DEPARTMENT HEALTH INNOVATION AND RESEARCH INSTITUTE GHENT UNIVERSITY HOSPITAL

WETENSCHAPPELIJKE INTEGRITEIT

Prof. Dr. Catherine Van Der Straeten, MD, PhD, FIOR Diensthoofd Health Innovation & Research Institute UZ Gent DEFINITIE WETENSCHAPPELIJKE INTEGRITEIT: FWO • niet helemaal hetzelfde als onderzoeksethiek. • Integriteit: aspecten van kwaliteit van de wetenschapspraktijk en haar resultaten. • Ethiek: normen en waarden met het oog op welzijn van mensen en dieren in het onderzoek en de resultaten daarvan. e.g. data vervalsen, zonder onmiddellijk mens of dier in gevaar te brengen: = geen integere wetenschap, resultaten zijn onbetrouwbaar direct onethisch gedrag tegenover mens, dier en hun milieu. • Het toepassen van die gemanipuleerde resultaten kan uiteindelijk toch mensen, dieren en hun omgeving schaden: integriteit en ethiek nooit volstrekt te scheiden. • In de ruime betekenis van ethiek is vervalsen van onderzoeksresultaten of knoeien met wetenschap onaanvaardbaar. Wetenschappelijke integriteit is dus te beschouwen als een bijzondere dimensie van wetenschappelijke ethiek. 2 UGENT

3 SCIENTIFIC INTEGRITY: DEFINITIE KUL

Scientific or academic integrity = conducting scientific research in a careful, reliable, controllable, reproducible, repeatable, objective, neutral, independent way. Authenticity is of great importance.

Principles of scientific integrity: • integrity of authorship • correct citing of peers • mentioning acknowledgements • mutual respect, e.g. equal contribution in group work • transparency • veracity Replication Minimise breaches • authenticity Collaboration Identify when they occur Peer review ⎬

4 ‘Truth nowadays is not what is, but what others can be brought to accept’

Michel de Montaigne 1533-1592

Elsevier Editorial on World Conference on Research Integrity 2016 The Oxford English Dictionary: • fraud = “wrongful or criminal deception intended to result in financial or personal gain” • deceit = “the action or practice of deceiving someone by concealing or misrepresenting the truth.” Research organizations and literature define these behavioral patterns within the umbrella title of “Research Misconduct”. “Behaviour by a researcher, intentional or not, that falls short of good ethical and scientific standard.” UK Committee on Public Ethics (COPE): misconduct = the “intention to cause others to regard as true that which is not true.”

6 7 WETENSCHAPPELIJKE FRAUDE OF WANGEDRAG

8 9 USA Office of Research Integrity (ORI): FFP model:

10 TAXONOMY OF RESEARCH MISCONDUCT

11 12 13 Academic pressure Personal desire for fame “Sloppy” science Financial gain Inability to determine right from wrong

Careerism is the cause of much research fraud 14 “PUBLISH OR PERISH” 16 17 18 Time Magazine: one of “100 people who matter in 2004”

