Ecologic versus Case-Control Studies, revisited

["R. William Field" <bill-field@uiowa.edu>]

Bill Field's (BF) responses to Jim Muckerheide's (JM)  previous comments ---  

JM states -- A good case-control study, with small numbers, can have better
>statistics than a "small" ecological study (in my ref to Cohen, his "small"
>subset studies may be a million people of the 200 million total
population, 20
>million in a group in the whole study?).


BF RESPONSE - I still do follow Jim's thinking that "better statistics"
guarantees a more powerful study.  The POWER of the study is dependent upon
the BOTH the sample size and the Quality of the data.  I fail to see how
you have better data in an ecologic study when all you have is summary data
collected or downloaded from some spreadsheet found at the Census Bureau.
Performing advanced statistics on summary data (county radon
concentrations, tobacco sales taxes) does not make a study more valid.  The
statistical manipulation may be advanced, but that does not mean the
results are valid.  In ecologic studies, you do not know the smoking
history or the average radon concentration for even 1 of those 2 million
individuals. You call this good data?

Nonetheless, I am glad you agree that a case control study has more a
priori validity than a small ecologic study.  I think I also take it that
you think any study smaller than 
200 million people is small.  Given that, small ecologic radon studies are
all studies other than Dr. Cohen's.  So what I think you are doing is
comparing the validity of case-control studies versus only Dr. Cohens Study.  

JM  states  --- But, radon case-control studies can't know the dose. Radon
studies measure the house. Two "equivalent" people (women) in the same
house will _likely_ have a significant actual difference in lung dose; 2
people in different houses with
>the same measurement are likely to have an even larger variation in actual
>lung dose. 

BF RESPONSE -- I think we have 3 items to consider when calculating an
"exposure" variable. 

Some case control studies use only radon concentrations, not exposure.  A
few case-control studies look at occupancy rates and concentration to get
radon exposure.  Only one case control study I know of actually calculates
dose to an individual and that is the one we are performing in Iowa.  To
calculate dose, you need to know the activity size distribution of the
radon progeny in the home.   We are presently looking at how well the radon
concentration of the home approximates the dose to the individual.

I again refer you to our the methods paper for the Iowa Study (Journal of
Exposure Analysis and Environmental Epidemiology  6:181-195, 1996), don't
stereotype all case-control studies as being the same.

In ecologic studies, you have county mean radon concentrations.  Not
exposure.  Not dose.  There are huge variations in radon concentrations
within counties.  When you collect more and more information from counties,
you don't get linear relationships between radon concentrations and dose to
the county population.  Biases are introduced that can not even be
measured, as the sample size gets larger these bias become magnified.  The
bias do not average out as you suggest, they get magnified. 

 JM states --- As you think about it, the "dose" in the case-control study
is now not a known quantity, but is a statistical mean or average, just as
with the ecological study. 

BF RESPONSE -- In the case control study in Iowa, we calculate a dose for
EACH individual in the study.  We know their home radon concentrations, we
know their historic home radon concentrations, we know their occupancy,
etc.   In ecologic studies, you do not have that information for even 1
individual within the county.  Dr. Cohen understands this.  In a way, that
is why he uses the collective dose concept and the LNT to derive individual
dose from aggregate data.   Unfortuantely, others put a spin on Dr. Cohen's
findings that go beyond, I think, what he is even comfortable with. 

JM States ---  In Bernie's many independent studies of various, independent
>subsets, because the dose and cancer data statistics are so much more
>powerful, the variations in results are small. Not only that, the value of
any
>confounding factor that could substantially effect the basic results become
>very large. 

BF Response ---- The ecologic study is not more powerful because of the non
quantifiable biases within the data set, you have no idea what types of
cross-level biases have been introduced.  Again, what Dr. Cohen has is a
large data set, this does not make a study more powerful.


