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D A Berry

Publications and source records attributed to D A Berry.

80 records · Page 5Linked to original sources
PubMed1980

Statistical inference and the design of clinical trials.

According to the likelihood principle of statistics, a decision to stop or otherwise alter a clinical trial can be made on the basis of accumulating information without losing the ability to draw inferences from the results of the trial. In particular, balanced, randomized designs are not necessary. The probability that a particular treatment is the best among those in the trial can be calculated after each patient response, and may suggest that the treatment should be used predominantly in the next stage of the trial. Doing so results in more effective treatment of the patients in the trial while sacrifacing some of the information on the other treatments. Not doing so results in equal information on the treatments but sacrifices effective treatment. There are many trials in which compromise is possible between these antagonistic consequences.

Clinical Trials as Topic↗
PubMedDate not supplied

Regression analysis applied to PVC histories: a statistical procedure for evaluating antiarrhythmic drug efficacy.

Suppression of premature ventricular contractions (PVCs) is one of the goals of antiarrhythmic therapy. In a clinical trial, however, it may be difficult to distinguish antiarrhythmic drug effect from spontaneous variation in PVCs. We propose the application of linear regression to PVC histories to ascertain drug effect in individual patients. The model determines which variables are important in explaining a patient's PVCs. One such variable indicates the presence or absence of the drug; the model determines whether the drug has an effect on the patient's PVCs, while compensating for the other explanatory variables. In addition to determining the statistical significance of any drug effect, the model estimates the strength of the effect for each patient. We demonstrate the method with data from a three-day clinical trial which used 24-hour Holter monitoring. The method is flexible and can be modified to apply to any clinical study design. It allows for inferences concerning populations and subpopulations of patients.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

Optimal designs for clinical trials with dichotomous responses.

We consider two-stage designs for clinical trials that involve two treatments with dichotomous responses. The first is the information-gathering stage; the treatment chosen as the better from first stage and prior data is used exclusively in the second stage. Determination of treatment allocation in the first stage results from weighing the anticipated gain in information with effective treatment; the objective is to maximize the expected number of successes in the entire trial. This is in contrast to randomized controlled trials with the restricted objective of obtaining information concerning treatment differences. We allow the length of the first stage to be arbitrary and fixed in advance, or optimized as a function of prior information and the 'patient horizon'. We can regard this patient horizon as either the number of patients in the trial or the number who have the condition under treatment. We consider two forms of prior information: both success probabilities known but the better of the two treatments is unknown, and one success probability known whereas the other has an arbitrary distribution. In many instances of the latter case the optimal first stage size is of the order of the square root of the patient horizon.

Clinical Trials as Topic↗
PubMedDate not supplied

Interim analyses in clinical trials: classical vs. Bayesian approaches.

This paper concerns interim analysis in clinical trials involving two treatments from the points of view of both classical and Bayesian inference. I criticize classical hypothesis testing in this setting and describe and recommend a Bayesian approach in which sampling stops when the probability that one treatment is the better exceeds a specified value. I consider application to normal sampling analysed in stages and evaluate the gain in average sample number as a function of the number of interim analyses.

Bayes Theorem↗
PubMedDate not supplied

Stopping a clinical trial early: frequentist and Bayesian approaches applied to a CALGB trial in non-small-cell lung cancer.

In May 1984, the Cancer and Leukemia Group B (CALGB) opened a phase III clinical trial for patients with stage III non-small-cell lung cancer (NSCLC). The experimental design entailed randomization of 240 patients equally to one of two treatments: radiotherapy alone or chemotherapy followed by radiotherapy. The original design was a fixed sample size design with the intent to analyse the results after 190 deaths. Shortly after the trial began, it was decided to apply group sequential concepts by using a truncated O'Brien-Fleming stopping rule, implemented via a Lan-DeMets alpha-spending function. A study monitoring committee was established to review the analyses as they were produced. The study was stopped at the fifth interim analysis in May 1987 after 155 eligible patients had been entered. This paper reviews the statistical and other considerations leading to this decision and presents later follow-up information on these patients. Some Bayesian alternatives to the standard frequentist approaches are also explored and it is demonstrated how these alternatives provide a natural way to address many of the issues raised in monitoring clinical trials.

Bayes Theorem↗
PubMedDate not supplied

Testing for the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes: a decision analysis.

OBJECTIVE: The authors developed a Markov decision model to evaluate the health implications of testing for mutations in the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes. Prophylactic measures considered included various combinations of immediate and delayed bilateral mastectomy and oophorectomy or taking no action. METHODS: The model incorporated the likelihood of developing breast and/or ovarian cancer, survival, and quality of life. Parameter values were taken from public databases, the published literature, and a survey of cancer experts. Outcomes considered were additional life expectancy and quality-adjusted life years (QALYs). Results are reported for 30-year-old cancer-free women at various levels of hereditary risk. RESULTS AND CONCLUSIONS: The vast majority of women will not benefit from testing because their pre-test risks are low and surgical prophylaxis is undesirable. However, women who have family histories of early breast and/or ovarian cancer may gain up to 2 QALYs by allowing genetic testing to inform their decisions.

Adult↗
PubMedDate not supplied

A million dollar measles outbreak: epidemiology, risk factors, and a selective revaccination strategy.

Between February 8 and April 4, 1986, an outbreak of measles occurred in the State of Arkansas. A total of 489 suspected measles cases were reported from 53 counties; 86 schools statewide reported suspected measles cases. There were 284 cases confirmed in 18 counties; 23.6 percent among students in one university and 41.2 percent among students in kindergarten through 12th grade in 32 schools. An epidemiologic investigation was carried out to evaluate risk factors for vaccine failure and to assess the effectiveness of a selective revaccination strategy in the outbreak setting. A cohort study conducted at a junior high school showed that, compared with students vaccinated against measles at ages 15 months or older, those vaccinated at ages 12-14 months had a three-fold increased risk of measles (relative risk 3.2, 95 percent confidence interval 1.5, 6.9). For schools reporting measles, the Arkansas Department of Health and the Department of Education jointly required reimmunization of students vaccinated at ages younger than 15 months and the exclusion of students not vaccinated at ages 15 months or older until they were vaccinated or until 2 weeks after the last rash onset. To implement these recommendations, more than 100,000 doses of combined measles-mumps-rubella vaccine were distributed at a cost greater than $1 million.

Adolescent↗