Advertisement

Identifying Treatment Effect Modifiers in the STarT Back Trial: A Secondary Analysis

  • Jason M. Beneciuk
    Correspondence
    Address reprint requests to Jason M. Beneciuk, PT, PhD, MPH, Department of Physical Therapy, UFHSC, PO Box 100154, Gainesville, FL 32259.
    Affiliations
    Department of Physical Therapy, University of Florida, Gainesville, Florida

    Brooks Rehabilitation–College of Public Health and Health Professions (University of Florida) Research Collaboration, University of Florida, Gainesville, Florida
    Search for articles by this author
  • Jonathan C. Hill
    Affiliations
    Arthritis Research UK Primary Care Centre, Research Institute of Primary Care and Health Sciences, Keele University, Staffordshire, United Kingdom
    Search for articles by this author
  • Paul Campbell
    Affiliations
    Arthritis Research UK Primary Care Centre, Research Institute of Primary Care and Health Sciences, Keele University, Staffordshire, United Kingdom
    Search for articles by this author
  • Ebenezer Afolabi
    Affiliations
    Arthritis Research UK Primary Care Centre, Research Institute of Primary Care and Health Sciences, Keele University, Staffordshire, United Kingdom
    Search for articles by this author
  • Steven Z. George
    Affiliations
    Department of Physical Therapy, University of Florida, Gainesville, Florida

    Brooks Rehabilitation–College of Public Health and Health Professions (University of Florida) Research Collaboration, University of Florida, Gainesville, Florida
    Search for articles by this author
  • Kate M. Dunn
    Affiliations
    Arthritis Research UK Primary Care Centre, Research Institute of Primary Care and Health Sciences, Keele University, Staffordshire, United Kingdom
    Search for articles by this author
  • Nadine E. Foster
    Affiliations
    Arthritis Research UK Primary Care Centre, Research Institute of Primary Care and Health Sciences, Keele University, Staffordshire, United Kingdom
    Search for articles by this author
Published:October 17, 2016DOI:https://doi.org/10.1016/j.jpain.2016.10.002

      Highlights

      • We conducted a secondary analysis to identify treatment effect modifiers within the STarT Back trial at 4-month follow-up.
      • Socioeconomic status was identified as an effect modifier for disability outcomes with education level and number of pain medications meeting criteria for effect modification with weaker evidence.
      • We have provided preliminary exploratory findings about characteristics of patients who might least likely benefit from prognostic stratified care treatment for low back pain.

      Abstract

      Identification of patient characteristics influencing treatment outcomes is a top low back pain (LBP) research priority. Results from the STarT Back trial support the effectiveness of prognostic stratified care for LBP compared with current best care, however, patient characteristics associated with treatment response have not yet been explored. The purpose of this secondary analysis was to identify treatment effect modifiers within the STarT Back trial at 4-month follow-up (n = 688). Treatment response was dichotomized using back-specific physical disability measured using the Roland-Morris Disability Questionnaire (≥7). Candidate modifiers were identified using previous literature and evaluated using logistic regression with statistical interaction terms to provide preliminary evidence of treatment effect modification. Socioeconomic status (SES) was identified as an effect modifier for disability outcomes (odds ratio [OR] = 1.71, P = .028). High SES patients receiving prognostic stratified care were 2.5 times less likely to have a poor outcome compared with low SES patients receiving best current care (OR = .40, P = .006). Education level (OR = 1.33, P = .109) and number of pain medications (OR = .64, P = .140) met our criteria for effect modification with weaker evidence (.20 > P ≥ .05). These findings provide preliminary evidence for SES, education, and number of pain medications as treatment effect modifiers of prognostic stratified care delivered in the STarT Back Trial.

      Perspective

      This analysis provides preliminary exploratory findings about the characteristics of patients who might least likely benefit from targeted treatment using prognostic stratified care for LBP.

      Key words

      To read this article in full you will need to make a payment
      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Adler N.E.
        • Newman K.
        Socioeconomic disparities in health: Pathways and policies.
        Health Aff (Millwood). 2002; 21: 60-76
      1. American Psychological Association: Report of the APA Task Force on Socioeconomic Status. Available at: http://www.apa.org/pi/ses/resources/publications/task-force-2006.pdf. Accessed October 15, 2015

