Randomized Controlled Clinical Trials

  • Alexandrina L. Dumitrescu


The randomized clinical trial (RCT) is a research design used to compare two or more forms of therapy. Four traits that distinguish an RCT from routine clinical care are (1) an RCT is controlled (all subjects in the RCT are selected based upon stringent predetermined entrance criteria), (2) it is randomized (subjects are assigned to treatment groups by chance, independent of their individual characteristics), (3) the final outcome is established through statistical analysis (criteria are established for measuring differences among the two groups prior to initiation of the study, and the data are analysed to determine of the preset level of significance is obtained), (4) most often, a double-blind technique is employed.


  1. Abaid LN, Grimes DA, Schulz KF. Reducing publication bias of prospective clinical trials through trial registration. Contraception. 2007;76(5):339–41.PubMedGoogle Scholar
  2. Al-Namankany AA, Ashley P, Moles DR, et al. Assessment of the quality of reporting of randomized clinical trials in paediatric dentistry journals. Int J Paediatr Dent. 2009;19:318–24.PubMedGoogle Scholar
  3. Altman DG. Endorsement of the CONSORT statement by high impact medical journals: survey of instructions for authors. BMJ. 2005;330(7499):1056–7.PubMedGoogle Scholar
  4. Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, et al.; CONSORT GROUP (Consolidated Standards of Reporting Trials). The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med. 2001;134:663–94.Google Scholar
  5. Altman DG. Statistics and ethics in medical research: III How large a sample? Br Med J. 1980;281(6251):1336–8.PubMedGoogle Scholar
  6. Antczak AA, Tang J, Chalmers TC. Quality assessment of randomized controlled trials in dental research. II. Results: periodontal research. J Periodontal Res. 1986;21:315–21.PubMedGoogle Scholar
  7. Bahrami M, Deery C, Clarkson JE, Pitts NB, Johnston M, Rickettes I, et al. Effectiveness of strategies to disseminate and implement clinical guidelines for the management of impacted and unerupted third molars in primary dental care, a cluster randomized controlled trial. Br Dent J. 2004;197:691–6.PubMedGoogle Scholar
  8. Bailar 3rd JC, Mosteller F. Guidelines for statistical reporting in articles for medical journals. Amplifications and explanations. Ann Intern Med. 1988;108:266–73.PubMedGoogle Scholar
  9. Bang H, Ni L, Davis C E. Assessment of blinding in clinical trials. Controlled Clinical Trials. 2004;25:143–156.Google Scholar
  10. Barbui C, Cipriani A, Malvini L, et al. Validity of the impact factor of journals as a measure of randomized controlled trial quality. J Clin Psychiatry. 2006; 67:37–40.PubMedGoogle Scholar
  11. Bassler D, Ferreira-Gonzalez I, Briel M, Cook DJ, Devereaux PJ, Heels-Ansdell D, Kirpalani H, Meade MO, Montori VM, Rozenberg A, Schünemann HJ, Guyatt GH. Systematic reviewers neglect bias that results from trials stopped early for benefit. J Clin Epidemiol. 2007;60:869–73.PubMedGoogle Scholar
  12. Bassler D, Montori VM, Briel M, Glasziou P, Guyatt G. Early stopping of randomized clinical trials for overt efficacy is problematic. J Clin Epidemiol. 2008;61:241–6.PubMedGoogle Scholar
