Patient-reported outcome measures in severe asthma: an expert consensus

Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ijas20 Journal of Asthma ISSN: (Print) (Online) Journal homepage: www.tandfonline.com/journals/ijas20 Patient-reported outcome measures in severe asthma: an expert consensus Eva Martínez-Moragón, Ignacio Antepara Ercoreca, María Muñoz García, on behalf of the PROs-SA group of experts, Francisco Casas Maldonado, Marta Calvín Lamas, Eusebi Chiner Vives, Carlos Crespo Diz, David Díaz- Pérez, Ibon Eguiluz Gracia, Sara García Gil, Ruperto González-Pérez, Alicia Habernau Mena, Tamara Hermida Valverde, Sònia Jornet Montaña, Valentín López-Carrasco, Icíar Martínez López, Vicente Merino-Bohórquez, Álvaro Moreno-Ancillo, Ana Cristina Mínguez Cabeza, Emilio Monte-Boquet, Jose Luis Revuelta-Herrero & Silvia Sánchez-Cuellar To cite this article: Eva Martínez-Moragón, Ignacio Antepara Ercoreca, María Muñoz García, on behalf of the PROs-SA group of experts, Francisco Casas Maldonado, Marta Calvín Lamas, Eusebi Chiner Vives, Carlos Crespo Diz, David Díaz-Pérez, Ibon Eguiluz Gracia, Sara García Gil, Ruperto González-Pérez, Alicia Habernau Mena, Tamara Hermida Valverde, Sònia Jornet Montaña, Valentín López-Carrasco, Icíar Martínez López, Vicente Merino-Bohórquez, Álvaro Moreno-Ancillo, Ana Cristina Mínguez Cabeza, Emilio Monte-Boquet, Jose Luis Revuelta- Herrero & Silvia Sánchez-Cuellar (26 Dec 2023): Patient-reported outcome measures in severe asthma: an expert consensus, Journal of Asthma, DOI: 10.1080/02770903.2023.2297372 To link to this article: https://doi.org/10.1080/02770903.2023.2297372 © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. View supplementary material Published online: 26 Dec 2023. Submit your article to this journal Article views: 1057 View related articles View Crossmark data Journal of asthma Patient-reported outcome measures in severe asthma: an expert consensus Eva Martínez-Moragón, MD, PhDa, Ignacio Antepara Ercoreca, MD, PhDb, María Muñoz García, PharmD PhDc , on behalf of the PROs-SA group of expertsd, Francisco Casas Maldonado, MD PhDe, Marta Calvín Lamas, PharmD PhDf, Eusebi Chiner Vives, MD PhDg, Carlos Crespo Diz, PharmD PhDh, David Díaz-Pérez, NursingDi, Ibon Eguiluz Gracia, MD PhDj, Sara García Gil, PharmDk, Ruperto González-Pérez, MD PhDl, Alicia Habernau Mena, MD PhDm, Tamara Hermida Valverde, MDn, Sònia Jornet Montaña, PharmDo, Valentín López-Carrasco, NursingDp, Icíar Martínez López, PharmD PhDq, Vicente Merino-Bohórquez, PharmDr, Álvaro Moreno-Ancillo, MDs, Ana Cristina Mínguez Cabeza, PharmDt, Emilio Monte-Boquet, PharmD PhDu, Jose Luis Revuelta-Herrero, PharmDv and Silvia Sánchez-Cuellar, MD PhDw aservicio de neumología, hospital universitario Doctor Peset, Valencia, spain; bservicio de alergología, hospital universitario de Basurto, Bilbao, spain; cservicio de farmacia, hospital universitario ramón y Cajal, IrYCIs, madrid, spain; dnominal group participants; eservicio de neumología, hospital universitario Clínico san Cecilio, Granada, spain; fservicio de farmacia, Complexo hospitalario universitario a Coruña, a Coruña, spain; gservicio de neumología, hospital universitario san Juan de alicante, alicante, spain; hservicio de farmacia, Complejo hospitalario universitario de Pontevedra, Pontevedra, spain; iservicio de neumología, hospital universitario nuestra señora de Candelaria, santa Cruz de tenerife, spain; jservicio de alergología, hospital regional universitario de málaga, málaga, spain; kservicio de farmacia, hospital universitario de Canarias, la laguna, spain; lservicio de alergología, hospital universitario de Canarias, la laguna, spain; mservicio de alergología, Complejo hospitalario de mérida, Badajoz, spain; nservicio de neumología, hospital universitario Central de asturias, oviedo, spain; oservicio de farmacia, hospital universitari Joan XXIII, tarragona, spain; pservicio de alergología, hospital universitario la Paz, madrid, spain; qservicio de farmacia, hospital universitari son Espases, Palma de mallorca, spain; rservicio de farmacia, hospital universitario Virgen de la macarena, sevilla, spain; sservicio de alergología, hospital General nuestra señora del Prado, talavera de la reina, spain; tservicio de farmacia, hospital universitario de araba, Álava, spain; uservicio de farmacia, hospital universitario y Politécnico la fe, Valencia, spain; vservicio de farmacia, hospital General universitario Gregorio marañón, madrid, spain; wservicio de neumología, hospital universitario ramón y Cajal, madrid, spain ABSTRACT Objective: The study aimed to reach a consensus on the