Memory Hole (8 October): Illusions of due diligence

The Scientific Misconduct Blog Memory Hole: Events of October the 8th

This quotation from the movie Syriana is appropriate to many of these events:
"We're looking for the illusion of due diligence, Mr. Pope. Two criminal acts successfully prosecuted -- it gives us that illusion."

60 years ago today: Attempt to hide secret human radiation experiments

On 8 October 1947, J.C.Franklin, operations manager of Oak Ridge, wrote to the general manager of the US Atomic Energy Commission: "There are a large number of papers which do not violate security but do cause considerable concern to the Atomic Energy Commission insurance branch, and may well compromise the public prestige and best interests of the commission". He added that such documents "are definitely prejudicial to the best interests of the Government" and ordered that "any such documents be edited or kept secret".

He was writing about the need to keep secret many research experiments involving radiation in humans. These had been carried out without consent or public knowledge.

Source: "Inquiry Links Test Secrecy To A Cover-up," New York Times, 15 December 1994

8 years ago today: Further adventures of Professor Martin Keller

On 8 October 1999 it was reported that Professor Martin Keller of Brown University had received "hundreds of thousands of dollars from drug companies" while he was receiving federal funds to test new drugs, and then provided favorable reports on those drugs without notifying the payments. Keller was paid more than half a million dollars in consulting fees in 1998, most of it from pharmaceutical companies whose drugs he touted.

Scientists seeking US funds are required to disclose to their research institutions any "significant financial interests" that could be affected by the proposed study. Then it's up to the institutions to assess the financial interests. If the institutions find a conflict, they must report it to the US funding agency and protect the research from bias. According to the newspaper report, Brown University appeared unconcerned about the regulations or the conflict of interest. The American Psychiatric Association announced that they were "investigating". For Keller's later involvement in shonky research see here or here or read about his depressing involvement in GSK's study 329 here.
Source: Boston Globe 8 October 1999, page B01

8 years ago today: London professor struck off for bullying and dishonesty

On 8 October 1999 A British professor of respiratory medicine with an international reputation in asthma research was struck off the medical register for bullying and threatening a junior colleague to cheat in a drug trial. See report of the case in the BMJ here and here.

Former Professor Robert Davies had threatened and abused a young doctor and tried to persuade him to break the trial code in order to fiddle the results. Davies threatened that Ramsay's career would be "finished" if he told anyone about the request to break the code blinding the study of the SmithKline Beecham drug Prankulast.

• The case involved tape recording of Professor Davies by Dr Ramsay. It is likely that without that recording the incident would have ended the career of Dr Ramsay instead of his senior "old-tie" boss. Davies told another colleague that he did not "know a microscope from a fucking hole in the ground". On the tape, Professor Davies is heard saying: "If I hear you speak to anybody you’re finished, OK." Davies said he had been "flabbergasted" to learn Ramsay had taped their conversations. He said when he had told Ramsay he would be finished if he spoke out, it was "in no way a threat to his career".
• The case included a strange comment from Joanna Glynn, counsel for the GMC. She said that "there was no body, other than the General Medical Council on which the pharmaceutical industry could rely to regulate doctors' activities in clinical trials". Kindly contact me for some education Ms Glynn or read this or this about the corruption of the GMC.
• The case is important in terms of definition of research misconduct. According to the current tortuous definition promulgated by the ORI and others, the actions of Professor Davies would not constitute research misconduct. Bullying with intent to disrupt the scientific record is not so defined.

Reference: BMJ 1999;319:938 London Professor struck off for bullying and dishonesty

5 years ago today: Pioglitazone data - when all 30 authors are wrong

On 8 October 2002 Nick Freemantle (University of Birmingham) reported in the BMJ (BMJ 2005;331:836-838) that clinical trial findings involving the drug Pioglitazone (the PROactive trial) had been misrepresented and that the conclusions were unsafe.

A response by a reader (Dr James Penston) was pertinent and bears on the responsibilities of authorship. His letter was entitled "When all thirty authors are wrong".

Penston writes: "Perhaps this was simply an innocent error. But it is hard to believe that none of the thirty authors – including 27 professors – were aware that it would be misleading to interpret the data as showing that pioglitazone reduced macrovascular events. Given that 28 of the 30 authors had financial links with the pharmaceutical industry and that the study was funded by Takeda and Eli Lilly, it would have been prudent to avoid at all cost the charge that this manipulation of data stemmed from a conflict of interest."

4 years ago today: Nigeria versus Pfizer

On 8 October 2003 the US Court of Appeals reinstates a Nigerian research case against Pfizer.

"The central events at issue in this lawsuit occurred in 1996, not long after epidemics of bacterial meningitis, measles and cholera broke out in Kano, Nigeria. Pfizer established a treatment center at the Infectious Disease Hospital in Kano to treat victims of the meningitis epidemic.

Plaintiffs allege that Pfizer, instead of using safe and effective bacterial meningitis treatments, used the epidemic as an opportunity to conduct biomedical research experiments on Nigerian children involving Pfizer's "new, untested and unproven" antibiotic, trovaflozacin mesylate, better known by its brand name, Trovan."

