DIAGNOSIS AND TREATMENT
Diagnostic Reasoning
Jerome P. Kassirer, M D
Research in cognitive science, decision sciences, and artifi-
cial intelligence has yielded substantial insights into the
nature of diagnostic reasoning. Many elements of the diag-
nostic process have been identified, and many principles of
effective clinical reasoning have been formulated. Three rea-
soning strategies are considered here: probabilistic, causal,
and deterministic. Probabilistic reasoning relies on the statis-
tical relations between clinical variables and is frequently
used in formal calculations of disease likelihoods. Probabilis-
tic reasoning is especially useful in evoking diagnostic hy-
potheses and in assessing the significance of clinical findings
and test results. Causal reasoning builds a physiologic model
and assesses a patient's findings for coherency and complete-
ness against the model; it functions especially effectively in
verification of diagnostic hypotheses. Deterministic reason-
ing consists of sets of compiled rules generated from routine,
well-defined practices. Much human problem solving may
derive from activation and implementation of such rules. A
deeper understanding of clinical cognition should enhance
clinical teaching and patient care.
Annals of Internal Medicine. 1989;110:893-900.
From Tufts University School of Medicine and the New
England Medical Center, Boston, Massachusetts. For
current author address, see end of text.
lifficient and accurate diagnosis is one of the foremost
cognitive functions of the physician, and in the past
decade many fundamental features of diagnostic rea-
soning have been disclosed. Probabilistic approaches
have dominated recent discussions of diagnosis, be-
cause iterative engineering has converted them into
practical clinical tools. Eclipsed by the probabilistic
approach, however, are other powerful concepts that
embody fundamental principles and important cogni-
tive strategies of diagnostic reasoning. These strate-
gies—causal reasoning and deterministic (rule-based)
reasoning—are derived from research in new disci-
plines that have only just begun to influence medical
practice, namely cognitive science, cognitive psycholo-
gy, and artificial intelligence. Many insights from
these fields can be applied directly to the medical diag-
nostic process.
We discuss elements of diagnostic reasoning. First,
we give an overview of the cognitive aspects of the
diagnostic process, and then discuss the principles of
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probabilistic, causal, and deterministic reasoning stra-
tegies. Finally, we consider the interrelationships be-
tween reasoning strategies and the circumstances in
which one strategy may be preferable to another. The
discussion centers on the cognitive aspects of diagno-
sis, not on the other aspects of the patient encounter
(social and psychological factors, interviewing tech-
niques, or precision of information).
Elements of the Diagnostic Process
In the diagnostic process, the clinician makes a series
of inferences about the nature of malfunctions of the
body. These inferences are derived from existing ob-
servations (historical data, physical findings, and rou-
tine tests) as well as from invasive tests and responses
to various manipulations. Inferential reasoning pro-
ceeds until the clinician has discovered a diagnostic
category sufficiently acceptable to either establish a
prognosis, yield a therapeutic action, or both ( 1 ) .
When making diagnostic inferences from clinical data,
the clinician uses many strategies to combine, inte-
grate, and interpret the data (2, 3). Clinicians make
extensive use of rules of thumb, or shortcuts (heuris-
tics) in the process of gathering and interpreting infor-
mation. These heuristics are essential: they reduce the
need to ask an unnecessarily large number of questions
and to order superfluous diagnostic tests, and they
make the task of information gathering manageable
and efficient (4, 5).
Studies of human cognition suggest that the kinds of
heuristics used depend on the nature of the clinical
problem being addressed and on the expertise of the
clinician. Nonexperts tend to use nonselective search-
and-seek strategies that, although they are applicable
across a wide range of clinical settings, are weak in
generating specific hypotheses (6-9). Experts, howev-
er, typically employ strong diagnostic approaches tai-
lored to their expertise. They quickly focus on a prob-
lem by recognizing patterns, formulating problems in
semantically meaningful "chunks," gathering data rel-
evant to a solution to the problem, and applying pre-
compiled actions (2, 7, 9-15).