most relevant patient-reported outcomes (PROs), the corresponding measures (PROMs), and measurement frequency during severe asthma patient follow-up. Methods: Two Delphi rounds were conducted. The questionnaire was developed based on a systematic literature review, a focus group with patients, and a nominal group with experts. It assessed PROs’ relevance and the appropriateness (A) and feasibility (F) of PROMs using a Likert scale (1=totally agree; 9=totally disagree). The consensus was established when ≥75% of participants agreed (1-3) or disagreed (7-9). Results: Sixty-three professionals (25 hospital pharmacists, 14 allergists, 13 pulmonologists, and 11 nurses) and 5 patients answered the Delphi questionnaire. A consensus was reached on all PROs regarding their relevance. Experts agreed on the use of ACT (A:95.24%; F:95.24%), mini AQLQ (A:93.65; F:79.37%), mMRC dyspnea scale (A:85.71%; F:85.71%), TAI (A:92.06%; F:85.71%), MMAS (A:75.40%; F:82%), and the dispensing register (A:96.83%; F:92.06%). Also considered suitable were: SNOT-22 (A:90.48%; F:73.80%), PSQI (A:82.54; F:63.90%), HADS (A:82.54; F:64%), WPAI (A:77.78%; F:49.20%), TSQM-9 (A:79.37; F:70.50%) and knowledge of asthma questionnaire (A:77%; F:68.80%); however, their use in clinical practice was considered unfeasible. Panelists also agreed on the appropriateness of EQ-5D, which was finally included despite being considered unfeasible (A: 84.13%; F:67.20%) in clinical practice. Agreement was reached on using ACT, TAI, mMRC, and a dispensing register every three months; mini-AQLQ and MMAS every six months; and EQ-5D every twelve months. Conclusion: This consensus paves the way toward patient-centered care, promoting the development of strategies supporting routine assessment of PROs in severe asthma management. © 2023 the author(s). Published with license by taylor & francis Group, llC. CONTACT Eva martínez-moragón [email protected] head of servicio de neumología, hospital universitario Doctor Peset, avda Gaspar aguilar 90, Valencia 46017, spain. supplemental data for this article can be accessed online at https://doi.org/10.1080/02770903.2023.2297372. https://doi.org/10.1080/02770903.2023.2297372 this is an open access article distributed under the terms of the Creative Commons attribution license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. the terms on which this article has been published allow the posting of the accepted manuscript in a repository by the author(s) or with their consent. ARTICLE HISTORY received 16 october 2023 revised 14 December 2023 accepted 16 December 2023 KEYWORDS severe asthma; patient-centered care; patient-reported outcomes; patient-reported outcome measures 2 E. MARTÍNEZ-MORAGÓN ETAL. Introduction Asthma is a serious global health problem, affecting 339 million people worldwide (1). It is a chronic inflammatory disease of the airways, usually associated with bronchial hyperresponsiveness and a variable degree of airflow limitation. Its severity can vary from intermittent to severe persistent, depending on the intensity of the process and response to treatment (2,3). Therefore, disease management requires a multidisciplinary and individualized approach, which must be periodically adjusted to minimize symptoms and prevent exacerbations (4). Severe asthma is characterized by intense symptomatology, frequent exacerbations, multiple comorbidities, and the need for high-intensity treatment (3,5–7). It affects between 3% and 10% of the asthmatic population (2,8) and has a major impact on their health-related quality of life (HRQoL) (7–9). In fact, despite high-intensity treatment, patients with severe disease are usually refractory to therapy, and poor symptom control affects their social, working, physical and mental wellbeing (2,6,8,10). In addition, this condition is associated with higher direct and indirect medical costs compared to mild or moderate asthma (11,12). Given the significant impact of severe asthma on HRQoL, disease management has moved toward a patient-centered approach. As a result, pharmacologic and behavioral interventions have become more widespread, targeting disease control, assessing and treating related risk factors and comorbidities, and improving patients’ HRQoL (4). Additionally, recent studies have recommended using asthma-specific HRQoL measures in clinical trials for moderate-to-severe asthma, in order to assess the long-term response to treatments (7,13–15). In this context, patient-reported outcomes (PROs) play an increasingly important role when assessing the impact of severe asthma healthcare interventions (16–18). PROs are reported directly by the patient regarding their health condition status associated with the health care or treatment (16). Therefore, their implementation in clinical practice is essential to improve shared decision-making, symptom monitoring and management, patient satisfaction, and HRQoL (19). Patient-reported outcome measures (PROMs) are the instruments used to report PROs. These tools must be carefully defined and accurately used to capture relevant patient-reported information and compare it with other measurements (20). PROMs can be generic or disease-specific; they assess symptoms, functional and health status, and social and psychological wellbeing (8,15). Multiple PROMs have been developed and validated in the context of airway diseases such as severe asthma (18). However, the increasing implementation of PROMs in clinical practice (16) makes it necessary to standardize their use. This project aims to reach a consensus on the most relevant PROs, PROMs, and their measurement frequency during severe asthma patient follow-up, taking into account both the patients’ and healthcare professionals’ (HCP) perspectives, within the Spanish National Health System framework. Material and methods The project was led and coordinated by a scientific committee consisting of healthcare professionals who are experts in the management of severe asthma: a pulmonologist (EM), an allergologist (IA), and a hospital pharmacist (MM). The project comprised five phases: 1) literature review; 2) focus group with patients; 3) first scientific committee meeting; 4) two nominal groups with healthcare professionals; 5) Delphi consultation with patients and healthcare professionals, and 6) final scientific committee meeting (Figure 1). Literature review To identify PROs, PROMs, and frequency of measurement used during severe asthma patient follow-up, a systematic literature review according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (21) was performed by consulting the international PubMed/ Medline database. Observational studies, randomized clinical trials, and systematic reviews published in English or Spanish between 03/01/2016 and 03/01/2020 were selected and Figure 1. Project phases. JOuRNAL OF ASTHMA 3 reviewed. Search terms and strategy are shown in Supplementary Table S1. In addition, Clinical Practice Guidelines (CPGs) for severe asthma with information on PROs and PROMs were reviewed. Focus groups with patients The focus group is a variant of the group interview in which participants describe their perceptions, opinions, beliefs, and attitudes toward a specific topic (22). An online focus group with severe asthma patients was conducted to explore the most relevant PROs and how they were assessed during medical visits from the patients’ perspective. Patients were contacted and invited to participate in the focus group by the Spanish patient advocacy group (Federación Española de Asociaciones de Pacientes Alérgicos y con Enfermedades Respiratorias, FENAER). During the focus group, PROs identified in the literature were presented, and various questions were asked for discussion: the impact of the disease and its treatment on their daily life, the disease-related symptomatology, and their perception of the assessment of PROs during medical visits. First scientific committee meeting The first online meeting with the scientific committee was organized to present the literature review results and the focus group conclusions. The objective of this meeting was to establish the most relevant PROs and PROMs to be presented in the nominal group meetings with healthcare professionals. Nominal groups with healthcare professionals The nominal group technique is a qualitative research methodology based on a semi-structured group discussion that guarantees all participants have the opportunity to express their ideas, ensuring that their participation is balanced (23). Two online multidisciplinary nominal group meetings with healthcare professionals were held to reach a preliminary consensus on the most relevant PROs, PROMs, and their frequency of measurement, for their inclusion in the Delphi consultation. Members of the nominal groups were contacted and invited to participate in the nominal group meetings by the coordinating team (on behalf of the scientific committee). They were selected based on their experience in severe asthma management, PRO measurement, implementing strategies to standardize health outcomes, and their availability and interest in the project. The PROs and PROMs selected by the scientific committee were presented to