1. Background. Review of PROs for Bronchiectasis

Transcription

1 1. Background Over the past 20 years, tremendous progress has been made in defining and measuring patient-reported outcomes (PROs), with a growing recognition of their importance in health-outcomes research (Goss & Quittner, 2007; Palermo et al., 2008; Quittner et al., 2008). A PRO instrument is defined as any measure of a patient s health status that is elicited directly from the patient and assesses how the patient feels or functions with respect to his or her health condition (Food and Drug Administration [FDA] Guidance; nces/ucm pdf). This may include observable symptoms, behaviors or feelings (e.g., coughing; lack of appetite; expressions of anger), or unobservable outcomes known only to the patient (e.g., perceptions of pain; symptoms of depression). PROs range from single-item symptom ratings to complex, multidimensional health-related quality of life (HRQOL) measures. Regardless of the structure of the instrument, in order to utilize a PRO as a primary or secondary endpoint in a clinical trial, it must meet rigorous psychometric criteria, including a well-defined conceptual framework and strong evidence of reliability and validity (Frost et al., 2007; Revicki et al., 2000). The FDA Guidance and a special issue of Value in Health (Supplement 2, 2007) have provided specific guidelines on both how PROs should be developed (e.g., specification of a conceptual framework, structured interviews, and focus groups with patients) (Turner et al., 2007) and how they should be validated for use in clinical trials. Although generic measures of HRQOL, such as the SF-36 and the Quality of Well-Being Scale (Kaplan et al., 1989; Ware & Sherbourne, 1992), were initially the most widely-used instruments, a substantial body of literature now suggests that disease-specific measures are more sensitive to change, and provide information that is more relevant for clinical interventions (Goss & Quittner, 2007; Hays, 2005). This has led to the development of condition-specific PROs in a variety of conditions (Fayers & Hays, 2005; Palermo et al., 2008; Quittner et al., 2008). Review of PROs for Bronchiectasis Prior to developing a new PRO, existing measures should be evaluated (Turner et al., 2007). A review of the available PROs for bronchiectasis yielded three measures: the Leicester Cough Scale (LCS; Birring et al., 2003), the Chronic Respiratory Questionnaire (CRQ; Guyatt et al., 1987), and the St. George s Respiratory Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 1

2 Questionnaire (SGRQ; Jones et al., 1991). Each instrument was evaluated for use in non-cf bronchiectasis on the basis of its psychometric properties, including reliability and validity; a brief summary of the evaluation is presented herein. Leicester Cough Scale (LCS; Birring et al., 2003). The Leicester Cough Scale (LCS) was developed in 2003 to assess chronic cough in a variety of medical conditions, including bronchiectasis. Three domains were identified: Physical (8 items), Psychological (7 items), and Social (four items). Good item-total correlations supported this domain structure (r values of 0.79 to 0.89) and internal consistency coefficients (Cronbach s alpha) indicated good reliability. Test-retest reliability was assessed in 24 patients over a period of 2 weeks. Intraclass correlation coefficients indicated good stability in LCS scores, with coefficients ranging from 0.88 to The LCS has several strengths, including a minimal respondent burden (i.e., 5 minutes to complete), a recall interval of 2 weeks, and an established minimal important difference (MID) score (Birring et al., 2003). Despite these strengths, the LCS does not include a comprehensive list of respiratory symptoms (See Table 1). Chronic Respiratory Disease Questionnaire (CRQ; Guyatt et al., 1987; Jaeschke et al., 1989; Martin, 1994; Wijkstra et al., 1994; Schünemann et al., 2005). The CRQ is an interviewer-administered questionnaire consisting of 20 items that measure both the physical and emotional aspects of chronic respiratory disease. Four domains are measured: Dyspnea, Fatigue, Emotional Functioning, and Mastery. The CRQ has been used most often for patients with COPD. Psychometric analyses of the CRQ were performed with 40 patients with COPD, who completed the instrument on two consecutive days (Wijkstra et al., 1994). Internal consistency for three of the four domains was good, with Chronbach s alpha values ranging from 0.71 to However, internal consistency for the Dyspnea dimension was low (α = 0.53). Test-retest reliability was also strong for these three domains (Spearman-Brown coefficients above 0.90), but was lower for the Dyspnea domain (0.73). In a 3-year longitudinal study of patients with COPD, pulmonary function tests and the CRQ were administered every 6 months. For the 147 patients who completed the study, scores on the Dyspnea, Fatigue and Emotional Functioning domains declined slowly, but significantly, over the 3 years. The authors calculated it would take 6 years before the cumulative change reached the MID score of 0.5. Further, none of the changes on the CRQ were correlated with changes in pulmonary function tests. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 2

