Korean J Pain.  2021 Apr;34(2):139-155. 10.3344/kjp.2021.34.2.139.

The quality of subgroup analyses in chronic pain randomized controlled trials: a methodological review

• AminiLari M
• Ashoorian V
• Caldwell A
• Rahman Y
• Nieuwlaat R
• Busse JW
• Mbuagbaw L

• KMID: 2514414
• DOI: http://doi.org/10.3344/kjp.2021.34.2.139

Abstract

The quality of subgroup analyses (SGAs) in chronic non-cancer pain trials is uncertain. The purpose of this study was to address this issue. We conducted a comprehensive search in MEDLINE and EMBASE from January 2012 to September 2018 to identify eligible trials. Two pairs of reviewers assessed the quality of the SGAs and the credibility of subgroup claims using the 10 criteria developed by Sun et al. in 2012. The associations between the quality of the SGAs and the studies’ characteristics including risk of bias, funding sources, sample size, and the latest impact factor, were assessed using multivariable logistic regression. Our search retrieved 3,401 articles of which 66 were eligible. The total number of SGAs was 177 of which 52 (29.4%) made a subgroup claim. Of these, only 15 (8.5%) were evaluated as being of high quality. Among the 30 SGAs that claimed subgroup effects using an appropriate method of performing interaction tests, the credibility of only 5 were assessed as high. None of the subgroup claims met all the credibility criteria. No significant association was found between the quality of SGAs and the studies’ characteristics. The quality of the SGAs performed in chronic pain trials was poor. To enhance the quality of SGAs, scholars should consider the developed criteria when designing and conducting trials, particularly those which need to be specified a priori.

Keyword

Bias; Chronic Pain; Logistic Models; MEDLINE; Methods; Pain; Research Design; Uncertainty

Figure

• 

  Fig. 1 Study flow diagram. SGA: subgroup analysis.

Reference

1. Ospina M, Harstall C. 2002. Prevalence of chronic pain: an overview. Alberta Heritage Foundation for Medical Research;Edmonton:

2. Elzahaf RA, Tashani OA, Unsworth BA, Johnson MI. 2012; The prevalence of chronic pain with an analysis of countries with a Human Development Index less than 0.9: a systematic review without meta-analysis. Curr Med Res Opin. 28:1221–9. DOI: 10.1185/03007995.2012.703132. PMID: 22697274.

3. Venekamp RP, Rovers MM, Hoes AW, Knol MJ. 2014; Subgroup analysis in randomized controlled trials appeared to be dependent on whether relative or absolute effect measures were used. J Clin Epidemiol. 67:410–5. DOI: 10.1016/j.jclinepi.2013.11.003. PMID: 24508145.

4. Sun X, Briel M, Busse JW, You JJ, Akl EA, Mejza F, et al. 2012; Credibility of claims of subgroup effects in randomised controlled trials: systematic review. BMJ. 344:e1553. DOI: 10.1136/bmj.e1553. PMID: 22422832.

5. Varadhan R, Wang SJ. 2014; Standardization for subgroup analysis in randomized controlled trials. J Biopharm Stat. 24:154–67. DOI: 10.1080/10543406.2013.856023. PMID: 24392983. PMCID: PMC4313927.

6. Byth K, Gebski V. 2004; Factorial designs: a graphical aid for choosing study designs accounting for interaction. Clin Trials. 1:315–25. DOI: 10.1191/1740774504cn026oa. PMID: 16279257.

7. McCormack R, Lamontagne M, Vannabouathong C, Deakon RT, Belzile EL. 2017; Comparison of the 3 different injection techniques used in a randomized controlled study evaluating a cross-linked sodium hyaluronate combined with triamcinolone hexacetonide (Cingal) for osteoarthritis of the knee: a subgroup analysis. Clin Med Insights Arthritis Musculoskelet Disord. 10:1179544117725026. DOI: 10.1177/1179544117725026. PMID: 28839449. PMCID: PMC5560514.

8. Saragiotto BT, Maher CG, Moseley AM, Yamato TP, Koes BW, Sun X, et al. 2016; A systematic review reveals that the credibility of subgroup claims in low back pain trials was low. J Clin Epidemiol. 79:3–9. DOI: 10.1016/j.jclinepi.2016.06.003. PMID: 27297201.

9. Oxman AD, Guyatt GH. 1992; A consumer's guide to subgroup analyses. Ann Intern Med. 116:78–84. DOI: 10.7326/0003-4819-116-1-78. PMID: 1530753.

10. Sun X, Briel M, Walter SD, Guyatt GH. 2010; Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses. BMJ. 340:c117. DOI: 10.1136/bmj.c117. PMID: 20354011.

11. Oxman A, Guyatt G, Cook D, Montori V. Guyatt G, Rennie D, editors. 2002. Summarizing the evidence. Users' guides to the medical literature: a manual for evidence-based clinical practice. AMA Press;Chicago: p. 155–173.

12. Akl EA, Sun X, Busse JW, Johnston BC, Briel M, Mulla S, et al. 2012; Specific instructions for estimating unclearly reported blinding status in randomized trials were reliable and valid. J Clin Epidemiol. 65:262–7. DOI: 10.1016/j.jclinepi.2011.04.015. PMID: 22200346.

13. Hosmer DW, Lemeshow S. 1980; Goodness of fit tests for the multiple logistic regression model. Commun Stat Theory Methods. 9:1043–69. DOI: 10.1080/03610928008827941.

14. Landis JR, Koch GG. 1977; The measurement of observer agreement for categorical data. Biometrics. 33:159–74. DOI: 10.2307/2529310. PMID: 843571.

15. Harris RJ, Quade D. 1992; The minimally important difference significant criterion for sample size. J Educ Stat. 17:27–49. DOI: 10.3102/10769986017001027.

16. Lachenbruch PA. 1988; A note on sample size computation for testing interactions. Stat Med. 7:467–9. DOI: 10.1002/sim.4780070403. PMID: 3368673.

17. Mistry D, Patel S, Hee SW, Stallard N, Underwood M. 2014; Evaluating the quality of subgroup analyses in randomized controlled trials of therapist-delivered interventions for nonspecific low back pain: a systematic review. Spine (Phila Pa 1976). 39:618–29. DOI: 10.1097/BRS.0000000000000231. PMID: 24480951.

18. Rothwell PM. 2005; Treating individuals 2. Subgroup analysis in randomised controlled trials: importance, indications, and interpretation. Lancet. 365:176–86. DOI: 10.1016/S0140-6736(05)17709-5. PMID: 15639301.

19. Sun X, Briel M, Busse JW, You JJ, Akl EA, Mejza F, et al. 2011; The influence of study characteristics on reporting of subgroup analyses in randomised controlled trials: systematic review. BMJ. 342:d1569. DOI: 10.1136/bmj.d1569. PMID: 21444636. PMCID: PMC6173170.

20. Barton S, Peckitt C, Sclafani F, Cunningham D, Chau I. 2015; The influence of industry sponsorship on the reporting of subgroup analyses within phase III randomised controlled trials in gastrointestinal oncology. Eur J Cancer. 51:2732–9. DOI: 10.1016/j.ejca.2015.08.030. PMID: 26608121.