JM states ----- After considering many confounding factors, Bernie is quite
justified in
>looking at the other side of the issue and concluding, by the direct
>arithmetic of Statistics 101, that a confounding factor that could change the
>slope would have to be larger than the effect of smoking (and not seen in any
>study to date), but even more significantly would also have to be in a direct
>negative correlation with radon concentration levels (and then wouldn't reach
>the BEIR slope unless it was MUCH larger than smoking :-)
>

BF RESPONSE - It is very difficult to control confounding on the ecologic
or aggregate level.  Sometimes things that may not even be (or appear to
be) confounders on the individual level become confounders on the aggregate
level.  It also does not make a study more valid by increasing the number
of adjustments you do.  A study with 1000 attempted adjustments has no more
validity than a study with 100 adjustments.  If you actually knew what the
confounder is, only 1 adjustment would be needed.  In ecologic studies the
confounders are generally non-linear and not apparent, which makes
adjustments almost impossible.


JM states  (At the same time, there is biological evidence that the
association is being confirmed by: animal biology data, and cellular and
molecular biology, that
>confirms the "stimulating" effect of moderate levels of alpha exposure to the
>lung, (and the whole organism, with early studies in mice and rats that
>uranium dusts and other alpha-contaminants resulted in long lives and
improved
>physiological factors, see eg, Henry, JAMA, 1961 review article and
summary of
>an Oak Ridge report.)
>

BF Response -- Jim, we may be in agreement on something today.  Data is
available on both sides of the table on this issue.  I think the work of
scientists like Dr. Raabe is extremely important and should be considered
in the whole picture.

I have no qualms with where you are headed, I just think there may be more
valid ways to get there than depending on ecologic studies.  I think the
use of ecologic studies may be credible within a small segment of the
Health Physics Society, but I think the following decreases outside that
area.  I think if you (and your special interest organization) want to make
a more credible case for your theories, animal and cellular models may be
the area to focus.  


Two last thoughts on ecologic studies.

1) Case-control studies follow-up the findings of ecologic studies.  I have
never seen it go the other way.  There must be a reason for this.
Case-control studies are analytical in nature, while ecologic studies are
hypotheses generating.

2) Dr. Cohen's  Study is not the only large ecologic study that has found
paradoxical findings.  Absurd paradoxical findings have been found in other
ecologic studies surveying numerous countries.  For example, a huge
ecologic study in Europe has found that high blood pressure protects you
from having a stroke.  Obviously this is a ludicrous finding.  But, that is
what they found using a large ecologic study.  The European study used
"powerful and advanced statistics" , but still found a paradoxical rather
non believable finding.

Dr. Cohen has been unable to explain how his ecologic study can produce
false results.  He asks others to explain his findings.  Dr. Cohen has
stated he can explain the false results of any other ecologic study (other
than his own).  He has frequently offered in the past to show how other
ecologic studies can produce false results.  I challenge Dr. Muckerheide or
Dr. Cohen to explain the paradoxical findings published in the study by
Menotti et al., European Journal of Epidemiology 13: 379-386, 1997.  

I apologize for the long monologue, but I think this is an important issue.
 In order not to clutter the listserv, I would be glad to continue the
dialogue via email off the listserv.  Several papers on this issue are
coming up in the Health Physics Journal in the coming months.  I urge all
radsafers to read those papers with an open mind.   

I do not see this whole issue on the validity of ecologic study as a debate
between Epidemiologist and Health Physicist.  While I have "recent"
training in Epidemiology, my background is in Health Physics.  I have
performed laboratory surveys;  I have overseen bioassay programs; and I
have performed environmental measurements.  In fact, the majority of my
published papers are non epidemiologic in nature.   I think we have to move
beyond this Epidemiology versus Health Physics and focus on the science.
Let's try to look at the best methodologies to answer the questions at
hand.  As coordinator of the Iowa Radon Lung Cancer Study, my goal is to
use the best dose assessment methods possible to examine the relationship
(positive or negative) between residential radon exposure and lung cancer. 

Best regards, Bill Field
bill-field@uiowa.edu 

******************************
R. William Field, Ph.D.
Division of Epidemiology
Department of Preventive Medicine
  and Environmental Health
N222 Oakdale Hall
University of Iowa
Iowa City, Iowa 52242
319-335-4413 (phone)
319-335-4747 (fax)
mailto:bill-field@uiowa.edu
******************************