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Biomedical subjects

L W Huson

Publications and source records attributed to L W Huson.

7 recordsLinked to original sources

Missing data imputation in two phase III trials treating HIV1 infection.

In most longitudinal clinical trials, some patients drop out before the end of the planned follow-up, and, in order to allow an all-patient intent-to-treat analysis to be performed, it is common practice to use some method of imputation to estimate values for missing data. However, different imputation methods may provide different results, and it is essential to investigate the sensitivity of the analysis using different imputation rules. In our analysis of two trials of the new HIV1 fusion inhibitor enfuvirtide, we compared some standard methods of imputing and analyzing HIV1-RNA data with two novel alternatives, to check the robustness of the primary endpoint results. The standard methods were: (1) last-observation-carried-forward, (2) baseline carried forward, and (3) multiple imputation. These were compared with a nearest-neighbour hot-deck method, specifically proposed for imputation of missing HIV1-RNA data, and with a heuristic approach: censored regression analysis of the last-observation-carried-forward. To supplement this analysis of real clinical trial data, we investigated the performance of the same imputation methods on simulated datasets designed to cover a broader range of missing data patterns.

Algorithms↗

Multiple polyexponentials and quasipolynomials as empirical nonlinear regression models: a case study with HIV viral load data.

Measurements of HIV1-RNA plasma concentrations are an important method of assessing patient response to anti-HIV1 treatment, and in most clinical trials of such treatments HIV1-RNA levels are assessed at regular intervals of time. HIV1-RNA levels in successfully treated patients tend to follow a standard pattern of biphasic decline-a rapid early decline in viral load, followed by a period of slower decline or a steady level. Fitting nonlinear regression models to these patterns of declining HIV1-RNA levels can be of value in comparing different treatment regimes and in predicting treatment outcome. Simple exponential-decline models can give an adequate fit to the typical pattern of HIV1-RNA decline, but we have explored the extent to which curve-fitting can be improved by using two novel nonlinear model forms. Specifically, we describe the fitting of multiple polyexponential and quasipolynomial forms to longitudinal HIV1-RNA plasma data collected in two recent trials of the novel anti-HIV1 treatment Fuzeon. We comment on the practicalities of fitting these nonlinear models, and compare the fit using various criteria.

Data Interpretation, Statistical↗

Effects of light treatment upon mood and melatonin in patients with seasonal affective disorder.

Ten patients with seasonal affective disorder received the following treatments for 5 days each: (a) artificial daylight (2500 lux) from 20.00 to 23.00 and from 07.00 to 10.00 hours; (b) red light (300 lux) from 20.00 to 23.00 and from 07.00 to 10.00 hours; (c) artificial daylight (2500 lux) from 22.00 to 23.00 and from 07.00 to 08.00 hours. The antidepressant effect of treatment (a) was superior to that of treatment (b), suggesting that the effect of light treatment in winter depression is more than that of a placebo. The antidepressant effect of treatment (a) was superior to that of treatment (c), although these two treatments equally suppressed plasma melatonin concentrations. Consequently, in these patients there is a dissociation between the effect of light treatment on melatonin and the reduction of depression ratings.

Adult↗

Statistical analysis of comparative field trials of acute rodenticides.

The present method of analysis of data from comparative field trials of acute rodenticides was compared with two alternative methods of analysis, using computer simulation techniques. One of the proposed alternative analyses, the use of post-treatment census takes as a percentage of pre-treatment census takes in an analysis of variance, was found to be more accurate, to avoid a theoretical difficulty associated with the present method, and is computationally much simpler.

Animals↗

Warfarin-resistance genotype determination in the Norway rat, Rattus norvegicus.

The 2-stage determination is based on changes in blood coaggulation activity brought about both by the administration of warfarin in conjunction with vitamin K1 epoxide and by feeding a vitamin K-free diet for 4 days. When it was applied to laboratory-bred rats of known warfarin-resistance genotype, 35/35 homozygous susceptible, 44/44 homozygous resistant and 131/133 heterozygous rats were correctly classified. This method was equally effective in identifying the genotype of wild rats carrying the warfarin-resistance gene, Rw2. The procedure is rapid and accurate.

Animals↗