19 20 21 Recente opmerkelijke gevallen van wetenschapsfraude Nederland en België

• De Vrije Universiteit (VU) in Amsterdam wil het hele oeuvre van professor ruimtelijke economie Peter Nijkamp laten onderzoeken, vanwege mogelijk plagiaat. Hieronder een overzicht van recente gevallen van wetenschapsfraude. • Januari 2014: De VU wil het werk van Peter Nijkamp, zeker honderden publicaties, laten beoordelen op (zelf)plagiaat. Aanleiding voor het onderzoek is ophef rond een proefschrift van een promovenda die Nijkamp tot voor kort begeleidde. Daarin zou sprake zijn geweest van zelfplagiaat van het werk van de promovenda zelf en van Nijkamp. • September 2013: Gepensioneerd hoogleraar aan de Vrije Universiteit Mart Bax heeft in tientallen van zijn publicaties verzinsels opgeschreven. Ook hebben een boel prestaties van hem in werkelijkheid niet plaatsgevonden. Dat concludeert een onderzoekscommissie van de Amsterdamse universiteit in een rapport. Verdenking van fraude kwam in oktober 2012 naar voren. • Augustus 2013: Het LUMC in Leiden ontslaat een Belgische onderzoekster van de afdeling reumatologie, nadat uit intern onderzoek blijkt dat zij laboratoriumonderzoek heeft gemanipuleerd. Het medisch centrum trekt twee wetenschappelijke publicaties van haar terug. • Maart 2013: Een Belgische professor die in eigen land op staande voet is ontslagen, blijkt ook verbonden te zijn geweest aan de Universiteit Leiden, als gastmedewerker. Zijn rol in Leiden zou ‘heel beperkt’ geweest zijn, volgens de universiteit. De biomedicus deed onderzoek naar epilepsie. • Juni 2012: De Erasmus Universiteit in Rotterdam maakt bekend dat twee wetenschappelijke artikelen worden teruggetrokken van professor Dirk Smeesters. De hoogleraar Consumentengedrag en Samenleving zou data zodanig geselecteerd hebben dat de gezochte effecten statistisch significant werden. Smeesters heeft zelf ontslag genomen. • November 2011: Het Erasmus MC in Rotterdam maakt bekend dat hoogleraar Don Poldermans is ontslagen wegens schending van de wetenschappelijke integriteit. De internist en vasculair geneeskundige zou gegevens hebben gefingeerd en bij verschillende studies zouden onregelmatigheden gevonden zijn of data niet meer te achterhalen. • November 2011: Het Universitair Medisch Centrum St Radboud in Nijmegen maakt bekend dat een senior onderzoeker zijn ontslag heeft ingediend, nadat is gebleken dat hij oncontroleerbaar en mogelijk onjuist heeft gehandeld bij het verzamelen van onderzoeksgegevens. De onderzoeker was betrokken bij een onderzoek naar pijnbeleving bij patiënten. • September 2010: De Tilburgse hoogleraar sociale psychologie Diederik Stapel blijkt op grote schaal te hebben gefraudeerd met onderzoeksgegevens. Drie commissies bestuderen zijn publicaties en komen tot de conclusie dat hij met zeker 55 artikelen en 10 boekhoofdstukken heeft gefraudeerd. Bij 10 artikelen, waarvan er twee ook als hoofdstuk in een boek zijn gepubliceerd, bestaat een sterk vermoeden van fraude. In juni 2013 schikt Stapel met justitie: hij accepteert een werkstraf van 120 uur en verliest het recht op een aantal uitkeringen, ter waarde van circa 1,5 jaarsalaris. 22 ̶ Yoshitaka Fujii (Japan), an anesthesiologist, was found to have fabricated data in at least 183 scientific papers, setting what is believed to be a record for the number of papers by a single author requiring retractions. A committee reviewing 212 papers published by Fujii over a span of 20 years found that 126 were entirely fabricated, with no scientific work done. Only 3 were found to be valid. He was also found to have forged the signatures of scientists he listed as co-authors without their knowledge.[67][68][69] ̶ Alfredo Fusco (Italy), a cancer researcher at the University of Naples, has since 2012 been under criminal investigation for fraud, including manipulation of images in his published studies.[70][71] Fusco has had 21 of his publications retracted.[72] ̶ Dong-Pyou Han (US), former assistant professor of biomedical sciences at Iowa State University, added human antibodies to samples of rabbit blood in an effort to falsely enhance the utility of an experimental HIV vaccine.[73][74] In 2015 Han was sentenced to nearly five years in prison and ordered to return $7.2 million to the NIH.[75] ̶ Marc Hauser (US), an evolutionary biologist and former Professor of Psychology at Harvard University, was found by a University committee and the US Office of Research Integrity to have fabricated and falsified data in his research.[76][77][78][79] ̶ Friedhelm Herrmann and Marion Brach (Germany), formerly of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, admitted to fabricating data in their research on cancer. [80][81] Herrmann has had 21 of his publications retracted.[82] ̶ Woo-suk Hwang (Hwang Woo-suk) (South Korea), former Professor of Biotechnology at Seoul National University, was found by a University committee to have committed "deliberate fabrication" in his research on stem cells, and to have coerced female members of his research team to donate their eggs.[83] In 2009 Hwang was found guilty by the Seoul Central District Court of embezzlement and bioethical violations in connection to his research program.