Aim

The overall aim of this project was to explore how MC affects the bothersome (activity-limiting) LBP around treatment periods, new episodes of LBP and pain-free periods between episodes as compared to patients receiving care when experiencing a symptomatic relapse. The specific objectives were to compare the following for i) all participants in the trial as well as the ii) psychological subgroups defined by the MPI-S instrument:

1. The pain trajectory before and after a single visit or the first visit in every new treatment period. 2. The time to and risk of a new episode following the first recovery period. 3. The length of consecutive pain-free periods and total number of pain-free weeks during the study period.

Design

This study is a secondary analysis of data from a pragmatic, multicenter, investigator- and assessor- blinded randomized controlled trial with a two-arm parallel design [22,23,24]. The trial was based on the findings of the Nordic Maintenance Care program and made use of all the current evidence in the field [13,14,15,16,17,18,19,20,21]. The primary aim of the trial was to measure the differences in outcome of MC on patients with recurrent or persistent LBP. A total of 35 licensed chiropractors from the Swedish Chiropractic Association requited patients in a nationwide practice-based research-network. The follow-up period was 52 weeks and the primary outcome of the trial was “number of days with bothersome (activity-limiting) LBP” measured using weekly text-messages, SMS. The trial design has been extensively reported in a published protocol paper [22] and in two previous papers evaluating the outcomes of MC [23, 24].

Participants

Patients with recurrent and persistent LBP, who had responded favorably to an initial course of chiropractic care, were recruited in a consecutive sequence between 2012 and 2016 from chiropractic clinics that were part of a nationwide practice-based research network in Sweden. Patients were screened in a three-stage procedure, i.e. at the first visit (baseline 1), the fourth visit (baseline 2), and at study start (baseline 3). See Table 1 for the inclusion criteria at each stage of the trial. Both clinicians and patients received follow-up questionnaires at 12 months. During the inclusion procedure (baseline 1, 2, and 3) patients followed a normal treatment pathway and were included in the trial (i.e. randomly allocated to one of the treatment arms), when the clinician would, as in clinical practice, either schedule the patient for MC or end the current treatment plan.

Table 1 Eligibility Screening in a study of patients with recurrent or persistent low back pain from a randomized clinical trial investigating the comparative effectiveness of chiropractic maintenance care Full size table

One of the key components and inclusion criterion of the trial was to select patients who reported clinical benefit from chiropractic care during the initial treatment. Initial clinical benefit was assessed at the 4th visit using the global perceived improvement scale (single question with one answer in 5 levels: definitely worse, probably worse, unchanged, probably improved, definitely improved). If the patients stated that they were “definitely improved” by the fourth visit, initial clinical benefit was considered evident. Previous research has shown that using the global perceived improvement scale in this way can predict a favourable long-term outcome from chiropractic care at 3, 6, and 12 months [34,35,36,37]. According to research from the Nordic Maintenance Care program, early favorable treatment response is an indication for recommending MC and this step was therefore a core component of the design to reinforce the pragmatic nature of the trial [10, 16,17,18, 20, 21].

Once patients were screened at the 3 baseline steps and considered candidates for the study, they were invited to partake in the study and asked to sign an informed consent form with information about the trial. It was also made clear to patients in the written information that they were free to withdraw from the project at any point without detriment to their relationship with the clinician.

Interventions

The two arms of the trial have been described as MC (preventive treatment, i.e. clinician-controlled) and control (symptom-guided treatment, i.e. patient controlled). The MC group received regularly scheduled treatments, 1–3 months apart during the 52 weeks of follow-up. If the patient had a relapse of pain, a more intense period of visits was scheduled until the patient once again was suitable for a MC plan. The control group was instructed to seek care only if they experienced a symptomatic relapse. In such cases a period of frequent visits would be scheduled until maximum benefit was reached, after which the patients were again instructed to seek care if the LBP reoccurred. Content of care within the two treatment arms were similar, consisting of spinal manipulation, information/advice and soft tissue treatment, as was the level of attention given to the patients [23]. Both groups had 50% of the treatment fee subsidized by the participating clinicians. Prior to the start of the trial, clinicians were given a carefully written study protocol with instructions about the trial procedures. Much effort, by means of physical meetings and telephone contact, was made to ensure that all clinicians had understood and would comply with the study procedures.

Randomization and information to participants

A statistician at Karolinska Institutet generated 40 permuted blocks of 10 participants with a 1:1 allocation ratio according to a randomization schedule. Each clinician received 10 opaque, sealed envelopes containing information about the procedure the patient had been randomly allocated to. The envelopes were opened in front of the patient at the initial visit of the study. Clinicians were instructed to inform patients that 1) the two treatment arms were different procedures currently being used in practice, and 2) there was no evidence to suggest that one strategy was more effective than the other [22].