The diagnostic process focuses on one or more
evolving diagnostic hypotheses (2, 3, 16, 17). A hy-
pothesis can be either general or specific. It can take
several forms, including a state (inflammatory pro-
cess), a clinical disorder (acute transplant rejection),
a syndrome (nephrotic syndrome), or a specific dis-
ease entity (polycythemia vera) (1-3, 18). Hypothesis
generation, a process described as diagnostic trigger-
ing, is the first step at the inception of a diagnostic
©1989 American College of Physicians 893
 encounter (2, 3, 16, 17, 19). Triggering, the formula-
tion of a preliminary hypothesis on the basis of only a
few observations is critically dependent on the cogni-
tive ability to relate a new situation to past experience.
Typically, the clinician triggers initial hypotheses
merely from a patient's age, sex, race, and presenting
complaints, but sometimes such hypotheses emerge
exclusively from physical findings or laboratory data
(2, 3, 16, 17). Additional hypotheses are triggered as
new findings emerge.
Hypotheses serve an essential function: They form a
context within which further information gathering
takes place (20, 21). This context, a diagnostic catego-
ry of some kind (acute bacterial meningitis, for exam-
ple), provides a model against which a given patient's
findings can be assessed (2, 21, 22). The diagnostic
category specifies the findings that should be present
and those that should be absent if the patient has a
given disorder. Diagnostic reasoning proceeds by pro-
gressive hypothesis modification and refinement. Some
hypotheses are made more specific, some previously
triggered hypotheses are deleted, and some new ones
are added. Evidence suggests that only about seven
hypotheses are active at any one time, constrained by
the limited capacity of short-term memory (2, 23-25).
It is not clear how much of the diagnostic process is
driven by hypotheses, and how much is driven by the
availability of data from the physical examination or
laboratory (the so-called data-driven approach [7, 14,
2 6 ] ) . Possibly, elements of the hypothesis-driven and
data-driven approaches are intermingled.
Verifying a diagnostic hypothesis is the next, and
often penultimate task. Because the diagnostic process
is inferential, all diagnostic hypotheses necessarily re-
flect a belief or a conviction by the physician regarding
the nature of the patient's condition. Verifying a hy-
pothesis involves assessing its coherency (for the pa-
tient in question, are all physiologic linkages, predis-
posing factors, and complications appropriate for the
suspected disease), its adequacy (does the suspected
disease encompass all the patient's findings, normal
and abnormal), and its parsimonious nature (is the
suspected disease a simple explanation of the patient's
findings) ( 2 ) . It also requires eliminating competing
hypotheses in a process analogous to disproving com-
peting scientific hypotheses (can any other diseases
better explain the patient's findings) ( 7 ) . This process
produces one or more working hypotheses that form
the basis for the next step in patient management—ob-
serving the patient, ordering additional tests, or treat-
ing the patient (27-30).
Types of Diagnostic Reasoning
There exists no comprehensive description of diagnos-
tic problem solving (indeed, no generally accepted
theory of human problem solving exists), yet some of
the elements used to carry out the inferences described
above have been elaborated. We discuss three clinical
reasoning techniques: probabilistic, causal, and deter-
ministic reasoning.
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The probabilistic approach is based on associations
between clinical variables, usually described as statisti-
cal relationships. This approach utilizes data such as
the prevalence of coronary disease in asymptomatic
40-year-old men, the frequency of hypocomplemente-
mia in membranoproliferative glomerulonephritis, and
the frequency of false-positive tests for antibodies to
the human immunodeficiency virus ( H I V ) in various
populations at risk for the acquired immunodeficiency
syndrome ( A I D S ) .
Causal reasoning is based on the physiologic or
cause-and-effect relations between clinical variables.
For example, the diagnosis of hyperthyroidism is
strengthened in a patient with "soft" clinical manifes-
tations of the disease and a moderate elevation of plas-
ma thyroxine if the level of thyroid stimulating
hormone is also found to be suppressed, because high
levels of thyroid hormone inhibit pituitary production
of thyroid-stimulating hormone; a possible diagnosis
of superior vena caval syndrome is strengthened if a
mass lesion is identified in the right side of the me-
diastinum on chest roentgenogram, because mass le-
sions in this location are known to obstruct the superi-
or vena cava.
Deterministic, or categorical reasoning, is based on
compiled strategies in the form of well-defined rules.
Examples of this approach include: If plasma bicar-
bonate is less than 8 m m o l / L and blood p H is low, the
diagnosis is metabolic acidosis. If an elderly patient
has patches of osteosclerosis in the pelvis, check the
alkaline phosphatase level, and if it is elevated, the
diagnosis is Paget disease.