[84][85] ̶ Sophina ("Sophie") Jamal (Canada), former Professor of Medicine at University of Toronto and former staff Endocrinologist at Women's College Hospital, Toronto, falsified data from studies of nitroglycerin compounds in osteoporosis.[86] Results published in the Journal of the American Medical Association (JAMA) in 2011 were retracted by the Journal in 2016.[87] In 2016 Jamal received a lifetime funding ban from the Canadian Institutes of Health Research,[88][89] and in 2018 had her license to practice medicine revoked by the College of Physicians and Surgeons of Ontario in 2018.[90] ̶ Santosh Katiyar (US, India), former associate professor at the University of Alabama, Birmingham and the Birmingham VA Medical Center who investigated the effects of "natural products" upon cancer, was in 2017 dismissed from his academic positions following an institutional investigation that found evidence of image manipulation in 20 of his research papers, all of which UAB has called to be retracted.[91][92][93] Katiyar has had 12 of his research papers retracted.[94] ̶ Kim Tae-kook (South Korea), formerly of the Korea Advanced Institute of Science and Technology, falsified research on modulating cellular proteins with the synthetic compound CGK733.[95][96] ̶ Gideon Koren (Canada), former Director of the Motherisk Program at The Hospital for Sick Children in Toronto, published an article without the informed consent of co-author Nancy Olivieri, and sent her anonymous harassing letters.[97][98] A December 2018 article in The Toronto Star reported apparent problems in more than 400 papers coauthored by Koren, including "inadequately peer-reviewed, failed to declare, and perhaps even obscure, conflicts of interest, and, in a handful of cases, contain lies about the methodology."[99] Koren has threatened a defamation lawsuit against the editor of Therapeutic Drug Monitoring for retracting one of Koren's papers.[100] ̶ Steven A. Leadon (US), former professor of radiation oncology and head of the molecular radiobiology program at the University of North Carolina, falsified and fabricated data in his research on DNA repair.[101][102][103] Leadon has had seven of his research papers retracted.[104] ̶ Paolo Macchiarini (Sweden, Italy), a thoracic surgeon and researcher formerly at the Karolinska Institutet, was in 2017 found by an ethics review board to have committed research misconduct, including false claims of clinical success and falsely claiming ethical approval for his surgical interventions, in his work on the surgical implantation of artificial trachea seeded with patients' own stem cells.[105][106][107] The review board recommended that six of Macchiarini's publications be retracted.[108] Macchiarini has had five of his research papers retracted, and two have received an expression of concern.[109] ̶ William McBride (Australia), a physician who discovered the teratogenicity of thalidomide, was found by an Australian medical tribunal to have "deliberately published false and misleading scientific reports and altered the results of experiments" on the effects of Debendox/Bendectin on pregnancy.[110][111][112] ̶ Michael W. Miller (US), former Professor and Chair of Neuroscience at SUNY Upstate Medical University, falsified data in research publications, one manuscript submitted for publication, and four grant applications.[116][117][118] Miller has had three of his research publications retracted.[119][120] ̶ H.M. Krishna Murthy (US), a protein crystallographer and former research associate professor at the University of Alabama at Birmingham, was found in 2009 by a University committee to be "solely responsible for ... fraudulent data" on protein structures published in nine papers.[123][124] In 2018 the Office of Research Integrityplaced a 10-year ban on Federal funding for Murthy.[125] As of 2019 ten of Krishna Murthy's publications have been retracted.[126] ̶ Haruko Obokata and Yoshiki Sasai of RIKEN (Japan) falsified data in the widely-publicized STAP cell fraud.[127] Obokata has had three research papers retracted,[128] and Sasai has had two papers retracted.[129] ̶ Luk Van Parijs (US), former Associate Professor at the Massachusetts Institute of Technology (MIT) fabricated and falsified data in research papers, unpublished manuscripts, and grant [130] [131] applications. He was convicted in 2011 of making a false statement on a federal grant application. Parijs has had five research publications retracted. 23 ̶ Malcolm Pearce (UK), former senior consultant and obstetrician at St George's Hospital in London, falsified his claims of successful reimplantation of an ectopic pregnancy,[132][133] and fabricated a study on the effects of Human chorionic gonadotrophin on pregnancy outcome.[134] ̶ Milena Penkowa (Denmark), a neuroscientist and former Professor at the Panum Institute of the University of Copenhagen, was in 2010 convicted of fraud and embezzlement of research funds, and in 2012 was found to have committed "deliberate scientific malpractice."