Aerobic exercise therapy for chronic low back pain

Objectives

This is a protocol for a Cochrane Review (intervention). The objectives are as follows:

To assess the benefits and harms of aerobic exercise on pain, function, quality of life, psychological functioning, and adverse events, compared with placebo, sham treatment, attention control, or no treatment.

Background

The global impact of low back pain on individuals, healthcare systems, and society is substantial; this condition has remained one of the leading causes of disability worldwide for more than 30 years (Chen 2022; GBD 2023). Low back pain results in enormous healthcare and lost productivity costs (Dagenais 2008; GBD 2023; Hayden 2009; Lim 2012; Martin 2008; Wu 2020), and even greater societal costs (Alonso‐García 2020; Grabovac 2019). Most social and economic costs associated with the condition are attributable to prolonged disability caused by longstanding or recurrent low back pain (Hartvigsen 2018).

Despite a tremendous volume of research in the area, there remains uncertainty about the most effective treatment approaches. Recent work suggests that management of acute and chronic low back pain with exercise compared with usual care can lower healthcare system costs and increase quality‐adjusted life years (Miyamoto 2019). A previous Cochrane review found that exercise (all types combined) is probably effective for treating chronic low back pain (Hayden 2021). That review did not investigate specific forms of exercise, such as aerobic exercise. Two other systematic reviews investigating the effect of aerobic exercise on chronic low back pain found that activities such as running, cycling, or walking may be better than a variety of different treatments (ranging from passive treatment to different aerobic exercise programmes) for improving symptoms (Gordon 2016; Meng 2015). However, the effect of aerobic exercise in the included studies varied by outcome and was not always clinically relevant. In addition, both systematic reviews had some methodological limitations (e.g. no or insufficient risk of bias assessment, inclusion of non‐randomised studies).

Therefore, this review will aim to assess the benefits and harms of aerobic exercise for chronic low back pain.

Description of the condition

Low back pain refers to pain, muscle tension, or stiffness localised below the costal margin and above the inferior gluteal folds, with or without pain referral to the legs (Hayden 2021). Most people who experience this condition are considered to have non‐specific low back pain, which means their symptoms are not attributable to a recognisable, known, specific pathology (e.g. fracture, ankylosing spondylitis, spondyloarthritis, infection, neoplasm, or metastasis). Although different structures of the back have been implicated in symptoms of non‐specific low back pain, including the musculature, joints, and discs, research has also demonstrated psychosocial risk factors, such as maladaptive pain coping behaviours, psychiatric comorbidities, high baseline functional impairment, and low general health status (Chou 2010).

In this review, as in the overarching collaborative review (Hayden 2021), we focus on chronic low back pain (defined as pain, muscle tension, or stiffness lasting longer than 12 weeks) and recurrent low back pain (defined as two or more episodes in a year, lasting more than 24 hours each, with more than 30 pain‐free days between episodes). These two types of back pain are often described as 'persistent'.

Description of the intervention

Exercise treatment is a common management strategy for people with low back pain. This review focusses specifically on aerobic exercise treatment.

Aerobic exercise refers to physical activity in which the body's large muscles move in a rhythmic manner for a sustained period of time (ACSM 2022). Aerobic activity that increases the heart rate and oxygen uptake, also called endurance activity, improves cardiorespiratory endurance. Examples include walking, running, swimming, and cycling (Bull 2020).

Aerobic exercise treatment is prescribed or planned by a health professional. Aerobic exercise treatments are heterogeneous in design (e.g. standard, tailored), dose (duration, frequency, intensity), delivery format (e.g. clinician supervised, group), and type (e.g. walking programmes, swimming training), and may be combined with other conservative treatments (Hayden 2021).

Aerobic exercises can be categorised by skill demands and intensity. For example, walking, aqua‐aerobics, and leisurely cycling require a lower level of skill or physical fitness (or both) compared with vigorous intensity endurance activities such as jogging, aerobics, spinning, and recreational sports such as football or skiing (ACSM 2022; Bull 2020).

How the intervention might work

Researchers have proposed that aerobic exercise acts through a combination of mechanisms to accelerate patient recovery, reduce pain, improve function, and assist with return to usual activities. Biomechanical mechanisms include increased muscle strength and endurance (Powell 2011). Proposed psychological/cognitive mechanisms include reduced fear avoidance behaviours, kinesiophobia, and competing pain behaviours. Additionally, aerobic exercise may improve mood or coping strategies, which may lead to decreased pain and improved function (Wertli 2014). Neurophysiological mechanisms include increased blood flow, decreased inflammation, and activation of descending pain inhibitory mechanisms and endogenous opioid and cannabinoid systems (e.g. release of endorphins), which reduce pain sensitisation (Bruehl 2020; Sitges 2021). Cardiometabolic mechanisms include improved general health and fitness (Bruehl 2020; Sitges 2021).

Why it is important to do this review

Exercise is a common approach to the treatment of chronic low back pain. Clinical practice guidelines, including those of the American College of Physicians (ACP; Qaseem 2017) and the UK National Institute for Health and Care Excellence (NICE; National Guideline Centre 2016), recommend exercise as the first line of care for chronic low back pain. The guidelines specify that exercise programmes should be tailored to individual needs, preferences, and capabilities. The Cochrane review 'Exercise therapy for chronic low back pain', published in 2021, found evidence for the effectiveness of exercise in chronic back pain populations relative to comparisons at all follow‐up periods (Hayden 2021). However, the most effective components of exercise interventions for people with chronic low back pain are yet to be identified.

This will be one of nine focused reviews comprising an overarching collaborative review (Hayden 2022), which was designed to update Hayden 2021. The review teams will work together to screen and extract relevant trial data. We will then synthesise trials that meet our focused review selection criteria.

The eight other Cochrane reviews in the collaborative review have the following titles.

