Original ArticleSearching ClinicalTrials.gov did not change the conclusions of a systematic review
Introduction
The underlying principle of systematic reviews is a consideration of all relevant available evidence. As standards have developed on how to conduct and report systematic reviews, an Achilles heel has remained: are we really considering all available evidence? Missing relevant information in systematic reviews because of reporting bias, such as publication bias and outcome reporting bias, may lead to biased and incorrect conclusions. Systematic review guidelines, such as the Cochrane Handbook and the Agency for Healthcare Research and Quality's Methods Guide, recommend searching for trials through registries, such as ClinicalTrials.gov, to assess and possibly ameliorate the effects of reporting bias [1], [2].
We sought to assess the effect of searching ClinicalTrials.gov on the conclusions and strength of evidence grading of a systematic review.
Section snippets
Methods
We conducted this study concurrently with a systematic review on the effectiveness of treatment options for symptoms of diabetic peripheral neuropathy. Our protocol for this case study can be found at www.effectivehealthcare.ahrq.gov [3].
Search results
There were 81 randomized controlled trials from the published literature search of the concurrent systematic review [4]. Our search of ClinicalTrials.gov yielded 266 records. Of these, 53 records met the inclusion criteria (Fig. 1). From both the peer-reviewed literature and ClinicalTrials.gov, we included a total of 106 trials that evaluated pharmacologic interventions to treat the symptoms of diabetic peripheral neuropathy. Thirty trials were identified in both the peer-reviewed literature
Discussion
We identified 53 trials comparing the effectiveness of treatment options for symptoms of diabetic peripheral neuropathy by searching ClinicalTrials.gov. However, most of the identified trials had no results posted in the registry to inform our conclusions or evidence grades in the concurrent systematic review.
We noted discrepancies between the 30 ClinicalTrials.gov records and their matched publications in terms of the number enrolled, the reported primary outcome, outcomes results, and adverse
Conclusion
In this case study, our search of ClinicalTrials.gov was mostly useful in bolstering the suspicion of reporting biases but did not meaningfully change either the conclusions or the strength of evidence grading of a systematic review. Further research is needed to determine the usefulness of searching ClinicalTrials.gov on the conclusions and strength of evidence grading for systematic reviews across different topic areas and as the new rules for reporting results in ClinicalTrials.gov are
Acknowledgments
The authors would like to thank the other authors of the “Effectiveness and Treatment Options for the Prevention of Complications and Treatments of Symptoms of Diabetic Peripheral Neuropathy, including Wendy L. Bennett, MD, MPH; Allen Zhang, BS; Suzanne Amato Nesbit, PharmD, BCPS, CPE; Hsin-Chieh Yeh, PhD; Yohalakshmi Chelladurai, MD, MPH; and Dorianne Feldman, MD, MSPT, for sharing the results of their systematic review.
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Funding: This project was funded under contract no. 290-2015-00006I-2 from the Agency for Healthcare Research and Quality and U.S. Department of Health and Human Services. The authors of this manuscript are responsible for its content.
Statements in the manuscript should not be construed as endorsement by the Agency for Healthcare Research and Quality (AHRQ) or the U.S. Department of Health and Human Services. AHRQ retains a license to display, reproduce, and distribute the data and the report from which this manuscript was derived under the terms of the agency's contract with the author.