[135][136][137] In 2017 the University of Copenhagen revoked Penkowa's doctoral degree,[138] and as of 2019 she has had seven of her publications retracted.[139] ̶ Eric Poehlman (US), a former Professor in the Department of Medicine at the University of Vermont, was convicted in 2005 of grant fraud after falsifying data in as many as 17 grant applications between 1992 and 2000. He was the first academic in the United States to be jailed for falsifying data in a grant application.[140][141] Poehlman has had seven of his publications retracted.[142] ̶ Anil Potti (US), a former Associate Professor of Medicine at Duke University, engaged in "by including false research data in ... published papers, [a] submitted manuscript, [a] grant application, and the research record."[143][144] Potti's misconduct resulted in the suspension of three clinical trials based on his research and a lawsuit filed against Duke by patients enrolled in those studies.[145] Potti has had 11 of his publications retracted.[146] ̶ Azza El-Remessy (US), a former Associate Professor of the University of Georgia College of Pharmacy, falsified Western blot data in published manuscripts.[147][148] El-Remessy has had six research papers retracted, three papers corrected, and two papers attached to an expression of concern.[149] ̶ Scott Reuben (US), a former Professor of Anesthesiology at Tufts University, falsified and fabricated clinical trials involving painkiller medications.[150][151] Reuben pleaded guilty in 2010 to one count of health care fraud and was sentenced to six months in prison.[152] Reuben has had 25 of his publications retracted.[153] ̶ José Román-Gómez (Spain), a leukemia researcher at the University of Córdoba (Spain) who has been described as "a serial image manipulator/misappropriator," altered and misappropriated gel images from the work of others for his own published papers.[154][155][156][157] Román-Gómez has had six of his publications retracted.[158] ̶ Steven S. Rosenfeld (US), a former Harvard undergraduate, forged letters of recommendation for himself in the name of David Dressler, whose laboratory he used. His research on transfer factor, on which two articles were published in the Proceedings of the National Academy of Sciences and one article in Annals of Internal Medicine, could not be successfully replicated by other scientists.[159][160] ̶ Robert Ryan (UK), formerly of the University of Dundee, was found by a University committee in 2016 to have committed research misconduct in his work on molecular bacteriology.[161] Four of Ryan's publications have been retracted.[162] ̶ Fazlul Sarkar (US), a pathologist formerly at Wayne State University, was in 2015 found by a University committee to have "engaged in and permitted (and tacitly encouraged) intentional and knowing fabrication, falsification, and/or plagiarism of data, and its publication in journals, and its use to support his federal grant applications."[163] Sarkar, who in 2015 lost a lawsuit he brought against the University of Mississippi (and other defendants) after a job offer there was rescinded,[164] and who in 2016 lost a defamation lawsuit he brought against anonymous critics of his work,[165] has had 40 of his publications retracted, and at least a dozen others corrected.[166][167] ̶ Yoshihiro Sato (Japan), a researcher in osteoporosis at Mitate Hospital in Tagawa, published more than 200 papers involving 33 clinical trials, of which 30 trials have been retracted (as of August 2018) either by Sato or by the journals.[168] As of 2019 Sato has had 51 publications retracted.[169] ̶ Eric J. Smart (US), a former nutrition researcher, associate professor, vice-chairman of the Department of Pediatrics and the Barnstable-Brown Chair in Diabetes Research at the University of Kentucky, was in 2012 found by the US Office of Research Integrity to have committed scientific misconduct over a period of 10 years by falsifying data in 10 published papers and seven grant applications.[170][171][172] Smart has had eight of his publications retracted.[173] ̶ Alfred Steinschneider (US), a medical doctor formerly based at Upstate Medical University, in 1972 developed the theory, published in the journal Pediatrics (journal), that SIDS was caused by prolonged Sleep apnea,[174][175] although none of his research or research conducted subsequently by others supported the theory.[176][177][178] The case-study upon which Steinschneider's theory was based was later revealed to involve Infanticide committed by the mother, with Steinschneider allegedly having ignored evidence and reports that the children were being abused.[179][180] In 1997 the editor of Pediatrics (journal), Jerold Lucey, stated that Steinschneider's original paper on the subject was "seriously flawed" and should not have been published.[181] ̶ Marc Straus (US), former Chief of Oncology and Associate Professor of Medicine at Medical Center, in 1982 admitted to "serious deficiencies," including the use of false data, in research studies he supervised. He also admitted to using ineligible patients in his studies, administering drug dosages different from those in his plan, and not assuring compliance with rules of informed consent.