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Feeling good rather than feeling better matters more to patients.

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Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 55, No. 4, August 15, 2006, pp 526 –530
DOI 10.1002/art.22110
© 2006, American College of Rheumatology
ORIGINAL ARTICLE
Feeling Good Rather Than Feeling Better Matters
More to Patients
FLORENCE TUBACH,1 MAXIME DOUGADOS,2 BRUNO FALISSARD,3 GABRIEL BARON,1
ISABELLE LOGEART,4 AND PHILIPPE RAVAUD1
Objective. To determine the most appropriate means to assess the response to treatment in terms of pain and functional
impairment in a chronic rheumatic condition (knee osteoarthritis [OA]) and an acute rheumatic condition (rotator cuff
syndrome [RCS]).
Methods. Two prospective studies were conducted consisting of 1,019 outpatients with knee OA and 271 patients with
acute RCS. The minimal clinically important improvement and the patient acceptable symptom state were determined for
knee OA pain using a visual analog scale, and for knee OA function using the Western Ontario and McMaster Universities
Osteoarthritis Index function subscale; for acute RCS pain, a numeral rating scale was used, and the Neer function
subscale was used for RCS function.
Results. The minimal clinically important improvement was shown to be the change required to achieve the patient
acceptable symptom state, whatever the baseline level of symptom, the outcome (pain or function), or type of condition
(chronic or acute). This acceptable state for pain was higher for chronic (27.0 –36.4 across the baseline score) than acute
(16.7–24.1) conditions. The level of functional impairment considered satisfactory by patients with knee OA was higher
for more disabled patients (43.1) than for less disabled patients (20.4).
Conclusion. Patients consider that they experienced an important improvement only if this improvement allowed them
to achieve a state they consider satisfactory. The most appropriate means to assess the response to therapy seems to be
to assess whether patients feel good (i.e., achieve the patient acceptable symptom state).
KEY WORDS. Minimal clinically important improvement; Patient acceptable symptom state; Patient’s perspective; Outcome criteria.
INTRODUCTION
In chronic diseases, the aim of treatment is to improve
patient symptoms, function, and well-being. Consequently, patient-reported outcomes (PROs) are widely
used in assessing the result of care in clinical practice,
Supported by an unrestricted grant from Merck Sharp
and Dohme Chibret, Paris, France.
1
Florence Tubach, MD, Gabriel Baron, MSc, Philippe Ravaud, MD, PhD: Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, INSERM U738, Université Paris 7-Denis
Diderot, Paris, France; 2Maxime Dougados, MD: Assistance
Publique-Hôpitaux de Paris, Hôpital Cochin, Université
Paris-Descartes, Paris, France; 3Bruno Falissard, MD, PhD:
INSERM U669 Hôpital Cochin, Paris, France; 4Isabelle
Logeart, MD: Merck Sharp and Dohme Chibret Laboratories,
Paris, France.
Address correspondence to Florence Tubach, MD, Département d’Epidémiologie, Biostatistique et Recherche Clinique, INSERM U 738, Groupe-Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75018 Paris, France. E-mail:
florence.tubach@bch.ap-hop-paris.fr.
Submitted for publication July 11, 2005; accepted in revised form December 9, 2005.
526
clinical trials, and longitudinal epidemiologic studies.
PROs are valid and reliable measures, and are sensitive to
clinically important changes (1,2). PROs range from reported symptoms such as pain to the impact of physical
function, social function, mental health, and general
health perception. Because these measures describe what
the patient has experienced as a result of medical care,
they are useful and important supplements to traditional
physiologic or biologic measures of health status.
Several tools are available to assess PROs, but their
results, usually expressed as continuous data, are not
meaningful to most people. How can clinicians determine
what constitutes a clinically relevant treatment success
when using PROs? Two concepts could help in interpreting PRO scores at the individual level: 1) the minimal
clinically important difference (3–5) or minimal clinically
important improvement (MCII) (6), defined as the smallest
change in measurement that signifies an important difference/improvement in symptom; and 2) the patient acceptable symptom state (PASS) (7), an intermediate state between activity of the disease and complete remission,
defined as the score below which patients consider them-
Feeling Good Matters to Patients
selves well. Inference at the individual level allows for
describing the proportion of responders or nonresponders
(patients who have improved or achieved an acceptable
state or not) in addition to mean effects. Such inference
will add useful information and aid in the interpretation of
trial and longitudinal results to decide whether a treatment should be used. These thresholds also allow for
monitoring individual response to therapy over time and
adapting treatment at the individual level (e.g., determining whether to modify or interrupt a treatment). However,
it is not known how the MCII and PASS are interrelated,
and is unclear which one should be recommended.
The aim of this study was to evaluate how the concepts
of MCII and PASS relate to each other in terms of pain and
function scores in a chronic rheumatic condition (knee
osteoarthritis [OA]) and an acute condition (rotator cuff
syndrome [RCS]), and therefore to determine the most
appropriate means to assess the response to treatment in
these conditions in terms of pain and functional impairment.
MATERIALS AND METHODS
Role of the funding source. Merck Sharp and Dohme
Chibret participated in the study design, data collection,
agreement to submit the manuscript, and approval of the
content of the manuscript. They did not participate in the
data analysis or in the writing of the manuscript.
Study population. Data from 2 previous studies were
used. The first study was a prospective cohort of 4 weeks’
duration, involving 1,019 outpatients with painful knee
OA (pain score ⱖ30 mm on a 0 –100-mm visual analog
scale [VAS]), as defined by the American College of Rheumatology criteria (8). The design was described in detail
elsewhere (6,7). Briefly, after an initial baseline visit, patients received nonsteroidal antiinflammatory drugs
(NSAIDs) for 4 weeks. At both the baseline visit and final
visit (week 4), patients assessed pain on movement measured on a VAS, and functional impairment measured
with the Western Ontario and McMaster Universities
(WOMAC) Osteoarthritis Index function subscale (Likert 5
version, where higher scores indicate higher degree of
functional impairment) (9). All scores were normalized to
0 –100 scale. At the final visit, a random two-thirds (n ⫽
688) sample of patients were asked to assess their response
to NSAID treatment using a 5-point Likert scale (possible
responses were none, poor, fair, good, excellent). In the
total sample, patients’ opinion of their state was recorded.
Patients were asked to respond yes or no to the question
“Taking into account all the activities you have during
your daily life, your level of pain, and also your functional
impairment, do you consider that your current state is
satisfactory?”
The second study was a 3-arm randomized, doubleblind, double-dummy, 7-day trial comparing treatment
with 2 different NSAIDs or placebo in 271 patients with an
acute painful flare (pain on movement ⱖ5 on a 0 –10 numeral rating scale [NRS]) with clinically diagnosed RCS
lasting ⬍7 days (10). Patients in all 3 arms were considered
527
together in the analysis (whether they received NSAIDs or
placebo). After a baseline visit, the patients received
NSAID therapy for 7 days. At the baseline and final (day 7)
visits, patients assessed their pain on movement, as measured on an NRS; and functional impairment, as measured
on the Neer rating function subscale (where higher scores
indicate higher degree of functional impairment) (11). All
scores were normalized to 0 –100 scores. At the final visit,
the patients assessed their response to NSAID treatment on
a 15-point Likert scale (where –7 ⫽ a very great deal worse,
0 ⫽ no change, ⫹7 ⫽ a very great deal better), and the
patients’ opinion of their state was also recorded by their
answering “Yes” or “No” to the question “Taking into
account your level of pain and also your functional impairment, if you were to remain for the next few months as
you are today, would you consider that your current state
is satisfactory?”
Both studies were conducted in compliance with the
Good Clinical Practice and the Declaration of Helsinki
principles. In accordance with French national law, all
patients gave written informed consent.
Statistical analysis. An anchoring method based on the
patient’s assessment of response to therapy was used to
determine the MCII and the PASS for each outcome criteria. As described previously (6), the MCII was estimated by
constructing a curve of cumulative percentages of patients
as a function of the change in score (e.g., difference in pain
score) among patients whose final evaluation of response
to therapy was “good.” This procedure was used because
we wanted to focus on the improvement that was clinically important. Logistic regression was used to model the
observations. We targeted the point at the flattening of the
curve at which most subjects stated they had improved. To
determine the change in score corresponding to this point,
we first looked at the 2-parameter logistic model that best
fit the data. Then we determined the square root of the
third derivative of this logistic function that corresponded
to the MCII. One can demonstrate that this point corresponds by construction to the 78.9th percentile of the
change in score, and thus we propose to define the MCII as
the 75th percentile of the change in score, because it is
very close to the point defined above and easier to derive.
The model permitted us first to determine that the target
point was correctly approached by the 75th percentile, and
second to estimate the 95% confidence intervals (95% CI).
The MCII was therefore defined as the 75th percentile of
the change in score between the baseline and final visits
among patients whose final evaluation of response to therapy was good (i.e., in the knee OA study, those who
answered “good,” and in the acute RCS study those who
answered “a great deal better” [⫹5 score] or “a good deal
better” [⫹6 score]). This means that this change (the MCII)
or a higher change was experienced by 75% of these patients.
Following the same methods as for the MCII (by constructing a curve of cumulative percentages of patients as
a function of the score of interest at final visit among
patients who considered their state satisfactory) (7), the
PASS was defined as the 75th percentile of the final score
528
Tubach et al
Table 1. Baseline characteristics of patients in knee osteoarthritis (OA) study and acute
rotator cuff syndrome (RCS) study*
Characteristic
Female, no. (%)
Age, years
Disease duration, years
Pain score (scale 0–100)
Baseline score
Change
WOMAC function score (scale 0–100)
Baseline score
Change
Neer function score (scale 0–100)
Baseline score
Change
Knee OA
(n ⴝ 914)
Acute RCS
(n ⴝ 252)
637 (69.7)
67.8 ⫾ 10.2
4.8 ⫾ 5.8
156 (61.9)
47.6 ⫾ 10.4
58.3 ⫾ 16.9
⫺24.5 ⫾ 22.1
67.9 ⫾ 14.7
⫺36.8 ⫾ 24.9
42.9 ⫾ 16.6
⫺11.6 ⫾ 14.4
42.1 ⫾ 15.0
⫺18.3 ⫾ 19.4
* Values are mean ⫾ SD, unless otherwise indicated. Change ⫽ final score minus baseline score;
WOMAC ⫽ Western Ontario and McMaster Universities Osteoarthritis Index.
(at the final visit) for patients who considered their state
satisfactory. This means that this level of symptom (the
PASS) or a lower level was achieved by 75% of these
patients. Logistic regression was used to model the observations and compute the 95% CI.
Because the baseline score (pain or functional impairment) was previously demonstrated to have a modifying
effect on the MCII and PASS (6,7) for each study we
stratified the analysis on the baseline score of interest (i.e.,
for pain the WOMAC function score and Neer rating function score) divided into tertiles (i.e., low, intermediate,
and high baseline score) to assess whether the baseline
scores affected the PASS estimates. Statistical analyses
were performed with SAS software, release 9.1 (SAS Institute, Cary, NC) and S-Plus, version 6.2 (Insightful, Seattle,
WA).
seems to be the change that makes the pain decrease from
baseline to the PASS.
The MCII (95% CI) for pain in patients with knee OA
varied from –10.8 (⫺12.7, 8.7) to –36.6 (⫺38.3, ⫺34.7), and
RESULTS
Clinical and demographic characteristics of the patients
are shown in Table 1. A total of 914 (90%) patients with
knee OA and 252 (93%) with acute RCS completed the
final visit. Patients lost to followup were excluded from
the analysis; but their baseline characteristics did not differ from those who completed the study (data not shown).
The interrelationship between MCII and PASS is shown
in Figures 1 and 2. For example, in the pain analysis in
patients with knee OA in Figure 1, the low tertile initial
mean score (TIMS; i.e., the mean pain score in the lower
tertile of the baseline pain score) was 40.0 mm, the MCII
was ⫺10.8 mm (i.e., patients considered themselves clinically improved if the decrease in pain exceeded 10.8 mm
on the VAS), and the PASS was 27.0 mm (i.e., patients
considered their state satisfactory if the pain score at the
final visit was below 27 mm on the VAS). Whatever the
tertile, when subtracting the MCII from the TIMS, the
obtained value is very close to the PASS (in this example,
40.0 minus 10.8 ⫽ 29.2 mm; PASS ⫽ 27.0 mm). The
minimal change considered important to the patients
Figure 1. Minimal clinically important improvement (MCII) and
patient acceptable symptom state (PASS) for pain score in knee
osteoarthritis (top) and acute rotator cuff syndrome (bottom), by
baseline score of pain divided into tertiles. TIMS is the tertile
initial mean score in each tertile. The interrelationship is seen by
subtracting the MCII from the TIMS; the value obtained is very
close to the PASS. See Results section for further detail.
Feeling Good Matters to Patients
Figure 2. Minimal clinically important improvement (MCII) and
patient acceptable symptom state (PASS) for functional impairment in knee osteoarthritis (top) and acute rotator cuff syndrome
(bottom), by baseline score of function divided into tertiles. TIMS
is the tertile initial mean score in each tertile.
the MCII (95% CI) in patients with acute RCS varied from
⫺34.3 (⫺38.2, ⫺29.3) to ⫺62.5 (⫺68.3, ⫺54.0). The PASS
(95% CI) for pain in patients with knee OA varied from
27.0 (24.6, 29.9) to 36.4 (33.2, 40.0), and the PASS (95%
CI) in patients with acute RCS varied from 16.7 (13.4, 20.7)
to 24.1 (19.3, 30.0).
For functional impairment in knee OA, the MCII (95%
CI) varied from –5.3 (⫺6.5, ⫺3.8) to ⫺20.4 (⫺22.5, ⫺18.1),
and from –15.1 (⫺16.9, –12.9) to –37.3 (⫺39.4, –34.8) in
acute RCS. The PASS (95% CI) for functional impairment
in knee OA varied from 20.4 (19.1, 21.8) to 43.1 (40.8,
45.7), and from 12.7 (11.0, 14.8) to 21.1 (18.4, 24.3) in
acute RCS.
DISCUSSION
Medical decision making relies increasingly on PROs.
Therefore, providing physicians with PRO-based practical
tools that are comprehensive, and can meaningfully influence clinical decision making is crucial. The importance
of defining a minimal important difference or an acceptable state is widely accepted (12,13). This article adds to
existing knowledge about the MCII and PASS by explicitly
conceptualizing the relationship between the 2 concepts
using 2 types of PROs (pain or function) and 2 diseases
529
(chronic or acute). It also improves our knowledge concerning the most appropriate means to assess the response
to treatment regarding pain and functional impairment in
daily practice or in clinical trials.
The MCII varied greatly across tertiles of baseline scores
in both pain and function assessment and in chronic and
acute conditions. For patients with more severe disease, a
greater change in score was required to consider themselves improved than for patients with less severe disease.
The PASS was more constant across tertiles of the baseline
score for the assessment of pain in both types of diseases.
When subtracting the MCII from the TIMS, the obtained
value is very close to the PASS. This result has been
replicated in another independent study of patients with
knee OA (data not shown). The MCII clearly appears to be
the change needed to achieve the PASS, whatever the
baseline level of symptom, patient-reported outcome (pain
or function), or type of disease (chronic or acute). Patients
possibly consider that they experienced an important improvement only if this improvement allows them to
achieve a satisfactory state, a state in which they feel good.
Consequently, it seems that what is important to patients
is to feel good (concept of PASS) rather than to feel better
(concept of MCII). This finding suggests that the outcome
measure in clinical trials and in daily practice should be a
sense of well-being on the part of the patient rather than a
sense of improved health.
