer scientist said that there was no clear evidence that Celebrex posed a risk, members of the FDA committee stated: "That just doesn't pass the laugh test" (Dr. Alastair Wood, chairman of the hearing). Wood noted that Pfizer omitted from its presentation the key study that documented problems with Celebrex. One panel member accused Pfizer of hiding data. Dr. Curt Furberg of Wake Forest University stated "I'm troubled by some inconsistencies that I have found in the briefing document from Pfizer." Furberg suggested that all of Pfizer's mistakes seemed to benefit the company. "So I wonder how much trust can we put in these presentations" he said.

Professor Ralph D'Agostino told the committee "We really don't know what to make out of any long-term use" based on Pfizer's studies that lasted only a few weeks". Dr. Verburg of Pfizer responded simply, "We recognize all of the faults in what we are doing"

Dr. Byron Cryer of the University of Texas Southwestern Medical Center, described part of the Pfizer presentation as "misleading." Dr. Verburg of Pfizer responded simply, "Point taken."

But the point Dr. Verburg is that this is quackery and bad science. Perhaps it is not science at all. People die as a result.

Sources:
See FDA report 7 April 2005 http://www.fda.gov/cder/drug/InfoSheets/HCP/valdecoxibHCP.htm
Systematic review of Bextra in JAMA http://www.cox2drugreview.org/
Medical Panel Poses Pointed Questions to Drug Makers Over Risks of Painkillers, New York Times 17 Feb 2005

5 years ago today: UK Labour government brings integrity to the NHS

On 10 November 2002 the UK government Health Secretary Alan Milburn was criticized for hiring the American private insurer United Healthcare to help "cut costs in the NHS by keeping the elderly patients out of hospital".

As the Observer "discovered" without much difficulty "United Healthcare has been forced to pay millions of dollars in fines to settle charges that it had defrauded the US government, patients and doctors", had "falsely charged the US government for patients it claimed were in nursing homes" by inventing institutionalized patients, and had been fined for "cheating patients out of money". The firm had also been "failing to give proper notice of the right to appeal" when denying patients healthcare, and Michael Mooney, a United vice-president, was jailed for three and a half years for insider trading.

About time New Labour started saying the unthinkable and admitting their moral and intellectual bankruptcy in the area of healthcare and medicines regulation.

Milburn apparently holds a place on the board of PepsiCo. On 28 February 2007, he launched 2020 Vision, a website intended to promote policy debate (well debate then). There is a Chinese saying, "a fish begins to smell from the head down..."

Source: UK's elderly care plan run by US "cheats", the Observer, Nov 10

4 years ago today: Another P&G spying case

On 10 November 2003 Procter and Gamble were exposed in the Chicago Sun Times for their involvement with Wallmart in an escapade which involved spying on customers. Briefly, Lipfinity lipstick was tagged with an electronic (RFID) tracking device between March and July 2003. Customers unwittingly left the store carrying the tag.

At the same time a live video camera trained on the shelf allowed Procter & Gamble employees (700 miles away) to observe and videotape the Lipfinity display and consumers interacting with it. "Given the players, the Wal-Mart Lipfinity trial probably isn't an isolated incident," says CASPIAN spokeswoman Liz McIntyre. "documents suggest that other products, including Huggies baby wipes, Pantene shampoo, Caress soap, Purina Dog Chow and Right Guard deodorant were also slated for live RFID field trials".

In P&G's defense it could be said that the video material was apparently not kept, and the videos were mostly of the back of customer's heads. Bizarrely, it was also stated that "the test was not secret. There was a sign near the Lipfinity display that alerted customers that closed-circuit televisions and electronic merchandise security systems are in place in the store."

In 2006 P&G's received first prize in the annual Most Trusted Company for Privacy Award. They consolidated their position that year by releasing the long-denied raw data to researchers who had "authored" schlonky publications about their osteoporosis drug Actonel. Onwards and upwards.

See: more on RFID devices

8 years ago today: Scientific fraud involving three drugs - prison anyone?

On 10 November 1999 an editorial in JAMA discussed ondansetron, a drug that was being studied to prevent vomiting. Researchers analyzing the literature found 84 studies involving 11,980 patients -- or so they thought. Some of the data had been published twice, and when the researchers sorted it out, they realized that there were really only 70 studies, in 8,645 patients.

Since the duplicated data was the good data, the reviewers estimated this double-counting would lead to a 23 percent overestimate of the drug's effectiveness.

