Early Support after Exposure to Trauma (EASE): Protocol for a hybrid effectiveness-implementation trial of an internet-based intervention for PTSD prevention

Early Support after Exposure to Trauma (EASE): Protocol for a hybrid effectiveness-implementation trial of an internet-based intervention for PTSD prevention | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Early Support after Exposure to Trauma (EASE): Protocol for a hybrid effectiveness-implementation trial of an internet-based intervention for PTSD prevention Espen Rasmussen Lassen, Marianne Skogbrott Birkeland, Karina Egeland, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8039476/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Feb, 2026 Read the published version in Trials → Version 1 posted 4 You are reading this latest preprint version Abstract Background : Post-traumatic stress disorder (PTSD) can have detrimental effects for those afflicted and is associated with increased health care utilization and substantial societal costs. Thus, there is a need for accessible, effective, and cost-efficient preventive interventions for post-traumatic psychological sequelae. Research indicates that trauma-focused cognitive-behavioral therapy (CBT-T) could effectively prevent PTSD when applied as an indicated secondary prevention. CIPE is a scalable, low-threshold, therapist-assisted digital CBT-T, which could be readily implemented in services delivering psychosocial support after traumatic incidents if proven effective and cost-effective. The Early Support after Exposure to Trauma (EASE) study evaluates the effectiveness, cost-effectiveness, and implementation of Condensed Internet-delivered Prolonged Exposure (CIPE), applied as an indicated secondary prevention in the context of Norwegian municipal crisis teams. Methods/design : The EASE study is a hybrid Type 1 effectiveness and implementation trial. The effectiveness trial is a parallel two-armed multicenter randomized controlled add-on superiority trial, enrolling individuals who receive support from psychosocial crisis teams within 7 weeks after trauma. Participants are randomized to CIPE + treatment as usual (TAU) or TAU only. The primary outcome is the level of PTSD symptoms 6 weeks after randomization (10-13 weeks post trauma). Secondary outcomes include symptoms of depression and insomnia, quality of life, and CIPE cost-effectiveness. The implementation trial examines policy-level factors influencing CIPE implementation, using the Exploration, Preparation, Implementation, Sustainment framework. Discussion : This study will guide further research, policy shaping, and clinical initiatives for implementing preventive interventions aimed at reducing post-traumatic psychological sequelae by integrating evidence-based interventions into routine psychosocial services. Trial registration: ClinicalTrials.gov NTC302302. Date: 19.11.2024. Protocol version: Protocol version 3.0 (18.09.2025) is currently active. Prevention PTSD Psychosocial Support Cost-Effectiveness Implementation EPIS CBT-T CIPE Figures Figure 1 Structured summary Item Description Primary Registry and Trial Identifying Number {4} The trial is registered with ClinicalTrials.gov Identifier: NTC302302. Date: 19.11.2024. Secondary Identifying Numbers Na Source(s) of Monetary or Material Support The EASE study has received funding from the Research Council of Norway (project #344341). The study underwent full external peer review as part of the funding process. Primary Sponsor and contact information {3b} Norwegian centre for violence and traumatic stress studies. Pb. 181 Nydalen, 0409 Oslo, Norway. Role of sponsor and funder {3c} The sponsor covers indemnity insurance and legal liability for the current study, in addition to research infrastructure (e.g., personnel expenses, secure data storage, and data collecting systems). This study is designed and initiated by the PI and CoPIs. Thus, the funding organization (Research Council of Norway) has no role in the formulation of hypotheses, study design, data collection, analyses, or in the drafting of the manuscript. Contact for Public Queries Early Support after Exposure to Trauma (EASE) - NKVTS English Harald Bækkelund: Principal investigator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] Contact for Scientific Queries Harald Bækkelund: Principal investigator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] Public Title Early Support after Exposure to Trauma (EASE) Scientific title Early Support after Exposure to Trauma (EASE) Countries of Recruitment Norway Health Condition(s) or Problem(s) Studied F43.0 Acute stress reaction; F43.1 Post-traumatic stress disorder Intervention(s) Intervention arm: Condensed Internet delivered Prolonged Exposure (CIPE) + treatment as usual in municipal psychosocial crisis teams Comparator: Treatment as usual only in municipal psychosocial crisis teams Key Inclusion and Exclusion Criteria Inclusion Criteria: Receives support from a municipal crisis team Exposure to a traumatic event (as defined by criteria A for the diagnosis of post-traumatic stress disorder (PTSD) in the DSM-5) within the last seven weeks before randomization A total score of 10 or above on the PTSD Symptom Checklist-5 at the time of randomization Age 16 or above Written informed consent Writes and speaks English and/or Norwegian Exclusion Criteria: Severe psychopathology in need of specialized health care (e.g., psychotic symptoms, or high suicide risk) or substance dependence syndrome in need of specialized health care Known or evident severe cognitive impairment Ongoing traumatization, violence, or threats Unstable dose of psychotropic medication two weeks prior to randomization Concurrent therapy elsewhere before randomization Study Type A hybrid Type 1 effectiveness and implementation randomized controlled trial. RCT design: parallel two-armed multicenter randomized controlled superiority trial, designed to randomize participants to either CIPE + treatment as usual (TAU) or TAU only. Date of First Enrollment (planned) September 15 th 2024. Sample Size Power analysis: N = 150 Primary outcome(s) PTSD Checklist for DSM-5 (PCL-5) Key Secondary outcome(s) - Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) - Patient Health Questionnaire (PHQ-9) - Insomnia Severity Index (ISI) - Client Satisfaction Questionnaire (CSQ-8) - The EuroQol 5‑Dimension 5‑Level questionnaire (EQ-5D-5L) - The Recovering Quality of Life (ReQoL) - Traumatic grief inventory self report (TGI-SR+) Ethics Review The trial is approved by the Regional Committee for Medical and Health Research Ethics (REK-sør-øst, #708906) on 23.05.24, and is conducted following guidelines of good clinical practice (GCP) in accordance with the principle of the Declaration of Helsinki. All participants provide written informed consent before enrollment. Individual Trial Participant Data sharing statement In accordance with the ethical approval, deidentified individual clinical trial participant-level data is available from the trial PI upon reasonable request. Background The world is currently experiencing a deteriorating security situation characterized by increasing conflicts and wars. Climate change is expected to further escalate the frequency of disasters affecting individuals, families, and societies. The recent COVID-19 pandemic caused significant trauma worldwide, while civilian trauma from domestic abuse and suicide continues to rise in many societies. This convergence of threats underscores the critical importance of societal health preparedness as a priority for nations and multilateral bodies. Traumatic experiences represent a substantial cause of psychiatric disorders and poor mental health outcomes. A recent nationwide Swedish cohort study provides compelling evidence that traumatic stressors such as injury, assault, and bereavement lead to substantially elevated risks of subsequent psychological disorders, even after controlling for familial factors (1). Notably, the first year following the traumatic event emerges as an especially vulnerable period, highlighting that psychosocial support during this critical time window must be integrated into all preparedness plans. Posttraumatic Stress Disorder (PTSD) is the most prevalent psychiatric condition following traumatic experiences, affecting an estimated 1–9% of individuals over their lifetime (2,3). PTSD is associated with significant distress and increased risk of comorbid somatic and psychiatric conditions (4–6), as well as functional impairment, increased healthcare utilization, and substantial societal costs (7). However, the heterogeneity of victim needs after traumatic experiences presents a significant challenge for societal service planning. While acute stress symptoms—such as increased psychophysiological activation, anxiety, and intrusive memories or flashbacks—are common during the first months following potentially traumatic events (PTEs) (8), only approximately one in five individuals exhibit sustained or delayed-onset posttraumatic stress symptom (PTSS) trajectories. The majority demonstrate resilience or natural recovery (9). Consequently, the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines recommend watchful waiting in the aftermath of PTEs to identify those who develop persistent reactions before implementing interventions (10). Despite this cautious approach, both basic and clinical research indicate that processes occurring within the first weeks to months after a PTE may be decisive for PTSD development, suggesting that preventive interventions could be beneficial during this transitional period (11–14). Unfortunately, evidence for the efficacy of early preventive interventions after PTEs remains limited. A recent systematic review and meta-analysis reports the strongest support for cognitive-behavioral therapy with a trauma focus (CBT-T) applied as an indicated secondary preventive intervention (15). The pooled effect sizes of CBT-T range from small to moderate ( SMD = 0.49-0.70), depending on the control condition employed (15). Based on this evidence, the International Society for Traumatic Stress Studies’ practice guidelines recommend providing immediate information and support after PTEs, rapidly followed by CBT when indicated (16). Nevertheless, to our knowledge, CBT-T is not systematically implemented or routinely offered as an early intervention following PTEs in any health system. This gap may reflect the substantial resources required to establish and maintain such treatment capacity, as well as the limited high-quality evidence supporting such investments. Hence, there is an urgent need for low-threshold CBT-T interventions with proven efficacy and cost-effectiveness that can be readily implemented in services delivering psychosocial support after traumatic incidents. Condensed Internet-delivered Prolonged Exposure (CIPE) represents a promising solution to this challenge. CIPE is an indicated preventive intervention delivered soon after PTE exposure, designed to reduce acute stress symptoms and prevent PTSD development (17–19). The treatment is delivered as a written, therapist-assisted intensive intervention, with total therapist time typically ranging from one to three hours throughout the program. In a recent randomized controlled trial ( N = 102), CIPE significantly reduced PTSS compared to a waiting list control (17). The between-group effect size was moderate at week 3 ( d = 0.70) and large at week 7 ( d = 0.83), with effects maintained at 6-month follow-up and no severe adverse events reported. A qualitative follow-up study with a subsample ( N = 11) reports that participants describe CIPE as effective, demanding, feasible, and tolerable (18). These findings suggest that CIPE could represent an effective and cost-efficient approach to indicated PTSD prevention. However, demonstrating clinical effectiveness and cost-effectiveness is only the first step toward widespread implementation. The translation of evidence-based interventions into routine practice also requires careful consideration of the organizational and policy contexts in which they will be delivered. In Norway, responsibility for psychosocial support after PTEs is assigned to local municipalities, as mandated by various policy documents and laws (20). However, these policies provide limited specific guidance, resulting in considerable variation in how services are organized and delivered across municipalities. Most municipalities have established psychosocial crisis teams that are activated during crises and disasters to support those affected. These teams typically consist of professionals from diverse backgrounds who work in other services but are called upon during emergencies. Despite growing evidence for effective interventions that can be delivered following a PTE, systematic implementation of such interventions remains lacking in service delivery. Health policies can function as implementation determinants (i.e., factors that may be barriers or enablers), implementation strategies, or characteristics of the intervention being implemented (21). In this context, policy serves as an important contextual determinant that influences implementation outcomes (22). Unclear or conflicting policies may significantly impact crisis teams' capacity and opportunities to implement evidence-based interventions such as CIPE. As identified in the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, by examining the implementability of CIPE through the lens of EPIS inner (e.g., municipality, crisis services) and outer context (e.g., national, county) factors, innovation characteristics (e.g., CIPE), and bridging factors (i.e., bi-directional influences between outer and inner contexts) (23–25), we can better understand how existing policies influence the implementation of such interventions. This type of analysis can inform the development of targeted recommendations and guidelines to facilitate large-scale implementation, scale-up, and sustainment of evidence-based trauma interventions in Norwegian municipalities. Aims and hypotheses The study hypotheses and research questions are presented in Table 1. The primary aim is to examine the effectiveness of CIPE, delivered approximately one to two months after a trauma, as an indicated secondary prevention aimed at reducing PTSS and the incidence of PTSD. We will compare the effect of CIPE + TAU vs. TAU only, to examine whether CIPE has the potential to improve the ordinary psychosocial services provided by crisis teams. Secondary aims concerning the effectiveness of CIPE include examination of whether CIPE + TAU is superior to TAU in preventing symptoms of insomnia and depression at 6 weeks post randomization, and 6-, and 12- months after a PTE. Further, secondary aims concern the cost-effectiveness of CIPE. Specifically, this study will examine whether CIPE reduces demand for second-tier specialty mental health services and improves quality of life compared to TAU. EASE will also examine if the implementation of CIPE is cost-effective in a long-term perspective, including the effect on labor market participation. The final secondary aims concern the implementation of CIPE. The study will investigate how existing policies across outer and inner context-level influence implementation of CIPE, and what kinds of policy- and systems-level bridging factors are needed to support implementation and sustainment of CIPE. The EASE study design and data collection framework provide the opportunity to examine the extent of long-term mental health needs following traumatic events and to identify predictors of chronic post-traumatic difficulties. Although specific research questions addressing these longitudinal outcomes remain to be developed, such analyses represent potential avenues for future investigation within the project. Table 1 Hypotheses and research questions in the EASE study Hypotheses concerning the effectiveness and cost-effectiveness of CIPE H1. Participants receiving CIPE+TAU will have significantly less PTSS than participants receiving TAU at 6 weeks post T1, and at 6-, and 12- months after the traumatic incident. H2. Significantly fewer participants receiving CIPE+TAU will fulfill the criteria for PTSD compared to participants receiving TAU, at 6- and 12-months post trauma. H3. Participants receiving CIPE+TAU will have significantly less symptoms of depression and insomnia than participants receiving TAU at 6 weeks post T1, 6-, and 12- months after the traumatic incident. H4. Participants in the CIPE+TAU-condition will report significantly higher treatment satisfaction at post-treatment, compared to those in the TAU-condition. H5. Participants with traumatic loss receiving CIPE+TAU will have significantly less symptoms of prolonged grief than participants with traumatic loss receiving TAU 12 months after the loss. H6. Fewer participants in the CIPE+TAU-condition will be referred to second-tier specialty mental health services, and more will achieve improved quality of life within the first year after the traumatic incident, compared to participants in the TAU-condition. H7. The CIPE+TAU implementation is more cost-effective compared to TAU in the short run and may even dominate TAU in the long run (i.e., more effective and less costly). Research questions concerning the implementability of CIPE RQ1. How do existing policies across multi-level outer (i.e., national, county) and inner (i.e., municipality, crisis services) contexts influence implementation of CIPE? RQ2. What kinds of policy- and systems-level bridging factors are needed to support implementation and sustainment of CIPE? Note. CIPE: Condensed internet-delivered Prolonged Exposure; H: Hypothesis; PTE: Potentially Traumatic Experiences; PTSD: Post-traumatic stress disorder; PTSS: Post-traumatic stress symptoms; RQ: Research question; TAU: Treatment as usual. Methods Research context Twenty-one municipal crisis teams from the central-eastern parts of Norway participate in the study. The crisis teams are chosen to deliver the intervention due to their aforementioned role in the Norwegian health care system and the well-organized psychosocial services already offered by these teams. Participation requests were directed to municipal crisis teams by the Regional Resource Center for Violence, Traumatic Stress, and Suicide Prevention (RVTS East) to ensure variation in municipal population size, and municipalities from both rural and urban areas. A list of study sites is available in the trial registration (ClinicalTrials.gov Identifier: NTC302302). Trial design The EASE study is a hybrid Type 1 effectiveness and implementation trial (26) (for implementation, see section “implementation trial”). The first part of the study is a parallel two-armed multicenter randomized controlled add-on superiority trial, designed to randomize participants to either CIPE + TAU or TAU only. All participants will be offered ordinary crisis team services throughout the trial period. The CIPE group will be given CIPE as an add-on between T1 (4-7 weeks after trauma, dependent on the time of enrollment) and T2 (10-13 weeks after trauma, dependent on the time of T1 [i.e., T2 is always 6 weeks after T1]; see figure 1). For those included within three weeks from the incident, a screening assessment is performed at the time of recruitment (T0). Baseline assessment and evaluation of inclusion and exclusion criteria will be completed at T1. Outcome measures are gathered 6 weeks post randomization (T1), and follow-up measurements are accomplished at 6- and 12-month post PTE. This trial follows the SPIRIT guidelines and methodology (27) (see Additional file 1 for the SPIRIT checklist). Inclusion and exclusion criteria Inclusion criteria are a) persons that receive support from a municipal crisis team, after b) exposure to a traumatic event (as defined by criteria A of the PTSD-diagnosis in the DSM-5) (28) within four to seven weeks before