Re: Dr Lubin's reply concerning ecologic LNT study

[Bernard L Cohen <blc+@pitt.edu>]

> 
> Dr. Lubin's reply concerning Dr Cohen's ecologic LNT study.

>  These articles show that the methodology of 
> ecological analysis itself has such limitations that no meaningful inference 
> from the relationship observed at the grouped level can be made to the 
> dose-response relationship for individuals.

	--"Make an inference" is questionable. Those papers show that one
cannot determine the dose-response relationship for individuals. I agree,
and I have never claimed that my data determine that.

> Thus, Cohen's regression results 
> cannot serve as an evaluator of radon effects for individuals.

	--What is meant by "evaluator"? I use them to test the linear-no
threshold theory, following a universally accepted procedure for testing
theories.


>  Given diverse results from 
> ecological analyses and from analytic studies, analytic studies a priori have 
> the greater claim to validity.

	--There is no diversity of results, as I have shown. The slight
diversity arises because Lubin interprets my data as a determination of
dose-response to individuals, which is not a valid interpretation

> What is the flaw in ecological studies?  Again, many articles have 
> demonstrated that the principal source of the problem is that correlations 
> among risk factors can occur within counties.  Moreover, the correlations of 
> the risk factors may vary among the counties.  Therefore, one cannot simply 
> define a model for the within county correlations and apply it across 
> counties and claim adjustment of these effects.

	--I never claimed that I was making  an"adjustment" for effects of
confounders. I agree on the problems Lubin cites, but he should be able to
postulate some sorts  of correlations of risk factors within counties that
might explain our data. It is then up to me to perform an analysis to test
the plausibility of of that explanation. How I do this is my problem, and
my analyses should not be judged in advance. All I ask is that he suggest
such an explanation. He did this once, proposing that a correlation
between radon and smoking among individuals might explain our discrepancy,
but I was able to show that this explanation was completely implausible
(Health Phys 75:18-22;1998)

>   Cohen's repeated assertions that the 
> "ecological fallacy" does not apply, does not make it so.

	--If "the ecological fallacy" is defined as "the average dose does
not determine the average risk", which is the traditional definition, I
have shown mathematically that this does not apply if the linear-no
threshold theory is valid.

>  He cannot create 
> models that account for both the risk factor correlations within county and 
> their variations across counties.

	--For a specific risk factors, I believe that I can. At least, he
can suggest a specific risk factor and let me try. If I cannot make a
convincing argument about plausibility, I lose and will concede.

>  2.  Cohen suggests that his analysis is not confounded because the negative 
> trend of lung cancer rates and county "mean" radon level is unchanged after 
> adjusting for hundreds of different factors.  That is not the point at all, 
> and indeed is irrelevant to the control of within county confounding.  One 
> can never adjust for factors that operate within county by endlessly adding 
> more and more county-level information.  His ecological analysis has no more 
> claim to validity if he were to add thousands of additional county-level 
> variables. County-level factors are not the source of the limitations.
>  

	--This being the case, it should not be hard to propose a specific
explanation based on within county confounding. There is no need to show
that it is the correct explanation. It is then my responsibility to
analyze the explanation for plausibility. I ahve done this several times
on various proposed explanations, and, to the best of my knowledge,  no
one has claimed that my analyses were not convincing


>  3.  While the confounding problem is really paramount, it is also the case 
> that data used in many ecological analyses are often of limited quality and 
> difficult to interpret.  Cohen's data are no exception.  Lung cancer 
> mortality from death certificates are often misspecified and covariate 
> information is of poor quality.

	--If this is a proposed explanation, I would be happy to do an
analysis. The correlations between misspecification and radon levels would
have to be tremendous.

.  Of particular concern, Cohen uses mortality 
> rates where the disease-relevant exposure period is at least a decade or more 
> prior to available radon data.  The county "average" radon concentration may 
> bear little relationship to the "average" county radon concentration 
> prevailing 5-30 years prior to the mortality data.  The population 
> composition, risk factors, as well as lung cancer mortality rates, have 
> changed considerably in recent decades. (See for example the NCI cancer atlas 
> for changes in lung cancer mortality, ). This problem is exacerbated by the 
> further limitation that average radon level (and other risk factors) for a 
> county does not translate into lung cancer-relevant dose, and that the 
> correlations among risk factors may vary over time.
>  
	--All these problems were addressed in my papers. They also apply
to case-control studies. But if these are proposed explanations, I would
be happy to analyze them But one at a time, please.


> Residential radon studies in general do not suffer from the flaw that radon 
> measurements post­date the disease occurrence by 10-30 years.  While radon 
> measurements are contemporary, in residential studies, interviews provide 
> detailed information on residential history, so investigators know precisely 
> how long subjects were resident in the various houses, and on house 
> modifications, heating systems, etc.  In the Iowa study, enrollment in the 
> study required that
>  the subject has lived in the current house for at least the preceding 20 
> years.
>  
	--Cracks can open or close in the basement floor or walls,or in
the ground under the house. How were modifications in the heating systems
and other house modifications taken into account? What about changes in
window opening practices in a bedroom? These problems average out in
county averages, and are thus much less important in my studies. I ahve
done studies of radon levels vs age of house, and effects are not large. I
also have lung cancer rates for different time periods, and they do not
make a difference.


>  4.  It must also be pointed out that not all ecological studies agree with 
> Cohen's results, and big does not equate with valid.  Many ecological studies 
> have been published; some show decreasing trend, no trend, or increasing 
> trend.
> In an attempt to circumvent the limitation of mortality data and poor 
> exposure data, several investigators have used population registry files on 
> lung cancer cases to create lung cancer incidence rates for counties.  
> Analyzing these incidence rates together with county radon measurements and 
> other information from population-based case-control studies, investigators 
> have found patterns of associations that show increasing risks with radon.  
> None show decreasing
> risks.
>  
	--How about references? I know about no ecological study that
begins to approoach mine in scope, size, analysis, etc. Similar studies in
England, France, and Germany have given results similar to mine, but they
are much less robust. 

> 
Bernard L. Cohen
Physics Dept.
University of Pittsburgh
Pittsburgh, PA 15260
Tel: (412)624-9245
Fax: (412)624-9163
e-mail: blc+@pitt.edu


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