Low back pain (LBP) is one of the leading causes of disability and has a major socioeconomic impact [1–5]. The majority of the cost associated with LBP is generated by a small percentage of patients whose condition proceeds to chronicity [6, 7]. There is evidence that the prevalence and costs of chronic LBP are rising . Exercise therapy is a commonly used strategy to treat chronic LBP in and is one of several interventions which evidence suggests is moderately effective .
In back pain research, identification of relevant patient subgroups is an important goal . Previous interactions with clinical stakeholders identified the lumping together of heterogeneous patients who have non-specific LBP, as a source of frustration in LBP intervention research . There is a presumption that relevant subgroups of individuals with chronic LBP exist, and that our lack of understanding hampers clinical decision-making.
Treatment effect modification occurs when the treatment effect is consistently better for a subgroup of individuals than for the group as a whole. One or more characteristics (treatment effect modifiers) can define treatment-based subgroups (see Kamper et al., 2010, for a discussion of treatment-based subgroups) . Promising treatment effect modifiers can come from previous research findings, and clinical or biological rationale. Prognostic factors (characteristics associated with outcome over time) are not necessarily treatment effect modifiers. For LBP there is little conclusive evidence on treatment effect modifiers, although identifying relevant treatment subgroups has been a goal in recent years. LBP has been classified in many ways: on the basis of pathoanatomy, presence/absence of specific signs or symptoms (for example, sciatica), the duration of symptoms (acute, subacute, chronic), work status, diagnostic testing, patient history, or combinations of these. Systems and tools used to classify and subgroup patients with LBP were reviewed by Binkley et al. (1993) , Fritz et al. (2005) , and Karayannis (2012) ; Kamper et al. (2010) , discuss research on subgrouping in LBP. These authors report difficulties with most existing subgroup/classification systems, including unclear reliability or validity in clinical practice, non-comprehensive selection of predictor variables, and inclusion of measures or information that are not useful, nor feasibly collected in primary-care practice. Furthermore, most LBP trials are underpowered to detect treatment effect modifiers .
Systematic review is a study design that uses transparent and robust methods to search the literature, select appropriate studies, extract relevant data, assess risk of bias, and synthesize and interpret research evidence for a specific question . This is an extremely useful approach to summarize evidence about treatment effectiveness based on a complete body of literature. Meta-analysis, which is the quantitative synthesis of data from primary studies, is valuable to increase the number of patients (statistical power/precision) available to estimate a treatment effect, to better distinguish a clinically important true treatment effect from chance effects, and to identify and investigate sources of between-study heterogeneity in the magnitude of the treatment effect. Traditional meta-analyses that collect published aggregate study data and pool studies to estimate one overall effect have limitations: in particular, they often bring together heterogeneous information which, some argue, limits their relevance to managing individual patients in clinical practice . An alternative approach to evidence synthesis is meta-analysis of individual participant data (IPD), where the raw individual-level data are obtained for each study and used for synthesis. IPD relates to the data recorded for each individual in a study. This is in contrast to aggregate data that relates to information averaged or estimated across all individuals in a study (for example, information on mean treatment effect, mean age, proportion of male participants). Such aggregate data are derived from the IPD itself, so IPD can be considered the original source material. IPD meta-analyses are increasingly achievable .
The use of IPD has numerous potential advantages. Aggregate data are often not available, are poorly reported, or are derived and presented differently across studies (for example, odds ratio versus relative risk). They are more likely to be reported (and in greater detail) when statistically significant, amplifying the threat of publication bias. In contrast, IPD allows one to standardize analyses across studies and directly derive the information desired, independent of significance or how it was reported. IPD may also allow a longer follow-up time, more participants, and more outcomes than were considered in the original study publication. This means that IPD meta-analyses are potentially more reliable than aggregate data meta-analyses, and may lead to different conclusions. Perhaps most importantly, an IPD meta-analysis can produce more clinically relevant results, going beyond the grand mean toward individualized medicine and thereby reducing the heterogeneity in study results . For example, subgroups of patients with a common characteristic (for example, female gender) can be identified within IPD, and thus meta-analysis results can be derived specifically for them, with increased power compared to the individual studies themselves. Similarly, IPD allows more powerful and reliable examination of differential treatment effects across individuals [21, 22], as one can directly utilize within-trial information to estimate how patients’ characteristics modify treatment benefit .
In 2005 our team conducted a review within the framework of the Cochrane Collaboration to investigate the effectiveness of exercise therapy for treating LBP; 61 trials were included [24–26]. We concluded that exercise therapy appears to be effective in slightly decreasing pain and improving function in adults with chronic LBP; however, this earlier work was limited by the availability of only published aggregate data. Since our 2005 Cochrane review, almost 150 new, potentially relevant, randomized controlled trials (RCTs) have been published, warranting an important update. The very large number of recent trials available for this review provides an opportunity for comprehensive and novel syntheses beyond the Cochrane review and traditional meta-analyses. For exercise therapy, one small study is available that attempted to identify individual characteristics for patients likely to respond to stabilization exercises . This highly cited study included 54 subjects and developed a clinical predictive rule. However, these results are preliminary. Chou et al. (2010) note, More research on methods for selecting optimal therapy that are practical for use by primary care clinicians is urgently needed. . In this study we will investigate individual characteristics that may modify treatment outcomes in exercise therapy.