Memory Hole (21 October): What else happened?

Scientific Misconduct Blog Memory Hole: Events of October the 21st

48 years ago today: Operation Paperclip and government expediency

On 21 October 1959 President Eisenhower signed an order transferring Wernher von Braun and other ex-Nazi German scientists from the US Army to NASA. Operation Paperclip was the secret project to extract Nazi German scientists out of prosecution for warcrimes and into the US military. von Braun was key in the production of 6000 V-2 rockets 500 of which hit London. 20,000 slaves died during V-2 production - "you could see piles of prisoners every day who had not survived the workload" - during his frequent attendance "Prof. Wernher von Braun never once protested against this cruelty and brutality" [ref]. This entry is here because it relates to the wartime operation of scientists and the role of government in a democracy.
Source: Hunt,L "U.S. Coverup of Nazi Scientists" Bulletin of the Atomic Scientists. April, 1985

9 years ago today: Anonymous letters feature in a key scandal

On 21 October 1998 a senior academic in Toronto wrote this anonymous letter. It was one of several. Who was he and what did this have to do with a key academic freedom scandal?

Read on here: Anonymous threats in Toronto

2 years ago today: The Karasik conspiracy

On 21 October 2005 the Pharmaceutical Research and Manufacturers of America (PhRMA), the discredited American Pharmaceutical trade lobby group, admitted that they paid a publisher to have a thriller written about Croatian terrorists using Canadian pharmacy websites to slaughter millions of Americans. Jayson Blair working for Phoenix Books, was tasked with editing this book, called "The Karasik Conspiracy."

The goal was supposedly "to scare Americans into opposing any amendment to existing legislation" that formally bans the import of low-cost prescriptions from Canada.

PHRMA also made several editorial suggestions. "They said they wanted it somewhat dumbed down for women, with a lot more fluff in it, and more about the wife of the head Croatian terrorist, who is a former Miss Mexico," one of the authors told the newspaper. Apparently, women are among the most loyal buyers of Canadian drugs.

When the project fell through, PhRMA apparently offered $100,000 to the co-authors and publisher in a vain effort to shut it down. The authors went ahead anyway, writing a book of the same name about a drug company that funds a terrorist attack.

And PhRMA expect to get taken seriously. They also feature as apologists by proxy in the little saga of a bone drug, in which PhRMA was cited as stating that according to their guidelines scientific authors should never never ever have access to the data about which they are writing. Well that's OK then.

See:

• "U.S. drug group paid to support novel idea" Globe and Mail Oct 21, 2005
• The Karasik Conspiracy : http://www.thekarasikconspiracy.com/
• Washington post: Stranger Than Fiction?
• Slate: Truth Is Stranger Than Phiction

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Memory Hole (21 October): Vioxx and a quacking duck

8 years ago today: A story of ducks and a single death in a Vioxx clinical trial

On 21 October 1999 a 73-year-old woman died. That death and our response to it tells volumes about the health of our profession.

In medicine we sell our wares under the banner of science. The technique of science (the "scientific method") consists of a number of steps. For a double blind randomized clinical drug trial those steps might be:

1. State a meaningful hypothesis
2. Design a study and statistical methods to test it
3. Do the study in a double blind randomized way
4. Unblind the study AFTER deciding what happened to each patient and locking the database
5. Study authors analyze the results
6. Share the results with everyone

That is the usual way of science. This method is not used by the practitioners of any system of quackery.

So that takes us to the Merck Advantage trial of Vioxx, and a single 73-year-old female participant in that trial who died on this day - Oct. 21, 1999. She died a few minutes after calling her son to tell him she felt short of breath.

The Advantage trial was a very short (12-week) clinical trial in 5,500 patients. If you want to avoid showing up long term side effects, you keep your clinical trials short and scientifically irrelevant (that's about the meaningful hypothesis part).

Now eight people taking Vioxx suffered heart attacks or sudden cardiac death in the Advantage trial, compared with just one taking naproxen, according to data released by the F.D.A. in 2005. The difference was statistically significant, but Merck never showed the data that way.