the nominal groups. A selection of PROs and PROMs was established according to their relevance for severe asthma patient follow-up and availability in the current clinical setting. A consensus was reached when at least 70% of the healthcare professionals agreed on the inclusion/ exclusion of the PRO and PROM. Delphi consultation The Delphi technique is a widely used consensus method implemented in research to achieve a general agreement on a particular topic, preserving participants’ anonymity (24). It is typically conducted over consecutive rounds, answered by a panel of participants with relevant expertise in the research field (24,25). The survey rounds iteratively ask the panelists to rate different statements or questions, providing controlled feedback on the previous round’s group results (26). Participants may then adjust their initial ratings based on feedback from the overall group in several subsequent iterations (27). Two-round Delphi consultations with patients and healthcare professionals were conducted between November 2021 and January 2022. Participants were given two weeks to respond to the questionnaire for each round. In addition, three reminders were sent to non-respondents during each period. Two versions of the electronic questionnaire were developed, one for healthcare professionals and the other for patients, to make it easier for the latter to understand the wording. Furthermore, patients were not asked directly about PROMs due to their lack of knowledge on the existing PROMs and the difficulty in deciding on their suitability and feasibility of use in clinical practice. Panelists rated their responses on a nine-point scale (1 = Strongly disagree; 2= Disagree; 3 = Moderately disagree; 4 = Somewhat disagree; 5 = Neither agree nor disagree; 6 = Somewhat agree; 7 = Moderately agree; 8 = Agree; 9 = Strongly agree). The questionnaire of the first round consisted of four parts. 1. Baseline characteristics. Sociodemographic characteristics of healthcare professionals (age, gender, specialty, region, and years of 4 E. MARTÍNEZ-MORAGÓN ETAL. experience) and patients (age, gender, region, and age at diagnosis) were collected. 2. PROs. Panelists (healthcare professionals and patients) were asked to rate the relevance (R) of including each PRO (classified according to the nominal groups’ proposal) in severe asthma patient follow-up. 3. PROMs. Panelists (healthcare professionals only) were requested to rate the appropriateness (A) and feasibility (F) of the predefined PROMs for each PRO (classified according to nominal groups’ proposal). 4. Frequency of measurement. Panelists (healthcare professionals and patients) were asked to rate the appropriateness (A) and feasibility (F) of two PROMs frequencies of measurement proposals. In the case of the questionnaire for patients, the frequency was related to PROs (PROMs were not presented to them). See an example in Supplementary Material 1. In the second-round, an individualized reminder of the option that most participants had indicated accompanied the questions, and the panelists had to decide whether to maintain their assessment or to modify it. Moreover, reasons for disagreement were explored through some additional questions, and panelists were asked to prioritize the PROMs to be employed during severe asthma patient follow-up. Panelists Panelists were identified and invited to participate in the Delphi consultation by the scientific committee members in collaboration with patient advocacy groups (FENAER). Healthcare professionals were selected based on their experience managing severe asthma and their knowledge of PROs and PROMs. Panelists received the link to the Delphi questionnaire, username, and password (exclusive for each participant) by e-mail. Consensus definition The consensus was defined a priori as agreement on relevance (R), appropriateness (A), and feasibility (F) (scores 7-9) in a statement or question by 75% or more of the panel members. Data Analysis The percentage of panelists who selected each option and percentile distributions (25, 50, and 75) were calculated using STATA statistical software, V.14. The percentages described in the text refer to the final scores (score of the round in which consensus was achieved). Final scientific committee meeting A final meeting with the scientific committee was conducted to review the results obtained in the two rounds of Delphi consultation and to define the final standard set of PROs and PROMs for severe asthma patient follow-up. Results Literature review The literature search yielded 119 potentially relevant