Saturday, March 24, 2007

Anonymous awards

I have been tagged for a Thinking Blogger Award by two of the greatest anonymous medical bloggers over the past week - Pharmagossip award and Clinical Psychology and Psychiatry - award. These are two great pharmaceutical blogs. When one is nominated, it is apparently one’s duty to pass along five sites (and only five sites) that make one think.

Here are the rules.

Here is the graphic:

So, in the same spirit I offer up 5 blogs. I have specifically excluded the eight other special blogs already awarded.

Clinical Psychology and Psychiatry - a closer look
Furious Seasons
Health Care Renewal
The Last Psychiatrist
Pharma Giles
Peter Rost Blog

Given the limit of five, I have closen five others that deserve more thinking attention (and with no insult intended to the many other great blogs I read):

  1. The amazing and fearless Vera Sharav at the Alliance for Human Research Protection
  2. Seroxat Secrets A fascinating and excellent example of what our patients can achieve when us doctors don't care about the scientific evidence underlying the drugs we prescribe. A detailed and persistent probing of the functioning and malfunctioning of the UK drug regulator (the MHRA) and GlaxoSmithKline.
  3. From the great John Mack -The Pharma Marketing Blog
  4. Sisyphus’ Ledge by a thoughtful psychiatrist with bipolar disorder.
  5. And the ever amusing and intelligent Rita Pal of NHS Exposed now on the NHS Exposed Blog

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Sunday, March 18, 2007

It was Dr Purple in the Library - and things go bump in the night

The attempts by the good Dr Purple at Procter and Gamble to alter a scientific meeting abstract appears to be causing some hilarity across the blogsphere (See P&G Pharmaceuticals: how to deal with a public relations disaster [Link])

Pharmagossip [Link] posted the wonderful Deep Purple Smoke on the Water as a tribute to the good Dr Purple.

No matter what we get out of this
I know we'll never forget
Smoke on the water,
fire in the sky

Procter and Gamble Dr PurpleSeveral other blog entries discussed the Waddington game Clue (Cluedo for those in the UK).
"it was Dr Purple in the library with the poison" [Link]
Ghosts on the sly: [Link]
Other stuff [Link]
For the good Dr Purple: [Link]
CL Psych posted an excellent discussion about Purple Haze [Link] and
Roy Poses over at the excellent Health Care Renewal included an old Scottish poem that tells it all (See : Actonel, Procter and Gamble, and Things That Go Bump in the Night)

From ghoulies and ghosties
And long-leggedy beasties
And things that go bump in the night
Good Lord, deliver us!

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Wednesday, March 14, 2007

P&G Pharmaceuticals: how to deal with a public relations disaster

ghostly writer arrivingPatients get damaged by misrepresented pharmaceutical research. “Ghost-writing” has been repeatedly criticized - but this diverts attention from the more important problem – “ghost science”, of which “ghost-writing” is only a small part. Ghosts work behind the scenes at every level of the pharmaceutical scientific process. Sometimes these ghosts make mistakes and get startled by the headlamps - as Procter and Gamble discovered this week.

The steps P&G have taken to suppress concerns about their research procedures involving the drug Actonel seem to have derived from a Monty Python script. For the backstory read press reports, collated postings on this blog, report in AAAS, or Slate.

Last year, Procter and Gamble released previously hidden raw data underlying one published paper, several meeting abstracts, and two draft publications (with myself as first author). Work by independent statisticians has confirmed that the data does not provide credible support for P&G's reporting of a convenient "plateau" for Actonel in any of the three ghosted publications.