• General strength training for chronic low back pain (Bülow 2024)

• Motor control exercises for chronic low back pain (Saragiotto 2016)

• Core strengthening for chronic low back pain

• Pilates for chronic low back pain (Yamato 2015)

• Yoga for chronic low back pain (Wieland 2022

• Graded activity exercises for low back pain

• Community‐based exercises for chronic low back pain (Bejarano 2023)

• Exercises for treatment of low back pain in older adults

We will conduct this review using the same comprehensive methods and criteria as the other focused reviews. The evidence from this review will contribute to the overarching collaborative review comparing the effectiveness of various approaches and types of exercise treatment.

Objectives

To assess the benefits and harms of aerobic exercise on pain, function, quality of life, psychological functioning, and adverse events, compared with placebo, sham treatment, attention control, or no treatment.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs) published in any language with any length of follow‐up. We will exclude observational studies, non‐randomised trials, short reports, research letters, and trials published only as conference abstracts.

Types of participants

We will include studies involving adults (aged 18 years and older) with chronic or recurrent nonspecific low back (see Description of the condition for definitions). We will exclude studies of individuals with low back pain likely caused by specific pathologies (including radiologically confirmed disc herniation, spinal stenosis, piriformis syndrome, fracture, ankylosing spondylitis, spondyloarthritis, infection, neoplasm, or metastasis), pregnancy, or surgery. We will also exclude studies that focus exclusively on acute exacerbations of chronic low back pain. We will not consider osteoarthritis, osteoporosis, or disc bulge as specific pathologies for this review. Studies of people with leg pain will only be eligible for inclusion if nonspecific back pain is the main complaint for most participants (75% or more), or if separate data are available for participants with low back pain.

Participants can be recruited from any setting, including healthcare, occupational, general, and mixed settings.

Types of interventions

We will include all modes of aerobic exercise, including land‐ and water‐based exercises (walking, running, swimming, bicycling) and aerobic exercise using equipment such as treadmills and bicycle ergometers. We will include aerobic exercise of any intensity, ranging from light intensity to vigorous intensity, as described in the World Health Organization (WHO) physical activity guidelines (Bull 2020).

Eligible studies can provide aerobic exercise treatment alone or as part of a multicomponent physical activity or multidisciplinary treatment programme, provided the main component of the treatment is aerobic exercise (more than 75% of the exercise time). Aerobic exercise sessions should last 15 minutes or longer (Hoffman 2005).

We will categorise the aerobic exercise design as follows.

• Fully tailored: when the therapist completes a clinical history and physical examination and delivers an exercise treatment specifically designed for the individual participant.

• Partially tailored: when the exercise treatment includes the same type of exercises for all participants but varies in intensity or duration.

• Standard: when all participants receive the same treatment, varying only in intensity or duration.

We will categorise treatment delivery as follows.

• Independent: when participants meet the treating therapist once then perform the aerobic exercise at home without supervision.

• Independent with follow‐up: when participants meet the treating therapist initially, perform the aerobic exercise at home, then receive follow‐up with the therapist at least every six weeks.

• Group supervised: if participants attended supervised group therapy sessions with two or more participants.

• Group supervised with follow‐up: if participants attend supervised group therapy sessions then receive follow‐up with the therapist at least every six weeks.

• Individually supervised: when participants attend one‐on‐one sessions with the treating therapist.

We will describe the exercise dose by considering the duration of each session, number of sessions, programme duration, and adherence. We will also describe the reported intensity of the exercise, if available. We will describe the type of therapist and whether a graded activity approach was used in the exercise treatment. Finally, we will record all non‐exercise co‐interventions.

We will include studies that evaluate aerobic exercise versus the following comparators.

• Placebo, sham, or attention control

• No treatment

Placebo/sham/attention control is the primary comparator and is considered the least biased estimate of a treatment's effect. We will consider an intervention to be placebo/sham/attention control if described as such by the trial authors or if we consider it was intended as such (e.g. detuned electrotherapy). We do not consider regular electrotherapy to be an eligible comparator as it has not been proven ineffective. Waiting list and usual/normal care (not controlled by the trial) are eligible 'no treatment' comparators (Appendix 1).

Any co‐interventions must be offered to both study groups so the effect of the exercise treatment can be isolated.

If we find aerobic exercise is effective, future reviews could compare aerobic exercise with other treatments or compare different types of aerobic exercise.

Types of outcome measures

Major outcomes

As in the overarching collaborative review (Hayden 2022), we will fully report the following major outcomes when they are available.

• Pain intensity, measured on a pain scale such as a visual analogue scale (VAS), numerical rating scale (NRS; Chiarotto 2019; Von Korff 2000; Shafshak 2020), or the McGill pain score (Melzack 1975)

• Functional limitations, measured on a back pain‐specific scale such as the Roland‐Morris Disability Questionnaire (RMDQ; Roland 2000) or the Oswestry Disability Index (ODI; Fairbank 1980), as recommended in Chiarotto 2016 and Kopec 2000

• Health‐related quality of life, measured on a validated scale such as the RAND 36‐Item or 12‐Item Short Form Survey (SF‐36/SF‐12; Ware 1992), the Patient‐Reported Outcomes Measurement Information System 10‐Item Global Health Survey (PROMIS‐GH‐10; Hays 2009), the EuroQol Five‐Dimension Questionnaire (EQ‐5D; EuroQol 2019), the Centers for Disease Control and Prevention (CDC) 14‐Item Health‐Related Quality of Life Questionnaire (HRQOL‐14, or other versions; NCCDPHP 1993), the WHO Brief Quality of Life Scale (WHOQOL‐BREF; WHOQOL Group 1998), the Nottingham Health Profile (NHP; Wiklund 1990), the Flanagan Quality of Life Scale (QOLS; Burckhardt 2003), or the Sickness Impact Profile (Bergner 1976)

• Psychological functioning, measured as depressive symptoms using an instrument such as the Beck Depression Inventory (Beck 1987; Beck 1988), Zung Depression Index (Zung 1986), Patient Health Questionnaire‐9 (PHQ‐9; Kroenke 2001), Montgomery‐Asberg Depression Rating Scale (MADRS; Davidson 1986), Hamilton Rating Scale for Depression (HRSD; Hamilton 1986), Center for Epidemiologic Studies Depression Scale (CES‐D; Radloff 2012), Hospital Anxiety and Depression Scale (HADS; Zigmond 1983), or Hopkins Symptoms Checklist for anxiety and depression (HSCL; Derogatis 1974)

• Adverse events

• Withdrawals due to adverse events

The selection of major outcome domains and measurements is based on recommendations for the core outcome set for low back pain clinical trials (Chiarotto 2019). We will analyse pain, function, health‐related quality of life, and psychological functioning as continuous outcomes.

