Disclosure of negative trial results. A call for action Annalisa Capuano a, ⁎, Andrew J.S. Coats b , Cristina Scavone a , Francesco Rossi a , Giuseppe M.C. Rosano c,d a Second University of Naples, Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology L. Donatelli of Medicine and Surgery, Naples, Italy b Monash University, Australia and University of Warwick, UK c IRCCS San Raffaele, Roma, Italy d Cardiovascular & Cell Sciences Institute, St George's University of London, UK article info Article history: Received 1 June 2015 Accepted 27 June 2015 Available online 02 July 2015 Keywords: File drawer effect Clinical trial Withholding results In the past few years the scientific community has discussed on how to tackle research misconduct. However, little progress has been made in another important and relevant issue that can lead to incorrect as- sessments to be on the clinical efficacy of treatments, the reporting of negative clinical trials. Today the ethical scientific community is confronted with two urgent tasks: to ensure that negative clinical trial results are published and to prevent such results ending up filed “in a drawer”. The “file-drawer effect” influences publication of research results more than rejection by journals [1]. The “file drawer effect” is the non- reporting of results, often negative or neutral, from clinical trials in a specific area of research. This phenomenon is of extreme relevance as studies not published could potentially give different results from those that are published and alter the overall perception of the results of a treatment in a given treatment area [1]. It may even be possible that a given treatment is ineffective but that is only those of studies that by chance show that a statistically signifi- cant result is published, while the remaining trials where the null hy- pothesis was not rejected are not published. This will lead to the endorsement of the benefit of the treatment even though a true benefit is not there. There is evidence to support that editors tend to reject research where the results are not statistically significant. Furthermore, it has been suggested that clinical trials with significant positive results had International Journal of Cardiology 198 (2015) 47–48 ⁎ Corresponding author. E-mail address: annalisa.capuano@unina2.it (A. Capuano). a higher probability of being included in meta-analyses than studies showing negative results [2]. Dickersin investigated the association between trial characteristics, findings, and publication of NIH funded trials and found that trials with “significant” results were 12 folds more likely to be published than those showing “non-significant” results. Of interest, no other factor was positively associated with publication [3]. The trend to publication bias, the so called “positive-outcome bias”, is very common because reviewers and editors are less likely to publish negative results and findings that are not statistically significant. Issues related to publication bias enclose under-reporting research and hyper- claiming and concern the investigators who manipulate the actual re- sults of their research in order to get published [1,3]. Withholding results are an example of misconduct research which can result in the use of drug therapies that are harmful, ineffective, un- ethical, and expensive; since clinical research that doesn't confirm the expected benefits of those treatments and their related clinical trial data remain unpublished [4]. Moreover, underreporting research is not only restricted to the investigator's failure to report negative results, but also to the failure to report the results with enough detail to allow a full assessment of their validity. In order to improve the quality of published data and, at the same time, allow a full understanding of research findings, it has been sug- gested that investigators should in particular report their methods and analyses; in that way, reviewers can draft reasonable conclusions about the external validity of their research findings [5]. Of course, the majority of clinical trials are sponsored by the pharmaceutical industry and funding sources can exert considerable pressure on scientists to suppress or minimize inconclusive results and reports of adverse effects. The key to avoiding underreporting and hyper-claiming research should be to motivate investigators to submit all good quality studies for publication and, to contribute to the education of journal editors, re- viewers, and investigators alike that null or negative findings are as im- portant as positive ones. For all the above mentioned reasons, the only consideration underlying the decision to publish a trial should be the quality of the study design and conduct [6]. In truth, it seems that the scientific literature is mainly oriented towards positive results, some of which by such a selection may prove to be misleading, while the neg- ative result trails that reflect truly negative treatment effects are vanishing. Thus the “ethical scientific community” has a responsibility to change this situation. http://dx.doi.org/10.1016/j.ijcard.2015.06.157 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard