Effectiveness and cost-effectiveness of a structured integrated post-pulmonary embolism follow-up care model (Attend-PE): a rationale and protocol for a multicentre clinical pre-post study
Venous thromboembolism (VTE), clinically presenting as deep vein thrombosis or pulmonary embolism (PE), is the third most frequent cardiovascular disease globally, after myocardial infarction and stroke, and ranks high among causes of cardiovascular mortality. The incidence rate of PE is increasing, partly explained by ageing populations and improved diagnostic capabilities, while the case-fatality rate for patients with PE has been decreasing over the past decades. For a substantial number of patients surviving acute PE, their condition becomes chronic with persisting functional limitation, deconditioning, fatigue and anxiety, ultimately resulting in poor quality of life. Moreover, some patients will experience recurrence, and some may develop chronic thromboembolic pulmonary disease with or without hypertension. Hence, the prevalence of patients with PE requiring long-term care is projected to increase substantially. Aiming to reduce the burden of long-term PE complications, the European Society of Cardiology (ESC) clinical guidelines on the management of PE suggested that a structured integrated follow-up care model should (i) enhance compliance with anticoagulant therapy, (ii) provide appropriate care (exercise rehabilitation, treatment of comorbidity and behavioural education) and (iii) ensure early detection of chronic syndromes. However, there is currently no consensus on what such an optimal follow-up strategy should include, and high-quality evidence to provide guidance is lacking. In comparison, follow-up care programmes have proven effective in patients with heart failure, acute coronary syndrome and atrial fibrillation, showing a reduction in deaths, readmissions and healthcare costs, as well as an improvement in health-related quality of life. To comply with the ESC guideline recommendations and address the variation in follow-up care after PE in Denmark, the research programme ‘A structured integrated post-pulmonary embolism care model’ (Attend-PE) was initiated in 2021 with financial support from the Danish Heart Foundation. The purpose of the programme is to develop, test, implement and evaluate a structured care model for patients with PE. The proposed model aims to reduce the disease burden and improve patients’ quality of life, functional status, level of empowerment and medical adherence. The development process and details of the model are described in detail in the Methods and analysis section. Aims and objectives The present pre-post-intervention study will investigate the effectiveness of a structured follow-up care programme for patients with PE on both patient-reported outcomes (PROs) and clinical outcomes in comparison with usual care. Furthermore, a health economic evaluation will be conducted to investigate the cost-effectiveness of the follow-up care programme. The specific study objectives are as follows: Objective 1 To compare the effectiveness of the Attend-PE model at 6 month follow-up on the co-primary outcomes: (1) health-related quality of life and (2) adherence to medication and the secondary outcomes: anxiety, depression, sick leave, treatment satisfaction, recurrence of VTE, readmission and mortality, compared with usual care (ie, services provided before implementation of the Attend-PE model). Objective 2 To investigate the cost-effectiveness of the Attend-PE model from baseline (date of PE event) to 6-month follow-up compared to usual care from both a health care system perspective and a societal perspective. 

The present pre-post-intervention study will investigate the effectiveness of a structured follow-up care programme for patients with PE on both patient-reported outcomes (PROs) and clinical outcomes in comparison with usual care. Furthermore, a health economic evaluation will be conducted to investigate the cost-effectiveness of the follow-up care programme. The specific study objectives are as follows: Objective 1 To compare the effectiveness of the Attend-PE model at 6 month follow-up on the co-primary outcomes: (1) health-related quality of life and (2) adherence to medication and the secondary outcomes: anxiety, depression, sick leave, treatment satisfaction, recurrence of VTE, readmission and mortality, compared with usual care (ie, services provided before implementation of the Attend-PE model). Objective 2 To investigate the cost-effectiveness of the Attend-PE model from baseline (date of PE event) to 6-month follow-up compared to usual care from both a health care system perspective and a societal perspective. 

To compare the effectiveness of the Attend-PE model at 6 month follow-up on the co-primary outcomes: (1) health-related quality of life and (2) adherence to medication and the secondary outcomes: anxiety, depression, sick leave, treatment satisfaction, recurrence of VTE, readmission and mortality, compared with usual care (ie, services provided before implementation of the Attend-PE model). 

To investigate the cost-effectiveness of the Attend-PE model from baseline (date of PE event) to 6-month follow-up compared to usual care from both a health care system perspective and a societal perspective. 

