COPD: Journal of Chronic Obstructive Pulmonary Disease, 2:51–55

ISSN: 1541-2555 print / 1541-2563 online

Copyright D 2005 Taylor & Francis Inc.
DOI: 10.1081/COPD-200050641

INVITED SYMPOSIUM

Minimal Clinically Important Difference, Clinical

Perspective: An Opinion
Stephen I. Rennard (srennard@unmc.edu).
Pulmonary and Critical Care Medicine [Phone: (402) 559-7313, Fax: (402) 559-4878], University of Nebraska Medical Center,
985885 Nebraska Medical Center, Omaha, Nebraska 68198-5885, USA.

ABSTRACT
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The Minimal Clinically Important Difference has become a key feature for both the validation
of clinical tools and for the assessment of clinical studies. Several methods have been
developed to establish what a Minimal Clinically Important Difference is. The primary purpose
of the Minimal Clinically Important Difference, however, is to provide a measure of relevance
for a statistically applied measure. It does not, despite its name, necessarily relate to the
‘‘Clinical’’ condition. In this context, human beings are capable of extremely fine grades of
discrimination of very subtle differences, when they care about the measures. When they do
not care about the measure, large differences may be irrelevant. The flavors of wines or the
tone qualities of musical instruments are readily recognizable examples. The importance of an
outcome, for a clinician caring for an individual patient, therefore, will be highly patient
For personal use only.

specific. The Minimal Clinically Important Difference has great utility in assessing tools for
clinical investigation. It has limitations in assisting the clinician. The subtleties that may be
meaningful to individuals are often lost in discrimination tests in large populations where not
all have the same interests. In addition, readily applicable tests, for example, discriminating
degrees of salty water, for which Minimal Clinically Important Difference can be readily defined,
are often tests that have no interest for the majority of the population tested. This leads to
several paradoxes. Readily defined Minimal Clinically Important Differences are likely to be
defined for parameters that are of little interest to a large number of persons. Conversely,
parameters that are of great interest to selected individuals, that could be discerned by them
with great subtly are likely to be poorly generalizable. Without doubt, defining a Minimal
Clinically Important Difference will remain a key goal in the validation and application of tools
for clinical investigations. The limits of the concept, particularly as it relates to issues of
importance to patients, however, needs to be recognized.

INTRODUCTION pulmonary disease (COPD). This is an extremely important

The minimal clinically important difference (MCID) is an
important emerging concept. The conference, of which the
following presentation was part, attempts to address the MCID
for a variety of measures applied to chronic obstructive
Keywords: Discrimination, Clinical relevance, MCID,
Patient-centered outcomes.
Correspondence to:
Stephen I. Rennard
Pulmonary and Critical Care Medicine, University of Nebraska
Medical Center, 985125 Nebraska Medical Center, Omaha
NE 68198-5125
USA
phone: (402) 559-7313 fax: (402) 559-4878
email: srennard@unmc.edu
problem. COPD affects up to 24 million Americans (1) and is
currently the fourth leading cause of death in the United States
(2). Current therapy can do much to improve patient well-
being, but no treatment except smoking cessation (3) has been
shown to slow the loss of lung function that characterizes
COPD. In addition, new treatments that address the many
varied clinical manifestations of the disorder are needed.
Addressing these needs will require the application of a
number of clinical tools designed to measure various aspects
of this heterogeneous disorder. Understanding the MCID for
each of these tools will help assess the importance of potential.
The following presentation was designed to provide a clinical
perspective of the MCID and represents an opinion rather than
a review.
‘‘Clinical’’ has several definitions. In the medical context,
it generally refers to issues relevant to the patient. One of the

COPD: Journal of Chronic Obstructive Pulmonary Disease March 2005 51

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 great advances of our era has been the development of
statistical methods and their application to the evaluation of
clinical problems. These methods have improved the classi-
fication and staging of clinical disorders. Perhaps most
importantly, they have permitted rigorous evaluation of
therapeutic interventions. Specifically, by determining the
probability that an apparent effect may be due to chance, these
methods have permitted rigorous evaluation of therapeutic
interventions and have been crucial in the medical advances of
the last century. So important are these statistical methodol-
ogies, that their rigorous application is now a sine qua non for
approval of new medications and for acceptance of new
medical observations.
Statistical methods, however, have both requirements and
limitations. The major limitation, which is addressed in detail
in this symposium, is that statistical methods, while able to
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determine whether a difference is likely due to chance, are not
readily used to determine if a difference is meaningful.
Nevertheless statistical approaches to the problem of mean-
ingfulness have been explored. Norman and colleagues
evaluated a series of 38 studies (4). In these studies, 62
clinically important differences were reported. Interestingly,
the magnitude of the effect size that was deemed important
seemed to follow a normal distribution. With a few outliers, the
independently determined important difference was very close
to 0.5 standard deviations of the effect size. This observation is
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all the more striking as the standards used to define ‘‘impor-
tant’’ were generally based on ‘‘clinical judgment.’’ Finally,
this difference corresponded reasonably well with the seven
units that serves as a rough measure of the gradations that can
be readily perceived (5). Furthermore, defining the important
difference in terms of the population evaluated, rather than in
terms of the measure used to make the evaluation, is appealing
and suggest something general about ‘‘importance.’’
For a clinician concerned with individual patients,
however, the concept of a ‘‘one-half standard deviation’’
ignores patient specific concerns. It also seems to fail to pass a
plausibility test where a minimal important difference can be
easily defined. Consider, for example, the distribution of
scores, expressed as a difference between visitor and home
team for major league baseball for June of 2003, which
shows a strikingly bell-shaped curve (Figure 1A). Similarly,
the distribution of football scores for NCAA Division I teams
in the first three games of the 2003 season shows a similar
approximately normal distribution (Figure 1B). One-half
standard deviation for these distributions, however, represents
greater than two runs and greater than 10 points. These are
differences much larger than those clearly recognized as the
‘‘minimal important difference.’’ Perhaps the reason sports are
as compelling entertaining as they are is that the differences
observed are far subtler than can be expected statistically.
Another approach to define a meaningful difference is to
anchor the measure to a value with a generally recognized
meaning. In the context of exercise physiology, for example,
watts of worked performed is much less recognizable than
distance walked. Using distance walked, because it has an
52 March 2005 COPD: Journal of Chronic Obstructive Pulmonary Disease
everyday meaning, can put performance in an intuitively
understandable context. Nevertheless, this leaves important
questions unanswered. In a 6-minute walking test comparing
performance after an intervention, for example, how much of a
difference is important remains controversial. In fact, it seems
most likely that there will be no resolution to this issue
specifically because a meaningful difference is entirely
context specific. For individuals engaged in a competitive
race, very small differences can be crucially important. For
the same individuals in other situations, those differences can
be meaningless.
The context-specific nature of importance has another
implication. Specifically, the more important a measure is, the
more likely small differences are important. That is, in a race,
very small differences in distance traveled are crucial.
Similarly, for an artist, extremely subtle differences in color
are important that may be irrelevant to others. The same may
be said for flavors to the oenophile, sounds to the musician,
words to the poet, or elegance to the mathematician, to name a
few. Psychological approaches to define minimal important
differences are often based on the ability of a population to
distinguish among gradations in a measure. The ability of most
people, in contrast to a skilled chef, to distinguish seven
flavors of saltiness (5), for example, does not define the
importance of the difference, nor of saltiness. Unfortunately, it
should be expected that the more important a measure is for an
individual, the increasingly refined is the ability to distin-
guish differences.
The examples above demonstrating the ability of selected
individuals to discriminate a large number of subtle gradations
intentionally reflect the more specialized aspects of the human
activity. Clinically important differences are those differences
relevant to the individual patient and important to the patient’s
life. MCID is a concept that refers to groups of people, but
because of the wording used, it is likely that confusion will
arise. This is the problem for the clinician. People are
different, particularly in their perception of what is important.
In general, the most important differences for an individual
patient will require the most discerning measures. However,
just as the subtle flavors of wine are meaningless to the
teetotaller, small differences crucial to some are irrelevant for
others. Unfortunately (or rather for the sake of humanity,
fortunately), people are exceedingly variable in their ability to
discern and value differences. Thus, the major problem with
defining an MCID for any measure is that the most important
differences, which require the most subtle measures for an
individual patient, are likely to have the least general
application. Conversely, measures that can be generalized
are unlikely to have much individual importance and will,
therefore, be very crude tools. An MCID is unlikely, therefore
to influence a physician making a clinical decision with an
individual patient.
Combining measures, which may have differing impor-
tance for different individuals, has been suggested and there
have been many attempts to develop indices evaluating
multiple domains. Such measures have proved exceedingly
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Figure 1. Distribution of winning sports scores. Panel A: The difference at the end of the game for Major League Baseball games in June 2003 is
shown. Vertical axis, number of games; horizontal axis, difference home team – visitors. Panel B: The difference at the end of the game for NCAA
football in September 2003 is shown. Vertical axis, number of games; horizontal axis, difference home team – visitors.

useful. They also pose a number of theoretical and practical
problems, and considerable creative scholarly work has been
invested in their design and evaluation. Their utility is not in
doubt. They also have clear limitations. Adding apples to
oranges clearly can assess fruit. On the other hand, adding
apples to oranges loses information.
A simple approach to clinical problems might be to ask the
patient if a difference is important. Unfortunately, the
evidence from COPD is that such an approach is not helpful,
at least in many contexts. Because of the insidious nature
of the development of COPD, many patients greatly restrict
their activity (6, 7), thereby eliminating the major cause of
symptomatic dyspnea, namely exertion with its attendant
tachypnea and hyperinflation (8). As a result, patients can
become extraordinarily sedentary and, often, adjust their
expectations to their sedentary lifestyle (6, 7). Reality testing
is intact in that they recognize their limitations. It is striking,
however, that surveys such as Confronting COPD in America
(7) consistently show that individuals with severe dyspnea,
readily recognized with well-used questions, frequently regard
their disease as mild or moderate. Similarly, patients who are
dyspneic at rest or with speech will, 30 to 40% of the time
regard their disease completely or well controlled. These are
not self-evaluations that are appealing from a clinical context.

COPD: Journal of Chronic Obstructive Pulmonary Disease March 2005 53

 The same apparent lack of insight appears to apply to
exacerbations. Exacerbations of COPD are major determinants
of morbidity, mortality, and costs associated with the disease.
That they have major acute and long-standing effects on health
status is well established. Nevertheless, Seemungal and
colleagues prospectively assessed COPD patients with diary
cards and found that only about 50% of the exacerbations that
were experienced, according to the cards, were reported by
the patients when asked (9). Perhaps more surprisingly, the
severity of symptoms associated with the unreported exacer-
bations was similar to that of the reported exacerbations. This
observation has, appropriately, engendered considerable
controversy and discussion. It is consistent, however, with
the concept that important differences, in this case differences
from baseline status, are entirely context specific.
Physician assessment of differences is fraught with
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paradox as much as is patient assessment. In COPD, the
most widely used and best validated measure of disease is the
forced expiratory volume in 1 second. What a meaningful
difference in this measure may be, however, remains contro-
versial. For many years, 200 ml was regarded as the minimum
difference that was acutely important. Differences of 100 ml
or even 50 ml, however, are now accepted, at least by some,
as potentially important (2, 10). This is, at least in part, due to
the fact that people do not breathe with forced spirometric
maneuvers and that the FEV1 as an indirect reflection of
For personal use only.
real breathing.
The rate at which FEV1 declines over time is also an
important variable. In this case, normal individuals decline at a
rate of approximately 20 ml per year, and individuals
progressing to develop symptomatic COPD progress at 60 to
100 ml per year (11). Differences of 20 ml per year have been
regarded as meaningful and have been used as target effect
sizes for clinical interventions (12). None of the large studies
designed to evaluate inhaled glucocorticoids, for example,
were able to achieve such an effect size (13 –16), although
smaller differences that did not achieve statistical significance,
were noted. Meta-analyses have attempted, with varying
results, to combine these studies to increase the power to
determine if these small differences are likely random (17, 18).
It remains undetermined, however, if smaller differences
might not also be important. For example, a 2.5 ml/year dif-
ference, if sustained over a 40-year time frame, would result
in a 100 ml difference. Such a difference might have both
functional and survival implications. Currently available
treatments may be able to achieve an effect size in excess
of 2.5 ml/year (17, 18). A clinical trial to evaluate such an
effect, however, would need to be substantially larger than any
conducted to date.
While there are many theoretical issues regarding the
assessment of clinically important differences, that they have
practical utility is not in doubt. Regulatory agencies are
charged with approving novel medications based on efficacy
and safety. Both statistical rigor and clinical relevance is
generally required. Payors have similar issues. Assuring that
54 March 2005 COPD: Journal of Chronic Obstructive Pulmonary Disease
Table 1. Categorical nature of medical
decisions
Level Choice
Regulator Approve or not
Payor Reimburse or not
Clinician Prescribe or not
Patient Take or not
resources are committed to effective measures is essential. In a
resource-limited environment, moreover, resources must be
committed to the most important interventions. In this context,
the ability of various measures to compare heterogeneous
interventions applied across diverse populations can be used to
prioritize resource allocation. As noted above, however, such
collective assessments, using parameters that combine multi-
ple generalizable domains, are likely to provide a means of
comparison at the expense of concealing the differences that
are most individually important.
Finally, the concept of a minimal important difference im-
plies a categorical classification, i.e., a difference is important
or it is not. For a sports event, this is natural. . .winning or not.
For most of human experience, differences are expressed in a
continuum with no arbitrary ‘‘cut-point.’’ Statisticians recog-
nize the problem that forcing continuous variables into
categorical classifications poses for rigorous analysis. Never-
theless, making categorical decisions in the face of continuous
gradations is the nature of medical decisions (Table 1).
The clinical perspective, therefore, is fraught with paradox
and tension. There is paradox in that categorical decisions
must be made from continuous data. There is also tension as
the more important the issue for an individual, the more subtle
the measure should be, but the less general the applicability to
groups of patients. Medical issues require assessment among
groups of patients. We accept the veterinary application of
interventions to herds of cattle and flocks of chickens with the
expectation of a probability of success across the population.
In medicine, such approaches are regarded appropriate for
some public health interventions, e.g., vaccination. However,
the clinical perspective, the perspective from which this
opinion is offered, is one firmly connected to the individual
patient, and from that perspective, all valuation becomes
intensely personal. In that context, the concept of MCID is one
that applies to epidemiologic questions. It will not define
importance, or even what is important, for an individual
patient. As a means of defining and measuring importance
among groups, however, the MCID promises to be an
important addition to medical methodology.
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