Advertisement

Cost-Effectiveness of Manual Therapy for the Management of Musculoskeletal Conditions: A Systematic Review and Narrative Synthesis of Evidence From Randomized Controlled Trials

Open AccessPublished:June 27, 2014DOI:https://doi.org/10.1016/j.jmpt.2014.05.001

      Abstract

      Objectives

      The purpose of this study was to systematically review trial-based economic evaluations of manual therapy relative to other alternative interventions used for the management of musculoskeletal conditions.

      Methods

      A comprehensive literature search was undertaken in major medical, health-related, science and health economic electronic databases.

      Results

      Twenty-five publications were included (11 trial-based economic evaluations). The studies compared cost-effectiveness and/or cost-utility of manual therapy interventions to other treatment alternatives in reducing pain (spinal, shoulder, ankle). Manual therapy techniques (eg, osteopathic spinal manipulation, physiotherapy manipulation and mobilization techniques, and chiropractic manipulation with or without other treatments) were more cost-effective than usual general practitioner (GP) care alone or with exercise, spinal stabilization, GP advice, advice to remain active, or brief pain management for improving low back and shoulder pain/disability. Chiropractic manipulation was found to be less costly and more effective than alternative treatment compared with either physiotherapy or GP care in improving neck pain.

      Conclusions

      Preliminary evidence from this review shows some economic advantage of manual therapy relative to other interventions used for the management of musculoskeletal conditions, indicating that some manual therapy techniques may be more cost-effective than usual GP care, spinal stabilization, GP advice, advice to remain active, or brief pain management for improving low back and shoulder pain/disability. However, at present, there is a paucity of evidence on the cost-effectiveness and/or cost-utility evaluations for manual therapy interventions. Further improvements in the methodological conduct and reporting quality of economic evaluations of manual therapy are warranted in order to facilitate adequate evidence-based decisions among policy makers, health care practitioners, and patients.

      Key Indexing Terms

      Manual therapy is a skilled nonsurgical conservative management using the practitioner's hands and/or fingers on the patient's body for the purpose of assessing, diagnosing, and treating a variety of symptoms and conditions.
      • Farrell JP
      • Jensen GM
      Manual therapy: a critical assessment of role in the profession of physical therapy.
      • DeStefano LA
      • Greenman PE
      Greenman's principles of manual medicine.
      Manual therapy is used within the traditional medical (eg, physiotherapy, orthopedics, and sports medicine) and complementary and alternative medicine context (eg, chiropractic and osteopathy) and consists of different techniques (eg, manipulation, mobilization, static stretching, and muscle energy techniques). The definition and purpose of manual therapy vary across health care professionals.
      The use of manipulation and mobilization has been recommended in clinical practice guidelines in the United States, Great Britain, Canada, and the Netherlands.
      • Jette AM
      • Delitto A
      Physical therapy treatment choices for musculoskeletal impairments.
      • Bryans R
      • Decina P
      • Descarreaux M
      • et al.
      Evidence-based guidelines for the chiropractic treatment of adults with neck pain.
      • Brantingham JW
      • Cassa TK
      • Bonnefin D
      • et al.
      Manipulative and multimodal therapy for upper extremity and temporomandibular disorders: a systematic review.
      • Bryans R
      • Descarreaux M
      • Duranleau M
      • et al.
      Evidence-based guidelines for the chiropractic treatment of adults with headache.
      • Farabaugh RJ
      • Dehen MD
      • Hawk C
      Management of chronic spine-related conditions: consensus recommendations of a multidisciplinary panel.
      • Lawrence DJ
      • Meeker W
      • Branson R
      • et al.
      Chiropractic management of low back pain and low back-related leg complaints: a literature synthesis.
      • Globe GA
      • Morris CE
      • Whalen WM
      • Farabaugh RJ
      • Hawk C
      Chiropractic management of low back disorders: report from a consensus process.
      Although past research evidence on the clinical effectiveness
      • Furlan AD
      • Yazdi F
      • Tsertsvadze A
      • et al.
      A systematic review and meta-analysis of efficacy, cost-effectiveness, and safety of selected complementary and alternative medicine for neck and low-back pain.
      • Shekelle PG
      The appropriateness of spinal manipulation for low-back pain: project overview and literature review.
      • Shekelle PG
      • Adams AH
      • Chassin MR
      • Hurwitz EL
      • Brook RH
      Spinal manipulation for low-back pain.
      • Bigos SJ
      • United States
      • Agency for Health Care Policy and Research
      • American HC
      Acute low back problems in adults.
      • Di Fabio RP
      Clinical assessment of manipulation and mobilization of the lumbar spine. A critical review of the literature.
      • Ottenbacher K
      • DiFabio RP
      Efficacy of spinal manipulation/mobilization therapy. A meta-analysis.
      • Bronfort G.
      • Assendelft W.J.
      • Evans R.
      • Haas M.
      • Bouter L.
      Efficacy of spinal manipulation for chronic headache: a systematic review.
      • Bronfort G
      • Haas M
      • Evans R
      • Leininger B
      • Triano J
      Effectiveness of manual therapies: the UK evidence report.
      • Assendelft WJ
      • Morton SC
      • Yu EI
      • Suttorp MJ
      • Shekelle PG
      Spinal manipulative therapy for low back pain. A meta-analysis of effectiveness relative to other therapies.
      • Cherkin DC
      • Deyo RA
      • Battie M
      • Street J
      • Barlow W
      A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain.
      and safety
      • Ernst E
      Adverse effects of spinal manipulation: a systematic review.
      • Ernst E
      Deaths after chiropractic: a review of published cases.
      • Carnes D
      • Mars TS
      • Mullinger B
      • Froud R
      • Underwood M
      Adverse events and manual therapy: a systematic review.
      • Gouveia LO
      • Castanho P
      • Ferreira JJ
      Safety of chiropractic interventions: a systematic review.
      • Rubinstein SM
      • Peerdeman SM
      • van Tulder MW
      • Riphagen I
      • Haldeman S
      A systematic review of the risk factors for cervical artery dissection.
      • Vohra S
      • Johnston BC
      • Cramer K
      • Humphreys K
      Adverse events associated with pediatric spinal manipulation: a systematic review.
      • Stevinson C
      • Ernst E
      Risks associated with spinal manipulation.
      • Carlesso LC
      • Gross AR
      • Santaguida PL
      • Burnie S
      • Voth S
      • Sadi J
      Adverse events associated with the use of cervical manipulation and mobilization for the treatment of neck pain in adults: a systematic review.
      of manual therapy relative to other interventions is abundant, the evidence on cost-effectiveness is insufficient and inconclusive.
      • Maund E
      • Craig D
      • Suekarran S
      • et al.
      Management of frozen shoulder: a systematic review and cost-effectiveness analysis.
      • Indrakanti SS
      • Weber MH
      • Takemoto SK
      • Hu SS
      • Polly D
      • Berven SH
      Value-based care in the management of spinal disorders: a systematic review of cost-utility analysis.
      • Driessen MT
      • Lin CW
      • van Tulder MW
      Cost-effectiveness of conservative treatments for neck pain: a systematic review on economic evaluations.
      • Furlan AD
      • Yazdi F
      • Tsertsvadze A
      • et al.
      Complementary and alternative therapies for back pain II. Evidence Report/Technology Assessment No. 194. (Prepared by the University of Ottawa Evidence-based Practice Center under Contract No. 290-2007-10059-I (EPCIII). AHRQ Publication No.(11)E007.
      • Dagenais S
      • Roffey DM
      • Wai EK
      • Haldeman S
      • Caro J
      Can cost utility evaluations inform decision making about interventions for low back pain?.
      • Brown A
      • Angus D
      • Chen S
      • et al.
      Costs and outcomes of chiropractic treatment for low back pain [Technology report no 56].
      • Stevans JM
      • Zodet MW
      Clinical, demographic, and geographic determinants of variation in chiropractic episodes of care for adults using the 2005-2008 Medical Expenditure Panel Survey.
      • Grieves B
      • Menke JM
      • Pursel KJ
      Cost minimization analysis of low back pain claims data for chiropractic vs medicine in a managed care organization. [Erratum appears in J Manipulative Physiol Ther. 2010 Feb;33(2):164].
      • Haas M
      • Sharma R
      • Stano M
      Cost-effectiveness of medical and chiropractic care for acute and chronic low back pain.
      Moreover, to our best knowledge, a systematic review of full economic evaluations of recent evidence (ie, cost-effectiveness [CEA] and/or cost-utility analysis [CUA]) alongside randomized controlled trials (RCTs) of manual therapy has not been conducted.
      In light of limited health care resources, policy makers, health care providers, and researchers need to make informed decisions in prioritizing and allocating resources to the provision of health care interventions that are both effective and cost saving. Ideally, the decision-making process should be based on high-quality evidence summarizing incremental costs and effects of a health care intervention of interest compared with alternative interventions.
      The aim of this review was to systematically identify, appraise, and evaluate the evidence on trial-based economic evaluations (cost-effectiveness and/or cost-utility) of manual therapy relative to other alternative interventions used for the management of musculoskeletal conditions.

      Methods

      This review is part of a large technical report of comparative benefits and harms of manual therapy interventions for the management of musculoskeletal and nonmusculoskeletal conditions, commissioned by the Royal College of Chiropractors in the United Kingdom (http://www2.warwick.ac.uk/fac/med/research/hscience/pet/reportforcollegeofchiropractors/).
      A comprehensive literature search was undertaken as part of a wider search for this report. The following medical, health-related, science and health economic electronic databases were searched (through August 2011): MEDLINE (Ovid), Embase, Mantis, Index to Chiropractic Literature, CINAHL, Cochrane Airways Group trial register, Cochrane Complementary Medicine Field register, and Cochrane Rehabilitation Field register (via CENTRAL), Science Citation Index, AMED, CDSR, National Health Service (NHS) DARE, NHS HTA, NHS EED, CENTRAL, ASSIA, and Social Science Citation Index. The search strategy used in MEDLINE is provided in Appendix 1. Search terms were restricted to subject heading and free-text terms related to manual therapy. Broader terms such as “physiotherapy” were not included because initial tests suggested that the volume of the literature identified using such a broad search strategy would not be manageable. To keep the search as open as possible, no condition terms were included. The search was limited to the study types included in the wider report by the use of recognized search filters, including the NHS Centre for Reviews and Dissemination NHS EED filter (see: http://www.crd.york.ac.uk/). This performance of this filter has been tested.
      • Glanville J
      • Kaunelis D
      • Mensinkai S
      How well do search filters perform in identifying economic evaluations in MEDLINE and EMBASE.
      No date limits were applied. The search results were updated on February 15, 2013. Additional studies were sought through references of relevant primary studies and systematic reviews.
      This review included English-language full-text publications of RCTs that evaluated the cost-effectiveness and/or cost-utility of manual therapy (eg, manipulation, mobilization, static stretching, chiropractic care, muscle energy techniques alone or in combination) compared with alternative interventions (eg, no treatment, placebo, and usual care) used for the management of musculoskeletal conditions. We defined musculoskeletal conditions as disorders of muscles, nerves, tendons, ligaments, joints, cartilage, and spinal disks that develop over time. They can be categorized as spinal (eg, mid, low back or neck pain, sciatica, and headaches), upper extremity (eg, shoulder disorders, carpal tunnel syndrome, and lateral epicondylitis), and lower extremity (eg, ankle sprain) disorders.
      We excluded studies where manual therapy was used to treat acute injuries such as fractures and dislocations (eg, to realign bones), except when used for rehabilitation purposes. Studies reporting only costs, only outcomes, reviews, protocols, and conference abstracts were excluded. Cost-consequence studies were excluded because they present an array of different outcomes and cost measures. Studies for which there was insufficient information to calculate the incremental cost-effectiveness ratios (ICERs) for CEA or CUA were also excluded.
      Two independent reviewers (A.T. and P.S.) screened all identified bibliographic records for title/abstract and then for full text. Any disagreements were resolved through consensus or by recourse to a third-party reviewer (A.C.). The first author independently extracted relevant data from included studies which was checked by another reviewer (P.S). The extracted data included study characteristics (eg, author name, country, year of publication, sample size, and follow-up duration), types of participants (eg, condition, age, and sex), types of interventions/comparators, type of economic analysis (cost-effectiveness, cost-utility), perspective (societal, health care system, individual), study currency, discounting, and information pertinent to risk of bias (ROB)/study quality assessment items. The outcomes included pain/disability scores, quality of life (QOL) measures, quality-adjusted life-years (QALYs), costs, and ICERs. We converted mean costs to UK £2012 prices using country-specific gross domestic product deflators
      • World Bank
      World Economic Outlook Database.
      and Purchasing Power Parities from Organisation for Economic Co-operation and Development (£1 = US $1.45 in 2012 prices).
      • Organisation for Economic Co-operation and Development
      Annual national accounts: PPPs and exchange rates.
      We calculated ICERs for each study, if not reported directly. We chose a single willingness to pay (WTP) threshold of £20000 to £30000, which is currently used for the National Institute for Health and Care Excellence (NICE).
      The methodological and reporting quality of economic analyses of the included studies were assessed using the Drummond 10-item checklist.
      • Drummond MF
      • Sculpher MJ
      • Torrance GW
      Methods for the economic evaluation of health care programmes.
      This tool helps to assess the following domains: (a) adequacy of research question, (b) description of treatments, (c) identification of costs and consequences, (d) measurement of costs and consequences, (e) valuation and adjustment of costs and consequences for different timing, (f) incremental analysis of costs and consequences of alternative treatments, (g) uncertainty in the estimates of costs and consequences, and (g) presentation and discussion of study results and issues of concern.
      The ROB in relation to clinical outcomes (ie, pain and health-related QOL measures) was assessed using the 11-item checklist of internal validity criteria recommended by the Cochrane Back Review Group.
      • van Tulder MW
      • Furlan A
      • Bombardier C
      • Bouter L
      Updated method guidelines for systematic reviews in the Cochrane Collaboration Back Review Group.
      This tool is designed to assess the following domains of bias per each outcome: (a) selection bias (ie, methods of randomization and allocation concealment, similarity of groups in important prognostic factors at baseline), (b) performance bias (ie, blinding of patients and care providers, similarity of cointerventions across study groups), detection bias (ie, blinding of outcome assessors), and attrition bias (ie, noncompliance, dropouts, and intention-to-treat analysis). Based on the number of satisfied criteria (response: yes), the studies were assigned a low (at least 6 criteria satisfied) or a high (5 or fewer criteria satisfied) ROB. This threshold was selected given the empirical evidence showing that trials satisfying at least 6 criteria reported smaller effect sizes than trials satisfying fewer criteria (5 or less).
      • van Tulder MW
      • Suttorp M
      • Morton S
      • Bouter LM
      • Shekelle P
      Empirical evidence of an association between internal validity and effect size in randomized controlled trials of low-back pain.
      In support of this construct, the previous research has demonstrated that studies of low methodological quality (ie, higher ROB) tend to exaggerate the treatment effects.
      • Balk EM
      • Bonis PA
      • Moskowitz H
      • et al.
      Correlation of quality measures with estimates of treatment effect in meta-analyses of randomized controlled trials.
      • Moher D
      • Pham B
      • Jones A
      • et al.
      Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?.
      The results were organized by condition and, within each condition, by type of manual therapy. The results were summarized in text and tables.

