©Sideview Ethical research publication: who’s responsibility is it? Liz Wager PhD Publications Consultant, Sideview

"A discovery does not exist until it is safely reviewed and in print" EO Wilson ( )

"Words are, of course, the most powerful drug used by mankind" Rudyard Kipling ( )

Publication matters  Trial participants expect findings to contribute to medical knowledge  Misrepresenting findings (or not publishing them at all) is unethical  But who’s responsible for ensuring good practice? ©Sideview

Research and publication ethics are a spectrum Unethical research design Data fabrication Inappropriate analysis Lack of patient consent Data falsification Image manipulation Plagiarism Redundant publication DesignAnalysisReporting Authorship abuse Conduct Selective / non- publication

Many players are (or could be) involved:  Researchers (mentors / supervisors)  Journals (editors / publishers)  Funders  Institutions  Professional / academic organizations  RECs  Regulators ©Sideview

Does the system need to change?  Half of all clinical trials are never published ©Sideview Ross et al PLOS Med 2009;e

Does the system need to change?  About 50% of studies presented at conferences never get published in full (Scherer et al JAMA 1994;272:158-62)  Cohort of RCTs submitted to Swiss REC (to 1998) 52% published by 2006 (von Elm et al Swiss Med Wkly 2008;138: )  22% of trials on CT.gov reported results within 1 year of study end (Prayle et al BMJ 2012) ©Sideview

Does the system need to change?  German drug assessment body found 74% of data on the antidepressant reboxitine was unpublished  Including the unpublished data changed their recommendation (to “ineffective and potentially harmful”) ©Sideview Wieseler et al BMJ 2010;341:c4942 Eyding et al BMJ 2010;341:c4737

Does the system need to change?  585 registered trials with >500 participants  Completed before Jan 2009  29% (171) unpublished in November 2012  Of the unpublished trials 78% did not have results posted on CT.gov  “The lack of availability of results from these trials … constitutes a failure to honor the ethical contract that is the basis for exposing study participants to the risks inherent in trial participation. Additional safeguards are needed to ensure timely public dissemination of trial data.” ©Sideview Jones et al BMJ 2013;347:f6104 published 29 Oct 2013!

©Sideview Does the system need to change?  Comparison of protocols cf publications (N=102)  Found incomplete reporting of: 50% of efficacy 65% of safety/AE outcomes  Statistically significant outcomes more likely to be reported  62% of trials had at least one primary outcome changed, introduced or omitted Chan et al JAMA 2004;291:

Change probably requires a ‘systems’ approach  Incentives  Guidelines  Training  ‘Infrastructure’ / technology ©Sideview

Many players should be involved:  Researchers (mentors / supervisors)  Journals (editors / publishers)  Funders  Institutions  Professional / academic organizations  RECs  Regulators ©Sideview

Influence on clinical trials Funding decision Publication DesignAnalysisReporting Conduct Registration Ethical approval FundersRECs Institutions Agreement / contract Regulators Publishers

Opportunities  Funders could make final payment conditional on report / publication (eg HTA)  Funders could make publication of previous projects a criterion for future funding  Institutions could reward responsible publication (quality and quantity)  Institutions should promote and enforce good authorship practices  Alternative venues for disseminating results (registers, institutional repositories, databanks, websites)* ©Sideview

alternatives to traditional journals ©Sideview

More opportunities  Institutions and professional bodies could offer training in RCR / publication ethics  Journals could require use of reporting guidelines (or develop more structured reports)  Funders, RECs, journals could require trial registration ©Sideview

New trials registered at clinicaltrials.gov May – Oct 2005 Journal policies can be effective ICJME deadline

Good news! (Sept 2013) ©Sideview

Research ethics committees could help prevent other serious problems Unethical research design Data fabrication Inappropriate analysis Lack of patient consent Data falsification Image manipulation Plagiarism Redundant publication DesignAnalysisReporting Authorship abuse Conduct Selective / non- publication

Could RECs extend their remit?  Require researchers to publish all studies (on trial register / repository / journal)  Encourage / check posting on institutional repositories / company websites  Make publication of previous projects a requirement for future approvals ©Sideview

Are RECs behaving unethically?  “The fate of scientific data is no idle issue. Reliable research syntheses depend on ensuring that as much as possible of the potentially relevant evidence is taken into account in systematic reviews... Contrary to a widely held assumption, it is investigators and some research funders—and not necessarily journal editors—who are primarily responsible for under-reporting of research … Prevention of this form of scientific misconduct must therefore involve the bodies to which investigators are answerable, in particular research ethics committees.  The consequences of under-reporting of research are that patients are being expected to accept the harmful side effects of ineffective forms of care; accept advice about the effects of health care which is based on evidence that is less complete than it should be;… and contribute to research … which may not be published if the results come as a disappointment or an embarrassment to the investigators or sponsors. ©Sideview Savulescu et al BMJ 1996;313:1390-3

Conclusions  Unethical reporting is a ‘systems problem’  Unethical reporting may harm patients, harm trial participants, waste resources  Responsible research reporting is EVERYBODY’s responsibility including RECs ©Sideview