More on Vytorin - Confusion will be my epitaph

There is a worthwhile report in the Wall Street Journal today on the apparent manipulation of the Enhance trial of the drug Vytorin (zetia ezetimibe/simvastatin-combination). The explanation requiring the fewest assumptions is most likely to be correct. It is going to take more than a "duck and cover" approach to restore trust.

Despite their recidivism, one would hope that Schering Plough and Merck realize that they have not chosen an appropriate path yet again. Albert Einstein defined insanity as:

Insanity: doing the same thing over and over again and expecting different results.

If everything is against you, bully your critics. If critics aren't fooled, argue "data quality". I'll discuss the discreditable "data quality" defence and the statistics of data quality in clinical trials later. I have extracted the various data quality excuses forwarded by Schering Plough. These are unlikely to stand up to any form of serious scrutiny.

The full WSJ article (link below) is worth a read. In the meantime, the executives involved may want to listen to the 1970's song 'Epitaph' by King Crimson.

Epitaph (UTube here or here, full lyrics here)

Knowledge is a deadly friend
When no one sets the rules.
The fate of all mankind I see
Is in the hands of fools.

Confusion will be my epitaph.
As I crawl a cracked and broken path
If we make it we can all sit back
And laugh.
But I fear tomorrow Ill be crying,
Yes I fear tomorrow Ill be crying.

TRIAL AND ERROR: Delays in Drug's Test Fuel Wider Data Debate
By RON WINSLOW and SARAH RUBENSTEIN
Extracts from Wall Street Journal March 24, 2008; Page A1 Link to full article

"The firms said they had merely been trying to correct irregular data."

The companies brought in a second lab to compete to produce more accurate results than the original research team.

"The companies say they didn't peek at the results or know Vytorin had failed in the study until very recently".

"What we were trying to do was to improve...the precision and the accuracy of the data so that at the end, the results would be credible," says Enrico Veltri, Schering-Plough group vice president of global clinical development

They also emphasize that early data checks turned up another problem they found even more troubling: missing or "implausible" data that the companies have previously cited as the reason for the long delay in reporting the findings. In some cases they were concerned about wide fluctuations in readings that were supposed to be precise. Other researchers say variation in readings is inevitable in most imaging studies, and that enrolling enough randomly assigned patients spreads any problems among both groups to avoid affecting the overall results.

Early in 2006, the companies' committee proposed a different approach to reading the still-blinded data, and pitted Dr. Kastelein's lab against an outside research team to see whether one would be more accurate. There was no meaningful difference. In January 2007, an independent consultant told the companies that the quality of the Enhance data was similar to what was found in other comparable trials.

But company officials still weren't satisfied. They say they kept exploring different ways to eliminate wayward readings and hone the study's precision. "It's very atypical for a trial to go through this sort of scrutiny," says Allen Taylor, chief of cardiology service at Walter Reed Army Medical Center, Washington, D.C., and an expert in imaging of neck arteries.

The companies defend the effort. "It wasn't that the study looked like it was totally inadequate," says Merck's Dr. Musliner. "The more you can reduce your variability, the greater your chances of showing the significance of smaller differences."

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A Researcher's Credo - Two important letters in the BMJ

A letter in the British Medical Journal this week goes to the heart of the problems facing clinical medical research (authors Antonuccio and Healy). It discusses the critical status of raw data, the rights of study participants, and proposes a new credo for researchers. Patients who take part in clinical trials expose themselves to risk in the interest of all of us. They have a right to know that the information derived from their assumption of risk will not be misused, suppressed or distorted. The problem of cheating in commercial clinical trials will not be solved by any clinical trials register. Another letter by Geisler reinforces the point. Neither letter discusses the fact that raw data may not be accessible to "authors" either - a further layer of complexity. Both letters are in response to an excellent paper by Lenzer and Brownlee ( Lenzer, Jeanne; Shannon Brownlee (2008-03-08). "An untold story?". BMJ 336 (7643): 532-534 - PDF here). The adoption of such a credo will go a far way towards solving many of the problems of falsified clinical research.

Both letters are reproduced below:

Letter 1: The researcher’s credo
Antonuccio, David O; David Healy (2008-03-22). "The researcher's credo". BMJ 336 (7645): 629.