3 The strengths of the CRQ include a recall interval of 2 weeks and the established MID (Jones, 2002). Limitations include the need for an interviewer and the length of time it takes to complete (i.e., 20 minutes or more). This makes it less practical for use in clinical trials (Goss & Quittner, 2007). St. George s Respiratory Questionnaire (SGRQ; Jones et al., 1991; Jones, 2002). The SGRQ is one of the most widely used HRQOL instruments for respiratory patients, and has been translated into many other languages (Ferrer et al., 1996). This instrument contains 76 items which form three component scores: Symptoms, Activity, and Impact. A Total Score can also be calculated for all items. Each item on the SGRQ has been assigned a particular weight, based on responses from patients with asthma and COPD (Jones et al., 1991). Although the SGRQ has been used in studies of patients with non-cf bronchiectasis, the content validity of the questionnaire has not been confirmed in this patient population. The original reports on this instrument included data on test-retest reliability, but no data on internal consistency were presented (Jones et al., 1991; Jones, 2002). Test-retest reliability over a 2 week period was good. A normative database developed in Spain included responses from 461 patients who completed the SGRQ (Martinez- Garcia et al., 2006). Internal consistency coefficients ranged from 0.77 to 0.90 for the subscales and 0.95 for the SGRQ Total. Smaller studies have not found an association between SGRQ scores and FEV1 % predicted (Jones et al., 1991; Jones, 2002). The MID for the SGRQ Total was determined to be 4 points; MID values for the subscales were not reported. Strengths of the SGRQ include an established MID. Limitations of the SGRQ include substantial respondent burden (i.e., 76 items, 30 to 40 minutes to complete), as well as long and variable recall intervals (Part 1: 4 weeks to 1 year, Part 2: these days and usually ). Research in cognitive psychology (Schwarz & Sudman, 1996) has determined that 2 weeks is the longest interval over which respondents can accurately report symptoms and the impact of their disease. The Short Form of the SGRQ specifies no recall interval and has been shown to be less responsive to change than the original version (Meguro et al., 2007). Summary A review of existing PROs for bronchiectasis revealed a number of limitations, including: 1) limited coverage of respiratory symptoms (e.g., CRQ only measures dyspnea), 2) variable and lengthy recall intervals, 3) substantial response burden, and 4) lack of responsivity (e.g., SGRQ) in clinical trials. This review confirmed that a new PRO for non-cf bronchiectasis was needed. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 3

4 Review of Cystic Fibrosis Questionnaire-Revised (CFQ-R) The Cystic Fibrosis Questionnaire (CFQ) (and the CFQ-Revised [CFQ-R]) was initially developed in France (Henry et al., 2003) based on interviews with healthcare professionals, children with CF and their parents, and adolescents and adults with CF. Initial item generation and testing were performed in France. Next, the CFQ underwent independent forward and backward translation, and a two-phase cognitive testing protocol was then conducted in the United States (US) (Quittner et al., 2000). Internal consistency coefficients (Cronbach s alpha) for the domains of the CFQ domains ranged from 0.54 to 0.94, using data collected in the Epidemiological Study of CF (ESCFII; Quittner et al., 2004); this indicated good reliability. Test-retest reliability was assessed in the national validation study with two administrations of the CFQ separated by 10 to 14 days (r values of 0.45 to 0.90, Quittner et al., 2005). Convergence between the CFQ-R and the SF-36 and PedsQL indicated strong correlations between this disease-specific measure and two major generic HRQOL measures. The CFQ-R has also demonstrated good known-groups validity. It significantly differentiated between those with normal, mild, moderate, and severe disease based on FEV1 % predicted. It has also differentiated between male and female patients with CF (Quittner et al., 2005; Quittner et al., 2008). A recent study (Quittner et al., 2009) indicated that a change of 4.0 points on the CFQ-R Respiratory Symptoms Scale, measured on a standardized 0 to 100 scale, is the MID. Strengths of the CFQ-R include establishment of the MID for the Respiratory Symptoms Scale (Quittner et al., 2009) and a comprehensive set of items addressing respiratory symptoms (see Table 1). Three recent reviews of PROs suggested that the CFQ-R is the most well-established PRO currently available (Goss & Quittner, 2007; Palermo et al., 2008; Quittner et al., 2008). However, the questionnaire was not developed for non-cf bronchiectasis patients. Conclusions Because of the intensive effort, development of a new PRO instrument should not be undertaken if there is an existing measure that is appropriate for the proposed trial (Turner et al., 2007). After carefully reviewing the PROs that have been used in bronchiectasis, major limitations were identified. An analysis of the items on the LCS, CRQ, SGRQ and CFQ-R indicated that the CFQ-R currently contains the most comprehensive set of items addressing respiratory symptoms and physical functioning (see Table 1). Development of a bronchiectasis-specific PRO instrument (the QOL-B) thus began with the list of items from the CFQ-R. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 4