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

Dr. Lisse said that while he was listed as the paper's first author, Merck actually wrote the report (that's the authoring bit). "Merck designed the trial, paid for the trial, ran the trial," Dr. Lisse said. "Merck came to me after the study was completed and said, 'We want your help to work on the paper.' The initial paper was written at Merck, and then it was sent to me for editing."

Now, the other thing in usual science is not to allow company technocrats with a vested interest to decide themselves what happened to individual 73 year old women after the study is unblinded.

Neither patients nor their doctors were aware whether patients were receiving Vioxx or naproxen. Results from the trials were also supposed to be blinded when they were examined, so that Merck researchers could not bias the results. After examining the case, Dr. Eliav Barr, a Merck employee judged that the woman had probably died of a heart attack."

"Common things being common, the clinical scenario is likely to be MI (heart attack)" Dr. Barr wrote in an E-mail message in November 2000 to Dr. Reicin, the Merck clinical research executive.

Dr. Reicin quickly shot back: "I think this should be called an unknown cause of death." A few hours later, she wrote, "I would prefer unknown cause of death so we don't raise concerns."

"A fatal event not being treated as objectively as possible surprises me," said Dr. Myerburg, a prominent cardiologist. "It looks like they're playing around with this death."

In November 2001, an F.D.A. reviewer who had examined all the company's data concluded in a report to other agency officials that Merck had misclassified the death. But the F.D.A. never told anyone either.

Dr. Lisse, the study "author" said he had never heard of the case of the woman who died, until told of it by a reporter.

So can we really believe anything at all, and how to distinguish this from the worst type of quackery? As the old saying goes, ...If it looks like a duck, and it quacks like a duck...it's a bloody duck.

What is even more amazing is that the leadership of medicine says nothing -- nothing at all. Medical students learn none of this in any of their pseudo-ethics training.

Sources:

1. Correspondence in the Annals of Internal Medicine on the problem: Deeply disturbing evidence of medicine run amok
2. New York Times, April 24, 2005: "Evidence in Vioxx Suits Shows Intervention by Merck Officials"

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Memory Hole (20 October): The Protectors

Scientific Misconduct Blog Memory Hole: Events of October the 20th

Quotes of the day

This and no other is the root from which a tyrant springs; when he first appears he is a protector.
Plato circa 400 B.C.

A good deal of tyranny goes by the name of protection.
Louise Erdrich

60 years ago today: Academic Freedom is un-American

On 20 October 1947 the House Un-American Activities Committee opened hearings into supposed communist influence in the motion picture industry.

22 years ago today: Secret C.I.A funding at Harvard

On 20 October 1985 it was reported that Nadav Safran, a Harvard Professor of Near Eastern Studies had been receiving confidential research funding from the Central Intelligence Agency ("Harvard Widens Inquiry in C.I.A. Aid to Professor," New York Times 20 Oct 1985). Part of the agreement was that he should submit his manuscripts to the CIA for prior approval. Several scholars had earlier withdrawn from a conference on Islamic fundamentalism at Harvard after learning that the CIA was one of its sponsors. Safran was later forced by his colleagues to resign his Harvard position. See some discussion in the Harvard Crimson of 1986.

6 years ago today: UK Government accused of coverup over sheep research

On 20 October 2001 the UK Labour Government was accused of trying to hide details of the disastrous scientific investigation into BSE in sheep.

2 years ago today: Pargluva and regulatory failure

On 20 October 2005 an important article was published JAMA (Brophy JM. Selling safety - lessons from muraglitazar. JAMA 2005; 294) indicating various techniques used to provide a deceptive impression of the drug Pargluva (muraglitazar) to a puppet FDA panel. For the methods used to mislead see the summary at Health Care Renewal.

The FDA panel reviewing Muraglitazar had known of concerns, but had conflicts of interest. They backed the drug regardless of the absence of any evidence of meaningful efficacy (NYT). The summary of the FDA meeting (available on the internet archive here) indicates concerns about increased heart failure and cardiac death with Pargluva (short term cardiac death rate 0.3% with Pagluva 0% with Actos, CCF 0.75% for Pargluva vs 0% for Actos). Five clinical trials had been notified to the FDA (the "clinical trial register") but were not available in published form.