[182][183][184] ̶ Jon Sudbø (Norway), an oncologist and former Associate Professor at the University of Oslo, was found in a 2006 investigation to have manipulated and fabricated data in grant applications and 15 of his research papers.[185][186][187] Sudbø has had 12 of his publications retracted.[82] ̶ Akio Sugino (Japan), a former molecular biologist and professor at Osaka University, was dismissed from the University following an investigation that revealed he fabricated research data in two of his papers.[188][189][190] ̶ William Summerlin (US), a dermatologist formerly at Memorial Sloan-Kettering Cancer Center, in 1974 committed scientific misconduct in his work on transplant immunology.[191][192] It was from this case that the phrase "painting the mice" originated as a synonym for research fraud.[193][194] ̶ Kazunari Taira (Japan), formerly of the biochemistry and biotechnology department at the University of Tokyo, was found by a University committee to have faked experiments on RNA interference.[195][196][197][198] Taira has had five research papers retracted.[199] ̶ (UK), a former practicing physician and senior lecturer at the Royal Free Hospital in London, was found guilty of dishonesty in his research and banned from medicine by the UK General Medical Council following an investigation by Brian Deer of the London Sunday Times.[200] Wakefield's claims of a link between the MMR vaccine, autism and inflammatory bowel disease have been reported in the British Medical Journal as "based not on bad science but on a deliberate fraud,"[201] and the 1998 paper originally presenting his theory was retracted in 2010 by .[202][203] Wakefield was unsuccessful in an attempt to sue detractors/critics for libel and defamation.[204][205] Wakefield has had two papers retracted and one corrected.[206] ̶ Weishui Y. Weiser (US), a former Assistant Professor of Medicine at Harvard Medical School, falsified data supported by two Public Health Service (PHS) grants.[207][208]Weiser has had at least four publications retracted.[209] ̶ Industrial Bio-Test Laboratories fabricated research data to the extent that upon FDA analysis of 867 studies, 618 (71%) were deemed invalid, including many of which were used to gain regulatory approval for widely used household and industrial products.[210][211] ̶ Researchers at St. Jude Children’s Research Hospital retracted a 2012 paper published in Surgery in 2016 after an internal investigation determined that an image used in the paper was fabricated. The investigation was sparked by other scientists who questioned the paper’s claim to have presented the molecular underpinnings of how a form of curcumin could reduce the growth of neuroblastoma.[212] The official retraction stated, “The irregularities in Figure 3E have been investigated by the co-authors and St. Jude Children’s Research Hospital, and the investigation concluded that the image was fabricated. We therefore retract the publication.”[213] 24 ̶ Anna Ahimastos-Lamberti (Australia), a former medical researcher, admitted to fabricating scientific results published in numerous major international medical journals.[4] As a result, two journal articles about a three-year clinical trial involving a medication used to treat hypertension were retracted.[5][6] ̶ Bharat Aggarwal (US), a former Ransom Horne, Jr. Distinguished Professor of Cancer Research at the University of Texas MD Anderson Cancer Center,[7] resigned his position after fraud was discovered in 65 papers published by him in the area of curcumin as a treatment for cancer.[8] Aggarwal has had 28 of his publications retracted.[9] ̶ Elias Alsabti (Iraq, US), was a medical practitioner who posed as a biomedical researcher. He plagiarized as many as 60 papers in the field of cancer research, many with non-existent co-authors.[10][11][12] ̶ Piero Anversa (US, Italy) and Annarosa Leri (US, Italy), collaborators and former researchers at Harvard University, were found in a 2014 investigation to have "manipulated and falsified" data in their research on endogenous cardiac stem cells, and to have included "false scientific information" in grant applications; these events resulted in Partners HealthCare and Brigham and Women's Hospital paying a $10 million settlement to the US government, and pausing a clinical trial based on Anversa and Leri's work.[13][14][15] In October 2018, following many failed replications of their work, Harvard University and Brigham and Women's Hospital called for the retraction of 31 publications from the Anversa/Leri research group;[16] as of December 2018, 14 of Anversa and Leri's publications have been retracted.[17] Anversa and Leri lost a lawsuit they brought against Harvard that claimed the 2014 investigation had damaged their reputations.[18] ̶ Edward Awh and graduate student David Anderson (US), formerly of the University of Oregon, retracted nine of their publications due to data fabrication.[19][20] This included an action identified by The Scientist (magazine) as a Top 10 Retraction of 2015.