As part of PLOS ONE’s 10th anniversary celebrations, for our latest interview with Editorial Board Members who have joined the journal when it was first launched, we met with neurobiologist Björn Brembs. Björn Brembs is based
Emphasizing the fact that clinical trials can influence treatment decisions, the recent AllTrials campaign has called for all trials past and present to be registered, and the results reported. As one of the initiating organisations behind this initiative, PLOS is committed to continuously developing and adopting policies that might help rectify publication bias in the trials literature. Following in the footsteps of PLOS Medicine, this campaign has led the editorial staff at PLOS ONE to re-evaluate how we handle unregistered trials.
Previously, in line with the International Committee of Medical Journal Editors (ICMJE) policy and like several other journals, we required all clinical trials that began after July 1, 2005 to be registered prospectively (before patient recruitment) in a publicly available registry approved by the World Health Organization (WHO). To stress the need for prospective registration, papers that did not fulfill these criteria were rejected, but this potentially prevented the results of some trials from being published. Thus while we still expect prospective registration to be standard practice, as of today, we will also consider retrospectively registered clinical trials to help ensure the medical community has access to the results of these trials.
These retrospectively registered clinical trials must however meet the following criteria:
1) The trial must be registered in a WHO-approved registry before submission to the journal
2) The authors must explain the reason for late registration within the methods section of the manuscript
3) They must include a statement confirming that all ongoing or future related trials are registered
As a reminder, when determining what constitutes a clinical trial, PLOS ONE follows the WHO’s definition: “a clinical trial is any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes.” The ICMJE further clarifies that “health-related interventions include any intervention used to modify a biomedical or health-related outcome (for example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and process-of-care changes). Health outcomes include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events”.
The ICMJE also recommends that if scientists are unsure whether their trial meets the above definition, they should err on the side of registration.
We believe that while prospective trial registration remains the gold standard, this change in policy will be a positive step towards increased transparency and accountability and is in line with another recent initiative supported by PLOS ONE, the RIAT (Restoring Invisible and Abandoned Trials) initiative. This is also in accordance with the core values of the journal to publish all papers, including studies reporting negative results, provided they are technically sound and done to high scientific and ethical standards.
Image: by NHS Confederation on Flickr
Last month PLOS ONE attended the ISMB/ECCB 2013 conference in Berlin on Intelligent Systems for Molecular Biology. More than 1,500 delegates attended what is the largest conference on computational biology in the world to discuss the latest developments in computational methods that address biological questions.
The opening keynote from PLOS ONE Academic Editor Gil Ast focused on alternative splicing, a mechanism by which several mRNA transcripts are generated from the same mRNA precursor, thus enhancing transcriptome and proteome diversity. He mentioned a paper his group published earlier this year in PLOS ONE, in which they showed that pre-mRNA splicing influences nucleosome organization, suggesting that there is a bi-directional interplay between chromatin organization and splicing. While it is widely accepted that chromatin organization and DNA modification regulate transcription, it is intriguing that splicing can in turn affect chromatin organization, and this may constitute an additional layer of regulation of gene expression. He also presented exciting recent findings showing how pre-mRNA splicing and the creation of new exons in the human genome may be linked to certain genetic disorders and types of cancers.
Understanding the biology of complex human disease is also one of Goncalo Abecasis’s objectives, winner of the ISCB 2013 Overton Prize. Specifically, he is interested in better understanding genetic variation and its connections to human diseases using computational methods and statistical tools. In his talk, he emphasized that the identification and characterization of the genetic variants that affect human traits may be achieved by examining the link between these traits and the complete genome sequences of thousands of individuals. To collect DNA from as many people as possible, he wondered whether we should make use of social media to call for volunteers to send their DNA samples. Are Facebook and Twitter the key to understanding human genetics?
One topic that generated much discussion at the meeting was data sharing. In her talk, Carole Goble called for all scientists to share their data widely as to enable reproducibility, a principle underpinning the scientific method. Several journals, including PLOS ONE, require that all data (including all relevant raw data) described in the manuscript be made freely available to any scientist wishing to use them for the purpose of academic, non-commercial research. Well established and widely supported public repositories already exist for certain types of data such as nucleic acid sequences, and in cases where an appropriate repository does not exist, there are also general data repositories such as Dryad. Assigned accession numbers or digital object identifiers (DOIs) facilitate data citation and ensure accountability. An increasing number of research funding agencies also now support data sharing in the life sciences. Whilst there is indeed increasing discussion to make primary data from published research publicly available, Goble mentioned a paper by Ioannidis and colleagues showing that a substantial proportion of articles published in high-impact journals do not comply (or only weakly comply) with data availability requirements. According to Goble, a lack of data sharing, and thus reproducibility, could lead to an increase in retracted scientific papers.
She also urged the computational biology community to release their “dark data”, i.e. data that is not published and remains hidden on various USB drives and computers, the point being that if shared more people will be able to use these results, increasing visibility, accountability and reproducibility. As highlighted by a recent study, data sharing is not an end in itself, but rather a crucial form of scientific knowledge dissemination.
Keren-Shaul H, Lev-Maor G, Ast G (2013) Pre-mRNA Splicing Is a Determinant of Nucleosome Organization. PLoS ONE 8(1): e53506. doi:10.1371/journal.pone.0053506
Alsheikh-Ali AA, Qureshi W, Al-Mallah MH, Ioannidis JPA (2011) Public Availability of Published Research Data in High-Impact Journals. PLoS ONE 6(9): e24357. doi:10.1371/journal.pone.0024357
Wallis JC, Rolando E, Borgman CL (2013) If We Share Data, Will Anyone Use Them? Data Sharing and Reuse in the Long Tail of Science and Technology. PLoS ONE 8(7): e67332. doi:10.1371/journal.pone.0067332
Wikimedia by Angelineri
Modified from Schwartz S, Oren R, Ast G (2011) Detection and Removal of Biases in the Analysis of Next-Generation Sequencing Reads. PLoS ONE 6(1): e16685. doi:10.1371/journal.pone.0016685
Next week PLOS ONE will join PLOS Computational Biology at the ISMB/ECCB 2013 International Society for Computational Biology meeting held this year in Berlin, Germany, July 21-23.
The world’s largest bioinformatics/computational biology conference will bring together scientists from computer science, molecular biology, mathematics, statistics and other related fields to discuss the development and application of computational methods for biological questions. Keynote speakers include David Eisenberg, Gary Stormo, Lior Pachter, and PLOS ONE Academic Editor Gil Ast.
Whether you are interested in joining our Editorial Board or just want to talk about the journal or open access in general, please stop by the PLOS booth (booth #13)!
Academic Editors: If you are also attending, please get in touch ahead of the meeting with Associate Editor Christna Chap to schedule a meeting.
We hope to see you in Berlin!
Image: Salipante SJ, Sengupta DJ, Rosenthal C, Costa G, Spangler J, et al. (2013) Rapid 16S rRNA Next-Generation Sequencing of Polymicrobial Clinical Samples for Diagnosis of Complex Bacterial Infections. PLoS ONE 8(5): e65226. doi:10.1371/journal.pone.0065226