Perceptions of probity

facesI 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?Dr John Kastelein
  • 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

Sisyphus sleepingIt 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

sharpening teeth MHRA

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)
Medical Leadership
And it was good, really good.

Read on:


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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.

The truth

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

Spy vs Spy

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

Spy vs Spy

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.

The law

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

Crocodile

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.

The law

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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Memory Hole (7 November): What else happened

Scientific Misconduct Blog Memory Hole: Events of November 7th

Glaxo mission statement

3 years ago today: More high-science from GSK

On 7 November 2004 secret plans to "double sales" of the anti-depressant Seroxat "by marketing it as a cure for a raft of less serious mental conditions" (like "shyness") were revealed with exposure of a 250-page document GlaxoSmithKline (The Guardian, 7 Nov 04). Richard Brook, chief executive of Mind who submitted the secret GSK document to MPs said it was "all about developing new conditions for that drug and demolishing the arguments of other competitors about why their drug was not any good".

GSK is a another company based on the selling of honest science, so they do actually need to engage in honest science. Actual scientists are not that impressed (See "advantages" of Seroxat). "Science" from the same pot as colonic irrigation.

Glaxo Smithkline Mission statement: "We have a challenging and inspiring mission: to improve the quality of human life by enabling people to do more, feel better and live longer."

Gosh!

2 years ago today: Pfizer - science is our product

On 7 November 2005 an interesting scientific statement in the Wall Street Journal from Pfizer Chief Executive Officer (CEO) Henry A. McKinnell PhD:

"It looks like a combination of raising HDL and lowering LDL cholesterol could have dramatic impact, maybe eliminating cardiovascular risk".

Remember this is a company whose product is science. McKinnell's PhD is in business, from Stanford.

Pfizer mission statement: We demand of ourselves and others the highest ethical standards, and our products and processes will be of the highest quality. We play an active role in making every country and community in which we operate a better place to live and work, knowing that the ongoing vitality of our host nations and local communities has a direct impact on the long-term health of our business.

2 years ago today: Self regulation

On 7 November 2005 Bloomberg news published an important investigative series on commercial IRB's.

It was noted that In 1991, 80% of trials were done in academia. In 2005 most (75%) drug trials are done by commercial firms.

The FDA has farmed out much of the responsibility for overseeing safety in these tests to private companies known as institutional review boards. These boards are financed by pharmaceutical companies. The trials themselves are conducted in private experimental clinics rather than in a clinical context. "The fundamental problem is a system in which investor-owned businesses have control over the evaluation of their own products".

So, the drug industry is paying the people who do the tests, the people who write up the results, the people who analyze and filter the results, the people who regulate the system, the journals who publish the science, and the academic authors who put their names to all of this. Perhaps we should not be surprised that this has not always resulted in high quality, ethical, honest or innovative science.

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Memory Hole (7 November): Boots payout for scientific misconduct

10 years ago today: Scientific misconduct payouts: Boots Nov 1997, Merck Nov 2007

On 7 November 1997 it was reported that Knoll Pharmaceutical Co. agreed to pay at least $98 million to settle dozens of lawsuits charging that the company cheated consumers by suppressing publication of a study on one of its drugs. The story related to research performed 7 years ago by Betty Dong's group at the University of California, San Francisco.

Exactly ten years later this week, Merck has reached a $4.85 Billion settlement in 27,000 suits covering about 47,000 plaintiffs, three years after withdrawing Vioxx from the market.

In 1990, Dong, a researcher at UCSF was funded by Boots to carry out research on a widely use thyroid treatment (Synthroid). She discovered the Boots drug was no more effective than three much cheaper competitors. When she tried to publish, Boots threatened to sue. The publication was withdrawn. She received no institutional support. Company executives attempted successfully to publish an inaccurate version of the findings while excluding Dong and threatening legal action. Nine years later the sordid details were exposed in the press and Dong’s paper was published. The company paid around $170 million to "settle" class action lawsuits.

Both these settlements were "good" for the companies concerned and "good" for lawyers. In the case of the Dong affair, it is estimated that the company made a profit of $3billion in inflated costs during the nine year delay. They paid out less than $200 million in compensation. No company executives were prosecuted. The regulators turned a blind eye. In the case of Vioxx, the company has escaped serious sanction for the systematic misleading of patients/doctors and disobeying the rules of science leading to tens of thousands of excess deaths.

Some References:

April 1996: How a Drug Firm Paid for University Study, Then Undermined It," WSJ, 25 April 1996
July 1996: ""A cautionary tale" Science: 273. pp. 411
Nov 1997: Rennie D, "Thyroid storm" JAMA, Apr 1997; 277: 1238 - 1243
Nov 1997: Kaiser, Jocelyn. "Firm Pays Dearly for Suppressed Study", Science 278 (7 Nov 1997)
Nov 2007: Pharmalot: Law Prof On Vioxx Deal: A Good Gamble For Merck
Merck research excoriated by the Lancet
Vioxx and a quacking duck

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Memory Hole (7 November): Psychiatrist Ewen Cameron and professional collaboration with evil

Collusion and silence

19 years ago today: C.I.A funding of unethical research and professional silence

On 7 November 1988 Lawyer for victims of C.I.A LSD experiments wrote in the NY times about the out of court settlement with 9 Canadians who sued the US over experiments done by Dr. Ewen Cameron. The article was titled "The C.I.A. and the Evil Doctor". Cameron was a psychiatrist with McGill University. Experiments were carried with secret funding from the C.I.A without participant consent. The work involved LSD administration, sleep deprivation and so called psychic driving. These 9 patients formed only a tiny part of Cameron's research.

"...(H)e induced severe regression in the patients using combinations of extremely intensive electric shock, barbiturate- induced sleep for up to 60 days at a stretch, sensory deprivation, and hallucinogenic drugs. These techniques left patients dazed, confused, incontinent and often in a state of utter panic."

Many colleagues knew about this research for years and said nothing at all. Some of the research was discussed openly and published in the psychiatric literature.

D. Ewen Cameron, "Psychic Driving," American Journal of Psychiatry 112 (January, 1956), pp. 502-509.

"The effect of this procedure (psychic driving) has been studied under various conditions, among them drug disinhibition, ordinary and prolonged sleep treatment, hypnosis under stimulant drugs and after prolonged psychological isolation."

D. Ewen Cameron, et al., "Repetition of Verbal Signals: Behavioral and Physiological Changes," American Journal of Psychiatry 115 (May, 1959), pp. 985-996.

This paper states: "This work was carried out with the assistance of a grant from the Society for the Investigation of Human Ecology."

Just as some depression "support" groups are a front for GlaxoSmithKline and other pharmaceutical companies, "The Society for the Investigation of Human Ecology" was a front for the C.I.A.

"Dr. Cameron had the support of many psychiatrists and psychiatric residents, whom he trained or worked with, and not one had the guts or integrity to speak out or criticize his brainwashing methods. The Canadian Psychiatric Association and American Psychiatric Association are also culpable for refusing to denounce Dr. Cameron or his experiments. It is not only Dr. Cameron, the C.I.A. and the Canadian Government that should be on trial in these experiments, but psychiatry itself." [Link]

Here is a selection of quotes about collaborators, bystanders and the shame of all those who say nothing. There are many in medicine who remain silent while professing virtue:

Science may have found a cure for most evils; but it has found no remedy for the worst of them all - the apathy of human beings.
Helen Keller

Truth is not only violated by falsehood; it may be equally outraged by silence.
Henri Frederic Amiel

To assist Enron all they had to do is to do nothing, and they did nothing very well

He who passively accepts evil is as much involved in it as he who helps to perpetuate it.
Martin Luther King, Jr

Our lives begin to end the day we become silent about things that matter.
Martin Luther King, Jr.