The study protocol is reported in accordance with the SPIRIT guidelines and was registered at clinicaltrials.gov (NCT06037096) prior to the post-period of data collection as described below. Study design The study uses a pre-post-intervention study design, aiming to evaluate the predefined co-primary and secondary outcomes before and after implementation of the Attend-PE model of care, as shown in . Study setting The study is conducted in Denmark, where the healthcare system is tax-funded and services are freely available for all citizens, independent of income. Eligibility criteria Adult patients (≥18 years), diagnosed with PE confirmed by imaging, are eligible for inclusion. Patients with a cancer diagnosis and those who are not able to read and write Danish are excluded. The pre-cohort entails patients diagnosed in the period from March 2022 to May 2023, that is, prior to implementation of the Attend-PE model, while the post-cohort entails patients diagnosed in the period from March 2024 to May 2025, that is, after the implementation of the Attend-PE model. Intervention: the Attend-PE model The Attend-PE follow-up care model was developed in the period 2021–2022, based on the following steps: (1) a needs assessment performed by mapping clinical practice at all main hospital departments treating PE in Denmark, combined with patient journey maps conducted at 10 departments ; (2) definition of the overall goal and performance objectives of the Attend-PE model based on the needs assessment in combination with a literature review; (3) co-production of the Attend-PE model in workshops with patient representatives, healthcare professionals and experts in the field and (4) refinement of the structure and organisation of the Attend-PE model and production of patient education material. The final Attend-PE model outlines a structured approach for follow-up care, involving group-based patient education, individual consultations and systematic use of PROs to assess the patient’s physical and psychological well-being. The model thus supports a personalised post-hospitalisation care plan. Details of the development process, the final model and the feasibility test of the model have recently been published. An overview of the model is given in , and a more detailed description of each care element is provided in . Outcomes for the effectiveness evaluation Two primary outcomes are used: one PRO and one clinical outcome, as described below. The disease-specific questionnaire Pulmonary Embolism Quality of Life (PEmbQoL) is used as the PRO co-primary outcome. PEmbQoL assesses the overall impact of PE on the patient’s quality of life and has been validated in a Danish setting. The clinical co-primary outcome is adherence to the anticoagulant treatment and is measured as the percentage of redeemed prescriptions within the first 6 months. Thus, patients having redeemed ≥80% of the prescribed anticoagulant medication are considered adherent. Data on the redemption of medicine will be retrieved from the Danish National Prescription Registry. Secondary PROs are functional ability using the Post-VTE Functional Status Scale ; treatment satisfaction using the Anti-Clot Treatment Scale ; Patient Activation Measure ; anxiety and depression using the General Anxiety Disorder-7 ; the Patient Health Questionnaire and work ability using the Work Productivity and Activity Impairment questionnaire (WPAI:GH, V.2.0). Secondary clinical outcomes include recurrent VTE, major and clinically relevant nonmajor bleeding, as reported by the National Patient Registry, and VTE-related death as reported by the Danish Registry of Causes of Death. Outcomes for the health economic evaluation For the cost-effectiveness analysis (CEA), the PEmbQoL will be used, as described above, while for the cost-utility analysis (CUA), the EuroQol-5 Dimension-5 Levels (EQ-5D-5L) will be used. The EQ-5D-5L is a self-assessed, health-related, quality-of-life questionnaire, measuring the quality of life on a five-component scale, including mobility, self-care, usual activities, pain/discomfort and anxiety/depression scores. The score will be preference-weighted using the recent Danish value set. Costing Intervention costs of the Attend-PE model will be estimated using a microcosting approach that includes resources used for training the staff managing the intervention and working hours of the staff related to the Attend-PE model (eg, extra consultations), including noncontact time (eg, time used for administration related to the changed care model). Time spent will be valued using average salaries. Use of primary healthcare costs will be obtained for each patient from The National Health Service Registry and will include the number of visits and related activity-based tariffs, categorised by healthcare providers (eg, general practitioners, medical specialists and therapists). Data on the use of secondary healthcare services (number of services and national average diagnostic-related grouping (DRG) tariffs) will be extracted from the National Patient Registry. Costs of prescription medicine will be obtained from the Danish National Prescription Registry and valued using market prices. Costs related to lost productivity will be estimated using a human capital approach and data from the WPAI:GH, V.2.0. This questionnaire aims to capture the extent of days of sickness (‘absenteeism’) as well as lost productivity caused by a reduced productivity level (‘presenteeism’). Productivity loss will be estimated by multiplying days/time of absence with age- and gender-adjusted mean salaries. Participant Timeline Patients diagnosed with PE from March 2022 to May 2023 (pre-implementation period) will receive a questionnaire to be completed 6 and 12 months after their PE event (index