The Bronchiectasis Exacerbation Diary: a novel patient-reported outcome for non-cystic fibrosis bronchiectasis

Patient eligibility and recruitment

Patients were eligible for the study if they were US residents aged ≥18 years, had a diagnosis of bronchiectasis (confirmed by computed tomography (CT) scan) with ≥2 exacerbations and/or hospitalisations in the previous 2 years and had no other uncontrolled respiratory conditions. Key inclusion and exclusion criteria are detailed in table 1, and full inclusion and exclusion criteria are included in the supplementary table. Best efforts were made to recruit patients with two-lobe involvement and a blood eosinophil count of ≥150 cells·μL⁻¹ and to exclude patients with cardiac disease (i.e., cor pulmonale, class III or IV congestive heart failure, symptomatic right ventricular failure, symptomatic uncontrolled cardiac arrythmias, pulmonary oedema in the past 4 weeks or cardiomyopathy), clinically important pulmonary disease other than bronchiectasis (e.g., pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, α−1 anti-trypsin deficiency or primary ciliary dyskinesia), allergic bronchopulmonary aspergillosis requiring systemic steroid treatment in the past 6 months or radiological findings suggestive of another respiratory disease.

Patients were recruited by Global Perspectives using clinician referrals and social media outreach. Interested patients were informed about how to contact Global Perspectives, who then explained the study, confirmed the patient's willingness to participate via patient completion of an online or paper pre-consent form, and scheduled and conducted a screening call to determine patient eligibility. The interviews required patients to have access to a telephone and online screening platform.

Ethics

Following the screening call, each patient who participated in the study was required to provide written informed consent; their clinician was required to provide written confirmation of their diagnosis. After patient eligibility was confirmed with the necessary documentation, Global Perspectives scheduled an interview for the patient. Patients received an honorarium for their participation.

Ethics approval was obtained from the New England Institutional Review Board (IRB number: 120190514). This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, consistent with Good Clinical Practice and applicable regulatory requirements, as well as in accordance with the regulations of the US FDA as described in 21 CFR 50 and 56, applicable laws and the IRB requirements.

Study design and methods

The Bronchiectasis Exacerbation Diary (BED) PRO instrument was developed by AstraZeneca in collaboration with IQVIA through comprehensive qualitative research in accordance with FDA guidance, including a targeted literature review and three semi-structured interviews with clinicians in Europe who had expertise in respiratory conditions and experience of working with patients with bronchiectasis, with a goal of developing a preliminary bronchiectasis conceptual model (figure 1) [16]. The development of the preliminary conceptual model was an iterative process that incorporated key findings from the literature and clinician insight into the patient experience with bronchiectasis. Patient interviews (60–90 min long) were then conducted to revise and adjust the conceptual model based on the patient experience and to debrief the BED instrument (figure 2). Three (IQVIA) interviewers trained in interviewing patients for concept elicitation and cognitive interviews conducted the interviews.

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FIGURE 1

Development of the draft Bronchiectasis Exacerbation Diary. PRO: patient-reported outcome.

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FIGURE 2

Workflow for patient interviews. BED: Bronchiectasis Exacerbation Diary.

The objectives of the patient interviews were as follows:

1. identify the symptoms of bronchiectasis experienced by patients and understand the impacts of bronchiectasis on overall patient health and functioning;

2. determine the words and phrases used by patients to describe their bronchiectasis experience;

3. document the patient experience of symptoms and impacts identified through interviews, especially those related to exacerbations;

4. update the conceptual model by incorporating direct patient feedback and finalise the BED; and

5. assess the content validity of the BED among patients with bronchiectasis and revise as appropriate.

A pre-specified, semi-structured patient interview discussion guide was provided to interviewers to ensure study objectives were met in a consistent manner. Additional details about the patient interview discussion guide are included in the supplementary material. It contained open-ended questions to avoid bias and support a free-flowing discussion between the interviewer and the patient. Patient interviews consisted of two sections: concept elicitation and cognitive debriefing. Concept elicitation interviews were aimed at characterisation of symptoms and impacts related to bronchiectasis, including timing and triggers, evolution over time, degree of disturbance (scale of 0 to 10, with 10 being the most disturbing) and effect on the patient's life. The cognitive debriefing interviews assessed the patient's comprehension of the BED instrument, including instructions, instrument items, response scales and recall period, and provided an opportunity for patients to make suggestions for improvement of the instrument.

Data analysis

De-identified transcripts were coded using a qualitative coding dictionary, and concepts were categorised into symptoms and impacts. For each concept (i.e., symptoms and impacts), counts of the number of patients who mentioned the concept (including total, spontaneous and probed mentions) and the mean disturbance ratings on a scale from 0 (not disturbing at all) to 10 (extremely disturbing) were tabulated. Additional information about coding is reported in the supplementary material. Concepts were considered salient if they were mentioned by ≥50% of patients and had a mean disturbance rating of ≥5 out of 10. Salient concepts were considered important components of the patient experience and were therefore prioritised for inclusion in the finalised BED. To assess evidence of concept saturation, the 20 interviews conducted were split into four chronological waves consisting of five patients each. Saturation was defined as the point at which conducting additional patient interviews did not introduce new concepts.