  13. Bassler D, Briel M, Montori VM, Lane M, Glasziou P, Zhou Q, Heels-Ansdell D, Walter SD, Guyatt GH; STOPIT-2 Study Group, Flynn DN, Elamin MB, Murad MH, Abu Elnour NO, Lampropulos JF, Sood A, Mullan RJ, Erwin PJ, Bankhead CR, Perera R, Ruiz Culebro C, You JJ, Mulla SM, Kaur J, Nerenberg KA, Schünemann H, Cook DJ, Lutz K, Ribic CM, Vale N, Malaga G, Akl EA, Ferreira-Gonzalez I, Alonso-Coello P, Urrutia G, Kunz R, Bucher HC, Nordmann AJ, Raatz H, da Silva SA, Tuche F, Strahm B, Djulbegovic B, Adhikari NK, Mills EJ, Gwadry-Sridhar F, Kirpalani H, Soares HP, Karanicolas PJ, Burns KE, Vandvik PO, Coto-Yglesias F, Chrispim PP, Ramsay T. Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. JAMA. 2010;303:1180–7.Google Scholar
  14. Beller EM, Gebski V, Keech AC. Randomisation in clinical trials. Med J Aust. 2002;177:565–7.PubMedGoogle Scholar
  15. Blinkhorn AS, Gratrix D, Holloway PJ, Wainwright-Stringer YM. A cluster randomised, controlled trial of the value of dental health educators in general dental practice. Br Dent J. 2003;195:395–400.PubMedGoogle Scholar
  16. Boutron I, Ravaud P. Improving the reporting of clinical research. Br J Surg. 2009;96:449–50.PubMedGoogle Scholar
  17. Boutron I, Estellat C, Ravaud P. A review of blinding in randomized controlled trials found results inconsistent and questionable. J Clin Epidemiol. 2005;58:1220–6.PubMedGoogle Scholar
  18. Boutron I, Estellat C, Guittet L, Dechartres A, Sackett DL, Hrobjartsson A, et al. Methods of blinding in reports of randomized controlled trials assessing pharmacologic treatments: a systematic review. PLoS Med. 2006;3:e425.PubMedGoogle Scholar
  19. Boutron I, Guittet L, Estellat C, Moher D, Hrobjartsson A, Ravaud P. Reporting methods of blinding in randomized trials assessing nonpharmacological treatments. PLoS Med. 2007;4:e61.PubMedGoogle Scholar
  20. Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P, CONSORT Group. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med. 2008;148(4):295–309.PubMedGoogle Scholar
  21. Burns DR, Elswick RK. Equivalence testing with dental clinical trials. J Dent Res. 2001;80:1513–7.PubMedGoogle Scholar
  22. Cakir B, Gebski VJ, Keech AC. Flow of participants in randomised studies. Med J Aust. 2003;178:347–9.PubMedGoogle Scholar
  23. Campbell MK, Elbourne DR, Altman DG, CONSORT Group. CONSORT statement: extension to cluster randomised trials. BMJ. 2004;328(7441):702–8.PubMedGoogle Scholar
  24. Carpenter Jr WT, Appelbaum PS, Levine RJ. The Declaration of Helsinki and clinical trials: a focus on placebo-controlled trials in schizophrenia. Am J Psychiatry. 2003;160:356–62.PubMedGoogle Scholar
  25. Chalmers TC. Letters to the editor. When should randomization begin? Lancet. 1968;1:858.PubMedGoogle Scholar
  26. Chatellier G, Zapletal E, Lemaitre D, Menard J, Degoulet P. The number needed to treat: a clinically useful nomogram in its proper context. BMJ. 1996; 312(7028):426–9.PubMedGoogle Scholar
  27. Christensen E. Methodology of superiority vs. equivalence trials and non-inferiority trials. J Hepatol. 2007;46:947–54.PubMedGoogle Scholar
  28. Cioffi I, Farella M. Quality of randomised controlled trials in dentistry. Int Dent J. 2011;61:37–42.PubMedGoogle Scholar
  29. Accessed 11 May 2011.
  30. Colditz GA, Miller JN, Mosteller F. How study design affects outcomes in comparisons of therapy. I: Medical Stat Med. 1989;8:441–54.Google Scholar
  31. Committee for Proprietary Medicinal Products (CPMP). Points to consider on switching between superiority and non-inferiority. Br J Clin Pharmacol. 2001;52:223–8.Google Scholar
  32. Cooley WE, Castellion AW. International regulatory aspects of clinical periodontal research. Ann Periodontol. 1997;2:18–30.PubMedGoogle Scholar