What luck for the rulers that men do not think.
Adolph Hitler

And the multitude was silent, not a voice, not a sound was heard upon the hillsides, across the valleys where they stood.
Richard Bach, Illusions

To sin by silence when they should protest makes cowards of men.
Abraham Lincoln

There is no shame in not knowing; the shame lies in not finding out.
Russian proverb

A society of sheep must in time beget a government of wolves.
Juvenal

The average age of the world's greatest civilizations has been two hundred years. These nations have progressed through this sequence: From bondage to spiritual faith; from spiritual faith to great courage; from courage to liberty; from liberty to abundance; from abundance to selfishness; from selfishness to complacency; from complacency to apathy; from apathy to dependence and back into bondage.
Fraser Tyler

You may never know what results come from your action. But if you do nothing, there will be no results.
Gandhi

The world is a dangerous place to live; not because of the people who are evil, but because of the people who don't do anything about it.
Albert Einstein

Sources - Cameron and the C.I.A:
-Rubenstein, Leonard S. "The C.I.A. and the Evil Doctor," New York Times, 7 November 1988, p. A19.
-New York Times, "U.S. to Pay $750,000 In Suit on LSD Testing" 12 Oct 1988


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Memory Hole (5 November): What else happened?

Scientific Misconduct Blog Memory Hole: Events of November 5th

natrural strychnine

7 years ago today: "Naturalness" as a property of matter

On 5 November 2000 a reminder that "naturalness" is not always perfect goodness.

The pesticide, rotenone, is extracted from the dried roots, seeds and leaves of various tropical plants that produce their own "natural" pesticides. It is widely used on home-grown fruits and vegetable produces Parkinson's disease in rats. Because it is "naturally" occurring it is advertised as being safer than synthetic pesticides. It is also used to kill unwanted fish. It is allowed to be used to grow "organic" produce.

Science has to apply to the natural and unnatural.

"Pesticide Found to Produce Parkinson's Symptoms in Rats," New York Times, 5 Nov 2000

4 years ago today: FDA chair advises FDA to ignore own decision

On 5 November 2003 Dr. Thomas Whalen, Chairman of FDA's advisory committee that had voted on Nov 3 to approve resumption of silicone breast implants, wrote to FDA Commissioner, Marc McLellan, urging him to ignore the vote of his own committee and not approve. Whalen said "I felt morally compelled" to do so. "Long-term safety, the concern that prompted removal from the market 11 years ago was clearly not demonstrated".

I have a better idea: Why not publish the honest and complete raw data and let science work as it should? Patients (and their doctors) and scientists have a right to draw conclusions or even decide to make dumb decisions based on proper unfiltered data. It's called science.

FDA advisor: Ignore breast implant vote. Associated Press 5 Nov 2003.

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Memory Hole (5 November): Merck research excoriated by the Lancet

Scientific Misconduct Blog Memory Hole: Events of November 5th

Vioxx

3 years ago today: The Lancet accuses Merck of irresponsible deception

On 5 November 2004 the Lancet published an important paper and an excoriating editorial about Vioxx, accusing Merck and the FDA of acting "out of ruthless short-sighted and irresponsible self-interest".

From the Lancet - Editorial 5 Nov 2004 (Volume 364, Number 9448)

"Today we publish results from a cumulative meta-analysis which show that the unacceptable cardiovascular risks of Vioxx (rofecoxib) were evident as early as 2000-a full 4 years before the drug was finally withdrawn from the market by its manufacturer, Merck. This discovery points to astonishing failures in Merck's internal systems of post-marketing surveillance, as well as to lethal weaknesses in the US Food and Drug Administration's regulatory oversight. In a recent Editorial, we commended Merck for acting promptly in the face of new findings about the safety of Vioxx. Our praise was premature. The evidence showing that Vioxx caused significant adverse events was apparent well before data from the APPROVe trial triggered Merck's overdue intervention."