      Results

      We initially identified 25539 (16976 after de-duplication) bibliographic records, of which 1014 were included in the technical report through the 2-stage screening process (abstract/title and full text). The updated search contributed additional 229 potentially relevant records. Thus, a total of 1243 records were screened for the cost-effectiveness review, of which 129 passed at title/abstract screening level and were judged to be potentially relevant for full-text review. One hundred four of the 129 publications were excluded at full text (these included studies that reported information on costs [n = 31] or outcomes [n = 3] only, cost-consequence studies [n = 9], and CUAs where not enough information was provided to calculate the ICER [n = 2]). Figure 1 provides full details of the search results and reasons for exclusion. The remaining 25 publications, representing 11 unique RCTs included in the review, were the following: Bosmans et al,
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Koke AJ
      • Bouter LM
      • de Vet HC
      Comparison of the effectiveness of a behavioural graded activity program and manual therapy in patients with sub-acute neck pain: design of a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Knol DL
      • Vlaeyen JW
      • Bouter LM
      • de Vet HC
      Is a behavioral graded activity program more effective than manual therapy in patients with subacute neck pain? Results of a randomized clinical trial.
      Williams et al,
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • Williams NH
      • Wilkinson C
      • Russell I
      • et al.
      Randomized Osteopathic Manipulation Study (ROMANS): pragmatic trial for spinal pain in primary care.
      the UK Back Pain Exercise and Manipulation (BEAM) trial team 2004,
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Brealey S
      • Burton K
      • Coulton S
      • et al.
      UK Back pain Exercise and Manipulation (UK BEAM) trial—national randomised trial of physical treatments for back pain in primary care: objectives, design and interventions [ISRCTN32683578].
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: effectiveness of physical treatments for back pain in primary care.
      Niemisto et al,
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      • Niemisto L
      • Lahtinen-Suopanki T
      • Rissanen P
      • Lindgren KA
      • Sarna S
      • Hurri H
      A randomized trial of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain.
      Rivero-Arias et al,
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Frost H
      • Lamb SE
      • Doll HA
      • Carver PT
      • Stewart-Brown S
      Randomised controlled trial of physiotherapy compared with advice for low back pain.
      Bergman et al,
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Bergman GJD
      • Winters JC
      • van der Heijden GJMG
      • Postema K
      • Meyboom-de Jong B
      Groningen Manipulation Study. The effect of manipulation of the structures of the shoulder girdle as additional treatment for symptom relief and for prevention of chronicity or recurrence of shoulder symptoms. Design of a randomized controlled trial within a comprehensive prognostic cohort study.
      • Bergman GJD
      • Winters JC
      • Groenier KH
      • et al.
      Manipulative therapy in addition to usual medical care for patients with shoulder dysfunction and pain: a randomized, controlled trial.
      • Bergman GJ
      • Winters JC
      • Groenier KH
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual care for patients with shoulder complaints: results of physical examination outcomes in a randomized controlled trial.
      Whitehurst et al,
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Hay EM
      • Mullis R
      • Lewis M
      • et al.
      Comparison of physical treatments versus a brief pain-management programme for back pain in primary care: a randomised clinical trial in physiotherapy practice.
      Korthals-de Bos et al,
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Hoving JL
      • Koes BW
      • de Vet HC
      • et al.
      Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial.
      Lewis et al,
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      • Dziedzic K
      • Hill J
      • Lewis M
      • Sim J
      • Daniels J
      • Hay EM
      Effectiveness of manual therapy or pulsed shortwave diathermy in addition to advice and exercise for neck disorders: a pragmatic randomized controlled trial in physical therapy clinics.
      Lin et al,
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      • Lin CC
      • Moseley AM
      • Refshauge KM
      • Haas M
      • Herbert RD
      Effectiveness of joint mobilisation after cast immobilisation for ankle fracture: a protocol for a randomised controlled trial [ACTRN012605000143628].
      and Critchley et al.
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.
      Figure thumbnail gr1
      Fig 1Flowchart of the study selection process.
      The study, participant, treatment, methodology, and outcome characteristics for the 11 included trials are presented in Table 1. The studies were conducted in the United Kingdom,
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.
      the Netherlands,
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      Finland,
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      and Australia.
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      The sample size ranged from 94
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      to 1334 participants.
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      Duration of follow-up ranged from 6
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      to 24 months.
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      The mean age of participants ranged from 37
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      to 51 years.
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      The participants presented with spinal pain (low/upper back, neck),
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      low back pain,
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.
      neck pain,
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      shoulder pain,
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      and ankle fractures.
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      Most studies included participants with nonspecific pain (ie, patients with spinal/shoulder pathology, rheumatoid arthritis, malignancies, pregnancy, osteoarthritis, psychiatric disease, or herniated disk were excluded). In the reviewed studies, interventions whose main components included manual therapy techniques (eg, manipulation and mobilization) were compared with usual general practitioner (GP) care,
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      GP advice,
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      physiotherapist advice,
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      pain management program (back pain education, strengthening, stretching, aerobic exercise),
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.
      exercise,
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      physiotherapy (postural relaxation, walking exercises),
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      or advice and exercise (A&E).
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      Most interventions lasted from 6 to 12 weeks. The cost-effectiveness analyses were based on pain intensity and disability measures. The utility for QALY was based on the EuroQoL EQ-5D (European Quality of Life–5 Dimensions) or the Assessment of Quality of Life (AQoL). The perspective of economic evaluations was societal
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      or health care system.
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.
      All studies from a societal perspective included direct medical, direct nonmedical, and indirect costs. Given 12 months of follow-up in most studies, no discounting was undertaken (see Table 1).
      Table 1Included RCTs and Their Characteristics
      Study IDStudy Participants Eligibility CriteriaStudy Perspective Type of Costs MethodsInterventions (Components)Outcome Measures Follow-up
      Spinal (upper/low back, neck, or both) pain
      Williams 2004
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • Williams NH
      • Wilkinson C
      • Russell I
      • et al.
      Randomized Osteopathic Manipulation Study (ROMANS): pragmatic trial for spinal pain in primary care.


      UK
      Sample size: 201 patients (randomised), 136 patients (analysed)

      Age (mean): NR

      Male (%): NR

      Inclusion: patients aged 16-65 years with non-specific neck or back pain for 2-12 weeks

      Exclusion: patients with serious spinal pathology, nerve root pain, previous spinal surgery, or major psychological disorder
      Perspective: National Health Service

      Direct medical costs: GP and outpatient consultations, investigations, prescribing, hospital stay

      Direct non-medical costs: NA

      Indirect costs: NA

      Discounting: None (study duration < 1 year)
      Intervention 1: OSM (osteopathic manipulation + advice on keeping active, exercise regularly, and avoiding excessive rest) + Usual GP care [3-4 sessions]

      Intervention 2: Usual GP care

      [3-4 sessions]

      Duration: 2 months
      Mean QALY (based on quality of life score EuroQoL EQ-5D)

      ICER

      Last follow-up: 6 months
      Low Back Pain
      Critchley 2007
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.


      UK
      Sample size: 212 patients (randomised), 148 patients (analysed)

      Age (mean): 44 years

      Male (%): 50

      Inclusion: patients aged ≥18 years referred by GP with non-specific LBP >12 weeks

      Exclusion: previous spinal surgery, PT for LBP within 6 months prior to enrolment, chronic conditions such as rheumatoid arthritis or disabilities rendering unsuitable for the treatment
      Perspective: National Health Service

      Direct medical costs: Hospital stays and visits, staff time, procedures, investigations

      Direct non-medical costs: NA

      Indirect costs: NA

      Discounting: 3.5%
      Intervention 1: Individual PT (joint manipulation, mobilisation, massage, back care advice, individual exercises including trunk muscle retraining, stretches, and general spinal mobility) [12 sessions]

      Intervention 2: spinal stabilisation PT (transverses abdominis and lumbar multifidus muscle training, exercise for spinal stability) [8 sessions]

      Intervention 3: Pain management (back pain education, strengthening, stretching, aerobic exercise, cognitive behavioural approach) [8 sessions]

      Duration: NR
      Mean QALY (based on quality of life score EuroQoL EQ-5D)

      ICER

      Last follow-up: 18 months
      Niemisto 2005
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      • Niemisto L
      • Lahtinen-Suopanki T
      • Rissanen P
      • Lindgren KA
      • Sarna S
      • Hurri H
      A randomized trial of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain.


      Finland
      Sample size: 204 patients (randomised), 138 patients (analysed)

      Age (mean): 37 years

      Male (%): 46

      Inclusion: patients 24-46 years of age with non-specific LBP ≥ 3 months and disability measured with ODI of 16%

      Exclusion: malignancies, ankylosing spondylitis, severe osteoporosis, osteoarthritis, paralysis, progressive neurologic disorder, haemophilia, spinal infection, spinal operation, vertebral fracture within 6 months of trial, pregnancy, severe sciatica, and psychiatric disease
      Perspective: Societal

      Direct medical costs: Physician visits, physiotherapy visits, outpatient clinics, hospital stays, x-rays

      Direct non-medical costs: Drug and travel costs

      Indirect costs:

      Productivity loss costs

      Discounting: None
      Intervention 1: Manipulative combination treatment (manipulation with muscle energy technique to correct any biomechanical dysfunction in the lumbar or pelvic segments, stabilizing exercise to correct the lumbopelvic rhythm, GP advice)

      [4 sessions]

      Intervention 2: GP advice (booklet, advice on exercise, muscle stretch, and stability)

      [1 session]

      Duration: 4 weeks
      ICER (based on pain and ODI scores)

      Last follow-up: 24 months
      Rivero-Arias 2006
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Frost H
      • Lamb SE
      • Doll HA
      • Carver PT
      • Stewart-Brown S
      Randomised controlled trial of physiotherapy compared with advice for low back pain.


      UK
      Sample size: 286 patients (randomised and analysed)

      Age (mean): 41 years

      Male (%): 47.5

      Inclusion: patients ≥18 years with LBP ≥ 6 weeks

      Exclusion: patients with systemic rheumatologic disease, gynaecological problems, ankylosing spondylitis, tumours, infections, past spinal surgery, or treatment for physical problems
      Perspective: National Health Service and Societal

      Direct medical costs: NHS costs (intervention, GP visits, hospitalisations, prescribed items)

      Direct non-medical costs: Health care purchased by patient (private consultations with osteopaths, chiropractors, over the counter drugs)

      Indirect costs: employment costs (number of days off work)

      Discounting: None (12 months follow-up)
      Intervention 1: PT (joint manipulation, mobilisation, massage, stretching, spinal mobility and strengthening exercise, heat/cold therapy) + advice to remain active (back book) [5 sessions]

      Intervention 2: Advice to remain active (back book)[1 session]

      Duration: NR
      Mean QALY (based on quality of life score EuroQoL EQ-5D)

      ICER

      Last follow-up: 12 months
      UK BEAM 2004
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Brealey S
      • Burton K
      • Coulton S
      • et al.
      UK Back pain Exercise and Manipulation (UK BEAM) trial—national randomised trial of physical treatments for back pain in primary care: objectives, design and interventions [ISRCTN32683578].
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: effectiveness of physical treatments for back pain in primary care.


      UK
      Sample size: 1334 patients (randomised), 1287 patients (analysed)

      Age (mean): 43.1 years

      Male (%): 44

      Inclusion: patients 18-65 years of age with non-specific LBP ≥ 1 months and RMDQ ≥ 4

      Exclusion: patients with malignancies, ankylosing spondylitis, osteoporosis, infections, past spinal surgery, psychiatric disease, treatment for physical problems 3 months before trial, chronic use of steroids, cardiovascular condition, or previous attendance to pain management clinic
      Perspective: National Health Service

      Direct medical costs: GP care/consultations, visits, outpatient attendance, hospital stay, programmes of exercise, manipulation

      Direct non-medical costs: NA

      Indirect costs: NA

      Discounting: None (12 months follow-up)
      Intervention 1: GP care

      Intervention 2: Exercise + GP care [9 sessions]

      Intervention 3: Manipulation (a multidisciplinary group developed a package of techniques representative of those used by the UK chiropractic, osteopathic, and physiotherapy professions) + GP care [9 sessions]

      Intervention 4: Manipulation + exercise + GP care [9 sessions]

      Duration: 12 weeks
      Mean QALY (based on quality of life score EuroQoL EQ-5D)

      ICER

      Last follow-up: 12 months
      Whitehurst 2007
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Hay EM
      • Mullis R
      • Lewis M
      • et al.
      Comparison of physical treatments versus a brief pain-management programme for back pain in primary care: a randomised clinical trial in physiotherapy practice.


      UK
      Sample size: 402 patients (randomised and analysed)

      Age (mean): 41 years

      Male (%): 47

      Inclusion: patients 18-64 years of age with non-specific LBP < 12 weeks

      Exclusion: serious spinal or systemic disorders, long-term sick leave (> 12 weeks), osteoporosis, inflammatory arthritis, steroid treatment (> 12 weeks), pregnancy, previous hip/back surgery or fracture, abdominal surgery, back pain treatment by another professional
      Perspective: National Health Service

      Direct medical costs: |treatment sessions (PT and |BPM), outpatient attendance, inpatient attendance, primary care contacts, other health professionals (e.g., acupuncture, chiropractic, osteopathy, physiotherapy)

      Direct non-medical costs: NA

      Indirect costs: NA

      Discounting: None (12 months follow-up)
      Intervention 1: Manual PT (articulatory mobilisation, manipulation, or soft tissue techniques, spinal stabilisation, back exercise, ergonomic advice, back education) [7 sessions]

      Intervention 2: BPM (general fitness, exercise for spinal mobility, explanation about pain mechanisms, distress, coping strategies) [2-day course plus clinical tutoring]

      Duration: NR
      Mean QALY

      ICER (based on EuroQoL EQ-5D; RMDQ score)

      Last follow-up: 12 months
      Neck Pain
      Bosmans 2011
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Koke AJ
      • Bouter LM
      • de Vet HC
      Comparison of the effectiveness of a behavioural graded activity program and manual therapy in patients with sub-acute neck pain: design of a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Knol DL
      • Vlaeyen JW
      • Bouter LM
      • de Vet HC
      Is a behavioral graded activity program more effective than manual therapy in patients with subacute neck pain? Results of a randomized clinical trial.


      The Netherlands
      Sample size: 146 patients (randomised and analysed)

      Age (mean): 45 years

      Male (%): 40

      Inclusion: patients 18-70 years of age with non-specific neck pain (4-12 weeks)

      Exclusion: malignancy, neurologic disease, herniated disc, or systemic rheumatic disease
      Perspective: Societal

      Direct medical costs: Primary care (GP, SMT, BGA, massage, homeopathy, outpatient visit, x-ray, tomography, MRI), supportive care

      Direct non-medical costs: Informal care, paid home help

      Indirect costs: Absenteeism from paid/unpaid work

      Discounting: None (12 months follow-up)
      Intervention 1: SMT (manipulation using passive movement of a joint beyond its active and passive limit of motion with a localized thrust of small amplitude to regain motion, restore function, and reduce pain; mobilisation using skilled low grade passive movement with large amplitude to restore movement and relieve pain) [6 sessions]

      Intervention 2: BGA (gradually increasing exercise program) [18 sessions]

      Duration: 6 weeks
      Mean QALY

      ICER (based on mean QALY; pain; perceived recovery; NDI)

      Last follow-up: 12 months
      Korthals-de Bos 2003
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Hoving JL
      • Koes BW
      • de Vet HC
      • et al.
      Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial.


      The Netherlands
      Sample size: 183 patients (randomised), 178 patients (analysed)

      Age (mean): 45 years

      Male (%): 40

      Inclusion: patients 18-70 years of age with non-specific neck pain (≥ 2 weeks)

      Exclusion: previous neck surgery, malignancy, neurologic disease, fracture, herniated disc, or systemic rheumatic disease
      Perspective: Societal

      Direct medical costs: GP, SMT, PT, outpatient appointments, hospitalisation, exercise, home care

      Direct non-medical costs: Alternative therapy, home care, friend’s or partner’s help, travel

      Indirect costs: Absenteeism from paid/unpaid work

      Discounting: None (trial duration: 12 months)
      Intervention 1: SMT (combination of techniques described by Cyeariax, Kaltenborn, Maitland, and Mennel using hands-on muscular and articular mobilisation techniques, coordination or stabilisation techniques, and joint mobilisation with low-velocity passive movements) [6 sessions]

      Intervention 2: PT (active, postural, or relaxation exercises, stretching, massage, manual traction) [12 sessions]

      Intervention 3: GP care (standard care, advice on self-care, education, ergonomic issues, paracetamol or NSAIDs, if necessary) [1 session and optional biweekly follow-up visits]

      Duration: 6 weeks
      Mean QALY

      ICER (based on EuroQoL EQ-5D; pain; NDI)

      Last follow-up: 12 months
      Lewis 2007
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      • Dziedzic K
      • Hill J
      • Lewis M
      • Sim J
      • Daniels J
      • Hay EM
      Effectiveness of manual therapy or pulsed shortwave diathermy in addition to advice and exercise for neck disorders: a pragmatic randomized controlled trial in physical therapy clinics.


      UK
      Sample size: 350 patients (randomised), 346 patients (analysed)

      Age (mean): 51 years

      Male (%): 37

      Inclusion: patients ≥ 18 years with non-specific neck pain who consulted only primary care team in the previous 6 months

      Exclusion: weight loss, fever, progressive neurologic signs, muscle weakness, sensation disturbance, malignancy, systemic rheumatic disease, osteoporosis, contraindications to the study treatments, taking anticoagulants
      Perspective: National Health Service and Societal

      Direct medical costs: Study intervention sessions, GP consultations, outpatient attendance (e.g., rheumatology, physiotherapist, neurologist, emergency, radiographer, acupuncturist)

      Direct non-medical costs: patient expenses (e.g., prescription drugs, over-the-counter medicines, devices)

      Indirect costs: Absenteeism from paid work

      Discounting: None (trial duration: 6 months
      Intervention 1: A & E [8 sessions]

      Intervention 2: A & E + SMT (passive/active assisted hands-on movements, joint and soft tissue mobilisations or manipulations graded as appropriate to the patient’s signs and symptoms) [8 sessions]

      Intervention 3: A & E + PSWD [8 sessions]

      Duration: 6 weeks
      Mean QALY

      ICER (based on EuroQoL EQ-5D; NPQ)

      Last follow-up: 6 months
      Shoulder Pain
      Bergman 2010
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Bergman GJD
      • Winters JC
      • van der Heijden GJMG
      • Postema K
      • Meyboom-de Jong B
      Groningen Manipulation Study. The effect of manipulation of the structures of the shoulder girdle as additional treatment for symptom relief and for prevention of chronicity or recurrence of shoulder symptoms. Design of a randomized controlled trial within a comprehensive prognostic cohort study.
      • Bergman GJD
      • Winters JC
      • Groenier KH
      • et al.
      Manipulative therapy in addition to usual medical care for patients with shoulder dysfunction and pain: a randomized, controlled trial.
      • Bergman GJ
      • Winters JC
      • Groenier KH
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual care for patients with shoulder complaints: results of physical examination outcomes in a randomized controlled trial.


      The Netherlands
      Sample size: 150 patients (randomised), 140 patients (analysed; excluding 2 outliers)

      Age (mean): 48 years

      Male (%): 49

      Inclusion: patients ≥ 18 years with non-specific shoulder pain without shoulder treatment in the past 3 months

      Exclusion: fractures, ruptures or dislocations in the shoulder region, previous orthopaedic surgery, contraindications for manipulative therapy, cervical nerve root compression, rheumatic disorder, dementia, psychiatric disorder, or abdominal pathology
      Perspective: Societal

      Direct medical costs: treatment by GP, physiotherapist, manual, occupational, exercise or complementary health therapists, visits to consultant in orthopedic surgery, acupuncturist, neurology, rheumatology, rehabilitation medicine, and hospitalisation

      Direct non-medical costs: out-of-pocket expenses, costs for paid/unpaid help

      Indirect costs: loss of production due to sick leave from paid/unpaid work

      Discounting: None (trial duration: 6 months)
      Intervention 1: SMT (high velocity low amplitude manipulation and passive low velocity mobilisation within the range of joint motion) [6 sessions]

      + Usual GP care (advice on daily living, if needed analgesics, NSAIDs, corticosteroid injections, or PT including massage and exercise)

      Intervention 2: Usual GP care [number sessions: NR]

      Duration: 12 weeks
      ICER (based on perceived recovery; shoulder pain; shoulder disability; general health)

      Last follow-up: 6 months
      Ankle Fracture
      Lin 2008
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      • Lin CC
      • Moseley AM
      • Refshauge KM
      • Haas M
      • Herbert RD
      Effectiveness of joint mobilisation after cast immobilisation for ankle fracture: a protocol for a randomised controlled trial [ACTRN012605000143628].


      Australia
      Sample size: 94 patients (randomised), 92 patients (analysed)

      Age (mean): 41.5 years

      Male (%): 54

      Inclusion: patients ≥ 18 years with ankle fractures treated with cast immobilisation with cast removed the week before the trial entry, pain VAS ≥ 2, approved to weight-bear as tolerated or partial weight-bear

      Exclusion: patients with significant pathologies
      Perspective: Health care system and patient

      Direct medical costs: outpatient physiotherapy, medical specialists, GP, emergency department, hospitalisation, medication, investigations, private health providers,

      Direct non-medical costs: public transport, private vehicle

      Indirect costs: None

      Discounting: None (trial duration: 6 months)
      Intervention 1: MT (large amplitude oscillatory anterior-posterior glides of the talus) + PT (exercise, gait retraining, walking aids, advice, ice, elevation and progression if required) [8 sessions]

      Intervention 2: PT [5 sessions]

      Duration: 4 weeks
      ICER (quality of life AQol: QALY)

      Last follow-up: 6 months
      A&E, advice and exercise; BGA, behavioral graded activity; BPM, brief pain management; EQ-5D, European Quality of Life-5 Dimensions; GP, general practitioner; ICER, incremental cost-effectiveness ratio; LBP, lower back pain; MRI, magnetic resonance imaging; MT, manual therapy; NA, not applicable; NDI, Neck Disability Index; NHS, National Health Service; NPQ, Northwick Park Neck Pain Questionnaire; NR, not reported; NS, statistically nonsignificant; NSAIDs, nonsteroidal anti-inflammatory drugs; ODI, Oswestry Disability Index; OSM, osteopathic manual therapy; PSWD, pulsed shortwave diathermy; PT, physiotherapy/physical therapy; QALY, quality-adjusted life year; RMDQ, Roland-Morris Disability Questionnaire; SMT, spinal manual therapy.