Similarly data for the antipsychotic agent risperidone had been published multiple times in different journals, under different authors' names.

Other problems involving fluconazole (made by Pfizer) were reported. Fluconazole had been compared with Amphoteracin B, but on close inspection it appeared that the Amphoteracin had been given by mouth instead of intravenously (it is not at all effective orally and is supposed to be given by drip).

Dr. Michael O'Connell, deputy director of the Mayo Clinic Cancer Center in Rochester, Minn., an expert on clinical trials, said: "To publish the same data again with entirely different authorship, as if it were an entirely different data set, is reprehensible".

The problem is that the authors of the papers probably didn't even know, because they had almost certainly never seen the data, and were just brain-dead drones and fraudsters.

The reviewers tried to ask the authors about the design of the studies and for the data. Some ignored the requests, and others said they no longer had the data. Pfizer declined comment to JAMA.

Dr. Bert Spilker, senior vice president for scientific and regulatory affairs at PhRMA, the lobby group for drug manufacturers, said: "We don't have a perfect situation. It probably can be improved." Scientific fraud is not "a perfect situation" when your industry is supposed to be selling products under the banner of science. When patients die as a result of faulty misleading science it is obviously not "a perfect situation" either. As usual, nobody was held to account.

See: Medical Journal Cites Misleading Drug Research, NY Times, 10 Nov 1999

16 years ago today: A company employs "traditional and standard" methods to avoid exposure

On 10 November 1991 the New York Times reported on the way in which one powerful industry thought it was the government, gestapo secret police and the law rolled into one. It raised questions about the lengths to which powerful individuals will go to silence critics and avoid embarrassing disclosures. Although not about scientific misconduct, it is related to the corporate scientific crimes discussed here.

When Trans Alaska Pipeline felt in 1990 that confidential company documents had been taken and conveyed to regulators it hired Wackenhut Corporation.

"For three years in the late 1980's, the owners and operators of the 791-mile-long pipeline had been a target of the unrelenting criticism of a former oil broker from Virginia named Charles Hamel. Mr. Hamel, who was battling several oil companies in court, became a conduit for leaked documents about lapses in Alyeska's environmental and safety programs. The documents turned up in the hands of regulators and the news media, resulting in large fines and millions of dollars in expenditures by Alyeska to fix the problems. With unlimited funds supplied by Alyeska, Wackenhut hired highly trained investigators, bought sophisticated eavesdropping equipment, and set up a sting operation to induce Hamel to disclose his sources."

1. Wackenhut's investigative net stretched from Alaska to Florida to Washington
2. Miniature cameras were installed in hotel rooms in Alaska.
3. Trash was rifled at Mr. Hamel's home.
4. Motorized vans with electronic devices intercepted conversations for recording.
5. Using phony credentials from a fake environmental law group, Wackenhut's agents befriended Hamel, who invited them into his home, where they stole documents from his desk.
6. When Hamel talked with the House Interior Committee and its chairman George Miller, Wackenhut's agents and Alyeska's lawyers considered targeting him as well.

George R. Wackenhut, the company's founder and chairman said the actions taken to prevent the public from finding out were entirely legal and "traditional and standard".

Source: "A Case of Heavy-Footed Gumshoes" New York Times, 10 Nov 1991

17 years ago today: Plagiarism at Boston University

On 10 November 1990 it was reported that substantial parts of the late late Dr. Martin Luther King, Jr's doctoral dissertation and other academic papers from his student years appeared to have been plagiarized.

"analysis of the papers by researchers working on the project had uncovered concepts, sentences and longer passages taken from other sources without attribution throughout Dr. King's writings as a theology student." "scholars who have seen the papers declined to say how great a percentage of the material had been plagiarized, but they said it was enough to indicate a serious violation of academic principles."

Officials at Boston University stated that it is not likely the Ph.D. would be revoked "because neither Dr. King nor his dissertation adviser is alive to defend the work".

Source: DePalma, Anthony. "Plagiarism Seen by Scholars in King's Ph.D Dissertation". New York Times, 10 November 1990.

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Memory Hole (10 November): Stanford study too frightening to release

Scientific Misconduct Blog Memory Hole: Events of November 10th

8 years ago today: New Study Too Frightening To Release

On 10 November 1999 the Onion released important news of a Stanford University study that was too frightening to release. Researchers were refusing to release a comprehensive three-year interdisciplinary study on the grounds that the results are "too terrifying to reveal to the public at large". Dr. Desmond Oerter broke down while discussing the terrifying never-to-be-released study.

