Declaration of transparency for each research articlea

Douglas G. Altman, David Moher

Declaration of transparency for each research articlea

Douglas G. Altman1, David Moher2

“It is the responsibility of everyone involved to ensure that the published record is an unbiased, accurate representation of research”[1].

The research record is often manipulated for short term gain but at the risk of harm to patients. The medical research community needs to implement changes to ensure that readers obtain the truth about all research, especially reports of randomised trials, which hold a special place in answering what works best for patients.

Failure to publish the findings of all studies, especially randomised trials, seriously distorts the evidence base for clinical decision making. A recent systematic review of reboxetine for treating depression found that almost three quarters of included patients were in unpublished trials [2]. Of 904 completed trials of interventions for acute ischaemic stroke (1955–2008), a fifth were not properly published, “several of which may be large enough to influence clinical practice and the findings of systematic reviews and meta-analyses” [3].

Bad as non-publication is, incomplete or misleading publications cause greater problems. Results of clinical trials published in peer-reviewed publications may differ from what was previously submitted to regulatory agencies [4–6], with the published data being more positive. The primary outcome often differs from what the researchers had stated in the trial protocol [7, 8] or clinical trial registry [9, 10]. Selective non-publication favours statistically significant findings, biasing the literature [11, 12]. Furthermore, authors often distort the presentation and interpretation of their findings. One study found that such “spin”was common in 72 reports of randomised controlled trials with statistically non-significant primary outcomes [13]. Similar findings have been reported recently for studies of the accuracy of diagnostic tests [14].

Peer review is failing to ensure that journal articles contain the key clinical and methodological details that readers need. Reviews of published reports of randomised trials have found common defiiciencies in the details of the interventions being evaluated [15, 16], participant eligibility criteria [17], and outcomes [18, 19]. Details of study methods are also often inadequate, especially in relation to allocation. A 2006 study found that only a third of trial reports described how the randomisation sequence was generated and only a quarter described an adequate method of allocation concealment [20]. A review of 357 phase III oncology trials concluded that “numerous items remained unreported for many trials”[21]. Harms, too, are poorly reported [22, 23].

The problems associated with publishing and reporting other types of research may be worse than for randomised trials. Although less intensively studied, similar concerns have been expressed in relation to epidemiology [24, 25], pharmacoepidemiology [26], diagnosis research [27], prognosis research [28], and preclinical research [29, 30]. Of course, good reporting is not the same as high-quality research, but a full and clear report allows readers to judge a study’s reliability and relevance. There are concerns that commerciallysponsored research may be more likely to remain unpublished [2–31], but when published, these trials are reported more fully [32].

So what is needed? Published research articles should provide a clear and transparent description of how researchers conducted their study and what they found. Omission of important details of methods or study conduct should be deemed unacceptable, and journals should not publish them. Although detection of some defiiciencies requires external information (for example, from a trials register or protocol), most defiiciencies are inherent in a submitted manuscript and should be detected. Despite the availability of reporting guidelines such as CONSORT [33], improvements are slow to materialise [34].

By not making results of their research easily accessible, researchers are withholding knowledge, in contravention of the Declaration of Helsinki. Not only are current practices questionable on moral and scientific grounds, failure to publish all research findings is a massive waste of scarce resources and diminishes the social value of the research [35]. Researchers and funding organisations also fail the public when research findings are published in a misleading or inadequate way. Scientifically, this harms systematic reviewers who want to aggregate all of the evidence. Reviewing a partial picture provides biased and less precise estimates of effectiveness and safety than when the full information is used, and it may compromise the identification of what works best for patients.

We have a proposal that can be acted on almost immediately. We suggest that authors should sign a publication transparency declaration (box) as part of every journal submission. The same declaration could be appropriate for submissions in other contexts – for example, to regulatory agencies.

Transparency declaration:The lead author* affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

*The manuscript’s guarantor.

