Clinical Trials on Crossref

Linked Clinical Trials initiative gathers momentum

Kirsty Meddings — Tue, 21 Jun 2016 00:00:00 +0000

We now have linked clinical trials deposits coming in from five publishers: BioMedCentral, BMJ, Elsevier, National Institute for Health Research and PLOS. It’s still a relatively small pool of metadata - around 4000 DOIs with associated clinical trial numbers - but we’re delighted to see that “threads” of publications are already starting to form.

If you look at this article in The Lancet and click on the Crossmark button you will see that in the Clinical Trials section there are links to three other articles reporting on the same trial: two from the American Heart Journal and one from BMJ’s Heart. Readers can navigate between these four articles in three separate journals using the Crossmark functionality- a new set of links and routes for discovery have appeared.

In another example, three articles from PLOS ONE are threaded together around a trial for the treatment of Type 1 diabetes. And here another PLOS journal, Neglected Tropical Diseases links through to a PLOS ONE article about the same trial.

If you publish in the health sciences please do consider joining this exciting initiative so that we can expand these threads and build up the metadata. Read the tech specs here or drop me an email if you have questions.

Clinical trial data and articles linked for the first time

Daniel Shanahan — Tue, 17 May 2016 00:00:00 +0000

It’s here. After years of hard work and with a huge cast of characters involved, I am delighted to announce that you will now be able to instantly link to all published articles related to an individual clinical trial through the Crossmark dialogue box. Linked Clinical Trials are here!

In practice, this means that anyone reading an article will be able to pull a list of both clinical trials relating to that article and all other articles related to those clinical trials – be it the protocol, statistical analysis plan, results articles or others – all at the click of a button.

Linked Clinical Trials interface

Now I’m sure you’ll agree that this sounds nifty. It’s definitely a ‘nice-to-have’. But why was it worth all the effort? Well, simply put: “to move a mountain, you begin by carrying away the small stones”.

Science communication in its current form is an anachronism, or at the very least somewhat redundant.

You may have read about the ‘crisis in reproducibility’. Good science, at its heart, should be testable, falsifiable and reproducible, but an historical over-emphasis on results has led to a huge number of problems that seriously undermine the integrity of the scientific literature.

Issues such as publication bias, selective reporting of outcome and analyses, hypothesising after the results are known (HARKing) and p-hacking are widespread, and can seriously distort the literature base (unless anyone seriously considers Nicholas Cage to be causally related to people drowning in swimming pools).

This is, of course, nothing new. Calls for prospective registration of clinical trials date back to the 1980s and it is now becoming increasingly commonplace, recognising that the quality of research lies in the questions it asks and the methods it uses, not the results observed.

Uptake of trial registration year-on-year since 2000

Building on this, a number of journals and funders – starting with BioMed Central’s Trials over 10 years ago – have also pushed for the prospective publication of a study’s protocol and, more recently, statistical analysis plan. The idea that null and non-confirmatory results have value and should be published has also gained increasing support.

Over the last ten years, there has been a general trend towards increasing transparency. So what is the problem? Well, to borrow an analogy from Jeremy Grimshaw, co-Editor-in-Chief of Trials – we’ve gone from Miró to Pollock.

Although a results paper may reference a published study protocol, there is nothing to link that report to subsequent published articles; and no link from the protocol itself to the results article.

A single clinical trial can result in multiple publications: the study protocol and traditional results paper or papers, as well as commentaries, secondary analyses and, eventually, systematic reviews, among others, many published in different journals, years apart. This situation is further complicated by an ever-growing body of literature.

Researchers need access to all of these articles if they are to reliably evaluate bias or selective reporting in a research object, but – as any systematic reviewer can tell you – actually finding them all is like looking for a needle in a haystack. When you don’t know how many needles there are. With the haystack still growing.

That’s where we come in. The advent of trial registration means that there is a unique identifier associated with every clinical trial, at the study-level, rather than the article level. Building on this, the Linked Clinical Trials project set out to connect all articles relating to an individual trial together using its trial registration number (TRN).

By adapting the existing Crossmark standard, we have captured additional metadata about an article, namely the TRN and the trial registry, with this information then associated with the article’s DOI on publication. This means that you will be able to pull all articles related to an individual clinical trial from the Crossmark dialogue box on any relevant article.

This obviously has huge implications for the way science is reported and used. By quickly and easily linking to related published articles, it will enable editors, reviewers and researchers to evaluate any selective reporting in the study, and help to provide far greater context for the results.

As all the metadata will be open access (CC0), with no copyright, it will also be possible to access this article ‘thread’ through the Crossref Metadata Search, or independently through an application programming interface (API). This provides a platform for others to build on, with many already looking to take the next step, such as Ben Goldacre’s new Open Trials initiative.

However, in order for this to work, we must capture as many articles and trials as possible to create a truly comprehensive thread of publications. We currently have data from the NIHR Libraries, PLoS and, of course, BioMed Central, but need more publishers and journals to join us in depositing clinical trial metadata. After all, without metadata, this is all merely wishful thinking.

Let’s hope we’re the pebble that starts the landslide.

Linking clinical trials = enriched metadata and increased transparency

Kirsty Meddings — Mon, 18 Jan 2016 00:00:00 +0000

We will shortly be adding a new feature to Crossmark. In a section called “Clinical Trials” we will be using new metadata fields to link together all of the publications we know about that reference a particular clinical trial.

Most medical journals make clinical trial registration a prerequisite for publication. Trials should be registered with one of the fifteen WHO-approved public trial registries , or with clinicaltrials.gov which is run by the US National Library of Medicine. Once registered, a trial is assigned a clinical trial number (CTN) which is subsequently used to identify that trial in any publications that report on it.

Publications that result from any one trial are likely to be released in multiple journals from different publishers and at different times, for example secondary analyses coming some time after the publication of the initial results. Cross-publisher collaboration is paramount to linking all of these publications together so that researchers, funders, and regulatory agencies can understand the whole set of results from clinical trials. With this in mind, a group of medical publishers, led by BioMedCentral, approached Crossref to establish a working group, and here, they designed an approach to address this problem: “thread” all the various documents together surrounding a clinical trial.

Updated upstream

To implement threaded publications, publishers extract clinical trial numbers from papers, or ask authors to submit those numbers to them. Publishers add the CTNs to the Crossref DOI metadata via three new fields: clinical trial number, clinical trial registry where trial is registered, and trial stage (pre-results, results or post-results of the trial). Crossref has assigned unique IDs to each trial registry (much the same as we have done for funders in our Funder Registry and for the same reason - trial registry names and URIs can change over time and we need a persistent identifier). Using a combination of trial registry ID and clinical trial number, we can easily identify other content in the Crossref database that cites the same trial. Finally, Crossref displays the clinical trial metadata on the respective papers for all participating Crossmark publishers. Crossmark is a convenient place for readers to access the clinical trial information and is readily accessible directly from the journal article (online and PDF versions). And of course all of the data also goes into our open API so that anyone can make use of it.

The reporting of clinical trial results is notoriously inconsistent, something that the AllTrials initiative is also seeking to address. Publishers can help by collecting this information upstream and disseminating it using the existing Crossref infrastructure.

We ask all publishers to deposit the clinical trial data which is so critical to transparency in this area of research, and have already had the first data in from Crossref member the National Institute of Health Research. Once we launch the initial set of linked clinical trials, we will expand coverage of the threaded publications to include all content that reports on or references a clinical trial, from protocol to results to supporting data and systematic reviews.

Stay tuned and watch this space as threaded publications rolls out to journal articles across publishers!