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Biomedical subjects

D Byar

Publications and source records attributed to D Byar.

13 recordsLinked to original sources
PubMed1995

Tryptophan metabolites, pyridoxine (vitamin B6) and their influence on the recurrence rate of superficial bladder cancer. Results of a prospective, randomised phase III study performed by the EORTC GU Group. EORTC Genito-Urinary Tract Cancer Cooperative Group.

This double-blind randomised phase III trial was designed to assess the effect of pyridoxine administration on the recurrence of Ta and T1 transitional cell tumours of the bladder. The trial accrued 291 patients and showed no significant difference between the pyridoxine and placebo treatment groups with respect to the time to first recurrence or the recurrence rate. Adjustment for the main prognostic factors, namely the recurrence rate prior to entry, the number of tumours at entry, the G grade and the levels of the tryptophan metabolites kynurenine plus acetyl kynurenine at entry do not change the overall conclusions.

Administration, Oral↗
PubMed1990

Dietary fat reduction and plasma estradiol concentration in healthy postmenopausal women. The Women's Health Trial Study Group.

Concentrations of total and weakly bound plasma estradiol were significantly (P less than .01) reduced in 73 healthy post-menopausal women after 10-22 weeks of participation in a low-fat diet intervention program. Nonsignificant reductions in estrone sulfate and sex hormone-binding protein were also observed. The 17% reduction in average estradiol concentration was accompanied by an average reduction of 12 mg/dL in total plasma cholesterol (P less than .001), an average weight loss of 3.4 kg (P less than .001), and an average reduction in daily dietary fat from 68.5 to 29.5 g. Our review of case-control studies indicates that a 17% reduction in plasma estradiol may explain a noteworthy component of the international variation in breast cancer incidence. We find a need for further studies of (a) disease risk in relation to hormone concentrations and (b) changes in hormone concentrations as a function of the duration of low-fat diet intervention.

Aged↗
PubMed1990

Analysis of the costs of a large prevention trial.

Total direct costs of the Women's Health Trial (WHT), a large multicenter prevention trial, were reduced by more than 50% by means of research cost analysis conducted during the trial design phase. The unit costs of specific trial activities were estimated so that total direct costs of the trial could be predicted from design parameters. The relative costs of screening, treatment, and follow-up, and the fixed costs associated with each clinical center in a multicenter prevention trial were taken into account. Direct costs of the WHT were reduced from +195 million to +95 million by refinement of the trial protocol, selection of an efficient design, and consideration of trial logistics. The analyses suggest several ways to reduce costs in a prevention trial. Use of the case-cohort approach can reduce costs substantially when the protocol includes collection of specimens or data that are costly to process. When establishing and maintaining a clinical center represents a significant proportion of a clinical center's costs, use of a smaller number of larger clinical centers offers important cost savings. Because restrictive eligibility requirements reduce the recruitment potential of each clinical center, use of high-risk participants may not improve the efficiency of a prevention trial; its favorable impact on sample size may fail to compensate for its cost in terms of additional clinical centers and higher recruitment costs.

Aged↗
PubMed1989

Passive smoking on commercial airline flights.

In-flight exposure to nicotine, urinary cotinine levels, and symptom self-reports were assessed in a study of nine subjects (five passengers and four attendants) on four routine commercial flights each of approximately four hours' duration. Urine samples were collected for 72 hours following each flight. Exposures to nicotine measured during the flights using personal exposure monitors were found to be variable, with some nonsmoking areas attaining levels comparable to those in smoking sections. Attendants assigned to work in nonsmoking areas were not protected from smoke exposure. The type of aircraft ventilation was important in determining the levels of in-flight nicotine exposure. The environmental tobacco smoke levels that occurred produced measurable levels of cotinine (a major metabolite of nicotine) in the urine of passengers and attendants. Passengers who experienced the greatest smoke exposure had the highest levels of urinary cotinine. Changes in eye and nose symptoms between the beginning and end of the flights were significantly related both to nicotine exposure during the flight and to the subsequent urinary excretion of cotinine. In addition, subjects' perceptions of annoyance and smokiness in the airplane cabin were also related to in-flight nicotine exposure and urinary excretion measures.

Air Pollutants↗
PubMed1988

A quantitative study of the bias in estimating the treatment effect caused by omitting a balanced covariate in survival models.