T1, c) a total score of 10 or above on the PTSD Symptom Checklist (PCL-5) (29) at T1 (4-7 weeks post trauma, dependent on the time of inclusion), d) age 16 or above, e) written informed consent, and f) writes and speaks Norwegian and/or English. Exclusion criteria are a) severe psychopathology (e.g., psychotic symptoms, or high suicide risk) or substance dependence syndrome in need of specialized health care (harmful use is not an exclusion criteria, as long as participants commit to not being under the influence when completing the intervention), b) known or evident severe cognitive impairment, c) ongoing traumatization, violence, or threats, d) unstable dose of psychotropic medication two weeks prior to T1, and e) concurrent therapy elsewhere at the time of T1. Recruitment Table 2 presents the trials’ enrollment, intervention, and measurement schedule. Participants receive brief information regarding the trial in consultation with the crisis teams, within the first seven weeks after exposure to a PTE. If consenting, the participants receive exhaustive information about the study, along with a participation request from the research group. Written informed consent is gathered electronically before enrollment and stored in BASS. Crisis team staff repeatedly assure the participants that they will receive TAU, regardless of participation. This is also underscored in all written recruitment material. At enrollment, the crisis teams and the research group decide whether inclusion criterion B is met, using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) (30) A-criterion assessment. If eligible by self-report measures at T1, the participants are assessed with the Mini-International Neuropsychiatric Interview (MINI) (31) version 6 and the CAPS-5 by trained graduate clinical psychology students. The interviews are completed by telephone. ERL (licensed clinical psychologist and PhD candidate) monitors the process. To bolster response rates and diminish attrition, participants are given a symbolic monetary incentive (32,33) in the form of lottery tickets (value: 8€) upon completing all required self-report measures and interviews. The estimated flow of participants throughout the study phases is visualized in Figure 1. Randomization Eligible participants are randomized 1:1 in random block sizes of 4, 6, or 8 to either CIPE + TAU or TAU only, using the Sealed envelope software (34) at T1. To mitigate the risk of contamination across treatment conditions, participants from the same household are cluster-randomized. The randomization is stratified on the level of municipal crisis teams to ensure an even distribution of cases in each treatment condition across municipalities. An independent, blinded senior researcher is responsible for all randomization procedures. Interventions CIPE CIPE is an adaptation of Prolonged Exposure (PE) (35). PE is an exposure-based version of CBT-T that has been thoroughly empirically validated as a treatment for PTSD (36,37). CIPE consists of four written therapist-assisted modules, with corresponding homework assignments (17). The assignments comprise central treatment components, as well as questions regarding essential intervention components and principles, to ensure socialization. Participants are expected to work on these assignments for six hours weekly and are encouraged to have daily contact with their therapist via a secure email within the treatment platform. Phone sessions are also available when necessary. TAU Participants in the TAU condition receive standard psychosocial support that is routinely provided by the crisis teams. This could include a varying number of consultations (typically 1-4) consisting of psychoeducation and normalization of symptoms of acute stress, activation of the victim’s social network, practical support, and/or grief support (20). Although common practice is to follow the guidelines from the Norwegian Directorate of Health (20), there is considerable heterogeneity in what constitutes TAU within and between different crisis teams. This applies both to the content and frequency of support. Thus, consultation frequency, duration, type, and mode are assessed (see “other collected data”). Therapist training and fidelity The therapists in the current trial arecrisis team health care workers. They attend a one-day seminar held by the originator of CIPE (Bragesjö) or the study PI. The seminar consists of a thorough lecture on the theoretical basis of, and every intervention included in CIPE, as well as practical skills training in CIPE interventions. All therapists receive the CIPE treatment manual (unpublished). As all CIPE treatment components are delivered through standardized text, therapist drift is not possible other than in the secure emails. Continuous monitoring of therapist fidelity in these emails is thus accomplished by two senior consultant clinical psychologists, as well as the trial PhD/clinical psychologist (all trained in CIPE). Contamination For organizational and practical reasons, the majority of the crisis team therapists deliver both TAU and CIPE. Consequently, there is a risk of contamination across conditions at the therapist level. To reduce the risk of contamination, therapists are repeatedly instructed and reminded not to mix the conditions, and are prohibited from using the CIPE internet platform outside of the timeframe of CIPE delivery in each case. Cases of potential contamination will be reported, as the clinicians are instructed to report such cases to ERL. Data collection Table 2 presents the trials’ enrollment, intervention, and measurement schedule. Participants enrolled within three weeks after the incident are assessed with self-report measures at the time of enrollment (T0). All participants are subsequently assessed before randomization (T1), post-treatment (T2), and at 6-month (T3) and 12-month (T4) follow-ups. The main outcome will be measured at post-treatment (T2). Self-report data from participants are collected using an electronic survey solution offered by BASS at the Karolinska Institute, Stockholm. The same system is used to obtain written informed consent and to deliver CIPE. Links to questionnaires are sent to responders using SMS and email. Data from the therapists are collected using Nettskjema and Services of sensitive data (TSD) at the University of Oslo (see “data management and storing”). The research coordinator monitors the data collection process and sends reminders to reduce attrition rates. Assessments Primary outcome measure The PTSD Symptom Checklist (PCL-5) (29) is a 20-item questionnaire that measures DSM-5-specified symptoms of PTSD. The total score ranges from 0 to 80, with higher scores indicating more severe symptoms. Items are rated on a 0 (“not at all”) to 4 (“extremely”) Likert-type scale. The PCL-5 has satisfactory psychometric properties in various trauma populations (38–40). This study administers a validated Norwegian version of the PCL-5 (41,42). As the index trauma is only a few days before T0 for most participants, the recall period is revised to “since the traumatic event” for this measurement. In T1-T4, the standard recall period in the PCL-5 is applied (one month). PCL-5 constitutes the main outcome of this study. Secondary outcome measures The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) (30) is a 30-item structured interview, developed to assess current and lifetime PTSD diagnosis, as well as past-week PTSD symptoms. The instrument measures the 20 DSM-5 PTSD-symptoms, in addition to the onset and duration of symptoms, related subjective distress and functional impairment (social, occupational), amongst other aspects of the disorder. Standardized questions and probes are provided. A Norwegian version of the CAPS-5 (43) is administered at T1 and T3-4. CAPS-5 has excellent psychometric properties (30,44). The Mini-International Neuropsychiatric Interview (MINI) (31) version 6 is a brief, structured clinician-administered interview designed to assess 17 DSM/ICD diagnoses. Standardized questions and probes are provided. A Norwegian translation of the MINI (45) is administered at T1. The interview has good psychometric properties (31,46,47). A Norwegian version (48) of the Stressful Life Events Screening Questionnaire (SLESQ) (49) is administered at T1 to measure self-reported lifetime exposure to traumatic events. The respondents are asked to report exposure to 15 categories of traumatic events (“yes” or “no”), age at the time of the incident, as well as frequency and duration of the events. Other aspects of the incidents are reported, as well. The Norwegian version of the SLESQ incorporates two extra items compared to the original 13-item version: “Have you ever been directly affected by a natural disaster?” and “Has anyone outside your family, such as fellow pupils or colleagues, repeatedly ridiculed you, put you down, ignored you, or told you were no good?”. The SLESQ has satisfactory validity and reliability (49,50). The Patient Health Questionnaire (PHQ-9) (51) is a 9-item self-report measure of depressive symptom severity. The recall period is 2 weeks. Response is given on a 4-point Likert-type scale (0: not at all, 1: several days, 2: more than half the days, and 3: nearly every day), resulting in a total score ranging from 0 to 27. Higher scores indicate higher symptom severity. The instrument is sensitive for both clinical and sub-clinical levels of depressive symptoms and has good psychometric properties (51,52). We administer a validated Norwegian version of the PHQ-9 (53). The Insomnia Severity Index (ISI) (54) is a 7-item questionnaire that measures insomnia symptoms during the past two weeks. The instrument utilizes a 5-point Likert-type scale ranging from 0 to 4, yielding a total score of 0-28. Higher scores indicate more insomnia symptoms. The ISI has good psychometric properties (54–56). A Norwegian version of the ISI is applied. The Client Satisfaction Questionnaire (CSQ-8) (57) is an eight-item measure of participants’ service satisfaction. Response is given on a scale ranging from one to four, with a resulting total score ranging from eight to 32. Higher scores suggest higher service satisfaction. A validated Norwegian version of the CSQ-8 is applied (58). The CSQ-8 is adapted to the context of psychosocial crisis teams in the current trial (e.g., “treatment” adapted to “support”, “therapy” adapted to “support”). The Traumatic Grief Inventory-Self Report Plus (TGI-SR+) (59) is a 22-item self-report questionnaire measuring symptoms of DSM-5 persistent complex bereavement disorder (PCBD), and ICD-11 Prolonged grief disorder (PGD) in participants who experienced traumatic bereavement. Response is given on a 5-point Likert-type scale ranging from 1 (“never”) to 5 (“always”). The total score ranges from 22 to 110, with higher scores indicating more severe symptoms. The instrument, including the Norwegian version applied here, has good psychometric properties (60,61). The instrument is administered at a 12-month follow-up, and applies a recall period of the past month. The EuroQol 5‑Dimension 5‑Level Questionnaire (EQ‑5D‑5L) (62) assesses self-reported health-related quality of life. It has five items: Self-care, mobility, pain/discomfort, usual activities, and anxiety/depression, each measured on a 5-level severity scale (no, slight, moderate, severe, or unable/extreme problems). The instrument defines 3125 possible health states, valued by a representative sample of the general Norwegian population using the hybrid valuation method – composite time-trade-off and discrete choice experiment (63). The utility scores are anchored on a -0.453 – 1 scale, with 1 indicating ‘full-health’, 0 equivalent to ‘being dead’, and values below 0 are worse than being dead. The EQ-5D-5L data are used to generate quality-adjusted life year (QALY) used for cost-utility analysis (CUA). The instrument has excellent psychometric properties (64). The Recovering Quality of Life (ReQoL) is an 11-item outcome measure assessing psychopathology-specific quality of life in mental health contexts (65). For each item, response is given on a 5-point scale (never to most of the time or always). The study also uses the ReQoL utility index (ReQoL-UI), which is a recovery-focused generic preference-based measure derived from ReQoL. ReQoL-UI constitutes six mental health items (activity; belonging; choice, control, and autonomy; hope; self-perception; and well-being) and a physical health item, each with five severity levels. The ReQoL-UI defines 78,125 different health states valued by a representative member of the UK public using a conventional time-trade-off method (66). The ReQoL-UI is also used to generate QALYs for CUA in mental health interventions. The ReQoL-UI values range between -0.195 (for the worst health state) and 1 (for the full-health state), with zero indicating a health state equivalent to being dead. Other collected data A structured adverse events (AE) questionnaire applied in the aforementioned RCT of CIPE (17) is utilized. The questionnaire was used in a previous trial with similar results to face-to-face interviews (67). The instrument captures the frequency, duration, and nature of possible adverse events, and such events are further classified based on their perceived association with CIPE (related or unrelated). Both participants and clinicians are asked to report and rate participants’ short- and long-term discomfort of any AEs on a scale from 0 (‘did not affect me at all’) to 3 (‘affected me very negatively’). In both TAU and CIPE, all time and resource use of therapists (i.e., treatment, travel, online tasks, appointments, preparation, and competence level of therapists) are registered. Registry data is also utilized for all participants, using the Norwegian Patient Register (NPR), Control and Payment of Health Reimbursement (KUHR), Municipal patient- and user-register (KPR), and FD-Trygd. However, in the absence of reliable registry data on the use of health care resources in the municipalities, this study applies survey data reported every second month by the crisis teams’ personnel, via a generic questionnaire. Consultation duration, type (e.g., CIPE, grief support, practical support), and mode (e.g., telephone, video consultation, home visit), as well as the professional background of the involved personnel, are reported from T1 to T4. In the CIPE+TAU-arm, both clinicians and participants are assessed with a nine-item generic, unvalidated self-report measure of reasons for drop-out from CIPE, in cases where the participant did not finish CIPE. The questionnaire maps lack of motivation, disliking of e-therapy, lack of relevance, lack of reduction of PTSS, worsening of PTSS, remission, concurrent therapy elsewhere, and other (qualitative response category) as possible sources of drop-out. Response is given in one of two categories (0: no, 1: yes), except for the mentioned qualitative item. Participants are also asked to self-report sociodemographic and background data: year of birth, gender, relationship and cohabitation status, country of birth (self and parents), educational and employment status, current use of psychotropic medication, current psychological treatment (outside of the trial), and ongoing threats or violence. Statistical analyses H1-3 are tested with linear mixed effects models. The linear mixed effects model includes fixed effects for treatment group (intervention vs. control) and time (post-intervention, 6 and 12 months). In a hierarchical setup, a second step includes a treatment × time interaction. Random effects include random intercepts for participants to account for individual differences. The mixed effects models are applied using the R package nlme (68). H4-6 are examined using independent t-tests. The quality-of-life change (change in QALY) of participants in CIPE vs TAU (H6) is analyzed using the mixed effects model. Estimation is conducted using restricted maximum likelihood, with all available observations included, yielding unbiased estimates under the assumptions of missing at random or missing completely at random. For the t-tests, missing data are handled using multiple imputation. Hypothesis 7 involves a comprehensive economic evaluation comparing the cost-effectiveness of CIPE relative to TAU in terms of both costs and consequences/effectiveness (69). Costs are assessed using the ingredients approach, which involves three steps. First, identifying each resource required for the intervention, then measuring these resources, and finally valuing them. The effectiveness of the intervention is measured by QALY – a composite measure combining both quantity of life (mortality) and quality of life (morbidity) into a single metric (70). For each arm, mean costs and mean QALYS are estimated across all participants to calculate the incremental cost (ΔC) and incremental effect (ΔQALY). The incremental cost-effectiveness ratio (ICER) or incremental cost per incremental QALY (ΔC/ΔQALY) is then calculated for decision-making. To accept the intervention, ICER should be less than the willingness-to-pay or cost-effectiveness threshold. Since there is no official threshold in Norway, we apply a threshold recommended by the Norwegian Directorate of Health (NOK 500 000 at 2005 prices), adjusted to current price levels (71). This economic evaluation is conducted in two ways: trial- and model-based approaches. In the former, we compare trial-specific intervention costs and effects. Following recommendations by NICE (72), we perform a cost-utility analysis combining intervention-related and wider healthcare costs with changes in QALYs. In the latter, we develop a decision analytic model to simulate the long-term (lifetime) cost-effectiveness of CIPE. The model extrapolates beyond the trial period to estimate the potential lifetime costs and QALY outcomes under different assumptions. In both approaches, model parameter uncertainty are assessed using both probabilistic and deterministic sensitivity analyses. Power and sample size calculations Previous CIPE studies report effect sizes within the range of d = 0.6 - 0.8. For the primary hypothesis in this study, a more conservative effect size of d = 0.3 is expected. With 95% power and an α -level of 0.05, 150 participants (73 in each group minimum) are required to detect a significant between-group effect. Consequently, assuming a 20% data attrition rate, at least 183 participants should be recruited. The municipal crisis teams involved in the study currently cover approximately 1,080,000 inhabitants. Although official statistics on the number of traumatic events handled by these teams are lacking, based on the best unofficial statistics available, a conservative estimate suggests 0.5 to 1 case per 1000 inhabitants annually. With a cautious estimate of 0.5, and with each incident involving a mean of two victims aged 16 or older, about 2150 victims are eligible for recruitment over 2 years. Moreover, we assume a ~50% response rate (73) and that approximately 30% have PTSD symptoms one month after the incident (74). These parameters result in a sample of 360 participants, which constitutes the recruitment target. Assuming an overall attrition rate of 40%, 216 participants will complete the 12-month follow-up assessment. Oversight and monitoring Data management and storage Each enrolled participant is assigned a unique study ID. The ID number is linked to each participant’s social security number, stored in a separate coupling key-file in the Services of sensitive data (TSD) at the University of Oslo. TSD uses the highest possible level of IT security, and data files are continuously backed up. Participant self-report data is gathered in BASS (identical security procedures as TSD) and securely exported to TSD for statistical analyses. Trial data are stored at least five years after data collection is concluded (anticipated completion date: December 31st, 2027). A