Skip to main content
SpringerLink
Log in

Design, Implementation, and Interpretation of Clinical Trials

  • Chapter
Management of Breast Diseases

  • 1938 Accesses

Abstract

The findings from Phase III randomized clinical trials (RCTs) conducted since the 1950s have lead to major advances in the clinical treatment and prevention of breast cancer. The impact of these clinical trials is best evaluated by examining the substantial decline in mortality attributed to breast cancer in countries that have accepted and applied the results from Phase III clinical trials in the broader clinical setting [1]. Concomitant with the wider acceptance of the merits of RCTs for testing new therapeutic interventions, there have been important developments in the biostatistical methods utilized in RCTs that reflect recognition of the integral role of statistical science in clinical research.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Peto R, Boreham J, Clarke M, Davies C, Beral V. UK and USA breast cancer deaths down 25% in year 2000 at ages 20–69 years. Lancet. 2000;355(9217):1822

    CAS  PubMed  Google Scholar 

  2. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, et al Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer. 1976;34(6):585–612

    CAS  PubMed  Google Scholar 

  3. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, et al Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer. 1977;35(1):1–39

    CAS  PubMed  Google Scholar 

  4. Lilienfeld AM. Ceteris paribus: The evolution of the clinical trial. Bull Hist Med. 1982;56:1–18

    CAS  PubMed  Google Scholar 

  5. Witkosky, SJ. The evil that has been said of doctors: Extracts from early writers. Trans. with Annotations by T.C. Minor. The Cincinnati Lancet-Clinic. 1889; 41/New Series, 22:447–48

    Google Scholar 

  6. Bull JP. The historical development of clinical therapeutic clinical trials. J Chronic Dis. 1959;10:218–48

    CAS  PubMed  Google Scholar 

  7. Lind J. A treatise of the scurvy. In three parts. Containing an inquiry into the nature, causes and cure, of that disease. Together with a critical and chronological view of what has been published on the subject. Edinburgh: Printed by Sands, Murray and Cochran for A Kincaid and A Donaldson, 1753

    Google Scholar 

  8. Louis PCA. The applicability of statistics to the practice of medicine. Lon Med Gazette. 1837;20:488–91

    Google Scholar 

  9. Double M. The inapplicability of statistics to the practice of medicine. Lon Med Gazette, 1837

    Google Scholar 

  10. Fisher RA. The arrangement of field experiments. J Ministry Agric. 1926;33:503–13

    Google Scholar 

  11. Fisher RA, McKenzie WA. Studies in crop variation. II the manurial response of different potato varieties. J Agric Sci. 1923;13:315

    Google Scholar 

  12. Medical Research Council. Streptomycin in Tuberculosis Trials Committee. Streptomycin treatment of pulmonary tuberculosis. Br Med J. 1948;2:769–83

    Google Scholar 

  13. Armitage P. Trials and errors: the emergence of clinical statistics. J Roy Stat Soc, Series A. 1983;146:321–34

    Google Scholar 

  14. The National Program of Cancer Chemotherapy Research. Cancer Chemotherapy Rep. 1960;1:5–34

    Google Scholar 

  15. Henderson WG, Lavori PW, Peduzzi P, Collins JF, Sather MR, Feussner JR. Cooperative Studies Program, US Department of Veterans Affairs. In: Redmond CK, Colton T, editors. Biostatistics in clinical trials. Wiley; 2001. pp. 99–115

    Google Scholar 

  16. Sylvester R. European Organization for Research and Treatment of Cancer (EORTC). In: Redmond CK, Colton T, editors. Biostatistics in clinical trials. Wiley; 2001. P. 191

    Google Scholar 

  17. Fisher B. NSABP and advances in the treatment of breast cancer. In: Redmond CK, Colton T, editors. Biostatistics in clinical trials. Wiley; 2001. pp. 310–21

    Google Scholar 

  18. Schneiderman MA, Gehan EA. History, early cancer and heart disease trials. In: Redmond CK, Colton T, editors. Biostatistics in clinical trials. Chichester: Wiley: 2001. pp. 227–35

