Background Blinding is a cornerstone of treatment evaluation. Blinding is more difficult to obtain in trials assessing nonpharmacological treatment and frequently relies on “creative” (nonstandard) methods. The purpose of this study was to systematically describe the strategies used to obtain blinding in a sample of randomized controlled trials of nonpharmacological treatment. Methods and Findings We systematically searched in Medline and the Cochrane Methodology Register for randomized controlled trials (RCTs) assessing nonpharmacological treatment with blinding, published during 2004 in high-impact-factor journals. Data were extracted using a standardized extraction form. We identified 145 articles, with the method of blinding described in 123 of the reports. Methods of blinding of participants and/or health care providers and/or other caregivers concerned mainly use of sham procedures such as simulation of surgical procedures, similar attention-control interventions, or a placebo with a different mode of administration for rehabilitation or psychotherapy. Trials assessing devices reported various placebo interventions such as use of sham prosthesis, identical apparatus (e.g., identical but inactivated machine or use of activated machine with a barrier to block the treatment), or simulation of using a device. Blinding participants to the study hypothesis was also an important method of blinding. The methods reported for blinding outcome assessors relied mainly on centralized assessment of paraclinical examinations, clinical examinations (i.e., use of video, audiotape, photography), or adjudications of clinical events. Conclusions This study classifies blinding methods and provides a detailed description of methods that could overcome some barriers of blinding in clinical trials assessing nonpharmacological treatment, and provides information for readers assessing the quality of results of such trials.
References
[1]
Gluud LL (2006) Bias in clinical intervention research. Am J Epidemiol 163: 493–501.
[2]
Schulz KF, Chalmers I, Hayes RJ, Altman DG (1995) Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 273: 408–412.
[3]
Schulz KF, Chalmers I, Altman DG (2002) The landscape and lexicon of blinding in randomized trials. Ann Intern Med 136: 254–259.
[4]
Schulz KF, Grimes DA, Altman DG, Hayes RJ (1996) Blinding and exclusions after allocation in randomised controlled trials: Survey of published parallel group trials in obstetrics and gynaecology. BMJ 312: 742–744.
[5]
Devereaux PJ, Manns BJ, Ghali WA, Quan H, Lacchetti C, et al. (2001) Physician interpretations and textbook definitions of blinding terminology in randomized controlled trials. JAMA 285: 2000–2003.
[6]
Montori V, Bhandari M, Devereaux P, Manns B, Ghali W, et al. (2002) In the dark: The reporting of blinding status in randomized controlled trials. J Clin Epidemiol 55: 787.
[7]
Hrobjartsson A (2002) What are the main methodological problems in the estimation of placebo effects? J Clin Epidemiol 55: 430–435.
[8]
Hrobjartsson A, Gotzsche PC (2001) Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N Engl J Med 344: 1594–1602.
[9]
Noseworthy JH, Ebers GC, Vandervoort MK, Farquhar RE, Yetisir E, et al. (1994) The impact of blinding on the results of a randomized, placebo- controlled multiple sclerosis clinical trial. Neurology 44: 16–20.
[10]
Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, et al. (2001) The revised CONSORT statement for reporting randomized trials: Explanation and elaboration. Ann Intern Med 134: 663–694.
[11]
Moher D, Pham B, Jones A, Cook DJ, Jadad AR, et al. (1998) Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet 352: 609–613.
[12]
Juni P, Altman DG, Egger M (2001) Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ 323: 42–46.
[13]
Kjaergard LL, Villumsen J, Gluud C (2001) Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 135: 982–989.
[14]
Fergusson D, Glass KC, Waring D, Shapiro S (2004) Turning a blind eye: The success of blinding reported in a random sample of randomised, placebo controlled trials. BMJ 328: 432.
[15]
Sackett DL (2004) Turning a blind eye: Why we don't test for blindness at the end of our trials. BMJ 328: 1136.
[16]
Boutron I, Estellat C, Ravaud P (2005) A review of blinding in randomized controlled trials found results inconsistent and questionable. J Clin Epidemiol 58: 1220–1226.
