Teleoanalysis: combining data from different types of study

Editor,

Teleology, the explanation of phenomena by the purpose they
serve” [Oxford Dictionary], does not explain how such associations arise.
Phenomena may be associated fortuitously, linked through unsuspected
factors or, possibly, causal. Teleology contributes to the formulation of
hypotheses that should be tested experimentally, or, in clinical matters
by controlled prospective clinical trials. In the ‘teleoanalysis’ of Wald
and Morris 1 on avoidance of folate deficiency for reduction in neural
tube risk, the fact that naturally increased folate levels, increased
dietary intake and trials of supplementation are each associated with
reduction in risk warrant this approach. 1

Readers should, however, beware being misled by equally strong
associations where the specific effects of supposedly active factors have
not been trialled. Two recent examples, affecting large proportions of the
population, illustrate the problems that can arise when benefits are
expected from interventions based on ‘intuitive’ beliefs arising from
observed associations. In the first, eating fruit and vegetables reduces
ischaemic heart disease [IHD] risk. Increased circulating beta-carotene,
associated with eating fruit and vegetables, is associated with reductions
in IHD. However, published data from some large controlled trials of
supplementation reported sufficiently marked adverse effects that two had
to be stopped. Both lung [and other] cancers were increased with
supplementation and in one trial the incidence of IHD increased.3, 4 It
now appears that other factors in fruit and vegetables may explain the
original associations. In the second example, the intuitive belief that
hormone replacement therapy could counter the increased risk of ischaemic
heart disease risk seen in post-menopausal women by increasing hormone
levels to match those in pre-menopausal women has now been tested and the
findings of prospective controlled trials suggest that the incidence of
IHD increases in long-term users of HRT.5 IHD risk will not be the only
factor influencing decisions on the use of HRT but the new findings will
contribute more effectively to decision making than the evidence quoted on
beta-carotene seems to have done; 30% of UK adults continuing to use
supplemental vitamins and anti oxidants bought in supermarkets, chemists,
pharmacies and health-food shops.5 This is probably because HRT requires
prescription in the UK whilst vitamin supplements remain unregulated.

Since interventions can have unexpected effects it would be
interesting to know whether Wald and Law take, or would take, the combined
protective drug ‘cocktail’ they hypothesise could reduce IHD risk by 80%,
on the basis of trials on each separately, 6a,b without knowing the
outcome of prospective trials of combined medication?

References

1. Wald NJ, Morris JK. Teleoanalysis: combining data from different types
of study. BMJ 2003;3276:616-18

2. Albanes D, Heinonen OP, Huttunen JK, Taylor PR, Virtamon J, Edwards
BK, Haapakoski J, Rautalahti M, Hartman AM, Palmgren J et al. Effects of
Alpha-Tocopherol Beta-Carotene Cancer Prevention study. Am J Clin Nutr
1995;62(6Suppl):1427S-30S

3. Pryor WA, Stahl W, Rock CL. Beta carotene: from biochemistry to
clinical trials. Nutr Reviews. 2000; 58(2 Pt1):39-53

4. Kritharides L, Stocker R. The use of antioxidant supplements in
coronary heart disease [Review]. Atherosclerosis. 2002;164(2):211-9

5. Herrington DM. From presumed benefit to potential harm – Hormone
therapy and heart disease New Eng J Med 2003; 349(6):519-221

6. (a). Wald NJ, Law MR. A strategy to reduce cardiovascular disease by
more than 80%. BMJ 2003;326:1419-23. 6(b). Editorial comment:- Rodgers A.
A cure for cardiovascular disease? BMJ 2003;326:1407-8]

Dr B J Boucher

Honorary Senior Lecturer; Centre for Diabetes & Metabolic Medicine
Royal London Hospital, London E11 1BB.

Email = bboucher@doctors.org.uk

Competing interests:  
None declared

Wald and Morris [1] point out that teleoanalysis is different from
meta-analysis because it combines various categories of data rather than
one type of study. Teleoanalysis, therefore, is intuitively far more
reliable than meta-analysis of randomised trials as a guide of both
individual decisions and public-health policies, because the evidence
derived from those trials can be misleading, especially if their designs
are conceptually flawed.

For example, as Wald and Morris correcly observe, the effect of a
significant reduction in dietary fat on the risk of coronary heart disease
(CHD) can easily be underestimated, even when it is based on the results
of randomised trials. These investigations, indeed, by taking arbitrarily
for granted that 30% of energy as fat represents an ideal target, have
generally designed and studied "low-fat" diets containing at least 22-28%
of energy as fat. These percentages, however, are unnaturally high, not
low.

Conversely, a teleoanalysis aimed at clarifying the relation between
dietary fat and CHD will not ignore that humankind's metabolic physiology
has been genetically moulded by a low-fat nutritional environment, in
which, for millions of years, it was virtually impossible to consume the
currently advocated 30% of energy as fat, because game was very lean and
cattle-breeding, chicken farming, butter, dairy products, margarine, and
oils did not exist [2, 3].

Considering that humankind has been evolutionarily programmed for low
-fat diets [3], it is not surprising that populations consuming only 11-
13% of energy as fat are free of CHD [4]. In rural China, where the intake
of fat, per head, is less than half that of Americans and, consequently,
cholesterol levels are very low, CHD mortality is 16.7-fold lower than
that in the United States [2]. A really low-fat diet has a central role
not only in preventing CHD, but also in its reversal [5].

1. Wald NJ, Morris JK. Teleoanalysis: combining data from different
types of study. BMJ 2003;327:616-618 (13 September).

2. Baschetti R. Genetically unknown foods or thrifty genes? Am J Clin
Nutr 1999;70:420-421.

3. Baschetti R. Low-fat diets and HDL cholesterol. Am J Clin Nutr
1998;68:1143-1144.

4. Baschetti R. The low fat/low cholesterol diet. Eur Heart J
1997;18:1514-1515.

5. Ornish D, Scherwitz LW, Billings JH, et al. Intensive lifestyle
changes for reversal of coronary heart disease. JAMA 1998;280:2001-2007.

Competing interests:  
None declared

Epidemiological
studies are useful for creating new hypotheses about disease causation. However,
to prove that a statistical association is causal demands experimentation,
because even the strongest association may be secondary to the real cause.

     To bypass this elementary principle, Professor
Wald and Dr. Morris, representatives for a new branch in the medical sciences
named aetiological epidemiology, have invented a statistical instrument to
synthesise different categories of evidence.¹ By teleoanalysis as
they call it, it is possible to measure the extent to which a disease can be
prevented, for instance how much ischaemic heart disease that can be avoided by
reducing dietary saturated fat. They admit that the crucial experiments, the
dietary trials, have failed, but as we “know” that saturated fat intake
increases the risk of heart disease, we can use a surrogate outcome, the
intermediate factor cholesterol as evidence, implying that we also “know”
that high cholesterol increases the risk. Say Law and Morris, the latter has
been shown in epidemiological cohort studies and in trials of cholesterol
lowering drugs.

     These assumptions are false, however. The
allegation that patients with heart disease have eaten more animal fat than
healthy individuals has been falsified by at least 21 cohort studies and six
case-control studies including more than 150.000 individuals,² and
other types of epidemiological studies have been just as unsuccessful. For
instance, dynamic population studies, including data from more than 100 time
periods in 35 countries, have found no association between changes of saturated
fat consumption and changes of coronary mortality, and in four cohort studies no
association was found between degree of atherosclerosis at autopsy and dietary
intake of saturated fat.²

     The evidence from the cholesterol lowering drug
trials are just as invalid. Cholesterol lowering had no effect on heart
mortality before the statin era,³ and the effect of the statins is
most likely due to other, more beneficial effects on the cardiovascular system.
Dose-response has been claimed, but only by comparing mean values from the trials.
In all clinical and angiographic trials, where dose-response was calculated from
individual data, the effect was independent on the degree of cholesterol
lowering, a strong argument against causality.^4,5

     According to Wald and Morris the name
teleoanalysis was chosen to indicate thoroughness and completeness. It is
difficult to find a more misleading term considering that I have only mentioned
a few of the studies that contradict the diet-heart idea. There are many, many
more.^4-7 

1. Wald
   NJ, Morris JK. Teleoanalysis:
   combining data from different types of study.BMJ
   2003; 327: 616-618. [Full
   text][PDF]
2. Ravnskov
   U. The questionable role of saturated and polyunsaturated fatty acids in
   cardiovascular disease. J Clin Epidemiol 1998;51:443-460. [Abstract]
3. Ravnskov
   U. Cholesterol lowering trials in coronary heart disease: frequency of
   citation and outcome. BMJ 1992;305: 15-19. [Abstract]
4. Ravnskov
   U. A hypothesis out-of-date: The diet-heart idea. J Clin Epidemiol. 2002:1057-1063.
   [Abstract]
5. Ravnskov
   U. Is atherosclerosis caused by high cholesterol? QJM 2002; 95: 397-403.
6. THINCS,
   The International Network of Cholesterol Skeptics; www.thincs.org
7. Ravnskov
   U. The Cholesterol Myths. Washington DC: New
   Trends Publishing, 2000.