time). This means that 12-month follow-up data for the last participants are retrieved in May 2024. Correspondingly, patients diagnosed with PE from March 2024 to May 2025 (post-implementation period) will receive a questionnaire 6 and 12 months after their PE event, meaning that the last 12-month follow-up data will be retrieved in May 2026. Register data for all included patients (respondents and nonrespondents alike) will be retrieved at index time, 6 months and 12 months after the PE event. Recruitment and data collection methods For both the pre- and post-cohort, PROs and register data will be collected at 6 and 12 months after the index date. Patients will receive a digital letter with an invitation to complete an online questionnaire using the e-Boks system via their social security number. E-Boks is a mandatory method used by Danish public authorities in their communication with Danish residents. It was established in 2014 and is used by approximately 90% of Danish residents for their secured digital mail. No attempt will be made to collect survey data from the remaining 10%. The questionnaire includes validated PROs, as described in the ‘Outcomes for the effectiveness evaluation’ section, as well as questions about sociodemographic factors. The questionnaires are collected using the Research Electronic Data Caption system (REDCap) hosted at Aalborg University Hospital. Register data on clinical outcomes and the use of healthcare services for all patients will be retrieved through the Danish Health Data Authority. Data management PRO data will be exported from REDCap and stored on a secure server at the Danish Health Data Authority, where the data will be linked to the National Patient Registry and the National Register of Pharmaceutical Sales. All data will be pseudonymised before analysing the data. Statistical methods For the effectiveness evaluation, the post-implementation population will be compared with the pre-implementation population using linear regression with robust variance estimation for continuous outcomes. For an assessment of effectiveness on binary and time-to-event outcomes (eg, recurrence yes/no and readmission yes/no), we will apply Poisson regression with robust variance estimation to estimate risk ratios and incidence rate ratios. Risk estimates will be represented by cumulative incidences and be estimated using the Aalen-Johansen estimator. All-cause death will be considered a competing risk in analyses of nonfatal end points. All analyses will be presented as adjusted and unadjusted. Time-to-event analyses will be adjusted using inverse probability of treatment weights, and the remaining analyses will be adjusted using g-estimation. We will apply appropriate causal assessment techniques to assess which patient characteristics should be adjusted for. Prespecified subgroup analyses will be performed according to geography (region of residence), pre-existing patient pathway model, age, sex and socioeconomic background, as well as the level of implementation success of the hospital in charge. For the CEA and CUA, comparing the costs and effectiveness of the two strategies will be summarised using conventional summary statistics. The net benefit will be estimated using a range of hypothetical threshold values for decision-makers’ willingness to pay for a quality-adjusted life-year (QALY) (from DKK 0 to DKK 500,000) and present the incremental cost and incremental effects visually in a cost-effectiveness acceptability curve (CEAC). CEAC will be used to illustrate the probability of the Attend-PE model being cost-effective for the range of threshold values for willingness to pay for a QALY. CEA and CEAC will be estimated using seemingly unrelated linear regression with robust variance and area defined by the resulting confidence ellipse and willingness-to-pay line. To aid decision-makers in Denmark, the CEA will be supplemented with a budget impact analysis, providing information about the budget consequences for the different levels in the organisation. Sample size estimation The sample size is estimated based on assumptions about the two co-primary outcomes, PEmbQoL and adherence with medication. For the PEmbQoL, the minimal clinically relevant difference for PEmbQoL has previously been estimated to be 15 points with an SD of 25 points in each group. With a power of 90% and a significance level of 0.025 (as we have two primary outcomes), this would require a minimum of 69 patients in each group. For adherence with anticoagulant medication, studies including north European VTE populations have reported a nonadherence rate of 10–17% depending on the type of medication (eg, Direct oral anticoagulants (DOACs) or warfarin). Aiming for a reduction of nonadherence of 5% in the Attend-PE group, this will require a sample size of 1084 patients in each group at a power of 90% and a significance level of 0.025. We therefore aim to include 1000 patients in each group to account for subgroup analyses. With an expected response rate of 50% for questionnaires and 100% follow-up for registered data, this sample size will suffice for both co-primary outcomes. Patient and public involvement Patients have been involved on different levels throughout the present study. A patient research partner has been engaged in the steering group together with researchers and clinical experts, thereby being involved in the overall guidance of the study design and process and is co-authoring several papers. Furthermore, several patient representatives have been involved in the development of the Attend-PE model and related patient materials and in the cross-cultural translation of PRO measures. Furthermore, patient representatives will be invited to participate in the dissemination of study findings. 