      Methodological and Reporting Quality of Economic Evaluations

      The quality assessment showing the percentage of items with “yes” on the Drummond checklist is presented in Table 2. In all studies, the research question was clearly formulated, with good descriptions of the interventions and comparators. Most studies reported all important costs (ie, direct medical, direct nonmedical, and indirect) and consequences (ie, outcome measures). Because costs were not individually itemized for more than half of the studies, it was not clear what data were used to calculate the total costs. All studies reported valuation methods of costs and consequences, which were judged as adequate. The ICERs were reported in all studies, except for 1 study where information was provided to calculate this ratio.
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      • Lin CC
      • Moseley AM
      • Refshauge KM
      • Haas M
      • Herbert RD
      Effectiveness of joint mobilisation after cast immobilisation for ankle fracture: a protocol for a randomised controlled trial [ACTRN012605000143628].
      The studies provided detailed discussion sections by highlighting main study findings, interpretation of the findings, study strengths and limitations, consistency of findings with other studies, and future directions.
      Table 2Methodological Quality of Economic Evaluations in the Included Studies (the Drummond Checklist for Critical Appraisal of Economical Evaluation)
      • Drummond MF
      • Sculpher MJ
      • Torrance GW
      Methods for the economic evaluation of health care programmes.
      Item no.
      Responses to items: yes, no, can't tell.
      Bergman et al
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Bergman GJD
      • Winters JC
      • van der Heijden GJMG
      • Postema K
      • Meyboom-de Jong B
      Groningen Manipulation Study. The effect of manipulation of the structures of the shoulder girdle as additional treatment for symptom relief and for prevention of chronicity or recurrence of shoulder symptoms. Design of a randomized controlled trial within a comprehensive prognostic cohort study.
      • Bergman GJD
      • Winters JC
      • Groenier KH
      • et al.
      Manipulative therapy in addition to usual medical care for patients with shoulder dysfunction and pain: a randomized, controlled trial.
      • Bergman GJ
      • Winters JC
      • Groenier KH
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual care for patients with shoulder complaints: results of physical examination outcomes in a randomized controlled trial.
      Bosmans et al
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Koke AJ
      • Bouter LM
      • de Vet HC
      Comparison of the effectiveness of a behavioural graded activity program and manual therapy in patients with sub-acute neck pain: design of a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Knol DL
      • Vlaeyen JW
      • Bouter LM
      • de Vet HC
      Is a behavioral graded activity program more effective than manual therapy in patients with subacute neck pain? Results of a randomized clinical trial.
      Critchley et al
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.
      Korthals-de Bos et al
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Hoving JL
      • Koes BW
      • de Vet HC
      • et al.
      Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial.
      Lewis et al
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      • Dziedzic K
      • Hill J
      • Lewis M
      • Sim J
      • Daniels J
      • Hay EM
      Effectiveness of manual therapy or pulsed shortwave diathermy in addition to advice and exercise for neck disorders: a pragmatic randomized controlled trial in physical therapy clinics.
      Lin et al
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      • Lin CC
      • Moseley AM
      • Refshauge KM
      • Haas M
      • Herbert RD
      Effectiveness of joint mobilisation after cast immobilisation for ankle fracture: a protocol for a randomised controlled trial [ACTRN012605000143628].
      Niemisto et al
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      • Niemisto L
      • Lahtinen-Suopanki T
      • Rissanen P
      • Lindgren KA
      • Sarna S
      • Hurri H
      A randomized trial of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain.
      Rivero-Arias et al
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Frost H
      • Lamb SE
      • Doll HA
      • Carver PT
      • Stewart-Brown S
      Randomised controlled trial of physiotherapy compared with advice for low back pain.
      UK BEAM
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Brealey S
      • Burton K
      • Coulton S
      • et al.
      UK Back pain Exercise and Manipulation (UK BEAM) trial—national randomised trial of physical treatments for back pain in primary care: objectives, design and interventions [ISRCTN32683578].
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: effectiveness of physical treatments for back pain in primary care.
      Whitehurst et al
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Hay EM
      • Mullis R
      • Lewis M
      • et al.
      Comparison of physical treatments versus a brief pain-management programme for back pain in primary care: a randomised clinical trial in physiotherapy practice.
      Williams et al
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • Williams NH
      • Wilkinson C
      • Russell I
      • et al.
      Randomized Osteopathic Manipulation Study (ROMANS): pragmatic trial for spinal pain in primary care.
      Item 1YesYesYesYesYesYesYesYesYesYesYes
      Item 2YesYesYesYesYesYesYesYesYesYesYes
      Item 3YesYesYesYesYesYesYesYesYesYesYes
      Item 4YesYesCan't tell (costs)YesNo (costs)YesYesYesYesYesYes
      Item 5Can't tell (costs)YesCan't tell (costs)Can't tell (costs)Can't tell (costs)Can't tell (costs)Can't tell (costs)YesYesYesYes
      Item 6YesYesYesYesYesYesYesYesYesYesYes
      Item 7YesYesYesYesYesYesYesYesYesYesYes
      Item 8YesYesYesYesYesNoYesYesYesYesYes
      Item 9YesYesYesYesYesNoYesYesYesYesYes
      Item 10YesYesYesNoYesYesYesYesYesYesYes
      % of items with “yes” on Drummond checklist
      901008080807090100100100100
      Item 1: Was a well-defined question posed in answerable form? Item 2: Was a comprehensive description of the competing alternatives given? Item 3: Was the effectiveness of the programmes or services established? Item 4: Were all the important and relevant costs and consequences for each alternative identified? Item 5: Were costs and consequences measured accurately in appropriate physical units (e.g. number of physician visits, lost work-days, gained life-years)? Item 6: Were costs and consequences valued credibly? Item 7: Were costs and consequences adjusted for differential timing? Item 8: Was an incremental analysis of costs and consequences of alternatives performed? Item 9: Was allowance made for uncertainty in the estimates of costs and consequences? Item 10: Did the presentation and discussion of study results include all issues of concern to users?
      a Responses to items: yes, no, can't tell.

      Risk of Bias Assessment

      Risk of bias assessments are presented in Table 3. Briefly, 7 of the 11 included trials were rated as having low ROB
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.
      and 4 trials as having high ROB.
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      Patients and care providers in the studies were not blinded to the intervention type, and because the outcomes were self-reported (eg, pain, QOL), blinding of assessors was considered not applicable. Most of the studies reported adequate methods of randomization and treatment allocation concealment. Results of all studies were based on intention-to-treat analysis.
      Table 3Risk of Bias assessment of the Included RCTs (Adapted From van Tulder et al
      • van Tulder MW
      • Furlan A
      • Bombardier C
      • Bouter L
      Updated method guidelines for systematic reviews in the Cochrane Collaboration Back Review Group.
      )
      ROB ItemBergman et al
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Bergman GJD
      • Winters JC
      • van der Heijden GJMG
      • Postema K
      • Meyboom-de Jong B
      Groningen Manipulation Study. The effect of manipulation of the structures of the shoulder girdle as additional treatment for symptom relief and for prevention of chronicity or recurrence of shoulder symptoms. Design of a randomized controlled trial within a comprehensive prognostic cohort study.
      • Bergman GJD
      • Winters JC
      • Groenier KH
      • et al.
      Manipulative therapy in addition to usual medical care for patients with shoulder dysfunction and pain: a randomized, controlled trial.
      • Bergman GJ
      • Winters JC
      • Groenier KH
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual care for patients with shoulder complaints: results of physical examination outcomes in a randomized controlled trial.
      Bosmans et al
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Koke AJ
      • Bouter LM
      • de Vet HC
      Comparison of the effectiveness of a behavioural graded activity program and manual therapy in patients with sub-acute neck pain: design of a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Knol DL
      • Vlaeyen JW
      • Bouter LM
      • de Vet HC
      Is a behavioral graded activity program more effective than manual therapy in patients with subacute neck pain? Results of a randomized clinical trial.
      Critchley et al
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.
      Korthals-de Bos et al
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Hoving JL
      • Koes BW
      • de Vet HC
      • et al.
      Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial.
      Lewis et al
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      • Dziedzic K
      • Hill J
      • Lewis M
      • Sim J
      • Daniels J
      • Hay EM
      Effectiveness of manual therapy or pulsed shortwave diathermy in addition to advice and exercise for neck disorders: a pragmatic randomized controlled trial in physical therapy clinics.
      Lin et al
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      • Lin CC
      • Moseley AM
      • Refshauge KM
      • Haas M
      • Herbert RD
      Effectiveness of joint mobilisation after cast immobilisation for ankle fracture: a protocol for a randomised controlled trial [ACTRN012605000143628].
      Niemisto et al
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      • Niemisto L
      • Lahtinen-Suopanki T
      • Rissanen P
      • Lindgren KA
      • Sarna S
      • Hurri H
      A randomized trial of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain.
      Rivero-Arias et al
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Frost H
      • Lamb SE
      • Doll HA
      • Carver PT
      • Stewart-Brown S
      Randomised controlled trial of physiotherapy compared with advice for low back pain.
      UK BEAM
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Brealey S
      • Burton K
      • Coulton S
      • et al.
      UK Back pain Exercise and Manipulation (UK BEAM) trial—national randomised trial of physical treatments for back pain in primary care: objectives, design and interventions [ISRCTN32683578].
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: effectiveness of physical treatments for back pain in primary care.
      Whitehurst et al
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Hay EM
      • Mullis R
      • Lewis M
      • et al.
      Comparison of physical treatments versus a brief pain-management programme for back pain in primary care: a randomised clinical trial in physiotherapy practice.
      Williams et al
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • Williams NH
      • Wilkinson C
      • Russell I
      • et al.
      Randomized Osteopathic Manipulation Study (ROMANS): pragmatic trial for spinal pain in primary care.
      Was the method of randomization adequate?Don't knowYesYesYesYesYesDon't knowYesYesYesYes
      Was the treatment allocation concealed?YesYesYesYesDon't knowYesYesYesYesYesDon't know
      Were the groups similar at baseline regarding the most important prognostic indicators?YesYesYesNoNoYesNoNoYesYesYes
      Was the patient blinded to the intervention?NoNoNoNoNoNoNoNoNoNoNo
      Was the care provider blinded to the intervention?Don't knowDon't knowNoNoNoNoNoNoNoNoDon't know
      Was the outcome assessor blinded to the intervention?NANANANANANANANANANANA
      Were cointerventions avoided or similar?Don't knowDon't knowYesNoNoDon't knowYesNoDon't knowNoDon't know
      Was the compliance acceptable in all groups?YesNoDon't knowNoYesYesYesYesDon't knowNoDon't know
      Was the dropout rate described and acceptable?YesYesNoYesYesYesYesNoYesYesNo
      Was the timing of the outcome assessment in all groups similar?YesYesYesYesYesYesYesYesYesYesYes
      Did the analysis include an intention-to-treat analysis?YesYesYesYesYesYesYesYesYesYesYes
      Summary ROBLow ROBLow ROBLow ROBHigh ROBHigh ROBLow ROBLow ROBHigh ROBLow ROBLow ROBHigh ROB
      Yes, if item is satisfied; no, if item is not satisfied; Don't know, unclear if item was satisfied or not; Low ROB, if 6 or more items are satisfied (rated as “yes”); High ROB, if 5 or fewer items are satisfied (rated as “yes”).
      NA, not applicable; ROB, risk of bias.

      Cost-Effectiveness and/or Cost-Utility of Manual Therapy

      Results are presented by condition in the text below as well as in Table 4.
      Table 4Cost-Effectiveness/Cost-Utility of Manual Therapy Interventions According to Condition – RCTs
      Study IDAnalysisHealth OutcomesMean Costs

      Mean (SD) Health Effects
      Difference in Costs

      Incremental Ratio
      Spinal (upper/low back, neck, or both) pain
      Williams 2004
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • Williams NH
      • Wilkinson C
      • Russell I
      • et al.
      Randomized Osteopathic Manipulation Study (ROMANS): pragmatic trial for spinal pain in primary care.


      UK
      High risk of bias (≤ 5 items of the recommended criteria by the Cochrane
      Analysis: CUA

      Statistical analysis: Non-parametric bootstrap (1000 simulations)
      EuroQoL EQ-5DOSM + Usual GP care

      Costs: £402

      Health effects

      EQ-5D: 0.717 (0.248)

      QALY: 0.056 (0.101)

      Usual GP care

      Costs: £286

      Health effects

      EQ-5D: 0.656 (0.289)

      QALY: 0.031 (0.105)
      Incremental Costs:

      £117

      Cost per QALY gained:

      £4674
      Low Back Pain
      Critchley 2007
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.


      UK
      Low risk of bias (≥ 6 items of the recommended criteria by the Cochrane Back Review Group were satisfied)
      Analysis: CUA

      Statistical analysis: ANOVA, non-parametric bootstrap (number of simulations: NR)
      EuroQoL EQ-5DIndividual PT

      Costs: £574

      Health effects

      EQ-5D: 0.67

      QALY: 0.990

      Spinal stabilisation PT

      Costs: £459

      Health effects

      EQ-5D: 0.63

      QALY: 0.900

      Pain management

      Costs: £200

      Health effects

      EQ-5D: 0.68

      QALY: 1.000
      Individual PT – spinal stabilisation

      Incremental Costs:

      £115

      Cost per QALY gained:

      £1279

      Cost per QALY gained:

      Pain management dominant over both treatments (individual PT and spinal stabilisation)
      Niemisto 2005
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      • Niemisto L
      • Lahtinen-Suopanki T
      • Rissanen P
      • Lindgren KA
      • Sarna S
      • Hurri H
      A randomized trial of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain.


