Joao LOBO ANTUNES

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World Conference On Research Integrity J Lobo Antunes MD PhD FACS Lisbon, 16-19 September, 2007 “TO PUBLISH OR NOT TO PUBLISH: COMMUNICATING SCIENCE IN A NEW GLOBAL AND FINANCIAL ENVIRONMENT”

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“Philosophical Transactions: giving some Accompt of the Present Undertakings, Studies and Labours of the Ingenious in Many Considerable Parts of the World” March 6, 1665 “... That a proper person might be found out to discover plagiarys and to assert inventions to their proper authors” Henry Oldenburg (1617-1677) founder of Royal Society

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Between 1665 and 1666 Isaac Newton on retreat at his country estate invented calculus which he called the method of fluxions and fluents, but did not feel the need to publish it. He rather preferred to write his “New theory about light and colors” published in the Philosophical Transactions on Feb. 19, 1672 Newton (1643-1727)

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In 1675, while in Paris, Gottfried Wilhelm Leibniz independently invented calculus and the notations still used today. We waited ten years to publish it. Leibniz (1646-1716)

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In mean time Newton wrote very kindly of Leibniz: (his method) “is certainly extremely elegant and would sufficiently display the writer’s genius even if he should write nothing else”. However, he concealed some of his own data, “Because I cannot proceed with the explanation now. I have prefered to conceal it thus: 6 accdoe 13 eff 7i 319 n 404 qrr 4s8t 12ux”. (He translated this 20 years later!)

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Newton – “Commercium Epistolicum” Leibniz – “Charta Volans” In 1711 the CALCULUS WAR exploded

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“TO STUDY, TO FINISH, TO PUBLISH” Benjamim Franklin

Science does not exist until it is published.: 

Science does not exist until it is published. Drummond Rennie. Lancet 1998;352:SII18

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“The artist’s communication is linked forever with its original form, that of the scientist is modified, amplified, fused with the ideas and results of others, and melts into the stream of knowledge.” Max Delbrück (1906-1981) Nobel speech, 1969

“The Audit Society”: 

Publications are fundamental units of information exchange, proof of productivity and creativity, and bases for future research and development Academic promotion Productivity (quantity) Independence (first or senior authorship) Significance (impact factors) “The Audit Society”

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The record Paul Erdös 1400 papers, 500 co-authors?

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27% of the scientific papers are never cited Papers published Papers published in Nature 1999 citations in 2001 – 10 % (80 papers) = half of citations 1955 – 1987 55.7% 79,9% A few interesting numbers… 30 million 1 citation no more than 4 If 2/3 of accepted papers were replaced by 2/3 of the rejected, the quality of the journal would not alter (Adair et al. Phys Rev Letters 43:1969, 1979)

There are more >16000 medical journals : 

There are more >16000 medical journals Authors/article and Editors do NEJM Manuscripts submitted to NEJM Drummond Rennie. Lancet 1998;352:SII18

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972 authors 2 words/author

The Politics of Publication*: 

The journal more important than the message The craze for publicity Salami publication – Minimal Publishable Unit (MPU) Some tips – trendy stock phrases (“paradigm”) Short letter to Nature or report to Science better than full article in a more specialized journal * Peter Lawrence. Nature 422:259, 2003 The Politics of Publication* – tenous link to human disease

The Malefices of Covert Duplicate Publication: 

The Malefices of Covert Duplicate Publication Ondasetron on post-operative emesis 9 trials published in 14 further reports duplicating data from 3325 patients Inclusion of duplicate data in meta-analysis led to a 23% overestimation of the drugs antiemetic efficacy Tramer et al. Brit Med J 315:635, 1997 Example

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Pub Med 2000-2002 400,000 78 retracted articles (0.02%)

33% admitted one or more of the top 10: 

B. C. Martinson et al Scientists behaving badly Nature 435:737, 2005 33% admitted one or more of the top 10 Response rate Mid career 52% Early career 43%

Why do they cheat: 

Why do they cheat Hunger for scientific reputation and the esteem of colleagues The passionate belief in the truth and significance of a theory or hypothesis which is disregarded or not believed Peter Medawar “Scientific Fraud” In “The threat and the Glory” Sidney Brenner “My life in Science” Is the product of the work structure, because we now have a managerial structure There is the problem of the scientist who gets hold of an idea that he then falls in love with and can’t let go 1915-1987 1927-

The Peer-review system : 

The Peer-review system JAMA 9% Academic Medicine 15% Nature 5% but indispensable Remote Mysteriously Crude Understudied – Confirmatory bias Bias against negative results Give disproportionate credit to the already famous Orientation and theoretical persuasion Conflicts of interest [competitors antagonists] Agreement between referees 10-15% 86% of unpublished trials have negative results 45% of published trials have negative results The politically correct Blinding is not the solution. The authors can be guessed in 46% of manuscripts! (JAMA 272: 143, 1994) Gate-Keepers Rate of acceptance The pitfalls

Pressure to publishUnhealthy competition?: 