5 Table 1. Respiratory Symptoms Measured in PROs LCS CRQ SGRQ CFQ-R Respiratory Symptoms Increased dyspnea with exertion X X Decreased exercise tolerance X X Increased work of breathing X X X Cough X X X Day cough X Night cough X Control of cough/breathing X X X Chest congestion X Frequency of cough X X Cough up mucus X X Wheezing X X Sputum production/volume X X Change in sputum color/consistency X Chest pain from coughing X X Cough disturbed sleep X X X Hoarse voice from cough X Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 5

6 2. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Development Initial Steps As summarized in Section 1, existing PROs for respiratory diseases were reviewed. Unfortunately, currently available PROs for bronchiectasis (LCS, CRQ, SGRQ) were found to have significant limitations. Specifically, recall periods were often variable and lengthy, respondent burden was often significant, the SGRQ has not demonstrated consistent responsiveness to changes in respiratory symptoms, and many hallmark symptoms of bronchiectasis are not included in these instruments (the LCS and CRQ measure a limited set of respiratory symptoms; few items consider sputum production or color, or chest congestion). Second, a review of the literature on signs and symptoms of bronchiectasis was conducted. On the basis of this review, the following items were combined with the items from the CFQ-R (Table 1) to generate the initial version of the Quality of Life Questionnaire-Bronchiectasis (QOL-B Version 0): 1) feeling weak, 2) feeling depressed, 3) embarrassment when coughing, 4) smell of sputum, 5) dyspnea when sitting, 6) dyspnea upon exertion, 7) chest pain while coughing, 8) urinary incontinence, and 9) cyanosis. Two items present on the CFQ-R were not included in the initial version of the QOL B (problems with gas and eating problems). Physician Consensus Panel The preliminary set of items for the QOL-B was administered to a panel of five adult pulmonologists from geographically representative regions of the country (i.e., East Coast, West Coast, Midwest) and from both academic and non-academic practice settings. Questions were followed by a series of probes which measured the relevance, importance, and clarity of each item. Physicians independently completed these ratings on a scale from 1 not at all relevant to 4 very relevant. In addition, physicians were asked to suggest any items that were missing and make recommendations when necessary. After the measures were completed, the items were discussed among the physicians, with a moderator present to note any comments or suggestions. Results of the Physician Consensus Panel On average, most of the items received a rating of 3 or higher on the 4 point scale. Some of the items that received lower ratings (<2.0) were deleted (n = 4) and one item was deleted because of Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 6

7 redundancy with another item assessing respiratory symptoms. The remaining items that received lower ratings were retained, and their relevance and importance were examined from the patient perspective in the Cognitive Testing Study described below. Physicians also suggested rewording 16 items to make them more relevant to an older population with bronchiectasis (e.g., Performing vigorous activities, such as gardening or exercising. ). The Consensus Panel also recommended adding two items related to weight gain, one item related to feeling feverish and one item related to difficulty bringing up sputum. Preliminary Cognitive Testing of the QOL-B The preliminary cognitive testing protocol consisted of face-to-face audio-taped interviews of patients with bronchiectasis, first asking them to respond to each item, followed by interviewer-administered cognitive probes. The cognitive interviews used standard think aloud procedures to determine what the respondents were thinking about when rating each item, how they chose their answers, what would have to be different for them to choose an adjacent answer, how relevant the items were to them, and whether any relevant items had been left out (Quittner et al., 2000; Schwarz & Sudman, 1996). Patients were chosen to represent a range of ages and disease severities. Results of Cognitive Testing at Site 1 At Site 1 (Winthrop University Hospital, Mineola, NY), 10 patients completed the QOL-B Version 0.1 and the cognitive interview. A review of responses by these patients indicated that two items should be added (i.e., feeling anxious and I am concerned that my health will get worse ). These items were suggested by patients during the open-ended portion of the interview. Results of Cognitive Testing at Site 2 At Site 2 (Oregon Health & Science University, Portland, OR), 12 patients completed the QOL-B Version 0.2 and the cognitive interview. A review of the responses by these patients indicated that the general anxiety item should be reworded to reflect anxiety in relation to breathing difficulties ( During the past week, indicate how often you felt anxious about getting enough air. ). No other changes were suggested in the patient interviews. Results of Cognitive Testing at Site 3 At Site 3 (Pulmonary Associates, Phoenix, AZ), 13 patients completed the QOL-B Version 0.3 and the cognitive interview. A review of patient responses suggested addition of an item on intimacy ( It is difficult to be affectionate/intimate with others [kissing, hugging]. ) On the basis of patient responses, items on three domains were deemed not relevant for this patient population and the domains were deleted (Eating Disturbances, Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 7

8 Weight, and Body Image). Deletion of these domains was supported by their poor psychometric properties. The reliability of each domain was calculated using Cronbach s alpha. Overall, the reliability coefficients were adequate to strong for all domains (α = 0.73 to 0.96), except for the Weight (α = -1.6) and Body Image (α = -0.43) Domains. Distribution of responses on the Eating Disturbances Domain was negatively skewed (mean = 89.52, SD=15.70). In addition, scores on these three domains did not correlate as expected with Body Mass Index (BMI). Most of the participating patients did not experience shortness of breath when sitting and this item was also deleted. The Role Functioning Domain originally had four items. Revisions to this domain were made based on analyses of item-to-total correlations across the 35 cognitive interviews. The following items were added to the Role Functioning Domain because they were more strongly correlated with this domain than the domain to which they were originally assigned: I have to stay home more than I want. and It is difficult to make plans for the future (e.g., retirement, vacation, attending family events, etc.). These items were originally included in the Social and Emotional Functioning Domains. After reviewing the cognitive interviews, a question was added prior to the Treatment Burden items. The question asked patients whether they were currently on any treatments for bronchiectasis (inhaled or nebulized medications, chest PT, flutter, PEP mask, oral medications). If patients answered no, they were to skip the treatment burden items. These revisions generated QOL-B Version 1.0, which included 50 items on 8 domains. Open-Ended Interview Study of the QOL-B The Open-Ended Interview Study protocol consisted of open-ended interviews of adults with non-cf bronchiectasis. Patients were asked general questions about how bronchiectasis affects them, as well as questions about the frequency or difficulty of their symptoms and how bronchiectasis affects other specific aspects of their life, such as physical or emotional functioning. A total of 73 disease-related topics were mentioned by the participants. All but 2 of the 73 disease-related topics were mentioned by the first half of the participants (14 of 28) and no new topics were elicited from the last 5 participants. These results indicated that saturation had been reached. The interviews were transcribed and the review team coded the disease-related topics that were mentioned by each participant using Atlas.ti Version 5.0 (Scientific Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 8

9 Software Development, Berlin, Germany). Each interview was coded by at least two reviewers, and complicated concepts were coded by three reviewers. Coding of topics related to clinical concepts was also reviewed by a physician. For each topic, the transcripts were reviewed and compared to the relevant items on the QOL-B Version 1.0. Results of the Open-Ended Interview Study The results from the Open-Ended Interview Study confirmed in almost all cases that the items included on QOL B Version 1.0 captured the salient concerns and symptoms of patients living with bronchiectasis. The study also provided critical, patient-based evidence for additional modifications to the instrument. One item was slightly reworded to match the terms used by patients: dyspnea (shortness of breath) was changed to shortness of breath. Two items that contained multiple concepts were rewritten to include the one concept that best captured patients concerns: lifting and carrying was changed to carrying and affectionate/intimate was changed to intimate. In addition, one item was reworded to better represent the experiences reported by patients: chest pain with coughing was changed to chest pain. Parenthetical expressions providing examples of treatments for bronchiectasis were deleted from two items, since these expressions were redundant with the instructions located immediately above the items. The study also suggested that one topic was missing on QOL-B Version 1.0 and an item was added to the Social Functioning Domain to address it: patients were concerned about being around other people who were sick. Finally, a total of 15 items were deleted, either because they were not supported by the participants comments as concepts important to the experience of having bronchiectasis, or because they were adequately represented by other items. These revisions generated QOL-B Version 2.0, which included 36 items on 8 domains. Additional Modifications to QOL-B Version 2.0 to Generate QOL-B Version 3.0 Further refinements were made to the QOL-B Version 2.0 in accordance with feedback from a regulatory agency; this generated QOL-B Version 3.0. An item assessing shortness of breath with greater activity was moved from the Physical Functioning Domain to the Respiratory Symptoms Domain and an item assessing shortness of breath when talking was added to the Respiratory Symptoms Domain. Other changes included adding concrete examples to better define the meaning of a few items and modifying the wording of some response options to improve clarity. For one item on the Respiratory Symptoms Domain, responses describing sputum color as brownish-dark or as green with traces of blood were combined for scoring purposes. QOL-B Version 3.0 consists of 37 items on 8 domains (Table 2). Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 9