Data Protection Impact Assessment (DPIA) with risk and security measures is in place, collaborating with Sikt (the national agency providing shared digital services and infrastructure for the Norwegian knowledge sector). The Data Protection Official at Sikt and at the Norwegian Centre for Violence and Traumatic Stress Studies (sponsor’s) both acknowledge the DPIA. Only the principal investigators and ERL will have access to the final trial dataset. ANL and EK will have access to the data necessary for the investigation of H6-7. Safety and monitoring procedures for adverse events Despite the lack of severe adverse events (AE) in a recent RCT of CIPE (17), the trial has established procedures to monitor AEs and serious adverse events (sAE). Health personnel in the crisis teams are instructed to monitor and address AE continuously. Unmet healthcare needs that are discovered by the research teams in the T1-4 assessments are communicated to the individual’s therapist in the municipality. Moreover, self- and clinician-reported (s)AE are assessed at T2 (see instruments). Adverse events are defined as any unfavorable experience occurring to participants during the trial. Serious adverse events are defined as incidents including death, (attempted) suicide, serious self-harm, acute mania or psychosis, severe intoxication, or other psychological or somatic conditions requiring emergency medical care. After the first 18 participants are randomized (corresponding to 10% of the target sample size based on the power analysis), an internal pilot study will be conducted in accordance with the CONSORT guidelines for randomized feasibility and pilot trials (75,76). The pilot will assess AEs and sAEs. If the rate of AEs is substantially higher than reported in previous studies of CIPE and/or any sAEs occur, the advisory board will consider protocol modifications and/or discontinuation of the trial. Should such deliberations arise, the project owner will retain the final authority to decide whether the trial will be terminated. Blinding The graduate clinical psychology students performing the clinical interviews are blinded. Participants are instructed not to report their assigned condition in interviews. In case of spontaneous unblinding, the interview is terminated and repeated in its entirety by another blinded assessor. Blinding of participants and therapists is not possible due to the nature of the interventions. Data analysis is conducted by the trial statistician (MSB), who is blinded to treatment assignment for the entirety of the trial. ANL and EK perform health economic analyses and are blinded to treatment condition. Protocol violations and revisions All included participants are included in the intent-to-treat analyses. Participants who do not complete CIPE within T2, or report adjustment of psychotropic medication or concurrent therapy elsewhere, as well as ongoing traumatization, violence, or threats after T1, and drop out of the trial, are not included in the completers analyses. Protocol revisions have been and will be updated in the clinical trial registry and communicated to REK for approval in accordance with the contract. Implementation trial The overarching aim of the implementation trial is to understand how policy- and systems-level factors across national, regional, and municipal levels influence the uptake and sustainment of CIPE within municipal crisis services operating under multi-level governance. The study maps how national policies, regional agreements, and municipal plans interact to shape CIPE implementation, including considerations of costs and political support, as well as bridging factors such as policy directives, agreements, and/or contracts for services. It assesses how policy guidelines, regional arrangements, and municipal plans align with or diverge from CIPE requirements, with the goal of producing practical recommendations to strengthen bridging mechanisms, promote durable adoption, and inform scaling of CIPE across municipalities. To examine how existing policies across outer and inner contexts influence CIPE implementation (21,23,25), the study adopts a mixed qualitative design that combines document review, qualitative interviews, and observational methods. Key topics across document reviews and interviews include how policies influence service provision, how stakeholders at both policy and system level (e.g., municipal service providers, policy developers) consider costs, the level of political support for crisis services and CIPE, whether there are ambiguities in responsibility and decision-making, and misalignment between agencies, and organizational culture affecting CIPE uptake. The document review includes sentinel policy surveillance methods for tracking laws and policies over time regarding the organization of municipal crisis teams. The legal mapping is carried out at three governance levels: national (Ministry and Directorate of Health), county/regional (County Governors or equivalent regional authorities), and municipal (leaders or team members of psychosocial crisis teams). At the national and county level, relevant policy documents on psychosocial preparedness, follow-up, funding, responsibilities, and intergovernmental collaboration are identified and refined in consultation with the Ministry of Health and Care Services, the Directorate of Health, and the County Administrator. A structured document analysis maps how policies frame preparedness and follow-up, and define roles and accountability across levels. At the municipal level, a stratified sampling of municipalities is carried out to capture diversity in geographic and systemic contexts. Psychosocial preparedness plans are reviewed, focusing on content, organization, providers, context, and collaboration with GPs and referral pathways to specialized services. The qualitative interviews involve semi-structured interviews with actors at the same three governance levels: national, county, and municipality. At the national and county level, relevant persons who have participated in the formulation of, or are responsible for implementing relevant laws and policy documents at the Ministry of Health and Care Services, the Directorate of Health, and the County Administrator are interviewed. At the municipal level, municipal crisis team leaders or other psychosocial care providers are interviewed to understand which policies guide planning and organization. The output will be a policy map detailing alignment and gaps between national directives and municipal practices. In addition to document reviews and interviews, training materials, formal agreements, and observational notes collected during the CIPE testing are included. Data are analyzed iteratively and thematically to identify potential bridging factors, barriers, enablers, and how policy contexts and decision-making processes shape implementation choices. A logic model will illustrate how outer context and inner context factors can support sustainable CIPE implementation, including uptake, costs, political support, relational ties (e.g., partnerships), and processes (e.g., communication, data-sharing) and long-term viability. The analysis explicitly addresses bridging mechanisms and will culminate in actionable policy implementation strategies and recommendations for durable intergovernmental collaboration (contracts, partnerships, data-sharing). Dissemination The study results will be published in scientific journals irrespective of whether the results support the hypotheses or not. Discussion This study has three working packages with respective aims. First, the study aims to investigate the effectiveness of CIPE, as an add-on treatment to TAU in psychosocial crisis teams, in reducing post-traumatic psychological sequelae. Second, the cost-effectiveness of CIPE is examined. Third, the influence of existing policies on the implementation and sustainment of CIPE is researched. Although most individuals exposed to a PTE do not develop PTSD, a substantial minority experience prolonged post-traumatic sequela. There is promising meta-analytical evidence for indicated secondary preventive interventions based on CBT-T interventions (15), and such early interventions are efficacious and safe (17,77). This trial adds to the literature by examining the effectiveness of CIPE on reducing post-traumatic psychological distress in the context of Norwegian municipal crisis teams. Consequently, the trial could generate important knowledge regarding which individuals are at risk of developing PTSD after PTEs, and whether CIPE effectively reduces post-traumatic psychological distress. Beyond clinical outcomes, the trial generates knowledge about the economic implications of implementing CIPE, including potential reductions in the need for specialist secondary mental health care. Furthermore, EASE investigates the implementation of preventive interventions for PTSD in primary-level health services such as municipality crisis services. Additionally, we examine how health policies impact the implementation of evidence-based practices in this context. Both these research topics are understudied in implementation science (21). In summary, the EASE study addresses important knowledge gaps concerning evidence-based secondary prevention of PTSD and psychosocial care for victims of crises and disasters, and the health economics and implementation factors involved in such interventions. Strengths and limitations The current study has several strengths. First, the multi-center effectiveness design improves the external validity, providing policy makers and municipal crisis teams with important knowledge regarding evidence-based indicated preventive interventions after trauma. If CIPE is effective in reducing PTSS within the context of municipal crisis teams, this could enhance the generalizability of the findings significantly, as the implementation closely reflects how the crisis teams typically operate. Second, EASE represents an innovation in research on early interventions after PTEs and hybrid trial designs, by investigating the effectiveness, cost-benefits, and implementability of CIPE in a single trial. Finally, the use of a scalable, digitalized, evidence-based indicated preventive intervention (i.e., CIPE) in ordinary services (i.e., not ad-hoc services established after major disasters) is another strength. This study also has limitations that warrant consideration. First, the therapists and participants are not blinded, which could induce placebo effects. Nevertheless, the interviewers are blinded, ensuring single-blind assessments. Furthermore, there might be unequal treatment intensity across the groups (i.e., the TAU+CIPE condition receiving more treatment than the TAU-only condition). There is also a risk of contamination between conditions, due to the aforementioned design. Moreover, recruitment could be delayed due to multiple factors (e.g., low response rates, participant preference for avoidance instead of exposure, study implementation barriers on therapist- or system level). Trial status The recruitment started in September 2024 and is ongoing. The estimated recruitment completion date is September 2026. The estimated project completion date is December 31, 2027. Abbreviations AE: adverse events; CAPS-5: The Clinician-Administered PTSD Scale for DSM-5; CAPS-5 A-criteria: Only the assessment of whether the A-criteria has been fulfilled in the CAPS-5; CBT: Cognitive-Behavioral Therapy; CBT-T: Cognitive-Behavioral Therapy with a trauma focus; CIPE: Condensed Internet-Delivered Prolonged Exposure; CSQ-8: Client Satisfaction Questionnaire; CUA: Cost-Utility Analysis; DPIA: Data protection impact assessment; DSM-5: Diagnostic and Statistical Manual for Mental Disorders, fifth edition; EPIS: Exploration, Preparation, Implementation, Sustainment Framework; EQ-5D-5L: EuroQol 5-Dimension 5-Level Questionnaire; H: Hypothesis; ICER: Incremental Cost-Effectiveness Ratio; ISI: Insomnia Severity Index; KPR: Municipal Patient- and User-Register; KUHR: Control and Payment of Health Reimbursement; MINI: Mini-International Neuropsychiatric Interview version 6; NICE: National Institute for Health and Care Excellence; NPR: Norwegian Patient Register; PCL-5: PTSD Symptom Checklist for DSM-5; PE: Prolonged Exposure; PHQ-9: Patient Health Questionnaire-9; PTE: Potentially Traumatic Events; PTSD: Post-Traumatic Stress Disorder; PTSS: Post-Traumatic Stress Symptoms; QALY: Quality-Adjusted Life Year; ReQoL: Recovering Quality of Life; ReQoL-UI: ReQoL Utility Index; RQ: Research Question; (s)AE: Severe adverse events; SLESQ: Stressful Life Events Screening Questionnaire; TAU: Treatment as usual; TGI-SR+: Traumatic Grief Inventory – Self Report Plus. Declarations Ethics approval and consent to participate The trial is approved by the Regional Committee for Medical and Health Research Ethics (REK-sør-øst, #708906) on 23.05.24, and is conducted following guidelines of good clinical practice (GCP) in accordance with the principle of the Declaration of Helsinki. All participants provide written informed consent before enrollment. Consent for publication Upon providing informed consent, all participants are informed that the study results will be published in international scientific journals and that identification of individual participants will not be possible based on the manuscripts. A model consent from is available from the PI upon reasonable request. Availability of data and materials In accordance with the ethical approval, deidentified individual clinical trial participant-level data is available from the trial PI upon reasonable request. Only the principal investigators and ERL will have access to the final trial dataset. ANL and EK will have access to the data necessary for the investigation of H6-7. Competing interests MB is the developer of CIPE, but has no financial conflict of interest. The authors declare that they have no competing interests. Funding The EASE study has received funding from the Research Council of Norway (project #344341). The study underwent full external peer review as part of the funding process. Authors' contributions Conceptualization: HB, KE, MSB, ELC, GAA, DB, NPR. Securing funding and study leadership: HB, KE, MSB; Design: ERL, HB, KE, MSB. Obtaining ethical approval: ERL & HB. Writing first draft of the manuscript: ERL, HB, KE, LES, AL. Revision of the manuscript: all authors. All authors have read and agreed to the published version of the manuscript. Acknowledgements We are thankful for the contributions of all participants, user representatives, members of the psychosocial crisis teams, research assistants, and advisors. Administrative information Roles and responsibilities (contributorship): Harald Bækkelund: Principal investigator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] Marianne S. Birkeland: Co-Principal investigator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway. [email protected] Karina Egeland: Co-Principal investigator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] Lise E. Stene: Senior researcher. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] Espen R. Lassen: Trial PhD-candidate and coordinator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] Admassu N. Lamu: Associate investigator. NORCE Norwegian Research Centre– Health Services and Health Economics, Bergen, Norway. [email protected] Egil Kjerstad: Associate investigator. NORCE Research – Health Services and Health Economics, Bergen, Norway. [email protected] Belinda Ekornås: Associate consultant. RVTS East - Regionalt ressurssenter om vold, traumatisk stress og selvmordsforebygging. [email protected] Nils Petter Reinholdt: Associate consultant. RVTS East - Regionalt ressurssenter om vold, traumatisk stress og selvmordsforebygging. [email protected] Dorte Brodersen: Associate consultant. RVTS East - Regionalt ressurssenter om vold, traumatisk stress og selvmordsforebygging. [email protected] Maria Bragesjö: Associate consultant. Karolinska Institutet, Stockholm, Sweden. [email protected] Erika L. Crable: Associate investigator. Department of Health Policy and Management, University of California, Los Angeles, Los Angeles, CA, USA. [email protected] Gregory A. Aarons: Associate investigator. Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. [email protected] Roles and responsibilities (committees): The project owner for EASE is the trial sponsor (represented by Cecilie Daae and Geir Ove Kværk). The project group consists of HB, MSB, KE, LES, ERL, BE, NPR, and DB. EASE also has a scientific advisory board with leading experts in trauma interventions, methodology, implementation, and health policy (GAA, Miranda Olff, Joar Øveraas Halvorsen, Filip Arnberg). References Chen Y, Shen Q, Lichtenstein P, Gradus JL, Arnberg FK, Larsson H, et al. Incidence Trajectories of Psychiatric Disorders After Assault, Injury, and Bereavement. JAMA Psychiatry. 2024 Apr 1;81(4):374. Atwoli L, Stein DJ, Koenen KC, McLaughlin KA. Epidemiology of posttraumatic stress disorder: prevalence, correlates and consequences. Curr Opin Psychiatry. 2015 July;28(4):307–11. Koenen KC, Ratanatharathorn A, Ng L, McLaughlin KA, Bromet EJ, Stein DJ, et al. Posttraumatic stress disorder in the World Mental Health Surveys. Psychol Med. 2017 Oct;47(13):2260–74. Pietrzak RH, Goldstein RB, Southwick SM, Grant BF. Prevalence and Axis I comorbidity of full and partial posttraumatic stress disorder in the United States: Results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. J Anxiety Disord. 2011 Apr;25(3):456–65. Pietrzak RH, Goldstein RB, Southwick SM, Grant BF. Medical Comorbidity of Full and Partial Posttraumatic Stress Disorder in US Adults: Results From Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Psychosom Med. 2011 Oct;73(8):697. Taft CT, Stern AS, King LA, King DW. Modeling physical health and functional health status: The role of combat exposure, posttraumatic stress disorder, and personal resource attributes. J Trauma Stress Off Publ Int Soc Trauma Stress Stud. 1999;12(1):3–23. Bothe T, Jacob J, Kröger C, Walker J. How expensive are post-traumatic stress disorders? Estimating incremental health care and economic costs on anonymised claims data. Eur J Health Econ. 2020 Aug 1;21(6):917–30. Bryant RA. The Current Evidence for Acute Stress Disorder. Curr Psychiatry Rep. 2018 Oct 13;20(12):111. Galatzer-Levy IR, Huang SH, Bonanno GA. Trajectories of resilience and dysfunction following potential trauma: A review and statistical evaluation. Clin Psychol Rev. 2018 July;63:41–55. NICE. Post-traumatic stress disorder. National Institute for Health and Care Excellence; 2018. Cohen S, Kaplan Z, Zohar J, Cohen H. Preventing sleep on the first resting phase following a traumatic event attenuates anxiety-related responses. Behav Brain Res. 2017 Mar;320:450–6. Kearns MC, Ressler KJ, Zatzick D, Rothbaum BO. Early Interventions for Ptsd: A Review. Depress Anxiety. 2012;29(10):833–42. Norrholm SD, Vervliet B, Jovanovic T, Boshoven W, Myers KM, Davis M, et al. Timing of extinction relative to acquisition: A parametric analysis of fear extinction in humans. Behav Neurosci. 2008;122(5):1016–30. Rothbaum BO, Davis M. Applying Learning Principles to the Treatment of Post-Trauma Reactions. Ann N Y Acad Sci. 2003;1008(1):112–21. Bisson JI, Wright LA, Jones KA, Lewis C, Phelps AJ, Sijbrandij M, et al. Preventing the onset of post traumatic stress disorder. Clin Psychol Rev. 2021 June;86:102004. O’Donnell ML, Pacella BJ, Bryant RA, Olff M, Forbes D. Early intervention for trauma‑related psychopathology. In: Forbes D, Bisson JI, Monson C, Berliner L, editors. Effective treatments for PTSD: Practice guidelines from the International Society for Traumatic Stress Studies. 