"We have decided that it is in the best interest of public safety to withhold the results our study," "so soul-shaking are the conclusions we have drawn".

Oerter then produced a pair of ballpoint pens and plunged them into his eye sockets. At a press conference later that afternoon, Stanford president Gerhard Casper assured members of the general public that steps are being taken to prevent the release of what is being called "The Study Which Must Not Be Named."

"All primary data gathered in the study have been destroyed, as have all research materials used by those involved," Casper said. "The world must never know what was learned here."

Two of the study's coordinators had also taken their own lives, and three more remain on suicide watch. "I'm not talking about it, and you won't find anyone who will," said Craig Blom.

Read more....

[In contrast to everything else on this blog this is a realistic spoof]

Source: New Study Too Frightening To Release | The Onion - America's Finest News Source
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Will Merck settlement kill drug innovation?

Over on the ZDNet Healthcare Technology Blog ("Where Technology means Business", "Longer, better living through technology") Dana Blankenhorn asks Will Merck settlement kill drug innovation? A lawyer is cited : "Perhaps Merck's management just wanted peace, to lay the litigation and bad PR to rest. But with its shares up 80% in the last two years, the market was showing it believed that the Vioxx problem would turn out OK." and "Merck had a winnable case".

What case?

I sure hope it does kill innovation. This is the sort of innovation we are talking about:

Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation
Innovation

It is called bad science. Lawyers and shareholders don't seem to care much about that strangely, but they should. That said, Merck has more integrity than most of it's competitors, and I hope it gets out of this mess. Take the Gardasil roll-out : let us hope that is as transparent, non-coercive and as science-based as possible before we have another disaster.

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Memory Hole (8 November): Mostly about lawyers

Scientific Misconduct Blog Memory Hole: Events of November 8th

Definitions of the day

LAWFUL, adj. : Compatible with the will of a judge having jurisdiction.
LAWYER, n. : One skilled in circumvention of the law.
LITIGANT, n. : A person about to give up his skin for the hope of retaining his bones.
LITIGATION, n. : A machine which you go into as a pig and come out of as a sausage.
(The Devil's dictionary)

23 years ago today: Arthur Rudolph: US hides Nazi crimes

On 8 November 1984 it was reported that Arthur Rudolph imported from Nazi Germany to head the NASA Saturn Program (which led to the moon landing) was known to be an "Ardent Nazi" and a war criminal. He was operator of a slave camp. More importantly, the US knowingly provided cover for him. This is directly relevant to the more specific concerns on this blog - it concerns the role of government in a democracy.
"Papers Show Saturn Rocket Chief Was Called 'Ardent Nazi by U. S.": New York Times, 8 Nov 1984.

14 years ago today: Inventing scientific findings is not fraud say lawyers

On 8 November 1993 the muddle of Scientific Misconduct "rules" reached the outer limits of farce
(Hilts, Philip J. "Science and Law Clash Over Fraud-Case Appeals," New York Times, 8 November 1993).

Procedures of science are designed to ensure the integrity of the scientific record, just as court procedures are designed to make sure that the legal game is played. This is an article about attempts to alter the procedures for deciding whether a scientist is operating within the rules of science. This was the midst of the Baltimore and Gallo "investigations". New rules were put in place by Bernadine Healy when director of the NIH to make lawyers the judge of appropriate science, radically altering the game in retrospect, and leading to these two cases being "lost" (at least legally).

"In the first case before the hearing board under the new rules, Rameshwar Sharma, a scientist at the Cleveland Clinic Foundation, was charged with making false statements in an application to the National Institutes of Health. He wrote that he had done a series of experiments and described the results, when in fact he had not done the work."

By any definition that would constitute research misconduct and a major offense against science, the public, and patients. This is not a game, and it is exactly how patients die.

In his defense, he said that he no intent to deceive but that his statements were 'anticipator writing' because he expected to do the work later. The hearing said this was not misconduct because the Office of Research Integrity could not prove the deliberately false statements were intended to be false. The need to prove intent is part of the new definition. Falsifying results does not constitute intent.

This is lawyers and the "big boys" of science saying that saying that science and honesty don't matter. The muddle began here.