  33. Current Controlled Clinical Trials. Accessed 11 May 2011.
  34. De Angelis C, Drazen JM, Frizelle FA, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. N Engl J Med. 2004a;351:1250–1.PubMedGoogle Scholar
  35. De Angelis C, Drazen JM, Frizelle FA, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. Lancet. 2004b;364:911–2.PubMedGoogle Scholar
  36. De Angelis CD, Drazen JM, Frizelle FA, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. JAMA. 2004c;292:1363–4.Google Scholar
  37. Dennison DK. Components of a randomized clinical trial. J Periodontal Res. 1997;32:430–8.PubMedGoogle Scholar
  38. Devereaux PJ, Manns BJ, Ghali WA, Quan H, Guyatt GH. Physician interpretations and textbook definitions of blinding terminology in randomized controlled trials. JAMA. 2001;285:2000–3.PubMedGoogle Scholar
  39. Devereaux PJ, Manns BJ, Ghali WA, Quan H, Guyatt GH. The reporting of methodological factors in randomized controlled trials and the association with a journal policy to promote adherence to the Consolidated Standards of Reporting Trials (CONSORT) checklist. Control Clin Trials. 2002;23:380–8.PubMedGoogle Scholar
  40. Doig GS, Simpson F. Randomization and allocation concealment: a practical guide for researchers. J Crit Care. 2005;20:187–91.PubMedGoogle Scholar
  41. Duke SP, Garrett S. Equivalence in periodontal trials: a description for the clinician. J Periodontol. 1998; 69:650–4.PubMedGoogle Scholar
  42. Dumbrigue HB, Al-Bayat MI, Ng CC, et al. Assessment of bias in methodology for randomized controlled trials published on implant dentistry. J Prosthodont. 2006;15:257–63.PubMedGoogle Scholar
  43. Endacott R, Botti M. Clinical research 3: Sample selection. Accid Emerg Nurs. 2007;15(4):234–8.PubMedGoogle Scholar
  44. Egger M, Jüni P, Bartlett C. The value of patient flow charts in reports of randomized controlled trials: bibliographic study. JAMA. 2001;285:1996–9.PubMedGoogle Scholar
  45. Eng J. Sample size estimation: how many individuals should be studied? Radiology. 2003;227:309–13.PubMedGoogle Scholar
  46. Escribano M, Herrera D, Morante S, Teughels W, Quirynen M, Sanz M. Efficacy of a low-concentration chlorhexidine mouth rinse in non-compliant periodontitis patients attending a supportive periodontal care programme: a randomized clinical trial. J Clin Periodontol. 2010;37:266–75.PubMedGoogle Scholar
  47. Esposito M, Coulthard P, Worthington HV, Jokstad A. Quality assessment of randomized controlled trials of oral implants. Int J Oral Maxillofac Implants. 2001;16:783–92.PubMedGoogle Scholar
  48. Fenwick J, Needleman IG, Moles DR. The effect of bias on the magnitude of clinical outcomes in periodontology: a pilot study. J Clin Periodontol. 2008;35:775–82.PubMedGoogle Scholar
  49. Fergusson D, Glass KC, Waring D, Shapiro S. Turning a blind eye: the success of blinding reported in a random sample of randomised, placebo controlled trials. BMJ. 2004;328:432.PubMedGoogle Scholar
  50. Finch C, Braham R, McIntosh A, McCory P, Wolfe R. Should football players wear custom fitted mouthguards? Results from a group randomised controlled trial. Inj Prev. 2005;11:242–6.PubMedGoogle Scholar
  51. Fine D. Periodontal disease in Barnett ML, Pihlstrom BL. Methods for enhancing the efficiency of dental/oral health clinical trials: current status, future possibilities. J Dent Res. 2004;83:744–50.Google Scholar
  52. Fisher CG, Wood KB. Introduction to and techniques of evidence-based medicine. Spine (Phila Pa 1976). 2007;32:S66–72.Google Scholar
  53. Fleiss JL. General design issues in efficacy, equivalency and superiority trials. J Periodont Res. 1992;27:306–13.PubMedGoogle Scholar
  54. Florey CD. Sample size for beginners. BMJ. 1993;306(6886):1181–4.PubMedGoogle Scholar
  55. Forder PM, Gebski VJ, Keech AC. Allocation concealment and blinding: when ignorance is bliss. Med J Aust. 2005;182:87–9.PubMedGoogle Scholar
  56. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med. 1987;317:141–5.PubMedGoogle Scholar
  57. Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C, CONSORT Group. Reporting randomized, controlled trials of herbal interventions: an elaborated CONSORT statement. Ann Intern Med. 2006;144:364–7.PubMedGoogle Scholar
  58. Gansky SA, Ellison JA, Rudy D, Bergert N, Letendre MA, Nelson L, et al. Cluster-randomized controller trial of an athletic trainer-directed spit (smokeless) tobacco intervention for collegiate baseball athletes: results after 1 year. J Athl Train. 2005;40:76–87.PubMedGoogle Scholar
  59. Giraudeau B, Ravaud P, Donner A. Sample size calculation for cluster randomized cross-over trials. Stat Med. 2008;27:5578–85.PubMedGoogle Scholar
