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  • Review Article
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Primer: assessing the efficacy and safety of nonpharmacologic treatments for chronic rheumatic diseases

Nature Clinical Practice Rheumatology volume 2, pages 313–319 (2006)Cite this article

Abstract

Nonpharmacologic treatments (including surgery, technical operation, rehabilitation, physiotherapy, education or the use of external technical devices) represent a wide range of treatments for chronic rheumatic disease. Randomized, controlled trials (RCTs) are recognized as the best method for avoiding bias in assessing nonpharmacologic treatments. Designs such as nonrandomized studies, cluster-randomized trials, patient-preference trials, modified Zelen-design trials, tracker trials and expertise-based RCTs could, however, be used to assess such treatments. Assessing nonpharmacologic treatments involves methodologic issues linked to difficulties associated with blinding, duration of the study, main outcomes of the study, difficulties associated with standardizing the intervention and the influence of health-care providers. Hence, these treatments cannot be assessed according to the standards used for pharmacologic treatments. As well, specific instruments such as A CheckList to Evaluate A Report of a NonPharmacological Trial (CLEAR NPT) should be used to assess the quality of reports in this field. Important reporting guidelines that take an evidence-based approach to improve the quality of reports from RCTs, such as the Consolidated Standards of Reporting Trials (CONSORT) statement, should be extended to take these issues into account.

Key Points

  • The planning and reporting of randomized, controlled trials assessing nonpharmacologic treatments should take into account certain difficulties

  • Such difficulties are those associated with blinding, and the influence of health-care providers and the centers' number of procedures on the success of the treatment

  • A clear definition of all the components of the intervention is particularly important

  • Specific designs such as cluster-randomized trials, patient-preference trials, modified Zelen-design trials, tracker trials and expertise-based, randomized trials are also available for assessing these treatments

  • Efforts are required to enhance the assessment and reporting of harm associated with nonpharmacologic treatments

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References

  1. Pincus T (2002) Limitations of randomized clinical trials in chronic diseases: explanations and recommendations. Adv Mind Body Med 18: 14–21

    PubMed  Google Scholar 

  2. Hill CL et al. (2002) Secular changes in the quality of published randomized clinical trials in rheumatology. Arthritis Rheum 46: 779–784

    Article  Google Scholar 

  3. Boutron I et al. (2003) Methodological differences in clinical trials evaluating nonpharmacological and pharmacological treatments of hip and knee osteoarthritis. JAMA 290: 1062–1070

    Article  Google Scholar 

  4. Boutron I et al. (2004) Blinding was judged more difficult to achieve and maintain in nonpharmacologic than pharmacologic trials. J Clin Epidemiol 57: 543–550

    Article  Google Scholar 

  5. Abel U and Koch A (1999) The role of randomization in clinical studies: myths and beliefs. J Clin Epidemiol 52: 487–497

    Article  CAS  Google Scholar 

  6. Ioannidis JP et al. (2001) Comparison of evidence of treatment effects in randomized and nonrandomized studies. JAMA 286: 821–830

    Article  CAS  Google Scholar 

  7. Lauritzen JB et al. (1993) Effect of external hip protectors on hip fractures. Lancet 341: 11–13

    Article  CAS  Google Scholar 

  8. Puffer S et al. (2003) Evidence for risk of bias in cluster randomised trials: review of recent trials published in three general medical journals. BMJ 327: 785–789

    Article  Google Scholar 

  9. Donner A and Klar N (2000) Design and analysis of cluster randomization trials in health research. London: Arnold Publishing Co.

    Google Scholar 

  10. King M et al. (2005) Impact of participant and physician intervention preferences on randomized trials: a systematic review. JAMA 293: 1089–1099

    Article  CAS  Google Scholar 

  11. Torgerson D and Moffett JK (2005) Patient preference and validity of randomized controlled trials. JAMA 294: 41–42

    CAS  PubMed  Google Scholar 

  12. Torgerson DJ and Sibbald B (1998) Understanding controlled trials. What is a patient preference trial? BMJ 316: 360

    Article  CAS  Google Scholar 

  13. McPherson K et al. (1997) Are randomized controlled trials controlled? Patient preferences and unblind trials. J R Soc Med 90: 652–656

    Article  CAS  Google Scholar 

  14. Campbell R et al. (2005) Adapting the randomized consent (Zelen) design for trials of behavioural interventions for chronic disease: feasibility study. J Health Serv Res Policy 10: 220–225