Plaintiffs claim that Pfizer failed to obtain informed consent, and that some children were deliberately given inadequate doses of ceftriaxone so that Trovan would look more effective by comparison. Several children died. The case is ongoing (see AHRP or here).

What is the chance that justice will be served under the circumstances?

Four years later it seems that Pfizer is going to try to keep the whole thing quiet through some form of payment of money or perhaps a large bribe.
Source: AHRP http://www.ahrp.org/infomail/03/10/14.php

3 years ago today: FDA officials attempt to soften a report by Dr David Graham about Vioxx

On 8 October 2004 it was revealed that FDA officials had attempted to soften the conclusions of a scientific report about the drug Vioxx produced by Dr David Graham. Senator Grassley was reported as saying "Instead of acting as a public watchdog, the Food and Drug Administration was busy challenging its own expert" “Dr. Graham described an environment where he was ostracized, subjected to veiled threats and intimidation".

Vioxx was later withdrawn. It is estimated that the use of this drug has resulted in at least 100,000 deaths worldwide.
Source: "FDA Officials Tried To Tone Down Report on Vioxx" Wall Street Journal, 8 October 2004

2 years ago today: MHRA leadership asserts its integrity, but with what evidence

On 8 October 2005 Professor Alasdair Breckenridge and Professor Kent Woods coauthored a strange paper in the BMJ (BMJ 2005;331:834-836) subtitled "How does an agency funded by user fees make impartial decisions about the safety of new and licensed drugs?". Breckenridge and Woods are important people. Breckenridge is the chairman of the UK drug regulator (the Medicines and Healthcare Products Regulatory Agency, MHRA) and Woods is the chief executive of the agency.

And the answer to the question is?

Some have asked these gentlemen about the ongoing "independent criminal investigation" of GlaxoSmithKline (see see 1463 days to nothing).

Breckenridge sat on GSK's scientific advisory committee for years before taking up his post at the MHRA (reference). Ian Hudson, who was the worldwide safety director of GlaxoSmithKline (GSK) until 2001, is now director of licensing at the MHRA (reference). As Charles Medawar has pointed out here or here there is a lot of explaining to do.

Earlier|Later|Main Page

Procter and Gamble goes dumpster diving

I tape recorded Procter and Gamble and other "researchers" involved in some problematical sponsored clinical research. That was an important thing to do. I have been waiting a while for an honest response. I have been waiting for permission to make available the hidden (and now revealed) raw data upon which P&G relied in their three scheduled Actonel ghostwritten publications. I have been waiting for a few other refused things (like the text of consent forms from patients upon whom I performed measurements).

Here is the correct analysis for one of the publications. Here is the correct analysis for another of the publications (Eastell et al., 2003). Here are the Data underlying all three publications (encrypted).

So far all involved have been a little evasive, giving artful answers to "questions" that had not in fact been asked. That seems to be to be a bad idea John Eisman.

While being politely patient, I found some most interesting old news reports about P&G's own spying tactics.

New York Times Page C7, September 7, 2001
P.& G. Said to Agree to Pay Unilever $10 Million in Spying Case
By JULIAN E. BARNES (NYT); Business/Financial Desk
DISPLAYING ABSTRACT - Procter & Gamble will pay Unilever about $10 million and agree to unusual third-party audit to settle dispute that arose after P&G acknowledged that it had taken documents from trash cans outside Chicago office of Unilever; Unilever had made demand to ensure that Procter & Gamble did not change its marketing or product development plans for its hair care business after reviewing about 80 pages of confidential Unilever plans

Procter & Gamble Admits to Spying on Unilever

In a disclosure that shines a light on the shady world of corporate espionage, FORTUNE magazine recently reported that Procter & Gamble, one of the nation's largest and most admired corporations, has "recently engaged in a corporate espionage program against competitors in its hair care business that even the company itself admits spun out of control."

P&G claims it did not break any laws, but a spokeswoman conceded that spying activities undertaken by a "corporate intelligence" company that was hired by P&G "violated our strict guidelines regarding our business policies."

DEFINITION: Corporate or industrial espionage is the practice of spying on business competitors to steal proprietary information, including product designs and marketing plans. While corporate espionage sometimes includes computer hacking, it is just as likely to involve non-technology-related practices, such as rummaging through a competitor's trash ("dumpster diving") or simply interviewing disgruntled employees.

P&G has confirmed that at least one competitive intelligence company it hired engaged in dumpster diving to find information on rival Unilever's hair-care business. The competitive intelligence operatives are also said to have lied to Unilever employees - claiming they were market analysts in a further effort to gather information.

Procter & Gamble vs. Unilever
In 2001, P&G undertook a corporate-espionage program by hiring a "consulting firm" to rummage through Unilever's trash and steal the secret formula for a new hair-care product. The two companies eventually reached a settlement; P&G agreed to pay Unilever $10 million. The firm hired to do the dirty work is headed by a former Green Beret and U.S. government intelligence operative who served in the Phoenix Program, a covert operation during the Vietnam War.