Editors and editorial groups can support this initiative by updating their instructions to authors so that a completed publication transparency pledge is required as part of the submission process. We see this action as a necessary scientific analogue of the currently widespread practice of asking authors about conflicts of interest. Subsequent revelation of withheld or incorrect information would be evidence of scientific misconduct, for which various actions could be taken. We hope that this step will encourage authors to reflect more carefully on how they write their article and encourage them to check that they have adhered to relevant reporting guidelines. TheBMJ, for which one of us (DGA) is the senior statistics editor, andBMJ Openare leading the way by implementing this policy immediately. We invite other journals to do likewise and support the transparency declaration on the EQUATOR website (www.equator-network.org).

The scientific community and the public at large deserve an accurate and complete record of research; we need to make changes to ensure that we will get one. Widespread endorsement and implementation of a publication transparency declaration is one way to help get the maximum value from medical research. It will, however, have no influence on the non-publication of studies, which is a continuing disgrace.

1. PLoS Medicine Editors. An unbiased scientific record should be everyone’s agenda. PLoS Med 2009;24:e1000038.

2. Eyding D, Lelgemann M, Grouven U, H?rter M, Kromp M, Kaiser T, et al. Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. Br Med J 2010;341:c4737.

3. Gibson LM, Brazzelli M, Thomas BM, Sandercock PA. A systematic review of clinical trials of pharmacological interventions for acute ischaemic stroke (1955–2008) that were completed, but not published in full. Trials 2010;11:43.

4. Turner EH, Knoepflmacher D, Shapley L. Publication bias in antipsychotic trials: an analysis of efficacy comparing the published literature to the US Food and Drug Administration database. PLoS Med 2012;9(3):e1001189.

5. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358(3):252–60.

6. Vitry AI. Reporting of studies on new medicines in major medical journals: a case study in breast cancer. Clin Pharmacol Ther 2010;87(4):398–400.

7. Dwan K, Altman DG, Cresswell L, Blundell M, Gamble CL, Williamson PR. Comparison of protocols and registry entries to published reports for randomised controlled trials. Cochrane Database Syst Rev 2011;(1):MR000031.

8. Nankervis H, Baibergenova A, Williams HC, Thomas KS. Prospective registration and outcome-reporting bias in randomized controlled trials of eczema treatments: a systematic review. J Invest Dermatol 2012;132(12):2727–34.

9. Mathieu S, Boutron I, Moher D, Altman DG, Ravaud P. Comparison of registered and published primary outcomes in randomized controlled trials. J Am Med Assoc 2009;302(9):977–84.

10. Rosenthal R, Dwan K. Comparison of randomized controlled trial registry entries and content of reports in surgery journals. Ann Surg 2013;257(6):1007–15.

11. Song F, Parekh S, Hooper L, Loke YK, Ryder J, Sutton AJ, et al. Dissemination and publication of research findings: an updated review of related biases. Health Technol Assess 2010;14(8): 1–193.

12. Dwan K, Kirkham JJ, Williamson PR, Gamble C. Selective reporting of outcomes in randomised controlled trials in systematic reviews of cystic fibrosis. Br Med J Open 2013;3(6):e002709.

13. Boutron I, Dutton S, Ravaud P, Altman DG. Reporting and interpretation of randomized controlled trials with statistically nonsignificant results for primary outcomes. J Am Med Assoc 2010;303(20):2058–64.

14. Ochodo EA, de Haan MC, Reitsma JB, Hooft L, Bossuyt PM, Leeflang MM. Overinterpretation and misreporting of diagnostic accuracy studies: evidence of “spin”. Radiology 2013;267(2):581–8.

15. Duff JM, Leather H, Walden EO, LaPlant KD, George TJ Jr. Adequacy of published oncology randomized controlled trials to provide therapeutic details needed for clinical application. J Natl Cancer Inst 2010;102(10):702–5.

16. Glasziou P, Meats E, Heneghan C, Shepperd S. What is missing from descriptions of treatment in trials and reviews? Br Med J 2008;336(7659):1472–4.

17. Shapiro SH, Weijer C, Freedman B. Reporting the study populations of clinical trials. Clear transmission or static on the line? J Clin Epidemiol 2000;53(10):973–9.

