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M Zelen

Publications and source records attributed to M Zelen.

At least 37 records · Page 2Linked to original sources
PubMed1987

State of the art in comparative cancer clinical trials.

In order to investigate the current state of the art in clinical cancer research, a survey of comparative cancer clinical trials was conducted using a MEDLINE literature search of the 6-month interval from July to December of 1985. Data were obtained primarily from the published abstracts. The major observations from the study are as follows. First, trials in cancer research are published in an extraordinarily wide range of journals covering most of the major medical specialties in addition to the many cancer specialty journals. Second, randomization is now used quite extensively. It is the predominant method of control in chemotherapy trials and in trials reported in cancer journals. However, its use is much less common in other specialties, especially surgery, so efforts to popularize randomization in these specialties would be beneficial. Third, sample sizes are highly variable, and the median sample size (96 patients) is too small to reliably detect and evaluate moderate treatment advances. Finally, our survey reveals that published trials show an inordinately large proportion of breakthroughs in treatment compared with the generally accepted view that only slow progress is being made in developing effective cancer treatments. Our view is that this result reflects the strong tendency to publish only studies with positive results. This hypothesis is supported by the fact that in nonrandom trials there tend to be more positive conclusions and an absence of a strong association between conclusions and sample size.

Clinical Trials as Topic↗
PubMed1986

Assessment of adjuvant trials in breast cancer.

In this paper, we discuss the analytic problems associated with the evaluation of overall survival for breast cancer adjuvant studies and results of pooling data from the published literature to determine if there is evidence showing an overall survival advantage to adjuvant therapy. An investigation of the effect of competing causes of death shows that trials on older patients have low statistical power. Hence many of the current trials have low statistical power and may fail to find overall survival advantage for adjuvant therapy even when a benefit exists. The implications of the assessment of short-term follow-up are discussed in the context of the heterogeneous distribution of residual disease after primary treatment. Short-term follow-up (less than 5 yr) precludes anyone from making any conclusions about benefit for patients with small residual tumor burdens who constitute the patient subgroup most likely to benefit from adjuvant therapy. We reviewed 15 published randomized trials (each having a control group receiving no systemic therapy) to determine if overall survival has been increased by adjuvant therapy. We conclude that there is a benefit from some chemotherapy regimens given to node-positive premenopausal women. However, the published data for tamoxifen are mixed, with some trials showing benefit and others not. As more follow-up time is accumulated, this matter should be settled.

Adult↗
PubMed1985

Exploratory data analysis and the use of the hazard function for interpreting survival data: an investigator's primer.

This report discusses how one can use the hazard function to gain important insights on the patterns of failure in clinical studies when the principal endpoint is a time metric. These new insights may help gain increased understanding into the pathogenesis of a chronic disease and how it is affected by treatment intervention. The qualitative behavior of the hazard function can reveal whether mortality is increasing, decreasing, or is constant over time. Simple graphic plots are all that is necessary to show characteristic failure patterns. These informal procedures are in the spirit of carrying out exploratory analyses on the data. This report discusses the organization of clinical data using a "branch and leaf" plot, outlines the calculation of the hazard function and life table, and uses examples from lung cancer and uveal melanoma to illustrate calculations and ways of interpreting hazard functions.

Adenocarcinoma↗
PubMed1985

Products liability issues in school asbestos litigation.

The hazards posed by deteriorating friable asbestos in the nation's schools are causing serious concerns for public health officials, school boards, parents and school employees. Reports by both the Environmental Protection Agency and the U.S. Attorney General's Office agree that both school children and school employees stand a substantially increased risk of contracting some form of asbestos-related disease as a result of exposure to deteriorating asbestos materials in school buildings. School systems plagued by the asbestos hazards are now filing suits against asbestos manufacturers alleging causes of action in breach of warranty, negligence and strict products liability in tort. Some plaintiffs in school asbestos litigation seek to recover the costs of EPA-mandated asbestos inspection and abatement programs which have already been completed. Still others request injunctions to compel the manufacturers themselves to conduct inspections and finance abatement. This Note examines the school asbestos situation from a legal perspective and focuses primarily on whether the schools' claims should be considered as economic losses or as property damage. It examines the impact of statutes of limitations on these cases under both contract and tort theories. The Note argues that school asbestos claims should be decided under a strict products liability standard.

Adult↗
PubMed1984

Inferring the natural time history of breast cancer: implications for tumor growth rate and early detection.

This review analyzes the results of 692 breast cancer patients from the Norwegian Radium Hospital. All cases were diagnosed during the period 1951-1959 and the average follow-up time was just under eight years. All patients received a radical mastectomy and had their diagnoses pathologically confirmed by a separate reviewer. The purpose of this paper is to apply a novel method of analysis in order to infer the longitudinal course of the disease as if it had not been interrupted by treatment. The method allows one to estimate the average times between changes in the biological factors which characterize the natural history of the disease. Applying this method to the Norwegian data has resulted in identifying three pathways of the natural history of the disease. The tumor growth rates differ for these pathways and are in the approximate ratio 1:5:27. Furthermore, we can estimate the potential benefit from earlier diagnosis. Two of the three pathways would seem to benefit from earlier detection.

Adult↗
PubMed1983

Cooperative groups and community hospitals. Measurement of impact in the community hospitals.