Minor outcomes

As in the overarching collaborative review (Hayden 2022), we will provide a narrative synthesis of the following outcomes (none will be meta‐analysed).

• Return to work/absenteeism (subjective or objective assessment of work absence or sick leave, or return to work rates for individuals absent from work at baseline)

• Global improvement or perceived recovery (any measure of participant‐reported recovery, resolution, or improvement, as defined by the trial authors)

• Satisfaction (any measure of participant‐reported satisfaction with treatment outcomes, as defined by the trial authors)

• Medication use (any measure of presence/absence or count of pain‐relieving medication use, as defined by the trial authors)

• Self‐efficacy (any measure of participant‐reported confidence to perform activities and achieve goals despite low back pain symptoms)

• Cost (any measurement of direct and indirect costs such as healthcare cost, cost due to sickness absence, productivity loss at work; or economic evaluations such as cost‐effectiveness or cost‐utility)

Timing of outcome assessment

We will consider the following time points for reporting outcomes.

• Short term: post‐randomisation assessment closest to three months

• Medium term: post‐randomisation assessment closest to six months

• Long term: post‐randomisation assessment closest to 12 months

The primary time point will be three months, which we consider the most clinically important follow‐up time interval for chronic low back pain.

Reporting of our major and minor outcomes will not be a study inclusion criterion.

Search methods for identification of studies

Electronic searches

We will search the following databases from the date of inception with no language restrictions (Appendix 2).

• Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (latest issue)

• MEDLINE (OvidSP; 1946 to date of search)

• Embase (OvidSP; 1947 to date of search)

Citations will be managed using EndNote X8 software (Clarivate 2017). The same search strategy will be used for related sub‐reviews as well as the Cochrane musculoskeletal review of exercise for acute low back pain.

Searching other resources

We will review the reference lists of included studies and relevant systematic reviews (identified in the electronic search and from team records) for other potentially relevant trials on aerobic exercise.

We will review trial registrations and protocols. We will contact the authors of all ongoing trials via REDCap to determine if they are complete and published (Harris 2019).

Prior to analysis and reporting, we will search for retractions and publication corrections within our set of eligible studies using the software Zotero, which is integrated into the Retraction Watch database (Retraction Watch).

Data collection and analysis

We will follow structured procedures for citation management, study selection, and data extraction, using evidence synthesis tools and online software. New search results will be pre‐screened using Cochrane Screen4Me resources, including a machine learning algorithm (Thomas 2021), and Cochrane Crowd RCT classification (Noel‐Storr 2021). Subsequent study screening, data extraction, and risk of bias assessment will be facilitated by a web‐based electronic systematic review software (DistillerSR). We will record all data on forms modified from those used in the overarching Cochrane review (Hayden 2021). All collaborative review team members contributing to study selection and data extraction will complete training to ensure reliability between review authors.

Selection of studies

Pairs of review authors from our collaborative review pool of 35 authors will independently screen citations based on the title and abstract, and then the full text, for inclusion in the review. We will resolve any disagreements by discussion or, if necessary, by consulting a third review author. We will assess selection criteria to judge the potential eligibility of each citation. At the full‐text assessment stage, we will contact study authors if an inclusion criterion remains unclear. Studies published only as conference proceedings, theses, opinion pieces, correspondence, and stand‐alone abstracts will be excluded. We will assess the eligibility of studies published in languages other than English using translation tools or by involving review authors or colleagues familiar with the language of publication.

Data extraction and management

We will extract the following study characteristics and outcome data from included studies using a data collection form that has been piloted on at least one study in the review.

• Methods: study design, total duration of study, details of any run‐in period, number of study centres and location, study setting, withdrawals, and date of study.

• Participants: number, mean age, age range, sex, disease duration, severity of condition, diagnostic criteria, important (condition‐specific) baseline data, and inclusion criteria and exclusion criteria.

• Interventions: we will classify (aerobic) exercise treatments by programme design (fully tailored, partially tailored, standard), delivery type (independent, independent with follow‐up, group supervised, group supervised with follow‐up, individually supervised), dose (low or high, considering intensity of the aerobic exercise, duration of sessions, number of sessions, programme duration, and adherence), and inclusion of additional treatments (see Appendix 3). We will extract a detailed description of the interventions using the Consensus on Exercise Reporting Template (CERT) for the aerobic exercise interventions as per Cochrane Musculoskeletal standards. We will describe the reporting quality of aerobic exercise therapy according to CERT (Major 2019; Slade 2016), and for each non‐exercise trial arm according to the Template for Intervention Description and Replication (TIDieR) checklist (Hoffmann 2014). Appendix 4 presents the CERT and TIDieR checklists.

• Outcomes: major and minor outcomes specified and collected, and time points reported.

• Notes: funding for trial, and notable declarations of interest of trial authors.

One review author (AZ) will extract the study characteristics and outcome data, and a second review author (WI) will check extracted data for accuracy. We will record how each trial collected information related to adverse events (e.g. if they were measured systematically for all participants or were only recorded when reported by the participants). Furthermore, we will extract the number of participants reporting any adverse event, classified as minor or major, recording whether the adverse events were considered to be related to the intervention and how this was determined within each trial (e.g. by trialists or by an independent monitoring board).

For continuous outcomes, if both final values and change from baseline values are reported for the same outcome, we will extract final values. If a trial reports both unadjusted and adjusted values for the same outcome, we will extract the primary results (as defined by the trial authors). If data are analysed based on an intention‐to‐treat (ITT) sample and another sample (e.g. per‐protocol, as treated), we will extract ITT data for all outcomes.

We will extract available data from multiple follow‐up periods of the same treatment groups by defining different outcomes based on different periods of follow‐up: short term (assessment closest to three months after randomisation (6‐12 weeks, but no more than 12 weeks)), moderate term (assessment closest to six months after randomisation (13‐47 weeks)), and long term (assessment closest to 12 months after randomisation (48 weeks or more)). We will use data from the earliest time point closest to short‐term (three months after randomisation) as the primary analysis.

Assessment of risk of bias in included studies

Two review authors (AZ and WI) will independently assess the risk of bias for each study using the original Cochrane risk of bias tool (RoB 1), which includes the following domains (Higgins 2017).

• Random sequence generation

• Allocation concealment

• Blinding of participants and personnel

• Blinding of outcome assessment

• Incomplete outcome data

• Selective outcome reporting

• Other bias

We will grade each potential source of bias at high, low, or unclear risk, and provide a quote from the study report together with a justification for our judgement in the 'Characteristics of included studies' table. We will resolve any disagreements by discussion or by involving a third review author (SMR). We will consider blinding separately for different key outcomes where necessary (e.g. self‐reported outcomes like pain, functional limitations, and quality of life separately from more objective outcomes). We will also consider the impact of missing data for each outcome. We will summarise the risk of bias judgements across different studies for each of the domains, as follows.

• Low overall risk of bias: all domains are low risk

• High overall risk of bias: at least one domain is high risk

• Unclear overall risk of bias: at least one domain is unclear and none are high risk

Where information on risk of bias relates to unpublished data or correspondence with a trialist, we will note this in the 'Characteristics of included studies' table. When considering treatment effects, we will take into account the risk of bias for the studies that contribute to that outcome.

We will present the figures generated by the risk of bias tool in the review to provide visual summary assessments; where possible, we will add this information to forest plots of meta‐analyses. The risk of bias results will inform the GRADE assessment.

Measures of treatment effect

We will analyse our continuous major outcomes as mean differences (MDs) and 95% confidence intervals (CIs) when all studies measure the outcome with a similar scale. We will enter data presented as a scale with a consistent direction of effect across studies. When studies use different scales to measure the same conceptual outcome, we will calculate standardised mean differences (SMDs) with the corresponding 95% CIs. We will then back‐translate SMDs to a scale of 0 to 100 by multiplying the SMD by a typical among‐person standard deviation (SD) estimated as the SD of the control groups at baseline from the most representative trials (Schünemann 2023a).

We will analyse dichotomous data as risk ratios (RRs) or Peto odds ratios (Peto ORs) when the outcome is a rare event (approximately less than 10%), together with their 95% CIs.

Similar to the collaborative review, we will initially consider a difference of 10% of the scale range to be a clinically important difference for comparison of exercise treatment with no treatment, for all continuous outcomes. We will interpret smaller differences in effectiveness of exercise treatment compared to other conservative treatments as 'probably meaningful' if the whole 95% CI is on one side of the no‐effect line. We consider this to be appropriate given similar inconveniences and adverse effects for comparison treatments considered in this review (Qaseem 2017).

For dichotomous outcomes, we will consider an RR below 0.8 or above 1.25 to represent a clinically important difference.

Unit of analysis issues

If we identify any trials with multiple trial arms, we will list all arms in the 'Characteristics of included studies' table, but will include only the relevant arms in our synthesis. If we combine two comparisons with shared participants in the same meta‐analysis (e.g. running versus no treatment and swimming versus no treatment, where the control group is the same in both comparisons), we will halve the shared group to avoid double‐counting (Higgins 2023a).

For any eligible cross‐over trials, we will conservatively extract data from the two treatment phases (before and after cross‐over) as if the trial was a parallel trial to avoid period and carry‐over effects. For cluster‐randomised trials, we will assess the appropriateness of analyses to control for correlation of individuals within clusters. If a trial has not accounted for clustering, we will reduce the sample size to an estimate of the effective sample size for continuous outcome data to down‐weight the study and limit potential unit of analysis error (Hayden 2023; Higgins 2023b).

Dealing with missing data

Where possible, we will compute missing SDs from other statistics (e.g. standard errors, CIs, or P values) according to the methods recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2023b). If we cannot calculate SDs, we will impute them (e.g. from other studies in the meta‐analysis).

For dichotomous outcomes (e.g. withdrawals due to adverse events), we will calculate the withdrawal rate using the number of participants randomised to the group as the denominator.

For continuous outcomes (e.g. mean change in pain score), we will calculate the MD or SMD based on the number of participants analysed at that time point. If the number of participants analysed is not presented for each time point, we will use the number of participants randomised to each group.

Assessment of heterogeneity

We will pool data if we consider studies to be clinically homogeneous with regard to study population, intervention, and outcomes.

To assess statistical heterogeneity, we will inspect the direction and size of effects and the degree of overlap between CIs in forest plots. We will also use the Chi² test (considering P < 0.1 to be significant) and the I² statistic, which describes how much of the total variation across included studies can be attributed to heterogeneity rather than to chance. To interpret the I² statistic, we will use the rough thresholds provided in the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2023).

• 0% to 40%: might not be important.

• 30% to 60%: may represent moderate heterogeneity.

• 50% to 90%: may represent substantial heterogeneity.

• 75% to 100%: considerable heterogeneity.

We will keep in mind that the observed value of I² depends on the magnitude and direction of effects and the strength of evidence for heterogeneity (e.g. P value from the Chi² test, or a CI for the I² statistic; there is substantial uncertainty in the value of the I² statistic when the number of studies is small).

If we identify substantial heterogeneity, we will report it and investigate possible causes by conducting subgroup and sensitivity analyses, following the recommendations in section 10.10 of the Cochrane Handbook for Systematic reviews of Interventions (Deeks 2023).

Assessment of reporting biases

If we include 10 or more studies in any meta‐analysis, we will create and examine funnel plots to explore possible small study biases, and we will undertake formal statistical tests to investigate funnel plot asymmetry (Egger 1997). When interpreting funnel plots, we will examine the different possible reasons for funnel plot asymmetry, as outlined in Chapter 13 of the Cochrane Handbook for Systematic Reviews of Interventions (Page 2023).

To assess outcome reporting bias, we will check trial protocols against published reports. For studies published after 1 July 2005, we will screen the trial registries ClinicalTrials.gov (clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (trialsearch.who.int/) for the trial protocol. We will evaluate whether selective reporting of outcomes is present.

Data synthesis

Our primary comparison will be aerobic exercise therapy versus placebo/sham/attention control. Our secondary comparison will be aerobic exercise therapy versus no treatment.

We will undertake meta‐analysis only if the treatments, participants, and underlying clinical question are sufficiently similar for pooling to make sense. We will use a random‐effects model and perform a sensitivity analysis with a fixed‐effect model. Our primary analysis will include all trials regardless of their risk of bias.

Subgroup analysis and investigation of heterogeneity

We plan to carry out the following subgroup analyses.

• Population source (healthcare, occupational, general, or mixed population)

• Recommended versus non‐recommended interventions according to recent international low back pain guidelines (e.g. Airaksinen 2006; National Guideline Centre 2016; Qaseem 2017). We will classify an intervention as recommended or non‐recommended when this is stated in two or more guidelines.

• Radiation versus no radiation of pain to the leg(s)

• Younger versus older participants (age < 60 years versus ≥ 60 years)

• Type of aerobic exercise (e.g. land based, water based)

We will use the following outcomes in subgroup analyses.

• Pain intensity

• Functional limitations

We will use the formal test for subgroup interactions in Review Manager (RevMan 2024), interpreting the result with caution, as advised in Chapter 10 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2023). To compare the magnitude of the effects between the subgroups, we will assess the overlap of the CIs of the summary estimate; non‐overlap of the CIs indicates statistical significance.

Sensitivity analysis

We plan to investigate the robustness of the treatment effect on pain intensity and functional disability though sensitivity analysis. To do this, we will repeat the analyses after excluding studies with the following characteristics.

• High/unclear risk of bias in any domain other than those related to blinding (blinding is unfeasible in these trials)

• Imputed data

• Improbable or outlying results (absolute difference between any exercise group and any comparison group over all available follow‐ups greater than a predetermined threshold of 30/100 for pain and 20/100 for functional limitations, selected based on clinical judgement; Hayden 2021; Hayden 2023)

• Poorly described or questionable comparison classifications

Summary of findings and assessment of the certainty of the evidence

To interpret our results, we will follow the guidelines in Chapter 14 and Chapter 15 of the Cochrane Handbook for Systematic Reviews of Interventions, taking care to distinguish a lack of evidence of effect from a lack of effect (Schünemann 2023a; Schünemann 2023b). We will base our conclusions only on findings from the quantitative or narrative synthesis of included studies. We will avoid making recommendations for practice, and our implications for research will suggest priorities for future research and outline the remaining uncertainties in the area.

We will prepare two summary of findings tables comparing aerobic exercise versus placebo/sham/attention control and aerobic exercise versus no treatment. The summary of findings tables will present the results for the following outcomes at short‐term follow‐up.

• Pain intensity

• Functional limitations

• Health‐related quality of life

• Psychological functioning

• Adverse events

Two review authors (AZ and WI) will independently assess the certainty of the evidence using the GRADE approach. They will resolve any disagreements by discussion or by involving a third review author (SMR). We will consider evidence from RCTs to be of high certainty to begin with, downgrading (to moderate, low, or very low) according to the following five GRADE considerations, as necessary.

• Study design and risk of bias: downgrade by one level if more than 25% of participants are from trials at high overall risk of bias; downgrade by two levels if more than 50% of participants are from trials at high overall risk of bias.

• Inconsistency: downgrade by one level if heterogeneity is greater than 50%; downgrade by two levels if heterogeneity is greater than 75%.

• Indirectness: downgrade by one level if more than 50% of participants are outside our target group.

• Imprecision: downgrade by two levels if the CI crosses the minimally important difference threshold (defined in Measures of treatment effect).

• Other bias including publication bias or studies with small sample size: downgrade by one level if publication bias is present based on funnel plots or total sample size is below 400.

We will interpret the results of the GRADE assessment as follows.

• High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.

• Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

• Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.

• Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

We will justify, document, and incorporate judgements into reporting of results for each outcome.

We will use GRADEpro software to prepare the summary of findings tables (GRADEpro GDT). We will justify all decisions to downgrade the certainty of evidence for each outcome using footnotes, and we will make comments to aid the reader's understanding of the review where necessary.

Appendices

Appendix 1. Description of comparators

Category for analysis	Category extracted	Description or guidance
Placebo/sham	Placebo/sham	The group is described as a sham, placebo, or attention control or is judged to be intended by the trial authors to be a sham, placebo, or attention control. Participants unknowingly participated in a placebo or sham treatment that was feasibly effective.
No treatment	Waiting list	Participants received no treatment while being on a wait list.
	Control group	Described specifically as no intervention.
	Usual/normal care	Publication states that participants could receive normal care; but this was not controlled by the trial and may be offered to all treatment groups.
	Same co‐interventions	The aerobic exercise and comparison groups are offered (or receive) the same interventions, so the effect of the aerobic exercise can be isolated.

