Procter research shenanigans 6: Who stands behind the word?

As of April 2006 the Journal of Bone and Mineral Research has placed an undated "Statement of Concern" on its home page (Not on Pubmed though).

The statement relates to one of the three intended Procter and Gamble publications about change in bone turnover and fractures in patients taking Actonel (Eastell et al. 2003 JBMR 18:1051-6). The other two publications based on overlapping data have only been published in abstract form. The intended first author declined to sign journal declarations while being refused access to underlying raw data.

Medical journals face a crisis of credibility (1-15). Collated correspondence with the JBMR over 2 years provides some insight into the real concerns underlying their "Statement of Concern".

And from (11) a quotation that provides an excellent summary of the crisis facing medicine.

1. 23 August 2006: Why Today's JAMA Editorial Doesn't Go Far Enough
2. PLoS takes a stand
3. NEJM and Vioxx
4. Manipulating a Journal Article: NYT
5. Audio interview with NEJM Editor Drazen -(the call from Hrachovec begins at 44:30)
6. For Science's Gatekeepers, a Credibility Gap
7. Just how much 'new research' can we trust?
8. Incident raises questions of editors' and publishers' corporate connections
9. Why you can't trust medical journals anymore
10. Commercial influence and the content of medical journals
11. Presentation by Gavin Yamey
12. A Story Involving JAMA, Harvard Medical School, Baxter International, Cytyc
13. More on lessons from Neuropsychopharmacology
14. Won't Get Fooled Again, Again, Again
15. About the paper in Am J Psychiatry 163:34A (2006)

Earlier|Later|Main Page

The MHRA - continues to duck weave and delay

The UK Medicines and Healthcare Products Regulatory agency - continues to duck weave and delay - read on...

See also the House of Commons Select Committee Report on the MHRA - why is the government not acting?

Addendum: Yet more ducking and delaying: "Delay Breeds Corruption" revealed through the persistence of Charles Medawar. The MHRA continues to function with duplicity.

Earlier|Later|Main Page

Procter research shenanigans 5: Research misconduct summarized in one graph

This is the key graph from Richard Eastell et al. (2003) J. Bone. Miner. Res. 18:1051-6.

The solid lines supposedly show the relationship between the change in bone turnover (NTX) and new spine fractures in patients taking Actonel (Risedronate) at 1 year and at 3 years. The dashed lines show patients taking placebo. The purpose of this posting is simply to show that the scale of graphs in ghost-written papers by P&G had been drawn so that a proportion of the data simply "fell off" the left hand end of plots. I was supposed to have signed off on two further publications containing similar graphs and opaque statistical analysis ...... all while being refused access to underlying data codes held by P&G.

The first step of any statistical analysis is to PLOT THE DATA. Following press exposure P&G eventually released the raw data to authors in April 2006. The distribution of the actual data for NTX change (the X axis variable) in the above paper (Eastell et al 2003) for patients taking Actonel is:
A third of the data would not have appeared within the range of the Procter and Gamble graph as plotted by them (P&G's graph ends at -60%). Strange that.

The relevance of the missing end of the plot will be discussed in later postings. Suffice to say that these patients show responses more typical of the drug produced by P&G's competitor (Merck, Fosamax).

Earlier|Later|Main Page

Why pharmaceutical companies need to be prevented from researching clinical aspects of their own drugs

The past month has seen much pontification in medical journals explaining why pharmaceutical companies should no longer be allowed to control and conduct research informing the public and doctors about the efficacy and clinical use of their own drugs. The Sheffield scenario (this blog) is another reason

Here are a few excellent publicly available ones.

Review of Pfizer internal documents relating to manipulation of science and the perception of science
Annals of Internal Medicine, August 2006

Evidence of an industry out of control
Journal of the Canadian Medical Association, August 2006

From optimism to disillusion
Professor Sir Ian Chalmers, Journal of The Royal Society of Medicine, July 2006

Can We Tame the Monster? "Drug companies should not be allowed to evaluate their own products."
Fiona Godley, Editor of the British Medical Journal, July 2006

Medical journals usually bend at the first sign of a legal raised eyebrow from their corporate masters. Are we seeing the start of a new sanity, or yet more fine words?

Earlier|Later|Main Page

Procter research shenanigans 4: Befriending the red herring

Pharmaceutical companies are accused of overturning the safeguards of science. The accountability of authors is the most fundamental of these safeguards. Readers expect that authors are the authors, that they vouch for the work and would be able to defend their findings if challenged. They expect that authors would be able to provide underlying raw data.

One of the many "red herring" excuses provided by Procter & Gamble to justify refusal to supply data codes underlying ghostwritten material (statistical reports, abstracts, two draft publications) to me as first author and to the Sheffield authors of a previous publication based on a subset of the same data (Eastell et al., 2003 JBMR 18:1051-6) is discussed here. The backstory is here and here.

This particular excuse (see correspondence here) was that they :

"use the approach described in PhRMA guidelines and that in these guidelines there is not access to the data (other than those from your center) for investigators".

So, what's wrong with this excuse:

1. PhRMA (the Pharmaceutical Researchers and Manufacturers of America) is the lobbying organization for the industry. It is recipient of recent awards: The Fox Guarding the Hen House Award (for pushing toothless voluntary guidelines) and The Truth is Stranger Than Fiction Award (for a scandal involving the bribing of authors to produce a thriller as a stealth marketing tool to frighten the public (see Karasik Conspiracy). PhRMA has no authority to override ethical guidance.
   