      Finland
      Low risk of bias (≥ 6 items of the recommended criteria by the Cochrane Back Review Group were satisfied)
      Analysis: CEA

      Statistical analysis: Repeated measures ANOVA, Intention to Treat analysis, bootstrap technique (5000 simulations)
      Pain (visual analogue score), Oswestry Disability Index (ODI), 15-D (HRQoL)MT + exercise + GP advice

      Costs: £4568

      Health effects: NR

      GP advice

      Costs: £5643

      Health effects: NR
      Incremental Costs:

      -£1075

      Cost per unit of outcome improved in:

      Pain (VAS)

      £165

      Disability (ODI)

      £384
      Rivero-Arias 2006
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Frost H
      • Lamb SE
      • Doll HA
      • Carver PT
      • Stewart-Brown S
      Randomised controlled trial of physiotherapy compared with advice for low back pain.


      UK
      High risk of bias (≤ 5 items of the recommended criteria by the Cochrane
      Analysis: CUA

      Statistical analysis: Mean differences and 95% CI using independent sample t test (for costs) and ANCOVA (for QALYs), multiple imputation for missing values using linear regression technique
      EuroQoL EQ-5DPT

      Costs: £320

      Health effects

      EQ-5D: 0.73 (0.25)

      QALY: 0.740 (0.18)

      Physiotherapist advice

      Costs: £247

      Health effects

      EQ-5D: 0.72 (0.26)

      QALY: 0.690 (0.23)
      Incremental Costs:

      £73

      Cost per QALY gained:

      £1454
      UK BEAM 2004
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Brealey S
      • Burton K
      • Coulton S
      • et al.
      UK Back pain Exercise and Manipulation (UK BEAM) trial—national randomised trial of physical treatments for back pain in primary care: objectives, design and interventions [ISRCTN32683578].
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: effectiveness of physical treatments for back pain in primary care.


      UK
      Low risk of bias (≥ 6 items of the recommended criteria by the Cochrane Back Review Group were satisfied)
      Analysis: CUA

      Statistical analysis: Bayesian Markov Chain Monte Carlo multilevel analysis
      EuroQoL EQ-5DGP (Best) care + manipulation

      Costs: £702

      Health effects

      QALY 0.659

      GP (Best) care + manipulation + exercise

      Costs: £612

      Health effects

      QALY: 0.651

      GP (Best) care + exercise

      Costs: £631

      Health effects

      QALY: 0.635

      GP (Best) care

      Costs: £449

      Health effects

      QALY: 0.618
      GP (Best) care + manipulation - GP (Best) care

      Incremental costs:

      £253

      Cost per QALY gained:

      £6175

      GP (Best) care + manipulation + exercise - GP (Best) care

      Incremental costs:

      £162

      Cost per QALY gained:

      £4918

      Dominant over GP (Best) care + exercise

      GP (Best) care + exercise - GP (Best) care

      Incremental costs:

      £182

      Cost per QALY gained:

      £10692
      Whitehurst 2007
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Hay EM
      • Mullis R
      • Lewis M
      • et al.
      Comparison of physical treatments versus a brief pain-management programme for back pain in primary care: a randomised clinical trial in physiotherapy practice.


      UK
      Low risk of bias (≥ 6 items of the recommended criteria by the Cochrane Back Review Group were satisfied)
      Analysis: CUA, CEA

      Statistical analysis: Intention to Treat analysis, multiple imputation based on multiple linear regression models, 95% CIs based on parametric tests if normal distribution, and if skewed, bootstrapping technique (5000 simulations)
      Disability (RMDQ score), EuroQoL EQ-5DManual PT

      Costs: £246

      Health effects

      Mean change disability (RMDQ): 8.887

      QALY: 0.777

      BPM

      Costs: £180

      Health effects

      Mean change disability (RMDQ): 8.553

      QALY: 0.755
      Incremental costs:

      -£66

      Cost per RMDQ change:

      £198

      Cost per QALY gained:

      £3006
      Neck Pain
      Bosmans 2011
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Koke AJ
      • Bouter LM
      • de Vet HC
      Comparison of the effectiveness of a behavioural graded activity program and manual therapy in patients with sub-acute neck pain: design of a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Knol DL
      • Vlaeyen JW
      • Bouter LM
      • de Vet HC
      Is a behavioral graded activity program more effective than manual therapy in patients with subacute neck pain? Results of a randomized clinical trial.


      Netherlands
      Low risk of bias (≥ 6 items of the recommended criteria by the Cochrane Back Review Group were satisfied)
      Analysis: CEA

      Statistical analysis: Intention to Treat analysis, multiple imputation, CIs based on bootstrapping (5000 simulations)
      Pain (VAS), disability (NDI), perceived recovery, and quality of life (SF-12)SMT (MOB + MAN)

      Costs: £823

      Health effects

      Mean change

      VAS: -3.5 (SE 0.31)

      NDI: -8.3 (SE 0.77)

      Recovery: 0.76 (SE 0.05)

      QALY: 0.770 (SE 0.01)

      BGA (increasing exercise program)

      Costs: £1,174

      Health effects

      Mean change

      VAS: - 4.4 (SE 0.31)

      NDI: -10.6 (SE 0.79)

      Recovery: 0.78 (SE 0.05)

      QALY: 0.750 (SE 0.01)
      Incremental costs:

      -£349

      Cost per unit of outcome improved in:

      BGA versus SMT

      Recovery: £17,444

      Pain: £388

      NDI: £152

      Cost per QALY gained:

      £17444
      Korthals-de Bos 2003
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Hoving JL
      • Koes BW
      • de Vet HC
      • et al.
      Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial.


      Netherlands
      High risk of bias (≤ 5 items of the recommended criteria by the Cochrane
      Analysis: CUA, CEA

      Statistical analysis: Intention to Treat analysis, CIs based on bootstrapping (500 simulations), ICERs based on bootstrapping (5000 simulations)
      Pain (VAS), disability (NDI), perceived recovery, EuroQoL EQ-5DSMT (mobilisation)

      Costs: £604

      Health effects

      Mean change

      VAS: 4.2 (2.4)

      NDI: 7.2 (7.5)

      Recovery: 71.7 (43)

      Utility: 0.820 (0.13)

      PT

      Costs: £1753

      Health effects

      Mean change

      VAS: 3.1 (2.9)

      NDI: 6.3 (8.0)

      Recovery: 62.7 (37)

      Utility: 0.790 (0.14)

      GP care

      Costs: £1864

      Health effects

      Mean change

      VAS: 4.1 (2.9)

      NDI: 8.5 (7.4)

      Recovery: 56.3 (36)

      Utility: 0.770 (0.16)
      SMT (mobilisation) – GP care

      Incremental costs:

      -£1260

      PT – GP care

      Incremental costs:

      -£111

      Cost per unit of outcome improved in:

      Dominance of SMT over GP care and PT in terms of recovery and pain

      Cost per QALY gained:

      Dominance of SMT over GP care and PT in terms of QALYs

      Cost per unit of outcome improved in:

      PT over GP care

      Pain

      £111

      NDI

      £50

      Cost per QALY gained:

      Dominance of PT over GP care in terms of QALYs
      Lewis 2007
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      • Dziedzic K
      • Hill J
      • Lewis M
      • Sim J
      • Daniels J
      • Hay EM
      Effectiveness of manual therapy or pulsed shortwave diathermy in addition to advice and exercise for neck disorders: a pragmatic randomized controlled trial in physical therapy clinics.


      UK
      High risk of bias (≤ 5 items of the recommended criteria by the Cochrane
      Analysis: CUA, CEA Statistical analysis: Intention to Treat analysis, CIs for differences in means using parametric methods, CIs for uncertainty in cost estimates were based on bootstrapping (5000 simulations), linear regression to adjust for baseline covariates, multiple imputation technique to account for missing dataDisability (NPQ), EuroQoL EQ-5DSMT (MOB + MAN) + A&E

      Costs: £367

      Health effects

      NPQ: 10.2 (14.1)

      QALY: 0.342 (0.114)

      PSWD + A&E (advice + exercise)

      Costs: £410

      Health effects

      NPQ: 10.3 (15.0)

      QALY: 0.360 (0.094)

      A&E (advice + exercise)

      Costs: £452

      Health effects

      NPQ: 11.5 (15.7)

      QALY: 0.362 (0.114)
      SMT (MOB + MAN) + A&E - A&E (advice + exercise)

      Incremental costs:

      -£84

      PSWD + A&E (advice + exercise) - A&E (advice + exercise)

      Incremental costs:

      -£42

      Cost per unit of outcome improved in NPQ:

      A&E over SMT

      £65

      Cost per QALY gained:

      A&E over SMT

      £4672
      Shoulder Pain
      Bergman 2010
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Bergman GJD
      • Winters JC
      • van der Heijden GJMG
      • Postema K
      • Meyboom-de Jong B
      Groningen Manipulation Study. The effect of manipulation of the structures of the shoulder girdle as additional treatment for symptom relief and for prevention of chronicity or recurrence of shoulder symptoms. Design of a randomized controlled trial within a comprehensive prognostic cohort study.
      • Bergman GJD
      • Winters JC
      • Groenier KH
      • et al.
      Manipulative therapy in addition to usual medical care for patients with shoulder dysfunction and pain: a randomized, controlled trial.
      • Bergman GJ
      • Winters JC
      • Groenier KH
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual care for patients with shoulder complaints: results of physical examination outcomes in a randomized controlled trial.


      Netherlands
      Low risk of bias (≥ 6 items of the recommended criteria by the Cochrane Back Review Group were satisfied)
      Analysis: CEA

      Statistical analysis: paired sample t-test, bootstrapping (2000 replications) to compare mean costs between the groups and estimate 95% CIs, Intention to Treat analysis
      Perceived recovery (%), shoulder pain, shoulder disability, general healthSMT (MOB + MAN) + GP care

      Costs: £1443

      Health effects

      Recovery: 41%

      Pain: 5.9 (5.4)

      Disability: 33.0 (34.6)

      General health: 0.11 (0.19)

      GP care

      Costs: £686

      Health effects

      Recovery: 35%

      Pain: 5.2 (5.5)

      Disability: 20.3 (35.9)

      General health: 0.08 (0.21)
      Incremental costs:

      £757

      Cost per unit of outcome improved in:

      Recovery: £151

      Pain: £1081

      Disability: £60

      General health: £25222
      Ankle Fracture
      Lin 2008
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      • Lin CC
      • Moseley AM
      • Refshauge KM
      • Haas M
      • Herbert RD
      Effectiveness of joint mobilisation after cast immobilisation for ankle fracture: a protocol for a randomised controlled trial [ACTRN012605000143628].


      Australia
      Low risk of bias (≥ 6 items of the recommended criteria by the Cochrane Back Review Group were satisfied)
      Analysis: CUA

      Statistical analysis: Intention to Treat analysis, ANCOVA for group-differences, imputation of missing values, two sample t-test and bootstrapping (1000 replications) 95% CIs for group-differences in costs
      Quality of life (AQoL), activity limitation (LEFS)MT + PT

      Costs: £2267

      Health effects: NR

      PT

      Costs: £1754

      Health effects: NR
      Incremental costs:

      £513

      Incremental effects:

      between-group difference

      AQoL: 1.3 (0.1, 2.5)

      QALY: -0.09 (-0.6, 0.4)

      Cost per QALY gained:

      -£1075
      AQoL, assessment of quality of life; BGA, behavioral graded activity; BPM, brief pain management; CEA, cost-effectiveness analysis; CI, confidence interval; CUA, cost-utility analysis; EQ-5D, European Quality of Life-5 Dimensions; GP, general practitioner; HRQoL, health-related quality of life; LEFS, lower extremity functional scale; MAN, manipulation; MOB, mobilization; MT, manual therapy; NDI, Neck Disability Score; NPQ, Northwick Park Neck Pain Questionnaire; NR, not reported; ODI, Oswestry Disability Index; OSM, osteopathic manual therapy; PT, physiotherapy; QALY, quality-adjusted life year; RMDQ, Roland-Morris Disability; SMT, spinal manual therapy; VAS, visual analogue scale.
      a High risk of bias (≤ 5 items of the recommended criteria by the Cochrane
      b Low risk of bias (≥ 6 items of the recommended criteria by the Cochrane Back Review Group were satisfied)

      Spinal Pain (Low Back, Upper Back, and/or Neck)

      In a trial by Williams et al
      • Williams NH
      • Edwards RT
      • Linck P
      • et al.
      Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
      • Williams NH
      • Wilkinson C
      • Russell I
      • et al.
      Randomized Osteopathic Manipulation Study (ROMANS): pragmatic trial for spinal pain in primary care.
      the addition of osteopathic manipulation to usual GP care was more costly compared with GP care alone (£402 vs £286). The associated ICER was £4674 per QALY gained. This estimate was lower than the threshold of £30000 used by the NICE, suggesting the addition of osteopathic manipulation to usual GP care as a potentially cost-effective option for patients with spinal pain.