The study uses a pre-post-intervention study design, aiming to evaluate the predefined co-primary and secondary outcomes before and after implementation of the Attend-PE model of care, as shown in . 

The study is conducted in Denmark, where the healthcare system is tax-funded and services are freely available for all citizens, independent of income. 

Adult patients (≥18 years), diagnosed with PE confirmed by imaging, are eligible for inclusion. Patients with a cancer diagnosis and those who are not able to read and write Danish are excluded. The pre-cohort entails patients diagnosed in the period from March 2022 to May 2023, that is, prior to implementation of the Attend-PE model, while the post-cohort entails patients diagnosed in the period from March 2024 to May 2025, that is, after the implementation of the Attend-PE model. 

The Attend-PE follow-up care model was developed in the period 2021–2022, based on the following steps: (1) a needs assessment performed by mapping clinical practice at all main hospital departments treating PE in Denmark, combined with patient journey maps conducted at 10 departments ; (2) definition of the overall goal and performance objectives of the Attend-PE model based on the needs assessment in combination with a literature review; (3) co-production of the Attend-PE model in workshops with patient representatives, healthcare professionals and experts in the field and (4) refinement of the structure and organisation of the Attend-PE model and production of patient education material. The final Attend-PE model outlines a structured approach for follow-up care, involving group-based patient education, individual consultations and systematic use of PROs to assess the patient’s physical and psychological well-being. The model thus supports a personalised post-hospitalisation care plan. Details of the development process, the final model and the feasibility test of the model have recently been published. An overview of the model is given in , and a more detailed description of each care element is provided in . 

Two primary outcomes are used: one PRO and one clinical outcome, as described below. The disease-specific questionnaire Pulmonary Embolism Quality of Life (PEmbQoL) is used as the PRO co-primary outcome. PEmbQoL assesses the overall impact of PE on the patient’s quality of life and has been validated in a Danish setting. The clinical co-primary outcome is adherence to the anticoagulant treatment and is measured as the percentage of redeemed prescriptions within the first 6 months. Thus, patients having redeemed ≥80% of the prescribed anticoagulant medication are considered adherent. Data on the redemption of medicine will be retrieved from the Danish National Prescription Registry. Secondary PROs are functional ability using the Post-VTE Functional Status Scale ; treatment satisfaction using the Anti-Clot Treatment Scale ; Patient Activation Measure ; anxiety and depression using the General Anxiety Disorder-7 ; the Patient Health Questionnaire and work ability using the Work Productivity and Activity Impairment questionnaire (WPAI:GH, V.2.0). Secondary clinical outcomes include recurrent VTE, major and clinically relevant nonmajor bleeding, as reported by the National Patient Registry, and VTE-related death as reported by the Danish Registry of Causes of Death. 

For the cost-effectiveness analysis (CEA), the PEmbQoL will be used, as described above, while for the cost-utility analysis (CUA), the EuroQol-5 Dimension-5 Levels (EQ-5D-5L) will be used. The EQ-5D-5L is a self-assessed, health-related, quality-of-life questionnaire, measuring the quality of life on a five-component scale, including mobility, self-care, usual activities, pain/discomfort and anxiety/depression scores. The score will be preference-weighted using the recent Danish value set. Costing Intervention costs of the Attend-PE model will be estimated using a microcosting approach that includes resources used for training the staff managing the intervention and working hours of the staff related to the Attend-PE model (eg, extra consultations), including noncontact time (eg, time used for administration related to the changed care model). Time spent will be valued using average salaries. Use of primary healthcare costs will be obtained for each patient from The National Health Service Registry and will include the number of visits and related activity-based tariffs, categorised by healthcare providers (eg, general practitioners, medical specialists and therapists). Data on the use of secondary healthcare services (number of services and national average diagnostic-related grouping (DRG) tariffs) will be extracted from the National Patient Registry. Costs of prescription medicine will be obtained from the Danish National Prescription Registry and valued using market prices. Costs related to lost productivity will be estimated using a human capital approach and data from the WPAI:GH, V.2.0. This questionnaire aims to capture the extent of days of sickness (‘absenteeism’) as well as lost productivity caused by a reduced productivity level (‘presenteeism’). Productivity loss will be estimated by multiplying days/time of absence with age- and gender-adjusted mean salaries. 