2. Even PhRMA does not suggest research findings should be closed to scrutiny by authors, or that authors should lie to journals. The cited PhRMA suggestion is that some paid recruiters of patients in multiple-center studies might not get to share in complete data access. This has nothing to do with the rights and obligations of a principal investigator or first author.


3. Inability of a scientist to supply raw data constitutes prime facie evidence of research misconduct. Ability to provide data is an explicit condition of submission to any respectable Journal.


4. Innumerable guidelines make the obligations of authors perfectly clear. For example:
   
   • The European charter for researchers: "details of the data should be open to internal and external scrutiny"
   
   
   • The Association of American Medical Colleges affirms right of "investigator to receive, analyze, and interpret all data generated in the research, and to publish results, independent of outcome" and affirms "an investigator’s accountability for the integrity of any publication that bears his or her name", and "Institutions should not enter, nor permit a covered individual to enter, research agreements that permit a sponsor ..to interfere with an investigator’s access to the data or ability to analyze the data independently".
   
   
   • The International Committee of Medical Journal Editors (ICMJE) requirements: "researchers should not enter into agreements that interfere with their access to the data and their ability to analyze it independently" Editors may request that authors of a study funded by an agency with a proprietary interest in the outcome sign a statement, “I had full access to all of the data in this study and I take complete responsibility for the integrity of the data and the accuracy of the data analysis.”
   
   
   • The World Association of Medical Editors (WAME) state : "Authors should be asked to affirm in writing that they have not entered into an agreement with the funding organization that limited their ability to complete the research as planned and to publish the results". "Authors should state in writing that they have had full control of all primary data. Authors' should agree in writing to allow the journal to review their data if requested."
   
   
   • CIOMS state: "investigators should not enter into agreements that interfere unduly with their access to the data or their ability to analyze the data independently, to prepare manuscripts, or to publish them."
   
   
5. Concealment of raw data is contrary to the rules of any respectable University. Guidance at the University of Sheffield states:
   "research evidence should be made available to other researchers on request, prior to or following the publication of results".
   "Publication of research results does not negate the need to retain original records of research evidence"
   "evidence for research based on clinical samples or relating to public health be retained for twenty years."
   "Errors detected following the publication of results could be mistaken for research misconduct if a researcher could not subsequently provide valid corroborative research evidence."

Scientists may disagree about the presentation of data. There can be no legitimate debate when that data is not available for scrutiny even to authors.

Earlier|Later|Main Page

Procter research shenanigans 3: Research misconduct explained in one letter

Background to the dilemma involving Actonel research in Sheffield is here, here and here. The research involved a secondary endpoint in randomized trials used to demonstrate the efficacy of risedronate (Actonel) for regulatory approval. The company violated the norms of science under whose banner they claim to sell their products.

There were three elements to the problem:

1. A pharmaceutical benefactor (Proctor & Gamble) repeatedly refused to provide raw data including randomization codes to academic "collaborators". Data was required by the academics to verify scientific reports, statistical analyses, meeting abstracts (1,2), and draft publications "ghost written" in their names.


2. Data was provided to authors 3 years later, in early 2006, following press exposure. "Fair" analysis of the data would not have yielded findings desired by the sponsor.


3. There were multifaceted and intriguing attempts to prevent the problem from being raised or discussed.

A single letter summarizes problem 1:

The writer is Professor Richard Eastell, collaborator in this research, and then Research Dean of Sheffield Medical School. It was written after numerous attempts to gain access to data from the company, and after some information had emerged to suggest that the analysis performed by P&G was implausible. A publication based on overlapping data had already appeared in press (Eastell et al., 2003 J. Bone. Miner. Res. 18:1051-6) - the raw data underlying this overlapping paper had also not been disclosed to Sheffield authors (BBC broadcast).

This letter from Professor Eastell was written in response to two letters from myself here and here. Eastell's "response":

1. attempts to rationalize why it was appropriate for authors to be refused access to critical raw data


2. suggests that the first author (Blumsohn) would be removed even as a coauthor unless prepared to sign a journal declaration in the absence of data

Click here for PDF version of letter or on images above to enlarge.

Abstracts underlying intended publications

1. A. Blumsohn, IP Barton, A Chines, R Eastell Relative Contributions Of The Early Changes In Bone Resorption And Later Changes In Hip Bone Mineral Density To The Reduction In Vertebral Fracture Risk With Risedronate. [J Bone Miner Res 2003;18(S2):S157 Abst#SA337


2. A. Blumsohn, IP Barton, A Chines, R Eastell. Relationship Of Early Changes In Bone Turnover To The Reduction In Vertebral Fracture Risk With Risedronate - The HIP Study. [J Bone Miner Res 2003;18(S2):S89 Abst#F338

Earlier|Later|Main Page

Procter research shenanigans part 2: On graphs and honeybees

Misleading graphs form part of the attempt by Procter and Gamble Pharmaceuticals (P&G) to interfere with scientific evidence about their osteoporosis drug Actonel (backstory here, here and here). Several similar graphs (with supposedly supportive statistics) appeared in reports prepared by P&G based on data generated in Sheffield. They also appeared in a P&G funded publication (Eastell et al. 2003 J.Bone.Miner.Res. 18:1051-6), underpinned meeting abstracts, and two draft ghostwritten P&G publications with myself as intended first author -- all while P&G refused authors access to randomization codes and other underlying raw data.

Here is an example (from Eastell et al (2003) J. Bone. Miner. Res. 18:1051-6).



Much more of this later. However I was reminded of some correspondence in Science 30 years ago in response to a graph and statistics in a paper by Roubik (Science 1978: 201;1030).




Which prompted Robert Hazen to respond (Science 1978 202:823):



Earlier|Later|Main Page