      Low Back Pain

      In the study by Critchley et al,
      • Critchley DJ
      • Ratcliffe J
      • Noonan S
      • Jones RH
      • Hurley MV
      Effectiveness and cost-effectiveness of three types of physiotherapy used to reduce chronic low back pain disability: a pragmatic randomized trial with economic evaluation.
      pain management dominated both individual physiotherapy and spinal stabilization physiotherapy. Individual physiotherapy was more effective and marginally more costly than spinal stabilization physiotherapy, with a mean ICER of £1279 per QALY gained.
      The trial by Niemisto et al
      • Niemisto L
      • Rissanen P
      • Sarna S
      • Lahtinen-Suopanki T
      • Lindgren KA
      • Hurri H
      Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
      • Niemisto L
      • Lahtinen-Suopanki T
      • Rissanen P
      • Lindgren KA
      • Sarna S
      • Hurri H
      A randomized trial of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain.
      evaluated the cost-effectiveness of combination of manual therapy, stabilization exercise, and physician consultation compared with physician consultation alone in patients with low back pain. This study demonstrated significantly reduced pain intensity for the combination treatment compared with physician consultation alone at 24-month follow-up (visual analog scale [VAS] score: 30.7 vs 33.1, P = .01). The associated ICER was £165 per score improvement on VAS and was £384 per score improvement on disability scale.
      The trial by Rivero-Arias et al
      • Rivero-Arias O
      • Gray A
      • Frost H
      • Lamb SE
      • Stewart-Brown S
      Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain.
      • Frost H
      • Lamb SE
      • Doll HA
      • Carver PT
      • Stewart-Brown S
      Randomised controlled trial of physiotherapy compared with advice for low back pain.
      compared physiotherapy with physiotherapist advice in participants with low back pain. At 12 months of follow-up, physiotherapy was more expensive (£320 vs £247) and more effective (QALYs gained: 0.74 vs 0.69) than the physiotherapist advice group, but neither the incremental mean costs nor the incremental mean QALYs between the 2 treatment groups was statistically significant. The cost per QALY gained was £1454. If the decision maker is willing to pay £5000, the probability of physiotherapy being more cost-effective than physiotherapist advice was 60%.
      The UK BEAM
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
      • Brealey S
      • Burton K
      • Coulton S
      • et al.
      UK Back pain Exercise and Manipulation (UK BEAM) trial—national randomised trial of physical treatments for back pain in primary care: objectives, design and interventions [ISRCTN32683578].
      • UK BEAM Trial Team
      United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: effectiveness of physical treatments for back pain in primary care.
      assessed the cost-utility of adding manipulation, or exercise, or manipulation followed by exercise to GP care in patients with low back pain. For 12 months, all 3 groups of exercise (£631), manipulation (£702), and manipulation plus exercise (£612) incurred higher mean total costs compared with GP care (£449). The mean number of QALYs gained was also greater for the 3 groups (0.635, 0.659, and 0.651, respectively) compared with GP care (0.618). The ICERs for adding manipulation alone, exercise alone, or manipulation plus exercise to GP care relative to GP care alone were £6175, £10692, and £4918, respectively. The combination of manipulation and exercise dominated exercise alone because of lower costs and better outcomes in terms of the number of QALYs gained. The findings of this study also indicated that for additional £91, manipulation alone could gain an extra 0.008 QALYs compared with manipulation plus exercise (ICER of £11360). If the decision maker was willing to pay £10000, the most cost-effective treatment option for patients with low back pain was the addition of manipulation to GP care.
      Whitehurst et al
      • Whitehurst DG
      • Lewis M
      • Yao GL
      • et al.
      A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.
      • Hay EM
      • Mullis R
      • Lewis M
      • et al.
      Comparison of physical treatments versus a brief pain-management programme for back pain in primary care: a randomised clinical trial in physiotherapy practice.
      compared manual physiotherapy with a brief pain management program in patients with acute low back pain. At 12 months of follow-up, the mean cost per patient for the manual physiotherapy was greater compared with brief pain management, with a mean difference of £66. Although the gains in disability (Roland-Morris Disability Questionnaire [RMDQ] mean score, 0.33) and utility (mean QALYs, 0.022) were in favor of manual physiotherapy vs brief pain management, these differences were not statistically significant. The ICER for manual physiotherapy relative to brief pain management was £3006 per QALY gained. If the NHS were willing to pay £10000 per QALY gained, there was 83% chance that manual physiotherapy was more cost-effective compared with brief pain management.

      Neck Pain

      In 1 trial,
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Koke AJ
      • Bouter LM
      • de Vet HC
      Comparison of the effectiveness of a behavioural graded activity program and manual therapy in patients with sub-acute neck pain: design of a randomized clinical trial.
      • Pool JJ
      • Ostelo RW
      • Knol DL
      • Vlaeyen JW
      • Bouter LM
      • de Vet HC
      Is a behavioral graded activity program more effective than manual therapy in patients with subacute neck pain? Results of a randomized clinical trial.
      Bosmans et al evaluated the cost-effectiveness of behavioral graded activity program relative to manual therapy in patients with neck pain. Compared with manual therapy, treatment with behavioral graded activity was associated with a statistically significant reduction in pain intensity (mean VAS score, 0.88) and disability (mean Neck Disability Index score, 2.40). Behavioral graded activity was shown to be more cost-effective than manual therapy in reducing pain intensity (ICER: £388 per improvement in pain score) and disability (ICER: £152 per improvement in disability score) but not for perceived recovery (ICER: £17444 per improvement in recovery score).
      One trial by Korthals-de Bos et al
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Hoving JL
      • Koes BW
      • de Vet HC
      • et al.
      Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial.
      evaluated manual therapy, physiotherapy, and GP care in patients with neck pain. After 1 year of follow-up, manual therapy was significantly less costly than physiotherapy (−£1149) and GP care (−£1260). Moreover, manual therapy was significantly more effective in reducing neck pain than physiotherapy (mean difference, 1.20), but not disability (mean difference, 0.90). The mean differences in pain intensity (0.10) and disability (−1.40) between manual therapy and GP care were not statistically significant. The manual therapy demonstrated dominance (both less costly and more effective) over both physiotherapy and GP care for perceived recovery and utility. Also, manual therapy was dominant over physiotherapy for pain intensity. Physiotherapy and GP care did not differ in either costs or in improving neck pain or disability.
      Lewis et al
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      • Dziedzic K
      • Hill J
      • Lewis M
      • Sim J
      • Daniels J
      • Hay EM
      Effectiveness of manual therapy or pulsed shortwave diathermy in addition to advice and exercise for neck disorders: a pragmatic randomized controlled trial in physical therapy clinics.
      conducted an economic evaluation in which A&E plus manual therapy or pulsed shortwave diathermy was compared with A&E alone in patients with neck pain. At 6 months, the differences in costs, disability, and QALYs gained between the treatment groups were not statistically significant. In terms of societal perspective, for disability, the A&E plus manual therapy had a higher probability of being cost-effective (up to 55%) than A&E alone or A&E plus pulsed shortwave diathermy (PSWD), but only at WTP thresholds of less than £100. For QALYs, at £30000 per QALY gained threshold, the probabilities for A&E alone, A&E plus manual therapy, and A&E plus PSWD were 30%, 44%, and 26%, respectively.

      Shoulder Pain

      The trial by Bergman et al
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      • Bergman GJD
      • Winters JC
      • van der Heijden GJMG
      • Postema K
      • Meyboom-de Jong B
      Groningen Manipulation Study. The effect of manipulation of the structures of the shoulder girdle as additional treatment for symptom relief and for prevention of chronicity or recurrence of shoulder symptoms. Design of a randomized controlled trial within a comprehensive prognostic cohort study.
      • Bergman GJD
      • Winters JC
      • Groenier KH
      • et al.
      Manipulative therapy in addition to usual medical care for patients with shoulder dysfunction and pain: a randomized, controlled trial.
      • Bergman GJ
      • Winters JC
      • Groenier KH
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual care for patients with shoulder complaints: results of physical examination outcomes in a randomized controlled trial.
      evaluated spinal manual therapy plus usual GP care (relative to usual GP care alone in patients with shoulder pain. At 6 months of follow-up, the manual therapy group incurred nonsignificantly higher total costs compared with the GP care alone group (mean difference, £757). The mean improvements in perceived recovery (5.0%), shoulder pain (0.7), and general health (0.03) were in favor of the manual therapy group, but the differences were not statistically significant. The mean shoulder disability score was the only outcome significantly favoring the manual therapy over GP care (12.7). The ICERs for the manual therapy plus GP care vs GP care alone for perceived recovery, pain, disability, and general health were £151, £1081, £60, and £25222, respectively.

      Ankle Fracture

      Lin et al
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      • Lin CC
      • Moseley AM
      • Refshauge KM
      • Haas M
      • Herbert RD
      Effectiveness of joint mobilisation after cast immobilisation for ankle fracture: a protocol for a randomised controlled trial [ACTRN012605000143628].
      compared manual therapy added to physiotherapy with physiotherapy in patients with ankle fractures. At 6 months of follow-up, the mean between-group differences in mean AQoL score (1.3, P = .04), lower extremity function (−1.0, P = .70), and QALYs gained (−0.09) were not statistically significant. Similarly, there was no difference in total health care costs between the study groups (£513).

      Discussion

      This review identified limited evidence indicating that manual therapy techniques (eg, osteopathic spinal manipulation, physiotherapy consisting of manipulation and mobilization techniques, and chiropractic manipulation), in addition to other treatments or alone, are more cost-effective than usual GP care (alone or with exercise), spinal stabilization, GP advice, advice to remain active, or brief pain management for improving low back pain and/or disability. Similarly, one study
      • Bergman GJ
      • Winter JC
      • van Tulder MW
      • Meyboom-de JB
      • Postema K
      • van der Heijden GJ
      Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.
      demonstrated that spinal manipulation in addition to GP care was more cost-effective than GP care alone in reducing shoulder pain and related disability. The extra costs needed for 1-unit improvement in low back or shoulder pain/disability score or 1 QALY gained were lower than the WTP thresholds reported across the studies.
      The cost-effectiveness of manual therapy for improving neck pain, disability, and QALYs gained in comparison with other treatments was not consistent across the studies. For example, one trial
      • Korthals-de Bos IBC
      • Hoving JL
      • van Tulder MW
      • et al.
      Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.
      • Hoving JL
      • Koes BW
      • de Vet HC
      • et al.
      Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial.
      demonstrated the domination of chiropractic manipulation over physiotherapy or GP care in improving neck pain and QALYs gained. In 2 other trials, either alternative intervention (behavioral graded activity) was more cost-effective than manual therapy
      • Bosmans JE
      • Pool JJM
      • de Vet HCW
      • van Tulder MW
      • Ostelo RWJG
      Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
      or the probability for manual therapy being more cost-effective compared with advice plus exercise was too low.
      • Lewis M
      • James M
      • Stokes E
      • et al.
      An economic evaluation of three physiotherapy treatments for non-specific neck disorders alongside a randomized trial.
      The evidence regarding cost-effectiveness of manual therapy compared with physiotherapy for reducing pain and disability related to ankle fractures, as reported in one study,
      • Lin CW
      • Moseley AM
      • Haas M
      • Refshauge KM
      • Herbert RD
      Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.
      has been insufficient and inconclusive because of small sample size and uncertainty around the cost-effectiveness measure.
      It is difficult to draw definitive conclusions regarding the comparative cost-effectiveness of manual therapy techniques in patients with spinal pain due to the paucity, clinical heterogeneity (eg, different techniques, wide variety of comparators), and study-related shortcomings (eg, small sample, short follow-up, high uncertainty in the estimates of ICERs) of the identified evidence. For example, the use of different manual therapy techniques (eg, manipulation, mobilization, and chiropractic care) in combination with other interventions (eg, physiotherapy, exercise, and GP care) leads to differential effectiveness profiles, thereby limiting the comparability of results across studies. The nonspecific or contextual effects (eg, intervention fidelity, placebo effect, practitioner's experience) due to the complexity of interventions and lack of patient blinding may have biased the study results for subjective outcome measures such as pain, disability, and QOL. Because none of the studies used a sham/control arm, it is difficult to tease out the specific effects of treatment from patients' differential expectation (or practitioner's experience/skill set) across the study treatment arms.
      • Craig P
      • Dieppe P
      • Macintyre S
      • Michie S
      • Nazareth I
      • Petticrew M
      Developing and evaluating complex interventions: the new Medical Research Council guidance.
      All the included studies were trial-based economic evaluations. None of the studies used economic modeling to extrapolate beyond the trial data to look at the longer-term cost-effectiveness of the different interventions. Studies reporting cost-effectiveness acceptability curves (CEACs) used bootstrapping, none of the studies used simple one-way or multiway sensitivity analyses to check for uncertainty in any of the key cost factors, which may be driving the ICER.