    Google Scholar 

  19. Zelen M, Gehan E, Glidewell O, Biostatistics. In: Hoogstraten, editor. Cancer research: Impact of the cooperative groups. Paris: Masson; 1980. pp. 291–312

    Google Scholar 

  20. Hill Sir AB. The clinical trial III. In: Statistical methods in clinical and preventive medicine. London: E And S Livingstone; 1962, p. 291

    Google Scholar 

  21. Ellenberg JH. Biostatistical collaboration in medical research. Biometrics. 1990;46:1–32

    CAS  PubMed  Google Scholar 

  22. Simon R. Optimal two-stage designs for Phase II clinical trials. Control Clin Trials. 1989;10:1–10

    CAS  PubMed  Google Scholar 

  23. Thall PF, Simon R. Practical Bayesian guidelines for Phase IIB clinical trials. Biometrics. 1994;50:337–49

    CAS  PubMed  Google Scholar 

  24. Thall PF, Simon R. A Bayesian approach to establishing sample size and monitoring criterion for Phase II clinical trials. Control Clin Trials. 1994;15:463–81

    CAS  PubMed  Google Scholar 

  25. Bryant J, Day R. Incorporating toxicity considerations into the design of two-stage Phase II clinical trials. Biometrics. 1995;51:1372–83

    CAS  PubMed  Google Scholar 

  26. Piantadosi S. Clinical trials: A methodologic perspective. Second Edition. Wiley-Interscience; 2005

    Google Scholar 

  27. Schwartz D, Lellouch J. Explanatory and pragmatic attidudes in therapeutic trials. J Chronic Dis. 1967;20:637–48

    CAS  PubMed  Google Scholar 

  28. Fisher B, Bauer M, Margolese R, Poisson R, Pilch Y, Redmond C, et al Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Eng J Med. 1985;312:665–73

    Article  CAS  Google Scholar 

  29. Fisher B, Redmond C, Brown A, Wickerham, DL, Wolmark N, Allegra J, Escher G, Lippman M, Savlov E, Wittliff J et al Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer. J Clin Oncol. 1983a;1(4):227–41

    CAS  PubMed  Google Scholar 

  30. Fisher B, Wickerham DL, Brown A, Redmond CK. Breast cancer estrogen and progesterone receptor values: their distribution, degree of concordance, and relation to number of positive axillary nodes. J Clin Oncol. 1983;1(6):349–58

    CAS  PubMed  Google Scholar 

  31. Fisher B, Redmond CK, Fisher ER. Evolution of knowledge related to breast cancer heterogeneity: A 25-year retrospective. J Clin Oncol. 2008;26:2068–71

    PubMed  Google Scholar 

  32. Redmond CK, Fisher B. Design of the controlled clinical trial. In: Pilch YF, editor. Surgical oncology. McGraw-Hill; 1984. pp. 254–72

    Google Scholar 

  33. Fleming TR, DeMets DL. Surrogate endpoints in clinical trials: Are we being misled? Ann Int Med. 1996;125:605–13

    CAS  PubMed  Google Scholar 

  34. Wittes, J. Randomized treatment allocation. In: Redmond CK, Colton T, editors. Biostatistics in clinical trials. Wiley; 2001. pp. 384–92

    Google Scholar 

  35. Rockette HE, Redmond CK, Fisher B. Impact of randomized clinical trials on therapy of primary breast cancer: The NSABP overview. Control Clin Trials. 1982;3:209–25

    CAS  PubMed  Google Scholar 

  36. Investigators Writing Group WHI. Risks and benefits of estrogen plus progesterone in healthy postmenopausal women. J Am Med Assoc. 2002;288:321–33

    Google Scholar 

  37. Latakos E. Sample size determination. In: Colton T, Redmond CK, editors. Biostatistics in clinical trials. Wiley; 2001