[21] ̶ Werner Bezwoda (South Africa), formerly of the University of Witwatersrand, admitted to scientific misconduct in trials on high-dose chemotherapy on breast cancer, stating that he had "committed a serious breach of scientific honesty and integrity."[22][23][24] ̶ Philippe Bois (US), a former postdoctoral fellow in biochemistry at St. Jude Children’s Research Hospital was found by the Office of Research Integrity to have used misleading data for one image in a 2005 Journal of Cell Biology paper and completely faked another image in a Molecular and Cellular Biology article published the same year. The JCB paper was retracted later in May 2007 and the MCB paper was corrected.[25] ̶ Joachim Boldt (Germany), an anesthesiologist formerly based at the Justus Liebig University Giessen, was stripped of his professorship and criminally investigated for forgery in his research studies.[26] Boldt has had 96 of his publications retracted.[27] ̶ C. David Bridges (US), a researcher at Purdue University and formerly at Baylor College of Medicine, was found by a NIH investigation panel to have stolen ideas from a rival's manuscript that Bridges had been asked to review, and used that information to produce and publish his own research.[28][29] The investigating panel described Bridges' conduct as "an egregious misconduct of science that undermines the entire concept and practice of scientific experimentation and ethical responsibility,"[30] with NIH later stripping Bridges' of his funding.[31] ̶ Silvia Bulfone-Paus (Germany, UK), an immunologist at the Research Center Borstel and the University of Manchester, has had 13 of her publications retracted following investigations of alleged scientific misconduct involving image manipulation.[32][33] ̶ Ranjit Chandra (Canada), former nutrition researcher at Memorial University of Newfoundland and self-proclaimed "father of nutritional immunology,"[34] was in 2015 stripped of his Order of Canada membership following accusations of scientific wrongdoing in his research.[35] In 2015 Chandra lost a $132 million case against the CBC, which in 2006 presented a documentary in which 10 of Chandra's publications were identified as “fraudulent or highly suspicious;”[36] Chandra was ordered to pay the CBC $1.6 million to cover the defendant's legal fees.[37] At least four of Chandra's publications have been retracted.[38] ̶ Ching-Shih Chen (US), the former chair of cancer research at The Ohio State University, was investigated by OSU and the federal Office of Research Integrity after being anonymously reported for falsifying data. The investigation found that he falsified information in at least 11 publications, and that he did not keep any laboratory notebooks on his research, a violation of federal research policies.[39][40] ̶ Carlo M. Croce (US), an oncologist and professor of medicine at Ohio State University, has been the subject of several allegations of scientific misconduct, including data falsification, and related institutional investigations.[41][42][43] Croce has filed lawsuits against critics,[44] including a defamation lawsuit against David Sanders (biologist) of Purdue University[45] and a defamation claim against that in 2018 was largely dismissed,[46] and has also sued OSU to reclaim a department chair position from which he was removed.[47] Croce has had nine of his publications retracted and 15 others corrected.[48] ̶ John Darsee (US), a cardiologist formerly based at Harvard University, fabricated data in published research articles and more than 100 abstracts and book chapters.[49][50] In 1983 Darsee was disbarred for ten years by the US National Institutes of Health.[51] Darsee has had at least 17 of his publications retracted.[52] ̶ Dipak Das (US), former director of the Cardiovascular Research Center at the University of Connecticut Health Center, was found in a University investigation to be guilty of 145 counts of fabrication or falsification of research data.[53] Das has had 20 of his publications retracted.[54] ̶ Evan B. Dreyer (US), former Associate Professor of Ophthalmology at Harvard University Medical School, reported falsified and/or fabricated experimental results in manuscripts and grant applications. In 2000 Dreyer was blocked for 10 years from receiving NIH-sponsored research grants.[55][56][57] ̶ Richard Eastell (UK), a medical doctor and Professor at the University of Sheffield, was found in a 2009 General Medical Council hearing to be negligent in making "untrue" and "misleading" declarations involving a trial of the osteoporosis drug Actonel.[58] Eastell had in 2006 resigned as director of research at Sheffield National Health ServiceTrust following allegations of "financial irregularities" connected to his research program.[59][60][61] ̶ Masoumeh Ebtekar (Iran), head of the Iranian Department of Environment at Tarbiat Modares University in Tehran, substantially plagiarized several previously-published articles in a 2006 paper that was later retracted.[62][63] ̶ Terry Elton (US), Professor of Pharmacology at Ohio State University, was found guilty of scientific misconduct by both a University committee and the Office of Research Integrity.[64][65] Elton has had seven of his publications retracted.[66]