Lenzer and Brownlee hit the nail on the head regarding the important issue of data access.[1] We owe all human subjects who volunteer for behavioural and medical research more than they have been getting. For years, the top scientific journals have required that all clinical trials be publicly registered before data collection begins, in order to be eligible for publication. This was an important step designed to reduce publication bias, but it did not go far enough. The recent FDA Amendments Act mandating public access to data summaries is another step in the right direction, but, as Lenzer and Brownlee say, this too may not go far enough. Several examples from the psychopharmacology literature have shown that nothing short of total public access to raw human subject data on efficacy and safety will be enough to ensure that data are independently and thoroughly evaluated.[2,3] Issues of distorted or selective publication continue to corrupt our ostensible scientific database.[4,5]

We urge all institutional review boards to require that, in exchange for the privilege of doing human subject research, researchers make their raw data (not just summaries of the data) accessible (without identifying information) within a reasonable period of time via the internet or in some other suitable fashion. We believe scientists owe this unfettered access to all participants who have ever volunteered for a scientific study with the hope, belief, and promise that their sacrifices would help science advance. We offer the following brief universal commitment to human subjects that can be used by any institutional review board in the world:

"I agree, in exchange for the privilege of doing research with human subjects, to not only register the trial in a publicly accessible clinical trials database, but also to make summaries of the primary results and the actual raw data internet accessible (without identifying information) within 1 year of collecting data on the last human subject, or within 2 years after the start of the study, whichever is sooner. This is my commitment to all human subjects who volunteer with the hope, expectation and promise that their efforts and sacrifices will result in independently verifiable contributions to science. I recognize that failure to follow through on this commitment may jeopardize approval for any future research protocols in which I may participate."

David O Antonuccio, Professor of psychiatry and behavioral sciences, University of Nevada School of Medicine
David Healy, Professor, North Wales Department of Psychological Medicine, Cardiff University
References

1. Lenzer J, Brownlee S. Antidepressants. An untold story? BMJ 2008;336:532.
2. Antonuccio DO, Danton WO, McClanahan TM. Psychology in the prescription era: building a firewall between marketing and science. Am Psychol 2003;58:1028-43.
3. Healy D. Let them eat Prozac: the unhealthy relationship between the pharmaceutical industry and depression. New York: New York University Press, 2004.
4. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: A meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008;5:260-8.
5. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358:252-60.

Letter 2: Excessively closed science hurts
Geisler, Fred H. (2008-03-22). "Excessively closed science hurts". BMJ 336 (7645): 629-a.

I would like to add to Lenzer and Brownlee’s reporting of my comments on how excessively closed science can hurt physicians and patients.[1]

Statistician Michael Bracken led the NASCIS 2 and 3 studies of high dose steroids in acute spinal cord injury.[2] The National Institute of Neurological Disorders and Stroke conducted a public campaign in advance of the scientific publication of NASCIS 2 on 17 May 1990. The institute sent a fax on 13 April 1990 to some 19 000 emergency room physicians and hospitals, after a press release had resulted in coverage by the New York Times and the Chicago Tribune on 31 March 1990, by Science News on 7 April 1990, by Newsweek on 9 April 1990.

This led to widespread use of steroids, off label. No application for regulatory approval for this indication was completed, and no agency ever approved it. Surgeons report that methylprednisolone is administered from fear of litigation, not belief in efficacy.[3] Bracken reinforced this fear by testifying against physicians; he was deposed on 9 June 1998 in Civil Action File No 96A-7768-6, Superior Court of Fulton County, GA.

We have criticised NASCIS science.4 The later guidelines for the management of acute cervical spine and spinal cord injuries from the American Association of Neurological Surgeons and the Congress of Neurological Surgeons (AANS/CNS)[5] rated the NASCIS publications as evidence class III, citing flaws in study design, data presentation, interpretation, and analysis. They listed steroid treatment only as an "option."

The lack of demonstrated benefit must be weighed against documented risks. The CRASH trial showed a 3% greater mortality when corticosteroids were given to a multitrauma group with head injury.[6] If this increased death rate held in SCI, then 5000 extra patients may have died in the US since 1990.

Yet it’s difficult to stop the momentum—especially when primary data are unavailable for independent review.

Fred H. Geisler, Director, Illinois Neuro-Spine Center

References

1. Lenzer J, Brownlee S. Antidepressants. An untold story? BMJ 2008;336:532. (8 March.)[Free Full Text]
2. Bracken MB, Shepard MJ, Collins WF Jr, Holford TR, Baskin DS, Eisenberg HM, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the second national acute spinal cord injury study. N Engl J Med 1990;322:1405-11.
3. Eck JC, Nachtigall D, Humphreys SC, Hodges SD. Questionnaire survey of spine surgeons on the use of methylprednisolone for acute spinal cord injury. Spine 2006;31:E250-253.
4. Coleman WP, Benzel E, Cahill DW, Ducker T, Geisler F, Green B, et al. A Critical appraisal of the reporting of the NASCIS II and III studies of MPSS in acute spinal cord injury. J Spinal Disord 2000;13:185-99.
5. Hadley MN, Walters BC. Pharmacological therapy after acute cervical spinal cord injury. In: Guidelines for the management of acute cervical spine and spinal cord injuries. Neurosurgery 2002;50:S63-S72.
6. Edwards P, Arango M, Balica L, Cottingham R, El-Sayed H, Farrell B. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet 2005;365:1957-9.