Intervention costs of the Attend-PE model will be estimated using a microcosting approach that includes resources used for training the staff managing the intervention and working hours of the staff related to the Attend-PE model (eg, extra consultations), including noncontact time (eg, time used for administration related to the changed care model). Time spent will be valued using average salaries. Use of primary healthcare costs will be obtained for each patient from The National Health Service Registry and will include the number of visits and related activity-based tariffs, categorised by healthcare providers (eg, general practitioners, medical specialists and therapists). Data on the use of secondary healthcare services (number of services and national average diagnostic-related grouping (DRG) tariffs) will be extracted from the National Patient Registry. Costs of prescription medicine will be obtained from the Danish National Prescription Registry and valued using market prices. Costs related to lost productivity will be estimated using a human capital approach and data from the WPAI:GH, V.2.0. This questionnaire aims to capture the extent of days of sickness (‘absenteeism’) as well as lost productivity caused by a reduced productivity level (‘presenteeism’). Productivity loss will be estimated by multiplying days/time of absence with age- and gender-adjusted mean salaries. 

Patients diagnosed with PE from March 2022 to May 2023 (pre-implementation period) will receive a questionnaire to be completed 6 and 12 months after their PE event (index time). This means that 12-month follow-up data for the last participants are retrieved in May 2024. Correspondingly, patients diagnosed with PE from March 2024 to May 2025 (post-implementation period) will receive a questionnaire 6 and 12 months after their PE event, meaning that the last 12-month follow-up data will be retrieved in May 2026. Register data for all included patients (respondents and nonrespondents alike) will be retrieved at index time, 6 months and 12 months after the PE event. 

For both the pre- and post-cohort, PROs and register data will be collected at 6 and 12 months after the index date. Patients will receive a digital letter with an invitation to complete an online questionnaire using the e-Boks system via their social security number. E-Boks is a mandatory method used by Danish public authorities in their communication with Danish residents. It was established in 2014 and is used by approximately 90% of Danish residents for their secured digital mail. No attempt will be made to collect survey data from the remaining 10%. The questionnaire includes validated PROs, as described in the ‘Outcomes for the effectiveness evaluation’ section, as well as questions about sociodemographic factors. The questionnaires are collected using the Research Electronic Data Caption system (REDCap) hosted at Aalborg University Hospital. Register data on clinical outcomes and the use of healthcare services for all patients will be retrieved through the Danish Health Data Authority. 

PRO data will be exported from REDCap and stored on a secure server at the Danish Health Data Authority, where the data will be linked to the National Patient Registry and the National Register of Pharmaceutical Sales. All data will be pseudonymised before analysing the data. 

For the effectiveness evaluation, the post-implementation population will be compared with the pre-implementation population using linear regression with robust variance estimation for continuous outcomes. For an assessment of effectiveness on binary and time-to-event outcomes (eg, recurrence yes/no and readmission yes/no), we will apply Poisson regression with robust variance estimation to estimate risk ratios and incidence rate ratios. Risk estimates will be represented by cumulative incidences and be estimated using the Aalen-Johansen estimator. All-cause death will be considered a competing risk in analyses of nonfatal end points. All analyses will be presented as adjusted and unadjusted. Time-to-event analyses will be adjusted using inverse probability of treatment weights, and the remaining analyses will be adjusted using g-estimation. We will apply appropriate causal assessment techniques to assess which patient characteristics should be adjusted for. Prespecified subgroup analyses will be performed according to geography (region of residence), pre-existing patient pathway model, age, sex and socioeconomic background, as well as the level of implementation success of the hospital in charge. For the CEA and CUA, comparing the costs and effectiveness of the two strategies will be summarised using conventional summary statistics. The net benefit will be estimated using a range of hypothetical threshold values for decision-makers’ willingness to pay for a quality-adjusted life-year (QALY) (from DKK 0 to DKK 500,000) and present the incremental cost and incremental effects visually in a cost-effectiveness acceptability curve (CEAC). CEAC will be used to illustrate the probability of the Attend-PE model being cost-effective for the range of threshold values for willingness to pay for a QALY. CEA and CEAC will be estimated using seemingly unrelated linear regression with robust variance and area defined by the resulting confidence ellipse and willingness-to-pay line. To aid decision-makers in Denmark, the CEA will be supplemented with a budget impact analysis, providing information about the budget consequences for the different levels in the organisation. 