Although these three reasoning strategies are pre-
sented as separate and distinct entities with well-de-
fined boundaries, we show how these strategies over-
lap and complement each other.
Probabilistic Reasoning
Medical diagnosis and test interpretation involves con-
siderable uncertainty, which can be represented as
probabilistic associations between clinical variables
(30, 31). A probability represents a belief in the state
of a patient or in the meaning of a test result: We may
believe, for example, that a patient may be either high-
ly likely or highly unlikely to have a given disease, and
that a certain test result either increases or decreases
the likelihood of that disease. In assessing clinical find-
ings and test results, these relations among clinical
variables must be integrated. When combining such
data, clinicians ordinarily use ill-defined expressions
for likelihood such as "quite likely," "common," "fre-
quent," and "rare." However, because nonquantitative
terms do not have standardized meanings (32-34), the
clinician's ability to combine clinical data character-
ized by such nonquantitative measures of uncertainty
is compromised (35). A more satisfactory technique
for interpreting clinical data uses formal probabilities
and likelihood ratios, and combines such probabilities
quantitatively (36). We will discuss many of the im-
portant principles of probability theory that relate to
interpretation of tests and other clinical findings.
 Requirements
To combine clinical findings in the form of probabili-
ties requires a rigorous definition of disease (30). This
definition, referred to as the "gold standard," often is
based on histologic findings or radiologic studies, but
sometimes it must be based on clinical criteria alone.
The first task in applying the probabilistic approach is
estimating the prevalence, or prior probability, of all
diseases of interest from the patient's demographic
data and presenting clinical findings. The prior proba-
bility for an individual patient must reflect as closely
as possible the population from which that patient is
derived. A carefully selected assessment of this proba-
bility is critical because its value has a major influence
on the interpretation of any clinical feature or test re-
sult (30, 31, 37). The second task is to determine the
frequency of features associated with a defined disease
entity, namely the conditional probabilities (30, 31,
37). Typical questions that could be used to derive
these data might include: How often is plasma IgA
elevated in the entity; how often is it slightly, moder-
ately, and markedly elevated? This information must
be coupled with similar data about other diseases
under consideration and about findings in normal indi-
viduals (38). The sensitivity and specificity of diag-
nostic tests are special terms for certain kinds of con-
ditional probabilities (30, 31, 36).
Given an appropriate gold standard and data on the
prior and conditional probabilities of the set of diseas-
es in question, clinical findings and test results can be
interpreted according to mathematical principles (30,
31, 36, 39). The output of this quantitative approach
is a revised view of the likelihood that a patient has
one or more diseases, a concept known as the posterior
probability. The numerical values in these calculations
are ordinarily based on data from the literature, but
when such information is unavailable, subjective as-
sessments of prior and conditional probabilities may
be used.
Caveats
This process requires particular care. The list of possi-
ble diagnoses must be exhaustive, because if one diag-
nosis is left out it will never emerge as a potential
cause of the patient's symptoms or signs (39). Many
test results cannot be described only as positive or neg-
ative, and for such tests it may be necessary to de-
scribe several levels of positivity. To do this, results
that are continuous variables usually must be broken
into discrete intervals to use in calculations (39). To
avoid a repeat count of the same information, each
disease must be mutually exclusive of all other diseases
and each conditional probability used in a calculation
must be independent of the others (30). Finally, cer-
tain diseases cannot be appropriately considered as ei-
ther present or absent. Because stages of diseases often
have different manifestations, any quantitative analysis
must recognize the clinical manifestations and test re-
sults in various stages of the disease in terms of sever-
ity or time course, or both (40).
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If all these precautions are heeded, the probabilistic
approach can be a valuable tool. Most important, it
provides an explicit means of test interpretation and
thus helps to illuminate the diagnostic process. Aside
from its value in analyzing complex and disparate
data, the probabilistic approach is helpful in hypothe-
sis generation because associations between clinical
findings trigger diagnostic hypotheses according to
their frequency. For example, crushing chest pain in a
60-year-old man promptly conjures up a diagnosis of
acute myocardial infarction; whereas acute pleuritic
chest pain in a 20-year-old man triggers the possibility
of spontaneous pneumothorax. The probabilistic ap-
proach also teaches many important principles of di-
agnostic testing: If the pretest probability of a disease
is extremely low, a positive test result will rarely con-
firm a diagnosis unless the test is highly specific (the
test result probably will be false-positive). When the
likelihood of a given disease is extremely high, a nega-
tive test result usually does not exclude the presence of
the disease unless the test is highly sensitive.
Taking the Next Step
Both nonquantitative working hypotheses and calcu-
lated posterior probabilities are constructed for the
purpose of taking action. The action may be only to
arrive at a certain forecast about the patient's subse-
quent clinical course, but most often it is a plan of
further testing or treatment or sometimes no more
testing or treatment. These choices are a function of
the probability that a patient has one or more diseases,
the benefits to be derived from further testing, the
risks of further testing, and the benefits and risks of
the treatment.
These concepts are elaborated in the form of testing
and treatment thresholds (27, 28). A threshold can be
calculated using the methods of decision analysis from
data on the benefits and risks of diagnostic tests and
treatments (27, 28), or it can be estimated (29). A
threshold is the probability of a disease at which two
choices (for example, treating or not treating) have
equivalent value. The threshold is thus a benchmark
for action: At disease probabilities lower than the
threshold one action is appropriate, whereas at disease
probabilities greater than the threshold a different ac-
tion is appropriate.
Suspected pulmonary embolism provides an exam-
ple of how thresholds can be applied. If at one ex-
treme, the suspicion of pulmonary embolism, based on
clinical findings and a ventilation-perfusion scan is ex-
tremely low, we should do no more tests and not give
treatment. If, at the other extreme, the physician be-
lieves there is a near certainty that a patient has had a
pulmonary embolism, it is preferable to give anticoag-
ulants without more testing. Between these two ex-
tremes, more testing with pulmonary arteriography
might or might not be the optimal strategy. Using data
on the accuracy and risks of pulmonary arteriography
and data on the efficacy and risks of anticoagulants,
895
 the no-treatment/testing threshold and the testing/
treatment threshold can be calculated, providing spe-
cific guidance concerning how low the probability of
pulmonary embolism must be before choosing not to
give treatment and not to order an arteriogram, and
how high the probability must be before abandoning
arteriography and treating with anticoagulants. At
probabilities of pulmonary embolism between these
two thresholds, the optimal choice is to carry out arte-
riography because the study results will determine
whether to administer anticoagulants.
Implicit in the threshold approach is the concept
that although a diagnosis has a greater or lesser degree
of uncertainty, this uncertainty should not impede the
clinician from making a testing or treatment decision.
When formal threshold calculations have not been
done, the choices to treat, to continue testing, or to
withhold testing or treatment should be made after
consideration of the disease likelihood and the benefits
and risks of relevant tests and treatments.
Causal Reasoning
We are seldom explicit about the diagnostic value of
the cause-and-efFect relations among clinical variables
although we expend enormous resources on the inves-
tigation and teaching of pathophysiology. Yet causal
(physiologic) reasoning remains a fundamental un-
derpinning of diagnostic reasoning, and, when applica-
ble, it enhances the diagnostic process with the rich-
ness of its explanatory power.
Causal reasoning relies on the cause-and-effect rela-
tions between clinical variables or chains of variables
( 1 , 18, 41-46). It derives from common sense notions
of causality. For example, if we see a field of shriveled
crops, we might draw several inferences. First, the
crops might be lacking nutrients; second, cold weather
might have affected them; and third, pollutants might
have poisoned them. If, however, we are already aware
that the region has been subject to a prolonged
drought, we could conclude that the cause of the with-
ered plants is lack of water because we know that lack
of water dehydrates crops. This and countless other
examples in medicine are based on a causal or physio-
logic model of reality; the capacity to make inferences
from the observed clinical findings also depends on the
principles embedded in this model.
A causal model might be defined as a description of
mechanisms (anatomic, physiologic, biochemical)
that can be used to simulate the normal workings of
the human body, its pathophysiologic behavior in dis-
ease, and the idiosyncracies of a particular patient
(42). The causal model supports a clinician's perform-
ance by simulating possible courses of the disease and
its modification by treatment. It also serves as a coher-
ency criterion on hypotheses about the patient, and
provides a common framework for explanations and
discussion among clinicians ( 4 2 ) .
When applying causal reasoning, clinical variables
are examined and included if they help explain the
model. A model is created for each patient, although a
single model can apply for many patients in various
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clinical settings. Such a model is a coherent system
capable of explaining its components, the range of pos-
sible variations, and the nature of findings in a particu-
lar patient. If the same model is not applicable for
another patient with a problem similar to that for
which it was created, additional physiologic features
might be required. Physiologic models exist in all ar-
eas in medicine.
For example, in models for fluid and electrolyte
equilibrium (47), assume that a patient with clinical
and laboratory findings suggestive of the syndrome
of inappropriate secretion of antidiuretic hormone
( S I A D H ) has a high urinary sodium excretion. Does
this finding influence the suspected diagnosis? We
could assess this finding in a probabilistic framework
(for example, we might say that 8 5 % to 9 5 % of pa-
tients with S I A D H have a high sodium excretion) or,
alternatively, by understanding the pathophysiology of
the syndrome, we could examine how the finding
"fits" with the diagnosis. If our model of S I A D H con-
tains (as it should) the concepts that such patients are
volume expanded, that volume expansion promotes
sodium excretion, and that sodium excretion in the
syndrome typically matches sodium intake, we would
readily understand that a high urine sodium excretion
is consistent with a diagnosis of S I A D H and adds to
the credibility of the diagnosis. We also would be in a
position to explain a low urine sodium excretion if that
were the finding instead. In this instance, despite the
presence of S I A D H , urine sodium is low presumably
because the patient is ingesting little salt.
Judging Causality
Research in causality in nonmedical contexts provides
a systematic framework for judging cause-and-effect
relations as they apply to medical diagnosis (43, 4 8 ) .
We often are alerted to the possibility that we should
use a causal model when abnormal findings or events
violate normal physiologic expectations. This devia-
tion produces the context within which further data
gathering and interpreting take place. To carry out
this interpretive process, we generate a causal model,
typically a chain of physiologically related features
consisting of stimuli and their responses.
When invoking a causal hypothesis involving two or
more variables, the links between stimuli and respons-
es must be assessed for their strength (43, 4 8 ) . Several
criteria can be used to assess the strength of this link.
Is the entire causal chain credible? Does a change in a
response correlate closely with the change in the stim-
ulus? Is there substantial congruity of duration and
magnitude between response and stimulus? Is there
close contiguity in time and space between a response
and a stimulus (did one event follow another closely
enough to allow us to accept that the first event caused
the second)? When these tests are satisfied, one gains
confidence that a given response and a suspected stim-
ulus (or a given stimulus and a suspected response)
are related.
This process of testing, validating, verifying, and
falsifying causal connections is a fundamental aspect
 of medical practice. The final process in assessing a
causal hypothesis is testing it for alternate possible ex-
planations (43, 48). Because a given causal hypothesis
appears to explain a set of findings, it does not neces-
sarily prove that this causal chain is the correct one.
Alternative constructions of the causal chain must be
sought and their strengths assessed before accepting
one model and not another.
Application in Diagnosis
Causal reasoning can be applied in several steps of the
diagnostic process. It may be useful in the formulation
of a context: If the possibility of a pathophysiologic
state has been triggered by some findings, the state
may provide the context for further data gathering
(for example, the context of possible volume contrac-
tion should lead a physician to take a detailed history
of fluid loss). A causal model also can be used to help
verify a diagnosis: In a patient suspected of having
hyperthyroidism from clinical findings and a slightly
elevated plasma thyroxine, the finding of a suppressed
level of thyroid stimulating hormone verifies the diag-
nosis. Assessing the coherency of a diagnosis, namely
determining whether the physiologic or causal associa-
tions are reasonable and appropriate, is frequently a
late step in gaining confidence in a diagnosis. This step
involves determining whether a patient's findings are
consistent with recognized pathophysiologic manifes-
tations of a suspected disease.
Benefits
An important strength of causal reasoning is its capac-
ity to provide an explanation for a given finding, espe-
cially when the relation is not immediately obvious
from either probabilistic associations or from previ-
ously compiled concepts. Another strength is the ca-
pacity to use such a model to return to first principles
when findings do not fit an idealized pattern. A causal
model also makes it possible to unite various clinical
findings in a common framework: for example, the ef-
fect of dietary sodium intake and sodium excretion in
patients with S I A D H . A causal approach provides a
consistency check among related findings: Two com-
mon findings may have a strong probabilistic (or
statistical) relationship, yet they may be causally in-
consistent. Causal reasoning can help identify such
discrepancies. Proper application of the causal ap-
proach yields a rigorous guide to therapy because the
treatment can be based on efforts to reverse the string
of events that produced the disordered state. Finally,
causal reasoning also has been applied in the develop-
ment of computer-based "expert systems" for medical
diagnosis. One program used several causal models at
increasing levels of detail to deal with fluid and elec-
trolyte disorders (49, 50), and another used a network
of causal associations to deal with general problems of
internal medicine (51).
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Deterministic Reasoning
Deterministic or categorical reasoning consists pre-
dominately of compiled knowledge from any source in
the form of unambiguous rules. Such knowledge may
originate in probabilistic or causal associations be-
tween clinical findings. Because so many diagnostic
problems that physicians confront daily are simple
and straightforward, the exercise of the diagnostic
process for such problems is routine, well defined and
thus, as a practical matter, deterministic.
Production Rules
To specify reasoning in a deterministic fashion re-
quires that we identify the rules that describe our rou-
tine practices. Such deterministic assertions, referred
to as production rules, are in this form: "If (certain
conditions are m e t ) , then (a certain action is appro-
priate)." Investigators have built an elaborate hypoth-
esis on the nature of human problem solving using
these kinds of if-then rules (6, 52-56). They assume
that production rules are the basic building blocks of
human cognition and that they specify both a condi-
tion that must be met and an action that derives from
satisfaction of that condition (6, 52, 56). The condi-
tion is presumably a recognizable, semantically mean-
ingful piece of information, and the action is a speci-
fied, predetermined consequence that derives from the
triggering of the condition (6, 25). Such production
rules, the theory argues, form the framework for de-
veloping the mental models that enhance human prob-
lem solving. Without them we would have to rely on a
complex storage system of examples and episodes.
Rules can have many purposes, and can describe
therapeutic approaches or prognostic implications. An
example of a rule constructed specifically to describe a
diagnostic strategy might be: If a young, otherwise
healthy black woman has hilar adenopathy, consider a
diagnosis of sarcoidosis. Another compiled rule from
our S I A D H model: If S I A D H is present, and the pa-
tient is ingesting an average diet, expect renal salt
wasting. Presumably many rules operate in parallel,
compete with others for satisfaction, and either win or
lose depending on their strength or relevance (6, 53).
Clinical Algorithms
In medicine, deterministic reasoning often has been
imbedded in a printed, one- or two-page branching
algorithm, or flow chart. An algorithm is an ordered
set of instructions for carrying out a specific task
through a structure of simple steps. Most algorithms
are designed by authors who have simulated their per-
ception of the diagnostic process for a particular prob-
lem (57-64), but some have been derived from deci-
sion analysis or published studies of a clinical problem
(65). Many algorithms are designed to help the clini-
cian interpret single findings, for example, hyperkale-
mia. In the typical algorithm, each nonterminal node
requests information and requires decisive and
unequivocal answers, which are the labels of the
897
 branches leaving that node. The terminal nodes of the
algorithm represent outcomes, each also precise and
explicit.
Flow charts are used in various ways. In some in-
stances the user encounters a node that requires a test
result. In a flow chart for the differential diagnosis of
hyperkalemia, for example, a node might have a label
that asks whether renal function is normal, whether
adrenal function is normal, or whether the patient is
receiving certain drugs. Therefore, in this approach
diagnostic tests considered necessary are specified, al-
though the rationale for their application is not usual-
ly described. A flow chart also may specify which tests
are appropriate as outcomes, or terminal nodes, of the
branching logic.
An algorithm that accurately and realistically repre-
sents actual clinical decision making has a substantial
payoff: Because it requires each user to follow the
specified pathway exactly, the user cannot forget to
ask an important question or do an essential test ( 6 6 ) .
Algorithms are useful for some diagnostic problems,
particularly those in which the logic can be defined
clearly and precisely. To solve complex problems,
however, algorithms frequently become so complicat-
ed that they cannot be represented readily as a printed
figure.
