Optimizing the Diagnostic Journey in Interstitial Lung Disease: The OPTIMIZE-ILD-1 Trial

Time elapsed from the randomization to the date of the multidisciplinary team (MDT) meeting where a final diagnostic consensus is reached. This measure evaluates the internal efficiency of the clinical work-up and the diagnostic decision-making process prior to patient communication.

Time elapsed from the randomization to the date of initiation of the first pharmacological or non-pharmacological treatment. This measure will be calculated only for participants for whom treatment is clinically indicated according to the multidisciplinary team (MDT) consensus.

Total time required for the patient and caregivers to complete the diagnostic work-up (Home-to-Home), including the cumulative time spent travelling from home to the hospital and back for all diagnostic visits, as well as the cumulative in-hospital time needed to complete scheduled tests, evaluations and procedures.

This outcome assesses the private economic impact and "Financial Toxicity" on the family unit. It evaluates:

1. Direct Non-Medical Costs: Private expenses related to transportation, parking, and logistics required for hospital attendance.
2. Indirect Costs (Productivity Loss): Economic value of the time dedicated to the diagnostic process by both the patient and the primary caregiver, including work absenteeism and disruption of daily obligations.
3. Caregiver Burden: Impact on the support network, analyzed to identify potential gender gaps in caregiving.

Data is expressed in Euros (€). Higher values indicate a greater socioeconomic burden and higher "Time Burden" imposed by the diagnostic circuit.

This measure calculates the total economic impact on the healthcare system during the diagnostic pathway. It includes:

1. Direct Clinical Costs: Outpatient visits, multidisciplinary committee reviews, and diagnostic tests (CT scans, lung function tests, and biopsies) based on standard hospital billing rates.
2. Operational Costs: Administrative staff time dedicated to the coordination and scheduling of the circuit.
3. Inefficiency Costs: Opportunity costs derived from non-attended appointments (no-shows), missed or incomplete diagnostic procedures requiring rescheduling, and unscheduled emergency visits.

All values are calculated in Euros (€). Higher scores indicate higher healthcare resource utilization and lower operational efficiency

Estimated carbon dioxide equivalent emissions (CO₂-equivalent emissions) generated by patient and caregiver travel to the hospital during the diagnostic process.

The EQ-5D-5L is a standardized instrument for measuring generic health status. It consists of a descriptive system covering 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and the EQ Visual Analogue Scale (EQ-VAS). The 5 dimensions are scored on 5 levels (1=no problems to 5=extreme problems). The EQ-VAS records the patient's self-rated health on a scale from 0 (worst health) to 100 (best health). Results are reported as an index score (ranging from <0 to 1, where 1 is perfect health) and the VAS score. Higher scores in the index and VAS indicate better quality of life.

The K-BILD is a validated 15-item health-related quality of life questionnaire specifically designed for patients with interstitial lung disease (ILD). It assesses three domains: psychological, breathlessness and activities, and chest symptoms. Each item is scored on a 7-point Likert scale. A total score and three domain scores are calculated. Scores are transformed to a range of 0 to 100, where 100 represents the best health status and 0 the worst. A higher score reflects a better quality of life related to the respiratory disease.

The GAD-7 is a validated 7-item self-report questionnaire used to screen for and measure the severity of generalized anxiety. Each item is scored on a 4-point Likert scale (0=Not at all to 3=Nearly every day). The total score ranges from 0 to 21. Established severity thresholds are: 0-4 minimal, 5-9 mild, 10-14 moderate, and 15-21 severe anxiety. Higher scores indicate greater anxiety severity.

The PHQ-9 is a validated 9-item self-report questionnaire used to screen for and measure the severity of depression. Each item is scored on a 4-point Likert scale (0=Not at all to 3=Nearly every day). The total score ranges from 0 to 27. Established severity thresholds are: 0-4 minimal, 5-9 mild, 10-14 moderate, 15-19 moderately severe, and 20-27 severe depression. A score of >=10 is commonly used as the threshold for clinically significant depression. Higher scores indicate greater depressive symptom severity.

The CFS is a 9-point scale used to assess the overall level of fitness or frailty in older adults or patients with chronic conditions. It is based on clinical judgment of the patient's mobility, activity, and independence in daily living. The scale ranges from 1 (Very Fit) to 9 (Terminally Ill). A score of ≥5 is generally considered to represent frailty. Higher scores indicate a higher degree of clinical frailty.

Social risk assessed with the Social-Familial Evaluation Scale, TSO version (Escala de Valoración Sociofamiliar TSO; Giménez-Bertomeu et al., 2020), a revalidated Spanish instrument derived from the Gijón Social-Familial Evaluation Scale. It evaluates 5 domains: family structure and function, social contacts, help needed and received for activities of daily living, income, and housing. Each domain is scored 1 to 5; the total score ranges from 5 to 25, with higher scores reflecting greater social vulnerability. Cut-offs: ≤12 = no social problem; >12 and ≤15 = risk of social problem; >15 = social problem.

The Oslo-3 is a brief 3-item instrument that assesses the level of perceived social support. It evaluates the number of close confidants, the sense of concern from others, and the ease of obtaining practical help from neighbors. The total score ranges from 3 to 14 and is categorized as: 3-8 poor support, 9-11 moderate support, and 12-14 strong support. Higher scores indicate greater perceived social support.

