Pediatricians need to provide the best treatment available for children and their families but are possibly less skilled than trialists or clinical researchers in appraising scientific literature, especially if they work in busy settings.
Bambino Gesù Children’s Hospital, where I’ve worked since 2001, is the biggest pediatric hospital in Rome, Italy. It has 607 beds, 40 specializations, and during a year, 27 thousand hospitalizations, 77 thousand outpatient procedures, 1.4 million outpatient visits, 72 thousand emergency room admissions, and 28 thousand surgical procedures, including heart, liver and kidney transplantations.
My every day mission in the hospital is to identify results from well-designed published clinical trials and encourage other busy pediatricians to appraise the evidence-based literature critically and reliably
My every day mission in the hospital is to identify results from well-designed published clinical trials and encourage other busy pediatricians to appraise the evidence-based literature critically and reliably.
To facilitate this task, along with a group of national and international experts and without pharmaceutical industry sponsorship, I set up an annual workshop in my hospital in 2003, named G.A.L.I.L.E.O. (Group for Appraising Literature and Implementing Levels of Evidence in hOspitals), as well as weekly hospital meetings on critical appraisal.
Discrepancies between pediatric clinical trial registries and published reports
What originally prompted me to look into suspected discrepancies between what pediatric clinical trial registry (CTR) records and published randomized controlled trial (RCT) reports?
It was simple; pediatricians need to know about and critically appraise possible discrepancies in reporting when seeking reliable evidence from trials to guide their day-to-day clinical practice.
Our research, published today in Trials, is the first effort to try to score discrepancies in pediatric clinical trials.
The paper shows the long journey we made. In an unfunded research project lasting about 3 years, we critically appraised 20 pediatric RCTs.
We assessed discrepancies across six reporting domains: funding and conflicts of interests, sample size, inclusion and exclusion criteria or cross-over, primary and secondary outcomes, early study completion, and main outcome reporting.
We found major and widely ranging discrepancies between what CTR records and published pediatric RCT reports
We found major and widely ranging discrepancies between what CTR records and published pediatric RCT report, including changes in the original study hypotheses, trial designs, study conduction and reporting outcomes (across all 20 RCTs). These findings raise concerns about whether published scientific pediatric research can be accepted at face value.
As well as highlighting trial fallacy, our study should stimulate users to investigate how the clinical research protocols progressed from trial registration to publication.
Investigating published, scientific, pediatric research more closely, as we have done, by mapping and coding information from clinical trial registries to the published literature has a major disadvantage: it takes time and skill.
How can we best identify and score these discrepancies?
First, we could include new reporting domains, for example, was a change in trial design justified in the published RCT results?
Second, we could reduce the time spent in weighting trials, by exploiting our method for scoring discrepancies in hospital smart-web support systems.
Third, we need to validate our scoring method by analyzing a larger RCT sample from other high impact factor journals and assess inter-observer reliability for the different assessor times.
What next for the field?
We encourage pediatricians to use the CTR-RCT discrepancy scoring method we propose to obtain more reliable scientific evidence on therapeutic options and to think more critically.
We encourage pediatricians to use the clinical trial registry-randomized controlled trial discrepancy scoring method we propose to obtain more reliable scientific evidence on therapeutic options and to think more critically.
We hope our paper also stimulates developers of guidelines and systematic review researchers to use our CTR-RCT discrepancy scoring method, thus alerting journal editors to possible CTR-RCT discrepancies and so as to decide what the final trial publication should state.
Last, we want to stimulate International Regulators to require editors to include in the RCT publications, along with the CTR number, possible reporting domain discrepancies; refusing papers from researchers who are unable to produce software databases supporting their reporting outcome, introducing explicit criteria that require investigators to submit the original institutional review board-approved protocol and explain any changes, and allocating research funds, such as awards that will stimulate researchers to report their findings completely.
We recommend others to consider these proposals to provide greater transparency in pediatric research, and across all research.
I want to thank Franz Porzsolt, Gabriella Ricciotti, Giuseppina Testa, Rita Inglese, Ferruccio Giustini, Ersilia Fiscarelli, Marco Zazza, Cecilia Carlino, Valerio Balassone, Roberto Fiorito and Roberto D’Amico, Director of the Cochrane, Italy, for their great help and support in conducting this research.