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M Zelen

Publications and source records attributed to M Zelen.

At least 19 recordsLinked to original sources
PubMed1990

Randomized consent designs for clinical trials: an update.

Randomized consent designs were introduced to make it easier for physicians to enter patients in randomized clinical trials. Physician reluctance to participate in randomized clinical trials is often a reflection that the physician-patient relationship could be compromised if the physician makes known to the patient his/her inability to select a preferred therapy. Clinical trials having a no-treatment control or placebo amplify this concern. This paper reviews the main ideas of randomized consent designs (single and double) and the statistical model underlying the analysis, and presents some recent experiences.

Informed Consent↗
PubMed1989

An investigation of a reported cancer cluster in Randolph, Massachusetts.

An increasingly common public health problem is the perception that disease incidence has increased or a cluster of disease has occurred in a community. In most cases, the disease of concern is cancer and a local hazardous waste site or other environmental problem is involved. These problems can be difficult to investigate and public health officials are frequently criticized for their inability to address community concerns. This paper reports a case study of such a situation occurring in the Barlett-Green Acres (BGA) neighborhood of Randolph, Massachusetts. Study data were obtained by interviews in households of persons belonging to a list of alleged cancer cases initially supplied by residents and supplemented using records available in town and state public health offices. One objective of the investigation was to develop methods that may be of value in similar situations arising in other communities. From a list of names compiled prior to and during the investigation, 45 incident cases of cancer were identified and found suitable for analysis. An additional four cases were added from the Massachusetts Cancer Registry. The analysis showed the existence of a cancer cluster, but overall cancer incidence and mortality in the BGA neighborhood were not elevated. Residence history, disease site, and other features of the cancer cases were investigated using methods less sensitive to incomplete reporting than total incidence. No unusual features of the cancer data other than the initiating cluster were identified and no environmental hazard likely to impact the BGA neighborhood was discovered, hence we conclude that the most likely cause of the cancer cluster was random variation in cancer rates.

Adolescent↗
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↗
PubMed1979

A new design for randomized clinical trials.

This paper proposes a new method for planning randomized clinical trials. This method is especially suited to comparison of a best standard or control treatment with an experimental treatment. Patients are allocated into two groups by a random or chance mechanism. Patients in the first group receive standard treatment; those in the second group are asked if they will accept the experimental therapy; if they decline, they receive the best standard treatment. In the analyses of results, all those in the second group, regardless of treatment, are compared with those in the first group. Any loss of statistical efficiency can be overcome by increased numbers. This experimental plan is indeed a randomized clinical trial and has the advantage that, before providing consent, a patient will know whether an experimental treatment is to be used.

Clinical Trials as Topic↗
PubMed1978

The Radiation Therapy Oncology Group: a progress report.

The Radiation Therapy Oncology Group (RTOG), founded in 1971, comprises 35 university hospitals which are participating in 21 active protocols, four registries and eight pilot studies, including Phase I/II studies. Case accession has grown to over 1000 in 1977 with 19,801 patients being entered in the RTOG initial registration. Goals of the RTOG include: advancing knowledge of the role of radiation therapy in disease management; improving control of primary and regional disease; reducing morbidity and complications from treatment; and collaborating with other oncology disciplines to obtain data on multimodality therapy.

Clinical Trials as Topic↗
PubMed1977

Therapeutic trials in the management of metastatic brain tumors by different time/dose fraction schemes of radiation therapy.

Two consecutive studies have been performed by the Radiation Therapy Oncology Group on patients with metastatic brain tumors. Approximately 1,000 patients were entered into each trial. Treatment schedules of varying dose-time fractionations were used. Results were evaluated on the basis of improvement in general performance and neurologic function status. Survival also was recorded. Patients who received corticosteroids in conjunction with radiation therapy experienced a more rapid improvement in neurologic function than patients who did not receive steroid therapy. This was noted particularly in patients with poor neurologic function status. However, by the 4th week this difference had disappeared. Survival times were not altered by the addition of steroid therapy. Preliminary results of the second study suggest that ultra-short fractionation schedules are less effective than the longer ones used in the first study. A dose of 3,000 rads given in 10 equal fractions for a period of 2 weeks appeared to be the most satisfactory schedule for most patients with intracranial metastases.

Adrenal Cortex Hormones↗
PubMed1976

Immunocompetence, immunodeficiency and prognosis in cancer.

Immunocompetence and prognosis are related in solid tumors, malignant lymphomas, and acute leukemia. Among the parameters of immunocompetence vigorous delayed-type hypersensitivity responses to recall antigens or to primary immunization with Keyhole limpet hemocyanin, vigorous in vitro lymphocyte blastogenic responses to mitogens such as PHA, and relatively high B-lymphocyte levels, all correlate with a good prognosis. The spectrum of immune reactivity as measured by established delayed-type hypersensitivity to recall antigens and in vitro blastogenic responses to mitogens and antigens is similar in melanoma patients and their nontumor-bearing spouses. In melanoma, only patients with widespread inoperable metastatic disease show severe immunological deficiency and this is selective for certain antigens. There are highly significant differences in response to specific antigens when patients with melanoma and lung cancer are compared. Immunotherapy with BCG and C. parvum can boost immunocompetence as measured by recall DTH skin testing. However, the relationship between the initial immunocompetence and prognosis still holds in patients receiving BCG immunotherapy to prevent recurrence of melanoma. These data indicate that a broader survey of immunological reactivity in cancer patients is needed, that immunological testing is useful in cancer prognosis clinically, and that the results of immunological testing can be used to evaluate therapy and to indicate new pathways for improved treatment.

B-Lymphocytes↗
PubMed1975

L-Phenylalanine mustard (L-PAM) in the management of primary breast cancer. A report of early findings.

Prolonged l-phenylalanine mustard (L-PAM) administration as an adjuvant to mastectomy in the management of patients with primary breast cancer and pathologically positive axillary nodes was evaluated by a prospective, randomized, clinical trial. Treatment failures occurred in 22 per cent of 108 patients receiving placebo and 9.7 per cent of 103 women given L-PAM (p = 0.01). A statistically significant difference (p = 0.02) existed in favor of L-PAM relative to disease-free interval. In premenopausal women, the difference with respect to disease-free interval of treated and control groups was highly significant (p = 0.008). A treatment failure occurred in 30 per cent of premenopausal patients receiving placebo and 3 per cent of those treated with L-PAM (p = 0.008). Whereas a similar trend was observed in postmenopausal patients, the difference is not statistically significant. Thus, L-PAM has been demonstrated to be effective in the treatment of women with primary breast cancer, particularly those who are premenopausal. Results were achieved with minimal undesirable side effects.

Bone Marrow↗