Remarkably this isn't the first time P&G has gotten caught in corporate espionage against Unilever. In 1943, a Procter & Gamble executive bribed an employee of Lever Brothers (as Unilever was then called) to steal prototype bars of a new soap Lever was developing. P&G used the stolen formula to rework its own Ivory Soap, which soon became one of the most familiar brand names in America. P&G ended up having to pay Lever $5 million for patent infringement.

One year later, P&G Pharmaceuticals signed a research agreement.

See also
The Ethics of Competitive Intelligence

The moral:
Before you criticize people, you should walk a mile in their shoes.
That way, when you criticize them, you've got a mile-long head start.
And you have their shoes.
The Lion (in The Wizard of Oz)

(Thank you John - a medical publication professional - for the tip)

Earlier|Later|Main Page

On decorum in medicine

A quotation by the Irish priest Steve Gilhooley set me thinking about medicine, and the Alice in Wonderland world of medical leadership in particular. 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'."

For the background to this sermon and its consequences read here. 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 desire to maintain decorum and status in medicine seems also to overwhelm all standards of decency. Our profession is inclined to fixate on the irrelevant while ignoring some very bad things. Does civility matter? 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.

The desire to maintain civility, decorum and status instead of ethics explains for example why we as doctors feel quite comfortable with a drug "regulatory" agency in the UK (the MHRA) that simultaneously

1. conducts a high profile campaign against the nutritionist "Poo lady" Dr Gillian McKeith for selling unproven herbal sex aids [Link]
2. ignores all of the very worrying revelations about the drugs we ourselves prescribe

The need to maintain decorum means that it is hard to deal with the difficult and important problems or to deal honestly with the failures of "important" people. It is a lot easier to think about the "Poo lady" than to explore honestly how we were misled by both companies and regulators over Zyprexa, SSRI's, Vioxx and many other drugs (Link,Link,Link, Link,Link).

The emphasis on decorum and status explains why it is considered by some as "impolite" that I accrued extensive tape recordings (sample here or here) of colleagues and pharmaceutical company executives involved in an unsavory scientific "collaboration" that threatened to damage the science I love and to distort our understanding of a drug [Link]. Does civility matter under such circumstances?

The emphasis on decorum and status explains why the BBC had to conduct it's own investigation [Link] of the worrying events surrounding clinical trials of the drug Seroxat and the company GlaxoSmithKline (GSK) as the medicines regulator (the MHRA) simply dragged it's feet for years conducting an internal investigation of its own collusion with the deception. And to cap it all, key figures within the MHRA are previous employees of GSK.

The need to maintain decorum means that even though it seems very likely that both patients and doctors have been misled, that prescribing decisions have been made on the basis of faulty or hidden data, and that patients have suffered or have died as a result of regulatory malfunction, we doctors remain silent (see extensive discussion here and here).

The need for decorum explains why the General Medical Council (GMC) muttered into their beards when presented with evidence of alleged research misconduct involving Dr David Jefferys. Jefferey's was high in the pecking order, and in a position where the need for integrity was part of the job description. He was former director of the Medicines Control Agency and chief executive of the former Medical Devices Agency (both organisations merged to become the Medicines and Healthcare Products Regulatory Agency, the MHRA). This week the General Medical Council also refused to scrutinise in any way the activities of another very important doctor, Dr. Alastair Benbow of GlaxoSmithKline. This despite obvious public concern and a BBC investigation. The GMC refused on the basis that there has not been a criminal or regulatory investigation of GSK (taking the obfuscation full circle). I have no idea how much Dr Benbow knew and when he knew it, but a proper, open and transparent public investigation is urgently required. The GMC cannot claim to be concerned about the scientific integrity of doctors when it behaves in this manner. Indeed the GMC appears to care nothing about the integrity of the research upon which our patients rely.

At the other end of the pecking scale, the GMC has felt quite happy to persecute whistleblowers such as Dr Rita Pal while hiding reports relating to the very serious problems she raised. The recent suspension of yet another Asian doctor for shouting abuse at a Pfizer drug representative was also easy for the GMC, and was presumably felt to have had less impact on the reputation of anyone who mattered [Link].

Earlier|Later|Main Page

Procter research shenanigans part 1: The origins of misconduct

It's all down to money


Alternative MP3 player and download here.

Conversation Eastell and Blumsohn 10 September 2003

Blumsohn: So far as the plenary poster if we go through all the things I said I would be comfortable with that.
Eastell: Mmm
Blumsohn: ... and for the other poster I am comfortable with the poster but I have still never seen the data... which to give an oral presentation at the ACR meeting I would find a difficult thing to do.
Eastell: The only thing that we have to watch all the time is our relationship with P&G. Because we are ... because we have the big Sheffield Centre Grant [from P&G] which is a good source of income, we have got to really watch it. So.... the reason why I worry is the network within P&G is like lightening. So if Ian is unhappy it goes to Arkadi, it goes from Arkadi to Nora and before we know it, there is an issue, there is a problem... and it has to be addressed and so forth. and so I was getting worried that the whole thing might be activated and that would affect our relationship.

Earlier|Later|Main Page