10 Cognitive Testing of QOL-B Version 3.0 and Additional Modifications to Generate QOL-B Version 3.1 QOL-B Version 3.0 was tested in a cognitive debriefing study with 40 adult patients with bronchiectasis. Patients from four different sites (University of Miami, Coral Gables, FL; University of Connecticut, Farmington, CT; Medical University of South Carolina, Charleston, SC; Georgetown University, Washington, DC) were chosen to represent a range of ages and disease severities. Results of this study verified that items and response options on the QOL-B Version 3.0 were well understood by patients and that patients interpretations of the questions on the QOL-B were accurate. No new content emerged in the participant interviews. This study also supported the further minor refinement of one response option for an item on the Social Functioning Domain which assessed intimacy with a partner (added N/A for widows or divorced adults), and the addition of sexual activity to the parenthetical example for the same item ( kissing, hugging, sexual activity ); these changes to item 19 were the only changes made to QOL-B Version 3.0 to generate QOL B Version 3.1 (Table 2). The items on the QOL-B are ordered sequentially to provide a mixture of positively and negatively worded statements or questions to minimize respondents response fatigue (Fayers and Machin, 2007; Epstein and McPartland, 1976). The inclusion of positively worded items also serves to support respondents engagement with a questionnaire that addresses potentially difficult issues related to living with a chronic disease. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 10

11 Table 2. Domains, Items, and Scoring on QOL-B Version 3.0 and Version 3.1 Total Number of Items on Domain Item Numbers on QOL-B Version 3.0 and Version 3.1 Points Corresponding to a Change of One Answer Category for One Item a QOL-B Domain Respiratory 29, 30, 31, 32, 33, 34, 9 Symptoms 35, 36, Physical Functioning 5 1, 2, 3, 4, Vitality 3 6, 8, Role Functioning 5 17, 20, 25, 27, Health Perceptions 4 5, 15, 21, Emotional Functioning 4 7, 10, 11, Social Functioning 4 18, 19, 22, Treatment Burden 3 12, 13, a After standardizing scores on a 100-point scale; assuming responses were provided for all items on the domain (i.e. no missing responses) Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 11

12 3. Psychometric Analyses of the QOL-B Psychometric Properties of QOL-B Version 2.0 Demographics The QOL-B was administered to 131 adult subjects with bronchiectasis at a screening visit in a Phase 2 clinical trial (QOL-B Validation Study; ClinicalTrials.gov identifier NCT ); 89 of these subjects went on to enter a 28-day open label treatment course with an aerosolized antibiotic (aztreonam inhalation solution [AZLI]). Demographic and participant characteristics are provided in Table 3. Table 3. Demographics and Baseline Characteristics for Subjects in the QOL-B Validation Study Subjects Screened Subjects Treated Number of Subjects; n Participant Age, years; mean (SD) 63 (14.1) 64 ( 14.7) FEV1 % Predicted; mean (SD) 60.1 (23.44) 60.4 (21.34) Body Mass Index (BMI); mean (SD) 25.0 (5.27) 24.8 (5.45) Female; n (%) 91 (69.5%) 62 (69.7%) Smoking History Previously smoked cigarettes; n (%) 45 (34.4%) 34 (38.2%) Pack years for previous smokers; mean (SD) 23 (21.4) 21 (21.0) Etiology of Bronchiectasis; n (%) ABPA 2 (1.5%) 2 (2.2%) Aspiration/GERD 3 (2.3%) 1 (1.1%) Ciliary dysfunction 12 (9.2%) 10 (11.2%) Idiopathic 37 (28.2%) 27 (30.3%) Immune Defect 5 (3.8%) 3 (3.4%) Post-infection 35 (26.7) 26 (29.2%) Rheumatoid arthritis 4 (3.1%) 4 (4.5%) Other 23 (17.6%) 16 (18.0%) Missing 10 (7.6%) 0 (0%) Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 12

13 Reliability of QOL-B Version 2.0 Internal consistency is measured by Cronbach s alpha; values for alpha should be 0.7 (Ware, 1980). Internal consistency of the QOL-B Version 2.0 was strong; alphas were 0.70 for all domains except Social Functioning, which had an alpha of 0.69 (Table 4). An item was added on the Social Functioning Domain after the Open-Ended Interview Study (Item 19) and is not included in the alphas presented here. Table 4. Internal Consistency of the QOL-B Version 2.0 QOL-B Domain Number of Respondents (N = 131) Cronbach s Alpha Respiratory Symptoms Physical Functioning Vitality Role Functioning Health Perceptions Emotional Functioning Social Functioning a Treatment Burden a Analyses did not include Item 19 (item added after Open-Ended Interview Study) Note: Total N = 131 screened subjects. Test-retest reliability is a measure of the stability or reproducibility of a measure over a short period of time during which the patient s status on the underlying construct has not changed. It is measured with intraclass correlations between the individual patients scores at 2 time points within that period. Test-retest reliability was calculated over a 2-week interval. Disease status, based on several enrollment criteria, was evaluated at both time points to ensure that subjects had not undergone any significant changes in health status. Stability of participants QOL-B responses was calculated using intraclass correlation coefficients (ICCs). Correlations of 0.70 or greater indicate good stability of scores over the two-week interval (Landis, 1977). As presented in Table 5, ICCs ranged from 0.67 to 0.88 across domains with all domains meeting criteria for stability except Vitality, which was slightly lower. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 13