"These findings also come in the wake of new disclosures that suggest Merck was indeed fully aware of Vioxx's potential risks by 2000. Investigations by the Wall Street Journal have revealed e-mails that confirm Merck executives' knowledge of their drug's adverse cardiovascular profile-the risk was "clearly there", according to one senior researcher. Merck's marketing literature included a document intended for its sales representatives which discussed how to respond to questions about Vioxx-it was labelled "Dodge Ball Vioxx". "Merck's own understanding of Vioxx's true risk profile and its attempt to gloss over these risks in their public statements at the time"

"The FDA's position is no less comfortable."

"But, too often, the FDA saw and continues to see the pharmaceutical industry as its customer." "Worse still, the FDA's Office of Drug Safety co-exists in the same centre - the Centre for Drug Evaluation and Research (CDER) - as the Office of New Drugs, the part of the agency that works most closely with the industry to license new medicines. Once a licensing approval has been made, it is naturally in CDER's own interest to stand by its original decision."" The inherent precedence that licensing of new drugs takes over safety evaluation is a serious flaw". ". . . the FDA tried to shore up its tarnished reputation by posting on its website an early version of a recently completed observational study into the safety of Vioxx."

"its [FDA's] decision to try to undermine the integrity of [Graham's] work shows, that the agency's senior management is more concerned with external appearance than rigorous science".

"… with Vioxx, Merck and the FDA acted out of ruthless short-sighted and irresponsible self-interest."

"Another important point to come out of this is how little confidence we can have in our medical specialists to act in any independent and critical manner. Virtually every expert rheumatologist, gastroenterologist and cardiologist who should have been ringing the alarm bells is a consultant for the same companies."

In the parallel study published in the November 5, 2004 of the Lancet researchers' pooled data from more than 25,000 patients who participated in 18 clinical trials and 11 observational studies all conducted before 2001. The results showed that patients taking Vioxx had 2.3 times the risk of heart attack as those prescribed placebos or other NSAIDs. This increased risk applied to short trem therapy as well.

In concluding, the researchers stated that "If Merck's statement in their recent press release that 'given the availability of alternative therapies, and the questions raised by the data, we conclude that a voluntary withdrawal is the responsible course to take.' was appropriate in September, 2004, then the same statement could and should have been made several years earlier, when the data summarized here first became available. Instead, Merck continued to market the safety of Rofecoxib. This clearly demonstrated that Merck had, by the end of 2000, sufficient statistically significant information that required the immediate withdrawal of Vioxx".
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Memory Hole (4 November): What happened this day

Scientific Misconduct Blog Memory Hole: Events of November 4th

hat tip

19 years ago today: If you won't supply raw data we won't publish

This is about the status of raw data (Hat Tip - Al Higgins). On this day, 4 November 1988, the Editor of the journal Cell (Benjamin Lewin) stated that it is the policy of Cell that if authors are unwilling to share raw data, they should not publish (in Cell or presumably anywhere).

It is hard to know why anyone honest would disagree. Presumably we agree that a large part of the research published by the pharmaceutical industry should not be published either, and is not science in the conventional sense.

What made Lewin's statement odd was that Cell had published the infamous paper by Baltimore, et. al. in 1986. When asked by concerned scientists to supply the raw data, Baltimore et al., refused.

Bowledge, Tabitha M. "Getting Serious About Fraud and Misconduct," AAAS Observer, Science supplement (4 November 1988), pp. 1ff.

19 years ago today: The Phillip Berger case

On 4 November 1988 it was reported that a Stanford Inquiry had cast doubt on 11 papers. Very prominent scientist Phillip Berger was involved. He had resigned in May 1987.

Stanford had earlier been criticized for sham internal procedure, delay, secrecy and attempts to minimize the problem. More to follow.