The sample size is estimated based on assumptions about the two co-primary outcomes, PEmbQoL and adherence with medication. For the PEmbQoL, the minimal clinically relevant difference for PEmbQoL has previously been estimated to be 15 points with an SD of 25 points in each group. With a power of 90% and a significance level of 0.025 (as we have two primary outcomes), this would require a minimum of 69 patients in each group. For adherence with anticoagulant medication, studies including north European VTE populations have reported a nonadherence rate of 10–17% depending on the type of medication (eg, Direct oral anticoagulants (DOACs) or warfarin). Aiming for a reduction of nonadherence of 5% in the Attend-PE group, this will require a sample size of 1084 patients in each group at a power of 90% and a significance level of 0.025. We therefore aim to include 1000 patients in each group to account for subgroup analyses. With an expected response rate of 50% for questionnaires and 100% follow-up for registered data, this sample size will suffice for both co-primary outcomes. 

Patients have been involved on different levels throughout the present study. A patient research partner has been engaged in the steering group together with researchers and clinical experts, thereby being involved in the overall guidance of the study design and process and is co-authoring several papers. Furthermore, several patient representatives have been involved in the development of the Attend-PE model and related patient materials and in the cross-cultural translation of PRO measures. Furthermore, patient representatives will be invited to participate in the dissemination of study findings. 

The project will be conducted by the Declaration of Helsinki and comply with all applicable laws, regulations and guidance regarding patient protection, including patient privacy. The study will be conducted in compliance with the General Data Protection Regulation (GDPR), and all data will be handled, stored, analysed and reported according to the GDPR. The study is exempt from approval (journal no.: 2023-0 00 206) in accordance with the Danish Act on Health Research Ethics §14. The use of survey responses in research (in anonymous form) is, however, contingent on participants’ consent, and the invitation letter therefore included information about the purpose of the study and participants’ rights to withdraw consent at any time, and that completion of the questionnaire is considered as consent to their survey data to be included in research. Study findings will be disseminated (i) scientifically as articles in international peer-reviewed journals and national and international conferences; (ii) presentations for health professionals and decision-makers at participating hospitals; (iii) presentations for funding bodies (ie, the Danish Heart Association) and (iv) presentations for patients and relatives through, for example, webinars and talks arranged by the research group in collaboration with the Danish Heart Association. The study pre-implementation cohort was initiated in March 2022 and the last follow-up in the post-implementation cohort is expected in March 2026, as shown in . Study details are outlined in . 

This will be the first study to examine the effectiveness of a structured follow-up programme for patients with PE. Additionally, this study will clarify whether the Attend-PE model is beneficial from a health economic perspective. These results are crucial for informed resource allocation and improving the quality assurance of current healthcare services, which is an important step towards providing sustainable follow-up care post-PE that will improve the functional status and quality of life for patients who find everyday life impacted by PE. The study is underpinned by a high level of stakeholder involvement, including researchers and national and international experts, hospital clinicians and patient research partners, who will guide the study process and evaluation. These stakeholders have been part of co-designing the Attend-PE model, including content and mode of delivery, patient education materials, study design and the implementation process. Due to the pragmatic realist design, this study will also help identify facilitators and barriers to the implementation of a structured follow-up care model in a hospital setting. If found to be effective, the trial will have important implications for policy, as it will serve to establish consensus on what an optimal follow-up strategy for post-PE care should include and inform future guideline development and implementation both nationally and internationally. The main limitation of the study is the lack of randomisation, as estimates of effectiveness may be biased if study populations are not comparable in pre- and post-cohorts. To mitigate this, a sufficient number of patients will be included to allow for adjustments for relevant confounders (N ≈ 2000). We expect all relevant confounder variables to be available. A second limitation is the expected response rate of 50%. We do, however, expect that the level of nonresponders will be the same in pre- and post-cohorts, and as mentioned above, we will retrieve registry data from 100% of patients and will therefore be able to investigate systematic differences between responders and nonresponders in pre- and post-cohorts. Finally, we expect that there may be some limitations in terms of organisational issues related to the implementation of the Attend-PE model at hospitals. A process evaluation is therefore included in the study, where any variations in the timing and quality of delivery of the model will be registered, along with several process data determining implementation success or barriers. This information can be subsequently used for sensitivity analyses. 