Pressure to publish Unhealthy competition? “They chose reviewers who they knew to be positive (...) They did not allow their experiments to be reproduced” Robert Laughtin (Nobel Prize physics) “Given the exciting claims made by the papers, we were certainly hoping that the outcomes would be positive” Karl Ziemeli (Chief physical sciences editor, Nature) The Schön Scandal

The Editors’ Pressure: 

The Editors’ Pressure Manipulation of the impact factor of the journal, encouraging the citation of other papers published in the journal (*) and yet “Impact factors tell you more about sociology of science than about science itself” S. Brenner (*) (M. Farthing, Science and Engineering Ethics 12:45-52, 2006)

Pressures To Delay or Prevent Publication: 

Pressures To Delay or Prevent Publication The values Communalism Shared ownership Free exchange of methods and results The pressures Personal – competion for priority, recognition and funding External – commercial patenting Forbidden knowedge

Competing goals in medical research: 

Academic investigators – Industry – Competing goals in medical research Publication in peer-reviewed journals Approval and marketing of drug. Without approval, publication is not worth a cent. Publication in prestigious journals important for the marketing No drug company gives away its stockholders’ money in an act of desinterested generosity Journal of Commercial Molecular Biology Journal of Commercial Neurobiology Sidney Brenner “My life in Science”

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Amount (dollars) Therapeutic effect. A news report on angiostatin and endostatin’s promise did wonders for WEntreMed’s stock

Industry support of biomedical research : 

Industry support of biomedical research USA 1980 32% 2000 62% Lead authors 1 every 3 articles hold relevant financial interests.* In biomedicine, with rare exceptions, is the private sector, not academics that develops diagnostic, therapeutic and preventive products and brings them to market. 2/3 of academic institutions hold equity in “start-up” businesses that sponsor research by their faculty * Quoted in Bekelman et al. JAMA 289:454, 2003

Study biases: 

Companies may design studies more likely to favor their products Testing in healthier populations (younger, fewer existing or associated pathologies and milder illnesses) (NSAID – 2.1% of patients younger than 65)* Comparing with insufficient doses of competing product Include many surrogate endpoints and publish results only of those that favor the product. Study biases * Rochon et al. Arch Intern Med 154:157, 1984

Data withholding: 

Data withholding 58% of life science companies that report academic research refrain to publish for more than 6 months Data withholding more frequent in human genetics Higher publication rates <> withholding Scientists in training are discouraged to show data Blumenthal et al Jama 277: 1220, 1997 Blumenthal et al. Acad Med 81: 137, 2006 42% genetic 38% other life sciences

Preventing Publication: 

Preventing Publication The study of bioequivalence of different thyroid preparations (7 year delay) “The infamous case of Dr. Nancy Olivieri” deferiprone (iron-chelation) in thalassaemia (*) Rennie JAMA 277:1238, 1997 (**) Olivieri et al. N Eng Med J 339:417, 1998 Examples Boots – Knoll pharmaceutics (*) Apotex Inc. (**)

A convenient omission: 

A convenient omission A 4x increase in heart atacks was ommitted The journal sold 929.000 offprints (Revenue $ 679.000 to $ 836,000)

Sponsorship, authorship, and accountability: 

(The Editors of Ann Int Med, JAMA, New England J Med, Canad MAJ, J Danish M A, Lancet, Medline, etc, Sep 2001) When authors submit manuscript they are responsible for disclosing all financial and personal relationships that might bias their work Researchers should not enter in agreements that interfere Their access to the data Ability to analyze data independently Prepare manuscripts Publish them Sponsorship, authorship, and accountability

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Science June 8th 2007

Forbidden knowledge : 

Forbidden knowledge How to build your own atomic bomb * How to modify Influenza virus to relase snake venom Ten easy modifications of the E.coli genome How to modify small pox to counteract the smallpox vaccine How to build self guiding, low flying air plane using inexpensive aircraft computer, GPS and a notebook computer * Nate Ciccolo, 15 year-old high school student built a papier-maché model very accurate. He found 563 web pages on atomic bomb design! (Adapted from Ray Kurzweil: “Promise and Peril” in “Living with the Genie, ed Alen Ligthman et al. 2003) Articles we would rather not see published

Forbidden Knowledge : 

Forbidden Knowledge Inacessible, unattainable Prohibited by religious, moral or secular authority Dangerous, destructive Fragile, delicate Double – bound Ambiguous Consciousness, free will Reproductive clonning, stem cell research Atomic bomb, bioweapons Particles & waves afected by the act of observation “Knowledge about a thing is not the thing itself” (W.James) The “political” science (adapted from Roger Shattuck “Forbidden Knowledge”, 1996)

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“Scientific” has become an all purpose term of epistemic praise meaning “strong, reliable, good” and yet... like all human enterprises it is thoroughly fallible, imperfect, uneven in its achievements, often fumbling, sometimes corrupt, and of course incomplete

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“Many people say that is the intellect which makes a great scientist. They are wrong: it is character” Albert Einstein