    Google Scholar 

  38. Lakatos E, Lan KKG. A comparison of sample size methods for the logrank statistic. Stat Med. 1992;11:179–91

    CAS  PubMed  Google Scholar 

  39. Shuster JJ. CRC handbook of sample size guidelines for clinical trials. CRC Press: Boca Raton FL; 1990

    Google Scholar 

  40. Press WH, Teukolsky SA, Vetterling WT, Flannery BP. Numerical recipes in C: The art of scientific computing. 2nd ed. Cambridge: Cambridge University Press; 1992

    Google Scholar 

  41. Efron B. Forcing a sequential experiment to be balanced. Biometrika. 1971;58:403–17

    Google Scholar 

  42. Begg CB, Iglewicz BA. A treatment allocation procedure for sequential clinical trial. Biometrics. 1980;36:81–90

    CAS  PubMed  Google Scholar 

  43. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31:103–15

    CAS  PubMed  Google Scholar 

  44. The Nuremberg Code, 1947. Br Med J. 1996;313:1449

    Google Scholar 

  45. World Medical Association. Declaration of Helsinki (1964, 1975, 1983, 1989, 1996). Br Med J. 1996;313:1449–50

    Google Scholar 

  46. National Commission for Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, DC: DHEW Publication Number (OS) 78-0012. Appendix I, DHEW Publication No. (OS) 78-0012. Appendix II, DHEW Publication No. (OS) 78-0014, 1978

    Google Scholar 

  47. Hill Sir, AB. Medical ethics and controlled trials. Br Med J. 1963;1:1043

    Google Scholar 

  48. Zelen M. A new design for randomized clinical trials. New England of Medicine. 1979;300:1242

    Article  CAS  Google Scholar 

  49. Rutstein DR. Ethical aspects of human experimentation. Daedalus. J Am Acad Arts Sci. 1969; Spring:523

    Google Scholar 

  50. Taylor KM, Margolese RG, Soskolne CL. Physicians’ reasons for not entering eligible patients in a randomized clinical trial of surgery for breast cancer. N Eng J Med. 1984;310:1363–7

    Article  CAS  Google Scholar 

  51. Fisher B, Redmond C, Poisson R, Margolese R, Wolmark N, Wickerham DL, et al Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Eng J Med. 1989;320:822–8

    Article  CAS  Google Scholar 

  52. Fisher B, Anderson S, Redmond C, Wolmark N, Wickerham DL, Cronin W. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Eng J Med. 1995;333(22):1456–61

    CAS  Google Scholar 

  53. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N. Twenty-year follow-up of a randomized trial comparingtotal mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Eng J Med. October 17, 2002; 347(16):1233–1241

    Google Scholar 

  54. Fisher B, Jeong J, Anderson S, et al Twenty-five year findings from a randomized clinical trial comparing radical mastectomy with total mastectomy and with total mastectomy followed by radiation therapy. N Eng J Med. 2002;347:567–75

    Google Scholar 

  55. Buyse M, Evans S. Fraud in clinical trails In: Redmond C and Colton, TE, editors. Biostatistics in clinical trials. Wiley; 2001. p. 200–8

    Google Scholar 

  56. Peto R, Collins R, Sackett D, et al The trials of Dr. Bernard Fisher: A European perspective on an American episode. Control Clin Trials. 1997;18:1–13

    CAS  PubMed  Google Scholar 

  57. Meinert, CL. Clinical trials. Design, conduct and analysis. New York: Oxford University Press; 1985

    Google Scholar 

  58. Therasse P, Arbuck SG, Eisenhauer EA, et al New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92:205–16

    CAS  PubMed  Google Scholar 

  59. Meinert, CL. Workshop on interim data monitoring. Annual Meeting of the Society for Clinical Trials. 1996

    Google Scholar 

  60. Ellenberg S, Fleming T, DeMets D. Data monitoring committees in clinical trials: A practical perspective. West Sussex, England: Wiley; 2002