A declaration of Mea Culpa would have served Procter and Gamble far better than the endless attempts to collude with other script writers (like the editors of the Journal of Bone and Mineral Research). Instead P&G have now stepped further into the mud:

  1. They refused to allow me to place the data they eventually provided (underlying three publications) into the public domain. This did not serve to enhance their credibility.
  2. They refused to allow me as author to submit raw data directly to a journal editor requesting such data.
  3. They declined to provide a copy of the consent form patients would have signed upon agreeing to participate in this research. Did patients consent to have the measurements I performed? Did participants realize that data derived from their risk would not be open to scrutiny by authors of the publications, or that it could be misrepresented?
  4. But wait .... whatever next .... the Python team would be impressed by P&G's new attempt to act behind the scenes to have a perfectly valid conflict of interest declaration removed from the first of several scientifically correct meeting abstracts submitted about this research.

Read what happened and laugh (or cry):

Step 1: The abstract below (authored by myself and an independent statistician) was submitted on 22 January for presentation at The International Bone and Mineral Society Meeting (to be held in Montreal). The statistical aspects have been redacted pending publication. The electronic submission was accompanied by a declaration of funding leading to the footer as shown - "Study funded by Procter & Gamble Pharmaceuticals".

Control/Tracking: 07-A-464-IBMS Current Date/Time: 1/22/2007 3:53:26PM
Relationship of fracture risk to change in bone resorption with risedronate in the HIP study - is there a plateau response?
Authors: A. Blumsohn(1), J. L. Hutton(2)
1 Sheffield Teaching Hospitals, Sheffield, UNITED KINGDOM,
2 Department of Statistics, University of Warwick, Coventry, UNITED KINGDOM.

Understanding the determinants of bisphosphonate induced change in fracture risk is a prerequisite to rational prescribing and therapeutic monitoring. A previous abstract (Blumsohn, Barton, Chines, Eastell. JBMR 2003;18 S2:S89), and draft publications failed to shed light on the true relationship between change in bone resorption (uNTX/Cr) and fracture risk in the HIP study. The study included 938 women (FN T score <-3, age 74 SD 3) who received Ca and either 5mg risedronate/day, 2.5mg or placebo for 3 years. Randomization and event codes were supplied to authors in 2006. Data did not provide evidence to support previous conclusions.
Previous reports on these data suggested risk of incident vertebral fracture (V#) was non-decreasing when NTX decreases beyond -30% (%?NTX < -30%), and the relationship was "non linear" with "little further improvement in fracture benefit below a decrease of 30 to 35%". It further suggested that another marker (%?PINP) was significantly predictive of V#.
We used several statistical models as well as visual inspection to evaluate a potential "plateau" effect at a putative threshold -30% or -40%.
--- --- -------- ---------- ------ ---- ----, ---- ---------- -- ---- --- ----, --- --- --------------- -- ---: ----- --- ---------- --- -------- --- ------- -- ---- --------- ------ ----- --- ----- --- ---------, --- ---- ------ --- --------- ---------- ----------- ---- ----------- --- ---- --- --- ------, ---- -- ------- --------- -- ---- -- --- ---------- ------- -----
------ ---------- ------ -- -------- -- - ------- ---- --- -------- ---------- ---- --- ----------- ---- ------ -------- -- -------- ---- ------ -- --- ------ --- -------- ---- --------- ------- ----- ---- -- --- ------ -- -------- ---- ----- - ---- --------- -- ----- --- ---- --- ----------- ----- ----- -- ---- ----- --------- -- ------- -- --- --------- ------- --- -- -------- -- --- --- ----- - -----
---------- ------ ------ -- -------- --- - ------- -- ------ ---------, --- ----------- -------- -- -- ------- ---- - - ------ --- ---- --- --- --- ----- --- ---- -- -- --------- ------------- ---- ------- --- ---------- ---------- ------ ------ ----------- ---------- --- -------- -- ----- -- --- ------- ------- ------ --- - --- --------- ---- -------, ------ ------- -- - ---- --------- --------, ------ -------- -- ----------- ------------ ------- ------ --- -- --- ----- -- ---------- -- ------- -- ---------- ------ ---- - -------

In conclusion, this study provides no evidence to support a plateau relationship between NTX change and fracture risk with threshold near -30% in patients taking risedronate.
Author Disclosure Block: Study funded by Procter & Gamble Pharmaceuticals.