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BMJ Advertising Watch : 22 March 2008 (The fabric of civilization)

This is the British Medical Journal Advertising analysis for this week.


Rules: As usual this is for the UK version of the BMJ. The classified advertisement section is excluded, as are advertisements for the BMA, products of the BMJ/BMA/BNF or the government.

The Devils Dictionary Defiled defines Truth in Advertising thus:

Truth in Advertising - n. a fiction whose realization is impossible. Advertising's end is selling, and should truth enter the practice it would mean the end of selling. The end of selling is the end of civilization.
Stephen R. Brubaker, 2006

Truth in advertising would drain the advertising field of all creative talent and energy. All the talent would have to be absorbed by the fields of politics, journalism, and law. In several of these fields, good fiction writers would be welcome, as they would be able to raise the standards of the craft measurably. But once all fantasy has been removed from the process of product disclosure, there will be an expectation that product flaws be disclosed as well. When consumers discover the full extent by which goods and services are likely to fall short of their once fantasized ideal of function, durability, economy, and satisfaction, all commerce will cease. The white-hot economy will freeze solid, fracture, and shatter like glass. It would prove the undoing of civilization. Fabrication is the fabric of civilization.
- American Enterprise Trade Commission

Click here for collated BMJ Advertising analyses.

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Scientific integrity: Another resignation from the British Psychological Society

Another psychologist, Cole Davis, has recently resigned from the British Psychological Society (BPS) over their ignoring of scientific integrity. His resignation letter submitted today for publication in the BPS Journal (The Psychologist) is below - but not yet published.

17 March 2008
To the British Psychological Society

Further to my resignation last year, the last straw being your encouragement of the appellation 'Chartered Scientist', available to people who do not necessarily embrace scientific methods:

I no longer accept the British Psychological Society's claim to be acting in the public interest, and support the recently declared stance of another ex-member. Although I personally do not need to use the term in order to make a living, I shall call myself a psychologist and will give any support to a body which can regulate psychology in a responsible manner.

Over the years it has become apparent that the BPS is not such an organisation.

Cole Davis
Psychologist
formerly "Chartered Occupational Psychologist"

Davis previously wrote to the Psychologist in 2007 detailing BPS failure to uphold scientific integrity.

The BPS - value for money in the public service?
Published in The Psychologist, February 2007

Sir

The BPS regularly refers to its duty to the public when defending itself against i) accusations of failure to support its members, ii) ostentatious advertising of members under a cloud and iii) being over-expensive.

I no longer subscribe to such a defence. Three times, spread over some years, I have sought either support or guidance on ethical matters. On none of these occasions was I offered any.

In the last instance, when I told officials that I was being repeatedly and overtly pressurised to falsify research findings for a public project, I was told that 'we don't give legal advice' and that I should consult the Code of Ethics. Apart from the fact that there is little in the Code of Ethics about corruption, other than an urging of the practitioner to behave professionally, I don't see why some guidance was not forthcoming. I was in touch with members of the BPS with responsibility for regulations and ethics; if all that is necessary is already on the web site, then I think there is a certain amount of redundancy in the organisation.

In short, I don't think members' subscriptions are benefiting the public and I think reorganisation, rethinking and refunds are in order.

Yours Sincerely

Cole Davis
Chartered Occupational Psychologist, London NW2

See also the resignation of Lisa Blakemore Brown. What of the regulatory body for doctors in the UK (The General Medical Council)? Do they have much real regard for honesty and for the integrity of science upon which our patients rely?

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BMJ Advertising Watch : 15 March 2008 (and summary of an important paper)

Before discussing the BMJ Advertising watch for this week, I thought I would summarize an excellent 2006 article in PLoS medicine about advertising in medical journals[1].