    Google Scholar 

  61. Jennison C, Turnbull BW. Group sequential methods with applications to clinical trials. Chapman & Hall/CRC; 2000

    Google Scholar 

  62. Pocock SJ. Group sequential methods in the design and analysis of clinical trials. Biometrika. 1977;64:191–99

    Google Scholar 

  63. Haybittle JL. Repeated assessment of results in clinical trials of cancer treatment. Br J Radiol. 1971;44:793–7

    CAS  PubMed  Google Scholar 

  64. O’Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979;35:549–56

    PubMed  Google Scholar 

  65. Lan KG, Demets DL. Discrete sequential boundaries for clinical trials. Biometrika. 1983;70:659–63

    Google Scholar 

  66. Pepe MS, Anderson GL. Two-stage experimental designs: early stopping with a negative result. J Roy Stat Soc, Series C (Applied Statistics). 1992;41:181–90

    Google Scholar 

  67. Wieand S, Schroeder G, O’Fallon JR. Stopping when the experimental regimen does not appear to help. Stat Med. 1994;13:1453–8

    CAS  PubMed  Google Scholar 

  68. Redmond CK, Costantino JP, Colton T. Challenges in monitoring the breast cancer prevetion trial. In: DeMets DL, Furberg CD, Friedman L, editors. Data monitoring in clinical trials: A case studies approach. Springer; 2006. pp. 118–35

    Google Scholar 

  69. Romond EH, Perez EA, Bryant J, et al Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Eng J Med. 2005;353:16,1673–84

    Google Scholar 

  70. Tan-Chiu E, Yothers G, Romond E, et al Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, Human Epidermal Growth Factor Receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005;23:7811–9

    CAS  PubMed  Google Scholar 

  71. Fleming TR, Harrington DP, O’Brien PC. Designs for group sequential tests. Control Clin Trials. 1984;5:348–61

    CAS  PubMed  Google Scholar 

  72. Pocock SJ. Clinical trials: A practical approach. New York: Wiley; 1983

    Google Scholar 

  73. Peto R, Peto J. Asymptotically efficient rank invariant test procedures (with discussion). J Roy Stat Soc, Series A (Statistics in Society). 1972;135:185–206

    Google Scholar 

  74. Cox DR. Regression models and life-tables (with discussion). J Roy Stat Soc, Series B. 1972;34:187–202

    Google Scholar 

  75. Kaplan EL, Meier P. Nonparametric estimator from incomplete observations. J Am Stat Assoc. 1958;53:457–81

    Google Scholar 

  76. Cutler SJ, Ederer F. Maximum utilization of the life table method in analyzing survival. J Chronic Dis. 1958;8: 699–712

    CAS  PubMed  Google Scholar 

  77. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies for disease. J Natl Cancer Inst. 1959;22:719–48

    CAS  PubMed  Google Scholar 

  78. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemotherapy Rep. 1967;50:163–70

    Google Scholar 

  79. Gehan EA. A generalized two sample Wilcoxon statistic for comparing arbitrarily censored data. Biometrika. 1965;52:650–3

    CAS  PubMed  Google Scholar 

  80. Tarone RE, Ware J. On distribution free tests for equality of survival functions. Biometrika. 1977;64:156–60

    Google Scholar 

  81. Efron B. Bootstrap methods: Another look at the jackknife. Ann Stat. 1979;7:1–26

    Google Scholar 

  82. Fisher B, Redmond C, Brown A, et al Treatment of primary breast cancer with chemotherapy and tamoxifen. N Eng J Med. 1981;305:1–6

    Article  CAS  Google Scholar 

  83. Gail M, Simon R. Testing for qualitative interactions between treatment effects and patient subsets. Biometrics. 1985;41:361–72

    CAS  PubMed  Google Scholar 

  84. Bonadonna G, Valagussa P. Dose-response effect of adjuvant chemotherapy in breast cancer. N Eng J Med. 1981;34:10–5

    Article  Google Scholar 

  85. Redmond C, Fisher B, Wieand HS. The methodologic dilemma in retrospectively correlating the amount of chemotherapy received in adjuvant therapy protocols with disease-free survival. Cancer Treatment Rep. 1983;67:519–26