Step 2: On the 6th of March a fascinating E-mail was sent from the meeting organizers to mysterious Dr C Purple at Procter and Gamble. Unfortunately for Dr Purple the E-mail was also copied to my own E-mail address which had accompanied the abstract submission, together with Dr Purple's earlier secret E-mail to the meeting organizers. Dr Purple had asked for my declaration of interests and funding to be removed from the abstract. The meeting organizers had complied with this request.

Subject: RE: Abstract Change
Date: Mon, 5 Mar 2007 17:33:59 -0500
From: "Paterson, Anne"
CC: Aubrey Blumsohn

Dear Dr. Purple,

I have adjusted the disclosure so it does not include the below disclosure for P&G. There is currently no disclosure. If there is to be, please let me know and I’ll make the appropriate change.

Thank you for your patience and please do not hesitate to let me know if you have additional questions or concerns.


Anne Paterson
International Bone and Mineral Society (IBMS)
Washington, DC 20036

From: []
Sent: Tuesday, February 27, 2007 10:47 AM
To: IBMS - Paterson, Anne
Subject: Abstract Change

Dear Anne:

Last Thursday we spoke about changing an abstract, here are the details;

Please check the abstract submitted by Blumsohn and Hutton (Title: Relationship of fracture risk to change in bone resorption with risedronate in the HIP study - is there a plateau response) for a statement in the disclosure block indicating that the study was funded by Procter & Gamble Pharmaceuticals. Would you please let me know if is this disclosure is still attached to the abstract. If it remains associated with the abstract, please tell me what is the process for having it removed from the abstract?

Thank you for your help with this.

Christopher Purple, Ph.D.
Medical & Technical Affairs
Procter & Gamble Pharmaceuticals

Step 3: Professor Hutton and I responded with some consternation. We were informed that the meeting organizers had been duped (misled) by Procter and Gamble.

From: Aubrey Blumsohn
Sent: Monday, March 05, 2007 5:59 PM
To: Paterson, Anne
Subject: RE: Abstract Change

Dear Ms Paterson

Kindly let me know the basis upon which you altered the abstract submitted by myself (removing the conflicts of interest/disclosure section). Please also state precisely who gave you permission to do so.

This is extremely strange. Dr Purple's rather unusual E-mail below your own appears to have derived from a commercial company.

I would appreciate your urgent response. I would also appreciate it if you would send be a copy of the IBMS conflicts of interest and disclosure policy as it applies to this meeting and to IBMS
activities in general.

The abstract as submitted is attached.

Yours Sincerely

Dr Aubrey Blumsohn
MBBCh, PhD, MSc, BSc(hons), MRCPath

Subject: RE: Abstract Change
Date: Mon, 5 Mar 2007 18:11:17 -0500
From: "IBMS - Paterson, Anne"
To: "Aubrey Blumsohn"

Dear Dr. Blumsohn,

I apologize for this misunderstanding as I was under the impression you knew about the conflict. I have reentered the disclosure in the abstract as indicated in your attached pdf.

Please let me know if you have any further questions. I will contact you if anything else comes up regarding this conflict.


Anne Paterson
International Bone and Mineral Society (IBMS)
2025 M Street NW, Suite 800
Washington, DC 20036

Subject: RE: Abstract Change
Date: Tue, 6 Mar 2007 09:19:10 -0500
From: "IBMS - Paterson, Anne"
To: "Professor Jane Hutton"

Dear Dr. Hutton,

Thank you for your concern. It is not our policy and I take responsibility for the misunderstanding. I was misled and can assure you that as soon as I realized that the authors were not notified, I alerted the submitter and immediately returned it to its original form.

I am not sure how Dr. Purple viewed the abstract.

Please do let me know if you have any additional concerns.

Kind regards,

Anne Paterson
International Bone and Mineral Society (IBMS)

Well thank you Anne Paterson and the IBMS for behaving properly so far. Award of an oral presentation to to 07-A-464-IBMS may help restore a little of the lost credibility in skeletal pharmaceutical research.