      Limitations and Strengths

      The findings of this review are not directly comparable with those of other systematic reviews,
      • Maund E
      • Craig D
      • Suekarran S
      • et al.
      Management of frozen shoulder: a systematic review and cost-effectiveness analysis.
      • Indrakanti SS
      • Weber MH
      • Takemoto SK
      • Hu SS
      • Polly D
      • Berven SH
      Value-based care in the management of spinal disorders: a systematic review of cost-utility analysis.
      • Driessen MT
      • Lin CW
      • van Tulder MW
      Cost-effectiveness of conservative treatments for neck pain: a systematic review on economic evaluations.
      • Furlan AD
      • Yazdi F
      • Tsertsvadze A
      • et al.
      Complementary and alternative therapies for back pain II. Evidence Report/Technology Assessment No. 194. (Prepared by the University of Ottawa Evidence-based Practice Center under Contract No. 290-2007-10059-I (EPCIII). AHRQ Publication No.(11)E007.
      • Dagenais S
      • Roffey DM
      • Wai EK
      • Haldeman S
      • Caro J
      Can cost utility evaluations inform decision making about interventions for low back pain?.
      • Brown A
      • Angus D
      • Chen S
      • et al.
      Costs and outcomes of chiropractic treatment for low back pain [Technology report no 56].
      • Canter PH
      • Coon JT
      • Ernst E
      Cost-effectiveness of complementary therapies in the United Kingdom—a systematic review.
      • Cherkin DC
      • Sherman KJ
      • Deyo RA
      • Shekelle PG
      A review of the evidence for the effectiveness, safety, and cost of acupuncture, massage therapy, and spinal manipulation for back pain.
      • Coon JT
      • Ernst E
      A systematic review of the economic evaluation of complementary and alternative medicine.
      • Herman PM
      • Craig BM
      • Caspi O
      Is complementary and alternative medicine (CAM) cost-effective? A systematic review.
      • Lin CWC
      • Haas M
      • Maher CG
      • Machado LAC
      • van Tulder MW
      Cost-effectiveness of general practice care for low back pain: a systematic review.
      • Lin CWC
      • Haas M
      • Maher CG
      • Machado LAC
      • van Tulder MW
      Cost-effectiveness of guideline-endorsed treatments for low back pain: a systematic review.
      • Van Der Roer N
      • Goossens MEJB
      • Evers SMAA
      • van Tulder MW
      What is the most cost-effective treatment for patients with low back pain? A systematic review.
      • White AR
      • Ernst E
      Economic analysis of complementary medicine: a systematic review.
      • Herman PM
      • Poindexter BL
      • Witt CM
      • Eisenberg DM
      Are complementary therapies and integrative care cost-effective? A systematic review of economic evaluations.
      • Lewis R
      • Williams N
      • Matar HE
      • et al.
      The clinical effectiveness and cost-effectiveness of management strategies for sciatica: systematic review and economic model.
      • Michaleff ZA
      • Lin CW
      • Maher CG
      • van Tulder MW
      Spinal manipulation epidemiology: systematic review of cost effectiveness studies.
      given the differences in scope, research question, study inclusion/exclusion criteria, types of economic evaluation, and interventions. The findings of these reviews were either inconclusive because of the paucity and heterogeneity of the evidence for manual therapy
      • Maund E
      • Craig D
      • Suekarran S
      • et al.
      Management of frozen shoulder: a systematic review and cost-effectiveness analysis.
      • Indrakanti SS
      • Weber MH
      • Takemoto SK
      • Hu SS
      • Polly D
      • Berven SH
      Value-based care in the management of spinal disorders: a systematic review of cost-utility analysis.
      • Driessen MT
      • Lin CW
      • van Tulder MW
      Cost-effectiveness of conservative treatments for neck pain: a systematic review on economic evaluations.
      • Furlan AD
      • Yazdi F
      • Tsertsvadze A
      • et al.
      Complementary and alternative therapies for back pain II. Evidence Report/Technology Assessment No. 194. (Prepared by the University of Ottawa Evidence-based Practice Center under Contract No. 290-2007-10059-I (EPCIII). AHRQ Publication No.(11)E007.
      • Dagenais S
      • Roffey DM
      • Wai EK
      • Haldeman S
      • Caro J
      Can cost utility evaluations inform decision making about interventions for low back pain?.
      • Brown A
      • Angus D
      • Chen S
      • et al.
      Costs and outcomes of chiropractic treatment for low back pain [Technology report no 56].
      or showed some cost-effectiveness of manual therapy over alternative treatments (eg, usual care and exercise).
      • Canter PH
      • Coon JT
      • Ernst E
      Cost-effectiveness of complementary therapies in the United Kingdom—a systematic review.
      • Lin CWC
      • Haas M
      • Maher CG
      • Machado LAC
      • van Tulder MW
      Cost-effectiveness of general practice care for low back pain: a systematic review.
      • Lin CWC
      • Haas M
      • Maher CG
      • Machado LAC
      • van Tulder MW
      Cost-effectiveness of guideline-endorsed treatments for low back pain: a systematic review.
      • White AR
      • Ernst E
      Economic analysis of complementary medicine: a systematic review.
      • Herman PM
      • Poindexter BL
      • Witt CM
      • Eisenberg DM
      Are complementary therapies and integrative care cost-effective? A systematic review of economic evaluations.
      • Michaleff ZA
      • Lin CW
      • Maher CG
      • van Tulder MW
      Spinal manipulation epidemiology: systematic review of cost effectiveness studies.
      The applicability of findings of the included studies, despite them being pragmatic, may be limited to only countries with similar health care system and considerations of utility (eg, calculations based on the same QOL instrument). The applicability may also be limited by the differences in components of manual therapy interventions and short follow-ups of the studies.
      The strengths of the current review include the reviewer's use of systematic and independent strategies to minimize the ROB in searching, identifying, selecting, extracting, and appraising the primary studies. The search strategy was applied to multiple electronic databases and other sources such as references of relevant primary studies and systematic reviews. Also, this review summarized the evidence from studies that evaluated costs and effectiveness simultaneously through cost-effectiveness and/or CUAs by providing ICERs. As a limitation, this review included only RCT-based cost-effectiveness evaluations.
      This paper provides a platform for further research into the cost-effectiveness of manual therapy for the management of musculoskeletal conditions. The findings underscore the paucity of good-quality published evidence on this issue. This is based on the small number of identified RCTs focus of which is rather limited (ie, nonspecific spinal pain). The insufficient evidence on cost-effectiveness may be explained by difficulties in obtaining cost data, lack of expertise in economic outcomes, and/or perceived societal discomfort with assigning monetary units to human health.
      • Dagenais S
      • Roffey DM
      • Wai EK
      • Haldeman S
      • Caro J
      Can cost utility evaluations inform decision making about interventions for low back pain?.
      Raising awareness among the chiropractic community about the importance of undertaking more high quality economic evaluations is needed.
      Because several studies did not use QALYs as an outcome measure, this presents difficulty for decision makers if they wish to compare value for money across musculoskeletal conditions with other health conditions such as cancer and cardiovascular disease, in line with the cost-effectiveness thresholds set by NICE. Consideration of the competing demand/supply side issues of manual therapy and how these issues may vary across countries is needed. Furthermore, it is not clear whether the affordability of manual therapy in countries where the provision of such services fall outside publicly funded arrangements is likely to influence utilization; this raises questions about the generalizability of the current reported findings.
      We recommend that future studies report unit cost calculation with costs broken down by each service to allow the judgment as to whether all relevant costs for a given perspective were considered and how the total costs were calculated. If ethically justifiable, future trials need to include sham or no treatment arm to allow the assessment and separation of nonspecific effects (eg, patient's expectation) from treatment effects. More exploration is warranted about which characteristics of manual therapy (eg, mode/frequency of administration or choice of spinal regions) are important for clinically relevant and patient-centered outcomes. Finally, greater consideration is needed to improve reporting quality of primary studies evaluating manual therapy.

      Conclusions

      Preliminary evidence from this review shows some economic advantage of manual therapy relative to other interventions used for the management of musculoskeletal conditions. However, at present, there is a paucity of evidence on the cost-effectiveness and/or cost-utility evaluations for manual therapy interventions. Further improvements in the methodological conduct and reporting quality of economic evaluations of manual therapy are warranted in order to facilitate adequate evidence-based decisions among policy makers, health care practitioners, and patients.

      Practical Applications

      • There is some limited evidence indicating that manual therapy techniques are more cost-effective than usual GP care, spinal stabilization, GP advice, advice to remain active, or brief pain management for improving low back and shoulder pain/disability.
      • The extra costs needed for 1-unit improvement in low back or shoulder pain/disability score or 1 QALY gained were lower than the WTP thresholds reported across the studies.
      • The cost-effectiveness of manual therapy for improving neck pain, disability, and QALYs gained in comparison with other treatments was not consistent across the studies.

      Funding Sources and Potential Conflicts of Interest

      The project was funded by the Royal College of Chiropractors. No conflicts of interest were reported for this study.

      Contributorship Information

      • Concept development (provided idea for the research): P.S.
      • Design (planned the methods to generate the results): A.T., C.C., R.C., P.S.
      • Supervision (provided oversight, responsible for organization and implementation, writing of the manuscript): P.S., A.C.
      • Data collection/processing (responsible for experiments, patient management, organization, or reporting data): C.C.
      • Analysis/interpretation (responsible for statistical analysis, evaluation, and presentation of the results): A.T., C.C., H.M.
      • Literature search (performed the literature search): A.T., C.C., R.C.
      • Writing (responsible for writing a substantive part of the manuscript): A.T., R.C., A.C., H.M., P.S.
      • Critical review (revised manuscript for intellectual content, this does not relate to spelling and grammar checking): A.T., C.C., H.M., P.S.

      Appendix 1.

      Medline via Ovid Searched on 25/08/2011.
      1Musculoskeletal Manipulations/647
      2Manipulation, Orthopedic/3196
      3Manipulation, Chiropractic/599
      4Manipulation, Spinal/947
      5Manipulation, Osteopathic/275
      6Chiropractic/2910
      7((orthopaedic or orthopedic or chiropract$ or chirother$ or osteopath$ or spine or spinal or vertebra$ or craniocervical or craniosacral or “cranio sacral” or cervical or lumbar or occiput or invertebral or thoracic or sacral or sacroilial or joint$) adj3 (manipulat$ or adjustment$ or mobilis$ or mobiliz$ or traction$)).tw.3748
      8((manual or manipulat$ or mobilis$ or mobiliz$) adj (therap$ or intervention$ or treat$ or rehab$)).tw.2087
      91 or 2 or 3 or 4 or 5 or 6 or 7 or 810834
      10Osteopathic Medicine/2395
      11osteopath$.tw.3382
      12chiropractic$.tw.2684
      13chirother$.tw.16
      1410 or 11 or 12 or 136949
      159 or 1414942
      16“friction massage$”.tw.22
      17naprapath$.tw.13
      18Rolfing.tw.17
      19“myofascial release”.tw.53
      20“Bowen technique”.tw.5
      21“apophyseal glide$”.tw.7
      22“bone setting”.tw.47
      23bonesetting.tw.14
      24“body work$”.tw.103
      25“high-velocity low-amplitude”.tw.94
      26HVLA.tw.21
      27((Maitland or Kaltenborn or Evejenth or Evjenth or Mulligan or McKenzie or Cyriax or Mills or Mennell or Stoddard) adj3 (manipulat$ or adjustment$ or mobilis$ or mobiliz$ or traction$)).tw.17
      2816 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27386
      2915 or 2815151
      30meta.ab.37484
      31synthesis.ab.356691
      32literature.ab.333797
      33randomized.hw.385278
      34published.ab.229952
      35meta-analysis.pt.30214
      36extraction.ab.106463
      37trials.hw.241415
      38controlled.hw.476605
      39search.ab.111279
      40medline.ab.37563
      41selection.ab.186391
      42sources.ab.136598
      43trials.ab.231023
      44review.ab.521671
      45review.pt.1668378
      46articles.ab.43106
      47reviewed.ab.273309
      48english.ab.34846
      49language.ab.55323
      5030 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 493593074
      51comment.pt.449950
      52letter.pt.723862
      53editorial.pt.282269
      54Animals/4854330
      55Humans/12014638
      5654 and 551282233
      5754 not 563572097
      5851 or 52 or 53 or 574613893
      5950 not 583118764
      6029 and 593786
      61meta-analysis.mp,pt.47915
      62review.pt.1668378
      63search$.tw.167947
      6461 or 62 or 631800589
      6529 and 641754
      6660 or 653869
      67randomized controlled trial.pt.314563
      68controlled clinical trial.pt.83211
      69randomized.ab.220397
      70placebo.ab.127540
      71drug therapy.fs.1488387
      72randomly.ab.159149
      73trial.ab.227916
      74groups.ab.1056224
      7567 or 68 or 69 or 70 or 71 or 72 or 73 or 742752777
      76exp animals/not humans.sh.3654092
      7775 not 762335094
      7829 and 772268
      79exp Cohort Studies/1124315
      80cohort$.tw.181429
      81controlled clinical trial.pt.83211
      82Epidemiologic Methods/27602
      83limit 82 to yr=“1971-1988”9410
      8479 or 80 or 81 or 831268588
      8529 and 841737
      8666 or 78 or 855540
      87interview$.mp.191377
      88experience$.mp.552122
      89qualitative.tw.86147
      90qualitative research/11344
      9187 or 88 or 89 or 90772947
      9229 and 911194
      9386 or 926056
      94Economics/26136
      95exp “costs and cost analysis”/159102
      96economics, dental/1829
      97exp “economics, hospital”/17368
      98economics, medical/8493
      99economics, nursing/3851
      100economics, pharmaceutical/2258
      101(economic$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab.343421
      102(expenditure$ not energy).ti,ab.14521
      103value for money.ti,ab.654
      104budget$.ti,ab.14687
      10594 or 95 or 96 or 97 or 98 or 99 or 100 or 101 or 102 or 103 or 104457195
      106((energy or oxygen) adj cost).ti,ab.2340
      107(metabolic adj cost).ti,ab.607
      108((energy or oxygen) adj expenditure).ti,ab.13432
      109106 or 107 or 10815754
      110105 not 109453621
      111letter.pt.723862
      112editorial.pt.282269
      113historical article.pt.278980
      114111 or 112 or 1131272089
      115110 not 114428994
      116Animals/4854330
      117Humans/12014638
      118116 not (116 and 117)3572097
      119115 not 118404419
      12029 and 119562
      12193 or 1206232