"Stanford Inquiry Casts Doubt on 11 Papers," Science 242, 4 Nov 1988

9 years ago today: Chris Chapman died

On 4 November 1998 Dr Chris Chapman, a biochemist in Leeds (UK) died at age 56 after drawing attention to serious research fraud and financial misconduct at Leeds University. The persistent but failed internal attempts at whitewashing had taken their toll. He was also dismissed (one day before he could legally receive an employer's pension).
See: Earlier post

1 years ago today: Angry whistleblowing doctor fired

I have included this mainly for the quotation. On this day, 4 November 2006 a news report discussed the plight of "whistleblower" Dr Phillip O'Dowd who had dared to discuss financial fraud involving the CEO of a US hospital. He was fired. The CEO (Robert Urcuioli) was later convicted of fraud.

In the article O'Dowd relates that the cited reason for his firing was "anger-management problems". Asked whether he had anger issues, he said:

'I did have anger-management problems. I was very angry at the management.'

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Memory Hole (3 November): Forgetfulnesss

Scientific Misconduct Blog Memory Hole: Events of November 3rd

Quote of the day

FORGETFULNESS, n.
A gift of God bestowed in compensation for destitution of conscience.

48 years ago today: Thalidomide saga - the Voss question

On 3 November 1959 a written report was received by Chemie Grunenthal from neurologist Dr Ralf Voss of Dusseldorf reporting more adverse effects. Voss asked if Thalidomide could cause damage to the peripheral nervous system. Chemie Grunenthal replied that such effects had never been observed before. At the trial this proved to have been a lie.

8 years ago today: Hidden deaths, hidden science and uninformed consent in gene trials

On 3 November 1999 it was reported that deaths in clinical trials involving gene therapy were being hidden on demand from companies who were worried that it would "have an impact on their business". The Washington post reports:

"Scientists and drug companies have failed to notify the National Institutes of Health about six deaths that occurred in gene therapy experiments in the past 19 months".

"The researchers said they reported the deaths to the Food and Drug Administration, which keeps such information secret". "they are filing reports with demands for confidentiality or maintaining that they don't have to file them with the NIH at all".

Researcher Ronald Crystal "cited concerns about the impact on his business if the death were made public". "Schering-Plough also had demanded confidentiality for three recently filed reports of serious patient illness during gene therapy trials. The lead scientists in two of those studies determined that the complications "probably" were caused by the gene therapy; Schering-Plough officials had downgraded those assessments, saying they were "possibly related" to the therapy".

My oh my. Confidential science, confidential deaths, and information-free "informed" consent. No learning from the experience. Collusion by regulators. Is this science? Is it ethical? Did participants know that even their deaths would not contribute to knowledge? Would they have consented to take part had they known this?

Persons and companies named: Schering-Plough, Ronald Crystal of Cornell, Jeffrey Isner of Tufts, Carol Goodrich of Parke-Davis

But, two weeks later on 21 November 1999 the Washington post provided further details about one death - the totally unnecessary death of 18 year old Jesse Gelsinger at the University of Pennsylvania following a gene therapy experiment. It is reported that:

"it wasn't the first time the researchers had seen it. Unbeknown to Gelsinger, .... that monkeys the Penn team had similarly treated had succumbed in very much the same way". "The original [Gelsinger] consent form, reviewed by the NIH, clearly notified prospective participants that monkeys had died from a related treatment, but the final version given to patients eliminated any mention of the deaths." The NIH committee members say they also never got word of a significant change in the consent form. Neither the FDA nor the Penn team can explain today why the reference to monkey deaths was dropped.

"all four rhesus monkeys that had been given high doses of the first-generation virus had died in previous experiments".

Bit it wasn't only monkey data that had been hidden: Schering-Plough Corporation and the University of California had done preliminary trials in dying cancer patients, but "lowered the dose when two early participants experienced serious drops in blood pressure. But even at that lower dose – which was lower than the total dose eventually given to Gelsinger – two patients suffered serious stroke-like attacks". Wilson (the researcher) said he was only vaguely aware of those studies, none of which had been published in peer-reviewed journals until after Gelsinger's death. "But neither did Wilson reveal in his [own] written report at the meeting that one [earlier] patient had suffered an especially serious reaction to the treatment. Gelsinger was not informed of any of this.