  60. GlaxoSmithKline. Clinical Trial Registry. Accessed 11 May 2011.
  61. CONSORT Glossary 2007. Available at Accessed 10 May 2011.
  62. Gordon JS, Andrews JA, Lichtenstein E, Severson HH, Akers L. Disseminating a smokeless tobacco cessation intervention model to dental hygienists: a randomized comparison of personalized instruction and self-study methods. Health Psychol. 2005;24:447–55.PubMedGoogle Scholar
  63. Greene WL, Concato J, Feinstein AR. Claims of equivalence in medical research: are they supported by the evidence? Ann Intern Med. 2000;132:715–22.PubMedGoogle Scholar
  64. Greenstein G, Nunn ME. A method to enhance determining the clinical relevance of periodontal research data: number needed to treat (NNT). J Periodontol. 2004;75:620–4.PubMedGoogle Scholar
  65. Grimes DA, Schulz KF. Clinical research in obstetrics and gynecology: a Baedeker for busy clinicians. Obstet Gynecol Surv. 2002;57:S35–53.PubMedGoogle Scholar
  66. Gunsolley JC. Clinical efficacy of antimicrobial mouthrinses. J Dent. 2010;38:S6–10.PubMedGoogle Scholar
  67. Gunsolley JC, Elswick RK, Davenport JM. Equivalence and superiority testing in regeneration clinical trials. J Periodontol. 1998;69:521–7.PubMedGoogle Scholar
  68. Haahr MT, Hróbjartsson A. Who is blinded in randomized clinical trials? A study of 200 trials and a survey of authors. Clin Trials. 2006;3:360–5.PubMedGoogle Scholar
  69. Harrison JE. Clinical trials in orthodontics II: assessment of the quality of reporting of clinical trials published in three orthodontic journals between 1989 and 1998. J Orthod. 2003;30:309–15.PubMedGoogle Scholar
  70. Hayes RJ, Bennett S. Simple sample size calculation for cluster-randomized trials. Int J Epidemiol. 1999;28:319–26.PubMedGoogle Scholar
  71. Heritier SR, Gebski VJ, Keech AC. Inclusion of patients in clinical trial analysis: the intention-to-treat principle. Med J Aust. 2003;179:438–40.PubMedGoogle Scholar
  72. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Intervention. Accessed 10 May 2011.
  73. Hodges JS. Intention-to-treat has implications for study planning and execution, not just subject retention and follow-up. J Clin Periodontol. 2008;35:683–4.PubMedGoogle Scholar
  74. Hopewell S, Altman DG, Moher D, Schulz KF. Endorsement of the CONSORT Statement by high impact factor medical journals: a survey of journal editors and journal ‘Instructions to Authors’. Trials. 2008a;9:20.PubMedGoogle Scholar
  75. Hopewell S, Clarke M, Moher D, Wager E, Middleton P, Altman DG, et al. CONSORT for reporting randomized controlled trials in journal and conference abstracts: explanation and elaboration. PLoS Med. 2008b;5:e20.PubMedGoogle Scholar
  76. Hrobjartsson A, Forfang E, Haahr MT, Als-Nielsen B, Brorson S. Blinded trials taken to the test: an analysis of randomized clinical trials that report tests for the success of blinding. Int J Epidemiol. 2007;36:654–63.PubMedGoogle Scholar
  77. Hróbjartsson A, Pildal J, Chan AW, Haahr MT, Altman DG, Gøtzsche PC. Reporting on blinding in trial protocols and corresponding publications was often inadequate but rarely contradictory. J Clin Epidemiol. 2009;62:967–73.PubMedGoogle Scholar
  78. Hugh M, Altman DG, Hammerschlag R, Hammerschlag R, Li YP, Wu TX, White A, Moher D, STRICTA Revision Group. Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement (Chinese version). Zhong Xi Yi Jie He Xue Bao. 2010;8:804–18.PubMedGoogle Scholar
  79. Hujoel PP, DeRouen TA. Determination and selection of the optimum number of sites and patients for clinical studies. J Dent Res. 1992;71:1516–21.PubMedGoogle Scholar