• The amount of money involved is large. In 2003 drug companies spent US$448 million on advertising in medical journals [1]. The American Medical Association (AMA) receives at least US$40 million annually from advertising[2].
• It is effective at increasing sales. Analysts calculate that the return on investment is about $5.00 for each $1.00 advertising spend [3].
• Advertising in general medical journals is almost exclusively for pharmaceuticals, and not other medical products, or consumer products of interest to doctors (computers, holidays and so on). Many journals have statements which exclude general consumer advertising [1]. For example the JAMA states "products or services eligible for advertising shall be germane to, effective in, and useful in the practice of medicine". It is proposed that accepting advertising for consumer goods would help minimize the conflict of interest inherent in pharmaceutical advertising, and would free editors from threats[1] made by advertisers which leads them to participate in editorial scientific fraud. Another option is to eschew journal advertising altogether (as has PLoS Medicine).
• "Military recruitment advertisements" were noted in JAMA as an important exception to pharmaceutical advertising[1]. During a single anomalous year (1997) JAMA ran advertisements for Land Rover vehicles, Steinway pianos, Wellcraft boats, pork, and Quaker oatmeal [1].
• The exclusivity of pharmaceutical advertisements is not due to affordability. After adjusting for circulation rates, advertising rates in medical journals are far less expensive than rates in consumer magazines (such as Vogue) [1].
• Various inappropriate "mottos" of journals are discussed [1]. The Journal of Clinical Endocrinology and metabolism states: "we use our know-how to help you reach the industry's thought leaders and maximize your return". The NEJM states "Place your ad in the New England Journal of Medicine and make our relationship with the medical community yours". The BMJ states "We protect our reputation by careful balance of editorial and advertising, which means your messages will always stand out".
• Advertisements are not "educational". The American College of Physicians (publisher of Annals) colluded with this excuse by arguing in court that profits on pharmaceutical advertising should not be taxed because advertisements were educational. Justice Marshall judged "we are bound to conclude that the advertising in Annals does not contribute importantly to the Journal's educational purposes"[4]. The notion of advertisements as "educational" is easily rebutted. Although there are more than 10,000 drugs on the market, 50% of the advertising expenditure is on only 50 of these. Competing drugs regularly cohabit in the same journal. Reviews of pharmaceutical advertisements conclude that 44% would lead to improper prescribing [5], about 60% of cited research was company sponsored, and 30% of advertisements with medical claims contain no scientific references. 19% cited "data on file" that is not open to scrutiny [6], impossible to obtain [7][8] and therefore potentially false.
• Apart from influencing doctors, advertising (or the threat of its withdrawal) is used to manipulate editorial decisions [1]. Several examples are given. In 1992, a study in Annals criticized the accuracy of advertisements in journals [5]. Large pharmaceutical companies subsequently withdrew advertising in that journal [7]. In 2004, an editor at Dialysis and Transplantation told an author that although the author's article had passed both editorial and peer review, the marketing department rejected it. The journal later reversed its decision, but the author refused to resubmit." [1].

References

1. Fugh-Berman, Adriane; Karen Alladin, Jarva Chow (2006-06-01). "Advertising in Medical Journals: Should Current Practices Change?". PLoS Medicine 3 (6): e130. Retrieved on 2008-03-16.
2. American Medical Association [AMA - 2004 Annual report]. AMA (2005). Retrieved on 2008-03-16.
3. Neslin, Scott (2008-03-16). ROI Analysis of Pharmaceutical Promotion (RAPP) - An Independent Study. Retrieved on 2008-03-16.
4. American College of Physicians v. US. 3 Cl.Ct 531 (1983)
5. Wilkes, M S; B H Doblin, M F Shapiro (1992-06-01). "Pharmaceutical advertisements in leading medical journals: experts' assessments". Annals of internal medicine 116 (11): 912-9. PMID 1580449.
6. Cooper, Richelle J; David L Schriger (2005-02-15). "The availability of references and the sponsorship of original research cited in pharmaceutical advertisements". CMAJ : Canadian Medical Association journal=journal de l'Association medicale canadienne 172 (4): 487-91. PMID 15710940.
7. Mindell, J; T Kemp (1997-12-13). "Evidence based advertising? Only two fifths of advertisements cited published, peer reviewed references". BMJ (Clinical research ed.) 315 (7122): 1622. PMID 9437300.
8. Hafeez, A; Z Mirza (1999-08-28). "Responses from pharmaceutical companies to doctors' requests for more drug information in Pakistan: postal survey". BMJ (Clinical research ed.) 319 (7209): 547. PMID 10463894.

This is the British Medical Journal Advertising analysis for this week.


New records have been set for the amount of advertising, and the ratio of advertising to content. The single half page that was not devoted to pharmaceutical advertising was for the army. Unfortunately both the problematical (evidence free) advertisement for testosterone, as well as the Pfizer fireman (? a fake fireman) were back.

Rules: As usual this is for the UK version of the BMJ. The classified advertisement section is excluded, as are advertisements for the BMA, products of the BMJ/BMA/BNF or the government.

Click here for collated BMJ Advertising analyses.

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The Osler Corner - On polypharmacy

Osler was one of the greatest physicians of all time. Here are some of his thoughts on polypharmacy from around a century ago.

For generations the people of the United States have indulged in an orgy of drugging. Between polypharmacy in the profession and quack medicines, the American Body has become saturated ad nauseum.
Sir William Osler (1849-1919), British Medical Journal (1910) 1470-2

The young physician starts life with twenty drugs for each disease, and the old physician ends life with one drug for twenty diseases.
Sir William Osler (1849-1919)

The battle against polypharmacy, or the use of a large number of drugs (the action of which we know little, yet put into bodies of which we know less), has not been fought to a finish.
Sir William Osler (1849-1919), in Aequanimitas p255

In 2008 polypharmacy may occur because treatment guidelines are imposed on doctors for multiple specific diseases. Even when guidelines are science-free or commercially biased, the legal and practical risks of disobeying them may override logic. Clinical trials (and guidelines) rarely take account of polypharmacy, and generally exclude patients taking other medicines.