Wilson, the researcher said: "If a mistake was made, we've got to own up to it and learn from it. Ultimately, the tragedy of Jesse's death would be if we don't learn anything." So let's think a little here - what have we learned over 8 years Dr Wilson?

Sources

3 years ago today: WHO is wagging WHO

On 3 November 2004 the World Health Organization was accused of hiding a report on food advertising "after pressure from the food industry". Yet more irrelevant paperwork perhaps, but is hiding things a proper part of the remit of the WHO.

A censor is a man who knows more than he thinks you ought to.
Granville Hicks (1901-1982)

Source: "WHO buried report to please food industry" The Guardian, Nov 3 2004

2 years ago today: USA is the sickest

On 3 November 2005 a report published in Health Affairs (Schoen C et al. Health Affairs 2005) showed that the USA lagged far behind other countries in several indicators of healthcare despite far greater expenditure. The US doesn't rank at all on mortality statistics either (nor for that matter does the UK). Other studies show that even the wealthiest in the US are worse off. Technology is not necessarily the same as good science.

2 years ago today: Ethics for sale

On 3 November 2005 Bloomberg News reported on commercial (for profit) IRBs (ethics committees) and their rubber stamping of ethical approval of clinical studies for industry. I will highlight just one quotation:

Angela Bowen, who runs Western IRB and founded this ethics company, the largest commercial IRB in the US, had overseen clinical trials "for which doctors were criminally charged and jailed for lying to the FDA and endangering the lives of trial participants." But no action was taken against Western IRB. Angela Bowen told Bloomberg reporters that she "didn't see human safety issues in those trials."

So, lies in clinical research are apparently not a safety issue according to the owner of an ethics board?? Neither is hiding of unwanted results that are derived from the risk undertaken by human research participants.

In 2000, Angela Bowen reported that her company was receiving 1400 protocols per year, and charged about $550 per protocol. Business is going "straight up" she said. In April 2007 private equity firm Boston Ventures bought a majority stake in Western IRB for an undisclosed amount.

How did we reach this point?

See also: Slate, Ethics for Sale, by Carl Elliott and Trudo Lemmens and Annals of Internal Medicine (2000) 132 (6) 513-6

2 years ago today: Guidant sued for misrepresenting cardiac device

On 3 November 2005 New York Attorney General Eliot Spitzer sued Guidant Corporation (now Boston Scientific) for alleged fraud in connection with its sales of implantable cardiac defibrillators. Guidant had admitted that it failed to disclose information about defects in the device to doctors and patients. The device is expensive ($25,000). Doctors and patients might have chosen not to implant them had they realized that the benefit and risk were different from those conveyed.

The product was a faulty product, not because it sometimes failed, but because the combination package of product+science was not based on truthful conveying of that science. A later review concluded that (NYT 21/3/2006) Guidant had indeed been guilty of such misrepresentation.

In January 2006 "Guidant agreed to be acquired by Boston Scientific for $27 billion. Executives of Boston Scientific said they were considering changing the name of Guidant's heart device as part of a plan to rebuild physician confidence in its products (NYT)". Hmmmmm.

Perhaps confidence results from honest and transparent science - not linguistic manipulation. Did anyone go to prison here - after all patients likely died?

Parexel bonus

1 years ago today: Reward for bad science a £1 million bonus (TGN1412)

On 3 November 2006 Lawyers on behalf of six men who almost died in a medical trials criticised the US research company for awarding its boss a bonus of £920,000. The boss is Parexel chief executive Josef von Rickenbach. The trial was the TGN1412 study.

This disaster was caused in part by non-application of brainpower by the UK drug regulator (the MHRA). The MHRA then exonerated themselves (of something). See also the Hoofnagle trial discussed in the 23 October and 29 October memory holes. Learning = zero.

Source: BBC, Parexel chief gets a million £ bonus, 3 Nov 2006

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