The parallel scientific report in JAMA concluded "muraglitazar should not be used or approved to treat patients with diabetes until an appropriate dedicated trial to assess cardiovascular outcomes is performed." - which is exactly the conclusion an honest FDA panel should have reached.

On 18 March 2006 Bristol-Myers Squibb discontinued the development of muraglitazar.

2 years ago today: Nature study on distortion of clinical guidelines

On 20 October 2005 the journal Nature reported on their investigation of "independent" clinical guidelines ("Cash interests taint drug advice" Vol 437/ 20 October 2005). The results of the survey showed that "drug companies are distorting decisions about how their products are being prescribed". Surprise.

"Nature found that more than one-third of authors declared financial links to relevant drug companies, with around 70% of panels being affected. In one case, every member of the panel had been paid by the company responsible for the drug that was ultimately recommended." Nature studied over 200 guidelines deposited with the US National Guideline Clearinghouse. Only 90 contained details about conflicts of interest. Of those, just 31 were free of industry influence.

In one example uncovered by Nature, guidelines for the treatment of anaemia in HIV positive patients were written by a working group selected by Paul Volberding at UCSF. Volberding convened the group at the request of Ortho Biotech. Ortho Biotech funded the meetings and all six members were paid by the company for lecturing or consultancy. The group's guidelines (P.Volberding et al. Clin. Infect. Dis. 38, 1454-1463; 2004) recommend use of epoetin alpha, a drug marketed by Ortho Biotech.

Patients die as a result of schlock science - does anyone care?

2 years ago today: David Healy, the BMJ and Academic Stalking

On 20 October 2005 Professor David Healy gave a landmark talk at Columbia University. Amongst other things he detailed the role of lawyers at the British Medical Journal in the peer review process: "our best journals refuse to take articles on the basis of sheer terror about what pharmaceutical companies might do to them rather than on the basis of any concerns about the scientific merits". The lecture was scheduled as a debate between Healy and James Coyne (University of Pennsylvania), but Coyne pulled out. Coyne had an interesting role in the stifling of academic debate (see Academic Stalking) as did academics at Oxford University. Sickening reading.

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Memory Hole (19 October): Harvard paper in "error"

12 years ago today: Harvard paper in "error"

On 19 October 1995 the journal Nature reported on the case of three Harvard Medical School researchers:

R. Alan B. Ezekowitz (now senior vice president at Merck),
John B. Mulliken and
Judah Folkman.

This is an instructive case and I have therefore provided it with an exclusive Memory Hole.

One wonders how scientific scientific misconduct or fraud might be defined given this piece. Below is the text reproduced from the database of Professor A.C. Higgins (highlighting added). Perhaps you can avoid anything simply by being important (see BMJ, 2007;335:582-583). This is Ouija board science.

The linguistics of the news report are Familiar to me relating to the first part of a publication trilogy involving myself.

"Inquiry at Harvard prompts research paper corrections,"
Dalton, Rex. Nature 377 (19 October 1995), p. 569.

Three prominent physicians from Harvard Medical School working at the Children's Hospital in Boston have been forced to publish an extensive correction in connection with federally funded research on a treatment for rare, life-threatening birthmarks in infants. The correction has been published in the New England Journal of Medicine (NEJM) after a lengthy investigation by Harvard into the conduct of the physicians, R. Alan B. Ezekowitz, John B. Mulliken and Judah Folkman. The latter is internationally renowned for his discoveries on angiogenesis, the process by which blood vessels grow.

It follows a briefer correction, published unilaterally last year by the three when the investigation was still under way, which included corrected data about some of the patients involved in the study, but without any accompanying comment - or even identification of the names of the authors.

The investigation concerned an article published in the NEJM (326, 1456 63; 1992) on the effectiveness of interferon alfa-2a in reducing large hemangiomas, growths that can occasionally block an infant's airway, affect its vision or compromise a vital organ.

The article, based on observations of 20 cases, claimed that the therapy had had a substantial effect. But Harvard officials say that after it was published, other physicians who had referred the children to the team complained about various inaccuracies.

The committee found that there was no misconduct or fraud, says Nathan. But it did find many errors needing correction. These included the fact that some hemangiomas were reported to have regressed more than they did; that the lesions were not measured, as the article suggested; that some patients were not treated for the period reported; that prior therapies used on some patients were not listed correctly; and that monthly blood tests were not taken on all patients as reported, with the result that no conclusion could be reached on drug toxicity.

