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The OPTIMIZE-ILD-1 trial is a prospective, randomized, open-label clinical trial designed to evaluate the impact of a coordinated diagnostic pathway on patients with suspected interstitial lung disease (ILD). In routine clinical practice, diagnostic workflows for ILD are frequently fragmented, involving multiple independent appointments that can lead to significant delays and increased burden for patients and caregivers. This study compares the standard diagnostic pathway against an optimized circuit where core diagnostic procedures-such as high-resolution CT, pulmonary function tests, and laboratory panels-are pre-bundled and scheduled within a coordinated and compressed timeframe.
All eligible patients referred for suspected ILD are included consecutively to ensure a pragmatic, real-world representation of the referral population. The primary objective is to measure the time to diagnostic communication, defined as the duration from randomization to the date the patient is formally informed of the final diagnosis following a multidisciplinary team (MDT) consensus. Secondary objectives include assessing the time to MDT diagnosis, the time to treatment initiation (when clinically indicated), socioeconomic cost-burden, and the environmental carbon footprint of the diagnostic journey. Furthermore, the study evaluates health-related quality of life, psychological distress, and clinical frailty, while exploring factors such as language proficiency as determinants of diagnostic equity. Caregiver-related outcomes, including burden and experience measures, are contingent upon the presence of a primary caregiver and the provision of their independent informed consent.
The design of this protocol was informed by a patient focus group and is officially endorsed by the 'AIRE' Associació Catalana de Malalts i Trasplantats Pulmonars, ensuring a patient-centered approach that prioritizes the diagnostic journey's efficiency and human impact.
The primary endpoint of this study is the time to diagnostic communication, defined as the interval from randomization to the date when the final diagnosis is formally communicated to the patient following multidisciplinary team (MDT) consensus. Interstitial lung diseases (ILD) require a complex, multidimensional evaluation involving radiology, pulmonary function testing, and clinical assessment; however, fragmented scheduling in routine care often delays diagnosis and exacerbates inequities. OPTIMIZE-ILD-1 is a single-center, prospective, randomized trial with 1:1 allocation.
To ensure a balanced representation of clinical entry routes and phenotypes, randomization is stratified into three groups: 1) Primary Care referral without a pre-existing autoimmune disease; 2) Specialized Care referral without a pre-existing autoimmune disease; 3) referral with a pre-existing autoimmune disease, from any source. The intervention streamlines the coordination of existing diagnostic steps-including high-resolution chest CT, complete pulmonary function tests, and comprehensive laboratory panels-by clustering them into a coordinated workflow designed to be completed in the minimum number of hospital visits possible, without modifying clinical content or prioritization rules.
Secondary outcomes evaluate the pathway's efficiency and economic impact, including time to MDT diagnosis, time to treatment initiation (where clinically indicated), and the socioeconomic cost-burden for the family unit, which accounts for direct logistical expenses, productivity loss, and hospital operational inefficiencies. Additionally, the environmental impact is quantified via the diagnostic journey's carbon footprint. Patient-centered metrics are captured through validated instruments: EQ-5D-5L and K-BILD for health-related quality of life; GAD-7 for anxiety and PHQ-9 for depression; the Oslo-3 Social Support Scale for perceived social support; the Social-Familial Evaluation Scale (TSO version) for social risk; and the CFS for clinical frailty. Caregiver burden (Caregiver Burden Inventory, CBI-15) and family experience measures (PREMs) are assessed contingent upon the presence of a primary caregiver and the provision of their independent informed consent. Satisfaction and process quality are further monitored using study-specific PREMs for patients, caregivers, and interdisciplinary professionals. A Patient Global Impression of Change (PGIC) is collected at the end of the study for patients, caregivers, and professionals to anchor the clinical significance of observed changes. A study-specific social work screening questionnaire is administered to identify patients with unmet social needs who may benefit from social work referral.
Finally, the study includes a pre-planned exploratory analysis to evaluate the equity of the intervention's impact across diverse populations. This analysis will investigate whether sociodemographic determinants-primarily socioeconomic status, social risk, ethnicity, language proficiency, and educational level, as well as the geographical distance to the hospital and the gender of both the patient and the primary caregiver-act as moderators of the intervention effect. The objective is to determine if the coordinated circuit effectively mitigates traditional barriers to care and provides equitable benefits regardless of the patient's or caregiver's sociodemographic profile, among other factors.
The design of this protocol was developed with active input from a patient focus group and the collaboration of the 'AIRE' association to ensure the outcomes reflect the real-world needs of the ILD community.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard ILD Diagnostic Pathway | Active Comparator | Participants in this arm will follow the standard ILD diagnostic pathway. After referral for suspected ILD and confirmation of eligibility, core diagnostic procedures-such as high-resolution chest computed tomography, complete pulmonary function tests (spirometry and diffusing capacity), six-minute walk test and a comprehensive ILD laboratory panel-are ordered and scheduled independently according to routine departmental workflows and waiting times. Additional procedures, including bronchoscopy with bronchoalveolar lavage, rheumatology or internal medicine assessment, or lung biopsy when indicated, are requested through usual clinical channels. These tests typically occur on different days. The final ILD diagnosis is assigned once all required results are available and reviewed in the ILD unit or in a multidisciplinary discussion when appropriate. The study team does not modify scheduling priorities, clinical decisions or the type of tests performed. |
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| Optimized ILD Diagnostic Circuit | Experimental | Participants in this arm will follow a coordinated ILD diagnostic circuit in which the same core diagnostic procedures-high-resolution chest computed tomography, complete pulmonary function tests with spirometry and diffusing capacity, six-minute walk test and a comprehensive ILD laboratory panel-are pre-bundled and scheduled within a compressed and coordinated timeframe, in as few hospital visits as possible. When clinically indicated, additional evaluations such as bronchoscopy or rheumatology/internal medicine consultation are integrated into the same coordinated workflow. All available diagnostic information is reviewed in a single multidisciplinary discussion to assign the final ILD diagnosis and initial therapeutic plan. The intervention does not introduce new diagnostic tests, alter clinical content or modify prioritization rules; it reorganizes the timing and coordination of existing diagnostic steps to reduce fragmentation and diagnostic delays. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard ILD Diagnostic Pathway | Other | Organizational usual-care comparator following the standard ILD diagnostic workflow. After referral for suspected ILD, core diagnostic procedures such as high-resolution chest computed tomography, complete pulmonary function tests (spirometry and diffusing capacity), six-minute walk test, and a comprehensive ILD laboratory panel are ordered and scheduled independently according to routine departmental workflows and waiting times. Additional procedures, including bronchoscopy with bronchoalveolar lavage or rheumatology/internal medicine assessment, are requested when clinically indicated. These diagnostic tests and visits usually occur on separate days, and the final diagnosis is assigned once all required results are available and reviewed in the ILD unit or in a multidisciplinary discussion. The intervention does not modify clinical content, scheduling priorities, or the type of tests performed. |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Diagnostic Communication | Time (measured in days) elapsed from the date of randomization to the date when the final diagnosis is formally communicated to the patient. This measure captures the complete diagnostic process, including the scheduling and performance of all tests (imaging, PFTs, labs), the Multidisciplinary Team (MDT) consensus meeting, and the subsequent clinical appointment where the patient is informed of the findings and the initial management plan. | From randomization until the date of diagnostic communication to the patient (up to 18 months). |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Multidisciplinary Team (MDT) Diagnosis | 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. | From randomization until the date of the MDT diagnostic consensus (up to 18 months). |
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Inclusion Criteria:
Age 18 years or older.
Referral for suspected or undiagnosed interstitial lung disease (ILD).
At least one of the following:
Ability to provide informed consent.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jaume Bordas-Martinez, MD, PhD | Hospital General de Granollers | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital General de Granollers | Recruiting | Granollers | Barcelona | 08402 | Spain |
Deidentified individual participant data (IPD) underlying the primary and secondary outcome results will be made available to qualified researchers upon reasonable request after publication of the main study results. Shared data will include variables required to reproduce the main analyses, excluding any information that could directly identify participants. No imaging files or raw free-text data will be shared.
Beginning 12 months after publication of the primary results and for a period of up to 5 years.
Access to IPD will be granted to researchers with a methodologically sound proposal and a clear scientific objective. Requests must be submitted to the Principal Investigator. Approval will require compliance with institutional data-protection policies, signing a data-use agreement, and ensuring secure data handling. No data containing personal identifiers will be provided.
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Prospective, consecutive, randomized, open-label, parallel-group clinical trial evaluating whether a coordinated diagnostic circuit reduces the time required to reach a confirmed ILD diagnosis compared with the standard diagnostic pathway. A total of 92 participants will be enrolled. Randomization is stratified into three groups: 1) Primary Care referral without a pre-existing autoimmune disease; 2) Specialized Care referral without a pre-existing autoimmune disease; 3) referral with a pre-existing autoimmune disease, from any source. Participants are included at first referral for suspected ILD prior to completion of a full diagnostic work-up.
