King's Brief Interstitial Lung Disease questionnaire: responsiveness and minimum clinically important difference

KBILD: previous studies

KBILD was developed in response to a paucity of easy-to-use, disease-specific health status questionnaires for ILD patients [14]. It was originally developed using Rasch analysis methodology (KBILD-R) [14] and re-examined using an impact factor approach (KBILD-I) [16]. Although the content of the two questionnaires varies slightly, both consist of 15 items with three domains and a total score, and both yield similar results [14, 16]. KBILD-R was used in this study as KBILD-I has not been released for use.

KBILD has been shown to correlate with lung function indices and health-related quality of life questionnaires (FVC % pred r=0.38–0.51, diffusing capacity of the lung for carbon monoxide % pred r=0.42–0.52, SGRQ r= −0.59– −0.89 and SF-36 r=0.33–0.70) [14], to be reproducible (intraclass correlation coefficient 0.86–0.92) [14], and to be responsive to ambulatory oxygen [3] and longitudinal change [15].

KBILD was the primary end-point in a crossover randomised controlled trial examining the effects of 2 weeks of ambulatory oxygen on health-related quality of life in 76 patients with fibrotic ILD (58% IPF, 69% male with mean±sd age 68±10 years, FVC 73±19% predicted and KBILD-T score 50.5±11.2) [3]. Following the intervention, there was a significant improvement in KBILD domain and total scores with ambulatory oxygen compared with placebo air (mean score change in KBILD-T 3.7 (95% CI 1.8–5.6); p<0.0001) [3]. This cohort had similar baseline characteristics and response to intervention as the patients in our study.

Similarly, Patel et al. [15] evaluated the responsiveness of KBILD over a mean of 9 months in 57 patients with ILD (17% IPF, 23% male with mean±sd age 62±11 years, FVC 80±25% predicted and KBILD-T score 60±23) and provided MCID estimates. Regarding change in KBILD-T, a total of 38% of patients deteriorated, 25% improved and 37% remained the same, but the mean (95% CI) change in KBILD-T was not reported [15]. Using anchor- and distribution-based methods the mean (range) MCID estimate for KBILD-T was 8 (6–10) points [15].

The MCID estimates of our study, excluding those of KBILD-C, contrast with those of Patel et al. [15]. Regarding KBILD-C, the MCID estimates in our study were comparable to those reported by Patel et al. [15] and may be explained by the use of distribution-based approaches. In contrast, the MCID estimates of the other domain and total scores were lower in our study. Several reasons may explain this variation. First, there were differences in the cohort characteristics and proportion of disease types between the studies, which may have influenced the MCID estimates. Our cohort had a greater proportion of male and IPF patients, who were older with greater lung function deficit. Second, our study had a larger sample size (n=209 in our study versus n=57 in Patel et al. [15]), which would have increased the statistical power to provide a more precise MCID estimate. Third, whereas Patel et al. [15] looked at longitudinal change over 9 months, our study examined the response of KBILD to an intervention, i.e. pulmonary rehabilitation. Finally, whereas we used a health-related quality of life questionnaire with similar construct to KBILD as our external anchor, the previous study utilised FVC and a global rating scale. FVC was not used as an external anchor in our study because it does not change with pulmonary rehabilitation, whereas health status was expected to improve. As such, change in FVC % pred would most likely not meet our criteria for a valid external anchor. In addition, we did not use a global rating scale to determine the MCID because it lacks objectivity. The presence of an intervention, timescale, the choice of external anchor and the direction of change are all plausible factors that might influence the MCID estimate.

Significance of findings

PROMs aim to “directly report the status of a patient's health condition without the interpretation of a patient's response by a clinician or anybody else” [28]. PROMs are particularly relevant in clinical care as they can highlight the impact of the disease on the patient, enabling the monitoring of health-related quality of life and tailoring of patient care. Additionally, in clinical trials PROMs may capture perceived treatment effects not detected by other outcome measures, e.g. biomarkers of disease [29]. They are also likely to become established as important secondary end-points in future trials [30] to ensure patients' perspectives are considered [31] and because research funding organisations have started to place a stronger emphasis on meaningful impact for patients [30].