Click here for collated posts from the Osler Corner

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Zetia - something brewing on Cafe Pharma

Cafe Pharma, the anonymous bulletin board for Pharmaceutical Sales Representatives, is always amusing and insightful. The mud flows freely. From these anonymous comments today on the Schering Plough board [Link, Link], one wonders what innovations are brewing with Zetia and a "49 day plan". Some great science I suspect.

Yesterday, 06:33 PM Zetia 49 Strategy
Wondered what everyone thinks about this Zetia 49 plan??

I hate having extra $$ that I have to spend on Drs that I can barely see. I have a hard time spending all my lunch/dinner $$ now. Can't get docs out to dinner anyway - especially the ones they've targeted for me...... This instruction that we are to have a lunch or dinner EVERY DAY - come on!! Like all the Drs offices aren't booked already for the year - or have stopped doing lunches/dinners altogether! ....

Throwing money at a problem is not the way to fix things - it will only make matters worse. Have the company come clean about the study, give us some good (or even not so good) evidenced based medicine - and let us earn back the business the right way.

Yesterday, 07:55 PM Zetia 49 Strategy
Hey how about replacing the Vytorin combination of Zetia and Simva with Zetia and Cheerios.... You could call it something creative like Cheatios. Come on, I know you SP shitheads can make something out of all of this. Run a trial call Son of Enhance and use a Priest as the "Head Investigator and enroll only 8 year old little boys. Then hold the results for 10 years until they reach legal age and then reveal the truth. Send this one up to your marketing team.....

Yesterday, 10:25 PM 49 day plan ... hahahahahahahahaha RIGHT !!!??
this is a joke....??? right.

Yesterday, 10:32 PM Re: 49 day plan ... hahahahahahahahaha RIGHT !!!??
My 49 day plan consists of seeing how many of the next 49 days I cannot work. Hell I'll probably extend the plan if it works out for me.

Today, 01:50 AM Re: 49 day plan ... hahahahahahahahaha RIGHT !!!??
at least you'll be kept busy until 1Q 08 numbers go public .....

Today, 06:08 AM Zetia 49 Strategy
Does any one think that having all this extra money thrown at us looks and feels like we are "buying" back the business - not "earning" back the business?
Once again, SP is seeing just how far it can go without crossing the line...
Hey Fred, Carrie - the line HAS been crossed! Integrity counts!...

Today, 06:08 AM Zetia 49 Strategy
Here is why it will not work: ...We have lost the trust of doctors. It is not the message, but until there is DATA showing that Zetia reduces CV events and mortality, doctors will say that we are just spewing the same old shit, and get even more pissed....

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The Shame of the British Psychological Society - Last chapter in the Lisa Blakemore Brown saga

A year ago I devoted several postings to the disgraceful and ludicrous abuse of a clinical psychologist, Lisa Blakemore Brown (LBB), by the British Psychological Society (see collated postings including this one). The abuse lasted 10 years, and was apparently motivated by factors other than evidence, logic or concern for patients. It has in my view brought this society into serious disrepute.

The treatment of LBB started as an obvious travesty when a commercially funded patient "support" group and the BPS itself appear to have colluded to create a triggering complaint. What followed was a protracted farce. The BPS seems to have realized that its actions would not be hidden, and the farce was terminated this week. It has left LBB financially destitute, with a destroyed career and ill health.



and a few days later



The abuse of health professionals by professional leadership is a key threat facing the safety of medical practice. Such abuse often takes place simply because these individuals have expressed a view, or because they have raised concerns. Abuse by professional regulatory bodies is particularly troubling.

The BPS has some important questions to answer, and it is not "closed" as they suggest. There are questions about the integrity, motives and honesty of BPS procedures. There are questions about the factors motivating the entirely spurious complaints, and who arranged for their invention. There are serious concerns about the way in which the BPS attempted to abuse one of its members through the misuse of psychology itself, and the way in which the medical profession assisted.

By contrast, professional regulators have remained silent in the face of gross abuses of science, obvious lies, fraud and the deaths of patients -- where these problems involve commercial companies or a network of powerfully connected colleagues. The BPS remains completely silent on the widespread fraud which is increasingly apparent within the pharmaceutical psychiatric literature. The regulatory body governing medicine in the UK (the General Medical Council) has also remained silent, and has refused to entertain a complaint of professional misconduct from patients and families involving the medical leadership of GlaxoSmithKline.

