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Nobuyuki Hamada

Publications and source records attributed to Nobuyuki Hamada.

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A generalisation of the method of regression calibration and comparison with Bayesian and frequentist model averaging methods

For many cancer sites low-dose risks are not known and must be extrapolated from those observed in groups exposed at much higher levels of dose. Measurement error can substantially alter the dose-response shape and hence the extrapolated risk. Recently, there has been considerable attention paid to methods of dealing with shared errors, which are particularly important in occupational and environmental settings. In this paper we test Bayesian model averaging (BMA) and frequentist model averaging (FMA) methods, the first of these similar to the so-called Bayesian two-dimensional Monte Carlo (2DMC) method, and both fairly recently proposed, against a very newly proposed modification of the regression calibration method, the extended regression calibration (ERC) method. The quasi-2DMC+BMA method performs well when a linear model is assumed, but poorly when a linear-quadratic model is assumed. FMA performs as well as quasi-2DMC+BMA when a linear model is assumed, and generally much better with a linear-quadratic model, although the coverage probability for the quadratic coefficient is uniformly too high. ERC yields coverage probabilities that are too low when shared and unshared Berkson errors are both large (50%), although otherwise it performs well, and coverage is generally better than the quasi-2DMC+BMA or FMA methods, particularly for the linear-quadratic model. The bias of predicted relative risk at a variety of doses is generally smallest for ERC, and largest for quasi-2DMC+BMA and FMA, with standard regression calibration and Monte Carlo maximum likelihood exhibiting bias in predicted relative risk generally somewhat intermediate between ERC and the other two methods. In general ERC performs best in the scenarios presented, and should be the method of choice in situations where there may be substantial shared error, or suspected curvature in the dose response.

q-bio.QM

Pneumonia after bacterial or viral infection preceded or followed by radiation exposure -- a reanalysis of older radiobiological data and implications for low dose radiotherapy for COVID-19 pneumonia

Currently, there are 14 ongoing clinical studies on low dose radiotherapy (LDRT) for COVID-19 pneumonia. An underlying assumption is that irradiation of about 1 Gy is effective at ameliorating viral pneumonia. Its rationale, however, relies on early human case series or animal studies mostly obtained in the pre-antibiotic era, where rigorous statistical analyses were not performed. It therefore remains unclear whether those early data support such assumptions. With standard statistical survival models, and based on a systematic literature review, we re-analyzed 14 radiobiological animal datasets in which animals received mostly fractionated doses of radiation before or after bacterial/viral inoculation, and assessing various health endpoints (mortality, pneumonia morbidity). In most datasets absorbed doses did not exceed 7 Gy. Various different model systems and types of challenging infection are considered. For 7 studies that evaluated post-inoculation radiation exposure (more relevant to LDRT for COVID-19 pneumonia) the results are heterogeneous, with 2 studies showing a significant increase (p<0.001) and another showing a significant decrease (p<0.001) in mortality associated with radiation exposure. For pre-inoculation exposure the results are also heterogeneous, with 6 datasets showing a significant increase (p<0.01) in mortality risk associated with radiation exposure and the other 2 showing a significant decrease (p<0.05) in mortality risk. Collectively, these data do not provide clear support for reductions in morbidity or mortality associated with post-infection radiation exposure. For pre-infection radiation exposure the inconsistency of direction of effect makes this body of data difficult to interpret. Nevertheless, one must be cautious about adducing evidence from the published reports of these old animal datasets.

q-bio.TO