references, of which 37 were considered eligible for inclusion (Figure 2). In addition, six CPGs with information on PROs and PROMs were reviewed (Supplementary Table S2). Thirty-two PROs and 21 PROMs were identified in the reviewed publications. PROs were categorized into symptom-related PROs (n = 24) and global PROs (n = 8). For the collection of PROs, validated PROMs and other assessment methods such as informal direct questions or a symptom diary were identified (Table 1). Focus group Four patients on treatment for severe asthma (gender: 75% females; age range: 22-62 years; time from diagnosis range: 3-6 years) participated in the focus group. Most of the symptom-related PROs identified in the literature review had been experienced by the patients, except for urticaria, eye symptoms (conjunctivitis), and taste/smell disorders. Patients selected chest tightness, dyspnea, feeling of suffocation, sleep disorders, and fatigue as the five most frequently occurring symptoms. In addition, fatigue, dyspnea, feeling of suffocation, sleep disorders, anxiety, and concentration difficulties were the symptoms with the most significant impact on daily routine, regardless of their frequency of occurrence. Finally, patients proposed gastroesophageal reflux, dental and oral problems (yellow teeth, oral candidiasis), corticosteroid-induced tremors, menstrual alterations (dysmenorrhea and menorrhagia), and migraine as other relevant symptom-related PROs, additional to those identified in the literature. Regarding the assessment of PROs in clinical practice, patients indicated that during follow-up of severe asthma, they were asked how the symptoms of the disease and its treatment affected their daily life. This JOuRNAL OF ASTHMA 5 assessment was done using open response and Likert scale questionnaires, Visual Analog Scales (VAS), and informal questions (asked by both the specialist and the nurse) during the medical visits, but not on a standardized basis. First scientific committee meeting The scientific committee considered as relevant 20 symptom-related PROs out of the 24 previously identified in the literature review and by the focus group. Apnea, localized pain, ear symptoms, and urticaria were not considered for inclusion. In addition, they decided to add five new symptom-related PROs: dental and oral problems, tremors, blocked nose, rhinitis, and sneezing. All global PROs were deemed relevant for presentation to the nominal groups. Furthermore, the scientific committee proposed one new global PRO (work productivity and activity impairment). Figure 2. PrIsma flow diagram. 6 E. MARTÍNEZ-MORAGÓN ETAL. Regarding PROMs, 8 of 21 PROMs identified in the literature were considered relevant: Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) (28); Asthma Control TestTM (ACT) (29); Leicester Cough Questionnaire (LCQ) (30); Sino-Nasal Outcome Test (SNOT-22) (31); Insomnia Severity Index (ISI) (32); European Quality of Life-5 Dimensions (EQ-5D) (33); Treatment Satisfaction Questionnaire for Medication-9 items (TSQM-9) (34); and Hospital Anxiety and Depression Scale (HADS) (35). The Asthma Quality of Life Questionnaire, Adult Carer Quality of Life Questionnaire, Asthma Control Questionnaire, Saint George Respiratory Questionnaire, Dyspnea-12 questionnaire, STOP-BANG questionnaire, Medical Outcomes Study Sleep Scale, 36-item Short Form Survey, Beck Depression Inventory-II, symptom diaries, self-reports, questions during medical visits, and electronic registration were not considered for inclusion. The scientific committee also proposed including 8 additional PROMs: the modified Medical Research Council dyspnea scale (mMRC) (36); Nijmegen Questionnaire (NQ) (37); Pittsburg Sleep Quality Index (PSQI) (38); Morisky-Green Medication Adherence Scale (MMAS) (39); Test of Adherence to Inhalers (TAI) (40); Work Productivity and Activity Impairment questionnaire (WPAI) (41); a visual analogical scale (VAS) for treatment satisfaction; and the medication dispensing register. Thus, the scientific committee selected 25 symptom-related PROs, nine global PROs, and 16 PROMs for presentation and evaluation during the nominal group meetings (Supplementary Table S3). Nominal groups of healthcare professionals Nineteen experts on severe asthma from different specialties (n = 9 hospital pharmacists, n = 4 pulmonologists, n = 4 allergologists, and n = 2 nurses) and various geographical areas of Spain participated in two nominal group meetings. Healthcare professionals assessed the relevance of symptom-related PROs and global PROs (Supplementary Tables S4, S5). Additionally, the most