486 Chinese cancer researchers were found guilty of engaging in a fraudulent peer-review scheme by China’s Ministry of Science and Technology. The investigation was initiated after the retraction of 107 papers published in Tumor Biology between 2012 and 2016. This is reported to be the most papers retracted from one journal. 25 RESEARCH MISCONDUCT META-ANALYSES

• 1) Fanelli (PLOS 2009): “scientific behaviors that distort scientific knowledge”: - 2% of the scientists admitted to serious misconduct at least once - up to 34% admitted other questionable research practices. - When participants were asked about their colleagues’ practices, results even higher:14% for falsification and 72% for other questionable practices - only a conservative estimate of the real prevalence of research misconduct

• 2) Ranstam et al. (J Med Ethics 2007): study of biostatisticians: - majority of respondents reporting at least one serious breach of fraudulent projects in the past 10 years.

26 Mostly retracted for scientific misconduct RETRACTION INDEX

All retractions Medline 1982-2002 – English total retracted = 395: 27.1% misconduct – 61.8% errors RETRACTED PUBLICATIONS PUBMED Search 20th October 2019

Search 21st October 2019

‘59-’99: n = 651

‘00-’19: n = 6439 (91%) 28 MISCITATIONS

As claims get cited they become facts

29 30 Fig 1. Self-citation rates as functions of author age as measured by prior publication count (top S panels). E L F C I T A T I O N Mishra S, Fegley BD, Diesner J, Torvik VI (2018) Self-citation is the hallmark of productive authors, of any gender. PLOS ONE 13(9): e0195773. https://doi.org/10.1371/journal.pone.0195773 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195773 Niet PER SE verkeerd wanneer belangrijke, relevante referentie ZELFPLAGIAAT

CITATIEPUSHING

32 ‘A HANDFUL OF PEER-REVIEWED JOURNALS SET THE AGENDA’ Michael Pollan (1955), Professor of Science and Environmental Journalism, UCBerkeley • Journal Ranking by the Institute for Technical Information (ISI) • Essential Science Indicators (ESI): Thomson Scientific Web Base > ranking scientists, institutions, countries, journals • “Impact Factor” = IF (E.Garfield, 1955) > Scientific Citation Index (SCI) SCI = frequency with which an article has been cited in a particular year IF = Number of all citations of art. from a particular journal during previous 2 years divided by the total nr of articles in that journal in those 2 years • Highest IF Biomedical 2017: Cell (31.398), Science (37.250), Nature (41.577), NEJM (79.258) DISADVANTAGES AND LIMITATIONS TO RANKING WITH CITATION INDEX & IMPACT FACTOR IR J OS ‘01 ̶ Bias from editors who know submitting authors ̶ “Padding effect”: experts only cite one another ̶ “Halo effect”: prominent scientists in prominent institutions are more likely to be published ̶ Potentially brilliant research from unknown scientist/institution may not be recognized ̶ IF inappropriate for assessment of journal quality ̶ IF inappropriate for assessment of individual author quality ̶ Self-citation rate: may be pushed by journals to enhance their IF “SALAMI SLICING”: “ONE IN 13 “ORIGINAL” ARTICLES IN THE JBJS ARE DUPLICATE OR FRAGMENTED PUBLICATIONS”

e.g. 22 papers on Oxford Nuffield Centre series of 19 patients with adverse local tissue reaction to metal debris from hip resurfacing 36 Scientific misconduct by violating ethical standards

ICH GCP THE TUSKEGEE SYPHILIS EXPERIMENT

• Clinical study between 1932 - 1972 in Tuskegee, Alabama, by the U.S. Public Health Service.