  80. International Clinical Trials Registry Platform. Accessed 11 May 2011.
  81. International Conference on Harmonisation (ICH). Choice of control group in clinical trials, ICH topic E10. London: EMEA; 2000.Google Scholar
  82. Ioannidis JP, Evans SJ, Gotzsche PC, O’Neill RT, Altman DG, Schulz K, et al.; CONSORT Group. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med. 2004;141:781–8.Google Scholar
  83. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.PubMedGoogle Scholar
  84. James KE, Lee KK, Kraemer HC, Fuller RK. An index for assessing blindness in a multicenter clinical trial: disulfiram for alcohol cessation – a VA cooperative study. Stat Med. 1990;15:1421–34.Google Scholar
  85. Jeffcoat M. What is clinical significance? J Clin Periodontol. 2002;29:S30–2.Google Scholar
  86. Jeffcoat M, Parry S, Sammel M, Clothier B, Catlin A, Macones G. Periodontal infection and preterm birth: successful periodontal therapy reduces the risk of preterm birth. BJOG. 2011;118:250–6.PubMedGoogle Scholar
  87. Jokstad A, Esposito M, Coulthard P, et al. The reporting of randomized controlled trials in prosthodontics. Int J Prosthodont. 2002;15:230–42.PubMedGoogle Scholar
  88. Jönsson B, Ohrn K, Oscarson N, Lindberg P. The effectiveness of an individually tailored oral health educational programme on oral hygiene behaviour in patients with periodontal disease: a blinded randomized-controlled clinical trial (one-year follow-up). J Clin Periodontol. 2009;36:1025–34.PubMedGoogle Scholar
  89. Jönsson B, Ohrn K, Lindberg P, Oscarson N. Evaluation of an individually tailored oral health educational programme on periodontal health. J Clin Periodontol. 2010;37(10):912–9.PubMedGoogle Scholar
  90. Jüni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ. 2001;323:42–6.PubMedGoogle Scholar
  91. Karlsson J, Engebretsen L, Dainty K, ISAKOS Scientific Committee. Considerations on sample size and power calculations in randomized clinical trials. Arthroscopy. 2003;19:997–9.PubMedGoogle Scholar
  92. Kelley K, Maxwell SE, Rausch JR. Obtaining power or obtaining precision. Delineating methods of sample-size planning. Eval Health Prof. 2003;26:258–87.PubMedGoogle Scholar
  93. Kelly PJ, Webster AC, Craig JC. How many patients do we need for a clinical trial? Demystifying sample size calculations. Nephrology (Carlton). 2010;15:725–31.Google Scholar
  94. Kiang H, Bian Z, Tai BJ, Du MQ, Peng B. The effect of a bi-annual professional application of APF foam on dental caries increment in primary teeth: 24-month clinical trial. J Dent Res. 2005;84:265–8.Google Scholar
  95. Kim H-Y, Preisser JS, Rozier RG, Valiyaparambil JV. Multilevel analysis of group-randomized trials with binary outcomes. Community Dent Oral Epidemiol. 2006;34:241–51.PubMedGoogle Scholar
  96. Kingman A. Specific statistical consideration relevant to the design and analysis of gingivitis trials demonstrating product superiority or equivalence. J Periodont Res. 1992;27:378–89.PubMedGoogle Scholar
  97. Kirby A, Gebski V, Keech AC. Determining the sample size in a clinical trial. Med J Aust. 2002;177:256–7.PubMedGoogle Scholar
  98. Koch GG, Paquette DW. Design principles and statistical considerations in periodontal clinical trials. Ann Periodontol. 1997;2:42–63.PubMedGoogle Scholar
  99. Kolahi J, Abrishami M. Multiple-blind: towards a new blinding protocol for future generations of clinical trials. Med Hypotheses. 2009;73:843–5.PubMedGoogle Scholar
  100. Kolahi J, Bang H, Park J. Towards a proposal for assessment of blinding success in clinical trials: up-to-date review. Community Dent Oral Epidemiol. 2009;37:477–84.PubMedGoogle Scholar
  101. Kunz R, Vist G, Oxman AD. Randomisation to protect against selection bias in healthcare trials. Cochrane Database Syst Rev. 2007;(2):MR000012.Google Scholar
