ADVANCE protocol tests scalable psychological support for migrants in Italy

Researchers have published a protocol for the ADVANCE trial, which will test two World Health Organization psychological interventions against a psychological placebo among adult migrants resettled in Italy. The planned three-arm, hybrid type-I randomized controlled trial will assess clinical effects alongside feasibility, acceptability, appropriateness, delivery costs, cost-effectiveness and prospects for wider implementation. It will enroll 237 participants in Verona and Rome and compare in-person Self-Help Plus, guided online Doing What Matters in Times of Stress and a psychological placebo without active intervention ingredients. Because this is a study protocol, the research has not yet established whether either program reduces symptoms, improves implementation or provides better value for money.

The trial is designed to address important gaps in the existing evidence on WHO stress-management programs for people exposed to adversity. Previous studies have evaluated Self-Help Plus and Doing What Matters in Times of Stress among refugees, asylum seekers, migrants and other vulnerable groups, but the protocol notes that intervention effects can attenuate over time. Most earlier comparisons used usual care or another intervention, limiting the ability to distinguish effects attributable to program-specific skills from nonspecific factors such as attention, expectation and contact with a helper. ADVANCE will give all three arms comparable numbers of contacts and similar levels of support, while its placebo contains no active intervention ingredients. The two WHO programs will also receive digital booster sessions to examine whether reinforcing core skills helps sustain effects through six-month follow-up.

Self-Help Plus, or SH+, is a five-session, group-based stress-management course grounded in acceptance and commitment therapy. It teaches participants ways to accommodate difficult thoughts and feelings while taking actions consistent with their values. Sessions use standardized audio recordings and accompanying materials, with facilitators providing structured organizational support rather than intensive psychotherapy. Groups can contain up to 30 people, and the program is intended to be delivered by trained non-specialist helpers. The ADVANCE materials were contextually adapted for migrants through the earlier REDEFINE project and translated into Italian under the WHO protocol. An online individual booster lasting about 20 minutes will summarize the five sessions, while WHO forms and observation of at least 10% of sessions will assess fidelity.

The psychological placebo consists of five scripted phone calls or online meetings with the same duration as the DWM sessions. At the start of each contact, participants will be reminded of locally available health, social, legal and educational services; the remainder will involve discussion of topics selected from a list prepared by the research team. One additional neutral individual session will mirror the duration of the booster sessions offered in the two active-program arms. Before randomization, every eligible participant will receive a 30- to 45-minute Psychological First Aid conversation intended to provide practical support and promote adaptive functioning. All participants will also receive enhanced care as usual, including information about local referral routes and health, social, legal, educational and community services.

Eligible participants must be at least 18 years old, live as migrants resettled temporarily or permanently in Italy and report elevated psychological distress, defined as a score above 15.9 on the 10-item Kessler Psychological Distress Scale. They must also have sufficient written and spoken mastery of English or Italian and provide informed consent. Recruitment will be proactive and involve governmental and nongovernmental organizations, targeted social media, word of mouth and community organizations offering legal, social, administrative, psychological or religious support. Clinical screening will exclude people for whom participation would be inappropriate or unsafe, including acute medical conditions, imminent suicide risk, severe mental or cognitive disorders, unstable psychotropic medication use or current specialized psychological treatment.

Randomization will be coordinated centrally by the WHO Collaborating Centre at the University of Verona, with participants allocated equally to SH+, DWM or the psychological placebo. It will be stratified by recruitment area and generated in REDCap with variable block sizes concealed from site investigators. Assessments will occur at screening, baseline, three months and six months, with the booster session occurring before the three-month assessment. The primary endpoint is the change from baseline in the 16-item Patient Health Questionnaire–Anxiety and Depression Scale at three months, combining its nine-item depression and seven-item anxiety components. A trained assessor masked to allocation will read each item verbatim and record the response without clinical interpretation. Participants, helpers and other research staff cannot be masked because of the nature of the interventions.

The primary analysis will follow the intention-to-treat principle and use linear mixed models with time as a fixed effect, baseline PHQ-ADS score as a covariate and participant as a random effect. Interactions between treatment and time at three months will estimate the difference between each active intervention and placebo, with the Benjamini–Hochberg procedure used to control for the two primary comparisons. The calculation assumed a time-by-treatment effect size of Cohen’s f of 0.34. Fifty-five evaluable participants per arm would provide 90% power, and recruitment of 79 per arm allows for an anticipated 30% attrition rate. A per-protocol analysis will provide a confirmatory check, while a Bayesian sensitivity analysis will account for modest clustering among participants in the same SH+ group.

Secondary outcomes will cover depressive and anxiety symptoms separately, current mental health, functioning, well-being, internalized stigma, health-related quality of life, use of health and other care services, losses to follow-up and intervention fidelity. Acceptability, appropriateness and feasibility will be examined with named questionnaires, adverse-event reporting and records of participation, including group sessions attended, DWM modules accessed and placebo calls completed. The economic evaluation will use a societal perspective and combine activity-based micro-costing with cost-effectiveness, cost-utility and extended cost-effectiveness analyses. Quality-adjusted life years will be derived from the EQ-5D-5L, and budget-impact scenarios will estimate costs under possible scale-up conditions. Because Italy has no formally adopted cost-effectiveness threshold, results will be examined across willingness-to-pay values of €20,000 to €40,000 per quality-adjusted life year, with €25,000 and €40,000 treated as illustrative reference points rather than national thresholds.

The protocol identifies limitations that will shape how any findings can be interpreted. Restricting eligibility to people proficient in English or Italian may exclude recently arrived refugees who have not acquired basic language skills, and recruitment in Verona and Rome may limit generalization to other Italian or European service settings. Most clinical and implementation outcomes will be self-reported, creating potential for reporting and social-desirability biases. Although the primary-outcome assessor and statistician will be masked, participants and helpers will know their allocation, which may influence expectations. Follow-up ends at six months, so the trial may not establish whether effects persist over the medium or longer term. The protocol, consent procedures and data-protection measures were approved by the Comitato Etico Territoriale Area Sud Ovest Veneto under approval number 68505, and the trial is registered as NCT07209306. Results are intended for peer-reviewed publication, scientific meetings and dissemination through the ADVANCE policy and scaling strategy.

Subject of Research: A planned randomized trial of WHO psychological interventions, implementation outcomes and costs for migrants resettled in Italy

Article Title: Effectiveness, cost-effectiveness and implementation of WHO psychological interventions for migrant populations resettled in Italy: study protocol for the ADVANCE hybrid type-I randomized controlled trial

Article References: Purgato, M., Tedeschi, F., Prina, E., Turrini, G., Compri, B., Chiccoli, A., Marti-Castaner, M., De Allegri, M., Nguyen, H. T., Feenstra, S., Khalil, S., Reininghaus, U., Fleck, L., Sanna, L., Välimäki, M., Satamo, M., Kazlauskas, E., Dumarkaite, A., Kliegel, M., … Barbui, C. (2026). Effectiveness, cost-effectiveness and implementation of WHO psychological interventions for migrant populations resettled in Italy: study protocol for the ADVANCE hybrid type-I randomized controlled trial. Frontiers in Public Health, 14, Article 1905759. https://doi.org/10.3389/fpubh.2026.1905759

Image Credits: AI Generated

DOI: 10.3389/fpubh.2026.1905759

Keywords: ADVANCE trial, migrant mental health, Self-Help Plus, Doing What Matters in Times of Stress, randomized controlled trial, implementation science, cost-effectiveness, psychological placebo, World Health Organization, digital mental health, task-sharing, Effectiveness