3rd edn The Guilford Press; 2020. p. 117–36. Bragesjö M, Arnberg FK, Olofsdotter Lauri K, Aspvall K, Särnholm J, Andersson E. Condensed Internet-delivered prolonged exposure provided soon after trauma: a randomised trial. Psychol Med. 2023 Apr;53(5):1989–98. Bragesjö M, Arnberg FK, Jelbring A, Nolkrantz J, Särnholm J, Olofsdotter Lauri K, et al. Demanding and effective: participants’ experiences of internet-delivered prolonged exposure provided within two months after exposure to trauma. Eur J Psychotraumatology. 2021 Jan 1;12(1):1885193. Bragesjö M, Arnberg FK, Särnholm J, Olofsdotter Lauri K, Andersson E. Condensed internet-delivered prolonged exposure provided soon after trauma: A randomised pilot trial. Internet Interv. 2021 Mar;23:100358. Norwegian Directorate of Health. Mestring, samhørighet og håp: Veileder for psykososiale tiltak ved kriser, ulykker og katastrofer. Norwegian Directorate of Health; 2016. Crable EL, Lengnick-Hall R, Stadnick NA, Moullin JC, Aarons GA. Where is “policy” in dissemination and implementation science? Recommendations to advance theories, models, and frameworks: EPIS as a case example. Implement Sci. 2022 Dec 12;17(1):80. Purtle J, Moucheraud C, Yang LH, Shelley D. Four very basic ways to think about policy in implementation science. Implement Sci Commun. 2023 Sept 12;4(1):111. Aarons GA, Hurlburt M, Horwitz SM. Advancing a Conceptual Model of Evidence-Based Practice Implementation in Public Service Sectors. Adm Policy Ment Health. 2011;38(1):4–23. Lengnick-Hall R, Willging C, Hurlburt M, Fenwick K, Aarons GA. Contracting as a bridging factor linking outer and inner contexts during EBP implementation and sustainment: a prospective study across multiple U.S. public sector service systems. Implement Sci. 2020 June 11;15(1):43. Moullin JC, Dickson KS, Stadnick NA, Rabin B, Aarons GA. Systematic review of the Exploration, Preparation, Implementation, Sustainment (EPIS) framework. Implement Sci. 2019 Jan 5;14(1):1. Curran GM, Bauer M, Mittman B, Pyne JM, Stetler C. Effectiveness-implementation Hybrid Designs. Med Care. 2012 Mar;50(3):217–26. Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013 Jan 9;346:e7586. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th edn. Washington, DC; 2013. Weathers FW, Litz BT, Keane TM, Palmieri PA, Marx BP, Schnurr PP. National center for PTSD. 2013. The PTSD Checklist for DSM-5 (PCL-5). Available from: https://www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp Weathers FW, Bovin MJ, Lee DJ, Sloan DM, Schnurr PP, Kaloupek DG, et al. The Clinician-Administered PTSD Scale for DSM–5 (CAPS-5): Development and Initial Psychometric Evaluation in Military Veterans. Psychol Assess. 2018 Mar;30(3):383–95. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(20):22–33. Parkinson B, Meacock R, Sutton M, Fichera E, Mills N, Shorter GW, et al. Designing and using incentives to support recruitment and retention in clinical trials: a scoping review and a checklist for design. Trials. 2019 Nov 9;20(1):624. Treweek S, Lockhart P, Pitkethly M, Cook JA, Kjeldstrøm M, Johansen M, et al. Methods to improve recruitment to randomised controlled trials: Cochrane systematic review and meta-analysis. BMJ Open. 2013 Jan 1;3(2):e002360. Sealed Envelope Ltd. Create a blocked randomisation list [Accessed 10th of May 2024]. [Internet]. 2022. Available from: https://www.sealedenvelope.com/simple-randomiser/v1/lists Foa EB, Hembree EA, Rothbaum BO, Rauch SAM. Prolonged Exposure Therapy for PTSD: Emotional processing of traumatic experiences - therapist guide. 2nd edn. Oxford University Press Inc; 2019. 200 p. Cusack K, Jonas DE, Forneris CA, Wines C, Sonis J, Middleton JC, et al. Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis. Clin Psychol Rev. 2016 Feb;43:128–41. McLean CP, Foa EB. State of the Science: Prolonged exposure therapy for the treatment of posttraumatic stress disorder. J Trauma Stress. 2024 Apr 23;jts.23046. Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation. J Trauma Stress. 2015;28(6):489–98. Mekawi Y, Silverstein MW, Walker A, Ishiekwene M, Carter S, Michopoulos V, et al. Examining the psychometric properties of the PCL-5 in a black community sample using item response theory. J Anxiety Disord. 2022;87:102555. Sveen J, Bondjers K, Willebrand M. Psychometric properties of the PTSD Checklist for DSM-5: a pilot study. Eur J Psychotraumatology. 2016;7(1):30165. Heir T. PCL-5. Norwegian centre for violence and traumatic stress studies; 2014. Lassen ER, Omre AN, Birkeland MS, Egeland K, Bækkelund H. Psychometric evaluation of the PTSD Checklist for the DSM-5 (PCL-5) in Norway. Eur J Psychotraumatology. 2025 Dec 31;16(1):2570951. Bækkelund H, Aareskjold J, Endsjø M. Norwegian centre for violence and traumatic stress studies. 2015. KLINIKERADMINISTRERT PTSD-SKALA FOR DSM-5: Versjon for vurdering av siste måned. Available from: https://www.nkvts.no/content/uploads/2018/03/KLINIKERADMINISTRERT-PTSD-SKALA-FOR-DSM-5-KAPS-5.pdf Marx BP, Lee DJ, Norman SB, Bovin MJ, Sloan DM, Weathers FW, et al. Reliable and clinically significant change in the clinician-administered PTSD Scale for DSM-5 and PTSD Checklist for DSM-5 among male veterans. Psychol Assess. 2022;34(2):197–203. Leiknes KA, Malt UF. Oslo University Hospital. 2009. MINI INTERNASJONALT NEVROPSYKIATRISK INTERVJU: Norwegian Translation Version 6.0.0 DSM-IV. Available from: https://www.oslo-universitetssykehus.no/4a7fdb/contentassets/895610f6458a4ab89886fa06395d5745/dokumenter/m.i.n.i-skaringskjema-norsk-versjon.pdf Lecrubier Y, Sheehan D, Weiller E, Amorim P, Bonora I, Harnett Sheehan K, et al. The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI. Eur Psychiatry. 1997 Jan 1;12(5):224–31. Sheehan D, Lecrubier Y, Harnett Sheehan K, Janavs J, Weiller E, Keskiner A, et al. The validity of the Mini International Neuropsychiatric Interview (MINI) according to the SCID-P and its reliability. Eur Psychiatry. 1997;12(5):232–41. Thoresen S, Øverlien C. Norwegian centre for violence and traumatic stress studies. 2013. KARTLEGGING AV BELASTENDE LIVSHENDELSER (KBL). Available from: https://www.nkvts.no/content/uploads/2018/03/Kartlegging-av-belastende-livshendelser_KBL.pdf Goodman LA, Corcoran C, Turner K, Yuan N, Green BL. Assessing traumatic event exposure: General issues and preliminary findings for the Stressful Life Events Screening Questionnaire. J Trauma Stress. 1998;11(3):521–42. Green BL, Chung JY, Daroowalla A, Kaltman S, DeBenedictis C. Evaluating the Cultural Validity of the Stressful Life Events Screening Questionnaire. Violence Women. 2006 Dec;12(12):1191–213. Kroenke K, Spitzer RL, Williams JB. The PHQ‐9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–13. Brattmyr M, Lindberg MS, Solem S, Hjemdal O, Havnen A. Factor structure, measurement invariance, and concurrent validity of the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder scale-7 in a Norwegian psychiatric outpatient sample. BMC Psychiatry. 2022 July 11;22(1):461. Wisting L, Johnson SU, Bulik CM, Andreassen OA, Rø Ø, Bang L. Psychometric properties of the Norwegian version of the Patient Health Questionnaire-9 (PHQ-9) in a large female sample of adults with and without eating disorders. BMC Psychiatry. 2021 Jan 5;21(1):6. Bastien C. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001 July;2(4):297–307. Buysse DJ, Ancoli-Israel S, Edinger JD, Lichstein KL, Morin CM. Recommendations for a Standard Research Assessment of Insomnia. Sleep. 2006 Sept 1;29(9):1155–73. Morin CM, Belleville G, Bélanger L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011;34(5):601–8. Larsen DL, Attkisson CC, Hargreaves WA, Nguyen TD. Assessment of client/patient satisfaction: Development of a general scale. Eval Program Plann. 1979 Jan 1;2(3):197–207. Pedersen H, Havnen A, Brattmyr M, Attkisson CC, Lara-Cabrera ML. A digital Norwegian version of the client satisfaction questionnaire 8: factor validity and internal reliability in outpatient mental health care. BMC Psychiatry. 2022 Oct 31;22(1):671. Boelen PA, Smid GE. The Traumatic Grief Inventory Self-Report Version (TGI-SR): Introduction and Preliminary Psychometric Evaluation. J Loss Trauma. 2017 Apr 3;22(3):196–212. Boelen PA, Djelantik AAAMJ, de Keijser J, Lenferink LIM, Smid GE. Further validation of the Traumatic Grief Inventory-Self Report (TGI-SR): A measure of persistent complex bereavement disorder and prolonged grief disorder. Death Stud. 2019 July 3;43(6):351–64. Lenferink LIM, van Dijk I, Eisma MC, Eklund R, Boelen PA, Sveen J. Psychometric evaluation of the Swedish Traumatic Grief Inventory Self-Report Plus (TGI-SR+) in bereaved parents. Clin Psychol Psychother. 2024;31(1):e2922. Herdman M, Gudex C, Lloyd A, Janssen MF, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727–36. Garratt AM, Stavem K, Shaw JW, Rand K. EQ-5D-5L value set for Norway: a hybrid model using cTTO and DCE data. Qual Life Res. 2025;34(2):417–27. Feng YS, Kohlmann T, Janssen MF, Buchholz I. Psychometric properties of the EQ-5D-5L: a systematic review of the literature. Qual Life Res. 2021 Mar 1;30(3):647–73. Keetharuth AD, Brazier J, Connell J, Bjorner JB, Carlton J, Buck ET, et al. Recovering Quality of Life (ReQoL): a new generic self-reported outcome measure for use with people experiencing mental health difficulties. Br J Psychiatry. 2018 Jan;212(1):42–9. Keetharuth AD, Rowen D, Bjorner JB, Brazier J. Estimating a Preference-Based Index for Mental Health From the Recovering Quality of Life Measure: Valuation of Recovering Quality of Life Utility Index. Value Health. 2021 Feb;24(2):281–90. Andersson E, Hedman E, Enander J, Radu Djurfeldt D, Ljótsson B, Cervenka S, et al. D-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants: A Randomized Clinical Trial. JAMA Psychiatry. 2015 July 1;72(7):659. Pinheiro JC, Bates DM. Mixed-Effects Models in S and S-PLUS [Internet]. New York: Springer; 2000 [cited 2024 June 10]. (Statistics and Computing). Available from: http://link.springer.com/10.1007/b98882 Drummond MF, Sculpher MJ, Claxton K, Stoddart GL, Torrance and GW. Methods for the Economic Evaluation of Health Care Programmes. Fourth Edition. Oxford, New York: Oxford University Press; 2015. 464 p. Whitehead SJ, Ali S. Health outcomes in economic evaluation: the QALY and utilities. Br Med Bull. 2010 Dec 1;96(1):5–21. NOU 2012: 16. Cost-Benefit Analysis [Internet]. Ministry of Finance; 2012. Available from: https://www.regjeringen.no/contentassets/5fce956d51364811b8547eebdbcde52c/en-gb/pdfs/nou201220120016000en_pdfs.pdf NICE. NICE health technology evaluations: the manual [Internet]. 2025. Available from: https://www.nice.org.uk/process/pmg36 Van Horn PS, Green KE, Martinussen M. Survey Response Rates and Survey Administration in Counseling and Clinical Psychology: A Meta-Analysis. Educ Psychol Meas. 2009 June 1;69(3):389–403. Riggs DS, Rothbaum BO, Foa EB. A Prospective Examination of Symptoms of Posttraumatic Stress Disorder in Victims of Nonsexual Assault. J Interpers Violence. 1995 June;10(2):201–14. Bond C, Lancaster GA, Campbell M, Chan C, Eddy S, Hopewell S, et al. Pilot and feasibility studies: extending the conceptual framework. Pilot Feasibility Stud. 2023 Feb 9;9(1):24. Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016 Oct 24;i5239. Rothbaum BO, Kearns MC, Price M, Malcoun E, Davis M, Ressler KJ, et al. Early Intervention May Prevent the Development of Posttraumatic Stress Disorder: A Randomized Pilot Civilian Study with Modified Prolonged Exposure. Biol Psychiatry. 2012 Dec;72(11):957–63. Table 2 Table 2 is available in the Supplementary Files section. Additional Declarations Competing interest reported. MB is the developer of CIPE, but has no financial conflict of interest. The authors declare that they have no competing interests. Supplementary Files Add1SPIRITEASE.docx Table2.docx Cite Share Download PDF Status: Published Journal Publication published 05 Feb, 2026 Read the published version in Trials → Version 1 posted Editorial decision: Revision requested 20 Nov, 2025 Editor assigned by journal 10 Nov, 2025 Submission checks completed at journal 10 Nov, 2025 First submitted to journal 05 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8039476","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":542554965,"identity":"aef62e19-8c30-42d4-bb2b-7c279f354b1c","order_by":0,"name":"Espen Rasmussen Lassen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqElEQVRIiWNgGAWjYDACdiD+wJBAihZmBgbGGUAtPCRpYeYhSQs/M/Pjz7Y70hL38x9ge/CBGC2SzWxm0rlnchJ7JBLYDWcQo8XgMIMZc25bhTGPBAObNFGusz/M/vmzJUgL0GHEaTFg5jGQZmzLkQMGAZFaJA7zlEn2tqXJ8dxIbJMkyi/87e2bP/xsS+Zh7z98TIKoEEMCjA0kahgFo2AUjIJRgBMAAEElJ0WAGfwaAAAAAElFTkSuQmCC","orcid":"","institution":"Norwegian Centre for Violence and Traumatic Stress Studies","correspondingAuthor":true,"prefix":"","firstName":"Espen","middleName":"Rasmussen","lastName":"Lassen","suffix":""},{"id":542554966,"identity":"be63173a-ea8c-4d88-8013-4d0fcc63a144","order_by":1,"name":"Marianne Skogbrott Birkeland","email":"","orcid":"","institution":"Norwegian Centre for Violence and Traumatic Stress Studies","correspondingAuthor":false,"prefix":"","firstName":"Marianne","middleName":"Skogbrott","lastName":"Birkeland","suffix":""},{"id":542554967,"identity":"24f17da8-8efa-4a73-b5d9-512656432551","order_by":2,"name":"Karina Egeland","email":"","orcid":"","institution":"Norwegian Centre for Violence and Traumatic Stress Studies","correspondingAuthor":false,"prefix":"","firstName":"Karina","middleName":"","lastName":"Egeland","suffix":""},{"id":542554968,"identity":"5b5e176a-80ca-4cf6-963a-26b3ba7d02b8","order_by":3,"name":"Lise Eilin Stene","email":"","orcid":"","institution":"Norwegian Centre for Violence and Traumatic Stress Studies","correspondingAuthor":false,"prefix":"","firstName":"Lise","middleName":"Eilin","lastName":"Stene","suffix":""},{"id":542554969,"identity":"a9783e99-5f07-44d8-82f8-bc181d336af3","order_by":4,"name":"Dorte Brodersen","email":"","orcid":"","institution":"Regional Resource Centre on Violence, Traumatic Stress and Suicide Prevention – Region East\t(RVTS East)","correspondingAuthor":false,"prefix":"","firstName":"Dorte","middleName":"","lastName":"Brodersen","suffix":""},{"id":542554970,"identity":"4d1c0e8b-7b93-4a74-9641-eae0406a0591","order_by":5,"name":"Belinda Ekornås","email":"","orcid":"","institution":"Regional Resource Centre on Violence, Traumatic Stress and Suicide Prevention – Region East\t(RVTS East)","correspondingAuthor":false,"prefix":"","firstName":"Belinda","middleName":"","lastName":"Ekornås","suffix":""},{"id":542554971,"identity":"f0ea0fb6-6317-4da9-ae37-58a969b8ca4f","order_by":6,"name":"Nils Petter Reinholdt","email":"","orcid":"","institution":"Regional Resource Centre on Violence, Traumatic Stress and Suicide Prevention – Region East\t(RVTS East)","correspondingAuthor":false,"prefix":"","firstName":"Nils","middleName":"Petter","lastName":"Reinholdt","suffix":""},{"id":542554972,"identity":"13b1f68c-d6f3-4634-b36c-ad178a1a316e","order_by":7,"name":"Egil Kjerstad","email":"","orcid":"","institution":"Norwegian Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Egil","middleName":"","lastName":"Kjerstad","suffix":""},{"id":542554973,"identity":"b769d247-4bca-461b-b198-a411c2be85ef","order_by":8,"name":"Admassu N. 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1","display":"","copyAsset":false,"role":"figure","size":54261,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of estimated participants in the trial.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8039476/v1/bd442baf21bf956faf3cfb11.png"},{"id":102234096,"identity":"37dc340b-d730-43ea-98a6-b9132d3ae7d1","added_by":"auto","created_at":"2026-02-09 16:06:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1027258,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8039476/v1/eb3efbf9-3381-4a54-91d1-d2ad4da54c53.pdf"},{"id":96242387,"identity":"e488e378-bf78-42b6-8b63-fdff3a1e5c06","added_by":"auto","created_at":"2025-11-19 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MB is the developer of CIPE, but has no financial conflict of interest. The authors declare that they have no competing interests.","formattedTitle":"Early Support after Exposure to Trauma (EASE): Protocol for a hybrid effectiveness-implementation trial of an internet-based intervention for PTSD prevention","fulltext":[{"header":"Structured summary","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eItem\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDescription\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrimary Registry and Trial Identifying Number {4}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThe trial is registered with ClinicalTrials.gov Identifier: NTC302302. Date: 19.11.2024.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSecondary Identifying Numbers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNa\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSource(s) of Monetary or Material Support \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThe EASE study has received funding from the Research Council of Norway (project #344341). The study underwent full external peer review as part of the funding process.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrimary Sponsor and contact information {3b}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNorwegian centre for violence and traumatic stress studies. Pb. 181 Nydalen, 0409 Oslo, Norway.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRole of sponsor and funder {3c}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThe sponsor covers indemnity insurance and legal liability for the current study, in addition to research infrastructure (e.g., personnel expenses, secure data storage, and data collecting systems). This study is designed and initiated by the PI and CoPIs. Thus, the funding organization (Research Council of Norway) has no role in the formulation of hypotheses, study design, data collection, analyses, or in the drafting of the manuscript.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eContact for Public Queries\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEarly Support after Exposure to Trauma (EASE) - NKVTS English\u003c/p\u003e\n \u003cp\u003eHarald Bækkelund: Principal investigator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eContact for Scientific Queries\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHarald Bækkelund: Principal investigator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePublic Title\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEarly Support after Exposure to Trauma (EASE)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eScientific title\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEarly Support after Exposure to Trauma (EASE)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCountries of Recruitment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNorway\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHealth Condition(s) or Problem(s) Studied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eF43.0 Acute stress reaction; F43.1 Post-traumatic stress disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIntervention(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIntervention arm: Condensed Internet delivered Prolonged Exposure (CIPE) + treatment as usual in municipal psychosocial crisis teams\u003c/p\u003e\n \u003cp\u003eComparator: Treatment as usual only in municipal psychosocial crisis teams\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eKey Inclusion and Exclusion Criteria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eInclusion Criteria:\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eReceives support from a municipal crisis team\u003c/li\u003e\n \u003cli\u003eExposure to a traumatic event (as defined by criteria A for the diagnosis of post-traumatic stress disorder (PTSD) in the DSM-5) within the last seven weeks before randomization\u003c/li\u003e\n \u003cli\u003eA total score of 10 or above on the PTSD Symptom Checklist-5 at the time of randomization\u003c/li\u003e\n \u003cli\u003eAge 16 or above\u003c/li\u003e\n \u003cli\u003eWritten informed consent\u003c/li\u003e\n \u003cli\u003eWrites and speaks English and/or Norwegian\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003eExclusion Criteria:\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eSevere psychopathology in need of specialized health care (e.g., psychotic symptoms, or high suicide risk) or substance dependence syndrome in need of specialized health care\u003c/li\u003e\n \u003cli\u003eKnown or evident severe cognitive impairment\u003c/li\u003e\n \u003cli\u003eOngoing traumatization, violence, or threats\u003c/li\u003e\n \u003cli\u003eUnstable dose of psychotropic medication two weeks prior to randomization\u003c/li\u003e\n \u003cli\u003eConcurrent therapy elsewhere before randomization\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStudy Type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eA hybrid Type 1 effectiveness and implementation randomized controlled trial.