Monday, October 08, 2007

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

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.

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Anonymous said...

Regarding Breckenridge:

In the BBC Panorama broadcast programme Breckenridge stated:

"There is very good clinical trial evidence that these drugs do not cause suicide, they do not cause suicidal thoughts in adults". This claim appears fully consistent with other statements Breckenridge made when interviewed.

He was asked:

"Why should the public now trust you when you say the benefits outweigh the risks in adults?" He replied: "Because of overwhelming evidence that it does … we have looked at over 300 studies of Seroxat in adults". Later in the same interview, he emphasised the same point: "There are in over 300 studies which have been analysed and studies using epidemiological databases the drugs do not cause suicide, they do not cause suicidal thoughts."

The question is, where did Breckenridge get his information which was so stunningly wrong, and why does a head of an agency that is supposed to protect the public stray so far away from the science. Has Breckenrige commented on the fakery in study 329 involving his previous employer GSK?

Anonymous said...

This is a great idea to show these old events.