14 Table 5. Intraclass Correlation Coefficients for QOL-B Version 2.0 Domain Scores for Clinically Stable Subjects QOL-B Domain Number of Respondents (N = 89) Intraclass Correlation Coefficient Respiratory Symptoms Physical Functioning Vitality Role Functioning Health Perceptions Emotional Functioning Social Functioning a Treatment Burden a Analyses did not include item 19 (item added after Open-Ended Interview Study) Note: Total N is 89 enrolled and treated subjects The QOL-B was administered at 2 visits that were separated by 2 weeks (±3 days for each visit). Psychometric properties of QOL-B Version 3.0 The psychometric properties and MID values for all domains of QOL-B Version 3.0 will be re-evaluated based on data from two ongoing Phase 3 clinical studies in which the QOL-B is being administered (ClinicalTrials.gov identifiers: NCT and NCT ). Initial psychometric analyses were performed using data from the second cognitive testing study. Demographics The QOL-B Version 3.0 was administered to 40 adult patients with bronchiectasis in the second cognitive testing study. Demographic and participant characteristics are provided in Table 6. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 14

15 Table 6. Demographics and Baseline Characteristics for Participants in the Second QOL-B Cognitive Testing Study Participants (N = 40) Age, years; mean (SD) 64.6 (12.3) FEV1 % Predicted; a mean (SD) 69.1 (19.8) Body Mass Index (BMI); a mean (SD) 25.2 (6.1) Female; n (%) 33 (82.5) Etiology of Bronchiectasis; n (%) Idiopathic 28 (60.0%) Other 10 (25.0%) Primary Ciliary Dyskinesia 2 (5.0%) a N = 39 Reliability of QOL-B Version 3.0 Internal consistency of the QOL-B Version 3.0 was strong; Cronbach s alpha s were 0.70 for all domains except Social Functioning, which had an alpha of 0.66 (Table 7). Table 7. Internal Consistency of the QOL-B Version 3.0 QOL-B Domain Number of Respondents (N = 40) Cronbach s Alpha Respiratory Symptoms Physical Functioning Vitality Role Functioning Health Perceptions Emotional Functioning Social Functioning Treatment Burden Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 15

16 4. Administration of the QOL-B Background The Quality of Life Questionnaire Bronchiectasis (QOL-B) is a bronchiectasis-specific quality of life measure encompassing both generic and bronchiectasis-specific domains. The eight domains include Physical Functioning, Role Functioning, Vitality, Emotional Functioning, Social Functioning, Treatment Burden, Health Perceptions, and Respiratory Symptoms. This is a self-administered questionnaire for adults ages 18 and older. This questionnaire takes approximately 10 minutes to complete. Schedule of Assessments As an intermittent measure of clinical status, the QOL-B can be completed annually or more frequently at clinic visits, which may be quarterly. When used as an endpoint in a clinical trial, the QOL-B should be completed as specified in the study protocol. Instructions for Administration The following suggestions are provided to maximize the quality of the data collected with the QOL-B and to minimize missing data. General Instructions Give the QOL-B to the respondent before completing any procedure or clinical examination (e.g., pulmonary function tests, height and weight measurement, interval history). This ensures that interactions between respondents and healthcare professionals do not influence the QOL-B responses. Tell the respondent that it is important to answer all questions. Remind the respondent that only one response may be given for each question. State that there are no right or wrong answers. If the respondent does not understand a question, assistance may be offered, but do not rephrase, interpret, or give examples. Reread the question exactly as Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 16

17 worded and ask the respondent to indicate the response that best describes them. Instructions for Self-Administration Provide the respondent with a pen and a quiet place to complete the QOL-B. Noisy waiting rooms in clinics can often be distracting. The respondent should be alone when completing the QOL-B. Spouses or other accompanying individuals should wait in a separate area during administration of the QOL-B. This minimizes the possibility that others may influence the respondent s answers. If the respondent has a visual impairment, it may be helpful to provide a reading magnifier or ruler. Instructions for Reviewing the Completed Questionnaire Review the completed questionnaire for missing responses When the respondent has completed the QOL-B, the member of the health care team administering the measure should review it to ensure that all questions have been completely answered. If there are any missing responses, point them out and ask the respondent to complete them. However, respondents are free to decline to answer any question that makes them feel uncomfortable. If it is not possible to query the respondent, incomplete questions should be left blank. Review the completed questionnaire for double answers If the respondent has marked two choices for a single question, please ask him or her to clarify which response is correct. Keep the QOL-B response sheet confidential The respondent may choose to discuss their answers with another person (e.g. spouse, significant other, or parent); however, their QOL-B response sheet should be kept confidential. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 17