And to Dr Purple of P&G: Please watch the Monty Python Parrot sketch below. Perhaps the PR staff at P&G should assist with research into soap and sanitary products like the Rely Tampon until you get some training from a proper pharmaceutical company - like Eli Lilly or Merck. Please invite me to give a seminar to your staff about the obligations of a doctor and how to deal with ethical problems in a more plausible way. I would be happy to do so any time.

You might also want to read some excellent blogs about pseudoevidence based medicine, a more effective public relations gambit, Conflicts of interest and other troubles with research. You are not alone.

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Tuesday, March 13, 2007

A journal editor does at least one right thing - well done Professor John A Eisman

fog at JBMRI posted previously about the attempt by the Editor of the Journal of Bone and Mineral Research (JBMR) to inhibit discussion about scientific misconduct and false declarations by authors of a published paper in JBMR (Richard Eastell et al. 2003 J.Bone.Miner.Res. 18:1051-6) as well as two draft publications and several meeting abstracts purportedly written by myself. That previous posting is reproduced below.

The editor, Professor John Eisman had agreed to present his case at the 3rd Annual Meeting of the International Society for Medical Publication Professionals (ISMPP, April 23 – 25, 2007, Philadelphia, PA). The meeting program is here. Thank you ISMPP for encouraging honest discussion about scientific procedure and publication ethics.

Update: However I now understand that Professor Eisman was "instructed" by someone not to attend. I have nothing to hide, and avoiding open honest discussion seems quite inappropriate Professor Eisman. Incredible.

Nevertheless Professor Eisman may be willing to read the evidence bundle, the independent statistical reports and the various corrected publications. He might even want to comment on the latest antics of Dr Purple at Procter and Gamble Pharmaceuticals and how that would be viewed by him as an honest editor. I will be detailing the various attempts of several parties to prevent the matter from being raised, and to allow those accused of misconduct (including a pharmaceutical company) to "independently" investigate themselves.

This is a meeting of medical writers (sometimes ghostwriters), perhaps not the most challenging of audiences. However I have always felt that over-emphasis on the problem of ghostwriting diverts attention from the more important problem of ghosted science. Medical writers do have a relevant role under proper circumstances, but under some circumstances they provide an easy conduit for scientific misconduct. The byline of the meeting is "Ensuring Integrity in Medical Publications: Conflicts, Credibility & Collaboration" and I will be reporting on the how the meeting addresses those goals.

"There is a demand today
for men who can make wrong appear right."
- Terence

I have a very old fashioned idea - that Medical Journal Editors should go about their business with as much objectivity and integrity as possible. They should act in the interests of the patients we serve. The Journal of Bone and Mineral Research (JBMR) is seeking a new editor to replace Professor John A. Eisman, MBBS, Ph.D. To apply, see here.

Editors wanting hints as to how to react when approached with concerns about research misconduct involving a major pharmaceutical sponsor and fellow friendly scientists, see the John A. Eisman approach. First try protracted delay. Then try meaningless gibberish, followed by excuses (or exasperation) when asked to reply properly. Then edit a letter of concern to remove all content, and offer to publish it giving a pharmaceutical company the right to respond. Express surprise when the offer is refused. Then decline to review any evidence at all, offering lame excuses. Decline to read statistical reports. Decline to read correspondence relating to denial of access to data. Decine to read anything relating to the concerns raised. Then suggest that those implicated will arrange for the concerns to be addressed. Good trick! It is always a good idea to address concerns that are different from those raised. When the matter reaches the press, write statements so at variance with your previous correspondence that it is hard not to laugh out loud. For collated correspondence and press statements see here. For press see here.

Will the JBMR eventually publish the truth about these three publications and how they came to be? Perhaps not. But then - who cares. Third rate conflicted medical journals that snuggle up to vested interests are steadily losing relevance.