The PREM-Patient is a study-specific, self-administered 11-item questionnaire developed by the investigators to assess the patient's healthcare experience in the ILD diagnostic pathway. As an ad hoc instrument, it evaluates 11 quality domains: 1) Clarity, 2) Coordination, 3) Accessibility (staff contact), 4) Logistical Efficiency, 5) Process Agility, 6) Prioritization (accompained visits), 7) Economic Impact, 8) Life Balance, 9) Information Redundancy, 10) Safety, and 11) Clinical Support. Each item is scored on a Likert scale from 0 (Completely Disagree) to 10 (Completely Agree). The total score is the sum of the 11 items (score ranges from 0 to 110), where higher scores indicate a more optimized and patient-centered experience. A 12th item assesses Global Satisfaction separately.

Study-specific 7-item screening questionnaire, developed with the Hospital Social Work Department, to identify patients who may benefit from social work assessment. Items: 1) prior contact with social services; 2) awareness of public resources for disability or chronic disease; 3) digital literacy barriers to appointment management; 4) need for home support or difficulty leaving home; 5) disability or dependency recognition; 6) perceived caregiver overburden; 7) willingness to receive social work consultation. Referral is offered when any item is positive, or when the Social-Familial Evaluation Scale (TSO version) indicates risk of social problem (>12), the Oslo-3 indicates poor social support (<=8), or the CBI-15 indicates high caregiver burden (>=25). The proportion meeting referral criteria, the effective referral rate and the unmet needs identified will be reported.

The PREM-Caregiver is a study-specific, self-administered 11-item questionnaire developed by the investigators to assess the healthcare experience of the caregiver in the ILD diagnostic pathway. This ad hoc instrument evaluates 11 quality domains: 1) Clarity, 2) Coordination, 3) Accessibility (staff contact), 4) Logistical Efficiency, 5) Process Agility, 6) Prioritization (accompained visits), 7) Economic Impact, 8) Life Balance, 9) Information Redundancy, 10) Safety, and 11) Clinical Support. Each item is scored on a Likert scale from 0 to 10. The total score ranges from 0 to 110, where higher scores indicate a more optimized experience and lower treatment burden for the family unit. A 12th item assesses Global Satisfaction separately.

Assessed only for participants with a primary caregiver who provides independent informed consent for this specific evaluation.

The CBI-15 is a validated 15-item multidimensional questionnaire that assesses caregiver burden across five domains: time-dependence burden (3 items), personal life burden (3 items), physical burden (3 items), social burden (3 items), and emotional burden (3 items). Each item is scored on a 5-point Likert scale (0=Not at all disruptive to 4=Very disruptive). Total score ranges from 0 to 60. A total score >=25 has been identified as a cut-off point to discriminate caregivers with probable mental disorder (sensitivity 70.6%, specificity 70.7%). The multidimensional structure allows identification of the specific type of burden most affected by the intervention. Spanish version validated by Vazquez et al. (Int J Environ Res Public Health 2019;16:217). Assessed only for participants with a primary caregiver who provides independent informed consent.

The PREM-Clinician is a study-specific, self-administered 11-item questionnaire developed by the investigators to assess the professional experience of all staff involved in the ILD diagnostic pathway, including clinicians and other involved healthcare professionals (including nursing, pharmacy, and social work). As an ad hoc instrument, it evaluates 11 quality domains: 1) Inter-professional Coordination, 2) Administrative Burden, 3) Protocol Clarity, 4) Process Agility, 5) Information Provided to Patient, 6) Caregiver Integration, 7) Operational Sustainability, 8) Resource Efficiency, 9) Perceived Patient/Family Satisfaction, 10) Clinical Safety, and 11) Multidisciplinary Support. Each item is scored on a Likert scale (0-10). Total score: 0 to 110. Higher scores indicate a more optimized and collaborative workflow. A 12th item assesses Global Satisfaction separately.

A single-item measure in which the patient rates their overall impression of how the organization of the diagnostic process compared to their expectations, using a 7-point Likert scale (1=Much better than expected to 7=Much worse than expected). This measure serves as an anchor to determine the minimal clinically important difference (MCID) of the study-specific PREMs. Lower scores indicate a more favorable impression of the diagnostic pathway organization.

A single-item measure in which the primary caregiver rates their overall impression of how the organization of their family member's diagnostic process compared to their expectations, using a 7-point Likert scale (1=Much better than expected to 7=Much worse than expected). Lower scores indicate a more favorable impression. Assessed only for participants with a primary caregiver who provides independent informed consent.

A single-item measure in which each healthcare professional involved in the ILD diagnostic pathway rates their overall impression of the pathway's organizational quality compared to their prior expectations, using a 7-point Likert scale (1=Much better than expected to 7=Much worse than expected). Lower scores indicate a more favorable professional impression of the coordinated circuit.

Pre-planned exploratory analysis measuring the variation in the primary outcome (time to diagnostic communication) and key secondary outcomes stratified by sociodemographic determinants -- including socioeconomic status (Social-Familial Evaluation Scale, TSO version), perceived social support (Oslo-3 Social Support Scale), unmet social needs (Social Work Screening Questionnaire), ethnicity, gender of both the patient and the primary caregiver, language proficiency, educational level, and geographical distance to the hospital. This analysis evaluates the magnitude of potential disparities and the intervention's capacity to ensure equitable access to the diagnostic pathway regardless of the patient's sociodemographic profile.