The silence is deafening.

Equally worrying is the fact that this abuse stirred scarcely a breath of protest amongst other members of the BPS. Few psychologists troubled themselves to ask the simplest of questions. Such silence is surely a badge of shame for any caring profession.

Lisa Blakemore Brown has now resigned from the BPS.



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The 2008 Pharma "Competitive Intelligence" Conference

Now this should be an interesting meeting.

The 2008 Pharma Competitive Intelligence (CI) Conference on Sept. 15-17 in New Jersey.

"This is one of the best and largest gathering of pharma Competitive Intelligence professionals".

Who is speaking?
Here is a sampling of the many pharma speakers:

• Monika Giese, Head Global Competitive Intelligence, Novartis Pharma AG
• Jerry Hoffman, Manager-Global Competitive Intelligence Strategy, Eli Lilly & Co.
• Daniel Pascheles, Vice President, Global Competitive Intelligence, Merck
• Renee Pierson, Global Intelligence Leader, Johnson & Johnson Pharmaceutical Services
• Chandra Ramanathan, Director, Global Business and Competitive Intelligence, Bristol-Myers Squibb
• Craig McHenry, Senior Director, Competitor Insights, Wyeth

What is competitive intelligence?
We don't really want to explain, but probably stuff that interferes with honest science and honest people. Perhaps spying and some bullying. Perhaps things like:

• Procter and Gamble goes dumpster diving
• Another P&G spying case
• P&G in yet another spying case
• A company employs "traditional and standard" methods to avoid exposure
• Wyeth and the bullying of Dr Hampshire (or see here)
• GSK and the intimidation of Dr Buse
• P&G and the Mysterious incident of Dr Purple

Is this ethical?
See The Ethics of Competitive Intelligence

If we are competing, why are we all there?
Depends who we are competing with

So who is the competition?
Proponents of the doctrine that black is black.

Please explain?
"There was a society of men among us,
bred from their youth in the art of proving,
by word multiplied for the purpose,
that white is black and black is white
according to how they are paid".
Jonathan Swift

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BMJ Advertising Watch : 08 March 2008 (giving obfuscators a voice)

This is the British Medical Journal Advertising analysis for this week.



The 1.5 pages of advertising material that was not devoted to pharmaceuticals comprised:

• An advertisement for an information technology company (half a page)
• A report from the Association of British Pharmaceutical Industry (ABPI) listing their token wrist slapping of companies deemed to have breached the ABPI code of practice. The ABPI is of course the lobby group for Pharmaceutical companies in the UK.

These ABPI reports are always puzzling. They seem to choose a few slightly important examples of system malfunction -- while selectively ignoring all serious scientific misconduct or fraud that have led to significant human misery. I might be cynical, but perhaps the intent is to convey an impression that some self-policing is taking place.

This time we are told that ProStrakan promoted a medicine "in a way that was inconsistent with its summary of product characteristics" and UCB Pharma "failed to maintain a high standard". How about dealing with some of the real problems of misrepresented science ABPI, or perhaps that doesn't matter much to your members.

So, ABPI, I suggest that you start with GSK and the problems raised in the report by Harvard Psychiatrist Professor Joseph Glenmullen. Perhaps the ABPI and its members regard the following as good scientific practice:
a) selective publication of positive data,
b) counting of events during the washout phase of clinical trials as if they were events on placebo
c) "recoding" of study events to misrepresent what they are.
Some scientists would regard these actions as serious scientific misconduct, but perhaps the ABPI would not agree. If so, I would be curious to know their reasons.
ABPI, you could even slap a few wrists over the misrepresented data and untruths told to journals and doctors about Procter and Gamble studies in Sheffield. Please do feel free to discuss if you care.

There were a few other depressing features in the BMJ this week. At least the BMJ continue to employ some excellent journalists (Jeanne Lenzer and Shannon Brownlee) who do tell it as it is. One wonders how long this will continue.

Rules: As usual this is for the UK version of the BMJ. The classified advertisement section is excluded, as are advertisements for the BMA, products of the BMJ/BMA/BNF or the government.

Click here for collated BMJ Advertising analyses.

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A Day of Shame for Science in the United Kingdom

This is the report of the so called "criminal" investigation of GlaxoSmithKline (GSK) by the UK Medicines and Healthcare Regulatory Authority (MHRA). It concerns fakery and misrepresentations of science involving the drug Seroxat/Paxil. Given the close links between the MHRA and GSK this can hardly be regarded as an independent or relevant investigation.

Nevertheless, the MHRA could hardly avoid acknowledging many of the scientific manipulations that took place within their report. Many others are not discussed. These include the apparent "recoding" of clinical records in randomized trials, and the counting of events in the washout phase of trials as events on placebo. There seems very little doubt as to what happened, and the fakery is not denied.

