Ecologic LNT study - reply from Dr. Lubin

[FIELDRW@aol.com]

This exchange has been very useful.  The fundamental disagreement that I have
with Dr. Cohen is simply whether one can "scale up" a model for individuals 
and
attain a meaningful model at the county level.  The answer is no; one cannot
"scale up" without accurate within-county information on risk factors (and the
county-to-county variation) - information that ecological studies do not have.
Let's state the issue in the reverse.  Suppose several counties have equal
county-level radon "means", and equal county-level data for all other risk
factors (the same mean ages, proportion of smokers, SES, etc), i.e., at the
county level the covariate information is identical across counties.  Is there
anything that can be inferred about the lung cancer rates in the counties?  
The
answer is no; one cannot draw any logical inference about the lung cancer 
rates
in the counties.  While the risk factor information is the same at the county
level (and thus no additional adjustments are ever possible using county
information), differences in lung cancer rates at the county level may occur 
due
to differences in the correlational relationhips among the risk factors within
the counties.

Population dose can be a valid indicator of population risk, and "scaling up"
can be valid only when the risk relationship between disease outcome and all
risk factors is linear in all risk factors.  However, there is overwhelming
evidence that the functional relationship between radon, other risk factors 
and
lung cancer is most decidedly not linear - it is linear in radon exposure, but
proportional to the background rate.  This non-linear relationship for risk 
has
been most clearly demonstrated in the greater than additive associations 
between
radon and numerous factors and lung cancer, such as radon and tobacco use (and
very likely exposure to environmental tobacco smoke, but this has not really 
be
explored), radon and attained age, radon and gender (only suggestive data),
radon and previous lung diseases, and radon and other mining exposures (in
populations occupationally exposed to radon).  Analyses have consistently
demonstrated a linear relationship between lung cancer and the excess relative
risk.  That functional form implies that conditional on other risk factors, 
lung
cancer risk increases proportionally to the background rate with increasing
radon progeny exposure.  While the relative risk may be linear, the absolute
excess risk with increasing exposure is dependent on the myriad of other risk
factors. This is the reason that even though counties may have equal (or 
greater
or lesser) radon concentrations, county lung cancer rates cannot be "scaled 
up"
with any validity and be compared without information (at the level of
individual) on other lung cancer risk factors.

My problem is then with ecological studies.  I do accept that it is a 
perfectly
valid scientific question to ask whether there is an excess risk of lung 
cancer
at the lowest levels of (residential) radon progeny exposure - but for
individuals.  In my view, the data are consistent with some excess risk at the
lowest exposures, but I will allow that this is an arguable proposition.
However, ecological analyses shed no light on this issue, since one cannot
"scale up" with validity.

Jay Lubin

Jay Lubin, PhD
National Cancer Institute
Biostatistics Branch, EPS/8042
6120 Executive Blvd
Bethesda, MD 20892-7244
Tel: 301-496-3357
Fax: 301-402-0081
Email: lubinj@exchange.nih.gov <mailto:lubinj@exchange.nih.gov> 
-----------------------------------
Bill Field
mailto:bill-field@uiowa.edu
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