(360) Inter-clinician diagnostic concordance assessing adults presenting with possible cystic fibrosis

Background: Improved systematic assessment of non-CF bronchiectasis is resulting in greater identification of adults who may not strictly fulfil cystic fibrosis (CF) diagnostic criteria yet display evidence of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function. Establishing the appropriate diagnosis and care needs in these cases is complex, and has consequences for patient care, including potentially determining access to highly effective modulator therapies. We hypothesized that the degree of concordance over the appropriate diagnosis in these cases would be weak and that this might lead to significant variation in the recommended follow-up schedule.

Methods: We surveyed adult-CF physicians in Canada, the USA, the UK, and Ireland using a custom digital questionnaire (Qualtrics XM^™, Qualtrics, Provo, UT USA). Responders were presented with anonymized vignettes of adult patients referred for assessment of possible CF and were asked to select the most appropriate diagnosis from the clinical vignettes, selecting from “CF”, “CF diagnosis not resolved - further testing needed”, “CFTR-related disorder” (CFTR-RD), “CF carrier” and “None of the above”. Inter-responder agreement over diagnosis, ease of classifying cases and appropriate follow-up were assessed. Analyses were performed in R Studio running R 4.1.2 using Krippendorf’s alpha statistic in the IRR package, where alpha 0 = perfect disagreement and 1 = perfect agreement. Finally, in a subsequent exploratory section, respondents were presented with a list of clinical findings (e.g., “bronchiectasis – diffuse”, “nasal polyposis”) and asked to subjectively rate the significance of each finding in contributing to a “Clinical Presentation of CF”.

Results: Between November 23^rd, 2021, and February 28^th, 2022, 67 responses were provided, with 55 completing assessments of all cases (82.1% completion rate) equating to 385 individual case reviews. 54 responders then completed all subsequent exploratory questions (80.1%). Agreement over diagnosis was weak (alpha=0.282), with six of the seven cases assigned a minimum of four of the five possible diagnoses, while all available diagnoses were selected in three cases (figure 1). Agreement over ease of classification (alpha=0.01) and recommended follow-up (alpha=0.054) for each case were also weak.

Only five features received >50% endorsement as “strongly supportive” of a clinical presentation of CF: pancreatic insufficiency, infertility/congenital bilateral absence of the vas deferens, diffuse bronchiectasis, and sputum positivity for Pseudomonas aeruginosa or Burkholderia cepacia complex organisms.

70% of respondents agreed that “distinction between CF and CFTR-RD has become significantly more pertinent with the advent of highly effective CFTR-modulators”, while 76% agreed that increasing CFTR-RD identification could have significant resource implications for CF centers. There was equipoise regarding the statement “the current guidelines for CF/CFTR-RD diagnosis provide a good framework for high inter-clinician agreement regarding final diagnosis and classification”.

Conclusions: Our results demonstrate low diagnostic concordance among CF specialists assessing cases of possible adult CF and highlights an area in need of improvement.

Acknowledgements: The authors wish to thank representatives of CF Canada, the CF Foundation, the European CF Society - Clinical Trials Network and the Irish Thoracic Society for their support with survey distribution.

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