• 400 impoverished black males with syphilis were offered "treatment" by the researchers, who did not tell the test subjects that they had syphilis and did not give them treatment, but rather just studied them to chart the progress of the disease.

• By the end of the study in 1972: only 74 of the 399 test subjects were alive, 28 had died of syphilis, 100 of related complications, • 40 of their wives had been infected • 19 of their children were born with congenital syphilis

• The study was not shut down until 1972, when its existence was leaked to the press. Holmesburg Prison Experiment from 1951 to 1974: injection of dioxine into 70 prisoners, mostly black in order to study the effect of herbicides on the skin

LSD and ‘truth serum’ experiments Ken Kesey, auteur van One flew over the cuckoo’s nest

40 “The Declaration of Geneva of the WMA is based on the Oath of Hippocrates (5th C BC). It binds the physician with the words, “The health of my patient will be my first consideration,”

“No national or international ethical, legal or regulatory requirement should reduce or eliminate any of the protections for research subjects set forth in this Declaration.” SCIENTIFIC MISCONDUCT VS UNINTENTIONAL MISTAKES • Misconduct: - falsification, fabrication, deletion of data - plagiarism, false authorship, false funding • Unintentional error: - sampling, procedures, data analysis - failure to reproduce findings - omission of info on methods, analysis

• Selection bias • Performance bias (placebo effect) • Detection bias (outcome assessment) • Underpowered studies • Reporting bias (selective reporting) • … UNINTENTIONAL ERRORS René Magritte (1898-1967)

43 CONFIRMATION BIAS

Associative thinking versus causality World-wide recall of Rofecoxib (Vioxx®) 30.09.04

§ Intermediate results of the APPROVe study 2004: - severe CV incidents 3.5% in Vioxx group vs 1.9% in placebo (p<0.001) § VIGOR Study 2000-2001: rofecoxib vs naproxen - Vioxx: increased risk MI vs naproxen group - explanation: cardioprotective effect of naproxen § Recall of some Cox-2 NSAIDS

Rofecoxib INDUSTRY SPONSORED LITERATURE Short- term studies > quick publication • In peer-reviewed journals: sponsoring must be stated clearly • Industry sponsored journals • White papers, handouts… • Product “literature” > often by ghost writers > no peer review – no Quality Control > quickly posted on internet THE INTERNET “Like with the weather, everyone complains of the quality of information on the Internet, but nobody does anything: neither phenomenon seems to be controllable” ̶ Easy access to quantity of info but no quality control ̶ Concealed publicity ̶ No legislation, no funding, no peer review ̶ Social media: premature advertising via twitter, FB, YouTube .. ̶ Patients: weblogs, chatgroups pressure 48 49 50 WHAT CAN JOURNAL EDITORS DO?

• Detect scientific misconduct • Prevent publication misconduct • Educate authors • Promote good practices • Inform employers and authorities • Correct literature

51 RESPONSIBLE AUTHORSHIP On the issue of authorship, progress has been made. The International Committee of Medical Journal Editors (ICMJE) published the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publications, defining the rules for authorship credit as being based upon meeting all three criteria below:

• 1) substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; • 2) drafting the article or revising it critically for important intellectual content; • 3) final approval of the version to be published.

52 RESPONSIBLE AUTHORSHIP: ICMJE general requirements : attest originality of article – review by co-authors ̶ Uniform Requirements for Manuscripts (www.icmje.org) ̶ Vancouver system for citing references ̶ No duplicate publication in other journal ̶ Description of individual contribution of authors ̶ RCT should comply with CONSORT statement ̶ Study protocol as approved by EC included ̶ All documents of relevance available for min 10yrs ̶ Systematic reviews / meta-analyses consensus statement • There is a perception that results published in high impact factor journals are automatically dependable. • Moreover, untimely retractions could result in the propagation of inaccurate information in other works. • Education and training of individual researchers and supervisors is crucial to combating misconduct, • as well as creating an environment for whistleblowers to speak out. (Wilmhurst)

54 U G E N T

55 Tell the truth and ruin your career

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