The results of Harvard's investigation were sent to the National Institutes of Health (NIH)'s Office of Research Integrity (ORI), which, according to Nathan, accepted the university's findings. But it appears that neither the National Cancer Institute (NCI), nor the National Center for Research Resources -the NIH agencies whose grants were cited as funding the research- was notified of the Harvard investigation or of any corrective actions. Collette Freeman, the NCI grant officer, described the situation as "extraordinary" and "bizarre" when told of the correction.

Harvard officials refuse to comment on the case, or to say whether any sanctions were issued against the researchers. Nor were any of the three physicians prepared to comment. But in their correction, published on 31 August, they wrote: "We are embarrassed by our errors and regret them. We apologize to the readers for any misunderstanding and thank our colleagues for their assistance in correcting our report." Nathan called the interferon research "a very important paper" by "distinguished investigators." But, he claims, the researchers "got very busy" and "just slapped this paper together." He accepts that almost all the errors in the eight-page article tend to improve the apparent success of the therapy. "That is how the original complaint was made," says Nathan. "It is curious that it turned out that way."

The lengthy investigation appears to have been marked by contention, defiance by the researchers and anger. Nathan says that when the Harvard review started, the three "became very irritable," submitting material for correction to the journal against his advice. "The first correction wasn't certified by Harvard," said Nathan. "I felt it was wiser to be patient, collect all the errors and deal with them in one fell swoop," he says, adding that the medical school feels strongly that corrections have to be certified by the institution.

Jerome P. Kassirer, who took over as editor-in-chief at the NEJM after the first correction was published, says that the Harvard researchers submitted "material that was very confusing" for this correction. Earlier this year, he says, the three physicians submitted further material, approved by Harvard, but this was little easier to interpret. "The editors had a great deal of trouble figuring out what they were driving at."

Despite the errors, Nathan said the conclusions of the study remain valid, and that interferon remains the preferred therapy for such hemangioma cases. But some physicians feel a random, prospective study is still required to back up this conclusion, as the lesions are known to regress on their own as children age.

"I have to express reservations about any non-randomized study, especially one in which it now appears that the data was brushed up," says Ajay J. Vora, a paediatric haematologist at Children's Hospital in Sheffield, in the United Kingdom, who originally questioned the interferon study in a letter to the NEJM in October 1992.

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Memory Hole (19 October): A collection of bloody shreds

Scientific Misconduct Blog Memory Hole: Events of October the 19th

Quote of the day

O Lord, our God, help us to tear their soldiers to bloody shreds with our shells; help us to cover their smiling fields with the pale forms of their patriot dead; help us to drown the thunder of the guns with the shrieks of their wounded, writhing in pain; help us to lay waste their humble homes with a hurricane of fire; help us to wring the hearts of their unoffending widows with unavailing grief; help us to turn them out roofless with their little children to wander unfriended the wastes of their desolated land in rags and hunger and thirst, sport of the sun-flames of summer and the icy winds of winter, broken in spirit, worn with travail, imploring Thee for the refuge of the grave and denied it - for our sakes who adore Thee, Lord, blast their hopes, blight their lives, protract their bitter pilgrimage, make heavy their steps, water their way with tears, stain the white snow with the blood of their wounded feet! We ask it, in the spirit of love, of Him Who is the source of love, and Who is the ever-faithful refuge and friend of all that are sore beset and seek His aid with humble and contrite hearts. Amen.
Mark Twain

What else happened today?

34 years ago on 19 October 1973 President Richard Nixon rejects an Appeals Court demand to turn over the Watergate tapes. The concept of tape recording in cases of scientific misconduct is of interest, hence this entry. Fortunately US Presidents now have less power to behave illegally.

22 years ago on 19 October 1984 the Journal Science reported the outcome of the NIMH "study" suggesting that 20% of Americans are mentally ill ("some recognizable disorder"). Taurus excreta cerebrum vincit.