\u003c/p\u003e\n \u003cp\u003eRCT design: parallel two-armed multicenter randomized controlled superiority trial, designed to randomize participants to either CIPE + treatment as usual (TAU) or TAU only.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDate of First Enrollment (planned)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSeptember 15\u003csup\u003eth\u003c/sup\u003e 2024.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSample Size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePower analysis: \u003cem\u003eN =\u003c/em\u003e 150\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrimary outcome(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePTSD Checklist for DSM-5 (PCL-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eKey Secondary outcome(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e- Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)\u003c/p\u003e\n \u003cp\u003e- Patient Health Questionnaire (PHQ-9)\u003c/p\u003e\n \u003cp\u003e- Insomnia Severity Index (ISI)\u003c/p\u003e\n \u003cp\u003e- Client Satisfaction Questionnaire (CSQ-8)\u003c/p\u003e\n \u003cp\u003e- The EuroQol 5‑Dimension 5‑Level questionnaire (EQ-5D-5L)\u003c/p\u003e\n \u003cp\u003e- The Recovering Quality of Life (ReQoL)\u003c/p\u003e\n \u003cp\u003e- Traumatic grief inventory self report (TGI-SR+)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEthics Review\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThe trial is approved by the Regional Committee for Medical and Health Research Ethics (REK-sør-øst, #708906) on 23.05.24, and is conducted following guidelines of good clinical practice (GCP) in accordance with the principle of the Declaration of Helsinki. All participants provide written informed consent before enrollment.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIndividual Trial Participant Data sharing statement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIn accordance with the ethical approval, deidentified individual clinical trial participant-level data is available from the trial PI upon reasonable request. \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Background","content":"\u003cp\u003eThe world is currently experiencing a deteriorating security situation characterized by increasing conflicts and wars. Climate change is expected to further escalate the frequency of disasters affecting individuals, families, and societies. The recent COVID-19 pandemic caused significant trauma worldwide, while civilian trauma from domestic abuse and suicide continues to rise in many societies. This convergence of threats underscores the critical importance of societal health preparedness as a priority for nations and multilateral bodies.\u003c/p\u003e\n\u003cp\u003eTraumatic experiences represent a substantial cause of psychiatric disorders and poor mental health outcomes. A recent nationwide Swedish cohort study provides compelling evidence that traumatic stressors such as injury, assault, and bereavement lead to substantially elevated risks of subsequent psychological disorders, even after controlling for familial factors (1). Notably, the first year following the traumatic event emerges as an especially vulnerable period, highlighting that psychosocial support during this critical time window must be integrated into all preparedness plans.\u003c/p\u003e\n\u003cp\u003ePosttraumatic Stress Disorder (PTSD) is the most prevalent psychiatric condition following traumatic experiences, affecting an estimated 1\u0026ndash;9% of individuals over their lifetime (2,3). PTSD is associated with significant distress and increased risk of comorbid somatic and psychiatric conditions (4\u0026ndash;6), as well as functional impairment, increased healthcare utilization, and substantial societal costs (7).\u003c/p\u003e\n\u003cp\u003eHowever, the heterogeneity of victim needs after traumatic experiences presents a significant challenge for societal service planning. While acute stress symptoms\u0026mdash;such as increased psychophysiological activation, anxiety, and intrusive memories or flashbacks\u0026mdash;are common during the first months following potentially traumatic events (PTEs) (8), only approximately one in five individuals exhibit sustained or delayed-onset posttraumatic stress symptom (PTSS) trajectories. The majority demonstrate resilience or natural recovery (9). Consequently, the United Kingdom\u0026rsquo;s National Institute for Health and Care Excellence (NICE) guidelines recommend watchful waiting in the aftermath of PTEs to identify those who develop persistent reactions before implementing interventions (10).\u003c/p\u003e\n\u003cp\u003eDespite this cautious approach, both basic and clinical research indicate that processes occurring within the first weeks to months after a PTE may be decisive for PTSD development, suggesting that preventive interventions could be beneficial during this transitional period (11\u0026ndash;14). Unfortunately, evidence for the efficacy of early preventive interventions after PTEs remains limited. A recent systematic review and meta-analysis reports the strongest support for cognitive-behavioral therapy with a trauma focus (CBT-T) applied as an indicated secondary preventive intervention (15). The pooled effect sizes of CBT-T range from small to moderate (\u003cem\u003eSMD = \u003c/em\u003e0.49-0.70), depending on the control condition employed (15). Based on this evidence, the International Society for Traumatic Stress Studies\u0026rsquo; practice guidelines recommend providing immediate information and support after PTEs, rapidly followed by CBT when indicated (16).\u003c/p\u003e\n\u003cp\u003eNevertheless, to our knowledge, CBT-T is not systematically implemented or routinely offered as an early intervention following PTEs in any health system. This gap may reflect the substantial resources required to establish and maintain such treatment capacity, as well as the limited high-quality evidence supporting such investments. Hence, there is an urgent need for low-threshold CBT-T interventions with proven efficacy and cost-effectiveness that can be readily implemented in services delivering psychosocial support after traumatic incidents.\u003c/p\u003e\n\u003cp\u003eCondensed Internet-delivered Prolonged Exposure (CIPE) represents a promising solution to this challenge. CIPE is an indicated preventive intervention delivered soon after PTE exposure, designed to reduce acute stress symptoms and prevent PTSD development (17\u0026ndash;19). The treatment is delivered as a written, therapist-assisted intensive intervention, with total therapist time typically ranging from one to three hours throughout the program. In a recent randomized controlled trial (\u003cem\u003eN = \u003c/em\u003e102), CIPE significantly reduced PTSS compared to a waiting list control (17). The between-group effect size was moderate at week 3 (\u003cem\u003ed = \u003c/em\u003e0.70) and large at week 7 (\u003cem\u003ed = \u003c/em\u003e0.83), with effects maintained at 6-month follow-up and no severe adverse events reported. A qualitative follow-up study with a subsample (\u003cem\u003eN = \u003c/em\u003e11) reports that participants describe CIPE as effective, demanding, feasible, and tolerable (18). These findings suggest that CIPE could represent an effective and cost-efficient approach to indicated PTSD prevention.\u003c/p\u003e\n\u003cp\u003eHowever, demonstrating clinical effectiveness and cost-effectiveness is only the first step toward widespread implementation. The translation of evidence-based interventions into routine practice also requires careful consideration of the organizational and policy contexts in which they will be delivered. In Norway, responsibility for psychosocial support after PTEs is assigned to local municipalities, as mandated by various policy documents and laws (20). However, these policies provide limited specific guidance, resulting in considerable variation in how services are organized and delivered across municipalities. Most municipalities have established psychosocial crisis teams that are activated during crises and disasters to support those affected. These teams typically consist of professionals from diverse backgrounds who work in other services but are called upon during emergencies. Despite growing evidence for effective interventions that can be delivered following a PTE, systematic implementation of such interventions remains lacking in service delivery.\u003c/p\u003e\n\u003cp\u003eHealth policies can function as implementation determinants (i.e., factors that may be barriers or enablers), implementation strategies, or characteristics of the intervention being implemented (21). In this context, policy serves as an important contextual determinant that influences implementation outcomes (22). Unclear or conflicting policies may significantly impact crisis teams\u0026apos; capacity and opportunities to implement evidence-based interventions such as CIPE. As identified in the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, by examining the implementability of CIPE through the lens of EPIS inner (e.g., municipality, crisis services) and outer context (e.g., national, county) factors, innovation characteristics (e.g., CIPE), and bridging factors (i.e., bi-directional influences between outer and inner contexts) (23\u0026ndash;25), we can better understand how existing policies influence the implementation of such interventions. This type of analysis can inform the development of targeted recommendations and guidelines to facilitate large-scale implementation, scale-up, and sustainment of evidence-based trauma interventions in Norwegian municipalities.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAims and hypotheses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study hypotheses and research questions are presented in Table 1. The primary aim is to examine the effectiveness of CIPE, delivered approximately one to two months after a trauma, as an indicated secondary prevention aimed at reducing PTSS and the incidence of PTSD. We will compare the effect of CIPE + TAU vs. TAU only, to examine whether CIPE has the potential to improve the ordinary psychosocial services provided by crisis teams. Secondary aims concerning the effectiveness of CIPE include examination of whether CIPE + TAU is superior to TAU in preventing symptoms of insomnia and depression at 6 weeks post randomization, and 6-, and 12- months after a PTE. Further, secondary aims concern the cost-effectiveness of CIPE. Specifically, this study will examine whether CIPE reduces demand for second-tier specialty mental health services and improves quality of life compared to TAU. EASE will also examine if the implementation of CIPE is cost-effective in a long-term perspective, including the effect on labor market participation. The final secondary aims concern the implementation of CIPE. The study will investigate how existing policies across outer and inner context-level influence implementation of CIPE, and what kinds of policy- and systems-level bridging factors are needed to support implementation and sustainment of CIPE. The EASE study design and data collection framework provide the opportunity to examine the extent of long-term mental health needs following traumatic events and to identify predictors of chronic post-traumatic difficulties. Although specific research questions addressing these longitudinal outcomes remain to be developed, such analyses represent potential avenues for future investigation within the project.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHypotheses and research questions in the EASE study\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cu\u003eHypotheses concerning the effectiveness and cost-effectiveness of CIPE\u003c/u\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eH1.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eParticipants receiving CIPE+TAU will have significantly less PTSS than participants receiving TAU at 6 weeks post T1, and at 6-, and 12- months after the traumatic incident.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eH2.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSignificantly fewer participants receiving CIPE+TAU will fulfill the criteria for PTSD compared to participants receiving TAU, at 6- and 12-months post trauma.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eH3.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eParticipants receiving CIPE+TAU will have significantly less symptoms of depression and insomnia than participants receiving TAU at 6 weeks post T1, 6-, and 12- months after the traumatic incident.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eH4.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eParticipants in the CIPE+TAU-condition will report significantly higher treatment satisfaction at post-treatment, compared to those in the TAU-condition.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eH5.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eParticipants with traumatic loss receiving CIPE+TAU will have significantly less symptoms of prolonged grief than participants with traumatic loss receiving TAU 12 months after the loss.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eH6.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFewer participants in the CIPE+TAU-condition will be referred to second-tier specialty mental health services, and more will achieve improved quality of life within the first year after the traumatic incident, compared to participants in the TAU-condition.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eH7.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThe CIPE+TAU implementation is more cost-effective compared to TAU in the short run and may even dominate TAU in the long run (i.e., more effective and less costly).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003e\u003cu\u003eResearch questions concerning the implementability of CIPE\u003c/u\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRQ1.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHow do existing policies across multi-level outer (i.e., national, county) and inner (i.e., municipality, crisis services) contexts influence implementation of CIPE?\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRQ2.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWhat kinds of policy- and systems-level bridging factors are needed to support implementation and sustainment of CIPE?\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eNote.\u003c/em\u003e CIPE: Condensed internet-delivered Prolonged Exposure; H: Hypothesis; PTE: Potentially Traumatic Experiences; PTSD: Post-traumatic stress disorder; PTSS: Post-traumatic stress symptoms; RQ: Research question; TAU: Treatment as usual.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eResearch context\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwenty-one municipal crisis teams from the central-eastern parts of Norway participate in the study. The crisis teams are chosen to deliver the intervention due to their aforementioned role in the Norwegian health care system and the well-organized psychosocial services already offered by these teams. Participation requests were directed to municipal crisis teams by the Regional Resource Center for Violence, Traumatic Stress, and Suicide Prevention (RVTS East) to ensure variation in municipal population size, and municipalities from both rural and urban areas. A list of study sites is available in the trial registration (ClinicalTrials.gov Identifier: NTC302302).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial design \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe EASE study is a hybrid Type 1 effectiveness and implementation trial (26) (for implementation, see section “implementation trial”). The first part of the study is a parallel two-armed multicenter randomized controlled add-on superiority trial, designed to randomize participants to either CIPE + TAU or TAU only. All participants will be offered ordinary crisis team services throughout the trial period. The CIPE group will be given CIPE as an add-on between T1 (4-7 weeks after trauma, dependent on the time of enrollment) and T2 (10-13 weeks after trauma, dependent on the time of T1 [i.e., T2 is always 6 weeks after T1]; see figure 1). For those included within three weeks from the incident, a screening assessment is performed at the time of recruitment (T0). Baseline assessment and evaluation of inclusion and exclusion criteria will be completed at T1. Outcome measures are gathered 6 weeks post randomization (T1), and follow-up measurements are accomplished at 6- and 12-month post PTE. This trial follows the SPIRIT guidelines and methodology (27) (see Additional file 1 for the SPIRIT checklist).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion and exclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInclusion criteria are a) persons that receive support from a municipal crisis team, after b) exposure to a traumatic event (as defined by criteria A of the PTSD-diagnosis in the DSM-5) (28) within four to seven weeks before T1, c) a total score of 10 or above on the PTSD Symptom Checklist (PCL-5) (29) at T1 (4-7 weeks post trauma, dependent on the time of inclusion), d) age 16 or above, e) written informed consent, and f) writes and speaks Norwegian and/or English.\u003c/p\u003e\n\u003cp\u003eExclusion criteria are a) severe psychopathology (e.g., psychotic symptoms, or high suicide risk) or substance dependence syndrome in need of specialized health care (harmful use is not an exclusion criteria, as long as participants commit to not being under the influence when completing the intervention), b) known or evident severe cognitive impairment, c) ongoing traumatization, violence, or threats, d) unstable dose of psychotropic medication two weeks prior to T1, and e) concurrent therapy elsewhere at the time of T1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecruitment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 presents the trials’ enrollment, intervention, and measurement schedule. Participants receive brief information regarding the trial in consultation with the crisis teams, within the first seven weeks after exposure to a PTE. If consenting, the participants receive exhaustive information about the study, along with a participation request from the research group. Written informed consent is gathered electronically before enrollment and stored in BASS. Crisis team staff repeatedly assure the participants that they will receive TAU, regardless of participation. This is also underscored in all written recruitment material.