Introduction and methods sections reproduced from: Early Breast Cancer Trialists' Collaborative Group, "Treatment of Early Breast Cancer. Volume 1. Worldwide Evidence 1985-1990"

Oxford University Press 1990

Disclaimer: The following was reproduced using optical character recognition software. Every effort has been made to ensure that the text has been reproduced correctly. We apologise for any errors which may remain.


3.1 Systematic public availability of randomized trial results
3.2 Informative overviews even of somewhat different trials, despite heterogeneity of design and of size of treatment effect
3.3 Importance of reliably assessing MODERATE treatment effects
3.4 Two main reasons for using overviews of properly randomized trials to assess MODERATE treatment effects: avoiding selection biases and reducing random errors
3.5 Review of many trials, with no data-dependent omissions, to limit selection bias in assessment of treatment effects
3.6 Other selection biases either in design or in analysis of trials
3.7 Proper randomization (with no subsequent exclusions) to limit selection bias in design of trials of moderate treatment effects
3.8 Selection biases from subgroup analyses: statistical difficulty in the assessment of qualitative "interactions" and of quantitative "interactions"
3.9 Specific categories of patient or of treatment: data-dependent emphasis on subgroup analyses versus indirect extrapolation of overall analyses
3.10 Use of recurrence data, as well as mortality data, to study interactions unbiasedly
3.11 Use of overviews to assess effects of treatment on other specific causes of early death, or other rare endpoints
3.12 Use of overviews to improve the reliability of data from particular trials


4.1 Summary of the inclusion criteria for trials in the present overviews
4.2 Principles of identification of trials: selection bias may be limited even without absolute completeness
4.3 Practice of identification of trials: multiple sources of information
4.4 Methods of seeking data from individual trials
4.5 Methods of checking data from individual trials
4.6 Methods of publishing data from individual trials


5.1 Medical assumptions: (1) modest sizes of treatment effects, and (2) differences of size but not of direction between effects in different circumstances
5.2 Comparisons only of like with like, based on "Observed minus Expected" (O-E) differences in each separate trial
5.3 Routine stratification of all main analyses by age (<50, 50+) and by year (1, 2, 3, 4, 5+) of follow-up
5.4 Additional stratification of selected analyses for the available information on nodal status or Estrogen Receptor status
5.5 Arithmetic procedures for calculation of Observed minus Expected (O-E) numbers of events among treatment-allocated patients, and for obtaining "two-sided" significance levels ( 2 P )
5.6 Interpretation of P-values: statistical significance and medical judgement
5.7 RESULTS OF RADIOTHERAPY TRIALS as an example of the summation of (O-E) values from different trials to provide an overall test of the "null hypothesis" of no treatment effect
5.8 Use of (O-E) values to provide a description of the typical reduction in the odds of treatment failure (i.e. to describe the "alternative hypothesis")
5.9 Graphical display methods for separate trial results, and for an overview
5.10 Similarities between risk ratios, death rate ratios and odds ratios when event rates are low
5.11 Logrank "year of death" analyses for statistical significance tests, and for estimation of reductions in annual odds of death
5.12 Life-table estimation for descriptive purposes
5.13 Test of heterogeneity between several different trial results
5.14 Arithmetic details of tests for trend, for heterogeneity and for interaction
5.15 Practical meaning of a clear effect of treatment in a single large trial
5.16 Practical meaning of a clear effect of treatment in an overview of many trials
5.17 Fixed-effect "assumption-free" methods, and random-effect "assumed representativeness" methods