18 QOL-B Administration DOs and DON Ts DOs DON Ts Do have respondents complete the QOL-B before they: Fill out any other health data forms, See their physician/nurses, Undergo any procedures and/or Undergo any clinical exams. Do be warm, friendly, and helpful. Do request and encourage respondents to complete the QOL-B based on their own experience with bronchiectasis. Do mention there are no right or wrong answers. Do read and repeat a question verbatim for respondents, as needed. Do tell respondents to answer a question based on what they think the question means. Do have respondents fill out the QOL-B unassisted. Do encourage respondents to answer all questions. Do check to make sure only one response has been marked. Do thank respondents for answering all questions. Don t discuss the respondents health, health data, or emotions with them before completion of the QOL-B. Don t force or command respondents to complete the QOL-B or a particular question. Don t accept an incomplete QOL-B without first encouraging the respondent to complete unanswered questions. Don t interpret or explain a question. Don t allow a third party (e.g., spouse, family members) to help with completion of QOL-B. Don t share the respondent s responses with family members. All responses to the QOL-B should be kept confidential. Don t minimize the importance of the QOL-B. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 18

19 5. Frequently Asked Questions If the respondent does not understand a question, may I offer assistance? Yes, but do not rephrase, interpret, or give examples. Reread the question exactly as worded and ask the respondent to indicate the response that best describes them. If a spouse or significant other asks to see the respondent s completed QOL-B, may I let them see it? No. The respondent may choose to share or discuss their answers with a spouse or significant other; however, their QOL-B responses should be kept confidential. If two responses have been marked, how is the correct response identified? Please make sure you review the QOL-B immediately after it is completed so you can ask the respondent to choose a single response. If the respondent has left the clinic or hospital, the answer that indicates the worst response will be used for data entry and scoring. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 19

20 Manual Scoring Instructions for QOL-B Version 3.1 Step 1: Item-by-item responses The values assigned to participants responses for each question are listed below. Enter them on the Item-by-Item Worksheet. For questions 1 4: A lot of difficulty = 1, Moderate difficulty = 2, A little difficulty = 3, No difficulty = 4 For questions 5 11: Always = 1, Often = 2, Sometimes = 3, Never = 4 For questions 12 15: Use the assigned number designated for each specific response For questions 16 26: Completely true = 1, Mostly true = 2, A little true = 3, Not at all true = 4 For question 27: Use the assigned number designated for each specific response For question 28: Always = 1, Often = 2, Sometimes = 3, Never = 4 For questions 29 31: A lot = 1, A moderate amount = 2, A little = 3, Not at all = 4 For question 32: Clear = 1, Clear to yellow = 2, Yellowish-green = 3, Brownish-dark = 4, Green with traces of blood = 5, Don t know = 6 For questions 33 37: Always = 1, Often = 2, Sometimes = 3, Never = 4 Step 2: Scoring multiple responses or skipped questions If two responses are marked and there is no opportunity to ask the respondent which one is correct, the worst response should be selected for data entry and scoring. This provides a conservative estimate of their response to this item. For example, item #29 asks: Have you felt congestion in your chest? The response choices range from A lot to Not at all. If the respondent marks a lot and a moderate amount you should enter a lot for this question. Please note that some items are reverse-keyed and therefore, the worst response is not necessarily the lower number. If participants skip a question, do not assign a response value (i.e. leave it blank). Step 3: Scaling item 32 and reverse coding Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 20

21 Item 32 (resp32) has 5 possible answers that are scored and all other items on the QOL-B questionnaire have only 4 possible answers. Possible scores for resp32 are 1, 2, 3, 4, 5 and 6, whereas for other questions the possible scores are 1, 2, 3, and 4. Resp32 and eight other items are also reverse coded; because of the wording for these particular items, reverse coding is necessary to make higher scores correspond to better health outcomes. Reverse coding is conducted for resp32, and for health5, vital8, treat12, treat14, health15, role20, health24, and role27. These items are marked with an asterisk on the Item-by-Item Worksheet and the reverse-coded values are shown in the box on the worksheet. For item 32: Original value = Reverse-coded value 1 = 5 2 = 4 3 = 3 4 = 2 5 = 1 6 = Not scored For items 5, 8, 12, 14, 15, 20, 24, 27: Original value = Reverse-coded value 1 = 4 2 = 3 3 = 2 4 = 1 Step 4: Preparing to calculate scaled scores and missing values Transfer the values from the Item-by-Item Worksheet to the Scaled Score Worksheet. For reverse-coded items, use the reverse-coded values. Do not enter any values for missing responses; leave the line blank. If the responses are missing for more than half the items in a scale, the score for that scale should not be calculated. Missing values are not imputed. Note that missing responses within a scale will change the number of points corresponding to a change of one answer category for one item for that respondent. Step 5: Calculate the scaled scores Calculate scores for the eight QOL-B domains using the formulas on the Scaled Score Worksheet. Note that a total QOL-B score is not calculated. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 21

