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S Durrleman

Publications and source records attributed to S Durrleman.

10 recordsLinked to original sources
PubMed1991

When to randomize?

Many clinical trials address the question of the duration of therapy or whether initial therapy can be improved by the addition of a consolidation or maintenance regimen. For such clinical trials, the question of when to perform the randomization is often difficult. Conventional statistical wisdom prescribes that randomization should take place as late as possible before treatment is effected. This is not always possible or desirable, however. In this report, we describe the factors that are influenced by the timing of randomization, quantify how timing affects these factors, and attempt to provide a tool to help investigators and statisticians determine the appropriate time to randomize for individual studies and particular circumstances.

Randomized Controlled Trials as Topic↗
PubMed1990

Prognostic factors for patients with diffuse large cell or immunoblastic non-Hodgkin's lymphomas: experience of the non-Hodgkin's Lymphoma Pathologic Classification Project.

Prognostic factors for long-term survival of 312 patients with diffuse large cell or immunoblastic non-Hodgkin's lymphoma are presented based on analysis of the multiinstitution clinicopathologic study sponsored by the National Cancer Institute. At the time of analysis, 75% of the patients had died and the median follow-up for patients still alive was 11 years. The distribution of Ann Arbor stages was 21% stage I, 32% stage II, 17% stage III, and 30% stage IV. Factors of prognostic significance for survival included age, stage, histologic subtype, presence of B symptoms, size of the largest lesion, number of extra-lymphoid organs involved, and extent of lymphatic involvement. Recursive partitioning analysis suggested a prognostic classification system based on stage, age, size of the largest lesion, and presence of mediastinal involvement. Stage I patient less than 50 years of age had a 10 year survival rate of 65% compared to 36% for older stage I patients. Stage II patients less than 65 years old without bulky lesions or mediastinal involvement had a 10 year survival rate of 45% compared to 10% for the poorer risk stage II patients. Although statistically significant prognostic factors were identified for the stage III/IV patients, they were not strong discriminants of 5-10 year survival rate. Because of the correlation among potential prognostic factors, there is no uniquely best classification system. Reasons for discrepancies among reported prognostic factor analyses are discussed, and a prognostic grouping that synthesizes our results with those of others is proposed.

Adult↗
PubMed1990

Planning and monitoring of equivalence studies.

Demonstrating therapeutic equivalence of two treatments is the goal of many clinical trials. For instance, when the toxicity of an effective standard treatment is of concern, much effort is devoted to developing new therapies that would be both as effective and less toxic. In this paper we review the special characteristics of these trials and describe sequential monitoring of equivalence studies using repeated confidence intervals. We show how sequential monitoring may be of particular value in this setting and critically discuss the choice of some important design parameters. We also provide tables for use when planning a sequential equivalence trial.

Biometry↗
PubMed1989

Flexible regression models with cubic splines.

We describe the use of cubic splines in regression models to represent the relationship between the response variable and a vector of covariates. This simple method can help prevent the problems that result from inappropriate linearity assumptions. We compare restricted cubic spline regression to non-parametric procedures for characterizing the relationship between age and survival in the Stanford Heart Transplant data. We also provide an illustrative example in cancer therapeutics.

Adult↗
PubMed1989

2'-Deoxycoformycin after failure of alpha-interferon in hairy cell leukemia.

Alpha-interferon (IFN) and 2'-deoxycoformycin (dCF) both exhibit substantial activity in the treatment of hairy cell leukemia (HCL). Anecdotal reports have suggested that patients who failed IFN could achieve durable responses with dCF, although the frequency with which this was said to have occurred was unknown. We reviewed the available data on the responsiveness of HCL to dCF after IFN therapy by analyzing cases reported in the literature and those treated under the Special Exception mechanism of the National Cancer Institute, Division of Cancer Treatment. Of 60 such cases identified there were 22 (37%) "compete responses" and 22 (37%) "partial responses" for a total response rate of 74%. Responses appeared to be durable in many cases, lasting up to 2 years at the time of reporting. dCF is an active agent in HCL both as initial therapy and for the salvage of patients who have failed IFN. The relative activity of these two agents and the optimal strategies for their use are currently under investigation in ongoing clinical trials.