        • Bartley E.J.
        • Fillingim R.B.
        Sex differences in pain: A brief review of clinical and experimental findings.
        Br J Anaesth. 2013; 111: 52-58
        • Bialosky J.E.
        • Bishop M.D.
        • Cleland J.A.
        Individual expectation: An overlooked, but pertinent, factor in the treatment of individuals experiencing musculoskeletal pain.
        Phys Ther. 2010; 90: 1345-1355
        • Brookes S.T.
        • Whitely E.
        • Egger M.
        • Smith G.D.
        • Mulheran P.A.
        • Peters T.J.
        Subgroup analyses in randomized trials: Risks of subgroup-specific analyses; power and sample size for the interaction test.
        J Clin Epidemiol. 2004; 57: 229-236
        • Burke A.
        • Nahin R.L.
        • Stussman B.J.
        Limited health knowledge as a reason for non-use of four common complementary health practices.
        PLoS One. 2015; 10: e0129336
        • Burke J.F.
        • Sussman J.B.
        • Kent D.M.
        • Hayward R.A.
        Three simple rules to ensure reasonably credible subgroup analyses.
        BMJ. 2015; 351: h5651
        • Campbell P.
        • Foster N.E.
        • Thomas E.
        • Dunn K.M.
        Prognostic indicators of low back pain in primary care: Five-year prospective study.
        J Pain. 2013; 14: 873-883
        • Carr J.L.
        • Klaber Moffett J.A.
        • Howarth E.
        • Richmond S.J.
        • Torgerson D.J.
        • Jackson D.A.
        • Metcalfe C.J.
        A randomized trial comparing a group exercise programme for back pain patients with individual physiotherapy in a severely deprived area.
        Disabil Rehabil. 2005; 27: 929-937
        • Carr J.L.
        • Moffett J.A.
        The impact of social deprivation on chronic back pain outcomes.
        Chronic Illn. 2005; 1: 121-129
        • Chapman J.R.
        • Norvell D.C.
        • Hermsmeyer J.T.
        • Bransford R.J.
        • DeVine J.
        • McGirt M.J.
        • Lee M.J.
        Evaluating common outcomes for measuring treatment success for chronic low back pain.
        Spine. 2011; 36: S54-S68
        • Cherkin D.C.
        • Sherman K.J.
        • Avins A.L.
        • Erro J.H.
        • Ichikawa L.
        • Barlow W.E.
        • Delaney K.
        • Hawkes R.
        • Hamilton L.
        • Pressman A.
        • Khalsa P.S.
        • Deyo R.A.
        A randomized trial comparing acupuncture, simulated acupuncture, and usual care for chronic low back pain.
        Arch Intern Med. 2009; 169: 858-866
        • Chesser A.
        • Burke A.
        • Reyes J.
        • Rohrberg T.
        Navigating the digital divide: A systematic review of eHealth literacy in underserved populations in the United States.
        Inform Health Soc Care. 2016; 41: 1-19
        • Costa-Black K.M.
        • Loisel P.
        • Anema J.R.
        • Pransky G.
        Back pain and work.
        Best Pract Res Clin Rheumatol. 2010; 24: 227-240
        • Costa Lda C.
        • Koes B.W.
        • Pransky G.
        • Borkan J.
        • Maher C.G.
        • Smeets R.J.
        Primary care research priorities in low back pain: An update.
        Spine. 2013; 38: 148-156
        • Costa Lda C.
        • Maher C.G.
        • McAuley J.H.
        • Hancock M.J.
        • Herbert R.D.
        • Refshauge K.M.
        • Henschke N.
        Prognosis for patients with chronic low back pain: Inception cohort study.
        BMJ. 2009; 339: b3829
        • Damush T.M.
        • Weinberger M.
        • Perkins S.M.
        • Rao J.K.
        • Tierney W.M.
        • Qi R.
        • Clark D.O.
        The long-term effects of a self-management program for inner-city primary care patients with acute low back pain.
        Arch Intern Med. 2003; 163: 2632-2638
        • Deyo R.A.
        • Dworkin S.F.
        • Amtmann D.
        • Andersson G.
        • Borenstein D.
        • Carragee E.
        • Carrino J.
        • Chou R.
        • Cook K.
        • DeLitto A.
        • Goertz C.
        • Khalsa P.
        • Loeser J.
        • Mackey S.
        • Panagis J.
        • Rainville J.
        • Tosteson T.
        • Turk D.
        • Von Korff M.
        • Weiner D.K.
        Report of the NIH Task Force on research standards for chronic low back pain.
        J Pain. 2014; 15: 569-585
        • Evans S.D.
        • Sheffer C.E.
        • Bickel W.K.
        • Cottoms N.
        • Olson M.
        • Piti L.P.
        • Austin T.
        • Stayna H.
        The process of adapting the evidence-based treatment for tobacco dependence for smokers of lower socioeconomic status.
        J Addict Res Ther. 2015; 6: 219
        • Ferreira M.L.
        • Herbert R.D.
        • Ferreira P.H.
        • Latimer J.
        • Ostelo R.W.
        • Nascimento D.P.
        • Smeets R.J.
        A critical review of methods used to determine the smallest worthwhile effect of interventions for low back pain.
        J Clin Epidemiol. 2012; 65: 253-261
        • Fillingim R.B.
        • King C.D.
        • Ribeiro-Dasilva M.C.
        • Rahim-Williams B.