22 Item-by-Item Worksheet Numbers correspond to items on the QOL-B Version 3.1 questionnaire. Fill in the values using the scoring rules described in steps * = * = * = * = 15.* = * = * = * = * = 33. *Reverse-Coded Values For items 5, 8, 12, 14, 15, 20, 24, 27: Original Value = Reverse-Coded Value 1 = 4 2 = 3 3 = 2 4 = 1 For item 32: Original Value = Reverse-Coded Value 1 = 5 2 = 4 3 = 3 4 = 2 5 = 1 6 = Not scored Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 22

23 Scaled Scores Worksheet Page 1 of 3 Enter the values from the Item-by-Item Worksheet. Use the reverse-coded values, if applicable. Do not enter any values for missing responses; leave the line blank. Assess the number of missing values and calculate scores as described in Steps 4 and 5 (see page 2). Physical Functioning Domain (5 items) If 3 or more responses are missing, do not score this domain. Scaled score = [(( )-1)/3] x 100 = mean of responses Role Functioning Domain (5 items) If 3 or more responses are missing, do not score this domain. Scaled score = [(( )-1)/3] x 100 = mean of responses Vitality Domain (3 items) If 2 or more responses are missing, do not score this domain. Scaled score = [(( )-1)/3] x 100 = mean of responses Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 23

24 Emotional Functioning Domain (4 items) Scaled Scores Worksheet Page 2 of 3 If 3 or more responses are missing, do not score this domain. Scaled score = [(( )-1)/3] x 100 = mean of responses Social Functioning Domain (4 items) If 3 or more responses are missing, do not score this domain. Scaled score = [(( )-1)/3] x 100 = mean of responses Treatment Burden Domain (3 items) If 2 or more responses are missing, do not score this domain. Scaled score = [(( )-1)/3] x 100 = mean of responses Health Perceptions Domain (4 items) If 3 or more responses are missing, do not score this domain. Scaled score = [(( )-1)/3] x 100 = mean of responses Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 24

25 Respiratory Symptoms Domain (9 items) *Item 32: (score/4)*3= enter result below Scaled Score Worksheet Page 3 of 3 If 5 or more responses are missing, do not score this domain. Scaled score = [(( )-1)/3] x 100 = mean of responses (including item 32, adjusted) Note: No total score is calculated. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 25

26 SPSS Programming Code for Scoring QOL-B V3.1 Note: To enter data, refer to Step 1: Item-by-item responses, and for decision rules regarding multiple responses or skipped questions, refer to Step 2: Scoring multiple responses or skipped questions (see page 1). SPSS Program Codes for Scoring the QOL-B Version 3.1 Note: To enter data, refer to Step 1: Item-by-item responses, and for decision rules regarding multiple responses or skipped questions, refer to Step 2: Scoring multiple responses or skipped questions (see page 1). *Recoding Some Items. recode health5 vital8 treat12 treat14 health15 role20 health24 role27 (1=4) (2=3) (3=2) (4=1). Execute. recode resp32 (1=5) (2=4) (3=3) (4=2) (5=1) (6=SYSMIS). Execute. *Calculating Scores. compute physical = (mean.2 (phys1, phys2, phys3, phys4, phys16)-1)/3*100. compute role = (mean.2 (role17, role20, role25, role27, role28)-1)/3*100. compute vitality = (mean.1 (vital6, vital8, vital9)-1)/3*100. compute emotion = (mean.2 (emot7, emot10, emot11, emot23)-1)/3*100. compute social = (mean.2 (social18, social19, social22, social26)-1)/3*100. compute treat = (mean.1 (treat12, treat13, treat14)-1)/3*100. compute health = (mean.2 (health5, health15, health21, health24)-1)/3*100. compute respirat = (mean.4 (resp29, resp30, resp31, ((resp32)/4*3), resp33, resp34, resp35, resp36, resp37)-1)/3*100. Execute. Quality of Life Questionnaire-Bronchiectasis (QOL-B) Page 26

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