    Article  Google Scholar 

  15. Torgerson DJ and Roland M (1998) What is Zelen's design? BMJ 316: 606

    Article  CAS  Google Scholar 

  16. Zelen M (1992) Randomised consent trials. Lancet 340: 375

    Article  CAS  Google Scholar 

  17. Altman DG et al. (1995) Randomised consent designs in cancer clinical trials. Eur J Cancer 31A: 1934–1944

    Article  CAS  Google Scholar 

  18. Lilford RJ et al. (2000) Trials and fast changing technologies: the case for tracker studies. BMJ 320: 43–46

    Article  CAS  Google Scholar 

  19. Devereaux PJ et al. (2005) Need for expertise based randomised controlled trials. BMJ 330: 88

    Article  CAS  Google Scholar 

  20. Lilford R et al. (2004) Trials in surgery. Br J Surg 91: 6–16

    Article  CAS  Google Scholar 

  21. Schulz KF et al. (1995) Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 273: 408–412

    Article  CAS  Google Scholar 

  22. Pildal J et al. (2005) Comparison of descriptions of allocation concealment in trial protocols and the published reports: cohort study. BMJ 330: 1049

    Article  Google Scholar 

  23. Noseworthy JH et al. (1994) The impact of blinding on the results of a randomized, placebo- controlled multiple sclerosis clinical trial. Neurology 44: 16–20

    Article  CAS  Google Scholar 

  24. Juni P et al. (2001) Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ 323: 42–46

    Article  CAS  Google Scholar 

  25. Moffett JK et al. (1999) Randomised controlled trial of exercise for low back pain: clinical outcomes, costs, and preferences. BMJ 319: 279–283

    Article  CAS  Google Scholar 

  26. Moseley JB et al. (2002) A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 347: 81–88

    Article  Google Scholar 

  27. Bradley JD et al. (2002) Tidal irrigation as treatment for knee osteoarthritis: a sham- controlled, randomized, double-blinded evaluation. Arthritis Rheum 46: 100–108

    Article  Google Scholar 

  28. Ravaud P et al. (1999) Effects of joint lavage and steroid injection in patients with osteoarthritis of the knee: results of a multicenter, randomized, controlled trial. Arthritis Rheum 42: 475–482

    Article  CAS  Google Scholar 

  29. Streitberger K and Kleinhenz J (1998) Introducing a placebo needle into acupuncture research. Lancet 352: 364–365

    Article  CAS  Google Scholar 

  30. Paterson C and Dieppe P (2005) Characteristic and incidental (placebo) effects in complex interventions such as acupuncture. BMJ 330: 1202–1205

    Article  Google Scholar 

  31. Spigt MG et al. (2005) The validity and ethics of giving placebo in a randomized nonpharmacologic trial was evaluated. J Clin Epidemiol 58: 350–356

    Article  CAS  Google Scholar 

  32. Hróbjartsson A and Gøtzsche PC (2004) Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment. J Intern Med 256: 91–100

    Article  Google Scholar 

  33. Auleley GR et al. (2004) The methods for handling missing data in clinical trials influence sample size requirements. J Clin Epidemiol 57: 447–453

    Article  Google Scholar 

  34. Baron G et al. (2005) Violation of the intent-to-treat principle and rate of missing data in superiority trials assessing structural outcomes in rheumatic diseases. Arthritis Rheum 52: 1858–1865

    Article  Google Scholar 

  35. Molenberghs G et al. (2004) Analyzing incomplete longitudinal clinical trial data. Biostatistics 5: 445–464

    Article  Google Scholar 

  36. van der Heijde D et al. (2005) Presentation and analysis of data on radiographic outcome in clinical trials: experience from the TEMPO study. Arthritis Rheum 52: 49–60

    Article  Google Scholar 

  37. Campbell M et al. (2000) Framework for design and evaluation of complex interventions to improve health. BMJ 321: 694–696

    Article  CAS  Google Scholar 

  38. Devereaux PJ et al. (2005) How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ 331: 313–321

    Article  CAS  Google Scholar 

  39. Herbert RD and Bo K (2005) Analysis of quality of interventions in systematic reviews. BMJ 331: 507–509

    Article  Google Scholar 

  40. Halm EA et al. (2002) Is volume related to outcome in health care? A systematic review and methodologic critique of the literature. Ann Intern Med 137: 511–520

    Article  Google Scholar 

  41. Begg CB et al. (2002) Variations in morbidity after radical prostatectomy. N Engl J Med 346: 1138–1144

    Article  Google Scholar 

  42. Harmon JW et al. (1999) Hospital volume can serve as a surrogate for surgeon volume for achieving excellent outcomes in colorectal resection. Ann Surg 230: 404–411

    Article  CAS  Google Scholar 

  43. Rothwell PM and Warlow CP (1999) Interpretation of operative risks of individual surgeons. European Carotid Surgery Trialists' Collaborative Group. Lancet 353: 1325

    Article  CAS  Google Scholar 

  44. Urbach DR and Baxter NN (2004) Does it matter what a hospital is “high volume” for? Specificity of hospital volume-outcome associations for surgical procedures: analysis of administrative data. Qual Saf Health Care 13: 379–383

    Article  CAS  Google Scholar 

  45. Ramsay CR et al. (2000) Assessment of the learning curve in health technologies. A systematic review. Int J Technol Assess Health Care 16: 1095–1108

    Article  CAS  Google Scholar 

  46. Cherkin DC et al. (2003) A review of the evidence for the effectiveness, safety, and cost of acupuncture, massage therapy, and spinal manipulation for back pain. Ann Intern Med 138: 898–906

    Article  Google Scholar 

  47. Ethgen M et al. (2005) Reporting of harm in randomized, controlled trials of nonpharmacologic treatment for rheumatic disease. Ann Intern Med 143: 20–25

    Article  Google Scholar 

  48. Ernst E (2001) Prospective investigations into the safety of spinal manipulation. J Pain Symptom Manage 21: 238–242

    Article  CAS  Google Scholar 

  49. Norheim AJ and Fonnebo V (1995) Adverse effects of acupuncture. Lancet 345: 1576

    Article  CAS  Google Scholar 

  50. Lee KP et al. (1995) Neurologic complications following chiropractic manipulation: a survey of California neurologists. Neurology 45: 1213–1215

    Article  CAS  Google Scholar 

  51. Moher D et al. (1999) Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet 354: 1896–1900

    Article  CAS  Google Scholar 

  52. Juni P et al. (1999) The hazards of scoring the quality of clinical trials for meta-analysis. JAMA 282: 1054–1060

    Article  CAS  Google Scholar 

  53. Moher D et al. (1995) Assessing the quality of randomized controlled trials: an annotated bibliography of scales and checklists. Control Clin Trials 16: 62–73

    Article  CAS  Google Scholar 

  54. Katrak P et al. (2004) A systematic review of the content of critical appraisal tools. BMC Med Res Methodol 4: 22

    Article  Google Scholar 

  55. Jadad AR et al. (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17: 1–12

    Article  CAS  Google Scholar 

  56. Verhagen AP et al. (1998) The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol 51: 1235–1241

    Article  CAS  Google Scholar 

  57. Khuri SF et al. (1999) Relation of surgical volume to outcome in eight common operations: results from the VA National Surgical Quality Improvement Program. Ann Surg 230: 414–429

    Article  CAS  Google Scholar 

  58. Soljak M (2002) Volume of procedures and outcome of treatment. BMJ 325: 787–788

    Article  Google Scholar 

  59. Boutron I et al.: Assessing the quality of randomized controlled trials evaluating nonpharmacological treatments: a checklist to evaluate a report of nonpharmacological treatment (CLEAR NPT). J Clin Epidemiol, in press

  60. Boutron I et al. (2005) A checklist to evaluate a report of a nonpharmacological trial (CLEAR NPT) was developed using consensus. J Clin Epidemiol 58: 1233–1240

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. a rheumatologist and a Professor of Epidemiology at the and the Director of the Department of Epidemiology, University of Paris VII, Biostatistics and Clinical Research at the Hospital Bichat (Assistance Publique de Hôpitaux de Paris), and researcher at INSERM U738, Paris, France

    Philippe Ravaud

  2. a researcher at and in the Department of Epidemiology, INSERM U738, an Assistant Professor in Clinical Epidemiology at the University of Paris VII, Biostatistics and Clinical Research at the Hospital Bichat (Assistance Publique de Hôpitaux de Paris),

    Isabelle Boutron

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Correspondence to Philippe Ravaud.

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The authors declare no competing financial interests.

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Ravaud, P., Boutron, I. Primer: assessing the efficacy and safety of nonpharmacologic treatments for chronic rheumatic diseases. Nat Rev Rheumatol 2, 313–319 (2006). https://doi.org/10.1038/ncprheum0194

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