In a chronic condition (knee OA), the PASS for functional impairment varied across tertiles of the baseline
score. This pattern was not observed for functional impairment in an acute condition (RCS), nor for pain in either
condition. It seems that a satisfactory level of pain in the
patients’ perspective is approximately the same, whatever
the initial level of pain or type of disease. Patients’ expectations about pain relief do not vary with time; one cannot
get used to a high level of pain. On the contrary, for
functional impairment in a chronic condition such as knee
OA, the most impaired patients seem to judge as satisfactory a higher level of functional impairment than the least
impaired patients. Patients seem to be resigned to functional impairment and can adapt to it with time. In an
acute condition such as RCS, the PASS for functional
impairment was, for the most part, stable, whatever the
initial level of impairment, as compared with chronic knee
OA. This discrepancy between acute and chronic conditions could be explained by the fact that patients with
chronic diseases have time to adapt to their limitation or,
perhaps because high pain intensity in acute RCS (unlike
that in knee OA) is associated with high functional impairment and low pain with low impairment, because the
limitation is largely due to pain intensity. Therefore, the
observed pattern for functional impairment in acute RCS
may copy the pain pattern, not the impairment pattern.
The PASS for pain was higher for the chronic condition
(knee OA) than the acute condition (RCS). Taking into
account that the baseline level of pain was higher in the
acute RCS study, the intermediate tertile in the knee OA
study (TIMS 58.0, PASS 34.5) corresponds to the low
tertile in the acute RCS study (TIMS 54.9, PASS 16.7) and
the high tertile in the knee OA study (TIMS 77.1, PASS
36.4) corresponds to the intermediate tertile in the acute
530
RCS study (TIMS 70.0, PASS 23.4). The PASS for functional impairment scores also seem to be higher in the
chronic condition study than the acute condition study;
however, the tools used to assess functional impairment
were disease-specific and therefore differed between the 2
studies. Although scores were normalized, such comparisons between the 2 must be made cautiously. Patients’
expectations seem to be different in chronic and acute
conditions.
Our study had several limitations. We studied only 2
conditions (knee OA and acute RCS) both in the rheumatologic field, and musculoskeletal conditions have been
shown to have a great impact on quality of life. Among
patients with a wide range of chronic diseases, those with
musculoskeletal diseases reported the lowest level of
physical functioning and the highest level of pain (14).
Otherwise, knee OA and acute RCS are believed to be 2
relevant pain and function models, one being an acute
condition and the other a chronic condition. The definition of a good response to therapy for pain or functional
impairment may not be specific to the disease, and therefore these results could be applied to other medical conditions in which patients have pain and/or functional impairment.
Another study limitation is that the wording for assessing patients’ opinion of their state (to determine the PASS)
differed slightly between the knee OA and RCS studies. It
has been demonstrated in a study of asthma patients using
an asthma-specific quality of life questionnaire (15) that
the external anchor’s wording has an impact on the clinically meaningful change data. Future studies should evaluate the impact of wording on evaluating the PASS.
Because the MCII seems to be the change required to
reach the PASS, the MCII and PASS might reveal the same
information. However, the importance of the baseline
score on the MCII justifies the use of 1 cutoff per tertile of
baseline score if using the MCII, which is less convenient
than using the same PASS for all patients.
In our opinion, the PASS rather than the MCII should be
recommended to assess response to treatment, first, because it is least sensitive to baseline levels of symptoms,
and second, because it is a simple and intuitively reasonable concept that seems to better reflect what is important
to patients. In daily practice, patients should be asked if
they feel good rather than if they feel better. This clearer
understanding of how the MCII relates to the PASS could
have important implications for defining treatment success and understanding what matters to patients. Our results might encourage the evaluation of treatment strategies as goal-directed therapy (treating and intensifying the
treatment until the patient achieves the PASS) in clinical
practice and determining the proportion of patients
achieving the PASS in clinical trials, in addition to the
difference between baseline and final scores. This finding
could help the physician better understand the expectations for treatment care of chronic patients with pain and
functional impairment and therefore adapt their treatment
to their objectives.
Tubach et al
In conclusion, the results of this study suggest that a
change is considered an important improvement to patients with knee OA or acute RCS if patients can achieve
an acceptable symptomatic state, and the most appropriate
means to assess response to treatment is to ask the patient
if they feel good rather than if they feel better. Patients
seem to accept higher levels of pain and functional impairment in chronic than in acute conditions. In chronic conditions, patients who are more disabled seem to accept a
higher degree of functional impairment than patients who
are less disabled, but not a higher level of pain.
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