The PROMs most frequently used to measure health-related quality of life in ILD include a mixture of generic, respiratory and IPF-specific tools, many of which have been designed for or adapted from other chronic respiratory diseases. Additionally, the validity, responsiveness, MCID and predictive capacity of these questionnaires in ILD patients remain unknown in the majority of cases. Furthermore, pulmonary rehabilitation programmes are typically designed for COPD patients, are largely generic and are not designed specifically for ILD patients. Accordingly, PROMS that are not ILD-specific, such as CRQ [13], COPD Assessment Test [25] or Clinical COPD Questionnaire [27], are currently being used in clinical practice.

Strengths

This study, the largest pulmonary rehabilitation study involving ILD patients, provides new knowledge on the psychometric properties of KBILD in ILD and IPF by demonstrating its responsiveness to an intervention and providing MCID estimates. The capacity of an outcome measure to detect improvement is an important aspect of concurrent validity and is necessary for data interpretation in both clinical and research settings [17]. This is facilitated by the MCID, which enables the assessor to understand the clinical significance of response data and forms an important part of the evidence required by regulatory agencies for approval for use in clinical trials [32]. These properties are essential traits in an outcome tool and accordingly KBILD has potential as a measure of disease-specific health-related quality of life in the pulmonary rehabilitation setting in ILD and IPF. We used CRQ, a measure of health-related quality of life, as an external anchor. Although it was not developed specifically for ILD patients, it measures a similar construct to KBILD which may influence the accuracy of the KBILD MCID estimates. Furthermore, this study provides 22 and 26 consistent MCID estimates of KBILD domain and total scores in patients with ILD and IPF, respectively. We used multiple anchor- or distribution-based methods to calculate MCID estimates as there is no consensus on the methodology on how to perform this type of analysis [17]. Distribution-based techniques are an indirect way of estimating MCID that do not consider patients' experiences. Instead, the change in the outcome of interest is based on a form of statistical variability, e.g. standard deviation [17], which may vary depending on patient ability or baseline measurements [33]. Anchor-based approaches account for the clinical significance of the intervention, and are considered clinically robust and meaningful, but a suitable external anchor that correlates significantly with the outcome measure of interest is required [17]. Revicki et al. [17] recommended that a correlation coefficient of r>0.3 is sufficient. As KBILD is a measure of health-related quality of life and accordingly captures multisystem properties, it is unlikely that a single anchor would be sufficient to estimate the MCID [34]. Therefore, use of multiple external anchors as well as different anchor- or distribution-based approaches used in this study provides a degree of reassurance on its validity.

Limitations

There are some limitations to this study. First, the study participants were symptomatic outpatients recruited from a pulmonary rehabilitation programme at the Royal Brompton and Harefield NHS Foundation Trust, a specialist, cardiorespiratory, tertiary care centre. Therefore, the data need to be corroborated in other settings and ILD populations (e.g. more symptomatic patients managed in the acute hospital setting). Second, the CRQ-Dyspnoea domain requires patients to rate how breathless they become doing five activities of their choice. A criticism of CRQ is that patients' activity choice may change over time. In this study, we ensured the activities selected in the CRQ-Dyspnoea domain in the pre-pulmonary rehabilitation assessment were kept the same for the post-pulmonary rehabilitation assessment. Third, despite demonstrating significant improvements with pulmonary rehabilitation, it was not possible to provide anchor-based MCID estimates for KBILD-C. This may have occurred because the external anchors did not capture the construct tested by this domain. Furthermore, the KBILD MCID may have been overestimated because it was calculated using distribution-based methods. These methods can produce estimates higher than the considered MCID [17]. Finally, few patients reported that they deteriorated with pulmonary rehabilitation; accordingly, these data estimate the MCID for improvement only. Further studies are required to assess whether patients perceive deterioration differently to the size of improvement in this context.

In summary, KBILD is responsive to pulmonary rehabilitation in patients with ILD, including those with IPF, with a mean MCID estimate of 3.9 points for KBILD-T.