This paper discusses the quantitative aspects of bias in estimates of treatment effect in survival models when there is failure to adjust on balanced prognostic variables. A simple numerical example of this bias is given along with approximate formulae for its calculation in the multiplicative exponential survival model. The accuracy of the formulae is checked by simulation. In addition, approximate calculations and simulations of power loss and the effects of omitting more than one prognostic covariate are presented. The Weibull and Cox models are also examined using simulation. Study of this bias is pertinent to much applied work, and shows that the effect of omitting balanced covariates can be modest unless the variables are strongly prognostic or many in number. This work emphasizes the need for thorough comparisons of adjusted and unadjusted analyses for sensible interpretation of treatment effects.

Humans↗
PubMed1988

Statistical design of the Women's Health Trial.

The National Cancer Institute has initiated a randomized trial to determine whether a low fat diet can reduce the incidence of breast cancer among women at increased risk for this disease. A feasibility trial involving 303 women has been conducted to examine recruitment strategies, study short-term compliance and, more generally, develop and refine trial procedures. The feasibility trial group also developed a detailed full-scale trial design plan, and randomization of participants to such a trial is currently underway. The purpose of this report is to describe the major design features of this Women's Health Trial, with particular emphasis on the statistical aspects of the design. The trial is planned to last 10 years and to include 32,000 participants. Of these 32,000 women, 12,800 will be assigned to a low fat diet intervention, and the other 19,200 will constitute a control group. The sample size of 32,000 arises from a range of estimates and assumptions pertaining to (a) the incidence of breast cancer at enrollment corresponding to selected eligibility criteria, (b) the relative risk of breast cancer as a function of a woman's history of dietary fat intake, (c) compliance assumptions in terms of average percent fat in the intervention and control groups as a function of time from randomization, and (d) rates of competing causes of death. These estimates and assumptions will be discussed, as will the robustness of the intended sample sizes to departures from such design assumptions.

Aged↗
PubMed1988

How dependent causes of death can make risk factors appear protective.

It is shown, using the results of Slud and Rubinstein (1983, Biometrika 70, 643-649) in a specially constructed theoretical example, that competing latent failure times Ti and Ci and a two-level covariate Vi, if analyzed as though Ti and Ci are independent for each Vi level, can lead to exactly the wrong conclusion about the ordering of Pr(Ti greater than or equal to t[Vi = 1) and Pr(Ti greater than or equal to t[Vi = 0) for every t. This phenomenon can never be excluded on purely statistical grounds using such data and should be considered when interpreting data analyses involving competing risks.

Cause of Death↗
PubMed1987

[Use of prognostic knowledge in the planning and analysis of randomized therapeutic trials].

For most diseases, one observes great variability in clinical course and response to therapy which should be taken into account in the design and the analysis of clinical trials. Eligibility criteria and stratified randomization use prognostic knowledge. A suitable analysis of randomized studies includes: (1) checking treatment effect groups for comparability, (2) adjustment of treatment effect by stratifying or modeling to account for any imbalances in prognostic factors and to increase the precision of the treatment comparison by reducing random variation, (3) looking for treatment-covariate interactions suggesting that response to treatment depends on patients' characteristics. Tests for interaction should be interpreted with caution in light of medical plausibility; multiple comparisons should be taken into account. Recording information on known prognostic factors in clinical trials is important, as is the continuing search for new ones.

Clinical Trials as Topic↗
PubMed1977

Comparisons of placebo, pyridoxine, and topical thiotepa in preventing recurrence of stage I bladder cancer.

Animal studies have shown that metabolites of tryptophan can cause bladder cancer, and human observations reveal an appreciable incidence of abnormalities of tryptophan metabolism in patients with bladder cancer. It has been suggested that pyridoxine (vitamin B6) may correct this abnormality and prevent recurrences of superficial bladder cancers. Intravesical instillation of thiotepa has been used for more than fifteen years in the treatment of superficial bladder cancer, but no controlled trials have been done. We report here a prospective clinical trial of 121 patients with Stage I bladder cancer randomized to placebo, pyridoxine, or intravesical thiotepa. The percentages of patients with recurrences over the period of study were 60.4, 46.9, and 47.4 for the three groups, respectively, and did not differ significantly. However, if patients having recurrences during the first ten months or followed up less than ten months were excluded, pyridoxine was significantly better than placebo (P = 0.03). Thiotepa significantly reduced the recurrence rate compared with placebo (P = 0.016) or pyridoxine (P = 0.015). These results suggest that a new trial of pyridoxine should be undertaken in which the tryptophan metabolites are measured and that further study of intravesical instillation of chemotherapeutic agents is warranted.

Administration, Oral↗