Identification of subgroup effect with an individual participant data meta-analysis of randomised controlled trials of three different types of therapist-delivered care in low back pain

Abstract

Background: Proven treatments for low back pain, at best, only provide modest overall benefits. Matching people to treatments that are likely to be most effective for them may improve clinical outcomes and makes better use of health care resources.

Methods: We conducted an individual participant data meta-analysis of randomised controlled trials of three types of therapist delivered interventions for low back pain (active physical, passive physical and psychological treatments). We applied two statistical methods (recursive partitioning and adaptive risk group refinement) to identify potential subgroups who might gain greater benefits from different treatments from our individual participant data meta-analysis.

Results: We pooled data from 19 randomised controlled trials, totalling 9328 participants. There were 5349 (57%) females with similar ratios of females in control and intervention arms. The average age was 49 years (standard deviation, SD, 14). Participants with greater psychological distress and physical disability gained most benefit in improving on the mental component scale (MCS) of SF-12/36 from passive physical treatment than non-active usual care (treatment effects, 4.3; 95% confidence interval, CI, 3.39 to 5.15). Recursive partitioning method found that participants with worse disability at baseline gained most benefit in improving the disability (Roland Morris Disability Questionnaire) outcome from psychological treatment than non-active usual care (treatment effects, 1.7; 95% CI, 1.1 to 2.31). Adaptive risk group refinement did not find any subgroup that would gain much treatment effect between psychological and non-active usual care. Neither statistical method identified any subgroups who would gain an additional benefit from active physical treatment compared to non-active usual care.

Conclusions: Our methodological approaches worked well and may have applicability in other clinical areas. Passive physical treatments were most likely to help people who were younger with higher levels of disability and low levels of psychological distress. Psychological treatments were more likely to help those with severe disability. Despite this, the clinical importance of identifying these subgroups is limited. The sizes of sub-groups more likely to benefit and the additional effect sizes observed are small. Our analyses provide no evidence to support the use of sub-grouping for people with low back pain.

Keywords: IPD; Low back pain; Physical interventions; Psychological interventions; Stratification; Subgroups; Therapist delivered interventions.

Fig. 1

One-step meta-analysis: Estimated difference between control (non-active usual care and sham) and all intervention treatments for each outcome with its 95% confidence intervals adjusted by its baseline value for short-, mid-, and long-term follow-up. Abbreviations: m, number of trials; nC, number of participants in the control arm; nI, number of participants in the intervention arm; short-, mid- and long-term follow-up, measurements taken 2 and 3 months, at 6 months and 12 months post randomisation or entry to the trial, respectively; FFbHR, Hannover functional ability questionnaire for measuring back-pain related functional limitations; RMDQ, Roland Morris disability questionnaire; PCS, physical component scale of SF-12/36; MCS, mental component scale of SF-12/36. a The original scale was rescaled from 0 to 100 for graphical representation purposes only. In order to obtain the estimated difference and its 95% confidence interval in its original scale, the value from graph is multiplied by (maximum value/100). For example, the estimated difference for RMDQ at short-term follow-up was 5.47*24/100 = 1.31. b One of the following instruments from each trial, where available, was chosen (in descending order): 1. individual VAS on average pain today. 2. average pain over the past 1 week. 3. average pain over the past 2 weeks, average pain over the past 1 month 4. average pain over the past 3 months. 5. the individual item of the CPG pain intensity score (CPG-PS) that is equivalent to the VAS if it is available. 6. the summary score of the CPG-PS or 7. the bodily pain domain of SF-12/36

Fig. 2

Moderator analysis for short-term outcomes (change from baseline to short-term follow-up) between control (non-active usual care and sham) and all intervention treatments with estimated interaction term and its 95% confidence interval. Abbreviations: RMDQ, Roland Morris disability questionnaire; FFbHR, Hannover functional ability questionnaire for measuring back-pain related functional limitations; QALY, quality-adjusted life-years. a estimate of the treatment effect for participants with positive belief (low fear avoidance) of fear avoidance belief was greater as opposed to those with the negative attitude; b estimate of the treatment effect for participants with moderate belief of fear avoidance was greater as opposed to those with the negative attitude; c estimate of the treatment effect for participants with positive attitude of catastrophising (low catastrophising score) was greater as opposed to those with the negative attitude (high catastrophising score); d estimate of the treatment effect for participants with moderate attitude of catastrophising was greater as opposed to those with the negative attitude; e estimate of the treatment effect for participants with low risk of anxiety was less as opposed to those with the high risk; f estimate of the treatment effect for participants with moderate risk of anxiety was less as opposed to those with the high risk; g estimate of the treatment effect for participants with positive attitude of coping strategy (high coping score) was less as opposed to those with the negative attitude (low coping score); h estimate of the treatment effect for participants with moderate attitude of coping strategy was less as opposed to those with the negative attitude; i estimate of the treatment effect for participants with SF-12/36 MCS score lower than general norm (< 50) was less as opposed to those with score at or above the general norm (≥50); j estimate of the treatment effect for male was less as opposed to female

Fig. 3

Treatment effect and its 95% confidence interval for each subgroup identified by the RP method for the short-term FFbHR, SF-12/36 MCS and SF-12/36 PCS outcomes