Outcome variables

The primary outcome of the trial was number of days with bothersome (activity-limiting) LBP. It was recorded weekly using an automated text message system (SMS-track®) [38,39,40] that allowed the researchers to monitor the data collection process from a web-interface in real-time. Thus, patients received the message: “On how many days during the past week were you bothered by your lower back (i.e. it affected your daily activities or routines)? Please answer with a number between 0 and 7”. If the patient failed to respond to the weekly SMS, an automatic reminder was sent after 48 h. If the patient failed to respond after 2 weeks, a research assistant called the patient to answer any concerns that may have caused the patient not to respond.

At follow-up the chiropractor filled in a questionnaire where they were asked to review each patient’s clinical record and document the dates of all visits during the study period. This information was then used to model the trajectory analysis.

To apply the definition by de Vet et al. [30]. as closely as possible to our data, a pain-free week was classified as a week with ≤1 day with activity-limiting LBP in the time-to-event analysis. The classification of pain-free weeks as “≤2 days with bothersome (activity-limiting) LBP” instead of “<2 days with bothersome (activity-limiting) LBP” minimized the risk of misclassification of weeks with temporary short (< 24 h) exacerbations of LBP as episodes. Thus, a new pain episode was defined as a week with ≥2 [2,3,4,5,6,7] days of bothersome (activity-limiting) LBP preceded by ≥4 consecutive pain-free weeks according to the suggested classification above. A pain episode was considered ongoing until ≥4 consecutive pain-free weeks were recorded.

A treatment-period was defined as a single visit or as the first of a series of visits with an interval of ≤2 weeks apart, followed by ≥3 consecutive weeks without any visits to the chiropractor (1 month between visits). MC visits were scheduled 1–3 months apart according to the normal procedures used in clinical practice [41] as reported in the study protocol [22]. The definition of treatment period was chosen to include each MC visit as a new period, any interval between treatments of less than 1 month was considered an active treatment period [41]. In the analysis, each study participant contributed with all treatment periods during the 52-week study period.

A pain-trajectory was defined as “the number of days with bothersome (activity-limiting) LBP per week, during a 7-week period around the week of a single visit or the first visit in a new treatment period” (3 weeks before and 3 weeks after the treatment). The trajectory (mean number of days with pain) for each of the 7 weeks for all single visits or new treatments periods for per group was estimated.

Psychological sub-groups

The MPI-S subgroups have been extensively described in the previous publication, which reported the sub-group evaluation of effect of MC [24]. Patients were classified by the MPI-S instrument, as part of the first visit screening procedure (baseline 1).

Statistical methods

The data from the RCT was analyzed with an intention to treat analysis. Estimates in this study were reported with arithmetic means and 95% confidence intervals. Only individuals who had > 12 weeks of complete SMS data and follow up data for number and dates of visits were included in the analyses.

Data relating to the first objective were analyzed in a longitudinal model which looked at the pain trajectory around the initial visit of each treatment period. Mean number of days with bothersome (activity-limiting) LBP was calculated for each group and for each week during the 7-week treatment period (3 weeks before the visit, week of the visit and 3 weeks after). If two visits were separated by 3 weeks without visits (i.e. defined as two separate treatment periods in the statistical model), the analysis would then double count the last 3 weeks [5,6,7] in the first treatment period and the first 3 weeks [1,2,3] in the following treatment period. The mean number of visits for the whole cohort over 12 months was six visits, so the probability of double counting weeks without pain (as described above) was considered low, with little risk of distorting the results. Data were analyzed by means of a Generalized Estimating Equations (GEE) linear regression model, using an appropriate correlation structure (the best ‘quasi-likelihood under the independence model criterion (QIC)’ value for each strata) and a robust estimator of variance (robust to non-constant error variance). The analysis included treatment group and time (both as study period (52 weeks) and treatment period (7 weeks)) as continuous variables. These covariates were tested as single variables in combinations as well as interaction terms. Co-variates were excluded based on test of model effects, and all variables with a significance level of p < 0.20 were considered for the regression model. The best model structure was further decided based on goodness of fit values (QIC-value). All remaining variables in the final models, chosen based on the best goodness of fit, ended up with significance levels of p < 0.05. Data were also analyzed using a Mixed Model framework. The results of the two procedures were very similar; GEE was chosen rather than the mixed model framework because of its ease of use. Results were presented in graphs, with lines representing mean values and estimated group differences for each week of days with bothersome pain, illustrating pain trajectories for the control and intervention groups.

Data relating to the second objective of this study were analyzed in a time-to-first event model using Cox regression in a survival analysis, estimating the Hazard Ratio of experiencing new LBP episodes. Only individuals who initially reached a recovered state (≥4 consecutive weeks free from bothersome LBP), were included in the Cox regression.

In the third objective, differences between groups for i) time-to-event and ii) length of consecutive pain-free periods and total number of pain-free weeks were tested using ANOVA.

Data were analyzed for all participants (included in the primary analysis [23]), in line with the intention to treat analysis as well as stratified according to the 3 MPI-S subgroups (adaptive copers, interpersonally distressed and dysfunctional included in the subgroup analysis [24]).