Re: Dr. Lubin's response to Cohen's statements

[Tom Mohaupt <tom.mohaupt@wright.edu>]

I've looked again at Lubin's Rejoiner to Cohen's comments in HP, Vol 77,#3,
9/1999. Fig 1 shows composite relative risk results from 9 international
studies. The data looks very clear that the relative risk to about 350
Bq/m3 is consistent with a RR of 1. Practically all the error bars extend
well below the relative risk of 1 line. The data seems more consistent with
a threshold than the predictions from miner data at these low levels. Of
course these data aren't perfect. They corrected for smoking through
questionaires completed by surviving relatives. I wouldn't be surprised if
5% or more of case smoking habits were misrepresented. [I use 5% because
that's the percentage of mothers whose memory of whether their children had
X rays in utero did not match medical records.] None of the studies
accounted for pulmonary diseases that may have afflicted the cases more so
than controls. This effect is well documented in other case-control studies
such as the Oxford Study of Childhood Cancer. 

So it looks to me that Lubin and Cohen came to the same conclusion that the
LNT is not applicable to doses below about 350 Bq/m3 by entirely different
methods.

Does any one have a reference for the Iowa radon study? Did they correct
for pulmonary diseases?

Tom

FIELDRW@aol.com wrote:
> 
> I feel that I must comment on the exchange by Cohen and Klugh.  Dr. Cohen's
> suggestion that because I made no attempt to claim his reward, I must have
> accepted the adequacy of his responses to articles by me and others is
> fatuous.
> It is not that I don't believe Cohen's results -- below 300 Bq/m3, county lung
> cancer rates are negatively correlated with "average" county radon
> concentrations --  but that his results have no relevance regarding risk to
> individuals.  They neither support nor contradict current risk estimates.
> Thus,
> continuing the exchange was pointless.  Upon re-reading his responses to the
> exchange in Health Physics and on this listserve, I can only conclude that Dr.
> Cohen has entirely missed the point of my comments and those of others.  Let's
> try one more time.
> 
> 1.  It is clear that Cohen's ecological analysis is markedly discrepant from
> the
> analytic studies of residential radon exposure and of radon-exposed miners,
> from animal studies and from current dosimetric/biophysical models.  As I
> made clear in my last letter in Health Physics, Cohen's linear-quadric model
> for lung
> cancer mortality rates and residential radon is not supported by the
> case-control studies or the miner studies.  His model in fact predicts a
> strong
> protective effect of living in houses with concentrations under about 300
> Bq/m3
> - this pattern just does not occur in the analytic data.
> 
> The relevant question then becomes -- how are we to interpret Cohen's results
> in
> light of the findings from the analytic studies?  More importantly, when
> considering whether and to what extent residential radon increases (or in
> light
> of Cohen's result, decreases) the risk of lung cancer, is it even necessary
> that
> Cohen's results should be "explained"?  The main point of my articles, as well
> as articles by Greenland and Robins, Samet et al, Piantadosi, Muirhead et al,
> and others, is that the answer is an emphatic no to the latter question.
> 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.
> Thus, Cohen's regression results cannot serve as an evaluator of radon effects
> for individuals.  This is why epidemiologists use ecological analyses only for
> hypothesis generating and not hypothesis testing.  In the real world of
> epidemiology, in order to have any credence, an association observed at the
> ecological level must first be demonstrated using individual-level studies.
> The
> converse is never the case.  One would never consider that results from
> analytic
> studies needed to be "validated" by ecological analysis; the very notion is
> absurd.  Thus, there is little point in trying to identify any specific reason
> why Cohen's regression results in a negative trend, since the analytic
> evidence
> is so strong.  The methodology itself is intrinsically flawed.  Given diverse
> results from ecological analyses and from analytic studies, analytic studies a
> priori have the greater claim to validity.
> 
> 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 those risk factors
> may
> vary among the counties.  Therefore, one cannot simply define a model for the
> within county correlations, apply it across counties and claim adjustment of
> these effects.  This is the central rationale for the proposal by Sheppard and
> Prentice to "correct" ecological studies by randomly sampling populations
> within
> county in order to estimate the joint distribution of risk factors.  Cohen's
> repeated assertions that the "ecological fallacy" does not apply to him, does
> not make it so.  He cannot create models that account for both the risk factor
> correlations within county and their variations across counties.  My original
> paper in Health Physics shows that the amount of correlation between radon
> level
> and another risk factor can be small indeed, on the order of 0.05.
> 
> 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.
> 
> 3.  While the within county confounding issue 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.  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
> up to 30 years and more prior to the mortality data.  The population
> composition, and 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.
> 
> 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.
> 
> 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 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.
> 
> This exchange has been going on for nearly a decade.  To paraphrase
> Piantadosi,
> given results from analytic studies and ecological studies, the former must
> carry the greater weight in our considerations.  Thus, the suggestion that
> Cohen's results must be "explained" is misplaced -- the results are
> irrelevant.
> It is time to move on and address the many important questions that remain:
> what
> are the consequences of exposure measurement error on risk estimates; what is
> a
> realistic level of uncertainty on the risk associated with long-term residence
> in houses in the range of 75-200 Bq/m3; are there specific genetic
> polymorphisms
> that define susceptible sub-populations?
> 
> 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
> ************************************************************************
> The RADSAFE Frequently Asked Questions list, archives and subscription
> information can be accessed at http://www.ehs.uiuc.edu/~rad/radsafe.html

-- 
Thomas Mohaupt, M.S., CHP
University Radiation Safety Officer

104 Health Sciences Bldg
Wright State University
Dayton, Ohio 45435
tom.mohaupt@wright.edu
(937) 775-2169
(937) 775-3761 (fax)

"An investment in knowledge gains the best interest." Ben Franklin
************************************************************************
The RADSAFE Frequently Asked Questions list, archives and subscription
information can be accessed at http://www.ehs.uiuc.edu/~rad/radsafe.html