  102. Lao L, Bergman S, Hamilton GR, Langenberg P, Berman B. Evaluation of acupuncture for pain control after oral surgery: a placebo-controlled trial. Arch Otolaryngol Head Neck Surg. 1999;125:567–72.PubMedGoogle Scholar
  103. LaRosa JC, Applegate W, Crouse 3rd JR, Hunninghake DB, Grimm R, Knopp R, et al. Cholesterol lowering in the elderly. Results of the cholesterol reduction in seniors program (crisp) pilot study. Arch Intern Med. 1994;154:529–39.PubMedGoogle Scholar
  104. Levine RJ, Carpenter WT, Appelbaum PS. Clarifying standards for using placebos. Science. 2003; 300:1659–61.PubMedGoogle Scholar
  105. Lewis JA, Jonsson B, Kreutz G, Sampaio C, van Zwieten-Boot B. Placebo-controlled trials and the Declaration of Helsinki. Lancet. 2002;359(9314):1337–40.PubMedGoogle Scholar
  106. Listgarten MA. General issues in efficacy, equivalency, and superiority trials: clinical considerations. J Periodont Res. 1992;27:314–9.PubMedGoogle Scholar
  107. MacPherson H, Altman DG, Hammerschlag R, Li Y, Wu T, White A, Moher D, STRICTA Revision Group. Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement. Acupunct Med. 2010a;28:83–93.PubMedGoogle Scholar
  108. MacPherson H, Altman DG, Hammerschlag R, Youping L, Taixiang W, White A, Moher D, STRICTA Revision Group. Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement. J Evid Based Med. 2010b;3:140–55.PubMedGoogle Scholar
  109. Marshman Z, Farid F. The quality of reporting of randomised controlled trials in dental public health. Community Dent Health. 2010;27:253–6.PubMedGoogle Scholar
  110. Masouredis CM, Hilton JF, Grady D, Gee L, Chesney M, Hengl L, et al. A spit tobacco cessation intervention for college athletes: three-month results. Adv Dent Res. 1997;11:354–9.PubMedGoogle Scholar
  111. McAlister FA, Sackett DL. Active-control equivalence trials and antihypertensive agents. Am J Med. 2001; 111:553–8.PubMedGoogle Scholar
  112. McNutt RA, Evans AT, Fletcher RH, Fletcher SW. The effects of blinding on the quality of peer review. JAMA. 1990;263:1371–6.PubMedGoogle Scholar
  113. Meinert CL. Clinical trials, design, conduct and analysis. New York: Oxford University Press; 1985. p. 71–89, 119–37, 288–96.Google Scholar
  114. Michalowicz BS, Hodges JS, DiAngelis AJ, Lupo VR, Novak MJ, Ferguson JE, et al. Treatment of periodontal disease and the risk of preterm birth. N Engl J Med. 2006;355:1885–94.PubMedGoogle Scholar
  115. Moher D, Jadad AR, Nichol G, Penman M, Tugwell P, Walsh S. Assessing the quality of randomized controlled trials: an annotated bibliography of scales and checklists. Control Clin Trials. 1995;16:62–73.PubMedGoogle Scholar
  116. Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, Tugwell P, Klassen TP. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet. 1998;352(9128):609–13.PubMedGoogle Scholar
  117. Moher D, Jones A, Lepage L. Use of the CONSORT statement and quality of reports of randomized trials: a comparative before and after evaluation? JAMA. 2001a;285:1992–5.PubMedGoogle Scholar
  118. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet. 2001b;357(9263):1191–4.PubMedGoogle Scholar
  119. Montenegro R, Needleman I, Moles D, Tonetti M. Quality of RCTs in periodontology – a systematic review. J Dent Res. 2002;81:866–70.PubMedGoogle Scholar
  120. Montori VM, Bhandari M, Devereaux PJ, Manns BJ, Ghali WA, Guyatt GH. In the dark: the reporting of blinding status in randomized controlled trials. J Clin Epidemiol. 2002;55:787–90.PubMedGoogle Scholar
  121. Montori VM, Devereaux PJ, Adhikari NK, Burns KE, Eggert CH, Briel M, Lacchetti C, Leung TW, Darling E, Bryant DM, Bucher HC, Schünemann HJ, Meade MO, Cook DJ, Erwin PJ, Sood A, Sood R, Lo B, Thompson CA, Zhou Q, Mills E, Guyatt GH. Randomized trials stopped early for benefit: a systematic review. JAMA. 2005;294:2203–9.PubMedGoogle Scholar
