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LETTER
‘Are fluoride levels in drinking
water associated with
hypothyroidism prevalence in
England? A large
observational study of GP
practice data and fluoride
levels in drinking water’:
comments on the authors’
response to earlier criticism
Academic debate is healthy and helps us
to clarify the evidence base for the inter-
ested reader. However, it is unusual for a
peer-reviewed paper in a reputable journal
to receive quite as much criticism as that
which greeted publication of the paper by
Peckham et al on fluoride and hypothy-
roidism.
1
Two highly critical commentar-
ies were published at the time.
23
A
subsequent review article
4
in the Journal
of Evidence-based Dental Practice con-
cluded that “this study is an ecologic one
that has several significant flaws, making it
almost meaningless with regard to asses-
sing any possible association between
water fluoridation and hypothyroidism.”
Published criticisms included lack of a
coherent basis for a prior hypothesis,
unbalanced citing of the literature, failure
to allow for potential confounding, inad-
equate recognition of the limitations of
ecological studies, imprecise measurement
of exposure and outcomes, and over inter-
pretation of the results to infer causation.
Statistical aspects of the study were par-
ticularly heavily criticised by Warren et al
4
for lack of transparency in reporting, the
use of arbitrary categorical cut points to
analyse a continuous variable, and by us
3
for some apparently anomalous results in
relation to deprivation.
The authors have now responded to the
criticism and readers can draw their own
conclusions as to the adequacy of that
response.
The quote from the NRC report is a
helpful clarification, but extensive discus-
sion in that report of the weaknesses of
the evidence base is still not acknowl-
edged. The relevant studies are mainly
correlation studies in rural developing
world communities with limited data on
intermediate end points and recognised
methodological weaknesses. These studies
have little, if any, relevance to exposures
due to water fluoridation schemes in the
UK. Also, Peckham et al accept that hypo-
thyroidism has multiple immediate causes
(auto-immune, surgical etc) but do not
acknowledge that this makes any unifying
hypothesis of association with fluoride
exposure intrinsically implausible.
We continue to believe that confounding
has been inadequately considered. Age and
sex may have been partly accounted for
but only at aggregate level not at individual
level (the ecological fallacy). The data pre-
sented in figures 1s and 2s are poorly
explained and are not clearly attributable
to, and indeed postdate, the reference
cited. The figures appear to show different
distributions of iodine intake in ‘fluori-
dated’compared to ‘non-fluoridated’
regions, which if anything suggests that
iodine exposure may indeed be an import-
ant confounder. However, having exam-
ined the source we do not understand how
the National Diet and Nutrition Survey
can be analysed by ‘fluoridated and non-
flouridated SHA areas’or for women aged
over 40 years, since it does not use such an
age range and is not sufficiently precise to
allow small-area aggregation (fluoridation
does not occur at SHA level). Peckham
et al are mistaken, we refer in our com-
mentary to a different article by
Vanderpump
5
to the one cited by Grimes.
Other potential confounders mentioned in
the NRC report such as selenium, calcium
and aluminium are not considered,
let alone a myriad of unknown and
unmeasured variables related to popula-
tion or health service factors.
On the comparisons made, there is
still no information on how the two city
areas were defined or why other areas
were excluded. It seems the journal peer
reviewer recommended a categorical
approach instead of the analysis of con-
tinuous variables. Without seeing the
review in question it is hard to comment
further, except to say that it would appear
to us to be poor advice. No explanation is
given as to why tertiles of deprivation and
hypothyroidism, respectively, were com-
bined into binary outcomes differently.
The justification for the fluoride exposure
category seems to be related to thera-
peutic efficacy which was not the subject
of the study. As has been pointed out
what we need to be confident about the
analysis is a clear descriptive table to help
us to understand the data not a few coeffi-
cients presented as outcomes.
We were fascinated to discover that the
direction of association between depriv-
ation and hypothyroidism switched direc-
tion in their model after adjustment for
proportion aged over 40 years (OR
changed from 0.49 to 1.7). Although
good to know that it was not an error,
discovery of such a statistical quirk in the
model (which we believe is an extreme
example of Simpson’s paradox
6
) raises
more questions than it provides answers
about the relevance and validity of the
model for the hypothesis being examined.