7 years ago on 19 October 2000 the journal Nature reported that historians found greater ties between German race scientists and the Hitler regime than previously thought. Scientists exploited scientific opportunities "beyond all morally acceptable limits for the benefit of their own research." They set the criteria for the castration of criminals, the forcible sterilization of "inferior" women, particularly those with "psychological" problems, and "an objective scientific background" for racism. The report also discussed the likely role of Nobel laureate Adolf Butenandt (later professor at the University of Munich) in the analysis of samples from Auschwitz experiments.

7 years ago on 19 October 2000 a panel of scientists recommended that the FDA ban the drug ingredient phenylpropanolamine (PPA), a common ingredient in decongestants (see cover-up and delay discussed in 13 October Memory Hole).

7 years ago on 19 October 200 a spate of people having seizures while taking the new anti-smoking drug Zyban (Bupropion) raised concern about its safety. Critics also claim "cold turkey" is twice as effective as Zyban in the real world, that clinical trials were fatally flawed because the majority of patients were able to guess their randomization correctly (drug or placebo), and both studies and followup were too short. However, patients were provided with extremely detailed information about the risk of convulsions in the Bupropion leaflet. That allows smokers to make proper informed decisions, and is far better than the meaningless non-quantitative risk information usually supplied. I personally would not be inclined to take the drug in a million years. Patients were not misled (presuming the information about risk and efficacy is honest) and I wish we would see more of this. Risks were stated as follows:

Bupropion is associated with seizures in approximately 0.4% (4/1000) of patients treated at doses up to 450 mg/day. The estimate seizure incidence for bupropion increases almost tenfold between 450 and 600 mg/day, which is twice the usually required daily dose (300 mg) and one and one-third the maximum recommended daily dose (450 mg). Given the wide variability among individuals and their capacity to metabolize and eliminate drugs, this disproportionate increase in seizure incidence with dose incrementation calls for caution in dosing. During the initial development, 25 among approximately 2400 patients treated with bupropion experienced seizures. At the time of seizure, seven patients were receiving daily doses of 450 mg or below for an incidence of 0.33% (3/1000) within the recommended dose range. Twelve patients experienced seizures at 600 mg per day (2.3% incidence); six additional patients has seizures at daily doses between 600 and 900 mg (2.8% incidence). A separate, prospective study was conducted to determine the incidence of seizure during an 8-week treatment exposure in approximately 3200 additional patients who received daily doses of up to 450 mg. Patients were permitted to continue treatment beyond 8 weeks if clinically indicated. Eight seizures occurred during the initial 8-week treatment period and five seizures were reported in patients continuing treatment beyond 8 weeks, resulting in a total seizure incidence of 0.4%.

5 years ago on 19 October 2002 presidents of the US National Academies accused the Bush administration of going too far in preventing publication of some research on the basis of national security.

2 years ago on 19 October 2005 the WSJ discussed Bunny Greenhouse, a top procurement official in the U.S. Army fired after questioning contracts awarded to Halliburton before the Iraq war. "If prison inmates don't like the warden who keeps them from breaking out," Greenhouse says, "do you replace the warden?" A heady mix of race, gender and war money.

2 years ago on 19 October 2006 President Bush proposed a $7.1 billion plan to protect the nation against a potential bird-flu pandemic (someone remind the man why there was bedlam in New Orleans).

1 year ago on 19 October 2006 a suppressed publication about cancer epidemiology in IBM semiconductor workers was finally published following extensive legal and editorial bullying (Clapp et al., Environ Health. 2006;5:30). See IBM's approach to scientific integrity.

Sources:
Richard M Nixon
"NIMH Finds One in Five Have Disorders," Science 226 (19 Oct 1984) p. 324
"Deep Roots of Nazi Science Revealed" Nature 407 (19 Oct 2000) p. 823
"Researchers Say Science Is Hurt By Secrecy Policy Set Up By the White House," NY Times,19 Oct 02
The Independent (London), Oct 19, 2000 "Spate of seizures among users of anti-smoking wonder drug"
"Whistle-Blower or Troublemaker, Bunny Greenhouse Isn't Backing Down", Wash. Post,Oct 19 05
Elsevier , IBM, Academic freedom and public health

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Memory Hole (18 October): Like deja vu all over again

6 years ago today: Jan Hendrik Schoen paper published - a scientific fraud

In the 18 October 2001 issue of Nature, Jan Hendrik Schoen of Bell Laboratories published an astonishing paper describing a transistor in which a single molecule acted as a "switch".