\u003c/p\u003e\n\u003cp\u003eAt enrollment, the crisis teams and the research group decide whether inclusion criterion B is met, using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) (30) A-criterion assessment. If eligible by self-report measures at T1, the participants are assessed with the Mini-International Neuropsychiatric Interview (MINI) (31) version 6 and the CAPS-5 by trained graduate clinical psychology students. The interviews are completed by telephone. ERL (licensed clinical psychologist and PhD candidate) monitors the process. To bolster response rates and diminish attrition, participants are given a symbolic monetary incentive (32,33) in the form of lottery tickets (value: 8€) upon completing all required self-report measures and interviews. The estimated flow of participants throughout the study phases is visualized in Figure 1. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eRandomization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEligible participants are randomized 1:1 in random block sizes of 4, 6, or 8 to either CIPE + TAU or TAU only, using the Sealed envelope software (34) at T1. To mitigate the risk of contamination across treatment conditions, participants from the same household are cluster-randomized. The randomization is stratified on the level of municipal crisis teams to ensure an even distribution of cases in each treatment condition across municipalities. An independent, blinded senior researcher is responsible for all randomization procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e CIPE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCIPE is an adaptation of Prolonged Exposure (PE) (35). PE is an exposure-based version of CBT-T that has been thoroughly empirically validated as a treatment for PTSD (36,37). CIPE consists of four written therapist-assisted modules, with corresponding homework assignments (17). The assignments comprise central treatment components, as well as questions regarding essential intervention components and principles, to ensure socialization. Participants are expected to work on these assignments for six hours weekly and are encouraged to have daily contact with their therapist via a secure email within the treatment platform. Phone sessions are also available when necessary. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e TAU\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants in the TAU condition receive standard psychosocial support that is routinely provided by the crisis teams. This could include a varying number of consultations (typically 1-4) consisting of psychoeducation and normalization of symptoms of acute stress, activation of the victim’s social network, practical support, and/or grief support (20). Although common practice is to follow the guidelines from the Norwegian Directorate of Health (20), there is considerable heterogeneity in what constitutes TAU within and between different crisis teams. This applies both to the content and frequency of support. Thus, consultation frequency, duration, type, and mode are assessed (see “other collected data”).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTherapist training and fidelity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe therapists in the current trial arecrisis team health care workers. They attend a one-day seminar held by the originator of CIPE (Bragesjö) or the study PI. The seminar consists of a thorough lecture on the theoretical basis of, and every intervention included in CIPE, as well as practical skills training in CIPE interventions. All therapists receive the CIPE treatment manual (unpublished). As all CIPE treatment components are delivered through standardized text, therapist drift is not possible other than in the secure emails. Continuous monitoring of therapist fidelity in these emails is thus accomplished by two senior consultant clinical psychologists, as well as the trial PhD/clinical psychologist (all trained in CIPE). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContamination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor organizational and practical reasons, the majority of the crisis team therapists deliver both TAU and CIPE. Consequently, there is a risk of contamination across conditions at the therapist level. To reduce the risk of contamination, therapists are repeatedly instructed and reminded not to mix the conditions, and are prohibited from using the CIPE internet platform outside of the timeframe of CIPE delivery in each case. Cases of potential contamination will be reported, as the clinicians are instructed to report such cases to ERL.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 presents the trials’ enrollment, intervention, and measurement schedule. Participants enrolled within three weeks after the incident are assessed with self-report measures at the time of enrollment (T0). All participants are subsequently assessed before randomization (T1), post-treatment (T2), and at 6-month (T3) and 12-month (T4) follow-ups. The main outcome will be measured at post-treatment (T2). Self-report data from participants are collected using an electronic survey solution offered by BASS at the Karolinska Institute, Stockholm. The same system is used to obtain written informed consent and to deliver CIPE. Links to questionnaires are sent to responders using SMS and email. Data from the therapists are collected using Nettskjema and Services of sensitive data (TSD) at the University of Oslo (see “data management and storing”). The research coordinator monitors the data collection process and sends reminders to reduce attrition rates. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessments \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e Primary outcome measure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe PTSD Symptom Checklist (PCL-5) (29) is a 20-item questionnaire that measures DSM-5-specified symptoms of PTSD. The total score ranges from 0 to 80, with higher scores indicating more severe symptoms. Items are rated on a 0 (“not at all”) to 4 (“extremely”) Likert-type scale. The PCL-5 has satisfactory psychometric properties in various trauma populations (38–40). This study administers a validated Norwegian version of the PCL-5 (41,42). As the index trauma is only a few days before T0 for most participants, the recall period is revised to “since the traumatic event” for this measurement. In T1-T4, the standard recall period in the PCL-5 is applied (one month). PCL-5 constitutes the main outcome of this study. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary outcome measures \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) (30) is a 30-item structured interview, developed to assess current and lifetime PTSD diagnosis, as well as past-week PTSD symptoms. The instrument measures the 20 DSM-5 PTSD-symptoms, in addition to the onset and duration of symptoms, related subjective distress and functional impairment (social, occupational), amongst other aspects of the disorder. Standardized questions and probes are provided. A Norwegian version of the CAPS-5 (43) is administered at T1 and T3-4. CAPS-5 has excellent psychometric properties (30,44).\u003c/p\u003e\n\u003cp\u003eThe Mini-International Neuropsychiatric Interview (MINI) (31) version 6 is a brief, structured clinician-administered interview designed to assess 17 DSM/ICD diagnoses. Standardized questions and probes are provided. A Norwegian translation of the MINI (45) is administered at T1. The interview has good psychometric properties (31,46,47). \u003c/p\u003e\n\u003cp\u003eA Norwegian version (48) of the Stressful Life Events Screening Questionnaire (SLESQ) (49) is administered at T1 to measure self-reported lifetime exposure to traumatic events. The respondents are asked to report exposure to 15 categories of traumatic events (“yes” or “no”), age at the time of the incident, as well as frequency and duration of the events. Other aspects of the incidents are reported, as well. The Norwegian version of the SLESQ incorporates two extra items compared to the original 13-item version: “Have you ever been directly affected by a natural disaster?” and “Has anyone outside your family, such as fellow pupils or colleagues, repeatedly ridiculed you, put you down, ignored you, or told you were no good?”. The SLESQ has satisfactory validity and reliability (49,50).\u003c/p\u003e\n\u003cp\u003eThe Patient Health Questionnaire (PHQ-9) (51) is a 9-item self-report measure of depressive symptom severity. The recall period is 2 weeks. Response is given on a 4-point Likert-type scale (0: not at all, 1: several days, 2: more than half the days, and 3: nearly every day), resulting in a total score ranging from 0 to 27. Higher scores indicate higher symptom severity. The instrument is sensitive for both clinical and sub-clinical levels of depressive symptoms and has good psychometric properties (51,52). We administer a validated Norwegian version of the PHQ-9 (53).\u003c/p\u003e\n\u003cp\u003eThe Insomnia Severity Index (ISI) (54) is a 7-item questionnaire that measures insomnia symptoms during the past two weeks. The instrument utilizes a 5-point Likert-type scale ranging from 0 to 4, yielding a total score of 0-28. Higher scores indicate more insomnia symptoms. The ISI has good psychometric properties (54–56). A Norwegian version of the ISI is applied.\u003c/p\u003e\n\u003cp\u003eThe Client Satisfaction Questionnaire (CSQ-8) (57) is an eight-item measure of participants’ service satisfaction. Response is given on a scale ranging from one to four, with a resulting total score ranging from eight to 32. Higher scores suggest higher service satisfaction. A validated Norwegian version of the CSQ-8 is applied (58). The CSQ-8 is adapted to the context of psychosocial crisis teams in the current trial (e.g., “treatment” adapted to “support”, “therapy” adapted to “support”).\u003c/p\u003e\n\u003cp\u003eThe Traumatic Grief Inventory-Self Report Plus (TGI-SR+) (59) is a 22-item self-report questionnaire measuring symptoms of DSM-5 persistent complex bereavement disorder (PCBD), and ICD-11 Prolonged grief disorder (PGD) in participants who experienced traumatic bereavement. Response is given on a 5-point Likert-type scale ranging from 1 (“never”) to 5 (“always”). The total score ranges from 22 to 110, with higher scores indicating more severe symptoms. The instrument, including the Norwegian version applied here, has good psychometric properties (60,61). The instrument is administered at a 12-month follow-up, and applies a recall period of the past month. \u003c/p\u003e\n\u003cp\u003eThe EuroQol 5‑Dimension 5‑Level Questionnaire (EQ‑5D‑5L) (62) assesses self-reported health-related quality of life. It has five items: Self-care, mobility, pain/discomfort, usual activities, and anxiety/depression, each measured on a 5-level severity scale (no, slight, moderate, severe, or unable/extreme problems). The instrument defines 3125 possible health states, valued by a representative sample of the general Norwegian population using the hybrid valuation method – composite time-trade-off and discrete choice experiment (63). The utility scores are anchored on a -0.453 – 1 scale, with 1 indicating ‘full-health’, 0 equivalent to ‘being dead’, and values below 0 are worse than being dead. The EQ-5D-5L data are used to generate quality-adjusted life year (QALY) used for cost-utility analysis (CUA). The instrument has excellent psychometric properties (64). \u003c/p\u003e\n\u003cp\u003eThe Recovering Quality of Life (ReQoL) is an 11-item outcome measure assessing psychopathology-specific quality of life in mental health contexts (65). For each item, response is given on a 5-point scale (never to most of the time or always). The study also uses the ReQoL utility index (ReQoL-UI), which is a recovery-focused generic preference-based measure derived from ReQoL. ReQoL-UI constitutes six mental health items (activity; belonging; choice, control, and autonomy; hope; self-perception; and well-being) and a physical health item, each with five severity levels. The ReQoL-UI defines 78,125 different health states valued by a representative member of the UK public using a conventional time-trade-off method (66). The ReQoL-UI is also used to generate QALYs for CUA in mental health interventions. The ReQoL-UI values range between -0.195 (for the worst health state) and 1 (for the full-health state), with zero indicating a health state equivalent to being dead. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOther collected data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA structured adverse events (AE) questionnaire applied in the aforementioned RCT of CIPE (17) is utilized. The questionnaire was used in a previous trial with similar results to face-to-face interviews (67). The instrument captures the frequency, duration, and nature of possible adverse events, and such events are further classified based on their perceived association with CIPE (related or unrelated). Both participants and clinicians are asked to report and rate participants’ short- and long-term discomfort of any AEs on a scale from 0 (‘did not affect me at all’) to 3 (‘affected me very negatively’).\u003c/p\u003e\n\u003cp\u003eIn both TAU and CIPE, all time and resource use of therapists (i.e., treatment, travel, online tasks, appointments, preparation, and competence level of therapists) are registered. Registry data is also utilized for all participants, using the Norwegian Patient Register (NPR), Control and Payment of Health Reimbursement (KUHR), Municipal patient- and user-register (KPR), and FD-Trygd. However, in the absence of reliable registry data on the use of health care resources in the municipalities, this study applies survey data reported every second month by the crisis teams’ personnel, via a generic questionnaire. Consultation duration, type (e.g., CIPE, grief support, practical support), and mode (e.g., telephone, video consultation, home visit), as well as the professional background of the involved personnel, are reported from T1 to T4.\u003c/p\u003e\n\u003cp\u003eIn the CIPE+TAU-arm, both clinicians and participants are assessed with a nine-item generic, unvalidated self-report measure of reasons for drop-out from CIPE, in cases where the participant did not finish CIPE. The questionnaire maps lack of motivation, disliking of e-therapy, lack of relevance, lack of reduction of PTSS, worsening of PTSS, remission, concurrent therapy elsewhere, and other (qualitative response category) as possible sources of drop-out. Response is given in one of two categories (0: no, 1: yes), except for the mentioned qualitative item.\u003c/p\u003e\n\u003cp\u003eParticipants are also asked to self-report sociodemographic and background data: year of birth, gender, relationship and cohabitation status, country of birth (self and parents), educational and employment status, current use of psychotropic medication, current psychological treatment (outside of the trial), and ongoing threats or violence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eH1-3 are tested with linear mixed effects models. The linear mixed effects model includes fixed effects for treatment group (intervention vs. control) and time (post-intervention, 6 and 12 months). In a hierarchical setup, a second step includes a treatment × time interaction. Random effects include random intercepts for participants to account for individual differences. The mixed effects models are applied using the R package nlme (68). H4-6 are examined using independent t-tests. The quality-of-life change (change in QALY) of participants in CIPE vs TAU (H6) is analyzed using the mixed effects model. Estimation is conducted using restricted maximum likelihood, with all available observations included, yielding unbiased estimates under the assumptions of missing at random or missing completely at random. For the t-tests, missing data are handled using multiple imputation. \u003c/p\u003e\n\u003cp\u003eHypothesis 7 involves a comprehensive economic evaluation comparing the cost-effectiveness of CIPE relative to TAU in terms of both costs and consequences/effectiveness (69). Costs are assessed using the ingredients approach, which involves three steps. First, identifying each resource required for the intervention, then measuring these resources, and finally valuing them. The effectiveness of the intervention is measured by QALY – a composite measure combining both quantity of life (mortality) and quality of life (morbidity) into a single metric (70). For each arm, mean costs and mean QALYS are estimated across all participants to calculate the incremental cost (ΔC) and incremental effect (ΔQALY). The incremental cost-effectiveness ratio (ICER) or incremental cost per incremental QALY (ΔC/ΔQALY) is then calculated for decision-making. To accept the intervention, ICER should be less than the willingness-to-pay or cost-effectiveness threshold. Since there is no official threshold in Norway, we apply a threshold recommended by the Norwegian Directorate of Health (NOK 500 000 at 2005 prices), adjusted to current price levels (71). \u003c/p\u003e\n\u003cp\u003eThis economic evaluation is conducted in two ways: trial- and model-based approaches. In the former, we compare trial-specific intervention costs and effects. Following recommendations by NICE (72), we perform a cost-utility analysis combining intervention-related and wider healthcare costs with changes in QALYs. In the latter, we develop a decision analytic model to simulate the long-term (lifetime) cost-effectiveness of CIPE. The model extrapolates beyond the trial period to estimate the potential lifetime costs and QALY outcomes under different assumptions. In both approaches, model parameter uncertainty are assessed using both probabilistic and deterministic sensitivity analyses.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePower and sample size calculations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrevious CIPE studies report effect sizes within the range of \u003cem\u003ed = \u003c/em\u003e0.6 - 0.8. For the primary hypothesis in this study, a more conservative effect size of \u003cem\u003ed = \u003c/em\u003e0.3 is expected. With 95% power and an \u003cem\u003eα\u003c/em\u003e-level of 0.05, 150 participants (73 in each group minimum) are required to detect a significant between-group effect. Consequently, assuming a 20% data attrition rate, at least 183 participants should be recruited. The municipal crisis teams involved in the study currently cover approximately 1,080,000 inhabitants. Although official statistics on the number of traumatic events handled by these teams are lacking, based on the best unofficial statistics available, a conservative estimate suggests 0.5 to 1 case per 1000 inhabitants annually. With a cautious estimate of 0.5, and with each incident involving a mean of two victims aged 16 or older, about 2150 victims are eligible for recruitment over 2 years. Moreover, we assume a ~50% response rate (73) and that approximately 30% have PTSD symptoms one month after the incident (74). These parameters result in a sample of 360 participants, which constitutes the recruitment target. Assuming an overall attrition rate of 40%, 216 participants will complete the 12-month follow-up assessment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOversight and monitoring\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e Data management and storage\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEach enrolled participant is assigned a unique study ID. The ID number is linked to each participant’s social security number, stored in a separate coupling key-file in the Services of sensitive data (TSD) at the University of Oslo. TSD uses the highest possible level of IT security, and data files are continuously backed up. Participant self-report data is gathered in BASS (identical security procedures as TSD) and securely exported to TSD for statistical analyses. Trial data are stored at least five years after data collection is concluded (anticipated completion date: December 31st, 2027). A Data Protection Impact Assessment (DPIA) with risk and security measures is in place, collaborating with Sikt (the national agency providing shared digital services and infrastructure for the Norwegian knowledge sector). The Data Protection Official at Sikt and at the Norwegian Centre for Violence and Traumatic Stress Studies (sponsor’s) both acknowledge the DPIA. Only the principal investigators and ERL will have access to the final trial dataset. ANL and EK will have access to the data necessary for the investigation of H6-7.