Returning to the question of interpret-
ation, we do not agree that an association
has been demonstrated let alone a causal
one. Peckham et al quote a recent Irish
review
7
—this is what it has to say in con-
clusion about their study: “There are
three reasons for assigning a low-quality
rating. First, the study design assigned was
incorrect. Second, the control for con-
founding was incomplete. Third, the
authors infer a causal relationship rather
than a theoretical relationship.”
It is a fact that a question has been raised
if not answered by this study. Rather than
continue to debate with its authors we plan
to repeat the analysis ourselves using more
conventional statistical methods. In the
meantime, it is unfortunate that this article
and its claims remain in the literature
despite its weaknesses. The BMJ website
shows that it has achieved an Altimetric
score at the time of writing of 357 with
extensive activity in North America whereas
the critical commentaries have scores of just
14 and 16 with no US coverage.
Water fluoridation is a well-established
and highly effective public health inter-
vention with a safety record that spans
many decades. It is important that the
public and policymakers receive clear and
measured advice on its safety and effect-
iveness based on the best available science.
John N Newton,
1
Julia Verne,
2
Mark Dancox,
2
Nicholas Young
3
1
Department of Chief Knowledge Officer, Public Health
England, London, UK
2
Department of South West Knowledge and Intelligence
Team, Public Health England, Bristol, UK
3
Department of Knowledge and Intelligence Team,
Public Health England, Bristol, UK
Correspondence to Professor John N Newton,
Department of Chief Knowledge Officer, Public Health
England, PHE, Wellington House 135-155 Waterloo
Road, London SE1 8UG, UK; john.newton@phe.gov.uk
Contributors All authors contributed to the drafting
of this response.
Competing interests None declared.
Provenance and peer review Commissioned;
internally peer reviewed.
Open Access This is an Open Access article
distributed in accordance with the Creative Commons
Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build
J Epidemiol Community Health Month 2017 Vol 0 No 0 1
PostScript
JECH Online First, published on January 16, 2017 as 10.1136/jech-2016-208649
Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd under licence.
upon this work non-commercially, and license their
derivative works on different terms, provided the
original work is properly cited and the use is non-
commercial. See: http://creativecommons.org/licenses/
by-nc/4.0/
To cite Newton JN, Verne J, Dancox M, et al.J
Epidemiol Community Health Published Online First:
[please include Day Month Year] doi:10.1136/jech-
2016-208649
Received 14 November 2016
Accepted 18 November 2016
J Epidemiol Community Health 2017;0:1–2.
doi:10.1136/jech-2016-208649
REFERENCES
1 Peckham S, Lowery D, Spencer S. Are fluoride
levels in drinking water associated with
hypothyroidism prevalence in England? A large
observational study of GP practice data and
fluoride levels in drinking water. J Epidemiol
Community Health 2015;69:619–24.
2 Grimes DR. Commentary on ‘Are fluoride levels in
drinking water associated with hypothyroidism
prevalence in England? A large observational study
of GP practice data and fluoride levels in drinking
water’.J Epidemiol Community Health
2015;69:616.
3 Newton JN, Young N, Verne J, et al. Water
fluoridation and hypothyroidism: results of this study
need much more cautious interpretation. J Epidemiol
Community Health 2015;69:617–18.
4 Warren JJ, Saraiva MC. No evidence supports the
claim that water fluoridation causes
hypothyroidism. JEvidBasedDentPract
2015;15:137–9.
5 Vanderpump MP, Tunbridge WM. Epidemiology and
prevention of clinical and subclinical hypothyroidism.
Thyroid 2002;12:839–47.
6 Hernán MA, Clayton D, Keiding N. The Simpson’s
paradox unraveled. Int J Epidemiol
2011;40:780–5.
7 Sutton M, Kiersey R, Farragher L, et al.Health effects
of water fluoridation. Ireland: Health Research Board,
2015.
2J Epidemiol Community Health Month 2017 Vol 0 No 0
PostScript