Many children and adults are likely to have died as a result of this fakery.

The upshot of this report is that scientific misconduct is acceptable in the United Kingdom. It is acceptable for doctors and patients to be misled.

The problem is that the MHRA is only concerned about information supplied to themselves by GSK. They are not concerned about the veracity and numeric accuracy of the information supplied by themselves to the public and to doctors. They regard the provision of false or incomplete information to themselves as legal so long as that information does not directly concern licensing. They ignore the fact that doctors and patients make decisions based on information in the scientific literature, and that this literature may be faked. They ignore the fact that they themselves rely on the "peer reviewed" scientific literature to make decisions. Despite this, the MHRA have previously declared that they have no remit to be concerned about the integrity of the scientific literature involving drugs, except where it is related to a licensing procedure. They maintain that the scientific literature is "exploratory" and that fraud in this literature is therefore not relevant.

It took the MHRA four years of "investigating" to reaffirm that fakery involving drugs no longer matters.

It is time for the honest members of the medical profession to say that they disagree.
This is a day of shame for science in this country, for our profession, and for the supine leadership of our profession.

No amount of legal tweaking over issues of data-supply to regulators is going to solve this problem. There are no right answers to the wrong questions.

The government might start by reassessing their failure to respond properly to the issues raised by the Commons select committee report of 2004/5. They might start by examining their refusal to address any of the critical issues raised by that report. They might make a clear statement that honest science matters. They might make it clear that in this country we expect the usual rules of science to be obeyed, and that raw and complete data should be made available both to regulators, authors of scientific publications and to concerned scientists. They might admit that the regulator has failed to scrutinize or retain actual raw data in the past, and has simply accepted the summary claims of industry with blind faith. They might think a little about the conclusions of the select committee concerning the honesty, integrity and independence of the MHRA. They might stop their cozy meetings with industry CEO's.

It was also most unusual that Gordon Brown should have invited the CEO of a company undergoing criminal investigation over the deaths of vulnerable patients to join his International Business Advisory Council.

No, I tell you. No, sir. Corruption charges! Corruption? Corruption is government intrusion into market efficiencies in the form of regulations......We have laws against it precisely so we can get away with it. Corruption is our protection. Corruption keeps us safe and warm. Corruption is why you and I are prancing around in here instead of fighting over scraps of meat out in the streets. Corruption is why we win.
(From the Movie Syriana)

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The Osler Corner - On the role of a university

A great University has a dual function: To teach and to think.
William Osler (1849-1919)
Aequanimitas and other addresses p120

Click here for collated posts from the Osler Corner

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The Osler Corner - on "education" by industry

A quote from 1909:

I would protest against the usurpation on the part of these men [purveyors of pharmaceuticals] of our function as teachers....... What right have Z. & Co. to send on a card directions for the treatment of anemia and dyspepsia, about which they know as much as newborn babe, and , if they stick to their legitimate business, about the same opportunity of getting information!
For years the profession has been exploited in this way until the evil has become unbearable.
William Osler 1909 (Can Lancet 1909;42:899-912)

Click here for collated posts from the Osler Corner

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Threats and Hipsavers in osteoporosis - rescuing science from lawyers

A Harvard researcher who published a study in JAMA that showed that a particular hip protector doesn't reduce the risk of fractures in the elderly is being sued by a company (Hipsaver). Hipsaver makes a different hip protector.

The story is covered in the Harvard Crimson and on the Wall Street Journal Health Blog (Hip-Protector Maker Sues Harvard Doc Over JAMA Study)

The JAMA study, published last year, involved more than 1,000 people at 37 different nursing homes. Participants wore a hip protector on one side of the body. Over 20 months of follow-up, the study found that there was no difference in fracture rate between the protected and unprotected sides. The upshot of the JAMA paper was that:

"In summary, this large multicenter clinical trial failed to demonstrate a protective effect of a hip protector on hip fracture incidence in nursing home residents despite high adherence, confirming the growing body of evidence that hip protectors are not effective in nursing home populations."

"These results add to the increasing body of evidence that hip protectors, as currently designed, are not effective for preventing hip fracture among nursing home residents"

So why is the author being sued? Well, the makers of the Hipsaver device state that

"The researcher’s JAMA-published conclusions have wrongfully damaged the entire field of hip protection, including the HipSaver brand".
"It would have been more appropriate and scientifically accurate for Dr. Kiel to limit his conclusions to the specific hip protector that he studied"
"It is totally irresponsible for public health opinion leaders with tax-funded grants to study and publish the results of a dud hip protector and then trash the entire field of hip protection."

According to the Harvard Crimson: "Representatives for HipSaver accuse Kiel of deliberately using one particular type of hip protector that is inferior to many of the protectors on the market and concluding that all hip protectors were not effective."