Source: Hilts, Philip J. "Science and Law Clash Over Fraud-Case Appeals" New York Times, 8 Nov 1993

10 years ago today: UK "initiatives" to tackle scientific misconduct

The Journal Science published a bit of reality-free gobbledegook about a November 8th 1997 meeting concerning UK initiatives to "tackle scientific misconduct and fraudulent publication in a more systematic way". There is a disconnect between what folk say and what they fear to do.

Williams, Nigel. "Editors Seek Ways to Cope With Fraud" Science 278 (14 November 1997), p. 1221 [Full report].

Some quotes from the article:

• A new committee, set up by the editors of nine prominent medical journals called last week for governments to tackle scientific misconduct and fraudulent publication in a more systematic way.
• Cases are still exposed mostly by chance, and we worry about the scale of the problem
• "Normal peer review can sometimes identify problems, but sorting through raw data to investigate them can be a miserable business".
• These incidents were described without revealing names because of worries about libel laws [describing scientific deviations is libel]
• The meeting backed calls by one of the legal experts on the committee, Ian Kennedy of University College London, for the development of a protocol for editors to help protect genuine whistle blowers.
• COPE's efforts are being matched by other initiatives in Europe.
• And at the most recent meeting of the European heads of research councils in Dublin last month, the problem of scientific misconduct was at the top of the agenda.
• The council heads are looking in particular at Danish efforts that have culminated in a new national committee on scientific dishonesty. Unlike the U.S. Office of Research Integrity, which can investigate misconduct claims only when they involve government funds, the Danish committee can work across the scientific spectrum.
• Editors can only go so far," says Kennedy. "Eventually you need an independent body to investigate claims fairly.

So what happened ten years later?:

See:
http://scientific-misconduct.blogspot.com/2007/10/memory-hole-15-october-uk-research.html
UK research misconduct Hit-Squad announced (UK-PRI)

Self quotation: You should treat any offer of support from UK-PRI in the same way you would treat the offer of fellatio from a crocodile.

8 years ago today: German Professor fakes 80 clinical studies - not a crime

On 8 November 1999 German investigators report that dozens of bogus scientific papers were published by a cancer research professor over 15 years.

The Professor was Friedhelm Herrmann, a leading cancer research specialist. The report states that "at least 80 of his published papers were faked", and "they developed an aversion to using genuine data."

The last sentence of the news report states: "Faking scientific research, however, is not a criminal offence under German law".

Source: German scientist 'faked cancer research', The Guardian, Nov 8, 1999

4 years ago today: Medical journal editors colluding with fraud

On 8 November 2003 there were some choice quotes from a BMJ article: Have editors got their priorities right? (BMJ 327:1113; 8 Nov 2003):

"Journal editors are much more frightened of being sued for libel by academics or drug companies than they are of publishing fraudulent research" Peter Wilmshurst claimed last week.

He said that every time that he submitted an article highlighting research fraud, every word was scrutinised by an army of libel lawyers and the article was frequently rejected.

"I have submitted many scientific articles for publication and many had implications for survival of patients, but no journal has ever asked me to prove that I got the results claimed. This might suggest that medical journal editors are more concerned with the reputations of academics and their institutions than the lives of patients.

"The simple truth is that editors are most concerned with money. Journals are never sued for publishing false results no matter how many patients died. In scientific research they can have the best of both worlds. They are absolved from blame if a study is wrong and gain an improved impact rating if the research is an important advance..."

"I would like to see whether the policies at journals changed if some were sued by patients harmed by implementation of treatments based on their publications."

"I believe that there should be random checks of raw data of work in progress and of submitted work. We know that the use of performance enhancing drugs is common in competitive sports because of enforced drug checks without warning at sporting events and between events. If we did not have these checks we might mistakenly conclude that doping was not common in sport."

"Failure to produce the raw data should be considered the equivalent of failing the inspection and should result in a ban on future research for a specified period and a review of previous research published.

"The code of silence that pervades the medical profession and the research establishment: There is still considerable reluctance to shop another doctor, no matter how dishonest".

2 years ago today: SSRI advertisements not exactly science-based

On 8 November 2005 PLoS medicine published as article titled: "Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature" (Lacasse JR, Leo J 2005 PLoS Med 2(12): e392).

Apparently direct to consumer advertisements for drugs are not exactly truthful. What a surprise. Next episode - the disconnect between the scientific literature and the underlying raw data. Hat tip HCR.

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