(1) ANON. Review of mortality results in randomized trials in early breast cancer. Lancet 1984; ii: 1205.
(2) EARLY BREAST CANCER TRIALISTS' COLLABORATIVE GROUP. Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. New Engl J Med 1988; 319: 1681-1692.
(3) CUZICK J, STEWART H, PETO R, ET AL. Overview of randomized trials of post-operative adjuvant radiotherapy in breast cancer. Cancer Treatment Reports 1987; 71: 15-29.
(4) PETO R. Why do we need systematic overviews of randomized trials? Stat Med 1987; 6: 233-240.
(5) YUSUF S, PETO R, LEWIS J, COLLINS R, SLEIGHT P. Beta-blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 1985; 27: 335-371.
(6) ANTIPLATELET TRIALISTS' COLLABORATION. Secondary prevention of vascular disease by prolonged antiplatelet treatment. Brit Med J 1988; 296: 320-331.
(7) CARTER SK. Acute lymphocytic leukemia. In Randomized trials in cancer: a critical review by sites (Staquet M, ed). New York: Raven Press, 1978, pp.l-24.
(8) ROZENCWEIG M, VON HOFF DD, DAVIS HL, JACOBS EM, MUGGIA FM, DEVITA VT. Hodgkin's Disease. In Randomized trials in cancer: a critical review by sites (Staquet M, ed). New York: Raven Press, 1978, pp.103-130.
(9) YUSUF S, COLLINS R, PETO R. Why do we need some large, simple randomized trials? Statistics in Medicine 1984; 3: 409-420.
(10) SILVERBERG E. Cancer Statistics, 1988. "Ca -- A cancer journal for clinicians". American Cancer Society, New York, 1988; 38(1): 5-22.
(11) DICKERSIN K, CHAN SS, CHALMERS TC, SACKS HS, SMITH H. Publication bias in randomized control trials. Controlled Clinical Trials 1987; 8: 343-353.
(12) SIMES RJ. Publication bias: the case for an international registry of clinical trials. J Clin Oncology 1986; 4: 1529-1541.
(13) REES JKH, GRAY RG, SWIRSKY D, HAYHOE FGJ. Principal results of the Medical Research Council's 8th Acute Myeloid Leukaemia Trial. Lancet 1986; ii: 1236-41.
(14) BYAR DP. Why data bases should not replace randomized clinical trials. Biometrics 1980; 36: 337-342.
(15) PETO R. Statistical aspects of cancer trials. In: The treatment of cancer (Halnan K, ed). London: Chapman & Hall, 1982, pp.867-871.
(16) GAIL M, SIMON R. Testing for qualitative interactions between treatment effects and patient subsets. Biometrics 1985; 41: 361-372.
(17) ISIS-2 COLLABORATIVE GROUP. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; ii: 349-360.
(18) ISIS-1 COLLABORATIVE GROUP. Randomised trial of intravenous atenolol among 16 027 cases of suspected acute myocardial infarction: ISIS-1. Lancet 1986; ii: 57-66.
(19) COLLINS R, GRAY R, GODWIN J, PETO R. Avoidance of large biases and large random errors in the assessment of moderate treatment effects. the need for systematic overviews. Stat Med 1987; 6: 245-250.
(20) FEINLEIB M. Breast cancer and artificial menopause: a cohort study. J Natl Cancer Inst 1968; 41: 315-329.
(21) COLDITZ GA, WILLETT WC, STAMPFER MJ, ROSNER 8, SPEIZER FE, HENNKENS CH. Menopause and the risk of coronary heart disease in women. New Engl J Med 1987; 316: 1105-1110.
(22) STAMPFER MJ, WILLETT WC, COLDITZ GA, ROSNER B, SPEIZER FE, HENNEKENS CH. A prospective study of postmenopausal estrogen therapy and coronary heart disease. New Engl J Med 1985; 313: 1044-1049.
(23) KEY TJA, PIKE MC. The dose-effect relationship between "unopposed" oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. Br J Cancer 1988; 57: 205-212.
(24) VESSEY MP. The Jephcott Lecture 1989: An overview of the benefits and risks of combined oral contraceptives. In Oral contraceptives and breast cancer: the implications of present findings for informed consent and informal choice(Mann RD,ed). Carnforth: Parthenon Publishing Group 1990.
(25) BYAR DP, CORLE DK. Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group Studies. National Cancer Institute Monographs 1988; 7: 165-170.
(26) INTERNATIONALAGENCY FOR RESEARCH ON CANCER. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans, Volume 41: Some antineoplastic and immunosuppressive agents. Lyon: IARC, 1981, pp.l-411.
(27) UNITED NATIONS SCIENTIFIC COMMITTEE ON THE EFFECTS OF ATOMIC RADIATION. Sources, effects and risks of ionizing radiation. New York: United Nations, 1988.
(28) UNITED NATIONS SCIENTIFIC COMMITTEE ON THE EFFECTS OF ATOMIC RADIATION. Sources and effects of ionizing radiation. New York: United Nations, 1977.
(29) MANTEL N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemotherapy Reports 1966; 50: 163-170.
(30) PETO R, PIKE MC, ARMITAGE P, ET AL. Design and analysis of randomised clinical trials requiring prolonged observation of each patient. Br J Cancer 1976; 34: 585-612.
(31) PETO R, PIKE MC, ARMITAGE P, ET AL. Design and analysis of randomised clinical trials requiring prolonged observation of each patient. Br J Cancer 1977; 35: 1-39.
(32) GREENLAND S, SALVAN A. Bias in the one-step method for pooling study results. Stat Med 1990; 9: 247-252
(33) HENNEKENS CH, BURING JE, SANDERCOCK P, COLLINS R, PETO R. Aspirin and other antiplatelet agents in the secondary and primary prevention of cardiovascular disease. Circulation 1989; 80: 749-756.
(34) PATERSON R. Breast cancer: a report of two clinical trials. J Roy Coll Surgeons Edin 1962; 7: 243-254
(35) HENDERSON IC. Adjuvant systemic therapy of early breast cancer and endocrine therapy of metastatic breast cancer. In: Harris JR, Hellman S, Henderson IC, Kinne DW, eds. Breast diseases. Philadelphia: J B Lippincott, 1987: 324-353.
(36) GRUPPO ITALIANO PER LO STUDIO DELLA STREPTOCHINASI NELL' INFARTO MIOCARDICO (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986: i: 397-402.