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| Optimized ILD Diagnostic Circuit | Other | Organizational intervention that coordinates and bundles core ILD diagnostic procedures into a compressed and structured workflow. For patients with suspected ILD, high-resolution chest computed tomography, complete pulmonary function tests (spirometry and diffusing capacity), the six-minute walk test, and a comprehensive ILD laboratory panel are pre-bundled and scheduled within a shortened timeframe, ideally within one or two coordinated visits. When required, bronchoscopy and rheumatology/internal medicine assessments are integrated into the same coordinated pathway. All available diagnostic results are reviewed in a single multidisciplinary discussion to assign the final ILD diagnosis and the initial therapeutic plan. The intervention does not introduce new tests or alter clinical decision-making; it reorganizes the timing and coordination of existing procedures without modifying waiting-list rules. |
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| Time to Treatment Initiation | 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. | From randomization until treatment initiation, if required (up to 18 months). |
| Diagnostic Time Burden | 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. | From randomization until the ILD diagnosis or treatment initiation, if required (up to 18 months). |
| Patient and Caregiver Socioeconomic Cost-Burden | This outcome assesses the private economic impact and "Financial Toxicity" on the family unit. It evaluates:
Data is expressed in Euros (€). Higher values indicate a greater socioeconomic burden and higher "Time Burden" imposed by the diagnostic circuit. | From randomization until the ILD diagnosis or treatment initiation, if required (up to 18 months). |
| Hospital Direct and Operational Costs | This measure calculates the total economic impact on the healthcare system during the diagnostic pathway. It includes:
All values are calculated in Euros (€). Higher scores indicate higher healthcare resource utilization and lower operational efficiency | From randomization until the ILD diagnosis or treatment initiation, if required (up to 18 months). |
| Carbon Footprint of the ILD Diagnostic Pathway | Estimated carbon dioxide equivalent emissions (CO₂-Equivalent Emissions) generated by patient and caregiver travel and healthcare resource use during the diagnostic process. | From randomization until the ILD diagnosis or treatment initiation, if required (up to 18 months). |
| EQ-5D-5L Health-Related Quality of Life Questionnaire | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| King's Brief Interstitial Lung Disease (K-BILD) Questionnaire | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| Generalized Anxiety Disorder 7-item Scale (GAD-7) | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| Patient Health Questionnaire-9 (PHQ-9) | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| Clinical Frailty Scale (CFS) | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| Social-Familial Evaluation Scale (TSO version) | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| Oslo-3 Social Support Scale | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| Patient-Reported Experience Measures (PREMs) - Patient | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| Social Work Screening and Referral | A study-specific 7-item screening questionnaire, developed in collaboration with the Hospital Social Work Department, designed to identify patients who may benefit from social work assessment. The instrument evaluates: 1) Prior contact with social services (informative), 2) Awareness of available public resources for disability or chronic disease, 3) Digital literacy barriers affecting appointment management, 4) Need for home support or difficulty leaving the home, 5) Disability or dependency recognition status, 6) Perceived caregiver overburden, and 7) Patient willingness to receive social work consultation. Referral to social work is offered when any item triggers a positive response, 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 of patients meeting referral criteria, the effective referral rate, and the specific un | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| Patient-Reported Experience Measures (PREMs) - Caregiver | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| Caregiver Burden Inventory - Shortened Version (CBI-15) | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| Interdisciplinary Professional Experience (Professional-PREMs) | 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. | At the end of the study, up to 18 months after first inclusion |
| Patient Global Impression of Change (PGIC) - Patient | 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. | At the diagnostic communication visit (up to 18 months) |
| Patient Global Impression of Change (PGIC) - Caregiver | 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. | At the diagnostic communication visit (up to 18 months) |
| Patient Global Impression of Change (PGIC) - Professional | 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. | At the end of the study, up to 18 months after first inclusion |
| Sociodemographic Determinants of Equity and Access | 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. | Baseline (at the first in-person visit) and at the diagnostic communication visit (up to 18 months) |
| ID | Term |
|---|---|
| D017563 | Lung Diseases, Interstitial |
| D054990 | Idiopathic Pulmonary Fibrosis |
| D011658 | Pulmonary Fibrosis |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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