Schoen was named as one of science's top young innovators. During 2001, Schoen churned out a new paper on average every 8 days. However science star soon turned to Icarus.

In April 2002 other researchers noticed a strange similarity between a figure in the Nature paper and another figure Science had published on a different device. Other apparent problems were soon found, and then many more. Ultimately 24 critical problems involving 25 papers and 20 co-authors were examined. In at least 16 of these cases Schoen had falsified or fabricated data. Crucially he had also deleted his data files, making it impossible to check.

All nice and tidy and easy to define as misconduct within the restrictive definitions.

Schoen said, "I have to admit that I made various mistakes in my scientific work, which I deeply regret,... However, I would like to state that all of the scientific publications that I prepared were based on experimental observations". Schoen apologized for his "mistakes". The words are familiar to me.

But it gets more difficult when the culpability of coauthors is raised. Although it was determined that there was "no evidence of misconduct by any of Schoen's co-authors" it is not clear that any of them bothered to check anything. That seems to be culpable negligence.

The coauthors were "certainly happy to bask in the glow when things looked wonderful. But you can't have it both ways and not accept some level of the burden of responsibility".

Source: "Bell Labs Fires Star Physicist Found Guilty of Forging Data" Science 298, 4 Oct 2002, 30-31

45 years ago today: Nobel Prize to Watson, Crick and Wilkins

On 18 October 1962 Dr. James Watson Dr. Francis Crick and Dr. Maurice Wilkins were awarded the Nobel Prize for their determination of the molecular structure of DNA. Watson and Crick had received crucial unpublished data from Rosalind Franklin's lab, perhaps without her knowledge.

22 years ago today: Dispute Over Access to Reye's Study Data

On 18 October 1985 Science reported on a dispute over raw data. Many epidemiological studies have shown that aspirin intake in children is a trigger for Reye's syndrome. Following advice about aspirin use in children, the incidence of Reye's syndrome decreased about 10 fold from a high of about 1/100,000 children per year (with mortality around 50%).

Plough (maker of St. Joseph's aspirin) were sued by a family. In their response to the case, Plough demanded that the US government release to it the raw data it has on aspirin. This was refused.

I think the government was entirely wrong to have refused (within the limits of patient confidentiality). Science which cannot be scrutinized is not science at all.

Schering-Plough is of course the company that writes £10,000 checks to doctors in exchange for prescribing their drugs. They also manufacture:

• Remicade (infliximab)
• Intron A & PEG-Intron(Interferon Alfa-2b)
• Levitra (vardenafil)
• Zetia (ezetimibe)
• Vytorin (ezetimibe/simvastatin)

Schering-Plough sell these products under the banner of science. They will of course supply raw data to scientists, prescribers and patients who wish to check the scientific and ethical basis of their prescribing. Such is the way of proper science and the meaning of that banner.

Source: "Dispute Over Access to Reye's Study Data," Science 230 (18 October 1985), pp. 297 298.

8 years ago today: Probe into deaths of 25 experimental subjects at Porton Down

On 18 October 1999 the BBC reported that police were investigating the deaths of 25 ex-servicemen in the UK who were used as guinea pigs in germ warfare experiments at Porton Down (the defence research establishment in Wiltshire). The investigation was sparked by a probe into the death of airman Ronald Maddison in 1953.

Maddison, then 20, died after 200mg of deadly nerve agent Sarin B was dripped onto a piece of uniform stuck to his arm.

"The investigation is hugely sensitive because it could lead to the prosecution of former Ministry of Defence staff"

Solicitor for relatives of the Porton Down victims, said the "guinea pigs" were tricked into believing they were taking part in research into the "common cold". Gordon Bell, 61, says he was paid two shillings. "In one test we had to stand in front of a stream of gas which I could not stand for more than a minute," he said. "It was a dirty trick, plain and simple."

Source: BBC

6 years ago today: UK Government science project confuses cows and sheep

On 18 October 2001 the UK government announced that a critical four-year government study looking at infection of sheep with BSE (mad cow disease) was dropped. The government claimed the scientist involved had been testing cow brains thinking they were sheep brains.

