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American Journal of Epidemiology Advance Access originally published online on January 6, 2009
American Journal of Epidemiology 2009 169(3):285-293; doi:10.1093/aje/kwn302
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American Journal of Epidemiology © The Author 2009. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

PRACTICE OF EPIDEMIOLOGY

Methodological Issues in Analyzing Time Trends in Biologic Fertility: Protection Bias

Jane Key, Nicky Best, Michael Joffe, Tina Kold Jensen and Niels Keiding

Correspondence to Dr. Michael Joffe, Department of Epidemiology and Public Health, Imperial College London, St. Mary’s Campus, Norfolk Place, London W2 1PF, United Kingdom (e-mail: m.joffe{at}imperial.ac.uk).

Received for publication January 8, 2008. Accepted for publication September 4, 2008.

One method of assessing biologic fertility is to measure time to pregnancy (TTP). Accidental pregnancies do not generate a valid TTP value and lead to nonrandom missing data if couples experiencing accidental pregnancies are more fertile than the general population. If factors affecting the rate of accidental pregnancies, such as availability of effective contraception and induced abortion, vary over time, then the result may be protection bias in the estimates of fertility time trends. Six European data sets were analyzed to investigate whether evidence of protection bias exists in TTP studies of fertility trends in Europe over the past 50 years. Couples experiencing accidental pregnancies tended to be more fertile than the general population. However, trends in accidental pregnancy rates were inconsistent across countries and were insufficient to produce substantial bias in fertility trends in simulated data. Where protection bias is suspected, the authors demonstrate use of 2 multiple imputation methods to generate realizations for the missing TTP values for accidental pregnancies. Simulation studies show that both methods successfully reduce or eliminate protection bias. The authors also demonstrate that standard sensitivity analyses for dealing with accidental pregnancies provide an upper bound on the extent of any bias.

bias (epidemiology); fertility; infertility; methods; trends


Abbreviations: TTP, time to pregnancy


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