“The registration of all interventional trials is a scientific, ethical and moral responsibility” – World Health Organization (WHO)
New research published today in Systematic Reviews suggests that the full potential of clinical trials registries is not being realized in the conduct of systematic reviews. The results revealed that only 35% of researchers used clinical trials registries in their search strategy; however, more than three quarters identified at least one completed or ongoing trial for inclusion.
Systematic reviews are the pinnacle of medical evidence available for clinical decision making. One of the greatest challenges a systematic reviewer faces is identifying all relevant studies for inclusion. Without an exhaustive sample of relevant studies the validity of the conclusions will be questionable.
Identifying and assessing all the relevant studies for inclusion in systematic reviews is not a simple task; it involves extensive literature searches as well as other resources available that might uncover relevant studies. Unfortunately, the medical literature is plagued with selective publication (where completed trials aren’t published) and selective reporting (where only some of the trial outcomes are reported). Without the full picture of what clinical trials have been done and what the results were, researchers cannot produce complete systematic reviews.
It is here that registries (part of what is referred to as the ‘gray literature’) would help.
Why such a focus on registries?
Recent changes to laws and policies mean registries are becoming one of the most comprehensive resources for identifying clinical trials. The first calls for trial registration were heard in the 1980s. In 2004, after a couple of decades of selective hearing on most accounts, the International Committee of Medical Journal Editors (ICMJE) announced that prospective registration of all clinical trials would be a prerequisite for publication of any trial. This was followed by the World Medical Association Declaration of Helsinki update in 2008, which states, “Every clinical trial must be registered in a publically accessible database”.
The United States (US) Food and Drug Administration (FDA) Amendment Act of 2007, and the more recent European Union (EU) Clinical Trials Regulation, which comes into effect in 2016/2017, both require the prospective registration of interventional clinical studies in the US and EU, respectively. Not only do these laws mandate the prospective clinical trial registration but both state that summary results must be posted within one year of trial completion, regardless of outcome.
By putting the existence of a clinical trial into the public domain, along with details such as primary outcomes and trial design, registries have the potential to not only identify trials for inclusion in a systematic review but also aid in the evaluation of the risk of bias within identified studies and between studies, two important steps of the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) checklist, used as the standard for systematic review reporting.
The current situation
Christopher Jones and colleagues’ study, published today in Systematic Reviews, highlights that this major resource for identifying clinical trials is being underutilized. The cross-sectional analysis analyzed systematic reviews of medical interventions published in the ‘big six’ medical journals (AIM, BMJ, JAMA, the Lancet, NEJM and PLoS Med) between July 2012 and June 2013. Only 35% described searching a registry in their methods.
Of the 29 reviews that included registry search details, 79% found at least one completed (but unpublished) or ongoing study for inclusion, with a median of two studies identified per systematic review (though this ranged from 0 to a substantial 49 studies).
Missing this number of studies could have a real impact on the effect estimate cited in a systematic review.
Registries have the capability to truly enhance systematic review search strategies. Many guidelines reference the use of registries in comprehensive searches and their use is commonly thought of as good practice during gray literature searches.
Clinical trials registries give us the ability to identify completed and ongoing trials that haven’t had results published, along with the potential to identify reporting bias by comparing the registry record and published record. Therefore, with registry utility, systematic review results can be discussed in a more accurate context of the current evidence.
Registries are evolving; new legislations aren’t just calling for registration itself, but also posting of results, updates on the numbers of patients recruited and details of statistical analysis plans, to name but a few.
As the usability and information registries hold develops they will become an even greater asset during systematic review trial searches. Even now, the WHO is calling on people to comment on their official statement on public disclosure of clinical trial results and how this will link to their International Clinical Trials Registry Platform.
This is a movement with momentum; clinical trial transparency is at the forefront of many people’s agendas and it looks like developments will increase both the usability and accessibility of clinical trials registries.
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