They admitted that testing on the wrong tissue had been carried out for the past five years. The supposed discovery of the mixup took place just two days before the research was due to be presented to the Spongiform Encephalopathy Advisory Committee. A positive result without the supposed mix-up would have led to millions of UK sheep being culled.

The UK's Rural Affairs Secretary, Margaret Beckett was accused of trying to hide news of the supposed confusion.

5 years ago today: Throwing science down the toilet - Judge Henry Kennedy and pediatric rule for regulators

On 18 October 2002 a federal District Court struck down the Food and Drug Administration's Pediatric Rule, saying that the agency did not have the authority to require drug makers to test some of their products for childhood use.

Several groups, including the "Competitive Enterprise Institute" sued the FDA to overturn the Pediatric Rule, arguing that it improperly expanded the agency's authority because it opened the door to greater oversight of "off label" uses of drugs.

Amazing stuff. Perhaps all drugs should be tested on 80 year old Mongolian men so that "off label" (read non scientific) use could be more widespread. The level of evidence for consumer products will then be similar to any other type of quack medicine, but mis-sold under the banner of "science".

Judge Henry H. Kennedy Jr., you have behaved like an impetiginous inquinate orosscrolest and have approached a problem of science with mental discalceation.

Sources: Washington Post, "Court Strikes Down FDA Rule", Oct 18 2002; Vera Sharav, Children in Clinical Research: A Conflict of Moral Values, American Journal of Bioethics 3(1) 2003

2 years ago today: FDA suggests that psychotropic manufacturers test their drugs

On 18 October 2005 the Wall Street Journal reports that the FDA has sent out feelers to drug manufacturers to provide "longer-term efficacy data" for psychotropic drugs.

So what happened to the feelers?

Are patients are told that most clinical trials of psychotropic drugs last only a few weeks, and that a majority have shown that the drugs work no better than placebo, and have non-efficacy to rival homeopathic medicines (which in turn work as well as placebo)?

High science.

Source: Wall Street Journal, "FDA May Require Longer Studies Before Clearing Psychiatric Drugs" Oct 18, 2005

2 years ago today: Serono plead guilty to scam pseudoscience

On 18 October 2005 the company's Serono Labs agreed to plead guilty to conspiracy to market the drug Serostim by "supplying doctors with scam "diagnostic software" that was about as science-based as colonic irrigation. Serostim is an injectable form of growth hormone marketed for AIDS wasting.

Basically Serono created some crappy software that sought to "redefine AIDS wasting". This computerized medical test ostensibly determined "body cell mass." The results signaled that patients had lost "body cell mass" and were "wasting", even if they had lost no weight or had actually gained weight. With these test results in hand, doctors would justify prescribing Serostim to treat the supposed problem - at $21,000 a treatment.

The company also agreed to plead guilty to the other part of the scam - offering doctors all-expense-paid trips to a medical "conference" in Cannes, France, in exchange for writing more prescriptions for Serostim.

85 percent of the prescriptions written for Serono's growth hormone Serostim weren't necessary.

$704 million penalty for drug maker.

But nobody went to jail (and what of the doctors who colluded with the scam?). I wonder if any were in the UK?

Sources: "Settlement in Marketing of a Drug for AIDS", New York Times, Oct 18, 2005; also Health care Renewal

1 year ago today: Cochrane verus industry influence on haemoglobin targets

On 18 October 2006 a Cochrane review reported that higher haemoglobin targets in dialysis and pre-dialysis patients is not associated with lower mortality. This clinical problem assumed some importance as one of inappropriate commercial influence over rational therapeutic strategy ([Link], [Link]).

Source: Strippoli GFM, Navaneethan SD, Craig JC. Haemoglobin and haematocrit targets for the anaemia of chronic kidney disease. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD003967.

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Memory Hole (17 October): The Panjandrum

Scientific Misconduct Blog Memory Hole: Events of October the 17th

Words of the day: Panjandrum and the superiorvator

October 17th was a lazy uneventful day in the history of important people in science and medicine. I'll restrict myself to the word of the day, and a brief roundup of salient events.