    CAS  Google Scholar 

  86. Fisher B, Anderson S, Fisher ER, Redmond C, et al Significance of ipsilateral breast tumor recurrence after lumpectomy. Lancet. 1991;338:327–31

    CAS  PubMed  Google Scholar 

  87. Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika. 1988;75:800–2

    Google Scholar 

  88. Cook RJ, Farewell VT. Multiplicity considerations in the design and analysis of clinical trials. J Roy Stat Soc, Series A. 1996;159:93–110

    Google Scholar 

  89. Taghian A, Jeong J, Anderson S, et al Pattern of loco-regional failure in patients with breast cancer treated by mastectomy and chemotherapy (+/− tamoxifen) without radiation: results from five NSABP randomized trials. J Clin Oncol. 2004;22:4247–54

    PubMed  Google Scholar 

  90. Gaynor JJ, Feuer EJ, Tan CC, et al On the use of cause-specific failure and conditional failure probabilities: Examples from clinical oncology data. J Am Stat Assoc. 1993;88: 400–9

    Google Scholar 

  91. Korn EL, Dorey FJ. Applications of crude incidence curves. Stat Med. 1992;11:813–29

    CAS  PubMed  Google Scholar 

  92. Lin DY. Non-parametric inference for cumulative incidence functions in competing risks studies. Stat Med. 1997;16:901–10

    CAS  PubMed  Google Scholar 

  93. Pepe MS, Mori M. Kaplan-Meier, marginal or conditional probability curves in summarizing competing risks failure time data? Stat Med. 1993;2:37–751

    Google Scholar 

  94. Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data. New York: Wiley; 1980

    Google Scholar 

  95. Gooley TA, Leisenring W, Crowley J, et al Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706

    CAS  PubMed  Google Scholar 

  96. Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat. 1988;16:1141–54

    Google Scholar 

  97. Benichou, J, Gail, MH. Estimates of absolute cause-specific risk in cohort studies. Biometrics 1990;46:813–26

    CAS  PubMed  Google Scholar 

  98. Jeong J. A new parametric distribution for modeling cumulative incidence function: Application to breast cancer data. J Roy Stat Soc, Series A (Statistics in Society). 2006;169:289–303

    Google Scholar 

  99. Jeong J, Fine J. Direct parametric inference for cumulative incidence function. J Roy Stat Soc, Series C (Applied Statistics). 2006;55:187–200

    Google Scholar 

  100. Bryant J, Dignam JJ. Semiparametric models for cumulative incidence functions. Biometrics. 2004;60:182–90

    PubMed  Google Scholar 

  101. Fine JP, Gray RJ. A proportional hazards model for the sub-distribution of a competing risk. J Am Stat Assoc. 1999;94:496–509

    Google Scholar 

  102. Jeong J, Fine J. Parametric regression on cumulative incidence function. Biostatistics. 2007;8:184–96

    PubMed  Google Scholar 

  103. Garg ML, Rao BR, Redmond CK. Maximum-likelihood estimation of the parameters of the Gompertz survival function. J Roy Stat Soc, Series C (Applied Statistics). 1970;19:152–9

    Google Scholar 

  104. Gompertz B. On the nature of the function expressive of the law of human mortality, and on the new mode of determining the value of life contingencies. Phil Trans Roy Soc London. 1825;115:513–80

    Google Scholar 

  105. Dabrowska DM, Doksum KA. Estimation and testing in a two-sample generalized odds-rate model. J Am Stat Assoc. 1998;83:744–9

    Google Scholar 

  106. Goss PE, Ingle JN, Martino S, et al A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Eng J Med. 2003;349:1793–802

    CAS  Google Scholar 

  107. Latouche A, Porcher R, Chevret S. Sample size formula for proportional hazards modeling of competing risks. Stat Med. 2004;23:3263–74