There is indeed increasing evidence from other sources that hip protectors are not as useful as initially hoped (See Cochrane Review : BMJ 2006;332:571-574 - "Pooling of data from three individually randomized trials of 5135 community dwelling participants showed no reduction in hip fracture incidence with provision of hip protectors.")

Robert L. Hernandez, who is representing HipSaver, described Kiel’s article as "disparaging" and "grandiose".

Disparaging?
Grandiose?

The bottom line however is that there is no good evidence that the Hipsaver device works any better to prevent fractures. Hipsaver imply (without any evidence) that their device would prevent more fractures than the chosen device. So what do Hipsavers cite as their "evidence". On their website, they cite their best evidence for efficacy - a 13 month long uncontrolled study of 38 individuals who wore a hip protector.

38

And guess what: "Number of hip fractures in HipSaver wearer group was: 0"

Now that is some evidence. Firstly, the expected hip fracture rate in elderly individuals at risk is (ballpark) 2% per annum. So the expected number of fractures in these 38 individuals would have been around ......... 1 fracture...... maybe.

Furthermore, we can calculate the upper confidence limit of a reported zero fracture rate at N=38 (See here for calculation). All we can say on the basis of Hipsaver's experiment is that the 95% upper confidence limit of the event rate in these "Hipsaver protected" individuals is around 7.5% per year. In other words the information content of HipSaver's experiment is almost zilch.

To make matters even more depressing, the JAMA paper received publicity last year when it was reported that three of the authors received money from makers of bone-strengthening drugs and failed to disclose that potential conflict to JAMA.

The field of osteoporosis - my field - is sadly a minefield of bad science. It is dominated by a powerful clique of characters who live in a parallel universe in which the normal rules of science are ignored. By their silence, these individuals have lent tacit support to all sorts of inappropriate things, including legal bullying. Dr Kiel is not part of that clique, but I didn't notice any enquires from the Harvard bone fraternity when I tried to stand up for honest science. Well you know guys, every time you remain silent, you are casting a vote for the kind of science you want.

Or, as Helen Keller said:

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, My Religion)

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BMJ Advertising Watch : 01 March 2008 (another day another lie - perhaps)

This is the British Medical Journal Advertising analysis for this week.



Having retired the misrepresented Dr Jarvik, the back cover Lipitor advertisement (Pfizer) features a fireman. Is he really a fireman? See Pharma Giles and Health Care Renewal on the "mis-impressions and distractions" of the Jarvik campaign. Now who is this un-named fireman, does he exist, and did he really say "What's terrifying for them is everyday for me"? As a doctor of average intelligence I am obviously deeply impressed by a fireman telling me about lipidology. We shall see:

Medical Information
Pfizer Limited
Walton Oaks
Dorking Road
Tadworth, Surrey
KT20 7NS

1 March 2008

Dear Sir

I note the photograph of a fireman on the back cover of the BMJ this week (issue 1 March 2008).

I would appreciate it if you would let me know the name of this fireman, since certain statements are attributed to him. I would like to know whether this fireman exists, whether he is an accredited fireman, and whether he really made the statements attributed to him. If he is not a fireman, please let me know which parts of this advertisement are truthful and science-based.

Best wishes

Dr Aubrey Blumsohn

In the meantime, the BMJ continues to advertise itself to advertisers thusly:

"We protect our reputation by careful balance of editorial and advertising, which means your messages will always stand out".

The BMJ seemed short of advertising material this month. There was however an advertisement for books! Sadly the troubling testosterone advertisement was back.

Rules: As usual this is for the UK version of the BMJ. The classified advertisement section is excluded, as are advertisements for the BMA, products of the BMJ/BMA/BNF or the government.

Click here for collated BMJ Advertising analyses.

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I am Shiva, God of Death

Just finished watching a good movie (Michael Clayton - 2007)

Lawyers have been instrumental in facilitating the great corporate scientific crimes that have soiled the landscape of medicine. Michael Clayton (George Clooney) is a legal fixer. He slips through various phases of complicity, guilt, and understanding of corporate lies and murder.

"I realized Michael, that I had emerged not from the doors of Kenner, Bach, and Odeen, not through the portals of our vast and powerful law firm, but from the asshole of an organism who's sole function is to excrete the... the... the poison, the ammo, the defoliant necessary for other, larger, more powerful organisms to destroy the miracle of humanity. And that I had been coated in this patina of shit for the best part of my life. The stench of it and the sting of it would in all likelihood take the rest of my life to undue. And you know what I did? I took a deep cleansing breath and I put that notion aside. I tabled it. I said to myself as clear as this may be, as potent a feeling as this is, as true a thing as I believe I witnessed today, it must wait. It must stand the test of time, and Michael, the time is now."

"I am Shiva, God of Death"

Worth watching.

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