The word of the day is: Panjandrum

panjandrum \pan-JAN-druhm\, noun: An important personage or pretentious official (like Lester Crawford). The rules that apply to a panjandrum are generally different from those that apply to anyone else.

The word used in a sentence:

"And so I have appointed myself the chairman, High Panjandrum, Grand Inquisitor, and sole member of a grievance committee of my own making."
-- Alan K. Simpson, Right in the Old Gazoo

The device pictured is a superiorvator (circa 1827).

The word Panjandrum was invented by by Samuel Foote (1720-1777) in a piece of nonsense writing. This was composed to challenge actor Charles Macklin's claim that he could memorize anything:

"So she went into the garden to cut a cabbage-leaf to make an apple-pie; and at the same time a great she-bear, coming up the street, pops its head into the shop. "What! No soap?" So he died, and she very imprudently married the barber: and there were present the Picninnies, and the Joblillies, and the Garyulies, and the grand Panjandrum himself, with the little round button at top, and they all fell to playing the game of catch-as-catch-can till the gunpowder ran out at the heels of their boots."

Reference: "The Great Panjandrum"

76 years ago today: Al Capone gets a wrist slap

On 17 October 1931 mobster and mass murderer Al Capone was convicted of income tax evasion and sentenced to 11 years in prison. He was released in 1939.

74 years ago today: Einstein arrives in USA as a refugee

On 17 October 1933 physicist Albert Einstein arrived in the United States as a refugee from Nazi Germany.

14 years ago today: Harrison Ford takes down a drug company

On 17 October 1993 "The Fugitive" was a hit movie. Richard Kimble (Harrison Ford) is a vascular surgeon who returns home to find his wife murdered. Kimble finally confronts his academic colleague Nichols with evidence that a drug was causing hepatic failure. Nichols is working with a large drug company, and faked trial results. Not serious but still fun to see.

4 years ago today: Study sets off debate over conducting research "offshore"

On 17 October 2003 there was debate in the press over the ethics of conducting research in "far away" places in order to bypass rules and watchful eyes.

I suspect this will become more important.

From a report in the Baltimore Sun
Debate surrounds the practice of shifting experiments overseas to circumvent U.S. regulations., 17 Oct 2003

"When Chinese and American researchers reported this week that they had used a cutting-edge DNA transfer to impregnate an infertile woman in China, they set off an ethical, political and scientific debate."

"The reason: The American scientist turned his technique over to Chinese colleagues because they could try it without waiting for permission from the U.S. Food and Drug Administration."

"The announcement touched a nerve in the scientific community. Should a U.S. researcher move experiments overseas to avoid regulations designed to protect human research subjects?"

"To some, the answer is clear. "I think in this situation, doing research in another country where the regulations are less protective of patients is not ethical. And there have been many situations before where that's been made clear," said Mildred K. Cho, associate director of the Stanford University Center for Biomedical Ethics."

"In their experiment, researchers from New York University and Sun Yat-Sen University of Medical Science in Guangzhou, China, took DNA from a prospective mother and father and transferred it into a hollowed-out donor's egg whose own nucleus had been removed.
The reconstructed product was then transferred into the mother's uterus."

"Dodging regulatory hurdles is not unheard of in medical research. In the United States, for example, it is unethical for scientists testing an experimental therapy to use placebos (sugar pills or drugs with inactive ingredients) on fatally ill test subjects if there are proven treatments available. But in recent years, critics have attacked U.S. pharmaceutical companies for testing therapies in the Third World, where regulations concerning placebos are less strict."

"At NYU, Dr. Keith M. Krasinski, chairman of the medical school's Institutional Review Board, said the university normally reviews all research on humans that it sponsors or that its faculty members conduct.

But he said the university's approval wasn't necessary in the Chinese fertility experiment because Grifo "didn't conduct the research."

"He didn't supervise the research. He was never in China," Krasinski added. "He's not in trouble in any way." He said Grifo is listed as a co-author in the research findings as matter of academic "courtesy."

'Think very carefully'

That reasoning is unlikely to satisfy many critics. Scientists "should think very carefully and be sure of their moral position when they go to a place like China to conduct research," said Alan Colman, chief scientific officer of ES Cell International in Singapore, a biotech firm that does stem cell research."

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