    PubMed  Google Scholar 

  108. Paik S, Shak S, Tang G, et al A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Eng J Med. 2004;351:2817–26

    CAS  Google Scholar 

  109. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statistical Soc, Series B 1995;57:289–300

    Google Scholar 

  110. Bair E, Tibshirani R. Semi-supervised methods to predict patient survival from gene expression data. PLoS Biol. 2004;2:511–22

    CAS  Google Scholar 

  111. Harrell FE, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. J Am Med Assoc. 1982;247:2543–6

    Google Scholar 

  112. Hanley JA, McNeil BJ. The meaning and use of the area under the receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36

    CAS  PubMed  Google Scholar 

  113. Pencina MJ, D’Agostino RB. Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation. Stat Med. 2004;23:2109–23

    PubMed  Google Scholar 

  114. Wang R, Lagakos, SW, Ware JH, Hunter, DJ. Drazen, JM. Statistics in medicine — reporting of subgroup analyses in clinical trials. N Eng J Med. 2007;357:2189–94

    CAS  Google Scholar 

  115. Campbell MK, Elbourne DR, Altman DG. CONSORT statement: extension to cluster randomised trials. Br Med J. 2004;328(7441):702–8

    Google Scholar 

  116. Boutron I, Moher D, Altman DG, Schulz K, Ravaud P, for the CONSORT group. Methods and processes of the CONSORT Group: Example of an extension for trials assessing nonpharmacologic treatments. Ann Int Med. 2008;W60–W67

    Google Scholar 

  117. Boutron I, Moher D, Altman DG, Schulz K, Ravaud P, for the CONSORT group. Extending the CONSORT Statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Int Med. 2008;295–309

    Google Scholar 

  118. Hopewell S, Clarke M, Moher D, Wager E, Middleton P, Altman DG, Schulz KF and the CONSORT Group. CONSORT for reporting randomized controlled trials in journal and conference abstracts: explanation and elaboration. PLoS Med 5(1): e20. doi:10.1371/journal, 2008

    PubMed  Google Scholar 

  119. Hopewell S, Clarke M, Moher D, Wager E, Middleton P, Altman DG, Schulz KF, the CONSORT Group. CONSORT for reporting randomised trials in journal and conference abstracts. Lancet. 2008;371:281–83

    PubMed  Google Scholar 

  120. Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, et al Improving the quality of reports of randomized controlled trials: the CONSORT Statement. J Am Med Assoc. 1996;276:637–9

    CAS  Google Scholar 

  121. Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, et al The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Int Med. 2001;134(8):663–94

    CAS  PubMed  Google Scholar 

  122. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet. 2001;357(9263):1191–4

    CAS  PubMed  Google Scholar 

  123. Moher D, Schulz KF, Altman D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. J Am Med Assoc. 2001;285(15):1987–91

    CAS  Google Scholar 

  124. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Ann Int Med. 2001;134(8):657–62

    CAS  PubMed  Google Scholar 

  125. Early Breast Cancer Trialists’ Collaborative Group. Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer: an overview of 61 randomized trials among 28, 896 women. N Eng J Med. 1988;319:1681–91

    Article  Google Scholar 

  126. Early Breast Cancer Trialists’ Collaborative Group. Treatment of early breast cancer. Vol. I: Worldwide evidence 1985–1990. Oxford University Press, 1990

    Google Scholar 

  127. Early Breast Cancer Trialists’ Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Lancet. 1992;339:1–15 & 71–85

    Google Scholar 

  128. Early Breast Cancer Trialists’ Collaborative Group. Effects of radiotherapy and surgery in early breast cancer: an overview of the randomized trials. N Eng J Med. 1995;333:1444–55

    Google Scholar 

  129. Early Breast Cancer Trialists’ Collaborative Group. Ovarian ablation in early breast cancer: overview of the randomised trials. Lancet. 1996;348:1189–96