Appendix 2. Current search strategies

	MEDLINE All (Ovid)
1	exp randomized controlled trial/
2	controlled clinical trial.pt.
3	pragmatic clinical trial.pt.
4	random*.ti,ab.
5	placebo.ab,ti.
6	drug therapy.fs.
7	trial.ab,ti.
8	groups.ab,ti.
9	or/1‐8
10	(animals not (humans and animals)).sh.
11	9 not 10
12	exp Back Pain/
13	Intervertebral Disc Displacement/
14	exp Sciatic Neuropathy/
15	exp Spondylosis/
16	(back ache* or backache* or back disorder* or back pain*).tw,kw,kf.
17	coccydynia.tw,kw,kf.
18	((disc? or disk?) adj1 (degenerat* or displace* or hernia* or prolapse* or slipped)).tw,kw,kf.
19	dorsalgia.tw,kw,kf.
20	(lumb* adj4 pain).tw,kw,kf.
21	lumbago.tw,kw,kf.
22	(sciatic neuropathy or sciatica or ischialgia).tw,kw,kf.
23	(spondylosis or spondylolysis or spondylolisthesis).tw,kw,kf.
24	or/12‐23
25	exp Exercise/
26	exp Exercise Therapy/
27	exp Exercise Movement Techniques/
28	Physical Therapy Modalities/
29	exp Recreation/
30	Recreation Therapy/
31	exp Physical Fitness/
32	exercis*.tw,kw,kf.
33	(kinesiotherapy or recreation*).tw,kw,kf.
34	McKenzie.tw,kw,kf.
35	Alexander.tw,kw,kf.
36	William.tw,kw,kf.
37	Feldenkrais.tw,kw,kf.
38	(McGill adj5 (method or technique)).tw,kw,kf.
39	(training adj2 (strength* or physical or fitness or core or ergonomic* or musc* or spine or spinal or balance or stabil*)).tw,kw,kf.
40	((core or musc*) adj2 (strengthen* or stabiliz* or stabilis* or stability or endurance or condition*)).tw,kw,kf.
41	functional restoration.tw,kw,kf.
42	pilates*.tw,kw,kf.
43	(yoga or hatha or ashtanga or bikram or iyengar or kripalu or kundalini or sivananda or vinyasa or raja or radja or bhakti or jnana or kriya or karma or yama or niyama or asana or pranayama or pratyahara or dharana or dhyana or samadhi or bandha or mudra or yin).tw,kw,kf.
44	aerobic*.tw,kw,kf.
45	(high intensity interval training or hiit).tw,kw,kf.
46	(walk* or run or running or jog or jogging or sport* or cycling or biking or swim* or dance or dancing or gymnastic* or boxing or kickboxing or stretch*).tw,kw,kf.
47	(aquacise or aquacize or aquasize or aquafit* or zumba or barre).tw,kw,kf.
48	(tai chi or tai ji or taiji or taijiquan or taijizhang).tw,kw,kf.
49	eldoa.tw,kw,kf.
50	(glad adj5 (hip? or knee? or osteoarthritis)).tw,kw,kf.
51	(otago adj5 (program* or balance or strength or training)).tw,kw,kf.
52	(bone fit or bonefit).tw,kw,kf.
53	walk tall.tw,kw,kf.
54	(dynamic neuromuscular stabili?ation or dns).tw,kw,kf.
55	active rehabilitation.tw,kw,kf.
56	or/25‐55
57	Alexander Disease/
58	Williams Syndrome/
59	or/57‐58
60	56 not 59
61	11 and 24 and 60
62	limit 61 to yr="2022 ‐Current"

	Embase (Elsevier)
1	'randomized controlled trial'/de
2	'controlled clinical trial'/exp
3	'controlled study'/de
4	'double blind procedure'/de
5	'single blind procedure'/de
6	'crossover procedure'/de
7	'placebo'/de
8	'randomization'/de
9	random*:ti,ab
10	placebo$:ti,ab
11	allocat*:ti,ab
12	assign*:ti,ab
13	blind*:ti,ab
14	'cross‐over':ti,ab OR crossover:ti,ab
15	compare:ti,ab OR compared:ti,ab OR comparing:ti,ab OR comparison:ti,ab OR comparative:ti,ab
16	(controlled NEAR/7 (study OR design OR trial)):ti,ab
17	((singl* OR doubl* OR trebl* OR tripl*) NEAR/7 (blind* OR mask*)):ti,ab
18	trial:ti,ab
19	#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18
20	'animal'/exp OR 'invertebrate'/exp OR 'animal experiment'/de OR 'animal model'/de OR 'animal tissue'/de OR 'animal cell'/de OR 'nonhuman'/de
21	'human'/de OR 'normal human'/de OR 'human cell'/de
22	#20 AND #21
23	#20 NOT #22
24	#19 NOT #23
25	'backache'/exp
26	'intervertebral disk hernia'/exp
27	'ischialgia'/exp
28	'sciatic neuropathy'/exp
29	'sciatica'/exp
30	'spondylosis'/exp
31	'back ache*':ti,ab,kw OR backache*:ti,ab,kw OR 'back disorder*':ti,ab,kw OR 'back pain*':ti,ab,kw
32	coccydynia:ti,ab,kw
33	((disc$ OR disk$) NEAR/1 (degenerat* OR displace* OR hernia* OR prolapse* OR slipped)):ti,ab,kw
34	dorsalgia:ti,ab,kw
35	(lumb* NEAR/4 pain):ti,ab,kw
36	lumbago:ti,ab,kw
37	'sciatic neuropathy':ti,ab,kw OR sciatica:ti,ab,kw OR ischialgia:ti,ab,kw
38	spondylosis:ti,ab,kw OR spondylolysis:ti,ab,kw OR spondylolisthesis:ti,ab,kw
39	#25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38
40	'exercise'/exp
41	'fitness'/de
42	'kinesiotherapy'/exp
43	'physical activity'/exp
44	'recreation'/exp
45	'recreational therapy'/exp
46	exercis*:ti,ab,kw
47	kinesiotherapy:ti,ab,kw OR recreation*:ti,ab,kw
48	mckenzie:ti,ab,kw
49	alexander:ti,ab,kw
50	william:ti,ab,kw
51	feldenkrais:ti,ab,kw
52	(mcgill NEAR/5 (method OR technique)):ti,ab,kw
53	(training NEAR/2 (strength* OR physical OR fitness OR core OR ergonomic* OR musc* OR spine OR spinal OR balance OR stabil*)):ti,ab,kw
54	((core OR musc*) NEAR/2 (strengthen* OR stabiliz* OR stabilis* OR stability OR endurance OR condition*)):ti,ab,kw
55	'functional restoration':ti,ab,kw
56	pilates*:ti,ab,kw
57	yoga:ti,ab,kw OR hatha:ti,ab,kw OR ashtanga:ti,ab,kw OR bikram:ti,ab,kw OR iyengar:ti,ab,kw OR kripalu:ti,ab,kw OR kundalini:ti,ab,kw OR sivananda:ti,ab,kw OR vinyasa:ti,ab,kw OR raja:ti,ab,kw OR radja:ti,ab,kw OR bhakti:ti,ab,kw OR jnana:ti,ab,kw OR kriya:ti,ab,kw OR karma:ti,ab,kw OR yama:ti,ab,kw OR niyama:ti,ab,kw OR asana:ti,ab,kw OR pranayama:ti,ab,kw OR pratyahara:ti,ab,kw OR dharana:ti,ab,kw OR dhyana:ti,ab,kw OR samadhi:ti,ab,kw OR bandha:ti,ab,kw OR mudra:ti,ab,kw OR yin:ti,ab,kw
58	aerobic*:ti,ab,kw
59	'high intensity interval training':ti,ab,kw OR hiit:ti,ab,kw
60	walk*:ti,ab,kw OR run:ti,ab,kw OR running:ti,ab,kw OR jog:ti,ab,kw OR jogging:ti,ab,kw OR sport*:ti,ab,kw OR cycling:ti,ab,kw OR biking:ti,ab,kw OR swim*:ti,ab,kw OR dance:ti,ab,kw OR dancing:ti,ab,kw OR gymnastic*:ti,ab,kw OR boxing:ti,ab,kw OR kickboxing:ti,ab,kw OR stretch*:ti,ab,kw
61	aquacise:ti,ab,kw OR aquacize:ti,ab,kw OR aquasize:ti,ab,kw OR aquafit*:ti,ab,kw OR zumba:ti,ab,kw OR barre:ti,ab,kw
62	'tai chi':ti,ab,kw OR 'tai ji':ti,ab,kw OR taiji:ti,ab,kw OR taijiquan:ti,ab,kw OR taijizhang:ti,ab,kw
63	eldoa:ti,ab,kw
64	(glad NEAR/5 (hip$ OR knee$ OR osteoarthritis)):ti,ab,kw
65	(otago NEAR/5 (program* OR balance OR strength OR training)):ti,ab,kw
66	'bone fit':ti,ab,kw OR bonefit:ti,ab,kw
67	'walk tall':ti,ab,kw
68	'dynamic neuromuscular stabili?ation':ti,ab,kw OR dns:ti,ab,kw
69	'active rehabilitation':ti,ab,kw
70	#40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69
71	'alexander disease'/exp
72	'williams beuren syndrome'/exp
73	#71 OR #72
74	#70 NOT #73
75	#24 AND #39 AND #74
76	#75 AND [2022‐2023]/py

