A generalisation of the method of regression calibration

Author:

Little Mark P.1,Hamada Nobuyuki2,Zablotska Lydia B3

Affiliation:

1. National Cancer Institute

2. Central Research Institute of Electric Power Industry (CRIEPI)

3. University of California, San Francisco, National Cancer Institute

Abstract

Abstract There is direct evidence of risks at moderate and high levels of radiation dose for highly radiogenic cancers such as leukaemia and thyroid cancer. For many cancer sites, however, it is necessary to assess risks via extrapolation from groups exposed at moderate and high levels of dose, about which there are substantial uncertainties. Crucial to the resolution of this area of uncertainty is the modelling of the dose-response relationship and the importance of both systematic and random dosimetric errors for analyses in the various exposed groups. It is well recognised that measurement error can alter substantially the shape of this relationship and hence the derived population risk estimates. Particular attention has been devoted to the issue of shared errors, common in many datasets, and particularly important in occupational settings. We propose a modification of the regression calibration method which is particularly suited to studies in which there is a substantial amount of shared error, and in which there may also be curvature in the true dose response. This method can be used in settings where there is a mixture of Berkson and classical error. In fits to synthetic datasets in which there is substantial upward curvature in the true dose response, and varying (and sometimes substantial) amounts of classical and Berkson error, we show that the coverage probabilities of all methods for the linear coefficient \(\alpha\) are near the desired level, irrespective of the magnitudes of assumed Berkson and classical error, whether shared or unshared. However, the coverage probabilities for the quadratic coefficient \(\beta\) are generally too low for the unadjusted and regression calibration methods, particularly for larger magnitudes of the Berkson error, whether this is shared or unshared. In contrast Monte Carlo maximum likelihood yields coverage probabilities for \(\beta\) that are uniformly too high. The extended regression calibration method yields coverage probabilities that are too low when shared and unshared Berkson errors are both large, although otherwise it performs well, and coverage is generally better than these other three methods. A notable feature is that for all methods apart from extended regression calibration the estimates of the quadratic coefficient \(\beta\) are substantially upwardly biased.

Publisher

Research Square Platform LLC

Reference51 articles.

1. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). UNSCEAR 2006 Report. Annex A. Epidemiological Studies of Radiation and Cancer. (United Nations, 2008).

2. Armstrong, B. et al. Radiation. Volume 100D. A review of human carcinogens., (International Agency for Research on Cancer, 2012).

3. Thyroid cancer following childhood low-dose radiation exposure: a pooled analysis of nine cohorts;Lubin JH;J. Clin. Endocrinol. Metab.,2017

4. Leukaemia and myeloid malignancy among people exposed to low doses (< 100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies;Little MP;Lancet Haematol,2018

5. Review of the risk of cancer following low and moderate doses of sparsely ionising radiation received in early life in groups with individually estimated doses;Little MP;Environ Int,2022

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