    Google Scholar 

  130. Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. 1998;351:1451–67

    Google Scholar 

  131. Early Breast Cancer Trialists’ Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet. 1998;352:930–42

    Google Scholar 

  132. Early Breast Cancer Trialists’ Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet. 2000;355:1757–70

    Google Scholar 

  133. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005a;365:1687–717

    PubMed  Google Scholar 

  134. Early Breast Cancer Trialists’ Collaborative Group. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and on 15-year survival: an overview of the randomised trials. Lancet. 2005b;366:2087–106

    Google Scholar 

  135. Moher D, Cook DJ, Eastwood, S, Olkin I. Rennie D, Stroup, DF, for the QUOROM Group. Improving the quality of reports of meta-analyses of randomized controlled trials: the QUOROM statement. Lancet 1999;354:1896–1900

    CAS  PubMed  Google Scholar 

  136. O’Quigley J, Pepe M, Fisher L. Continual reassessment method: A practical design for phase I clinical trials in cancer. Biometrics. 1990;46:33–48

    PubMed  Google Scholar 

  137. Gehan EA. The determination of the number of patients required in a preliminary and follow-up trial of a new chemotherapeutic agent. J Chronic Dis. 1961;13:346–53

    CAS  PubMed  Google Scholar 

  138. Assmann SF, Pocock SJ, Enos LE, Kasten LE. Subgroup analyses and other misuses of baseline data in clinical trials. Lancet. 2000;355:1064–9

    CAS  PubMed  Google Scholar 

  139. Benjamini Y, Yekutieli D. The control of the false discovery rate in multiple testing under dependency. Ann Stat. 2001;29:1165–88

    Google Scholar 

  140. Byar DP. The use of data bases and historical controls in treatment comparisons. Recent Results in Cancer Res. 1988;111:95–8

    CAS  Google Scholar 

  141. Elbourne DR, Altman DG, Pocock SJ, Evans SJW. Reporting of noninferiority and equivalence randomized trials: An extension of the CONSORT statement. J Am Med Assoc. 2006;295:1152–60

    Google Scholar 

  142. Harrell FE, Lee, KL, Mark, DB. Multivariable prognostic models: Issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1966;15:361–87

    Google Scholar 

  143. Paré A. Les oeuvres de M. Ambroise Paré conseiller, et premier chirurgien du Roy avec les figures & portraicts tant de l’Anatomie que des instruments de Chirurgie, & de plusieurs Monstres, Paris. Gabriel Buon 1575

    Google Scholar 

  144. Royall RM, Bartlett RH, Cornell RG. Ethics and statistics in randomized clinical trials. Stat Sci. 1991;6:52–88

    PubMed  Google Scholar 

  145. Piaggio G, Elbourne DRY Altman DG, Pocock SJ, Evans SJW. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA. 2006;295:1152–60

    CAS  PubMed  Google Scholar 

  146. Ioannidis JP, Evans, Gotzsche PC, O’Neil RT, Altman DG, Schulz K, Moher D. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med. 2004;141:781–8

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Pittsburgh, 318A Parran Hall, 130 DeSoto Street, Pittsburgh, PA, 15261, USA

    Carol K. Redmond

  2. University of Pittsburgh, 318B Parran Hall, 130 DeSoto Street, Pittsburgh, PA, 15261, USA

    Jong-Hyeon Jeong

Authors
  1. Carol K. Redmond
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jong-Hyeon Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carol K. Redmond .

Editor information

Editors and Affiliations

  1. Breast Care Center National Naval Medical Center, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD, 20814, USA

    Ismail Jatoi (Head) (Head)

  2. Women’s Hospital, University of Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany

    Manfred Kaufmann (Breast Unit Director) (Breast Unit Director)

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Redmond, C.K., Jeong, JH. (2010). Design, Implementation, and Interpretation of Clinical Trials. In: Jatoi, I., Kaufmann, M. (eds) Management of Breast Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69743-5_31

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-69743-5_31

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-69742-8

  • Online ISBN: 978-3-540-69743-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation