SPECIAL
ARTICLES
Causal
Thinking
in Practice:
Strengths
and
Weaknesses
of the Clinical
Vantage
Point
Mervyn
Susser,
MB, BCh, DPH, FRCP(E)
From the Faculty of Medicine, Columbia University, New York
ABSTRACT. The place of causal inference in clinical practice is considered. One function relates to the vali-dation of existing knowledge, as in the evaluation of the medical literature, and is exemplified by the process of
editorial selection. A second function relates to the
vali-dation of potential knowledge, as in the testing of
hy-potheses, and is exemplified by the pursuit of a
nutni-tional cause of retarded mental development. Features of
clinical practice that contribute strengths or weaknesses
to causal inference are then examined. These include the diagnostic process, the effect of cumulative clinical ex-perience, continuity of observation and follow-up, and the focus on disease. Pediatrics 1984;74:842-849; causal
inference, malnutrition and mental development,
diagno-sis, follow-up, history taking.
The philosophy of causal inference reaches deep
into abstractions. Applied in clinical pediatrics,
however, it yields some practical benefits. For
cli-nicians, inference is a constant and everyday
activ-ity. In going about their business of diagnosis and
treatment, clinicians are constantly making logical inferences, that is to say, drawing conclusions from
a set of facts and premises. In the determination of
causality, too-which factors caused what
out-comes-inference provides the logical and the
an-alytical grounds for decision. Causal inference has
preoccupied philosophers because it is fundamental
to science and the validation of knowledge, as it is
Received for publication July 29, 1983; accepted Feb 1, 1984. A version of this paper was presented at a symposium at the
Albert Einstein College of Medicine on Henry L. Barnett Day, March 15, 1982; the occasion honored Henry Barnett upon his retirement from the Departmenthe founded.
Reprint requests to (MS.) Faculty of Medicine, Columbia
Uni-versity, 630 W 168th St, New York, NY 10032.
PEDIATRICS (ISSN 0031 4005). Copyright © 1984 by the American Academy of Pediatrics.
too in the applications of science to medicine. This
logic is a bridge that enables the contemporary
clinician, in dealings with patients, to shift from
charismatic priest-like authority to the authority of
tried knowledge and of national predictions founded
on explicit models of causal relationships.
Causal inference has a long history; at the very
beginning the Hippocratic authors gave attention
to causality. Life is short, they wrote, and the arts
of acquiring knowledge long and difficult. Our many
errors show that the practice of causal inference
remains difficult; the forum for the controversies
and disagreements provided by our journals shows
that it remains an art. Although to assist us, we
have acquired analytic techniques, statistical
meth-ods and conventions, and logical criteria, ultimately the conclusions we reach are a matter of judgment.’
Judgment is neither value-free nor situation-free.
Each of us is limited by a frame of reference derived
from the ideas of our own socity and our own times,
from our training, and from the perspective from
which we perceive our problem, whether it be that
of biochemist, clinician, epidemiologist, geneticist,
or social scientist. Different observers see different
problems, and often reach different conclusions.
Ambiguity is heightened because analytic
sci-ence-whethen experimental or observational-is
by nature reductionist: one must simplify the con-ditions of observation; one must exclude as many
extraneous variables as possible from the field of
study; and one must remove on control effects of
the surrounding environment. To isolate the field
of observation in this way is often to contradict the
clinical function, because it is also to eliminate the
perception of the patient as a person, and to close
out the social milieu and the multifarious
condi-tions under which patients live. In the practice of
these reductions to become patient centered.
Causal inference embodies the critical and
skep-tical elements of scientific thinking. Although this
logic, when ill used, can shackle imagination, it is
also a brake on foolishness. Yet the discipline it
imposes is not merely constraining. Important functions of causal inference relate to two types of
validation, first of existing knowledge, and second
of evolving on potential knowledge. By validation, I mean a process, not the certification of invulnera-bility to all tests, trials, and other assessments. With the validation ofexisting knowledge, the
prod-ess requires a critical apparatus for reading and
evaluation; with the validation of potential
knowl-edge, it requires an ability to test hypotheses.
In each of these applications the process of
vali-dation is two sided: negative and positive,
destnuc-tive and creative. In the validation of existing
knowledge, on the negative side the process involves the sifting out of error and nonsense; on the positive side, it involves the extension of knowledge and even the creation of new knowledge. The negative function of sifting out nonsense from “nearsense”
and sense is a primary gatekeeping function of
editors and reviewers. Here one must face the inev-itability that in recognizing error we shall err. These
errors occur-all will know-even among those highly regarded journals that reject some 80% and more of submissions. Why do they err so often?
There is always a degree of unreliability and
disa-greement between the judgment of reviewers, and
so they are bound, on the one hand, to accept some
poor articles and, on the other, to reject some good
ones. Because errors ofjudgment will occur in both
these directions, and because we can be sure that
many more poor than good articles are submitted,
in absolute numbers editors are likely to make more
wrong judgments about poor articles than about
good ones. In one result derived from conservative
assumptions in a quantified model, only about half
(49%) of the good articles are likely to be accepted.
(The model assumes that 20% of submissions are
acceped, that acceptance follows on the agreement
of two reviewers, that two reviewers agree with each
other 70% of the time (about the rate for two
radiologists judging radiographs), that each is night 70% of the time in accepting good articles, and that 70% of the articles submitted are poor ones, ie,
below the exacting standards aimed at by the
jour-nal.) Equally important, more than a quarter
(26.5%) of all the papers accepted are likely to be
poor ones. An editor cannot be right enough of the
time to protect his readers from nonsense.
For the medical reader, knowledge may mean life
on health for his patients. In that situation, he must not only be able to defend himself against nonsense,
but to legitimate sense. Legitimation is the creative
side of validating existing knowledge. For this pun-pose, the reader needs a sound grasp of the
pninci-pies and procedures that strengthen causal
infer-ence, including the evaluation of research design,
the elaboration of analysis, and the application of an array of criteria to aid judgment.27 The analysis
of data can itself extend knowledge by eliciting new
relationships.7
Given these procedures, the last and best
affin-mation of positive results is in their independent replication. Exact replication of research design and
execution-John Stuart Mill’s “method of
differ-ence,” in which the situations compared are alike
in all circumstances but one-is only to be found
in the domain of the experimental sciences. In clinical and epidemiologic studies, one must rely on the consistent replication of results in the face of change in all other circumstances: this John Stuart Mill described as the “method of agreement,” when the situations compared “have only one cincum-stance in common.” The classic example is the association of cigarette smoking and lung cancer, which by now probably holds in more than half a hundred different instances.
To turn to the validation of potential knowledge:
on the negative side, this process involves attacks
on existing hypotheses in order to eliminate them; on the positive side, it involves the generation of
alternative hypotheses. Francis Bacon, who
devel-oped and systematized methods of scientific
infer-ence, wrote:
The induction which is to be available for the discovery and demonstration of sciences and arts, must analyze nature by proper rejections and exclusions; and then after a sufficient number of negatives, comes to a conclusion
on the affirmative instances.
In other words, the most cogent test of a hypothesis
is to attempt disproof. (Karl Popper likewise insists
that science can only proceed by refuting the
de-ductions from hypotheses,8 but he also holds that there can be no valid proof by induction from a particular positive instance to the general.9) In a formal sense, statistical conventions for hypothesis
testing are so structured that we do indeed seek disproof by framing a null hypothesis. And if our
study has sufficient statistical power to rule out the
mere failure to detect a positive result for lack of
numbers, we must then challenge our creativity in
framing new hypotheses.
A telegraphic outline of the evolution of one line
of thinking familiar to me may serve to illustrate how the rejection of each successive hypothesis leads to the creation of alternatives, and finally to an affirmative. Attempts to elucidate the common
nutrition have been a preoccupation of the past two decades. The explanatory hypothesis to be tested was that poor prenatal nutrition netands human fetal growth and subsequent development.’#{176}’2 In our own studies of a well-defined situation of acute starvation in a developed country, namely the Dutch famine of 1944/1945, we found no support for the idea that prenatal nutrition during the
pe-nod of the brain growth spurt had depressed the
cognitive performance in young adults 20 years
later.’3 In formal terms, we failed to reject the null hypothesis.
The procedures of inference, therefore, called for
alternative explanations. One alternative was that passably good previous nutrition in the mothers
protected their pregnancies in the prenatal period.
These women had no overt signs of malnutrition
and, during their growth period in The Netherlands before World Wan II, levels of nutrition were high. Perhaps then prenatal nutritional deprivation might affect subsequent development only in chronically malnourished mothers? This hypothe-sis would require testing in overtly malnourished
mothers, such as are found in less developed
coun-tries.
Another strong alternative was that, because the
prenatal period covered only about 10% of the
period of maximum brain growth during which the
brain was “sensitive” to insults,’4 the severe pre-natal nutritional deprivation would still leave suf-ficient reserve in the brain to protect subsequent function. This hypothesis would require a test of the combined and independent effects of prenatal
and postnatal malnutrition, again a likely situation
only in less developed countries.
In two studies in less developed countries, both these alternative hypotheses could be simultane-ously tested and eliminated. These studies of pre-natal and postnatal nutritional supplementation in malnourished women, one a quasiexpeniment in Guatemala, ‘ and the other a controlled trial in
Bogota,’6 failed to support the contention that in malnourished women better prenatal nutrition alone could improve postnatal cognitive perform-ance. In addition, prenatal nutrition had no demon-strable effect on cognition oven and above that of postnatal nutrition.’7”8 (In controlled trials of high-protein prenatal supplementation in New York as well as in Bogota, however, effects on visual
habit-uation occurred.’9 Some studies, but not all, have suggested a link between habituation in infancy and later measured
IQ.)
Remaining alternatives now were that the appar-ent variation in cognitive function with nutritional
conditions was owed either to postnatal nutritional deprivation, on to the social deprivation that
in-variably accompanies such malnutrition. The re-suits of the intervention studies in Guatemala and
Bogota both supported the idea of a positive effect
of postnatal nutrition on cognitive performance.
But here, also, a limiting negative emerged. In the
Bogota study, the detectable effects on cognition
are those of contemporaneous nutrition. This
find-ing points to a pathway leading from nutrition to
cognition through some current state of motivation, behavior, on health state.
We seem at last to have reached a Baconian affirmative instance. Thus, intensive longitudinal observational studies oven many years in a Mexican
village can be taken as supporting this result.2#{176}The poor mental performance observed in malnourished children was largely accounted for by the mothers’ access to external stimulation in the form of
listen-ing to the radio. Follow-up case-control studies of severe early malnutrition in Jamaica can also be
taken to support the result. Differences between
cases and control subjects were found mainly in the less stimulating environments, and, when
differ-ences were found, the degree of social stimulation
accounted for a good part of the differences.21’22 In
this study, the contribution of the current state of nutrition of the children is not known.
This brings us to one more Baconian rejection and exclusion. A study of postnatal intervention in Cali, Columbia,23 provided both good nutrition and social stimulation. In these children, well-fed at the time of last testing, there was a marked cognitive improvement. In one group given nutritional sup-plementation alone, however, no effect could be attributed to the intervention.23 For the present, then, one may conclude that the largest postnatal effects on cognitive performance come from social stimulation, and that the predominant nutritional effects occur either in interaction with stimulation, on are immediate and behavioral. The road along which hypotheses are eliminated and alternatives
created is never-ending; meanwhile, one must live
and act by the “affirmative instances.”
The conscientious use of the principles and
pro-cedures of causal inference makes us aware of error,
and humble before its pervasiveness. The
skepti-cism we learn thereby need not be arid, if we are led also to create alternative hypotheses and even alternative paradigms. In this regard, the world of the clinician has both strengths and limitations. The unique advantages that reside in clinical ex-penience must be balanced against its selectiveness and social confinement. In what follows I shall discuss a few of these strengths and weaknesses, some because they are subtle and seldom consid-ened, others because they lead to gross error and
DIAGNOSTIC PROCESS
The exquisite diagnostic precision attainable by
clinicians yields specificity and refinement of clas-sification. This refinement in diagnosis avoids the suppression of statistical associations by the
irrel-evant “noise” that accompanies the
misclassifica-tions of incorrect diagnosis.
The scientific penalty exacted by this process is
less evident. It flows from the subjective
contami-nation and bias inherent in diagnostic judgments.
Typically, diagnosis is a matter of pattern recogni-tion. Seldom, however, can the separate elements that comprise the pattern be assessed
independ-ently one from another, as they should be in a
research diagnostic procedure. In the clinical
pro-cedure, the assessment of the meaning of one
cni-tenon often influences the assessment of the mean-ing of the other.
Effects of this dependence differ in different
sit-uations. When a true and strong relationship exists
between two manifestations, such as between
crushing chest pain and a Q-wave on the ECG, the
usual clinical procedure is likely to contribute to
reaching a correct diagnosis. The presence of the
first criterion raises the conditional or a priori
probability that the presence of the second criterion
will be diagnostic. Moreover, recognition of the first criterion-chest pain-is likely to prompt an ECG
reader to a harden search for additional signs than
in its absence. The clinician is “sensitized.” In this
instance, in which a true and strong relationship
exists, one might guess that the proper research
procedure will be less sensitive than the clinical procedure. To collect and judge the diagnostic items independently might well reduce the chances of the signs being recognized by the unsensitized clinician,
and produce a false-negative finding.
In contrast, consider the situation in which there
is a
weak or doubtful relationship, for example between a history of maternal abuse of alcohol and the characteristic facies dubbed the fetal alcohol syndrome. In this instance, the bias created bynonindependence of the items of diagnostic data
favors a false-positive diagnosis. I believe the
false-positive error (type I on a error) is much the most
common in clinical medicine if only because of the fear and the costs of missing something serious (the false negative, type II, or
fi
error), and because inthe caring professions to do something toward ne-lieving pain or anxiety is more attractive than to do nothing. The costs of the false-positive error, however, includes needless and expensive investi-gation and its ensuing anxieties for the patient.
When an investigator is trying to establish the
existence of a syndrome from the recurrent
associ-ation of a number of typical features, as with the
fetal alcohol syndrome, then to combine
noninde-pendent criteria can be a flagrant error. It is just
this error that undermines the validity of the
greater part of the work done so fan on the fetal
alcohol syndrome.24 In many of the studies
pun-porting to establish the syndrome, the diagnosis
was made either in children of mothers with a
history of alcoholism already known to the diag-nostician, or in children referred to a
dysmorphol-ogist for confirmation of a suspected diagnosis. As
noted, in an established condition with established
associations, such a procedure could raise the
prob-ability of correct diagnosis; in the attempt to
estab-lish a condition, however, the procedure
compro-mises the objectivity of the judgments that must be
made. This is not to say that the syndrome does not exist. Two recent studies meet the obligation
of independent assessment of postulated cause and
outcome.25’26
A similar problem is engendered by medical
his-tory-taking. A benefit that follows from the
confi-dence so readily placed by patients in their doctors is the pediatrician’s ability to obtain a medical
history in depth and detail. Yet this traditional
procedure can be a threat to valid inference. Typical
medical history-taking falls somewhere between an
unstructured and a structured survey interview.
The unstructured interview is rich in information
that is left to the interviewer to organize and
inter-pret, and, therefore, the material is open to the
interviewer’s biased perception. The structured
in-terview seeks limited answers that must fit a
pre-determined form; at the sacrifice of information,
there is less play left for biased interpretation. The
usual medical history relies on the training of the interpreter-here the pediatrician-to limit
subjec-tive bias. The history remains vulnerable to this
bias, however, because of the nonindependence of
the items of data collected; in the manner discussed
above for the diagnostic process it may lead to
false-positive findings. A directive, limited probing was once taught as the standard means of controlling bias in history-taking and sometimes still is. Such
an approach may very well encourage the opposite
error, and produce false-negative findings. Medical
teachers seldom lack examples of diagnoses missed
because inadequate history-taking failed to elicit
significant facts.
CUMULATIVE
CLINICAL
EXPERIENCE
The storehouse of cases in the minds and hands
of clinicians adds much to the potential strength of
their inferences: observations of the concurrence of
symptoms, signs, and outcome aid in delineating
accumulated by cooperating specialists in numbers adequate for making inferences about rare diseases and their treatment, something beyond the reach
of representative longitudinal on cross-sectional
surveys.
This rich background of experience yields insight and stimulates hypotheses. In particular, it confers great inferential value on the “exceptional” case that departs fan from the norm. Indeed, the char-actenistics of the case may be so distinctive as to serve of itself to prove or disprove a hypothesis, without benefit of added numbers on statistical tests. Hill5 cites the exceptional case of Susannah
Eley, widow of a well-known London cartridge maker. As hen death certificate shows (Figure), she lived in the village of Hampstead, several miles
from the Broad Street pump in Golden Square,
Soho. There, in the autumn of 1854, John Snow
was investigating a fearsome cholera outbreak.27
Mrs Eley alone, among all the people of Hampstead,
went down with the cholera.
In doing so, she yielded a crucial affirmative instance for Snow’s hypothesis (30 years before the
definitive bacteriology of Koch) that cholera was caused by water-borne microorganisms. Previously, when living near the Broad Street pump, Mrs Eley
had grown fond of the taste of its water. When she
moved to Hampstead, she indulged that
idiosyn-cracy by regularly having Broad Street pumpwater
carted to her home, and ultimately died from the same contaminated source that Snow demonstrated
was the origin of the local epidemic.
The instruction to be gained from the exceptional
case is a strength of cumulative clinical experience.
Such experience has at least three weaknesses that
undermine inference. These are selectivity, lack of
controlled comparisons, and a post hoc view of the
evolution of disease. Although all three are familiar
epidemiologic problems, they may bean discussion here because they are so common and so misleading
to practicing clinicians. They are a consequence of
a natural human tendency to extrapolate from the
particular situation to the general. For this, one
always needs the safeguards provided by the rules
of inference. One must ask whether clinical
obser-vations have external validity.
Selectivity
The selectiveness of clinical populations is the
consequence of the many factors that impel some
persons who have a given disorder into medical
cane, and deter others. One of the most important
factors is the stage of the disorder: with tuberculo-sis, no therapeutic program could be truly effective
before the significance of the primary infection was
understood and the cases sought out; with
polio-myelitis, no sense could be made of the
transmis-sion of the disease until the significance of symp-tomless infection was understood29; with congenital
defects, when the defects are observed at birth on later, they represent the survivors from a much
larger pool of cases diminished by attrition between
conception and birth, and thus the factors
associ-ated with the defects at birth may be those
con-nected with survival rather than with the causes of
the defects.3#{176}
Selection works in complicated ways. When
Kannen3’ first described infantile autism, he had
observed the majority of cases among the children
of well-educated mothers who were seemingly
“cold.” The imputation grew widespread that
moth-ens, committed to their own career goals and uncar-ing and unloving of their children, generated the
disorder. The reality is otherwise: a concentration
of well-educated mothers of autistic children can
no longer be found.32’33 The concentration observed
earlier among the well-educated was probably the
result of the preferential recognition of the
diag-nosis, at the outset, in disturbed children in the upper social classes, and thus of their selective
transfer out of the ranks of the mentally retarded
and into those of the autistic. Now, however, the diagnosis is well-established and recognized in all classes. The “coldness” of the mothers, too, has
found another explanation. Many view it as the
mother’s reaction to the child’s inability to respond
to affection.
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Lack of Controlled
Comparisons
In the area of treatment, the need for controlled
experimental comparisons is universally accepted,
if not always practiced, and that subject can be left
aside. Controlled comparisons are essential to test
the validity (both internal and external) of virtually
all observations, natural as well as experimental.
Control subjects are usually not readily accessible,
however, in the settings natural to the clinician
who is concerned with his own individual cases.
The simplest form of this problem of
inference-much less common than it used to be, I
suspect-is to draw the conclusion, from the frequent con-currence of symptoms, signs, or disorders, that their
mere concurrence indicates an association among
them. For example, the clinical belief that headache
is a symptom of high blood pressure could not be
substantiated in a population survey34: both
condi-tions are common, and occur together, but not more often than expected for the population at large.
For pediatricians, the problem arises because many supposed symptoms and signs vary so mark-edly in the course of development. Tics and
twitches, nail biting, and bed-wetting, like tantrums
and negativism, are characteristically frequent at
particular ages, and disappear of their own accord35;
to establish that these are signs of emotional
dis-turbance and not merely of development requires more than their concurrence. A notoriously weak
inference of this kind is the supposed association
of minimal brain damage both with hyperactivity,
and with so-called “soft signs.” These associations
remain to be proved.36 Soft signs may be somewhat
more common in the hyperactive than in the
gen-eral population, but they seem as likely to be
tran-sient manifestations of behavior as of brain
dam-age.’7’38
Here pediatricians, in particular, are faced with
the perennially difficult distinctions to be made
between phenomena of development that will remit
naturally and health disorders that demand
treat-ment. Controlled comparisons are all the more
re-quired in cases in which there is marked cultural and social class variation in developmental norms, as with the acquisition of sphincter control. Twenty
years ago, enunesis in late preschool and early
school years was spoken of as a disorder rather than
as a delay in learning the adaptive behavior of
sphincter control, which it is for the vast majority.
Many treatments-psychotherapy, Benzedrine,
alarm conditioning-succeeded. This was less
sun-prising once the remission rate with age in the
population at large was shown to be more or less
exponential, in the given instance from nearly 20% at the age of 4 years, down to a residue of about 1%
at the age of 13 years. Secondary problems caused
by developmental delay in gaining sphincter control
are enough to justify treatment, but a randomized
trial might not easily find a treatment effect against
such rapid remission (although in fact an effect of
the alarm over Benzedrine was shown.39’40)
Even when control subjects are used for compar-ison, as in case-control studies, a problem of exter-nal validity in clinical work may arise in more
complex form. Although, in the population at large,
no association exists between one disease and
an-other, in a hospital series an association between
the two diseases is quite likely to be found. The
association occurs simply because, for individuals
with a chronic disease, the chance of admission to
a hospital will be higher if they should also have
another disease, especially if that additional disease
is a rare one. This is Berkson’s paradox,4’ in which
a hospital case-control study leads to spurious
causal inference because of a particular selective bias. The paradox can be generalized to all
case-control comparisons.42 One example is the
associa-tion of headache and high blood pressure discussed
above. When the rates of admission of “cases” and/
or control subjects differ according to the presence
of a hypothetic causal factor, then the apparent risk
for that factor will differ between the “cases” and
control subjects and give rise to a spurious
associ-ation.
Post Hoc View of Evolution
of Disease
A third source of mistaken inference induced by
cumulative clinical experience is the post hoc view
of the evolution of disease. Although this is a subset
of the problem of selectivity discussed above, the emphasis here is on the time-order of events. The indisputable tenets for a causal association are only two: that the cause shall precede the effect and that the cause produces something, that is, the associa-tion is asymmetrical and has direction from the
causal to the outcome variable.’7 By the nature of
the clinical situation, a disease process must almost always be well-advanced (by epidemiologic stand-ards) when it comes under the clinician’s
observa-tion. In the result, the time-order of the events
preceding entry to observation rests on indirect
evidence or assumption.
The weakness of such assumptions gains empha-sis from the numerous reversals in ideas of
time-order that have occurred in the medical literature:
for instance whether, in bullous emphysema, infec-tion and the destruction of alveoli precede or follow obstruction of the fine bronchioles43; whether salt
retention and/on raised levels of nenin precede or
follow high blood pressure”; whether the formation
of microthrombi in the coronary arteries precedes
or follows the formation of athenomatous plaques45;
autopsy of the role of “final court of appeal” for the
most part holds good in the narrow sense of
con-firming or refuting a clinical diagnosis of underlying pathology. Autopsy data are beset not only by
ex-treme selectivity, but by an incapacity to establish
certainty about the time-order of preceding events.
In the clinical sphere, the difficulty is hardly less.
To take just one example, there is an association
between mental disturbance and mild (as well as
severe) mental retardation.46’47 Does this
associa-tion have a common source in antecedent brain
damage? on does it arise because mental disturbance
impairs cognitive performance? or does it arise
because self-awareness of inferior cognitive
per-formance generates mental disturbance? Such
questions are difficult to answer, even in epidemi-ologic surveys with access to total populations and
early cases. From the clinical situation alone, these questions are often unanswerable.
CONTINUITY
OF OBSERVATION
AND
FOLLOW-UP
The clinical setting, well-used, provides an
excep-tional vantage point for the observation of course
and prognosis. Ill-used, inference from this vantage
point leads to serious error in estimates of
prog-nosis. The problems, simple in concept, are less simple to avoid in practice. They begin with obvious questions of selective ascertainment. With enuresis,
for instance, because only a fraction of
preschool-aged and early school aged children who wet their
bed will come into clinical view, a population
sam-ple reveals a different and more benign course than
a clinical sample would.
A second problem in predicting the course of
disease that is more within the control of clinicians than selective ascertainment-and often more of a
threat to sound inference-is selective follow-up.
Complete or nonselective follow-up is crucial to the
validity of all longitudinal observations.
Unfortu-nately, in clinics for chronic disorders the likelihood
of selective drop-out is high. The patients who
continue in care must be expected to be those with
more severe and intractable disease.
Selective follow-up results in a medical literature
riddled with misestimates of prognosis, nearly all
weighted toward a gloomier outcome. For example,
an often cited clinic follow-up of very
low-birth-weight infants (1,5O0 g) in the early 1970s found
that nearly one third (32%) had spastic diplegia at 10 years of age, but only 52% were followed.48
Compared with a large population study with good
follow-up, the rate is seen to be inflated exactly
tenfold (3.2%). In epilepsy, remissions-being
sei-zune-free for 5 years-for long were estimated as
occurring in about 30% of cases 20 years after
onset.5#{176}More complete follow-up shows the
nemis-sion rate at 20 years to be about 70% overall, 60%
for those not still using medication.5’
DISEASE
AS THE
FOCUS
The clinician, of necessity, concentrates his
thoughts and his vision on disease. Above, I have
stressed the insights into the disease process and
the fertile hypotheses about its origins yielded by
this focus. On the other hand, it is a commonplace that clinicians are unlikely to pursue the tasks of
primary prevention. We do not need to involve the
vested interest in disease that George Bernard
Shaw imputed to doctors, in the preface to The
Doctor’s Dilemma, as the grounds for their
reluc-tance to prevent disease. It would be surprising if
clinicians in general, with their well-defined
re-sponsibilities for caring for sick individuals who
solicit their help, set about the public health task
of providing unsolicited help to populations.
In seeking the causes of ill-health, the clinician
is well placed to come upon or suspect many
pos-sible causes of a given disease. The converse is not
true. Clinicians are not well placed to study and
recognize the many possible effects of a given
en-vinonmental cause. Thus, to study the effects of
contaminated water, or poverty, or life stress, or air
pollution, and to approach prevention from the
point of view of a given cause, falls outside the
clinical scope. That side of causality must be left
for others to pursue. More than 50 years ago, some
clinicians first began to suspect that smoking
caused lung cancer; 30 years ago early epidemiologic
studies demonstrated the association.5255 Many
years of investigation from an epidemiologic
stand-point were needed, however, to make clear the
multifarious ills caused by smoking. This
circum-scniption of role does not absolve the clinician from
the tasks of prevention in individual patients. Yet
all too often the result is neglect of these tasks.
This final observation is not an indictment. It is
to say that both the functions appropriate to
clini-cians, and the issues of causality they can hope to
address from a sound perspective through their own
experience,
must
be limited. What I have tried todo is to set out, in the matter of causal inference,
some limitations of clinical pediatrics as the mirror
image of its strengths. Extrapolations from the
clinical situation can be hazardous. Made con-sciously, with due attention to the principles and strategies of causal inference, the hazards can be
faced and dealt with and sometimes overcome.
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