[17]
Hrobjartsson A, Forfang E, Haahr M, Als-Nielsen B, Stig B (2004) Testing the success of blinding in randomised clinical trials [abstract]. 12th Cochrane Colloquium: Bridging the Gaps. pp. 138–139.
[18]
Boutron I, Tubach F, Giraudeau B, Ravaud P (2004) Blinding was judged more difficult to achieve and maintain in non-pharmacological than pharmacological trials. J Clin Epidemiol 57: 543–550.
[19]
Boutron I, Tubach F, Giraudeau B, Ravaud P (2003) Methodological differences in clinical trials evaluating nonpharmacological and pharmacological treatments of hip and knee osteoarthritis. JAMA 290: 1062–1070.
[20]
McCulloch P, Taylor I, Sasako M, Lovett B, Griffin D (2002) Randomised trials in surgery: Problems and possible solutions. BMJ 324: 1448–1451.
[21]
Lilford R, Braunholtz D, Harris J, Gill T (2004) Trials in surgery. Br J Surg 91: 6–16.
[22]
Devereaux PJ, Bhandari M, Clarke M, Montori VM, Cook DJ, et al. (2005) Need for expertise based randomised controlled trials. BMJ 330: 88.
[23]
Devereaux PJ, McKee MD, Yusuf S (2003) Methodologic issues in randomized controlled trials of surgical interventions. Clin Orthop Relat Res. pp. 25–32.
[24]
Bhandari M, Richards RR, Sprague S, Schemitsch EH (2002) The quality of reporting of randomized trials in the Journal of Bone and Joint Surgery from 1988 through 2000. J Bone Joint Surg Am 84-A: 388–396.
[25]
Jacquier I, Boutron I, Moher D, Roy C, Ravaud P (2006) The reporting of randomized clinical trials using a surgical intervention is in need of immediate improvement: A systematic review. Ann Surg 244: 677–683.
[26]
Ethgen M, Boutron I, Baron G, Giraudeau B, Sibilia J, et al. (2005) Reporting of harm in randomized, controlled trials of nonpharmacologic treatment for rheumatic disease. Ann Intern Med 143: 20–25.
[27]
Boutron I, Estellat C, Guittet L, Dechartres A, Sackett DL, et al. (2006) Methods of blinding in reports of randomized controlled trials assessing pharmacological treatments. A systematic review. PLoS Med 3: e425.. doi:10.1371/journal.pmed.0030425.
[28]
Lee KP, Schotland M, Bacchetti P, Bero LA (2002) Association of journal quality indicators with methodological quality of clinical research articles. JAMA 287: 2805–2808.
[29]
Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, et al. (2001) Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med 344: 710–719.
[30]
Balon J, Aker PD, Crowther ER, Danielson C, Cox PG, et al. (1998) A comparison of active and simulated chiropractic manipulation as adjunctive treatment for childhood asthma. N Engl J Med 339: 1013–1020.
[31]
Baker KR, Nelson ME, Felson DT, Layne JE, Sarno R, et al. (2001) The efficacy of home based progressive strength training in older adults with knee osteoarthritis: A randomized controlled trial. J Rheumatol 28: 1655–1665.
[32]
Wolsko PM, Eisenberg DM, Simon LS, Davis RB, Walleczek J, et al. (2004) Double-blind placebo-controlled trial of static magnets for the treatment of osteoarthritis of the knee: Results of a pilot study. Altern Ther Health Med 10: 36–43.
[33]
Quilty B, Tucker M, Campbell R, Dieppe P (2003) Physiotherapy, including quadriceps exercises and patellar taping, for knee osteoarthritis with predominant patello-femoral joint involvement: Randomized controlled trial. J Rheumatol 30: 1311–1317.
[34]
Edinger JD, Wohlgemuth WK, Radtke RA, Marsh GR, Quillian RE (2001) Cognitive behavioral therapy for treatment of chronic primary insomnia: A randomized controlled trial. JAMA 285: 1856–1864.