      References

        • Farrell JP
        • Jensen GM
        Manual therapy: a critical assessment of role in the profession of physical therapy.
        Phys Ther. 1992; 72: 843-852
        • DeStefano LA
        • Greenman PE
        Greenman's principles of manual medicine.
        4th ed. Lippincott Williams & Wilkins, 2010
        • Jette AM
        • Delitto A
        Physical therapy treatment choices for musculoskeletal impairments.
        Phys Ther. 1997; 77: 145-154
        • Bryans R
        • Decina P
        • Descarreaux M
        • et al.
        Evidence-based guidelines for the chiropractic treatment of adults with neck pain.
        J Manipulative Physiol Ther. 2014; 37: 42-63
        • Brantingham JW
        • Cassa TK
        • Bonnefin D
        • et al.
        Manipulative and multimodal therapy for upper extremity and temporomandibular disorders: a systematic review.
        J Manipulative Physiol Ther. 2013; 36: 143-201
        • Bryans R
        • Descarreaux M
        • Duranleau M
        • et al.
        Evidence-based guidelines for the chiropractic treatment of adults with headache.
        J Manipulative Physiol Ther. 2011; 34: 274-289
        • Farabaugh RJ
        • Dehen MD
        • Hawk C
        Management of chronic spine-related conditions: consensus recommendations of a multidisciplinary panel.
        J Manipulative Physiol Ther. 2010; 33: 484-492
        • Lawrence DJ
        • Meeker W
        • Branson R
        • et al.
        Chiropractic management of low back pain and low back-related leg complaints: a literature synthesis.
        . 2008; 31 ([Review] [126 refs]): 659-674
        • Globe GA
        • Morris CE
        • Whalen WM
        • Farabaugh RJ
        • Hawk C
        Chiropractic management of low back disorders: report from a consensus process.
        J Manipulative Physiol Ther. 2008; 31: 651-658
        • Furlan AD
        • Yazdi F
        • Tsertsvadze A
        • et al.
        A systematic review and meta-analysis of efficacy, cost-effectiveness, and safety of selected complementary and alternative medicine for neck and low-back pain.
        Evid Based Complement Alternat Med. 2012; 2012 ([Epub 2011 Nov 24]): 953139https://doi.org/10.1155/2012/953139
        • Shekelle PG
        The appropriateness of spinal manipulation for low-back pain: project overview and literature review.
        1st ed. Rand Corp, 1991
        • Shekelle PG
        • Adams AH
        • Chassin MR
        • Hurwitz EL
        • Brook RH
        Spinal manipulation for low-back pain.
        Ann Intern Med. 1992; 117: 590-598
        • Bigos SJ
        • United States
        • Agency for Health Care Policy and Research
        • American HC
        Acute low back problems in adults.
        US Dept. of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1994
        • Di Fabio RP
        Clinical assessment of manipulation and mobilization of the lumbar spine. A critical review of the literature.
        Phys Ther. 1986; 66: 51-54
        • Ottenbacher K
        • DiFabio RP
        Efficacy of spinal manipulation/mobilization therapy. A meta-analysis.
        Spine (Phila Pa 1976). 1985; 10: 833-837
        • Bronfort G.
        • Assendelft W.J.
        • Evans R.
        • Haas M.
        • Bouter L.
        Efficacy of spinal manipulation for chronic headache: a systematic review.
        J Manipulative Physiol Ther. 2001; 24: 457-466
        • Bronfort G
        • Haas M
        • Evans R
        • Leininger B
        • Triano J
        Effectiveness of manual therapies: the UK evidence report.
        Chiropr Osteopat. 2010; 18: 3
        • Assendelft WJ
        • Morton SC
        • Yu EI
        • Suttorp MJ
        • Shekelle PG
        Spinal manipulative therapy for low back pain. A meta-analysis of effectiveness relative to other therapies.
        Ann Intern Med. 2003; 138: 871-881
        • Cherkin DC
        • Deyo RA
        • Battie M
        • Street J
        • Barlow W
        A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain.
        N Engl J Med. 1998; 339: 1021-1029
        • Ernst E
        Adverse effects of spinal manipulation: a systematic review.
        J R Soc Med. 2007; 100: 330-338
        • Ernst E
        Deaths after chiropractic: a review of published cases.
        Int J Clin Pract. 2010; 64: 1162-1165
        • Carnes D
        • Mars TS
        • Mullinger B
        • Froud R
        • Underwood M
        Adverse events and manual therapy: a systematic review.
        Man Ther. 2010; 15: 355-363
        • Gouveia LO
        • Castanho P
        • Ferreira JJ
        Safety of chiropractic interventions: a systematic review.
        Spine (Phila Pa 1976). 2009; 34: E405-E413
        • Rubinstein SM
        • Peerdeman SM
        • van Tulder MW
        • Riphagen I
        • Haldeman S
        A systematic review of the risk factors for cervical artery dissection.
        Stroke. 2005; 36: 1575-1580
        • Vohra S
        • Johnston BC
        • Cramer K
        • Humphreys K
        Adverse events associated with pediatric spinal manipulation: a systematic review.
        Pediatrics. 2007; 119: e275-e283
        • Stevinson C
        • Ernst E
        Risks associated with spinal manipulation.
        Am J Med. 2002; 112: 566-571
        • Carlesso LC
        • Gross AR
        • Santaguida PL
        • Burnie S
        • Voth S
        • Sadi J
        Adverse events associated with the use of cervical manipulation and mobilization for the treatment of neck pain in adults: a systematic review.
        Man Ther. 2010; 15: 434-444
        • Maund E
        • Craig D
        • Suekarran S
        • et al.
        Management of frozen shoulder: a systematic review and cost-effectiveness analysis.
        Health Technol Assess. 2012; 16: 1-264
        • Indrakanti SS
        • Weber MH
        • Takemoto SK
        • Hu SS
        • Polly D
        • Berven SH
        Value-based care in the management of spinal disorders: a systematic review of cost-utility analysis.
        Clin Orthop Relat Res. 2012; 470: 1106-1123
        • Driessen MT
        • Lin CW
        • van Tulder MW
        Cost-effectiveness of conservative treatments for neck pain: a systematic review on economic evaluations.
        Eur Spine J. 2012; 21: 1441-1450
        • Furlan AD
        • Yazdi F
        • Tsertsvadze A
        • et al.
        Complementary and alternative therapies for back pain II. Evidence Report/Technology Assessment No. 194. (Prepared by the University of Ottawa Evidence-based Practice Center under Contract No. 290-2007-10059-I (EPCIII). AHRQ Publication No.(11)E007.
        Agency for Healthcare Research and Quality, Rockville, MDOctober 2010
        • Dagenais S
        • Roffey DM
        • Wai EK
        • Haldeman S
        • Caro J
        Can cost utility evaluations inform decision making about interventions for low back pain?.
        Spine J. 2009; 9 ([Review] [69 refs]): 944-957
        • Brown A
        • Angus D
        • Chen S
        • et al.
        Costs and outcomes of chiropractic treatment for low back pain [Technology report no 56].
        Canadian Coordinating Office for Health Technology Assessment, Ottawa2005
        • Stevans JM
        • Zodet MW
        Clinical, demographic, and geographic determinants of variation in chiropractic episodes of care for adults using the 2005-2008 Medical Expenditure Panel Survey.
        J Manipulative Physiol Ther. 2012; 35: 589-599
        • Grieves B
        • Menke JM
        • Pursel KJ
        Cost minimization analysis of low back pain claims data for chiropractic vs medicine in a managed care organization. [Erratum appears in J Manipulative Physiol Ther. 2010 Feb;33(2):164].
        J Manipulative Physiol Ther. 2009; 32: 734-739
        • Haas M
        • Sharma R
        • Stano M
        Cost-effectiveness of medical and chiropractic care for acute and chronic low back pain.
        J Manipulative Physiol Ther. 2005; 28: 555-563
        • Glanville J
        • Kaunelis D
        • Mensinkai S
        How well do search filters perform in identifying economic evaluations in MEDLINE and EMBASE.
        Int J Technol Assess Health Care. 2009; 25: 522-529
        • World Bank
        World Economic Outlook Database.
        WorldBank, International Monetary Fund, 2014 ([Accessed March 26, 2014 http://www.imf.org/external/pubs/ft/weo/2004/01/data/])
        • Organisation for Economic Co-operation and Development
        Annual national accounts: PPPs and exchange rates.
        National Accounts Statistics (database), 2014 ([Accessed March 26, 2014 http://www.oecd.org/std/prices-ppp/purchasingpowerparitiespppsdata.htm])
        • Drummond MF
        • Sculpher MJ
        • Torrance GW
        Methods for the economic evaluation of health care programmes.
        3rd ed. Oxford University Press, USA2005
        • van Tulder MW
        • Furlan A
        • Bombardier C
        • Bouter L
        Updated method guidelines for systematic reviews in the Cochrane Collaboration Back Review Group.
        Spine (Phila Pa 1976). 2003; 28: 1290-1299
        • van Tulder MW
        • Suttorp M
        • Morton S
        • Bouter LM
        • Shekelle P
        Empirical evidence of an association between internal validity and effect size in randomized controlled trials of low-back pain.
        Spine (Phila Pa 1976). 2009; 34: 1685-1692
        • Balk EM
        • Bonis PA
        • Moskowitz H
        • et al.
        Correlation of quality measures with estimates of treatment effect in meta-analyses of randomized controlled trials.
        JAMA. 2002; 287: 2973-2982
        • Moher D
        • Pham B
        • Jones A
        • et al.
        Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?.
        Lancet. 1998; 352: 609-613
        • Bosmans JE
        • Pool JJM
        • de Vet HCW
        • van Tulder MW
        • Ostelo RWJG
        Is behavioral graded activity cost-effective in comparison with manual therapy for patients with subacute neck pain? An economic evaluation alongside a randomized clinical trial.
        Spine. 2011; 36: E1179-E1186
        • Pool JJ
        • Ostelo RW
        • Koke AJ
        • Bouter LM
        • de Vet HC
        Comparison of the effectiveness of a behavioural graded activity program and manual therapy in patients with sub-acute neck pain: design of a randomized clinical trial.
        Man Ther. 2006; 11: 297-305
        • Pool JJ
        • Ostelo RW
        • Knol DL
        • Vlaeyen JW
        • Bouter LM
        • de Vet HC
        Is a behavioral graded activity program more effective than manual therapy in patients with subacute neck pain? Results of a randomized clinical trial.
        Spine. 2010; 35: 1017-1024
        • Williams NH
        • Edwards RT
        • Linck P
        • et al.
        Cost-utility analysis of osteopathy in primary care: results from a pragmatic randomized controlled trial.
        Fam Pract. 2004; 21: 643-650
        • Williams NH
        • Wilkinson C
        • Russell I
        • et al.
        Randomized Osteopathic Manipulation Study (ROMANS): pragmatic trial for spinal pain in primary care.
        Fam Pract. 2003; 20: 662-669
        • UK BEAM Trial Team
        United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care.
        BMJ. 2004; 329: 1381
        • Brealey S
        • Burton K
        • Coulton S
        • et al.
        UK Back pain Exercise and Manipulation (UK BEAM) trial—national randomised trial of physical treatments for back pain in primary care: objectives, design and interventions [ISRCTN32683578].
        BMC Health Serv Res. 2003; 3: 16
        • UK BEAM Trial Team
        United Kingdom Back Pain Exercise and Manipulation (UK BEAM) randomised trial: effectiveness of physical treatments for back pain in primary care.
        BMJ. 2004; 329: 1377
        • Niemisto L
        • Rissanen P
        • Sarna S
        • Lahtinen-Suopanki T
        • Lindgren KA
        • Hurri H
        Cost-effectiveness of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain: a prospective randomized trial with 2-year follow-up.
        Spine. 2005; 30: 1109-1115