Drug Administration Schedule↗
PubMed1989

Increasing trend of ALS in France and elsewhere: are the changes real?

We analyzed 9,005 deaths from amyotrophic lateral sclerosis recorded in France between the years 1968 and 1982. The overall adjusted mortality rates were 1.45/100,000 for men and 0.90/100,000 for women. We found excess male mortality in every age group. Age-specific mortality rates increased with age until 65-74 years and then declined in the older population. There was no meaningful regional pattern. We found a substantial increase in ALS mortality over time: the adjusted rates (per 100,000) in the period 1968 to 1971 were 1.11 for men and 0.63 for women. In the period 1979 to 1982, the corresponding figures were 1.92 and 1.12. The increase was mainly due to persons over 55 years of age and affected mostly the women during the first part of the study (1968 to 1978). In the recent years, increase appeared similar in both sexes. The temporal trends are consistent across studies in different countries.

Adult↗
PubMed1988

The Non-Hodgkin Lymphoma Pathologic Classification Project. Long-term follow-up of 1153 patients with non-Hodgkin lymphomas.

STUDY OBJECTIVE: To document the long-term prognosis of patients with non-Hodgkin lymphoma treated between 1971 and 1975 and to determine how the prognosis varies by histologic subtype and stage. SETTING: Three cancer referral centers in the United States and one center in Italy. PATIENTS: A consecutive sample of 1153 previously untreated patients with non-Hodgkin lymphoma. At the time of analysis, 71% of the patients had died and the median follow-up for patients still alive was 11.2 years. MEASUREMENTS AND MAIN RESULTS: The 10-year survival proportions were 45% (CI, 40% to 50%); 26% (CI, 22% to 30%); and 23% (CI, 18% to 30%) for patients with low-, intermediate-, and high-grade lymphomas, respectively. Patients with intermediate- and high-grade lymphomas were curable, but this was not apparent for patients with advanced stage low-grade lymphomas. For the low-grade follicular small cleaved and follicular mixed lymphomas, the Ann Arbor staging system distinguished the prognosis of patients with stage I disease from those with more extensive involvement. For the diffuse large cell and immunoblastic lymphomas, the Ann Arbor staging system distinguished long-term prognosis for patients with stage I disease from patients with stage II disease and those with more disseminated involvement. CONCLUSIONS: The probability of long-term survival for unselected patients with non-Hodgkin lymphoma can be substantial. Long-term prognosis depends on the histologic subtype of the tumor and the extent of dissemination. The Working Formulation for non-Hodgkin lymphomas is a simple and useful nomenclature for selecting treatment and reporting results. The Ann Arbor staging system is a useful but imperfect prognostic indicator.

Bone Marrow↗
PubMedDate not supplied

[Monitoring of clinical trials and interim analysis. 1. Monitoring committee].

In order to fulfil the ethical principles linked to the protection of patients randomized in a controlled clinical trial, monitoring procedures need to be set up. In this context, a committee of experts, called the data monitoring committee is in charge of reviewing regularly unblinded data to assess the quality and the relevance of the trial, to evaluate the evidence of an emerging treatment difference and to control the rate of occurrence of serious adverse events. After each meeting, the monitoring committee reports to the steering committee its recommendation to continue or to stop the trial prematurely. Protocol modifications might be proposed as well. Illustrated with several examples, this article reviews different situations a monitoring committee might have to tackle with.

Clinical Protocols↗
PubMedDate not supplied

[Monitoring of clinical trials and interim analysis. 2. Statistic methods].

Although the decision to continue or to stop prematurely a clinical trial is not solely based on statistical tests, they bring useful objective arguments to the data monitoring board. However, the multiple use of statistical tests leads to increase the risk of false positive conclusions in favor of one of the treatments, and several methods have been developed to address this problem. This article presents the four major strategies that are being used for monitoring clinical trials, as well as the rationale for planning and using such statistical monitoring procedures.

Bayes Theorem↗