Efficacy and safety of pharmacological, physical, and psychological interventions for the management of chronic pain in children; a WHO systematic review and meta-analysis

Emma Fisher, Gemma Villanueva, Nicholas Henschke, Sarah Nevitt, William Zempsky, Katrin Probyn, Brian Buckley, Tess E. Cooper, Navil F. Sethna, Christopher Eccleston

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Abstract

Chronic pain in childhood is an international public health problem. We conducted a systematic review and meta-analysis to provide a summary of the published evidence of pharmacological, physical, and psychological therapies for children with chronic pain conditions. We searched CENTRAL, MEDLINE, EMBASE, and PsycINFO from inception to April 2020, clinical trial registries, and other sources for randomised controlled trials or comparative observational trials. We extracted critical outcomes of pain intensity, quality of life, physical-, role-, and emotional functioning, sleep, and adverse events. We assessed studies for risk of bias and certainty of the evidence using GRADE. We included 34 pharmacological (4091 participants), 25 physical therapy (1470 participants), and 63 psychological trials (5025 participants). Participants reported a range of chronic pain conditions. Most studies were assessed to have unclear or high risk of bias across multiple domains. Pharmacological, physical, and psychological therapies showed some benefit for reducing pain, post-treatment but only physical and psychological therapies improved physical functioning. We found no benefit of any treatment modality for health-related quality of life, role functioning, emotional functioning, or sleep. Adverse events were poorly reported particularly for psychological and physical interventions. The largest evidence-base for the management of chronic pain in children supports the use of psychological therapies, followed by pharmacological and physical therapies. However, we rated most outcomes as low or very low-certainty, meaning further evidence is likely to change our confidence in the estimates of effects. This protocol was registered on PROSPERO (CRD42020172451).
Original languageEnglish
Pages (from-to)E1-E19
JournalPain
Volume163
Issue number1
Early online date19 Apr 2021
DOIs
Publication statusPublished - 1 Jan 2022

Bibliographical note

Funding Information:
The World Health Organisation financially supported the conduct of this systematic review. The authors thank the systematic reviewers at Cochrane Response, Paige Karadag and Maisoon Shah, for their help in screening articles, extracting data, and judging risk of bias for the included studies. The authors thank Joanne Abbott for conducting the database searches. The authors thank the World Health Organisation and Chairs of the Guideline Development Group for their guidance. Finally, the authors thank Bita Mesgarpour, Co-director for Cochrane Iran for helping in translating studies. Emma Fisher is funded by Versus Arthritis. Authors contributions: E. Fisher conceptualised the systematic review, screened abstracts, extracted data, assessed risk of bias and certainty of evidence, conducted analyses, and wrote the first draft. G. Villanueva contributed to study design, abstract and full-text screening, data extraction, risk of bias assessment, data analysis and interpretation, and drafting and editing the final manuscript. N. Henschke contributed to study design, abstract and full-text screening, risk of bias assessment, data analysis and interpretation, and drafting and editing the final manuscript. S.J. Nevitt provided statistical advice, assessed certainty of evidence, interpreted data, and contributed to writing the review. W. Zempsky advised on chronic pain and drug classifications, interpreted data, and contributed to writing the review. K. Probyn screened abstracts and full texts, data extraction, risk of bias assessment, and drafting and editing the final manuscript. B. Buckley screened abstracts and full texts, data extraction, risk of bias assessment, data analysis and interpretation, and drafting and editing the final manuscript. T.E. Cooper screened abstracts and full texts, extracted data, assessed risk of bias, and contributed to writing the review. N. Sethna interpreted data and contributed to writing the review. C. Eccleston oversaw the systematic review, acted as arbitrator when disagreements arose, interpreted data, and contributed to writing the review.

Funding Information:
Two studies reported conflicts of interests; Stephens et al. reported one author had received consultancy fees, speaking fees, or honoraria (less than $10,000) from Bristol Myers Squibb, and Ahlqwist et al. reported one or more of the author(s) has or have received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript and benefits will be directed solely to a research fund, foundation, educational institution, or other nonprofit organization that the author(s) has or have been associated with. Nineteen studies reported no conflicts of interest, and 4 studies did not provide a conflicts of interest statement. Seven studies did not report a funding statement, one study reported that no funding was received for the study, one study was sponsored by industry, and the remaining 16 studies were supported by government, hospital, or research charity grants.

Funding Information:
Of the 34 studies, 16 studies included an arm that was not another pharmacological intervention. When considering the funding, 18 studies did not report the source of funding for the trial. Four studies were supported by government or university funding. Eight studies were supported by pharmaceutical companies. Two studies were funded in partnership between a research foundation and pharmaceutical company. Two studies did not report funding, but we suspect they were funded by pharmaceutical companies because they thanked them in the acknowledgments or authors were employees of the company. There were 23 studies that did not report the presence of conflicts of interests in the article. Five studies explicitly reported that the authors had no conflicts of interest. Two studies did not report conflicts of interest, but one study reported that an author received consulting fees of less than $10,000 from Bristol Meyers Squibb, and in the other study, most authors were employees of Pfizer Inc. The remaining 4 studies reported conflicts of interest.

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