Systematic reviews that include only published data may overestimate the effectiveness of analgesic medicines for low back pain: a systematic review and meta-analysis

Matthew K Bagg; Edel O'Hagan; Pauline Zahara; Benedict M Wand; Markus Hübscher; G Lorimer Moseley; James H McAuley

doi:10.1016/j.jclinepi.2019.12.006

Systematic reviews that include only published data may overestimate the effectiveness of analgesic medicines for low back pain: a systematic review and meta-analysis

J Clin Epidemiol. 2020 Aug:124:149-159. doi: 10.1016/j.jclinepi.2019.12.006. Epub 2019 Dec 6.

Authors

Matthew K Bagg¹, Edel O'Hagan², Pauline Zahara³, Benedict M Wand⁴, Markus Hübscher³, G Lorimer Moseley⁵, James H McAuley⁶

Affiliations

¹ Neuroscience Research Australia, Randwick, NSW 2031, Australia; Prince of Wales Clinical School, University of New South Wales, Kensington, NSW 2052, Australia; New College Village, University of New South Wales, Kensington, NSW 2052, Australia. Electronic address: m.bagg@neura.edu.au.
² Neuroscience Research Australia, Randwick, NSW 2031, Australia; Prince of Wales Clinical School, University of New South Wales, Kensington, NSW 2052, Australia.
³ Neuroscience Research Australia, Randwick, NSW 2031, Australia.
⁴ School of Physiotherapy, The University of Notre Dame Australia, Fremantle, WA 6959, Australia.
⁵ Neuroscience Research Australia, Randwick, NSW 2031, Australia; IIMPACT in Health, University of South Australia, SA 5000, Australia.
⁶ Neuroscience Research Australia, Randwick, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, Kensington, NSW 2052, Australia.

PMID: 31816418
DOI: 10.1016/j.jclinepi.2019.12.006

Abstract

Objective: Systematic reviews of analgesics for low back pain generally include published data only. Obtaining data from unpublished trials is potentially important because they may impact effect sizes in meta-analyses. We determined whether including unpublished data from trial registries changes the effect sizes in meta-analyses of analgesics for low back pain.

Study design and setting: Trial registries were searched for unpublished data that conformed to the inclusion criteria of n = 5 individual source systematic reviews. We reproduced the meta-analyses using data available from the original reviews and then reran the same analyses with the addition of new unpublished data.

Results: Sixteen completed, unpublished, trials were eligible for inclusion in four of the source reviews. Data were available for five trials. We updated the analyses for two of the source reviews. The addition of data from two trials reduced the effect size of muscle relaxants, compared with sham, for recent-onset low back pain from -21.71 (95% CI: -28.23 to -15.19) to -2.34 (95% CI: -3.34 to -1.34) on a 0-100 scale for pain intensity. The addition of data from three trials (one enriched design) reduced the effect size of opioid analgesics, compared with sham, for chronic low back pain from -10.10 (95% CI: -12.81 to -7.39) to -9.31 (95% CI: -11.51 to -7.11). The effect reduced in the subgroup of enriched design studies, from -12.40 (95% CI: -16.90 to -7.91) to -11.34 (95% CI: -15.36 to -7.32), and in the subgroup of nonenriched design studies, from -7.27 (95% CI: -9.97 to -4.57) to -7.19 (95% CI: -9.24 to -5.14).

Conclusion: Systematic reviews should include reports of unpublished trials. The result for muscle relaxants conflicts with the conclusion of the published review and recent international guidelines. Adding unpublished data strengthens the evidence that opioid analgesics have small effects on persistent low back pain and more clearly suggests these effects may not be clinically meaningful.

Keywords: Analgesics; Back pain; Clinical trials; Meta-analysis; Publication bias.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Analgesics* / therapeutic use
Humans
Low Back Pain* / drug therapy
Reproducibility of Results
Research Design*
Systematic Reviews as Topic* / methods
Treatment Outcome

Substances

Analgesics