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety and monitoring procedures for adverse events\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDespite the lack of severe adverse events (AE) in a recent RCT of CIPE (17), the trial has established procedures to monitor AEs and serious adverse events (sAE). Health personnel in the crisis teams are instructed to monitor and address AE continuously. Unmet healthcare needs that are discovered by the research teams in the T1-4 assessments are communicated to the individual’s therapist in the municipality. Moreover, self- and clinician-reported (s)AE are assessed at T2 (see instruments). Adverse events are defined as any unfavorable experience occurring to participants during the trial. Serious adverse events are defined as incidents including death, (attempted) suicide, serious self-harm, acute mania or psychosis, severe intoxication, or other psychological or somatic conditions requiring emergency medical care. \u003c/p\u003e\n\u003cp\u003eAfter the first 18 participants are randomized (corresponding to 10% of the target sample size based on the power analysis), an internal pilot study will be conducted in accordance with the CONSORT guidelines for randomized feasibility and pilot trials (75,76). The pilot will assess AEs and sAEs. If the rate of AEs is substantially higher than reported in previous studies of CIPE and/or any sAEs occur, the advisory board will consider protocol modifications and/or discontinuation of the trial. Should such deliberations arise, the project owner will retain the final authority to decide whether the trial will be terminated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBlinding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe graduate clinical psychology students performing the clinical interviews are blinded. Participants are instructed not to report their assigned condition in interviews. In case of spontaneous unblinding, the interview is terminated and repeated in its entirety by another blinded assessor. Blinding of participants and therapists is not possible due to the nature of the interventions. Data analysis is conducted by the trial statistician (MSB), who is blinded to treatment assignment for the entirety of the trial. ANL and EK perform health economic analyses and are blinded to treatment condition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProtocol violations and revisions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll included participants are included in the intent-to-treat analyses. Participants who do not complete CIPE within T2, or report adjustment of psychotropic medication or concurrent therapy elsewhere, as well as ongoing traumatization, violence, or threats after T1, and drop out of the trial, are not included in the completers analyses. Protocol revisions have been and will be updated in the clinical trial registry and communicated to REK for approval in accordance with the contract.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplementation trial \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe overarching aim of the implementation trial is to understand how policy- and systems-level factors across national, regional, and municipal levels influence the uptake and sustainment of CIPE within municipal crisis services operating under multi-level governance. The study maps how national policies, regional agreements, and municipal plans interact to shape CIPE implementation, including considerations of costs and political support, as well as bridging factors such as policy directives, agreements, and/or contracts for services. It assesses how policy guidelines, regional arrangements, and municipal plans align with or diverge from CIPE requirements, with the goal of producing practical recommendations to strengthen bridging mechanisms, promote durable adoption, and inform scaling of CIPE across municipalities.\u003c/p\u003e\n\u003cp\u003eTo examine how existing policies across outer and inner contexts influence CIPE implementation (21,23,25), the study adopts a mixed qualitative design that combines document review, qualitative interviews, and observational methods. Key topics across document reviews and interviews include how policies influence service provision, how stakeholders at both policy and system level (e.g., municipal service providers, policy developers) consider costs, the level of political support for crisis services and CIPE, whether there are ambiguities in responsibility and decision-making, and misalignment between agencies, and organizational culture affecting CIPE uptake. \u003c/p\u003e\n\u003cp\u003eThe document review includes sentinel policy surveillance methods for tracking laws and policies over time regarding the organization of municipal crisis teams. The legal mapping is carried out at three governance levels: national (Ministry and Directorate of Health), county/regional (County Governors or equivalent regional authorities), and municipal (leaders or team members of psychosocial crisis teams). At the national and county level, relevant policy documents on psychosocial preparedness, follow-up, funding, responsibilities, and intergovernmental collaboration are identified and refined in consultation with the Ministry of Health and Care Services, the Directorate of Health, and the County Administrator. A structured document analysis maps how policies frame preparedness and follow-up, and define roles and accountability across levels. At the municipal level, a stratified sampling of municipalities is carried out to capture diversity in geographic and systemic contexts. Psychosocial preparedness plans are reviewed, focusing on content, organization, providers, context, and collaboration with GPs and referral pathways to specialized services.\u003c/p\u003e\n\u003cp\u003eThe qualitative interviews involve semi-structured interviews with actors at the same three governance levels: national, county, and municipality. At the national and county level, relevant persons who have participated in the formulation of, or are responsible for implementing relevant laws and policy documents at the Ministry of Health and Care Services, the Directorate of Health, and the County Administrator are interviewed. At the municipal level, municipal crisis team leaders or other psychosocial care providers are interviewed to understand which policies guide planning and organization. The output will be a policy map detailing alignment and gaps between national directives and municipal practices. In addition to document reviews and interviews, training materials, formal agreements, and observational notes collected during the CIPE testing are included. \u003c/p\u003e\n\u003cp\u003eData are analyzed iteratively and thematically to identify potential bridging factors, barriers, enablers, and how policy contexts and decision-making processes shape implementation choices. A logic model will illustrate how outer context and inner context factors can support sustainable CIPE implementation, including uptake, costs, political support, relational ties (e.g., partnerships), and processes (e.g., communication, data-sharing) and long-term viability. The analysis explicitly addresses bridging mechanisms and will culminate in actionable policy implementation strategies and recommendations for durable intergovernmental collaboration (contracts, partnerships, data-sharing).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDissemination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study results will be published in scientific journals irrespective of whether the results support the hypotheses or not.\u003c/p\u003e\n\n"},{"header":"Discussion","content":"\u003cp\u003eThis study has three working packages with respective aims. First, the study aims to investigate the effectiveness of CIPE, as an add-on treatment to TAU in psychosocial crisis teams, in reducing post-traumatic psychological sequelae. Second, the cost-effectiveness of CIPE is examined. Third, the influence of existing policies on the implementation and sustainment of CIPE is researched.\u003c/p\u003e\n\u003cp\u003eAlthough most individuals exposed to a PTE do not develop PTSD, a substantial minority experience prolonged post-traumatic sequela. There is promising meta-analytical evidence for indicated secondary preventive interventions based on CBT-T interventions (15), and such early interventions are efficacious and safe (17,77). This trial adds to the literature by examining the effectiveness of CIPE on reducing post-traumatic psychological distress in the context of Norwegian municipal crisis teams. Consequently, the trial could generate important knowledge regarding which individuals are at risk of developing PTSD after PTEs, and whether CIPE effectively reduces post-traumatic psychological distress.\u003c/p\u003e\n\u003cp\u003eBeyond clinical outcomes, the trial generates knowledge about the economic implications of implementing CIPE, including potential reductions in the need for specialist secondary mental health care. Furthermore, EASE investigates the implementation of preventive interventions for PTSD in primary-level health services such as municipality crisis services. Additionally, we examine how health policies impact the implementation of evidence-based practices in this context. Both these research topics are understudied in implementation science (21). In summary, the EASE study addresses important knowledge gaps concerning evidence-based secondary prevention of PTSD and psychosocial care for victims of crises and disasters, and the health economics and implementation factors involved in such interventions.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths and limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe current study has several strengths. First, the multi-center effectiveness design improves the external validity, providing policy makers and municipal crisis teams with important knowledge regarding evidence-based indicated preventive interventions after trauma. If CIPE is effective in reducing PTSS within the context of municipal crisis teams, this could enhance the generalizability of the findings significantly, as the implementation closely reflects how the crisis teams typically operate. Second, EASE represents an innovation in research on early interventions after PTEs and hybrid trial designs, by investigating the effectiveness, cost-benefits, and implementability of CIPE in a single trial. Finally, the use of a scalable, digitalized, evidence-based indicated preventive intervention (i.e., CIPE) in ordinary services (i.e., not ad-hoc services established after major disasters) is another strength.\u003c/p\u003e\n\u003cp\u003eThis study also has limitations that warrant consideration. First, the therapists and participants are not blinded, which could induce placebo effects. Nevertheless, the interviewers are blinded, ensuring single-blind assessments. Furthermore, there might be unequal treatment intensity across the groups (i.e., the TAU+CIPE condition receiving more treatment than the TAU-only condition). There is also a risk of contamination between conditions, due to the aforementioned design. Moreover, recruitment could be delayed due to multiple factors (e.g., low response rates, participant preference for avoidance instead of exposure, study implementation barriers on therapist- or system level). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe recruitment started in September 2024 and is ongoing. The estimated recruitment completion date is September 2026. The estimated project completion date is December 31, 2027.\u003c/p\u003e\n"},{"header":"Abbreviations","content":"\u003cp\u003eAE: adverse events; CAPS-5: The Clinician-Administered PTSD Scale for DSM-5; CAPS-5 A-criteria: Only the assessment of whether the A-criteria has been fulfilled in the CAPS-5; CBT: Cognitive-Behavioral Therapy; CBT-T: Cognitive-Behavioral Therapy with a trauma focus; CIPE: Condensed Internet-Delivered Prolonged Exposure; CSQ-8: Client Satisfaction Questionnaire; CUA: Cost-Utility Analysis; DPIA: Data protection impact assessment; DSM-5: Diagnostic and Statistical Manual for Mental Disorders, fifth edition; EPIS: Exploration, Preparation, Implementation, Sustainment Framework; EQ-5D-5L: EuroQol 5-Dimension 5-Level Questionnaire; H: Hypothesis; ICER: Incremental Cost-Effectiveness Ratio; ISI: Insomnia Severity Index; KPR: Municipal Patient- and User-Register; KUHR: Control and Payment of Health Reimbursement; MINI: Mini-International Neuropsychiatric Interview version 6; NICE: National Institute for Health and Care Excellence; NPR: Norwegian Patient Register; PCL-5: PTSD Symptom Checklist for DSM-5; PE: Prolonged Exposure; PHQ-9: Patient Health Questionnaire-9; PTE: Potentially Traumatic Events; PTSD: Post-Traumatic Stress Disorder; PTSS: Post-Traumatic Stress Symptoms; QALY: Quality-Adjusted Life Year; ReQoL: Recovering Quality of Life; ReQoL-UI: ReQoL Utility Index; RQ: Research Question; (s)AE: Severe adverse events; SLESQ: Stressful Life Events Screening Questionnaire; TAU: Treatment as usual; TGI-SR+: Traumatic Grief Inventory \u0026ndash; Self Report Plus.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial is approved by the Regional Committee for Medical and Health Research Ethics (REK-sør-øst, #708906) on 23.05.24, and is conducted following guidelines of good clinical practice (GCP) in accordance with the principle of the Declaration of Helsinki. All participants provide written informed consent before enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUpon providing informed consent, all participants are informed that the study results will be published in international scientific journals and that identification of individual participants will not be possible based on the manuscripts. A model consent from is available from the PI upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with the ethical approval, deidentified individual clinical trial participant-level data is available from the trial PI upon reasonable request. Only the principal investigators and ERL will have access to the final trial dataset. ANL and EK will have access to the data necessary for the investigation of H6-7.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMB is the developer of CIPE, but has no financial conflict of interest. The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe EASE study has received funding from the Research Council of Norway (project #344341). The study underwent full external peer review as part of the funding process.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: HB, KE, MSB, ELC, GAA, DB, NPR. Securing funding and study leadership: HB, KE, MSB; Design: ERL, HB, KE, MSB. Obtaining ethical approval: ERL \u0026amp; HB. Writing first draft of the manuscript: ERL, HB, KE, LES, AL. Revision of the manuscript: all authors. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are thankful for the contributions of all participants, user representatives, members of the psychosocial crisis teams, research assistants, and advisors.\u003cbr\u003e \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdministrative information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRoles and responsibilities (contributorship):\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHarald Bækkelund: Principal investigator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] \u003c/p\u003e\n\u003cp\u003eMarianne S. Birkeland: Co-Principal investigator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway. [email protected] \u003c/p\u003e\n\u003cp\u003eKarina Egeland: Co-Principal investigator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] \u003c/p\u003e\n\u003cp\u003eLise E. Stene: Senior researcher. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] \u003c/p\u003e\n\u003cp\u003eEspen R. Lassen: Trial PhD-candidate and coordinator. Norwegian centre for violence and traumatic stress studies, Oslo, Norway. [email protected] \u003c/p\u003e\n\u003cp\u003eAdmassu N. Lamu: Associate investigator. NORCE Norwegian Research Centre– Health Services and Health Economics, Bergen, Norway. [email protected] \u003c/p\u003e\n\u003cp\u003eEgil Kjerstad: Associate investigator. NORCE Research – Health Services and Health Economics, Bergen, Norway. [email protected] \u003c/p\u003e\n\u003cp\u003eBelinda Ekornås: Associate consultant. RVTS East - Regionalt ressurssenter om vold, traumatisk stress og selvmordsforebygging. [email protected] \u003c/p\u003e\n\u003cp\u003eNils Petter Reinholdt: Associate consultant. RVTS East - Regionalt ressurssenter om vold, traumatisk stress og selvmordsforebygging. [email protected] \u003c/p\u003e\n\u003cp\u003eDorte Brodersen: Associate consultant. RVTS East - Regionalt ressurssenter om vold, traumatisk stress og selvmordsforebygging. [email protected] \u003c/p\u003e\n\u003cp\u003eMaria Bragesjö: Associate consultant. Karolinska Institutet, Stockholm, Sweden. [email protected] \u003c/p\u003e\n\u003cp\u003eErika L. Crable: Associate investigator. Department of Health Policy and Management, University of California, Los Angeles, Los Angeles, CA, USA. [email protected] \u003c/p\u003e\n\u003cp\u003eGregory A. Aarons: Associate investigator. Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. [email protected] \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRoles and responsibilities (committees): \u003c/strong\u003eThe project owner for EASE is the trial sponsor (represented by Cecilie Daae and Geir Ove Kværk). The project group consists of HB, MSB, KE, LES, ERL, BE, NPR, and DB. EASE also has a scientific advisory board with leading experts in trauma interventions, methodology, implementation, and health policy (GAA, Miranda Olff, Joar Øveraas Halvorsen, Filip Arnberg).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChen Y, Shen Q, Lichtenstein P, Gradus JL, Arnberg FK, Larsson H, et al. Incidence Trajectories of Psychiatric Disorders After Assault, Injury, and Bereavement. JAMA Psychiatry. 2024 Apr 1;81(4):374. \u003c/li\u003e\n\u003cli\u003eAtwoli L, Stein DJ, Koenen KC, McLaughlin KA. Epidemiology of posttraumatic stress disorder: prevalence, correlates and consequences. Curr Opin Psychiatry. 2015 July;28(4):307\u0026ndash;11. \u003c/li\u003e\n\u003cli\u003eKoenen KC, Ratanatharathorn A, Ng L, McLaughlin KA, Bromet EJ, Stein DJ, et al. Posttraumatic stress disorder in the World Mental Health Surveys. Psychol Med. 2017 Oct;47(13):2260\u0026ndash;74. \u003c/li\u003e\n\u003cli\u003ePietrzak RH, Goldstein RB, Southwick SM, Grant BF. Prevalence and Axis I comorbidity of full and partial posttraumatic stress disorder in the United States: Results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. J Anxiety Disord. 