PONE-D-20-33147

An observational cohort study comparing ibuprofen and oxycodone in children with fractures

PLOS ONE

Dear Dr. Ali,

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: No

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: The authors report a well written paper on an interesting paper. However, the study design cannot support their conclusions. The administration of oxycodone was decided by the physician and this could lead to important bias. Moreover, the lack of blindness is a further important potential bias. An RCT would be the appropriate study design for the purposes of the authors' study. However, if the authors want to consider data from an observational study design, a propensity score analysis should be performed.

Reviewer #2: Ali and coll. made a prospective observational cohort study to compare the effectiveness and safety of ibuprofen and oxycodone for at-home management of an isolated fracture pain in 329 children aged 4-16 years (n=217 ibuprofen, n=112 oxycodone). They found that ibuprofen and oxycodone have similar analgesic effectiveness for at-home fracture pain, but oxycodone was associated with more adverse events and negatively impacted function. The study is well conducted and the topic is of interest while confirmatory of the efficacy and safety of ibuprofen for fracture-related pain.

My only concern regards the presence of a selection bias in the administration of oxycodone in children with a more severe fracture. In fact, oxycodone was more often prescribed in fractures needing procedural sedation and reduction, and in fractures later referred to the orthopedic surgeon. Also, more fractures involving the upper leg/hip, suspected for being higher energy injuries, were reported in the oxycodone group, while buckle fractures, low energy trauma, were fewer. This might suggest that fractures deemed clinically more important were selected into this group. This bias could also explain the more frequent use of adjuvant medications during the first 3 days in the oxycodone group compared to the ibuprofen group and, as a consequence, the higher adverse events incidence in children treated with oxycodone.

In my opinion, this study weakness, which is part of its observational nature, should be more highlighted and discussed.

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Reviewer #1: No

Reviewer #2: Yes: Simone Lazzeri

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Attachments

Attachment

Submitted filename: Comments to the Authors.docx

Attachment

Submitted filename: Response to the Editors.docx

An observational cohort study comparing ibuprofen and oxycodone in children with fractures

PONE-D-20-33147R1

Dear Dr. Ali,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Simone Lazzeri

Guest Editor

PLOS ONE

Additional Editor Comments (optional):

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Reviewers' comments: