The MCID of the Transition Dyspnea Index is a Total Score of One Unit

Abstract

The Baseline (BDI) and Transition (TDI) Dyspnea Indexes provide interview-based measurements of breathlessness related to activities of daily living. The BDI is a discriminative instrument that includes specific criteria for each of three components at a single point in time. The TDI is an evaluative instrument that includes specific criteria for each of three components to measure changes from a baseline state. Observational studies have shown that patients with COPD generally experience a gradual progression of breathing difficulty as measured by the TDI over time. Randomized controlled trials have demonstrated excellent measurement characteristics of the TDI; these include responsiveness (ability to detect change) and construct validity (a change in the TDI correlates with changes in other variables). Supporting evidence for one unit as the minimal clinically important difference (MCID) of the TDI is based on: expert preference; use of the physician's global evaluation score as an anchor; and distribution estimates (standard error of measurement and 0.5 of the standard deviation). As an alternative to the interview process, self-administered computerized (SAC) versions of the BDI/TDI have been developed to provide direct patient-reported ratings of dyspnea. To further establish the MCID of the interview-administered and/or the SAC TDI, we recommend that a patient's report of global ratings of change by used as an independent standard or anchor.

• Measurement of dyspnea
• Transition dyspnea index
• Responsiveness
• Construct validity
• Anchor-based minimal clinically important difference

Introduction

The Baseline (BDI) and Transition (TDI) Dyspnea Indexes provide measurements of breathlessness based on activities of daily living. The unique features of the BDI/TDI are the consideration of three components—functional impairment, magnitude of task, and magnitude of effort—that provoke breathing difficulty (Table 1) [[1]]. An interviewer asks the individual questions about his/her breathlessness as part of activities of daily living, and then selects a grade for each component according to the patient's responses. The BDI is a discriminative instrument that includes specific criteria for each of the three components at a single point in time. The TDI is an evaluative instrument that includes specific criteria for each of the three components to measure changes from the baseline state. Total scores for the BDI (range, 0 to 12) and for the TDI (range, − 9 to + 9) are obtained by adding the scores for each of the three components. The TDI can be used to measure dyspnea serially over time or throughout the course of a study, but each time the TDI refers back to the initial baseline condition.

Table 1.  Features of the Baseline and Transition Dyspnea Indexes.

Grades	Components
Baseline Dyspnea Index (BDI)—a discriminative instrument that measures dyspnea at an initial or baseline time
0 to 4	Functional impairment—effect of dyspnea on ability to perform daily activities and to work
0 to 4	Magnitude of task—range of various physical tasks that provoke dyspnea (e.g., walking on level, climbing stairs, etc.)
0 to 4	Magnitude of effort—degree of effort required to perform activities and tasks (e.g., need to pause or rest)
0 to 12	BDI total score
Transition Dyspnea Index (TDI)—an evaluative instrument that measures changes in dsypnea compared to the initial or baseline state
− 3 to + 3	Changes in functional impairment
− 3 to + 3	Changes in magnitude of task
− 3 to + 3	Changes in magnitude of effort
− 9 to + 9	TDI total score

In two studies the TDI has demonstrated that patients with COPD generally experience a gradual progression of breathing difficulty. For example, in an observational study Mahler et al. [[2]] reported that 76 male patients who had stable COPD at the time of enrollment had a significant decrease (− 0.7 ± 2.9 units; p = 0.04) in the TDI total score over a two-year time period. In a randomized clinical trial Casaburi et al. [[3]] showed a decline of ~ 0.3 in the TDI over 1 year in 325 patients with COPD who received placebo therapy. These remarkably similar results in different patient populationsdocument that patients with COPD generally experience worsening in the severity of breathlessness over time.

Measurement Characteristics of the BDI

Reliability

Dyspnea scores from a discriminative instrument, such as the BDI, should be similar in a stable patient upon repeat testing and between different interviewers. Guyatt and colleagues [[4]] found statistically significant correlation coefficients and kappa values for BDI total scores measured six different times at 2-week intervals in 43 symptomatic patients with respiratory disease. Eakin et al. [[5]] reported that the BDI demonstrated the highest level of reliability among six different dyspnea instruments.

In addition, it is important that there is good agreement for the BDI total scores between different interviewers (inter-rater reliability). In the original description of the instruments Mahler et al. [[1]] observed substantial congruence among different interviewers for the BDI total score based on percentage agreement (range, 85–94%) and the weighted kappa value (range, 0.53–0.73) [[1]]. More recently, we found a high correlation (r = 0.75; p < 0.0001) for the BDI total score among different experienced interviewers in 25 patients with COPD [[6]].

Validity

Factor analyses have clearly established that the BDI total score provides unique and distinct information than obtained from measures of lung function, exercise performance, and health status [7-9]. Furthermore, the BDI total score correlates with scores from other dyspnea scales such as the Medical Research Council scale, the oxygen cost diagram, and World Health Organization scale (concurrent validity) [[5]][10&11].

Measurement Characteristics of the TDI

Responsiveness

Responsiveness refers to an instrument's ability to detect change. For example, if a treatment results in an important difference in dyspnea, then the physician and/or investigator needs to be confident that the difference can be detected even if it is small.

In randomized controlled trials bronchodilator medications [[3]][12-20] and combination therapy with a long-acting β-agonist and an inhaled corticosteroid [21&22] provide relief of dyspnea (Table 2). However, exercise training as part of a pulmonary rehabilitation program [23-29] and inspiratory muscle training [30-35] generally achieve even greater benefits in relief of dyspnea based on the TDI total score than provided by pharmacotherapy in patients with COPD (Table 3).

Table 2.  Responsiveness of the TDI in Randomized Controlled Trials Evaluating Pharmacotherapy in Patients with COPD.

	TDI total score
Intervention/study		Treatment group		Placebo Group	p value
Anti-cholinergic
Ipratropium bromide
Mahler [[16]]–12 weeks			Δ 0.8		< 0.05
Tiotropium
Casaburi [[3]]–1 year			Δ 1.1 ± 0.2		< 0.001
Vincken [[18]]–1 year			Δ 0.9 ± 0.3 (Compared with ipratropium bromide)		0.001
Brusasco [[19]]–6 months			Δ 1.1 ± 0.3		< 0.001
O'Donnell [[20]]–6 weeks			Δ 1.6 ± 0.4		< 0.001
β-agonist
Formoterol
Aalbers [[15]]–12 weeks
	Dose (BID) p value	Δ 0.7	Δ 0.5	Δ 1.2
		4.5 mcg	9 mcg	18 mcg
		NS	NS	0.002
Salmeterol
Mahler [[16]]–12 weeks			Δ 0.2		NS
ZuWallack [[14]]–12 weeks		+ 1.3 ± 0.2		No placebo group	NP
Mahler [[21]]–6 months			Δ 0.5		NS
Brusasco [[19]]–6 months			Δ 0.7 ± 0.3		< 0.05
Theophylline
Kirsten [[13]]**–2–3 days		− 0.9 ± 1.9		+ 0.4 ± 2.6	< 0.05
Mahler [[12]]–4 weeks		+ 2.4 ± 2.8		− 0.7 ± 3.4	< 0.05
ZuWallack [[14]]–12 weeks		+ 1.1 ± 0.2		No placebo group	NP
Inhaled corticosteroid
Fluticasone
Mahler [[21]]–6 months (500 μg dose)			Δ 1.0		0.002
Hanania [[22]]–6 months (250 μg dose)			Δ 0.7		NS
Inhaled long-acting β-agonist and corticosteroid
Salmeterol and fluticasone combination
Mahler [[21]]–6 months (50/500 μg dose)			Δ 1.7		< 0.001
Hanania [[22]]–6 months (50/250 μg dose)			Δ 0.8		< 0.048

NP = not provided; NS = not significant.

Δ refers to difference in TDI between treatment and placebo groups unless otherwise stated.

^†At weeks 2, 4, 6, 8, 10, and 12 vs. placebo, p < 0.05.

*At weeks 2, 4, 8, and 10 vs. placebo, p < 0.05.

**The treatment group had theophylline withdrawn which caused a decrease in the TDI (i.e. more breathlessness), while the control group continued to receive theophylline.

Table 3.  TDI Responses to Various Standard Treatments for Patients with COPD Based on Randomized Controlled Trials.

Treatment	Δ TDI	Reference #
Bronchodilators
LAAC	+ 1.3	[[3]][19&20]
LABA	+ 0.6	[15&16][[19]][[21]]
LABA/ICS	+ 1.2	[21&22]
Theophylline	+ 1.6	[12&13]
Exercise training	+ 3.2	[23-29]
IMT	+ 2.7	[30-35]

LAAC = long-acting anticholinergic.

LABA = long-acting β-agonist.

ICS = inhaled corticosteroid.

IMT = inspiratory muscle training.

ΔTDI = mean difference in Transition Dyspnea Index between treatment and placebo (for bronchodilator studies) or control group (for exercise training and inspiratory muscle training studies) according to the references listed.

Construct Validity

Any change in the TDI total score should be expected to correlate with changes in other variables, such as lung function, albuterol rescue use, health status, and exercise performance, with various treatments. In fact, extensive testing has demonstrated that the TDI total score correlates significantly with changes in FEV₁, inspiratory mouth pressure, number of puffs or supplemental use of albuterol, etc., in different populations of patients with respiratory disease [[3]][[12]][[21]][[23]][[25]][30&31].