        • Riley 3rd, J.L.
        Sex, gender, and pain: A review of recent clinical and experimental findings.
        J Pain. 2009; 10: 447-485
        • Foster N.E.
        • Bishop A.
        • Thomas E.
        • Main C.
        • Horne R.
        • Weinman J.
        • Hay E.
        Illness perceptions of low back pain patients in primary care: What are they, do they change and are they associated with outcome?.
        Pain. 2008; 136: 177-187
        • Fried T.R.
        • O’Leary J.
        • Towle V.
        • Goldstein M.K.
        • Trentalange M.
        • Martin D.K.
        Health outcomes associated with polypharmacy in community-dwelling older adults: A systematic review.
        J Am Geriatr Soc. 2014; 62: 2261-2272
        • Garcia A.N.
        • Costa L.D.
        • Hancock M.
        • Costa L.O.
        Identifying patients with chronic low back pain who respond best to mechanical diagnosis and therapy: Secondary analysis of a randomized controlled trial.
        Phys Ther. 2016; 96: 623-630
        • Gnjidic D.
        • Hilmer S.N.
        • Blyth F.M.
        • Naganathan V.
        • Waite L.
        • Seibel M.J.
        • McLachlan A.J.
        • Cumming R.G.
        • Handelsman D.J.
        • Le Couteur D.G.
        Polypharmacy cutoff and outcomes: Five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes.
        J Clin Epidemiol. 2012; 65: 989-995
        • Green J.L.
        • Hawley J.N.
        • Rask K.J.
        Is the number of prescribing physicians an independent risk factor for adverse drug events in an elderly outpatient population?.
        Am J Geriatr Pharmacother. 2007; 5: 31-39
        • Grotle M.
        • Foster N.E.
        • Dunn K.M.
        • Croft P.
        Are prognostic indicators for poor outcome different for acute and chronic low back pain consulters in primary care?.
        Pain. 2010; 151: 790-797
        • Gurung T.
        • Ellard D.R.
        • Mistry D.
        • Patel S.
        • Underwood M.
        Identifying potential moderators for response to treatment in low back pain: A systematic review.
        Physiotherapy. 2015; 101: 243-251
        • Hallegraeff J.M.
        • Krijnen W.P.
        • van der Schans C.P.
        • de Greef M.H.
        Expectations about recovery from acute non-specific low back pain predict absence from usual work due to chronic low back pain: A systematic review.
        J Physiother. 2012; 58: 165-172
        • Hancock M.
        • Herbert R.D.
        • Maher C.G.
        A guide to interpretation of studies investigating subgroups of responders to physical therapy interventions.
        Phys Ther. 2009; 89: 698-704
        • Hay E.M.
        • Dunn K.M.
        • Hill J.C.
        • Lewis M.
        • Mason E.E.
        • Konstantinou K.
        • Sowden G.
        • Somerville S.
        • Vohora K.
        • Whitehurst D.
        • Main C.J.
        A randomised clinical trial of subgrouping and targeted treatment for low back pain compared with best current care. The STarT Back trial study protocol.
        BMC Musculoskelet Disord. 2008; 9: 58
        • Hayden J.A.
        • Chou R.
        • Hogg-Johnson S.
        • Bombardier C.
        Systematic reviews of low back pain prognosis had variable methods and results: Guidance for future prognosis reviews.
        J Clin Epidemiol. 2009; 62: 781-796.e1
        • Henschke N.
        • Maher C.G.
        • Refshauge K.M.
        • Herbert R.D.
        • Cumming R.G.
        • Bleasel J.
        • York J.
        • Das A.
        • McAuley J.H.
        Prognosis in patients with recent onset low back pain in Australian primary care: Inception cohort study.
        BMJ. 2008; 337: a171
        • Hill J.C.
        • Dunn K.M.
        • Lewis M.
        • Mullis R.
        • Main C.J.
        • Foster N.E.
        • Hay E.M.
        A primary care back pain screening tool: Identifying patient subgroups for initial treatment.
        Arthritis Rheum. 2008; 59: 632-641
        • Hill J.C.
        • Fritz J.M.
        Psychosocial influences on low back pain, disability, and response to treatment.
        Phys Ther. 2011; 91: 712-721
        • Hill J.C.
        • Whitehurst D.G.
        • Lewis M.
        • Bryan S.
        • Dunn K.M.
        • Foster N.E.
        • Konstantinou K.
        • Main C.J.
        • Mason E.
        • Somerville S.
        • Sowden G.
        • Vohora K.
        • Hay E.M.
        Comparison of stratified primary care management for low back pain with current best practice (STarT Back): A randomised controlled trial.
        Lancet. 2011; 378: 1560-1571
        • Hingorani A.D.
        • Windt D.A.
        • Riley R.D.
        • Abrams K.
        • Moons K.G.
        • Steyerberg E.W.
        • Schroter S.
        • Sauerbrei W.
        • Altman D.G.
        • Hemingway H.
        • PROGRESS Group
        Prognosis research strategy (PROGRESS) 4: Stratified medicine research.
        BMJ. 2013; 346: e5793
        • Johnell K.
        • Klarin I.
        The relationship between number of drugs and potential drug-drug interactions in the elderly: A study of over 600,000 elderly patients from the Swedish Prescribed Drug Register.
        Drug Saf. 2007; 30: 911-918
        • Jordan K.P.
        • Thomas E.
        • Peat G.
        • Wilkie R.
        • Croft P.
        Social risks for disabling pain in older people: A prospective study of individual and area characteristics.
        Pain. 2008; 137: 652-661
        • Kamper S.J.
        • Stanton T.R.
        • Williams C.M.
        • Maher C.G.
        • Hush J.M.
        How is recovery from low back pain measured? A systematic review of the literature.
        Eur Spine J. 2011; 20: 9-18
        • Kent P.
        • Keating J.L.
        • Leboeuf-Yde C.
        Research methods for subgrouping low back pain.
        BMC Med Res Methodol. 2010; 10: 62
        • Kongsted A.
        • Vach W.
        • Axo M.
        • Bech R.N.
        • Hestbaek L.
        Expectation of recovery from low back pain: A longitudinal cohort study investigating patient characteristics related to expectations and the association between expectations and 3-month outcome.
        Spine. 2014; 39: 81-90
        • Kraemer H.C.
        • Frank E.
        • Kupfer D.J.
        Moderators of treatment outcomes: Clinical, research, and policy importance.
        JAMA. 2006; 296: 1286-1289
        • Kraemer H.C.
        • Wilson G.T.
        • Fairburn C.G.
        • Agras W.S.
        Mediators and moderators of treatment effects in randomized clinical trials.
        Arch Gen Psychiatry. 2002; 59: 877-883
        • Kuyken W.
        • Hayes R.
        • Barrett B.
        • Byng R.
        • Dalgleish T.
        • Kessler D.
        • Lewis G.
        • Watkins E.
        • Brejcha C.
        • Cardy J.
        • Causley A.
        • Cowderoy S.
        • Evans A.
        • Gradinger F.
        • Kaur S.
        • Lanham P.
        • Morant N.
        • Richards J.
        • Shah P.
        • Sutton H.
        • Vicary R.
        • Weaver A.
        • Wilks J.
        • Williams M.
        • Taylor R.S.
        • Byford S.
        Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): A randomised controlled trial.
        Lancet. 2015; 386: 63-73
        • Lamb S.E.
        • Lall R.
        • Hansen Z.
        • Castelnuovo E.
        • Withers E.J.
        • Nichols V.
        • Griffiths F.
        • Potter R.
        • Szczepura A.
        • Underwood M.
        • BeST trial group
        A multicentred randomised controlled trial of a primary care-based cognitive behavioural programme for low back pain. The Back Skills Training (BeST) trial.
        Health Technol Assess. 2010; 14 (iii-iv): 1-253
        • Linton S.J.
        Occupational psychological factors increase the risk for back pain: A systematic review.
        J Occup Rehabil. 2001; 11: 53-66
        • Luijks H.
        • Biermans M.
        • Bor H.
        • van Weel C.
        • Lagro-Janssen T.
        • de Grauw W.
        • Schermer T.
        The effect of comorbidity on glycemic control and systolic blood pressure in type 2 diabetes: A cohort study with 5 year follow-up in primary care.
        PloS One. 2015; 10: e0138662
        • Macedo L.G.
        • Maher C.G.
        • Hancock M.J.
        • Kamper S.J.
        • McAuley J.H.
        • Stanton T.R.
        • Stafford R.
        • Hodges P.W.
        Predicting response to motor control exercises and graded activity for patients with low back pain: Preplanned secondary analysis of a randomized controlled trial.
        Phys Ther. 2014; 94: 1543-1554
        • Macfarlane G.J.
        • Pallewatte N.
        • Paudyal P.
        • Blyth F.M.
        • Coggon D.
        • Crombez G.
        • Linton S.
        • Leino-Arjas P.
        • Silman A.J.
        • Smeets R.J.
        • van der Windt D.
        Evaluation of work-related psychosocial factors and regional musculoskeletal pain: Results from a EULAR Task Force.
        Ann Rheum Dis. 2009; 68: 885-891
        • Makris U.E.
        • Pugh M.J.
        • Alvarez C.A.
        • Berlowitz D.R.
        • Turner B.J.
        • Aung K.
        • Mortensen E.M.
        Exposure to high-risk medications is associated with worse outcomes in older veterans with chronic pain.
        Am J Med Sci. 2015; 350: 279-285
        • Moffett J.A.
        • Underwood M.R.
        • Gardiner E.D.
        Socioeconomic status predicts functional disability in patients participating in a back pain trial.
        Disabil Rehabil. 2009; 31: 783-790
        • Murray C.J.
        • Barber R.M.
        • Foreman K.J.
        • Abbasoglu Ozgoren A.
        • Abd-Allah F.
        • Abera S.F.
        • Aboyans V.
        • Abraham J.P.
        • Abubakar I.
        • Abu-Raddad L.J.
        • Abu-Rmeileh N.M.
        • Achoki T.
        • Ackerman I.N.
        • Ademi Z.
        • Adou A.K.
        • Adsuar J.C.
        • Afshin A.
        • Agardh E.E.
        • Alam S.S.
        • Alasfoor D.
        • Albittar M.I.
        • Alegretti M.A.
        • Alemu Z.A.
        • Alfonso-Cristancho R.
        • Alhabib S.
        • Ali R.
        • Alla F.
        • Allebeck P.
        • Almazroa M.A.
        • Alsharif U.
        • Alvarez E.
        • Alvis-Guzman N.
        • Amare A.T.
        • Ameh E.A.
        • Amini H.
        • Ammar W.
        • Anderson H.R.
        • Anderson B.O.
        • Antonio C.A.
        • Anwari P.
        • Arnlöv J.
        • Arsic Arsenijevic V.S.
        • Artaman A.
        • Asghar R.J.
        • Assadi R.
        • Atkins L.S.
        • Avila M.A.
        • Awuah B.
        • Bachman V.F.
        • Badawi A.
        • Bahit M.C.
        • Balakrishnan K.
        • Banerjee A.
        • Barker-Collo S.L.
        • Barquera S.
        • Barregard L.
        • Barrero L.H.
        • Basu A.
        • Basu S.
        • Basulaiman M.O.
        • Beardsley J.
        • Bedi N.
        • Beghi E.
        • Bekele T.
        • Bell M.L.
        • Benjet C.
        • Bennett D.A.
        • Bensenor I.M.
        • Benzian H.
        • Bernabé E.
        • Bertozzi-Villa A.
        • Beyene T.J.
        • Bhala N.
        • Bhalla A.
        • Bhutta Z.A.
        • Bienhoff K.
        • Bikbov B.
        • Biryukov S.
        • Blore J.D.
        • Blosser C.D.
        • Blyth F.M.
        • Bohensky M.A.
        • Bolliger I.W.
        • Bora Başara B.
        • Bornstein N.M.
        • Bose D.
        • Boufous S.
        • Bourne R.R.
        • Boyers L.N.
        • Brainin M.
        • Brayne C.E.
        • Brazinova A.
        • Breitborde N.J.
        • Brenner H.
        • Briggs A.D.
        • Brooks P.M.
        • Brown J.C.
        • Brugha T.S.
        • Buchbinder R.
        • Buckle G.C.
        • Budke C.M.
        • Bulchis A.
        • Bulloch A.G.
        • Campos-Nonato I.R.
        • Carabin H.
        • Carapetis J.R.
        • Cárdenas R.
        • Carpenter D.O.
        • Caso V.
        • Castañeda-Orjuela C.A.
        • Castro R.E.
        • Catalá-López F.
        • Cavalleri F.
        • Çavlin A.
        • Chadha V.K.
        • Chang J.C.
        • Charlson F.J.
        • Chen H.
        • Chen W.
        • Chiang P.P.
        • Chimed-Ochir O.
        • Chowdhury R.
        • Christensen H.
        • Christophi C.A.
        • Cirillo M.
        • Coates M.M.
        • Coffeng L.E.
        • Coggeshall M.S.
        • Colistro V.
        • Colquhoun S.M.
        • Cooke G.S.
        • Cooper C.
        • Cooper L.T.
        • Coppola L.M.
        • Cortinovis M.
        • Criqui M.H.
        • Crump J.A.
        • Cuevas-Nasu L.
        • Danawi H.
        • Dandona L.
        • Dandona R.
        • Dansereau E.
        • Dargan P.I.
        • Davey G.
        • Davis A.
        • Davitoiu D.V.
        • Dayama A.
        • De Leo D.
        • Degenhardt L.
        • Del Pozo-Cruz B.
        • Dellavalle R.P.
        • Deribe K.
        • Derrett S.
        • Des Jarlais D.C.
        • Dessalegn M.
        • Dharmaratne S.D.
        • Dherani M.K.
        • Diaz-Torné C.
        • Dicker D.
        • Ding E.L.
        • Dokova K.
        • Dorsey E.R.
        • Driscoll T.R.
        • Duan L.
        • Duber H.C.
        • Ebel B.E.
        • Edmond K.M.
        • Elshrek Y.M.
        • Endres M.
        • Ermakov S.P.
        • Erskine H.E.
        • Eshrati B.
        • Esteghamati A.
        • Estep K.
        • Faraon E.J.
        • Farzadfar F.
        • Fay D.F.
        • Feigin V.L.
        • Felson D.T.
        • Fereshtehnejad S.M.
        • Fernandes J.G.
        • Ferrari A.J.
        • Fitzmaurice C.
        • Flaxman A.D.
        • Fleming T.D.
        • Foigt N.
        • Forouzanfar M.H.
        • Fowkes F.G.
        • Paleo U.F.
        • Franklin R.C.
        • Fürst T.
        • Gabbe B.
        • Gaffikin L.
        • Gankpé F.G.
        • Geleijnse J.M.
        • Gessner B.D.
        • Gething P.
        • Gibney K.B.
        • Giroud M.
        • Giussani G.
        • Gomez Dantes H.
        • Gona P.
        • González-Medina D.
        • Gosselin R.A.
        • Gotay C.C.
        • Goto A.
        • Gouda H.N.
        • Graetz N.
        • Gugnani H.C.
        • Gupta R.
        • Gupta R.
        • Gutiérrez R.A.
        • Haagsma J.
        • Hafezi-Nejad N.
        • Hagan H.
        • Halasa Y.A.
        • Hamadeh R.R.
        • Hamavid H.
        • Hammami M.
        • Hancock J.
        • Hankey G.J.
        • Hansen G.M.
        • Hao Y.
        • Harb H.L.
        • Haro J.M.
        • Havmoeller R.
        • Hay S.I.
        • Hay R.J.
        • Heredia-Pi I.B.
        • Heuton K.R.
        • Heydarpour P.
        • Higashi H.
        • Hijar M.
        • Hoek H.W.
        • Hoffman H.J.
        • Hosgood H.D.
        • Hossain M.
        • Hotez P.J.
        • Hoy D.G.
        • Hsairi M.
        • Hu G.
        • Huang C.
        • Huang J.J.
        • Husseini A.
        • Huynh C.
        • Iannarone M.L.
        • Iburg K.M.
        • Innos K.
        • Inoue M.
        • Islami F.
        • Jacobsen K.H.
        • Jarvis D.L.
        • Jassal S.K.
        • Jee S.H.
        • Jeemon P.
        • Jensen P.N.
        • Jha V.
        • Jiang G.
        • Jiang Y.
        • Jonas J.B.
        • Juel K.
        • Kan H.
        • Karch A.
        • Karema C.K.
        • Karimkhani C.
        • Karthikeyan G.
        • Kassebaum N.J.
        • Kaul A.
        • Kawakami N.
        • Kazanjan K.
        • Kemp A.H.
        • Kengne A.P.
        • Keren A.
        • Khader Y.S.
        • Khalifa S.E.
        • Khan E.A.
        • Khan G.
        • Khang Y.H.
        • Kieling C.
        • Kim D.
        • Kim S.
        • Kim Y.
        • Kinfu Y.
        • Kinge J.M.
        • Kivipelto M.
        • Knibbs L.D.
        • Knudsen A.K.
        • Kokubo Y.
        • Kosen S.
        • Krishnaswami S.
        • Kuate Defo B.
        • Kucuk Bicer B.
        • Kuipers E.J.
        • Kulkarni C.
        • Kulkarni V.S.
        • Kumar G.A.
        • Kyu H.H.
        • Lai T.
        • Lalloo R.
        • Lallukka T.
        • Lam H.
        • Lan Q.
        • Lansingh V.C.
        • Larsson A.
        • Lawrynowicz A.E.
        • Leasher J.L.
        • Leigh J.
        • Leung R.
        • Levitz C.E.
        • Li B.
        • Li Y.
        • Li Y.
        • Lim S.S.
        • Lind M.
        • Lipshultz S.E.
        • Liu S.
        • Liu Y.
        • Lloyd B.K.
        • Lofgren K.T.
        • Logroscino G.
        • Looker K.J.
        • Lortet-Tieulent J.
        • Lotufo P.A.
        • Lozano R.
        • Lucas R.M.
        • Lunevicius R.
        • Lyons R.A.
        • Ma S.
        • Macintyre M.F.
        • Mackay M.T.
        • Majdan M.
        • Malekzadeh R.
        • Marcenes W.
        • Margolis D.J.
        • Margono C.
        • Marzan M.B.
        • Masci J.R.
        • Mashal M.T.
        • Matzopoulos R.
        • Mayosi B.M.
        • Mazorodze T.T.
        • Mcgill N.W.
        • Mcgrath J.J.
        • Mckee M.
        • Mclain A.
        • Meaney P.A.
        • Medina C.
        • Mehndiratta M.M.
        • Mekonnen W.
        • Melaku Y.A.
        • Meltzer M.
        • Memish Z.A.
        • Mensah G.A.
        • Meretoja A.
        • Mhimbira F.A.
        • Micha R.
        • Miller T.R.
        • Mills E.J.
        • Mitchell P.B.
        • Mock C.N.
        • Mohamed Ibrahim N.
        • Mohammad K.A.
        • Mokdad A.H.
        • Mola G.L.
        • Monasta L.
        • Montañez Hernandez J.C.
        • Montico M.
        • Montine T.J.
        • Mooney M.D.
        • Moore A.R.
        • Moradi-Lakeh M.
        • Moran A.E.
        • Mori R.
        • Moschandreas J.
        • Moturi W.N.
        • Moyer M.L.
        • Mozaffarian D.
        • Msemburi W.T.
        • Mueller U.O.
        • Mukaigawara M.
        • Mullany E.C.
        • Murdoch M.E.
        • Murray J.
        • Murthy K.S.
        • Naghavi M.
        • Naheed A.
        • Naidoo K.S.
        • Naldi L.
        • Nand D.
        • Nangia V.
        • Narayan K.M.
        • Nejjari C.
        • Neupane S.P.
        • Newton C.R.
        • Ng M.
        • Ngalesoni F.N.
        • Nguyen G.
        • Nisar M.I.
        • Nolte S.
        • Norheim O.F.
        • Norman R.E.
        • Norrving B.
        • Nyakarahuka L.
        • Oh I.H.
        • Ohkubo T.
        • Ohno S.L.
        • Olusanya B.O.
        • Opio J.N.
        • Ortblad K.
        • Ortiz A.
        • Pain A.W.
        • Pandian J.D.
        • Panelo C.I.
        • Papachristou C.
        • Park E.K.
        • Park J.H.
        • Patten S.B.
        • Patton G.C.
        • Paul V.K.
        • Pavlin B.I.
        • Pearce N.
        • Pereira D.M.
        • Perez-Padilla R.
        • Perez-Ruiz F.
        • Perico N.
        • Pervaiz A.
        • Pesudovs K.
        • Peterson C.B.
        • Petzold M.
        • Phillips M.R.
        • Phillips B.K.
        • Phillips D.E.
        • Piel F.B.
        • Plass D.
        • Poenaru D.
        • Polinder S.
        • Pope D.
        • Popova S.
        • Poulton R.G.
        • Pourmalek F.
        • Prabhakaran D.
        • Prasad N.M.
        • Pullan R.L.
        • Qato D.M.
        • Quistberg D.A.
        • Rafay A.
        • Rahimi K.
        • Rahman S.U.
        • Raju M.
        • Rana S.M.
        • Razavi H.
        • Reddy K.S.
        • Refaat A.
        • Remuzzi G.
        • Resnikoff S.
        • Ribeiro A.L.
        • Richardson L.
        • Richardus J.H.
        • Roberts D.A.
        • Rojas-Rueda D.
        • Ronfani L.
        • Roth G.A.
        • Rothenbacher D.
        • Rothstein D.H.
        • Rowley J.T.
        • Roy N.
        • Ruhago G.M.
        • Saeedi M.Y.
        • Saha S.
        • Sahraian M.A.
        • Sampson U.K.
        • Sanabria J.R.
        • Sandar L.
        • Santos I.S.
        • Satpathy M.
        • Sawhney M.
        • Scarborough P.
        • Schneider I.J.
        • Schöttker B.
        • Schumacher A.E.
        • Schwebel D.C.
        • Scott J.G.
        • Seedat S.
        • Sepanlou S.G.
        • Serina P.T.
        • Servan-Mori E.E.
        • Shackelford K.A.
        • Shaheen A.
        • Shahraz S.
        • Shamah Levy T.
        • Shangguan S.
        • She J.
        • Sheikhbahaei S.
        • Shi P.
        • Shibuya K.
        • Shinohara Y.
        • Shiri R.
        • Shishani K.
        • Shiue I.
        • Shrime M.G.
        • Sigfusdottir I.D.
        • Silberberg D.H.
        • Simard E.P.
        • Sindi S.
        • Singh A.
        • Singh J.A.
        • Singh L.
        • Skirbekk V.
        • Slepak E.L.
        • Sliwa K.
        • Soneji S.
        • Søreide K.
        • Soshnikov S.
        • Sposato L.A.
        • Sreeramareddy C.T.
        • Stanaway J.D.
        • Stathopoulou V.
        • Stein D.J.
        • Stein M.B.
        • Steiner C.
        • Steiner T.J.
        • Stevens A.
        • Stewart A.
        • Stovner L.J.
        • Stroumpoulis K.
        • Sunguya B.F.
        • Swaminathan S.
        • Swaroop M.
        • Sykes B.L.
        • Tabb K.M.
        • Takahashi K.
        • Tandon N.
        • Tanne D.
        • Tanner M.
        • Tavakkoli M.
        • Taylor H.R.
        • Te Ao B.J.
        • Tediosi F.
        • Temesgen A.M.
        • Templin T.
        • Ten Have M.
        • Tenkorang E.Y.
        • Terkawi A.S.
        • Thomson B.
        • Thorne-Lyman A.L.
        • Thrift A.G.
        • Thurston G.D.
        • Tillmann T.
        • Tonelli M.
        • Topouzis F.
        • Toyoshima H.
        • Traebert J.
        • Tran B.X.
        • Trillini M.
        • Truelsen T.
        • Tsilimbaris M.
        • Tuzcu E.M.
        • Uchendu U.S.
        • Ukwaja K.N.
        • Undurraga E.A.
        • Uzun S.B.
        • Van Brakel W.H.
        • Van De Vijver S.
        • van Gool C.H.
        • Van Os J.
        • Vasankari T.J.
        • Venketasubramanian N.
        • Violante F.S.
        • Vlassov V.V.
        • Vollset S.E.
        • Wagner G.R.
        • Wagner J.
        • Waller S.G.
        • Wan X.
        • Wang H.
        • Wang J.
        • Wang L.
        • Warouw T.S.
        • Weichenthal S.
        • Weiderpass E.
        • Weintraub R.G.
        • Wenzhi W.
        • Werdecker A.
        • Westerman R.
        • Whiteford H.A.
        • Wilkinson J.D.
        • Williams T.N.
        • Wolfe C.D.
        • Wolock T.M.
        • Woolf A.D.
        • Wulf S.
        • Wurtz B.
        • Xu G.
        • Yan L.L.
        • Yano Y.
        • Ye P.
        • Yentür G.K.
        • Yip P.
        • Yonemoto N.
        • Yoon S.J.
        • Younis M.Z.
        • Yu C.
        • Zaki M.E.
        • Zhao Y.
        • Zheng Y.
        • Zonies D.
        • Zou X.
        • Salomon J.A.
        • Lopez A.D.
        • Vos T.
        Global, regional, and national disability adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: Quantifying the epidemiological transition.
        Lancet. 2015; 386: 2145-2191
        • Myers S.S.
        • Phillips R.S.
        • Davis R.B.
        • Cherkin D.C.
        • Legedza A.
        • Kaptchuk T.J.
        • Hrbek A.
        • Buring J.E.
        • Post D.
        • Connelly M.T.
        • Eisenberg D.M.
        Patient expectations as predictors of outcome in patients with acute low back pain.
        J Gen Intern Med. 2008; 23: 148-153
        • Newton J.N.
        • Briggs A.D.
        • Murray C.J.
        • Dicker D.
        • Foreman K.J.
        • Wang H.
        • Naghavi M.
        • Forouzanfar M.H.
        • Ohno S.L.
        • Barber R.M.
        • Vos T.
        • Stanaway J.D.
        • Schmidt J.C.
        • Hughes A.J.
        • Fay D.F.
        • Ecob R.
        • Gresser C.
        • McKee M.
        • Rutter H.
        • Abubakar I.
        • Ali R.
        • Anderson H.R.
        • Banerjee A.
        • Bennett D.A.
        • Bernabé E.
        • Bhui K.S.
        • Biryukov S.M.
        • Bourne R.R.
        • Brayne C.E.
        • Bruce N.G.
        • Brugha T.S.
        • Burch M.
        • Capewell S.
        • Casey D.
        • Chowdhury R.
        • Coates M.M.
        • Cooper C.
        • Critchley J.A.
        • Dargan P.I.
        • Dherani M.K.
        • Elliott P.
        • Ezzati M.
        • Fenton K.A.
        • Fraser M.S.
        • Fürst T.
        • Greaves F.
        • Green M.A.
        • Gunnell D.J.
        • Hannigan B.M.
        • Hay R.J.
        • Hay S.I.
        • Hemingway H.
        • Larson H.J.
        • Looker K.J.
        • Lunevicius R.
        • Lyons R.A.
        • Marcenes W.
        • Mason-Jones A.J.
        • Matthews F.E.
        • Moller H.
        • Murdoch M.E.
        • Newton C.R.
        • Pearce N.
        • Piel F.B.
        • Pope D.
        • Rahimi K.
        • Rodriguez A.
        • Scarborough P.
        • Schumacher A.E.
        • Shiue I.
        • Smeeth L.
        • Tedstone A.
        • Valabhji J.
        • Williams H.C.
        • Wolfe C.D.
        • Woolf A.D.
        • Davis A.C.
        Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013.
        Lancet. 2015; 386: 2257-2274
      2. Office of National Statistics: Education and Training Statistics for the United Kingdom. Available at: https://www.gov.uk/government/statistics/education-and-training-statistics-for-the-uk-2012 Accessed October 15, 2015

      3. Office of National Statistics: National Statistics Socio-Economic Classification (NS-SEC rebased on SOC2010). Available at: http://webarchive.nationalarchives.gov.uk/20160105160709/http://www.ons.gov.uk/ons/guide-method/classifications/current-standard-classifications/soc2010/soc2010-volume-3-ns-sec--rebased-on-soc2010--user-manual/index.html#top Accessed October 15, 2015

        • Ostelo R.W.
        • Deyo R.A.
        • Stratford P.
        • Waddell G.
        • Croft P.
        • Von Korff M.
        • Bouter L.M.
        • de Vet H.C.
        Interpreting change scores for pain and functional status in low back pain: Towards international consensus regarding minimal important change.
        Spine. 2008; 33: 90-94
        • Pincus T.
        • Miles C.
        • Froud R.
        • Underwood M.
        • Carnes D.
        • Taylor S.J.
        Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials: A consensus study.
        BMC Med Res Methodol. 2011; 11: 14
        • Pransky G.
        • Borkan J.M.
        • Young A.E.
        • Cherkin D.C.
        Are we making progress?: The tenth international forum for primary care research on low back pain.
        Spine. 2011; 36: 1608-1614
        • Reid M.C.
        • Bennett D.A.
        • Chen W.G.
        • Eldadah B.A.
        • Farrar J.T.
        • Ferrell B.
        • Gallagher R.M.
        • Hanlon J.T.
        • Herr K.
        • Horn S.D.
        • Inturrisi C.E.
        • Lemtouni S.
        • Lin Y.W.
        • Michaud K.
        • Morrison R.S.
        • Neogi T.
        • Porter L.L.
        • Solomon D.H.
        • Von Korff M.
        • Weiss K.
        • Witter J.
        • Zacharoff K.L.
        Improving the pharmacologic management of pain in older adults: Identifying the research gaps and methods to address them.
        Pain Med. 2011; 12: 1336-1357
        • Riley III, J.L.
        • Wade J.B.
        • Robinson M.E.
        • Price D.D.
        The stages of pain processing across the adult lifespan.
        J Pain. 2000; 1: 162-170
        • Rodeghero J.R.
        • Cook C.E.
        • Cleland J.A.
        • Mintken P.E.
        Risk stratification of patients with low back pain seen in physical therapy practice.
        Man Ther. 2015; 20: 855-860
        • Roland M.
        • Morris R.
        A study of the natural history of back pain. Part I: Development of a reliable and sensitive measure of disability in low-back pain.
        Spine. 1983; 8: 141-144
        • Rothwell P.M.
        Treating individuals 2. Subgroup analysis in randomised controlled trials: Importance, indications, and interpretation.
        Lancet. 2005; 365: 176-186
        • Rundell S.D.
        • Sherman K.J.
        • Heagerty P.J.
        • Mock C.N.
        • Jarvik J.G.
        The clinical course of pain and function in older adults with a new primary care visit for back pain.
        J Am Geriatr Soc. 2015; 63: 524-530
        • Sheffer C.E.
        • Stitzer M.
        • Landes R.
        • Brackman S.L.
        • Munn T.
        • Moore P.
        Socioeconomic disparities in community-based treatment of tobacco dependence.
        Am J Public Health. 2012; 102: e8-e16
        • Smeets R.J.
        • Maher C.G.
        • Nicholas M.K.
        • Refshauge K.M.
        • Herbert R.D.
        Do psychological characteristics predict response to exercise and advice for subacute low back pain?.
        Arthritis Rheum. 2009; 61: 1202-1209
        • Sun X.
        • Briel M.
        • Walter S.D.
        • Guyatt G.H.
        Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses.
        BMJ. 2010; 340: c117
        • Swearingen C.J.
        • McCollum L.
        • Daltroy L.H.
        • Pincus T.
        • Dewalt D.A.
        • Davis T.C.
        Screening for low literacy in a rheumatology setting: More than 10% of patients cannot read “cartilage,” “diagnosis,” “rheumatologist,” or “symptom”.
        J Clin Rheumatol. 2010; 16: 359-364
        • 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
        • Thorn B.E.
        • Day M.A.
        • Burns J.
        • Kuhajda M.C.
        • Gaskins S.W.
        • Sweeney K.
        • McConley R.
        • Ward L.C.
        • Cabbil C.
        Randomized trial of group cognitive behavioral therapy compared with a pain education control for low-literacy rural people with chronic pain.
        Pain. 2011; 152: 2710-2720
        • Valencia C.
        • Robinson M.E.
        • George S.Z.
        Socioeconomic status influences the relationship between fear-avoidance beliefs work and disability.
        Pain Med. 2011; 12: 328-336
        • van den Bos G.A.
        • Smits J.P.
        • Westert G.P.
        • van Straten A.
        Socioeconomic variations in the course of stroke: Unequal health outcomes, equal care?.
        J Epidemiol Community Health. 2002; 56: 943-948
        • Varghese M.
        • Sheffer C.
        • Stitzer M.
        • Landes R.
        • Brackman S.L.
        • Munn T.
        Socioeconomic disparities in telephone-based treatment of tobacco dependence.
        Am J Public Health. 2014; 104: e76-e84
        • Verkerk K.
        • Luijsterburg P.A.
        • Heymans M.W.
        • Ronchetti I.
        • Pool-Goudzwaard A.L.
        • Miedema H.S.
        • Koes B.W.
        Prognosis and course of disability in patients with chronic nonspecific low back pain: A 5- and 12-month follow-up cohort study.
        Phys Ther. 2013; 93: 1603-1614
        • Wideman T.H.
        • Hill J.C.
        • Main C.J.
        • Lewis M.
        • Sullivan M.J.
        • Hay E.M.
        Comparing the responsiveness of a brief, multidimensional risk screening tool for back pain to its unidimensional reference standards: The whole is greater than the sum of its parts.
        Pain. 2012; 153: 2182-2191
        • Witt C.M.
        • Schutzler L.
        • Ludtke R.
        • Wegscheider K.
        • Willich S.N.
        Patient characteristics and variation in treatment outcomes: Which patients benefit most from acupuncture for chronic pain?.
        Clinical J Pain. 2011; 27: 550-555