  122. Murray DM, Varnell SP, Blistein JL. Design and analysis of group-randomized trials: a review of recent methodological developments. Am J Public Health. 2004;94:423–32.PubMedGoogle Scholar
  123. Neaton JD, Mugglin AS. From observational studies to randomized trials: asking the right question at the right time. J Clin Periodontol. 2006;33:517–9.PubMedGoogle Scholar
  124. Needleman I, Suvan J, Gilthorpe MS, Tucker R, St George G, Giannobile W, Tonetti M, Jarvis M. A randomized-controlled trial of low-dose doxycycline for periodontitis in smokers. J Clin Periodontol. 2007;34:325–33.PubMedGoogle Scholar
  125. Needleman I, Moher D, Altman DG, Schulz KF, Moles DR, Worthington H. Improving the clarity and transparency of reporting health research: a shared obligation and responsibility. J Dent Res. 2008;87:894–5.PubMedGoogle Scholar
  126. Newnham JP, Newnham IA, Ball CM, Wright M, Pennell CE, Swain J, et al. Treatment of periodontal disease during pregnancy: a randomized controlled trial. Obstet Gynecol. 2009;114:1239–48.PubMedGoogle Scholar
  127. Noordzij M, Tripepi G, Dekker FW, Zoccali C, Tanck MW, Jager KJ. Sample size calculations: basic principles and common pitfalls. Nephrol Dial Transplant. 2010;25:1388–93.PubMedGoogle Scholar
  128. Noordzij M, Dekker FW, Zoccali C, Jager KJ. Sample size calculations. Nephron Clin Pract. 2011;118:c319–23.PubMedGoogle Scholar
  129. Odgaard-Jensen J, Vist GE, Timmer A, Kunz R, Akl EA, Schünemann H, Briel M, Nordmann AJ, Pregno S, Oxman AD. Randomisation to protect against selection bias in healthcare trials. Cochrane Database Syst Rev. 2011;(4):MR000012.Google Scholar
  130. Pandis N, Polychronopoulou A, Eliades T. An assessment of quality characteristics of randomised control trials published in dental journals. J Dent. 2010;38:713–21.PubMedGoogle Scholar
  131. Park J, Bang H, Cañette I. Blinding in clinical trials, time to do it better. Complement Ther Med. 2008;16:121–3.PubMedGoogle Scholar
  132. Persson GR, Samuelsson E, Lindahl C, Renvert S. Mechanical non-surgical treatment of peri-implantitis: a single-blinded randomized longitudinal clinical study. II. Microbiological results. J Clin Periodontol. 2010;37:563–73.PubMedGoogle Scholar
  133. Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJ, CONSORT Group. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA. 2006;295:1152–60.PubMedGoogle Scholar
  134. Pihlstrom BL. Reporting clinical trial results. J Am Dent Assoc. 2009;140:14–5.Google Scholar
  135. Pihlstrom BL, Barnett ML. Design, operation, and interpretation of clinical trials. J Dent Res. 2010;89:759–72.PubMedGoogle Scholar
  136. Pildal J, Hróbjartsson A, Jørgensen KJ, Hilden J, Altman DG, Gøtzsche PC. Impact of allocation concealment on conclusions drawn from meta-analyses of randomized trials. Int J Epidemiol. 2007;36(4):847–57.PubMedGoogle Scholar
  137. Rees JR, Wade TJ, Levy DA, Colford Jr JM, Hilton JF. Changes in beliefs identify unblinding in randomized controlled trials: a method to meet consort guidelines. Contemp Clin Trials. 2005;26:25–37.PubMedGoogle Scholar
  138. Rid A, Schmidt H. The 2008 Declaration of Helsinki – first among equals in research ethics? J Law Med Ethics. 2010;38:143–8.PubMedGoogle Scholar
  139. Scales DC, Rubenfeld GD. Estimating sample size in critical care clinical trials. J Crit Care. 2005;20:6–11.PubMedGoogle Scholar
  140. Schulz KF, Grimes DA. Allocation concealment in randomised trials: defending against deciphering. Lancet. 2002a;359(9306):614–8.PubMedGoogle Scholar
  141. Schulz KF, Grimes DA. Blinding in randomised trials: hiding who got what. Lancet. 2002b; 359(9307):696–700.PubMedGoogle Scholar