The Eastern Cooperative Oncology Group, composed of major cancer treatment centers, has an outreach program which involves community hospitals in ongoing cancer clinical trials. A prevalence survey was carried out in February 1981 among 104 community hospitals and 21 member institutions to determine the characteristics of patients being treated, their staffing, and reasons why patients were not on protocol studies. The survey sampled 25 (50) consecutive patients from community hospitals (member institutions). The purpose of the study was to assess the impact of a community cancer control program. The results of the study demonstrated that 16% of patients surveyed in the affiliated community hospitals were being treated on a research protocol. In addition, a further 35% had their treatment plan influenced by a protocol. Consequently protocols have impacted directly or indirectly on 51% of the patients. The corresponding figures in member institutions were 23% and 38% for a total of 61%. In studying protocol availability, it was found that 66% of all patients were ineligible for any protocol. Of patients eligible for a protocol but not registered on one, 52% were not registered because of physician preference for a specific treatment. The affiliates surveyed were shown to be on average half as large as member institutions in terms of number of beds and staff size. Also, staff/patient ratios are generally smaller in the community hospitals. The median age of patients was considerably lower than SEER incidence data. Also, elderly patients were slightly more prevalent in community hospitals than in member institutions. A clear relationship between disease stage and age in breast cancer patients was noted with the representation of early-stage disease much higher in young women.

Adult↗
PubMed1983

Innovations in the design of clinical trials in breast cancer.

The execution of clinical trials is perhaps the most difficult way of carrying out a scientific experiment. This is especially true of chronic diseases, such as breast cancer, which require long-term follow-up and large numbers of patients. As a result, it is necessary to involve many physicians who can contribute patients to these studies. Unfortunately, many physicians are not comfortable participating in randomized studies because they feel the patient-physician relationship may be compromised. This paper discusses new ways of planning randomized clinical trials which do not interfere with the patient-physician relationship. The new designs are called 'randomized consent' or 'prerandomized' designs. The study designs are discussed from the point of view of statistical efficiency and the new ethical problems which may arise.

Age Factors↗
PubMed1983

Guidelines for publishing papers on cancer clinical trials: responsibilities of editors and authors.

Guidelines are proposed for the reporting of clinical trials. These are meant to be used for both authors and journal editors. Specific proposals are made for: reporting the population under study, actual therapy used, describing the study design, accounting of patients, follow-up statistics, and describing the quality control of the data. Nonrandomized studies require special discussion. Such studies potentially have substantial biases which can lead to incorrect conclusions. Six areas of biases arising in nonrandomized studies are pointed out which should require a discussion in an acceptable published paper. The presentation of statistical results and the reporting of early studies present unusually difficult problems. Guidelines are presented for statistical analyses which, although simple to implement in practice, are not generally used. A proposal is made for the publication of early results of a study which require that the authors agree to follow and periodically report on their trial to the journal editor. If the early conclusions change with additional follow-up, the editor should notify its readers. The adoption of these guidelines can be an important force in raising the scientific level of the reporting of clinical trials.

Authorship↗
PubMed1983

Biostatistical science as a discipline: a look into the future.

The field of biostatistics is enjoying unparalleled developments. Never before have members of our profession been in such demand. Current applications are significantly influencing the direction of research in statistical methodology. It is not clear whether there is a discipline which can be termed 'biostatistics', but we are part of the emergence of a discipline which is termed 'biostatistical science'. It refers to the applications of statistics, probability, computing and mathematics to the life sciences, with the goal of advancing our knowledge of a subject-matter field in this area. This paper discusses the role of computing, some aspects of training, and future directions of biostatistical science. A special role is envisioned for the Biometric Society to be more active in problems associated with developing countries.

Animals↗
PubMed1982

Participation of community hospitals in clinical trials: analysis of five years of experience in the Eastern Cooperative Oncology Group.

The Eastern Cooperative Oncology Group (ECOG) initiated a program in 1976 to involve community hospitals in multi-institutional clinical trials. The community hospitals can be characterized as generally having no tradition of participating in clinical trials of cancer therapy, whereas the ECOG member institutions are university hospitals or major treatment centers. More than 100 community hospitals participated in 97 randomized trials involving 4506 patients from November 1976 through February 1981. Comparisons between the community hospitals and the ECOG member institutions indicate that the quality of participation was similar, as measured by rates of ineligibility, compliance with the protocol, and submission of data. Objective measures of outcome, such as survival, response, and toxicity, were also comparable. We conclude that under the mechanism adopted by the ECOG, it is possible to include community hospitals in clinical trials of cancer therapy without reducing the quality of the data or compromising the therapeutic outcomes.

Clinical Trials as Topic↗
PubMed1982

The contributions of Jerome Cornfield to the theory of statistics.

This paper is a review of the contributions of Jerome Cornfield to the theory of statistics. It discusses several highlights of his theoretical work as well as describing his philosophy relating theory to application. The three areas discussed are: linear programming, urn sampling and its generalizations to the analysis of variance, and Bayesian inference. It is not widely known that Jerome Cornfield was perhaps the first to formulate and approximately solve the linear programming problem in 1941. His formulation was made for the famous "Diet Problem". An early publication introduced the method of indicator random variables in the context of urn sampling. This simple method allowed straightforward calculations of the low order moments for estimates arising from sampling finite populations and was later generalized to the two-way analysis of variance. The application of the urn sampling model to the analysis of variance served to illuminate how one chooses proper error terms for making tests in the analysis of variance table. Jerome Cornfield's philosophy on applications of statistics was dominated by a Bayesian outlook. His theoretical contributions in the past two decades were mainly concerned with the development of Bayesian ideas and methods. A brief survey is made of his main contributions to this area. A particularly noteworthy result was his demonstration that for the two-sample slippage problem of location, the likelihood function under a permutation setting is uninformative for the slippage parameter. However, the posterior distribution differs from the prior distribution despite the fact that the likelihood is uninformative.

Bayes Theorem↗