What is the MCID for the TDI?

Supporting evidence for one unit as the MCID of the TDI is shown in Table 4. First, we have had numerous discussions with expert pulmonary physicians involved in clinical research of patients with COPD. In these focused discussions specific criteria of the TDI were reviewed. For example, an increase of one unit for each component of the TDI is described in the instrument as “slight improvement.” In particular, a one-unit improvement in functional impairment describes a patient who either [[1]]: was able to return to work or resumes some customary activities with more vigor due to an improvement in breathlessness. These expert physicians have considered such an improvement as being clinically important for the individual patient.

Table 4.  Supporting evidence for the Minimal Clinically Important Difference of the TDI.

Outcome measure: Transition Dyspnea Index (TDI)

Range: − 9 to + 9

SEM: 0.12 (tiotropium group) to 0.15 (placebo group)

Effect size: 0.47

Distribution-based MCID: 1.2 based on 0.5 of SD (2.4)

Anchor-based MCID: 1.0

Expert physician-based MCID: 1.0

Patient-based MCID: not determined

RECOMMENDED MCID: 1.0

Values for standard error of measurement (SEM) and standard deviation (SD) based on data from 1-year tiotropium-placebo controlled studies [From Ref. [[3]]].

Second, Witek and Mahler [36&37] used the physician's global evaluation (PGE) score as an anchor-based approach to compare with changes in the TDI total score in multicenter trials of the tiotropium clinical program. In 921 patients with COPD (50 centers in the United States) changes in the TDI total score were in the range of one unit when the group was stratified by a minimal change (− 1 or + 1) in the PGE [[36]].Moreover, TDI responders (≥ one unit increase in the TDI total score) used significantly less rescue albuterol, had fewer exacerbations, and had better health status as measured on the St. George's Respiratory Questionnaire.

In two sister studies involving 89 centers in 18 countries, Brusasco et al. [[19]] compared tiotropium, salmeterol, and placebo therapies in patients with COPD. In a retrospective analysis of these data Witek and Mahler [[37]] showed that a change of one category (i.e., two units on an 8-point scale) inthe PGE was associated with a mean TDI total score of ~ one unit (0.9 to 1.3 mean total score). As noted in the previous studies, TDI responders used less supplemental albuterol, had fewer exacerbations, and had significantly improved health status compared with nonresponders (< one unit increase in the TDI total score).

Third, Norman and colleagues [[38]] conducted a systematic review of the literature that identified studies that computed a MCID for health-related quality of life. These investigators concluded that the “threshold for discrimination for changes in health-related quality of life is very close to half a standard deviation (SD)” [[38]]. Since the questionnaire that measured the baseline status (BDI) was different than the questionnaire that measured changes in dyspnea (TDI), the above statistical method could not be readily used. However, the TDI in the 1-year tiotropium-placebo clinical trials had a SD of 2.4; one-half of the SD was 1.2 units [[36]]. This value approximates the 1.0 value identified by expert physicians and the PGE anchor approach used in clinical trials [36&37].

Recommendations for Future Studies

One concern raised about the BDI/TDI is that the instruments require that an interviewer question the patient and then select a grade for each of the three components [[1]],[[10]]. Although the interview process enables the physician or health care worker to obtain unique and specific information about the person's breathing, the actual selection of the grades requires some judgment by the interviewer. Written instructions are available and interview video tapes have been developed by pharmaceutical companies in order to provide training and guidance for the interviewer. In clinical trials at least two different interviewers should be trained and available at each study site in case one of the interviewers is ill or away. There has been wide interest in using the BDI/TDI in clinical trials such that these instruments have been translated into over 25 different languages using standard linguistic validation as supervised by Mapi Research Institute (Lyon, France).

As an alternative to the interview process, we have developed self-administered computerized versions of the BDI/TDI, each of which can be completed in 2–3 minutes by the patient [[6]]. For each component of the TDI the patient presses a key on the computer keyboard to move a vertical bar, which is positioned next to a visual analog scale which has anchors (mild, moderate, or major) for improvement (up arrow) or for deterioration (down arrow) in breathlessness. The self-administered computerized versions of the BDI/TDI are direct patient-reported outcomes that eliminate the need for an interviewer, but retain the key advantages of the instruments—i.e., the consideration of three dimensions that affect the patient's breathlessness.

One approach to determine the MCID of a parameter is to use anchor-based measure(s) that require an independent standard or anchor that is moderately correlated with the instrument being explored [[39]]. With the TDI we used an anchor-based approach was used that included the physician's global evaluation score, rescue albuterol use, number of exacerbations, and health status [36&37]. However, we recommend that a patient's report of global ratings of change be used as an anchor to confirm the MCID of the TDI.