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D L Demets

Publications and source records attributed to D L Demets.

10 recordsLinked to original sources
PubMed1994

On a model-based approach to estimating efficacy in clinical trials.

Treatment efficacy is of primary importance in phase III clinical trials. Determining the true size of the treatment effect is often complicated by patient non-compliance with the regimen. This paper examines a model-based approach in the spirit of Efron and Feldman utilizing drug and placebo compliance information. One of the assumptions of this analysis is 'comparability' of drug and placebo compliance. Robustness in estimation of subgroup and population treatment effects when this assumption is violated is investigated in a simulation study. We find that even moderate non-comparability (for example, normalized compliance correlations of 0.4) may produce severely biased estimates. The basis is modulated by the strength of the relationship between compliance and the response on placebo.

Bias↗
PubMed1992

Sample size determination for group sequential clinical trials with immediate response.

The use function approach to group sequential methods has been explored previously. Any group sequential design requires specifying the frequency and times of repeated analyses, but only the use function approach allows deviations from those specified in the design, without affecting the type I error in the analysis. This paper illustrates how the use function provides a simple and flexible design procedure and how the initially projected maximum sample size can be calculated for randomized clinical trials in which responses are known relatively soon after patient entry and for which there is an early stopping rule built into the study protocol. Also the consequence of using the proposed design procedure is investigated in terms of the operating characteristics of the subsequent group sequential analyses.

Breast Neoplasms↗
PubMed1989

Group sequential procedures: calendar versus information time.

This paper describes the relationship between information time and calendar time in the use of group sequential procedures to monitor interim analyses of clinical trials. Information time is the proportion of maximum subjects or events already observed. Interim analyses often occur at specified calendar times while the definition of classic group sequential procedures occurs in terms of information time. We extend the general group sequential approach of Lan and DeMets to include this situation as well.

Algorithms↗
PubMed1976

Reanalysis of some baboon descent data.

Wagner and Altmann [1973] recently reported an analysis of a set of baboon descent times, some of which were left censored due to varying arrival times at the observation site. Any transformation of the data which reverses order produced a set of right censored observations. In this way, the Kaplan-Meier [1958] estimate of the descent time distribution can be computed. Estimates of the mean and variance of the distribution are given, as well as the standard error of the estimate of the mean.

Animals↗
PubMedDate not supplied

Methods for combining randomized clinical trials: strengths and limitations.

Methods for combining data from several studies exist and appear to be quite useful. None satisfactorily addresses the question of what studies should be combined. This issue is the most serious methodological limitation. Even studies with statistically significant interaction might still be combined if the effect were in the same direction. Thus, substantial scientific input is required as to what criteria must be met by each potential study. Much can be learned from combining or pooling data but it must be done cautiously. Pooling exercises do not replace well designed prospective clinical trials. Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful.

Clinical Trials as Topic↗
PubMedDate not supplied

Practical aspects in data monitoring: a brief review.

Monitoring interim accumulating data in a clinical trial for evidence of therapeutic benefit or toxicity is a frequent policy, usually carried out by an independent scientific committee. Repeated testing at conventional critical values can substantially inflate the type I error rate. To maintain acceptable levels, group sequential and stochastic curtailment have been developed for clinical trials. One should not view such methods as absolute rules, but as useful guides. The decision process to terminate a trial early is complex and necessitates an accounting for many factors. The Beta-Blocker Heart Attack Trial provides an excellent example of many of these issues.

Clinical Trials as Topic↗
PubMedDate not supplied

Adequate survival of red cells from units "undercollected" in citrate-phosphate-dextrose-adenine-one.

The lower limit for the volume of whole blood that may be collected for transfusion into standard blood recipient sets is 405 ml. Each year it is estimated that 82,500 to 161,700 units are drawn which contain between 275 and 405 ml. This study evaluated whether these "undercollected" units would be suitable for transfusion. Twenty normal adults donated both a "standard" unit (450 ml) and an "undercollected" unit (275 ml) in 63 ml of citrate-phosphate-dextrose-adenine-one (CPDA-1). The units were packed within 4 hours (mean Hct 71%) and stored undisturbed at 4 degrees C for 35 days. Aliquots of 1 to 2 ml of red cells from each unit were then labeled with 51chromium (51Cr) and reinfused into the original donor. The mean 24-hour survival of the 450-ml units was 78.8 percent (SD 12.2, SEM 2.7), while the mean 24-hour survival of the 275-ml units was 87.7 percent (SD 10.7, SEM 2.4; p less than .01). Seven inadvertently undercollected units (mean vol: 295 ml) had a mean 24-hour survival of 91.9 percent. The higher concentration of dextrose and adenine in the undercollected units may improve posttransfusion red cell viability. These data suggest that 275 ml is the minimum acceptable volume for blood donated into CPDA-1.

Adenine↗
PubMedDate not supplied

A double blind study of the effects of zinc sulfate on taste and smell dysfunction.

A randomized, double blind crossover study of the effects of zinc sulfate and placebo was carried out in 106 patients with taste and smell dysfunction secondary to a variety of etiological factors. In the patient group prior to treatment, mean serum zinc concentration and leukocyte alkaline phosphatase activity were significantly lower than normal. Results indicate that zinc sulfate was effectively equivalent to placebo in the treatment of these disorders. Although these results demonstrate abnormalities of zinc metabolism in some patients with taste and smell dysfunction they fail to provide evidence for a single, therapeutic approach to the many disorders which are associated with abnormalities of taste and smell. However, the methods and procedures developed in this study demonstrate that taste and smell dysfunction can be studied in a quantitative, systematic manner.

Adult↗