	CENTRAL (Cochrane Library, Wiley)
1	MeSH descriptor: [Back Pain] explode all trees
2	MeSH descriptor: [Intervertebral Disc Displacement] explode all trees
3	MeSH descriptor: [Sciatic Neuropathy] explode all trees
4	MeSH descriptor: [Spondylosis] explode all trees
5	((back NEXT ache*) or backache* or (back NEXT disorder*) or (back NEXT pain*)):ti,ab,kw
6	coccydynia:ti,ab,kw
7	((disc* or disk*) near/1 (degenerat* or displace* or hernia* or prolapse* or slipped)):ti,ab,kw
8	dorsalgia:ti,ab,kw
9	(lumb* near/4 pain):ti,ab,kw
10	lumbago:ti,ab,kw
11	("sciatic neuropathy" or sciatica or ischialgia):ti,ab,kw
12	(spondylosis or spondylolysis or spondylolisthesis):ti,ab,kw
13	{or #1‐#12}
14	MeSH descriptor: [Exercise] explode all trees
15	MeSH descriptor: [Exercise Therapy] explode all trees
16	MeSH descriptor: [Exercise Movement Techniques] explode all trees
17	MeSH descriptor: [Physical Therapy Modalities] this term only
18	MeSH descriptor: [Recreation] explode all trees
19	MeSH descriptor: [Recreation Therapy] this term only
20	MeSH descriptor: [Physical Fitness] explode all trees
21	exercis*:ti,ab,kw
22	(kinesiotherapy or recreation*):ti,ab,kw
23	McKenzie:ti,ab,kw
24	Alexander:ti,ab,kw
25	William:ti,ab,kw
26	Feldenkrais:ti,ab,kw
27	(McGill near/5 (method or technique)):ti,ab,kw
28	(training near/2 (strength* or physical or fitness or core or ergonomic* or musc* or spine or spinal or balance or stabil*)):ti,ab,kw
29	((core or musc*) near/2 (strengthen* or stabiliz* or stabilis* or stability or endurance or condition*)):ti,ab,kw
30	"functional restoration":ti,ab,kw
31	pilates*:ti,ab,kw
32	(yoga or hatha or ashtanga or bikram or iyengar or kripalu or kundalini or sivananda or vinyasa or raja or radja or bhakti or jnana or kriya or karma or yama or niyama or asana or pranayama or pratyahara or dharana or dhyana or samadhi or bandha or mudra or yin):ti,ab,kw
33	aerobic*:ti,ab,kw
34	("high intensity interval training" or hiit):ti,ab,kw
35	(walk* or run or running or jog or jogging or sport* or cycling or biking or swim* or dance or dancing or gymnastic* or boxing or kickboxing or stretch*):ti,ab,kw
36	(aquacise or aquacize or aquasize or aquafit* or zumba or barre):ti,ab,kw
37	("tai chi" or "tai ji" or taiji or taijiquan or taijizhang):ti,ab,kw
38	eldoa:ti,ab,kw
39	(glad near/5 (hip* or knee* or osteoarthritis)):ti,ab,kw
40	(otago near/5 (program* or balance or strength or training)):ti,ab,kw
41	("bone fit" or bonefit):ti,ab,kw
42	"walk tall":ti,ab,kw
43	(("dynamic neuromuscular" NEXT stabili?ation) or dns):ti,ab,kw
44	"active rehabilitation":ti,ab,kw
45	{or #14‐#44}
46	MeSH descriptor: [Alexander Disease] this term only
47	MeSH descriptor: [Williams Syndrome] this term only
48	{or #46‐#47}
49	#45 not #48
50	#13 and #49 with Publication Year from 2022 to 2023, in Trials

Appendix 3. Exercise design and delivery characteristics to be used to describe (aerobic) exercise treatments.

