  Accurate estimation of cancer mortality rates and the comparison across
cancer sites, populations or time periods is crucial to public health, as
identification of vulnerable groups who suffer the most from these diseases may
lead to efficient cancer care and control with timely treatment. Because cancer
mortality rate varies with age, comparisons require age-standardization using a
reference population. The current method of using the Year 2000 Population
Standard is standard practice, but serious concerns have been raised about its
lack of justification. We have found that using the US Year 2000 Population
Standard as reference overestimates prostate cancer mortality rates by 12-91%
during the period 1970-2009 across all six sampled U.S. states, and also
underestimates case fatality rates by 9-78% across six cancer sites, including
female breast, cervix, prostate, lung, leukemia and colon-rectum. We develop a
mean reference population method to minimize the bias using mathematical
optimization theory and statistical modeling. The method corrects the bias to
the largest extent in terms of squared loss and can be applied broadly to
studies of many diseases.