  142. Schulz KF, Grimes DA. Generation of allocation sequences in randomised trials: chance, not choice. Lancet. 2002c;359(9305):515–9.PubMedGoogle Scholar
  143. Schulz KF, Grimes DA. Sample size slippages in randomised trials: exclusions and the lost and wayward. Lancet. 2002d;359(9308):781–5.PubMedGoogle Scholar
  144. Schulz KF, Grimes DA. Unequal group sizes in randomised trials: guarding against guessing. Lancet. 2002e;359(9310):966–70.PubMedGoogle Scholar
  145. Schulz KF, Grimes DA. Sample size calculations in randomised trials: mandatory and mystical. Lancet. 2005;365(9467):1348–53.PubMedGoogle Scholar
  146. Schulz KF, Altman DG, Moher D, for the CONSORT Group. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332.PubMedGoogle Scholar
  147. Simpson JM, Klar N, Donner A. Accounting for cluster randomization: a review of primary prevention trials, 1990 through 1993. Am J Public Health. 1995;85:1378–83.PubMedGoogle Scholar
  148. Sjögren P, Halling A. Quality of reporting randomised clinical trials in dental and medical research. Br Dent J. 2002;192:100–3.PubMedGoogle Scholar
  149. Stoner JA, Payne JB. Interpretation of treatment effects in periodontal research: a note on the number needed to treat. J Can Dent Assoc. 2008;74:435–7.PubMedGoogle Scholar
  150. Turpin DL. CONSORT and QUOROM guidelines for reporting randomized clinical trials and systematic reviews. Am J Orthod Dentofacial Orthop. 2005;128(6):681–5.PubMedGoogle Scholar
  151. Tu YK, Blance A, Clerehugh V, Gilthorpe MS. Statistical power for analyses of changes in randomized controlled trials. J Dent Res. 2005;84:283–7.PubMedGoogle Scholar
  152. Tu Y-K, Maddick I, Kellett M, Clerehugh V, Gilthorpe MS. Evaluating the quality of active-control trials in periodontal research. J Clin Periodontol. 2006;33:151–6.PubMedGoogle Scholar
  153. van der Putten GJ, De Visschere L, Schols J, de Baat C, Vanobbergen J. Supervised versus non-supervised implementation of an oral health care guideline in (residential) care homes: a cluster randomized controlled clinical trial. BMC Oral Health. 2010;10:17.PubMedGoogle Scholar
  154. Van der Weijden F, Slot DE, Rosema M, Timmerman M. ITT in respect to GCP: a matter of diligence. J Clin Periodontol. 2008;35:681–2.PubMedGoogle Scholar
  155. Varela VM, Heller D, Silva-Senem MX, Torres MC, Colombo AP, Feres-Filho EJ. Systemic antimicrobials adjunctive to a repeated mechanical and antiseptic therapy for aggressive periodontitis: a 6-month randomized controlled trial. J Periodontol. 2011;82:1121–30.PubMedGoogle Scholar
  156. Varnell SP, Murray DM, Janega JB, Blitstein JL. Design and analysis of group-randomized trials: a review of recent practices. Am J Public Health. 2004;94:393–9.PubMedGoogle Scholar
  157. Walter SD, Awasthi S, Jeyaseelan L. Pre-trial evaluation of the potential for unblinding in drug trials: a prototype example. Contemp Clin Trials. 2005;26:459–68.PubMedGoogle Scholar
  158. Wei LJ, Lachin JM. Properties of the urn randomization in clinical trials. Control Clin Trials. 1988;9:345–64.PubMedGoogle Scholar
  159. Weingarten MA, Paul M, Leibovici L. Assessing ethics of trials in systematic reviews. BMJ. 2004;328(7446):1013–4.PubMedGoogle Scholar
  160. World Health Organization Website. Accessed 11 May 2011.
  161. Zwarenstein M, Treweek S, Gagnier JJ, Altman DG, Tunis S, Haynes B, Oxman AD, Moher D, CONSORT Group, Pragmatic Trials in Healthcare (Practihc) Group. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ. 2008;337:a2390.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Alexandrina L. Dumitrescu
    • 1
    • 2
  1. 1.Department of PeriodontologyUniversity of Tromsø Institute of Clinical DentistryTromsøNorway
  2. 2.Private practiceBucharestRomania

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