Perhaps the new editor will join me in calling for Procter and Gamble to allow authors (including myself as first author of two of the three intended P&G publications) to make the raw data from the three publications publicly available. So far P&G have declined to allow that. I wonder why that might be?

Alternatively perhaps Professor John A. Eisman would care to perform a teensy tiny statistical analysis himself. He might even consider reading the statistical reports he was offered. Perhaps he would even care to review the evidence with me. Of course there is nothing whatever to hide Professor Eisman - or is there...

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Sunday, March 11, 2007

The Olivieri case: The Drug Trial debunked

obscuring the truthProgress in medicine relies on honest science. The bullying of scientists who have attempted to raise issues of integrity in medicine is a stain on our profession. So is the silence of colleagues.

Whistleblowers swim in shark-infested waters. They quickly learn about the iniquities of a system which protects the wrongdoers instead of patients. There is overt collusion between universities, professional regulatory bodies, drug licensing authorities and medical journals to obscure problems of science and scientific procedure. Often this is done to protect pharmaceutical patrons.

These stories expose the paranoid lengths our profession will go to keep scientific misconduct out of sight. Manipulation of the truth, whitewash, protectionism and lack of accountability are the standard response. We have ended up with pharmaceutical "science" that is in part a house of cards glued in place by vested interests.

The case of Nancy Olivieri at the University of Toronto continues to raise many worrying issues. The bullying of Olivieri was intense. Amongst the most awful things to happen to Olivieri was publication of a book which concentrated on her supposed personal attributes while ignoring the ethical principles she raised. Unfortunately the author of this book (Miriam Shuchman) failed to declare her conflicts of interest. Shuchman has now been exposed as mis-citing her anonymous sources, several of whom have complained. The University of Toronto have not distanced themselves, nor has it protected Olivieri from these attacks - there has been silence.

Sometimes the small sub-stories are most enlightening. The University of Toronto failed to take proper action against a malicious and very senior colleague who wrote anonymous threatening correspondence to Olivieri and several others. This individual, Professor Gideon Koren, repeadly denied doing so, until entrapped by DNA evidence. He remains an active researcher producing research "findings" which have relevance to patients. It is not clear whether our profession should accept such findings without question. The layer of Teflon coating some senior medical "thought leaders" is very thick.

I have previously written about this book [Link]. Now Arthur Schafer, a Canadian philosopher has written a scathing indictment of Shuchman's book and of her ethics (Bioethics , Vol. 21 (2) 2007, pp 111-115). The full review is here here. Extracts are below.

Review of the Drug Trial - by Arthur Schafer - Extracts
Full text here

The use of anonymous quotations, and the mis-citing of sources

The heavily biased manner in which Shuchman assembles her material seriously undermines The Drug Trial's credibility. Credibility is an especially important issue when evaluating the claims made in this book, because most of the hostile quotations are attributed to doctors and patients who are not identified. One of the few clearly identified patients, "Howard", has now gone on record as saying that his words, as quoted in the book, were twisted beyond recognition. He insists that, so far from being critical of Olivieri's patient care or ethics, he considers Dr. Olivieri to be a highly ethical doctor who is utterly dedicated to her patients.

A brief excerpt from Howard's letter of protest to Shuchman, which has now been made public, raises deep ethical concerns about the integrity of Shuchman's journalism: "Dear Miriam: You've used a smoke-and-mirrors approach to spinning my statements to inaccurately portray Nancy by misquoting me, attributing quotes to me that I didn't make, omitting portions of my comments that would alter the effect and taking these comments out of context."

My confidence in Shuchman's journalistic reliability, already shaken by numerous factual errors and skewed descriptions of key events was further eroded when I came across a passage in which she "quotes" from a commentary I published in The Globe and Mail. I wrote none of the words she attributes to me.