adequate and feasible PROMs and measurement frequency in clinical practice were also discussed by the nominal groups. Consensus was reached for 16 PROs and 12 measurement instruments, proposed by the scientific committee during the two nominal group meetings. In addition, it was agreed to include a questionnaire to assess the patient’s knowledge of the disease. The members of the nominal groups also reached an agreement on a new classification of PROs (symptom-related, comorbidity-related, and other) and PROMs (core and complementary) (Table 2). The core group of PROMs included all those considered essential for any patient with severe asthma (ACT, mini-AQLQ, EQ-5D, mMRC, TAI, and MMAS), along with the pharmacological dispensing register. Complementary PROMs included those to be used in certain circumstances or interventions (SNOT-22: when there are accompanying nasal symptoms; PSQI: when sleep problems are reported; HADS: when psychiatric symptoms are suspected; WPAI: in patients with work/academic impairment; TQSM-9: to assess Table 1. Pros and Proms identified in the literature review. Symptom-related PROs (n = 24) Chest tightness shortness of breath/difficulty in breathing (Dyspnea) Difficulty in exhaling Deep, labored breathing Wheezing feeling of suffocation Coughing Coughing (throat clearing) Phlegm sleep disorders nocturnal awakening snoring apnea Chest pain Pain (general) localized pain (face, back, abdomen) Ear symptoms (Ear pain; Itchy ears, Clogged ears) fatigue Gastrointestinal disorders (diarrhea, vomiting) Dizziness/vertigo urticaria Injection site reaction Eye symptoms (conjunctivitis) taste/ smell disorders Global PROs (n = 8) hrQol anxiety Embarrassment treatment satisfaction Depression Concentration difficulties treatment adherence frustration, irritability, and restlessness PROMs (n = 21) aQlQ Dyspnea-12 EQ-5D symptom diary mini-aQlQ lCQ sf-36 self-report aC-Qol snot-22 tsQm-9 Questions during medical visits aCQ stoP-BanG haDs Electronic registration aCt mos BDI-II sGrQ IsI Pros: Patient-reported outcomes; Proms: Patient-reported outcome measures; hrQol: health-related Quality of life; aQlQ: asthma-related Quality-of- life Questionnaire; mini-aQlQ: mini asthma Quality of life Questionnaire; aC-Qol: adult Carer Quality of life Questionnaire; aCQ: asthma Control Questionnaire; aCt: asthma Control test; sGrQ: st George’s respiratory Questionnaire; Dyspnea-12: multidimensional Dyspnea-12 Questionnaire; lCQ: leicester Cough Questionnaire; snot-22: 22-item sinonasal outcome test.; stoP-BanG: obstructive sleep apnea Questionnaire; mos: medical outcomes study sleep scale; IsI: Insomnia severity Index; EQ-5D: European Quality of life-5 Dimensions; sf-36: medical outcomes study 36-Item short-form health survey; tsQm-9: treatment satisfaction Questionnaire for medication; haDs: hospital anxiety and Depression scale; BDI-II: beck depression inventory-II. JOuRNAL OF ASTHMA 7 satisfaction with treatment; patient’s knowledge questionnaire: when an educational program is proposed). A minimum frequency of 3 months (at each follow-up visit) was established for measuring the core PROMs. In addition, the frequency of evaluation with complementary PROMs was set as follows: SNOT-22 (every 3 months); PSQI: (every 6 months); HADS (every 6 months); WPAI (every 6 months); TSQM-9 (every 6 months); Patient’s knowledge about the disease (every 12 months). Delphi consultation A total of 63 healthcare professionals involved in the management of severe asthma [n = 25 hospital pharmacists, n = 13 pulmonologists, n = 14 allergologists, and n = 11 nurses; mean time in specialty 15.32 (SD: 10.3) years)] and 5 patients (different from those of the focus group) with severe asthma [mean age: 47.2 (range: 23-62) years; mean age at diagnosis: 38 years (range: 14-59) years] participated in the first round of the Delphi consultation. Consensus was reached on all items included in the patients’ questionnaire in the first round; therefore, healthcare professionals (HCP) participated in the second round. The response rate of the second round was 96.8% (n = 61). Results of the Delphi consultation are shown in Supplementary Tables S6–S8. A consensus was reached regarding the relevance of all PROs presented in the Delphi questionnaire for severe asthma patient follow-up, namely: symptom-related [wheezing (97.06%), dyspnea (97.06%), coughing (97.06%), sleep disorders (97.06%), and chest tightness (88.24%)]; comorbidity-related [nocturnal awakening (98.53%), anxiety (94.12%), depression (91.18%), fatigue (88.24%), blocked nose (82.35%), and taste/smell disorders (77.94%)]; other PROs [treatment adherence (98.53%), treatment satisfaction (97.06%), knowledge about asthma (97.06%), HRQoL (95.59%), and work productivity impairment (95.59%)] (Table S6). During the first round, panelists proposed other PROs, such as allergic clinical pyrosis (n = 2), reflux (n = 1), plugged ears (n = 1), sore throat (n = 1), collection of side effects (n = 2), drug allergies (n = 1), and patient knowledge about their treatment (n = 3). However, the number of participants who proposed their inclusion was not sufficiently representative to be added to the second-round questionnaire. Consensus was reached for ACT (A:95.24%; F: 95.24%) for collecting data on dyspnea, nocturnal awakening, sleep disorders, HRQoL, and work productivity impairment (Table S8). Mini AQLQ (A: Table 2. Pros and Proms classification proposed by nominal groups. Pro Core Proms Complementary Proms aCt mini-aQlQ EQ-5D mmrC taI mmas Dispensing register* snot 22 PsQI haDs WPaI tQsm 9 Knowledge of asthma Symptom-related PROs Dyspnea X X X Chest tightness X Wheezing X Coughing X X nocturnal awakening X X X Symptom-related PROs Blocked nose X sleep disorders X X X X fatigue X taste/smell disorders X anxiety X X X Depression X X X X Other PROs hrQol X X X treatment satisfaction X treatment adherence X X X Work productivity and activity impairment X Knowledge about asthma X X Pro: Patient-reported outcome; Prom: Patient-reported outcome measure; hrQol: health-related Quality of life; aCt: asthma Control test; EQ-5D: European Quality of life-5 Dimensions; mini-aQlQ: mini asthma Quality of life Questionnaire;; mmrC: medical research Council modified Dyspnea scale; mmas: morisky-Green medication adherence scale; taI: test of the adherence to Inhalers; snot-22: 22-item sinonasal outcome test; PsQI: Pittsburgh sleep Quality Index; haDs: hospital anxiety and Depression scale; WPaI: Work Productivity and activity Impairment Questionnaire; tQsm-9: treatment satisfaction Questionnaire for medication; Knowledge of asthma: Patients’ knowledge of asthma questionnaire (51); *not a Prom, recommended to assess treatment adherence. 8 E. MARTÍNEZ-MORAGÓN ETAL. 93.65; F: 79.37%) was considered appropriate and feasible for assessing dyspnea, chest tightness, wheezing, coughing, sleep disorders, anxiety, depression, and HRQoL. The mMRC dyspnea scale (A: 85.71%; F: 85.71%) was chosen for assessing dyspnea. To assess adherence, panelists agreed to use TAI (A:92.06%; F: 85.71%), MMAS (A:75.40%; F:82%), and the dispensing register (A: 96.83%; F: 92.06%). Although panelists agreed on the appropriateness of EQ-5D (A: 84.13%; F: 67.20%) for HRQoL, anxiety, and depression assessment, this PROM was not considered feasible for implementation in clinical practice. A brief description of these questionnaires is included in Supplementary Table S9. See Table 2 for the PROs evaluated by each PROM. Regarding the frequency of measurement, panelists reached a consensus on the use of core PROMs at (1) diagnosis and (2) every three months (≥75%), except for MMAS (68.90%) and EQ-5D (65.60%). The alternative frequency proposed for MMAS was every six months (26.3%; n = 5) and every six or twelve months for EQ-5D (40.9%, n = 9). Mini-AQLQ frequency of measurement was not considered feasible in the second-round consultation (72.10%). The complementary PROMs SNOT-22 (A:90.48%; F:73.80%), PSQI (A:82.54; F:63.90%), HADS (A:82.54; F:64%), WPAI (A:77.78%; F:49.20%), TSQM-9 (A:79.37; F:70.50%) and knowledge of asthma questionnaire (A:77%; F:68.80%) were considered adequate to assess the proposed symptomatology or condition, but a consensus was not reached on their feasibility of use in clinical practice (Table S8). Nonetheless, there was consensus on the appropriateness of frequency of measurement for complementary PROMs (≥75%), except for WPAI (73.70%). Reasons for disagreement on PROMs feasibility (use and frequency of measurement) in clinical practice were explored. The main barriers identified were the lack of time and support staff, limited information about PROMs, and other administrative burdens, such as the lack of digital tools allowing systematic and automatic PROMs compilation. Finally, when panelists were asked to prioritize the PROMs to be employed during severe asthma patient follow-up, the following core PROMs order of priority was established: 1st) ACT; 2nd) TAI; 3r) Mini-AQLQ, 4th) mMRC, 5th) dispensing register 6th) EQ-5D; 7th) MMAS. Figure 3. Core group of measurement instruments in order of priority, Pros considered relevant for assessment of severe asthma, and frequency of measurement.