Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.
TL;DR: Efficient methods of analysis of randomized clinical trials in which the authors wish to compare the duration of survival among different groups of patients are described.
Abstract: Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses.
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TL;DR: The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death fromComorbid disease for use in longitudinal studies and further work in larger populations is still required to refine the approach.
39,961 citations
TL;DR: In this review the usual methods applied in systematic reviews and meta-analyses are outlined, and the most common procedures for combining studies with binary outcomes are described, illustrating how they can be done using Stata commands.
31,656 citations
TL;DR: The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions.
Abstract: Background Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently. We studied the effect of an angiotensin-converting-enzyme inhibitor, enalapril, on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35. Methods Patients receiving conventional treatment for heart failure were randomly assigned to receive either placebo (n = 1284) or enalapril (n = 1285) at doses of 2.5 to 20 mg per day in a double-bind trial. Approximately 90 percent of the patients were in New York Heart Association functional classes II and III. The follow-up averaged 41.4 months. Results There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036). Although reductions in mortality were observed in several categories of cardiac deaths, the largest reduction occurred among the deaths attributed to progressive heart failure (251 in the placebo group vs. 209 in the enalapril group; reduction in risk, 22 percent; 95 percent confidence interval, 6 to 35 percent). There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure. Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26 percent; 95 percent confidence interval, 18 to 34 percent; P less than 0.0001). Conclusions The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions.
7,460 citations
TL;DR: The 10-year and 15-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival are reported and it is found that the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.
6,309 citations
TL;DR: This update of the CONSORT statement improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias.
Abstract: Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.
5,957 citations
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TL;DR: In this article, the product-limit (PL) estimator was proposed to estimate the proportion of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t).
Abstract: In lifetesting, medical follow-up, and other fields the observation of the time of occurrence of the event of interest (called a death) may be prevented for some of the items of the sample by the previous occurrence of some other event (called a loss). Losses may be either accidental or controlled, the latter resulting from a decision to terminate certain observations. In either case it is usually assumed in this paper that the lifetime (age at death) is independent of the potential loss time; in practice this assumption deserves careful scrutiny. Despite the resulting incompleteness of the data, it is desired to estimate the proportion P(t) of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t). The observation for each item of a suitable initial event, marking the beginning of its lifetime, is presupposed. For random samples of size N the product-limit (PL) estimate can be defined as follows: L...
52,450 citations
Journal Article•
7,476 citations
TL;DR: Some comparisons are made for five cases of varying degrees of censoring and tying between probabilities from the exact test and those from the proposed test and these suggest the test is appropriate under certain conditions when the sample size is five in each group.
Abstract: H2: F1(t) F2(t) (t F2(t) (t < T). The asymptotic efficiency of the test relative to the efficient parametric test when the distributions are exponential is at least 0 75 and increases with degree of censoring. When Ho is true, the test is not seriously affected by real differences in the percentage censored in the two groups. Some comparisons are made for five cases of varying degrees of censoring and tying between probabilities from the exact test and those from the proposed test and these suggest the test is appropriate under certain conditions when the sample size is five in each group. A worked example is presented and some discussion is given to further problems.
3,318 citations
679 citations
"Design and analysis of randomized c..." refers background or methods in this paper
...If you have a statistician analysing your data for you, he may use your O's and E's to calculate something slightly different from your X2 to compare with the chi-square distribution (Peto and Pike, 1973; Breslow....
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...E) in the ith subgroup, Asum = Eixi and the Vexact is EXijcij, where summation is over all groups from first to last inclusive and cij, the covariance of xi with xj, is given by Peto and Pike (1973)....
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...E, extent of exposure to risk of death 51 95 38 -05 90-00 Relative death rate, O/E 0-77 1-31 1-00 * The name " logrank " derives from obscure mathematical considerations (Peto and Pike, 1973) which are not worth understanding; it's just a name....
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...Details are given by Peto and Pike (1973) and an example is given in Appendix 3....
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...H: ANALYSIS calculated for publication purposes (Peto and Pike, 1973 -see statistical note 7 on p. 38) if statistical assistance is available, and these will usuallv be slightly more extreme than the significance levels derived by this simple chi-squared analogy....
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TL;DR: The efficacy of active immunotherapy in the control of acute lymphoblastic leukaemia in man is demonstrated and patients treated by immunotherapy have not relapsed.
574 citations