[35]
Wang SM, Maranets I, Weinberg ME, Caldwell-Andrews AA, Kain ZN (2004) Parental auricular acupuncture as an adjunct for parental presence during induction of anesthesia. Anesthesiology 100: 1399–1404.
[36]
Carbajal R, Veerapen S, Couderc S, Jugie M, Ville Y (2003) Analgesic effect of breast feeding in term neonates: Randomised controlled trial. BMJ 326: 13.
[37]
Boutron I, Moher D, Tugwell P, Giraudeau B, Poiraudeau S, 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.
[38]
Paterson C, Dieppe P (2005) Characteristic and incidental (placebo) effects in complex interventions such as acupuncture. BMJ 330: 1202–1205.
[39]
Moseley JB, O'Malley K, Petersen NJ, Menke TJ, Brody BA, et al. (2002) A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 347: 81–88.
[40]
Spigt MG, Knipschild PG, van Schayck CP, Knottnerus JA (2005) The validity and ethics of giving placebo in a randomized nonpharmacologic trial was evaluated. J Clin Epidemiol 58: 350–356.
[41]
Zelen M (1992) Randomised consent trials. Lancet 340: 375.
[42]
Boter H, van Delden JJ, de Haan RJ, Rinkel GJ (2004) Patients' evaluation of informed consent to postponed information: Cohort study. BMJ 329: 86.
[43]
Bishop FL, Yardley L, Lewith G (2005) Developing a measure of treatment beliefs: The complementary and alternative medicine beliefs inventory. Complement Ther Med 13: 144–149.
[44]
Devilly GJ, Borkovec TD (2000) Psychometric properties of the credibility/expectancy questionnaire. J Behav Ther Exp Psychiatry 31: 73–86.
[45]
Torgerson D, Moffett JK (2005) Patient preference and validity of randomized controlled trials. JAMA 294: 41–42.
[46]
Torgerson DJ, Roland M (1998) What is Zelen's design? BMJ 316: 606.
[47]
McPherson K, Britton A (1999) The impact of patient treatment preferences on the interpretation of randomised controlled trials. Eur J Cancer 35: 1598–1602.
[48]
McPherson K, Britton A (2001) Preferences and understanding their effects on health. Qual Health Care 10 Suppl 1: i61–66.
[49]
McPherson K, Britton AR, Wennberg JE (1997) Are randomized controlled trials controlled? Patient preferences and unblind trials. J R Soc Med 90: 652–656.
[50]
McPherson K, Chalmers I (1998) Incorporating patient preferences into clinical trials. Information about patients' preference must be obtained first. BMJ 317: 78–79. discussion.
[51]
Halpern S (2003) Evaluating preference effects in partially unblinded, randomized clinical trials. J Clin Epidemiol 56: 109–115.
[52]
Wood L (2006) The association of allocation and blinding with estimated treatment effect varies according to type of outcome: a combined analysis of meta-epidemiological studies. 14th Cochrane Colloquium:Bridging the Gaps.
[53]
Gerritsen AA, de Vet HC, Scholten RJ, Bertelsmann FW, de Krom MC, et al. (2002) Splinting vs surgery in the treatment of carpal tunnel syndrome: A randomized controlled trial. JAMA 288: 1245–1251.
[54]
Altman DG, Schulz KF, Moher D (2004) Turning a blind eye: Testing the success of blinding and the CONSORT statement. BMJ 328: 1135–1136.
[55]
Sackett D, Gent M, Taylor D (1986) Tests for the blindness of randomized trials may not. Clin Res 34: 711A.
[56]
Senn SJ (2004) Turning a blind eye: Authors have blinkered view of blinding. BMJ 328: 1135–1136.
[57]
Pildal J, Chan AW, Hrobjartsson A, Forfang E, Altman DG, et al. (2005) Comparison of descriptions of allocation concealment in trial protocols and the published reports: Cohort study. BMJ 330: 1049.