The problem with Gideon Koren

Many of Shuchman's other allegations of ethical misconduct, directed against Olivieri, rely on the testimony of Olivieri's leading foe at Sick Kids, Dr. Gideon Koren. Koren, then a senior scientist and scientific administrator at the Hospital, has been found guilty of and severely disciplined for both professional and research misconduct, first by the hospital and the university, and later by the Ontario medical licensing body. The hospital and the university found that his actions, including persistent "lying" in connection with his efforts to discredit Dr. Olivieri, "constitute gross misconduct and provide sufficient grounds for dismissal."

The CAUT Report found that Dr. Koren "attempted to discredit Dr. Olivieri by dishonest means". In the words of the Discipline Committee of the College of Physicians and Surgeons of Ontario, Dr. Koren was guilty of "conduct unbecoming a physician". "His actions were childish, vindictive and dishonest", authoring "vicious diatribes" contained in anonymous "poison pen letters" against Dr. Olivieri. Koren was stripped by the University of his Endowed Chair, required to arrange that his ethically suspect research be deleted from the scientific record, publicly reprimanded by the licensing body, and required to pay substantial fines by the hospital, the university and the licensing body.

Shuchman has great admiration for Koren and devotes almost a full chapter of her book to trivializing his misconduct and praising his stellar virtues and research accomplishments. Unfortunately, she omits to inform her readers of the full extent of Dr. Koren's publicly reported misconduct.

Institutional obfuscation

Olivieri's hospital, The Hospital for Sick Children, and her university, the University of Toronto, have also taken a public drubbing for failing to provide her with effective support as she struggled with Apotex. Actually, not only was Olivieri denied effective support, she was fired from her position as the director of the Hospital's hemoglobinopathy programme, and both she and those colleagues brave enough to support her experienced harassment of many kinds. In the words of the CAUT Report: "Neither HSC nor the University …took effective action to defend principles of research ethics, clinical ethics and academic freedom." When it was discovered that the university was negotiating with Apotex for a huge financial donation, well, some people drew their own conclusions, and these were not flattering to the university

The veritable cornucopia of discredit which Shuchman heaps on Nancy Olivieri is, I'm sorry to say, standard punishment for those who have the temerity to challenge powerful vested interests. In the popular imagination David bravely slays Goliath. Alas, in the real world, the whistle-blower's issue of principle is easily re-described as an act of private disloyalty and, worse, as evidence of professional incompetence and psychological disturbance.

For every Erin Brockovitch, rewarded with fame and fortune (when Julia Roberts was cast by Hollywood to portray her brave struggle), there are a dozen other whistle-blowers consigned by employers and colleagues to professional oblivion. Typically, those who challenge authority find that their professional competence, personal lifestyle and mental stability are all brought into question. Most whistle-blowers are also labeled malcontents and publicity seekers, as Shuchman stigmatizes Olivieri. They are duly punished with demotion, suspension, and/or dismissal. The case of Dr. Aubrey Blumsohn, recently suspended from his job by Sheffield University after he blew the whistle on one of that University's major research funders, Proctor and Gamble, fits the same pattern. Few whistleblowers escape this fate.

Demonstrably false charges

To fill out her story, Shuchman compiles a lengthy charge sheet against Olivieri. The most serious accusation is that Olivieri negligently delayed the implementation (at Sick Kids Hospital) of proper guidelines for the treatment of sickle cell patients. Shuchman claims that this delay led directly to the death of a young patient, Sanchia Bulgin. Shuchman is unmoved by the fact that Olivieri was not one of the physicians treating this patient, and that the responsible physicians were found (by two official inquiries) to have violated established guidelines which had been in place for years. It's a bizarre accusation.

Reading The Drug Trial I was repeatedly struck by how often Shuchman's account of events is contradicted by the findings of a series of independent inquiries - all public documents, all easily obtainable. Almost all of the anti-Olivieri "revelations" presented in Shuchman's book are warmed-over versions of allegations already disproven by one or more of these impartial inquiries, and the others are undocumented hearsay. In short, Shuchman's way with well-established facts would have brought a smile to the face of Procrustes.

Related Links
Gideon Koren - misconduct [Link]

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