2011 Apr;25(3):456\u0026ndash;65. \u003c/li\u003e\n\u003cli\u003ePietrzak RH, Goldstein RB, Southwick SM, Grant BF. Medical Comorbidity of Full and Partial Posttraumatic Stress Disorder in US Adults: Results From Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Psychosom Med. 2011 Oct;73(8):697. \u003c/li\u003e\n\u003cli\u003eTaft CT, Stern AS, King LA, King DW. Modeling physical health and functional health status: The role of combat exposure, posttraumatic stress disorder, and personal resource attributes. J Trauma Stress Off Publ Int Soc Trauma Stress Stud. 1999;12(1):3\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eBothe T, Jacob J, Kr\u0026ouml;ger C, Walker J. How expensive are post-traumatic stress disorders? Estimating incremental health care and economic costs on anonymised claims data. Eur J Health Econ. 2020 Aug 1;21(6):917\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eBryant RA. The Current Evidence for Acute Stress Disorder. Curr Psychiatry Rep. 2018 Oct 13;20(12):111. \u003c/li\u003e\n\u003cli\u003eGalatzer-Levy IR, Huang SH, Bonanno GA. Trajectories of resilience and dysfunction following potential trauma: A review and statistical evaluation. Clin Psychol Rev. 2018 July;63:41\u0026ndash;55. \u003c/li\u003e\n\u003cli\u003eNICE. Post-traumatic stress disorder. National Institute for Health and Care Excellence; 2018. \u003c/li\u003e\n\u003cli\u003eCohen S, Kaplan Z, Zohar J, Cohen H. Preventing sleep on the first resting phase following a traumatic event attenuates anxiety-related responses. Behav Brain Res. 2017 Mar;320:450\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eKearns MC, Ressler KJ, Zatzick D, Rothbaum BO. Early Interventions for Ptsd: A Review. Depress Anxiety. 2012;29(10):833\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eNorrholm SD, Vervliet B, Jovanovic T, Boshoven W, Myers KM, Davis M, et al. Timing of extinction relative to acquisition: A parametric analysis of fear extinction in humans. Behav Neurosci. 2008;122(5):1016\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eRothbaum BO, Davis M. Applying Learning Principles to the Treatment of Post-Trauma Reactions. Ann N Y Acad Sci. 2003;1008(1):112\u0026ndash;21. \u003c/li\u003e\n\u003cli\u003eBisson JI, Wright LA, Jones KA, Lewis C, Phelps AJ, Sijbrandij M, et al. Preventing the onset of post traumatic stress disorder. Clin Psychol Rev. 2021 June;86:102004. \u003c/li\u003e\n\u003cli\u003eO\u0026rsquo;Donnell ML, Pacella BJ, Bryant RA, Olff M, Forbes D. Early intervention for trauma‑related psychopathology. In: Forbes D, Bisson JI, Monson C, Berliner L, editors. Effective treatments for PTSD: Practice guidelines from the International Society for Traumatic Stress Studies. 3rd edn The Guilford Press; 2020. p. 117\u0026ndash;36. \u003c/li\u003e\n\u003cli\u003eBragesj\u0026ouml; M, Arnberg FK, Olofsdotter Lauri K, Aspvall K, S\u0026auml;rnholm J, Andersson E. Condensed Internet-delivered prolonged exposure provided soon after trauma: a randomised trial. Psychol Med. 2023 Apr;53(5):1989\u0026ndash;98. \u003c/li\u003e\n\u003cli\u003eBragesj\u0026ouml; M, Arnberg FK, Jelbring A, Nolkrantz J, S\u0026auml;rnholm J, Olofsdotter Lauri K, et al. Demanding and effective: participants\u0026rsquo; experiences of internet-delivered prolonged exposure provided within two months after exposure to trauma. Eur J Psychotraumatology. 2021 Jan 1;12(1):1885193. \u003c/li\u003e\n\u003cli\u003eBragesj\u0026ouml; M, Arnberg FK, S\u0026auml;rnholm J, Olofsdotter Lauri K, Andersson E. Condensed internet-delivered prolonged exposure provided soon after trauma: A randomised pilot trial. Internet Interv. 2021 Mar;23:100358. \u003c/li\u003e\n\u003cli\u003eNorwegian Directorate of Health. Mestring, samh\u0026oslash;righet og h\u0026aring;p: Veileder for psykososiale tiltak ved kriser, ulykker og katastrofer. Norwegian Directorate of Health; 2016. \u003c/li\u003e\n\u003cli\u003eCrable EL, Lengnick-Hall R, Stadnick NA, Moullin JC, Aarons GA. Where is \u0026ldquo;policy\u0026rdquo; in dissemination and implementation science? Recommendations to advance theories, models, and frameworks: EPIS as a case example. Implement Sci. 2022 Dec 12;17(1):80. \u003c/li\u003e\n\u003cli\u003ePurtle J, Moucheraud C, Yang LH, Shelley D. Four very basic ways to think about policy in implementation science. Implement Sci Commun. 2023 Sept 12;4(1):111. \u003c/li\u003e\n\u003cli\u003eAarons GA, Hurlburt M, Horwitz SM. Advancing a Conceptual Model of Evidence-Based Practice Implementation in Public Service Sectors. Adm Policy Ment Health. 2011;38(1):4\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eLengnick-Hall R, Willging C, Hurlburt M, Fenwick K, Aarons GA. Contracting as a bridging factor linking outer and inner contexts during EBP implementation and sustainment: a prospective study across multiple U.S. public sector service systems. Implement Sci. 2020 June 11;15(1):43. \u003c/li\u003e\n\u003cli\u003eMoullin JC, Dickson KS, Stadnick NA, Rabin B, Aarons GA. Systematic review of the Exploration, Preparation, Implementation, Sustainment (EPIS) framework. Implement Sci. 2019 Jan 5;14(1):1. \u003c/li\u003e\n\u003cli\u003eCurran GM, Bauer M, Mittman B, Pyne JM, Stetler C. Effectiveness-implementation Hybrid Designs. Med Care. 2012 Mar;50(3):217\u0026ndash;26. \u003c/li\u003e\n\u003cli\u003eChan AW, Tetzlaff JM, G\u0026oslash;tzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013 Jan 9;346:e7586. \u003c/li\u003e\n\u003cli\u003eAmerican Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th edn. Washington, DC; 2013. \u003c/li\u003e\n\u003cli\u003eWeathers FW, Litz BT, Keane TM, Palmieri PA, Marx BP, Schnurr PP. National center for PTSD. 2013. The PTSD Checklist for DSM-5 (PCL-5). Available from: https://www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp\u003c/li\u003e\n\u003cli\u003eWeathers FW, Bovin MJ, Lee DJ, Sloan DM, Schnurr PP, Kaloupek DG, et al. The Clinician-Administered PTSD Scale for DSM\u0026ndash;5 (CAPS-5): Development and Initial Psychometric Evaluation in Military Veterans. Psychol Assess. 2018 Mar;30(3):383\u0026ndash;95. \u003c/li\u003e\n\u003cli\u003eSheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(20):22\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eParkinson B, Meacock R, Sutton M, Fichera E, Mills N, Shorter GW, et al. Designing and using incentives to support recruitment and retention in clinical trials: a scoping review and a checklist for design. Trials. 2019 Nov 9;20(1):624. \u003c/li\u003e\n\u003cli\u003eTreweek S, Lockhart P, Pitkethly M, Cook JA, Kjeldstr\u0026oslash;m M, Johansen M, et al. Methods to improve recruitment to randomised controlled trials: Cochrane systematic review and meta-analysis. BMJ Open. 2013 Jan 1;3(2):e002360. \u003c/li\u003e\n\u003cli\u003eSealed Envelope Ltd. Create a blocked randomisation list [Accessed 10th of May 2024]. [Internet]. 2022. Available from: https://www.sealedenvelope.com/simple-randomiser/v1/lists\u003c/li\u003e\n\u003cli\u003eFoa EB, Hembree EA, Rothbaum BO, Rauch SAM. Prolonged Exposure Therapy for PTSD: Emotional processing of traumatic experiences - therapist guide. 2nd edn. Oxford University Press Inc; 2019. 200 p. \u003c/li\u003e\n\u003cli\u003eCusack K, Jonas DE, Forneris CA, Wines C, Sonis J, Middleton JC, et al. Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis. Clin Psychol Rev. 2016 Feb;43:128\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003eMcLean CP, Foa EB. State of the Science: Prolonged exposure therapy for the treatment of posttraumatic stress disorder. J Trauma Stress. 2024 Apr 23;jts.23046. \u003c/li\u003e\n\u003cli\u003eBlevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation. J Trauma Stress. 2015;28(6):489\u0026ndash;98. \u003c/li\u003e\n\u003cli\u003eMekawi Y, Silverstein MW, Walker A, Ishiekwene M, Carter S, Michopoulos V, et al. Examining the psychometric properties of the PCL-5 in a black community sample using item response theory. J Anxiety Disord. 2022;87:102555. \u003c/li\u003e\n\u003cli\u003eSveen J, Bondjers K, Willebrand M. Psychometric properties of the PTSD Checklist for DSM-5: a pilot study. Eur J Psychotraumatology. 2016;7(1):30165. \u003c/li\u003e\n\u003cli\u003eHeir T. PCL-5. Norwegian centre for violence and traumatic stress studies; 2014. \u003c/li\u003e\n\u003cli\u003eLassen ER, Omre AN, Birkeland MS, Egeland K, B\u0026aelig;kkelund H. Psychometric evaluation of the PTSD Checklist for the DSM-5 (PCL-5) in Norway. Eur J Psychotraumatology. 2025 Dec 31;16(1):2570951. \u003c/li\u003e\n\u003cli\u003eB\u0026aelig;kkelund H, Aareskjold J, Endsj\u0026oslash; M. Norwegian centre for violence and traumatic stress studies. 2015. KLINIKERADMINISTRERT PTSD-SKALA FOR DSM-5: Versjon for vurdering av siste m\u0026aring;ned. Available from: https://www.nkvts.no/content/uploads/2018/03/KLINIKERADMINISTRERT-PTSD-SKALA-FOR-DSM-5-KAPS-5.pdf\u003c/li\u003e\n\u003cli\u003eMarx BP, Lee DJ, Norman SB, Bovin MJ, Sloan DM, Weathers FW, et al. Reliable and clinically significant change in the clinician-administered PTSD Scale for DSM-5 and PTSD Checklist for DSM-5 among male veterans. Psychol Assess. 2022;34(2):197\u0026ndash;203. \u003c/li\u003e\n\u003cli\u003eLeiknes KA, Malt UF. Oslo University Hospital. 2009. MINI INTERNASJONALT NEVROPSYKIATRISK INTERVJU: Norwegian Translation Version 6.0.0 DSM-IV. Available from: https://www.oslo-universitetssykehus.no/4a7fdb/contentassets/895610f6458a4ab89886fa06395d5745/dokumenter/m.i.n.i-skaringskjema-norsk-versjon.pdf\u003c/li\u003e\n\u003cli\u003eLecrubier Y, Sheehan D, Weiller E, Amorim P, Bonora I, Harnett Sheehan K, et al. The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI. Eur Psychiatry. 1997 Jan 1;12(5):224\u0026ndash;31. \u003c/li\u003e\n\u003cli\u003eSheehan D, Lecrubier Y, Harnett Sheehan K, Janavs J, Weiller E, Keskiner A, et al. The validity of the Mini International Neuropsychiatric Interview (MINI) according to the SCID-P and its reliability. Eur Psychiatry. 1997;12(5):232\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003eThoresen S, \u0026Oslash;verlien C. Norwegian centre for violence and traumatic stress studies. 2013. KARTLEGGING AV BELASTENDE LIVSHENDELSER (KBL). Available from: https://www.nkvts.no/content/uploads/2018/03/Kartlegging-av-belastende-livshendelser_KBL.pdf\u003c/li\u003e\n\u003cli\u003eGoodman LA, Corcoran C, Turner K, Yuan N, Green BL. Assessing traumatic event exposure: General issues and preliminary findings for the Stressful Life Events Screening Questionnaire. J Trauma Stress. 1998;11(3):521\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eGreen BL, Chung JY, Daroowalla A, Kaltman S, DeBenedictis C. Evaluating the Cultural Validity of the Stressful Life Events Screening Questionnaire. Violence Women. 2006 Dec;12(12):1191\u0026ndash;213. \u003c/li\u003e\n\u003cli\u003eKroenke K, Spitzer RL, Williams JB. The PHQ‐9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003eBrattmyr M, Lindberg MS, Solem S, Hjemdal O, Havnen A. Factor structure, measurement invariance, and concurrent validity of the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder scale-7 in a Norwegian psychiatric outpatient sample. BMC Psychiatry. 2022 July 11;22(1):461. \u003c/li\u003e\n\u003cli\u003eWisting L, Johnson SU, Bulik CM, Andreassen OA, R\u0026oslash; \u0026Oslash;, Bang L. Psychometric properties of the Norwegian version of the Patient Health Questionnaire-9 (PHQ-9) in a large female sample of adults with and without eating disorders. BMC Psychiatry. 2021 Jan 5;21(1):6. \u003c/li\u003e\n\u003cli\u003eBastien C. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001 July;2(4):297\u0026ndash;307. \u003c/li\u003e\n\u003cli\u003eBuysse DJ, Ancoli-Israel S, Edinger JD, Lichstein KL, Morin CM. Recommendations for a Standard Research Assessment of Insomnia. Sleep. 2006 Sept 1;29(9):1155\u0026ndash;73. \u003c/li\u003e\n\u003cli\u003eMorin CM, Belleville G, B\u0026eacute;langer L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011;34(5):601\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eLarsen DL, Attkisson CC, Hargreaves WA, Nguyen TD. Assessment of client/patient satisfaction: Development of a general scale. Eval Program Plann. 1979 Jan 1;2(3):197\u0026ndash;207. \u003c/li\u003e\n\u003cli\u003ePedersen H, Havnen A, Brattmyr M, Attkisson CC, Lara-Cabrera ML. A digital Norwegian version of the client satisfaction questionnaire 8: factor validity and internal reliability in outpatient mental health care. BMC Psychiatry. 2022 Oct 31;22(1):671. \u003c/li\u003e\n\u003cli\u003eBoelen PA, Smid GE. The Traumatic Grief Inventory Self-Report Version (TGI-SR): Introduction and Preliminary Psychometric Evaluation. J Loss Trauma. 2017 Apr 3;22(3):196\u0026ndash;212. \u003c/li\u003e\n\u003cli\u003eBoelen PA, Djelantik AAAMJ, de Keijser J, Lenferink LIM, Smid GE. Further validation of the Traumatic Grief Inventory-Self Report (TGI-SR): A measure of persistent complex bereavement disorder and prolonged grief disorder. Death Stud. 2019 July 3;43(6):351\u0026ndash;64. \u003c/li\u003e\n\u003cli\u003eLenferink LIM, van Dijk I, Eisma MC, Eklund R, Boelen PA, Sveen J. Psychometric evaluation of the Swedish Traumatic Grief Inventory Self-Report Plus (TGI-SR+) in bereaved parents. Clin Psychol Psychother. 2024;31(1):e2922. \u003c/li\u003e\n\u003cli\u003eHerdman M, Gudex C, Lloyd A, Janssen MF, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727\u0026ndash;36. \u003c/li\u003e\n\u003cli\u003eGarratt AM, Stavem K, Shaw JW, Rand K. EQ-5D-5L value set for Norway: a hybrid model using cTTO and DCE data. Qual Life Res. 2025;34(2):417\u0026ndash;27. \u003c/li\u003e\n\u003cli\u003eFeng YS, Kohlmann T, Janssen MF, Buchholz I. Psychometric properties of the EQ-5D-5L: a systematic review of the literature. Qual Life Res. 2021 Mar 1;30(3):647\u0026ndash;73. \u003c/li\u003e\n\u003cli\u003eKeetharuth AD, Brazier J, Connell J, Bjorner JB, Carlton J, Buck ET, et al. Recovering Quality of Life (ReQoL): a new generic self-reported outcome measure for use with people experiencing mental health difficulties. Br J Psychiatry. 2018 Jan;212(1):42\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eKeetharuth AD, Rowen D, Bjorner JB, Brazier J. Estimating a Preference-Based Index for Mental Health From the Recovering Quality of Life Measure: Valuation of Recovering Quality of Life Utility Index. Value Health. 2021 Feb;24(2):281\u0026ndash;90. \u003c/li\u003e\n\u003cli\u003eAndersson E, Hedman E, Enander J, Radu Djurfeldt D, Lj\u0026oacute;tsson B, Cervenka S, et al. D-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants: A Randomized Clinical Trial. JAMA Psychiatry. 2015 July 1;72(7):659. \u003c/li\u003e\n\u003cli\u003ePinheiro JC, Bates DM. Mixed-Effects Models in S and S-PLUS [Internet]. New York: Springer; 2000 [cited 2024 June 10]. (Statistics and Computing). Available from: http://link.springer.com/10.1007/b98882\u003c/li\u003e\n\u003cli\u003eDrummond MF, Sculpher MJ, Claxton K, Stoddart GL, Torrance and GW. Methods for the Economic Evaluation of Health Care Programmes. Fourth Edition. Oxford, New York: Oxford University Press; 2015. 464 p. \u003c/li\u003e\n\u003cli\u003eWhitehead SJ, Ali S. Health outcomes in economic evaluation: the QALY and utilities. Br Med Bull. 2010 Dec 1;96(1):5\u0026ndash;21. \u003c/li\u003e\n\u003cli\u003eNOU 2012: 16. Cost-Benefit Analysis [Internet]. Ministry of Finance; 2012. Available from: https://www.regjeringen.no/contentassets/5fce956d51364811b8547eebdbcde52c/en-gb/pdfs/nou201220120016000en_pdfs.pdf\u003c/li\u003e\n\u003cli\u003eNICE. NICE health technology evaluations: the manual [Internet]. 2025. Available from: https://www.nice.org.uk/process/pmg36\u003c/li\u003e\n\u003cli\u003eVan Horn PS, Green KE, Martinussen M. Survey Response Rates and Survey Administration in Counseling and Clinical Psychology: A Meta-Analysis. Educ Psychol Meas. 2009 June 1;69(3):389\u0026ndash;403. \u003c/li\u003e\n\u003cli\u003eRiggs DS, Rothbaum BO, Foa EB. A Prospective Examination of Symptoms of Posttraumatic Stress Disorder in Victims of Nonsexual Assault. J Interpers Violence. 1995 June;10(2):201\u0026ndash;14. \u003c/li\u003e\n\u003cli\u003eBond C, Lancaster GA, Campbell M, Chan C, Eddy S, Hopewell S, et al. Pilot and feasibility studies: extending the conceptual framework. Pilot Feasibility Stud. 2023 Feb 9;9(1):24. \u003c/li\u003e\n\u003cli\u003eEldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016 Oct 24;i5239. \u003c/li\u003e\n\u003cli\u003eRothbaum BO, Kearns MC, Price M, Malcoun E, Davis M, Ressler KJ, et al. Early Intervention May Prevent the Development of Posttraumatic Stress Disorder: A Randomized Pilot Civilian Study with Modified Prolonged Exposure. Biol Psychiatry. 2012 Dec;72(11):957\u0026ndash;63. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 2","content":"\u003cp\u003eTable 2 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Prevention, PTSD, Psychosocial Support, Cost-Effectiveness, Implementation, EPIS, CBT-T, CIPE","lastPublishedDoi":"10.21203/rs.3.rs-8039476/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8039476/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Post-traumatic stress disorder (PTSD) can have detrimental effects for those afflicted and is associated with increased health care utilization and substantial societal costs. Thus, there is a need for accessible, effective, and cost-efficient preventive interventions for post-traumatic psychological sequelae. Research indicates that trauma-focused cognitive-behavioral therapy (CBT-T) could effectively prevent PTSD when applied as an indicated secondary prevention. CIPE is a scalable, low-threshold, therapist-assisted digital CBT-T, which could be readily implemented in services delivering psychosocial support after traumatic incidents if proven effective and cost-effective. The Early Support after Exposure to Trauma (EASE) study evaluates the effectiveness, cost-effectiveness, and implementation of Condensed Internet-delivered Prolonged Exposure (CIPE), applied as an indicated secondary prevention in the context of Norwegian municipal crisis teams.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods/design\u003c/strong\u003e: The EASE study is a hybrid Type 1 effectiveness and implementation trial. The effectiveness trial is a parallel two-armed multicenter randomized controlled add-on superiority trial, enrolling individuals who receive support from psychosocial crisis teams within 7 weeks after trauma. Participants are randomized to CIPE + treatment as usual (TAU) or TAU only. The primary outcome is the level of PTSD symptoms 6 weeks after randomization (10-13 weeks post trauma). Secondary outcomes include symptoms of depression and insomnia, quality of life, and CIPE cost-effectiveness. The implementation trial examines policy-level factors influencing CIPE implementation, using the Exploration, Preparation, Implementation, Sustainment framework.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e: This study will guide further research, policy shaping, and clinical initiatives for implementing preventive interventions aimed at reducing post-traumatic psychological sequelae by integrating evidence-based interventions into routine psychosocial services.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration: \u003c/strong\u003eClinicalTrials.gov NTC302302. Date: 19.11.2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProtocol version: \u003c/strong\u003eProtocol version 3.0 (18.09.2025) is currently active.\u003c/p\u003e","manuscriptTitle":"Early Support after Exposure to Trauma (EASE): Protocol for a hybrid effectiveness-implementation trial of an internet-based intervention for PTSD prevention","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-14 07:26:34","doi":"10.21203/rs.3.rs-8039476/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-21T02:30:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-10T09:35:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-10T09:33:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Trials","date":"2025-11-05T14:28:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"562c4d05-5708-40b2-8769-627c302f93e7","owner":[],"postedDate":"November 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:03:07+00:00","versionOfRecord":{"articleIdentity":"rs-8039476","link":"https://doi.org/10.1186/s13063-026-09502-z","journal":{"identity":"trials","isVorOnly":false,"title":"Trials"},"publishedOn":"2026-02-05 15:59:31","publishedOnDateReadable":"February 5th, 2026"},"versionCreatedAt":"2025-11-14 07:26:34","video":"","vorDoi":"10.1186/s13063-026-09502-z","vorDoiUrl":"https://doi.org/10.1186/s13063-026-09502-z","workflowStages":[]},"version":"v1","identity":"rs-8039476","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8039476","identity":"rs-8039476","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}