18. Vera-Badillo FE, Shapiro R, Ocana A, Amir E, Tannock IF. Bias in reporting of end points of efficacy and toxicity in randomized, clinical trials for women with breast cancer. Ann Oncol 2013;24(5):1238–44.

19. Le Cleach L, Chassany O, Levy A, Wolkenstein P, Chosidow O. Poor reporting of quality of life outcomes in dermatology randomized controlled clinical trials. Dermatology 2008;216(1): 46–55.

20. Hopewell S, Dutton S, Yu LM, Chan AW, Altman DG. The quality of reports of randomised trials in 2000 and 2006: comparative study of articles indexed in PubMed. Br Med J 2010;340:c723.

21. Peron J, Pond GR, Gan HK, Chen EX, Almufti R, Maillet D, et al. Quality of reporting of modern randomized controlled trials in medical oncology: a systematic review. J Natl Cancer Inst 2012;104(13):982–9.

22. Bagul NB, Kirkham JJ. The reporting of harms in randomized controlled trials of hypertension using the CONSORT criteria for harm reporting. ClinExp Hypertens 2012;34(8):548–54.

23. Shukralla AA, Tudur-Smith C, Powell GA, Williamson PR, Marson AG. Reporting of adverse events in randomised controlled trials of antiepileptic drugs using the CONSORT criteria for reporting harms. Epilepsy Res 2011;97(1–2):20–9.

24. Knol MJ, Egger M, Scott P, Geerlings MI, Vandenbroucke JP. When one depends on the other: reporting of interaction in casecontrol and cohort studies. Epidemiology 2009;20(2):161–6.

25. Lee W, Bindman J, Ford T, Glozier N, Moran P, Stewart R, et al. Bias in psychiatric case-control studies: literature survey. Br J Psychiatry 2007;190:204–9.

26. Holmes MV, Shah T, Vickery C, Smeeth L, Hingorani AD, Casas JP. Fulfilling the promise of personalized medicine? Systematic review and field synopsis of pharmacogenetic studies. PLoS One 2009;4(12):e7960.

27. Zintzaras E, Papathanasiou AA, Ziogas DC, Voulgarelis M. The reporting quality of studies investigating the diagnostic accuracy of anti-CCP antibody in rheumatoid arthritis and its impact on diagnostic estimates. BMC Musculoskelet Disord 2012;13:113.

28. Kyzas PA, Denaxa-Kyza D, Ioannidis JP. Quality of reporting of cancer prognostic marker studies: association with reported prognostic effect. J Natl Cancer Inst 2007;99(3):236–43.

29. Kilkenny C, Parsons N, Kadyszewski E, Festing MFW, Cuthill IC, Fry D, et al. Survey of the quality of experimental design, statistical analysis and reporting of research using animals. PLoS One 2009;4(11):e7824.

30. Dirnagl U, Macleod MR. Stroke research at a road block: the streets from adversity should be paved with meta-analysis and good laboratory practice. Br J Pharmacol 2009;157(7): 1154–6.

31. Lundh A, Sismondo S, Lexchin J, Busuioc OA, Bero L. Industry sponsorship and research outcome. Cochrane Database Syst Rev 2012;12:MR000033.

32. Khan NA, Lombeida JI, Singh M, Spencer HJ, Torralba KD. Association of industry funding with the outcome and quality of randomized controlled trials of drug therapy for rheumatoid arthritis. Arthritis Rheum 2012;64(7):2059–67.

33. Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Br Med J 2010;340:c332.

34. Turner L, Shamseer L, Altman DG, Weeks L, Peters J, Kober T, et al. Consolidated standards of reporting trials (CONSORT) and the completeness of reporting of randomised controlled trials (RCTs) published in medical journals. Cochrane Database Syst Rev 2012;11:MR000030.

35. Chalmers I, Glasziou P. Avoidable waste in the production and reporting of research evidence. Lancet 2009;374(9683):86–9.

1. Centre for Statistics in Medicine, University of Oxford, Botnar Research Centre, Oxford, UK

2. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa Hospital –General Campus, Ottawa, ON K1H 8L6, Canada

aReproduced courtesy of BMJ Publishing Group Ltd. Cite as: BMJ 2013;347:f4796.