Algorithms also have other problems (63, 64, 67,
68). They often do not deal effectively with uncertain-
ty, which is a common feature of medical practice.
Some are flawed because they are based on the faulty
opinion of an individual rather than on data derived
from experimentation or rigorous clinical observa-
tions. The notations defining states or branch points
are ambiguous in some algorithms, thus yielding an
incorrect pathway through the branches. An algo-
rithm developed for one purpose may provide an
incorrect result if used in another context when the
entry point is the same for both. For example, an algo-
rithm designed exclusively for the diagnosis of urinary
tract infection and that has entry symptoms of dysuria
and urinary frequency will provide the wrong answer
if the patient has vaginitis. Finally, most algorithms
are unsuitable for patients with multiple complaints,
complex clinical problems, or multiple interacting dis-
ease entities.
Rule-Based Expert Systems
Another deterministic approach to diagnosis consists
of identifying lists of rules that clinicians use. Exhaus-
tively specifying all rules for a problem domain (rheu-
matology, for example) is a formidable, yet probably
feasible exercise. But using a long list of production
rules is impractical because it requires searching
through the set of them to ensure that all the appropri-
ate findings and rules are identified. Although a physi-
cian hardly could be expected to sift through a list to
achieve a diagnosis or to assess the need for a test, a
computer program can do this easily (52, 54, 69-71).
Several computer programs have been written using
sets of rules; these expert systems already have
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achieved some success but are still undergoing devel-
opment.
The Choice of an Approach
When is it appropriate to use the various kinds of clin-
ical reasoning described? Presumably many strategies
are used, as a reflection of the rich interplay character-
istic of human reasoning. Because much of our medi-
cal practice is repetitive and straightforward, many of
our decisions are guided by precompiled deterministic
rules. Probabilistic or rule-based reasoning is more
likely to be successful than causal reasoning in initiat-
ing inferences about causes from observed effects (that
is, triggering hypotheses). In turn, the probabilistic
and rule-based strategies can identify reasonable hy-
potheses that form the context for efficient causal rea-
soning. Because of its capacity to build an explanatory
model and its ability to permit us to return to diagnos-
tic and therapeutic first principles, causal reasoning is
a powerful approach especially when a complete or
nearly complete model can be constructed.
The various reasoning strategies described are com-
plementary. Causal models are exclusively dependent
on fundamental knowledge about physiologic function
and dysfunction. These models are specific to disease
entities and independent of the patient population. By
contrast, probabilistic models are dependent on the
specific population from which the patient is drawn.
Because diagnostic hypotheses are critically dependent
on disease prevalence, causal reasoning is a weak ap-
proach when the required task is triggering such hy-
potheses, whereas probabilistic reasoning is strong.
Once some hypothesis has proposed a possible cause,
however, causal reasoning allows us to verify whether
the cause can explain the observation. The S I A D H
example illustrates the interplay of these reasoning
strategies. Once the diagnosis was triggered, the causal
model made it possible to check the appropriateness of
a high urinary sodium excretion. Causal models also
help us to understand when certain findings do not fit
within the framework of a given hypothesis. Such a
signal becomes a trigger for generating new hypothe-
ses.
Reasoning strategies also interact in validating pro-
babilistic models. These models require that each dis-
ease under consideration be mutually exclusive of all
others and that conditional probabilities under consid-
eration be independent of each other. Because causal
models encode dependence among the parameters
they encompass and provide an understanding of the
relations between variables, they can identify circum-
stances in which the independent assumptions of a
probabilistic model are invalid and can provide valu-
able guidance for correcting a poorly constructed
model.
Our knowledge of the diagnostic process remains
too limited to precisely define the clinical situations in
which one kind of reasoning is most desirable. We
may find that an efficient, effective, expert clinician
uses all of these approaches, even in the same diagnos-
tic encounter. We still have much to learn about diag-
 nosis, but recent research efforts on the process bode
well for the enhancement of our diagnostic efficiency
and accuracy.
Grant Support: Supported in part by grant # 5 R01 LM04493 from the
National Library of Medicine.
Requests for Reprints: Jerome P. Kassirer, M D , 750 Washington Street,
Boston, MA 02111.
Current Author Address: Dr. Kassirer: 750 Washington Street, Boston,
Massachusetts 02111.
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