Exercise design and delivery characteristics to be used to describe (aerobic) exercise treatments

Exercise variable	Characteristic description or guidance
Exercise specificity	Focus of the exercises: whole body (many muscle groups from around the body, generally seeking to improve overall fitness), back‐specific (exercises concentrated around muscle groups that support the back), or both. Modes of aerobic exercise such as land‐ or water‐based exercises, and equipment used.
Programme design	Level of individualisation of exercise programme: fully tailored (specifically designed for the individual participant), standard design (fixed exercise program, which may vary slightly in intensity, frequency, and duration), or partially tailored (when the exercise treatment included the same type of exercises for all participants but varied in intensity or duration).
Programme delivery mode	Delivery mode of the exercise treatment: independent (home exercise), independent with therapist follow‐up, group, group with therapist follow‐up, or individual (1:1) with therapist.
Dosage	Length of sessions, number of sessions, programme duration, and adherence/completion.
Delivering therapist/provider	Therapist delivering the exercise treatment: healthcare professional (e.g. physiotherapist, chiropractor, other healthcare professional), exercise specialist (e.g. yoga, Pilates), other.
Graded activity approach	Whether the exercise progressed in a time‐contingent manner, regardless of pain, with use of quotas and pacing.
Co‐interventions provided	All co‐interventions delivered to the exercise treatment group, including (but not limited to) education, psychological therapy, mind‐body approach, medications, and manual therapies.

Appendix 4. CERT and TIDieR checklist

CERT: Consensus on Exercise Reporting Template

A Checklist for what to include when reporting exercise programs

Section/Topic	Item #	Checklist item	Location
			Primary paper (page, table, appendix)	Other (paper or protocol, website (URL))
WHAT: materials	1	Detailed description of the type of exercise equipment (e.g. weights, exercise equipment such as machines, treadmill, bicycle ergometer etc)
WHO: provider	2	Detailed description of the qualifications, teaching/supervising expertise, and/or training undertaken by the exercise instructor
HOW: delivery	3	Describe whether exercises are performed individually or in a group
	4	Describe whether exercises are supervised or unsupervised and how they are delivered
	5	Detailed description of how adherence to exercise is measured and reported
	6	Detailed description of motivation strategies
	7a	Detailed description of the decision rule(s) for determining exercise progression
	7b	Detailed description of how the exercise program was progressed
	8	Detailed description of each exercise to enable replication (e.g. photographs, illustrations, video etc)
	9	Detailed description of any home program component (e.g. other exercises, stretching etc)
	10	Describe whether there are any non‐exercise components (e.g. education, cognitive behavioural therapy, massage etc)
	11	Describe the type and number of adverse events that occurred during exercise
WHERE: Location	12	Describe the setting in which the exercises are performed
WHEN, HOW MUCH: dosage	13	Detailed description of the exercise intervention including, but not limited to, number of exercise repetitions/sets/sessions, session duration, intervention/program duration etc
TAILORING: what, how	14a	Describe whether the exercises are generic (one size fits all) or tailored whether tailored to the individual
	14b	Detailed description of how exercises are tailored to the individual
	15	Describe the decision rule for determining the starting level at which people commence an exercise program (such as beginner, intermediate, advanced etc)
HOW WELL: planned, actual	16a	Describe how adherence or fidelity to the exercise intervention is assessed/measured
	16b	Describe the extent to which the intervention was delivered as planned

The TIDieR (Template for Intervention Description and Replication) Checklist

Information to include when describing an intervention and the location of the information

Item number	Item	Where located
		Primary paper (page or appendix number)	Other (details)
	BRIEF NAME
1.	Provide the name or a phrase that describes the intervention.
	WHY
2.	Describe any rationale, theory, or goal of the elements essential to the intervention.
	WHAT
3.	Materials: Describe any physical or informational materials used in the intervention, including those provided to participants or used in intervention delivery or in training of intervention providers. Provide information on where the materials can be accessed (e.g. online appendix, URL).
4.	Procedures: Describe each of the procedures, activities, and/or processes used in the intervention, including any enabling or support activities.
	WHO PROVIDED
5.	For each category of intervention provider (e.g. psychologist, nursing assistant), describe their expertise, background and any specific training given.
	HOW
6.	Describe the modes of delivery (e.g. face‐to‐face or by some other mechanism, such as internet or telephone) of the intervention and whether it was provided individually or in a group.
	WHERE
7.	Describe the type(s) of location(s) where the intervention occurred, including any necessary infrastructure or relevant features.
	WHEN and HOW MUCH
8.	Describe the number of times the intervention was delivered and over what period of time including the number of sessions, their schedule, and their duration, intensity or dose.
	TAILORING
9.	If the intervention was planned to be personalised, titrated or adapted, then describe what, why, when, and how.
	MODIFICATIONS
10.	If the intervention was modified during the course of the study, describe the changes (what, why, when, and how).
	HOW WELL
11.	Planned: If intervention adherence or fidelity was assessed, describe how and by whom, and if any strategies were used to maintain or improve fidelity, describe them.
12.	Actual: If intervention adherence or fidelity was assessed, describe the extent to which the intervention was delivered as planned.

Contributions of authors

Drafting of the protocol: AdZ, WIJ
Critical revision of the protocol for important intellectual content: all review authors
Final approval of the protocol: all review authors

Sources of support

Internal sources

• Department of Health Sciences, Faculty of Sciences, Vrije Universiteit, Amsterdam, Netherlands

  In‐kind support

• Department of General Practice, Erasmus MC, Rotterdam, Netherlands

  In‐kind support

External sources

• Cochrane Back Review Group, Other

  Editorial support

Declarations of interest

AdZ and SMR work in their own private clinics as chiropractors. The remaining review authors have no conflicts of interest to declare.

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