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Biomedical subjects

J Whitehead

Publications and source records attributed to J Whitehead.

6 recordsLinked to original sources

Overrunning and underrunning in sequential clinical trials.

In a sequential (or group sequential) clinical trial the fulfillment of some pre-specified stopping rule will cause recruitment to be terminated. However, for various reasons, data on patients treated according to protocol may continue to accumulate for some time afterward. This phenomenon is called overrunning. On the other hand, a sequential clinical trial might be abandoned before the stopping rule has been fulfilled. This is called underrunning. In both of these situations the procedure for validly analyzing the study is unclear. In this paper we first review the arguments for sequential methodology and the practical way in which it can be integrated with normal clinical trial conduct. Turning next to the special situations of overrunning and underrunning, the conditions under which a valid analysis is possible are identified, and a method of analysis based on the frequentist philosophy is presented. The likelihood of first gaining and then losing significance due to overrunning and its consequences are examined. Examples based on experience with real studies are presented.

Clinical Trials as Topic

Estimating the ventilation-perfusion distribution: an ill-posed integral equation problem.

The distribution of ventilation-perfusion ratio over the lung is a useful indicator of the efficiency of lung function. Information about this distribution can be obtained by observing the retention in blood of inert gases passed through the lung. These retentions are related to the ventilation-perfusion distribution through an ill-posed integral equation. An unusual feature of this problem of estimating the ventilation-perfusion distribution is the small amount of data available; typically there are just six data points, as only six gases are used in the experiment. A nonparametric smoothing method is compared to a simpler method that models the distribution as a histogram with five classes. Results from the smoothing method are found to be very unstable. In contrast, the simpler method gives stable solutions with parameters that are physiologically meaningful. It is concluded that while such smoothing methods may be useful for solving some ill-posed integral equation problems, the simpler method is preferable when data are scarce.

Animals

Variation in energy intake of aldolescent schoolgirls.

Twenty-four 16 to 17 year-old grammar school girls completed daily dietary histories (for eight weeks), and recorded details of mood, appetite and menstrual cycle. Marked daily variation in energy intakes was noted: on average an individual's highest daily intake was nearly four times her lowest intake, one subject having a nearly tenfold difference. Fluctuations were not related to mood, suggesting that this has less influence on dietary patterns than is generally supposed. While sitting examinations, energy intake was reduced by an average of 11.85%. It was not significantly changed during a field trip or by menstruation. This study suggests that dietary patterns previously considered to be abnormal or unusual are exhibited by and firmly entrenched in normal school girls.

Adolescent

Biology of colon cancer: an overview.

The altered growth characteristics of neoplastic cells have recently been associated with changes in membrane glycoproteins present on the cell surface. Since the carbohydrate moieties of surface membrane glycoproteins are asymmetrically located on the external cell surface, these glycoconjugates are likely candidates for providing cell surfaces with many of their biological properties. Using specific external cell surface labeling techniques, we have broadened our investigation of tumor cell surface glycoconjugates to include studies on cultured human epithelial cells from fetal intestine and from colonic carcinoma. We have isolated by affinity chromatography and gel filtration and integral membrane glycoprotein, termed Galactoprotein I, from a cultured human colonic adenocarcinoma cell line, which appears to be identical in many respects to CEA. Further examination of cell surface glycoproteins regarding quantitative and qualitative alterations and topographical redistribution should provide an insight into the biological aspects of tumor development.

Carcinoma