Applying established frameworks for cultural adaptation of evidence-based programs (EBPs) is essential to ensure cost-effectiveness, adoption, and sustainability while advancing health equity. However, adaptation processes often lack systematic approaches, particularly outside academic contexts. This study explores how cultural adaptation processes of prevention programs are delivered to address adolescent substance use and common mental health issues, from the perspective of the main stakeholders involved in these processes. In parallel, it aims to empirically refine and specify the 11 stages synthesized in prior work that integrated insights from multiple cultural adaptation processes and frameworks. A qualitative analysis was conducted using content analysis of 22 semi-structured interviews with stakeholders from the quadruple helix model: 6 from Academia, 6 from Non-governmental organizations (NGOs), and 10 from Public administration, selected globally. Stakeholders were identified via brainstorming and purposive-convenience sampling, based on their roles in adapting, implementing, evaluating, or funding prevention programs addressing adolescent substance use and mental health issues. Despite extensive recruitment efforts, no representation from the Business helix was achieved, as only one business contact agreed to be interviewed, which was not considered sufficient for inclusion. The qualitative analysis refined and expanded the stages of a cultural adaptation sequence that reflects how cultural adaptation processes are conducted in practice: building synergies, local needs assessment, program selection, initial cultural adaptation, advisory group consultation, staff training, piloting, program refinement and readiness for implementation, implementation, monitoring and evaluation, and dissemination and sustainability. Notably, not all stakeholders followed or applied the steps uniformly. Furthermore, academics were the only group to report using formal cultural adaptation models, while NGOs and the Public administration relied on experiential and contextual knowledge. Findings underscore the importance of translating scientific knowledge into practice contexts while ensuring continuous evaluation, dissemination, and sustainability of adapted EBPs targeting adolescent substance use and mental health issues. Collaborative efforts and co-creative strategies are crucial to maintaining cultural relevance. This study contributes by offering empirical refinement and operational specification of an 11-step cultural adaptation sequence identified in a prior scoping review. Linking evidence from prior literature with practice provides greater clarity and applicability for implementers seeking to culturally adapt prevention programs across diverse contexts. Evidence-based prevention programs can help adolescents avoid substance use and improve mental health. However, these programs are often designed in different cultural contexts from where they are later used. This study explores how prevention programs are adapted to fit the cultural realities of adolescents in diverse settings. Drawing on 11 stages identified in a prior review, 22 interviews with individuals from academia, non-governmental organizations, and public institutions were analyzed to explore how these stages are applied in practice. The study refined and expanded the existing sequence into a 12-step integrative process that describes how cultural adaptations unfold—from assessing local needs and selecting programs to adapting content, training staff, and evaluating outcomes. Findings show that these steps are not applied consistently across sectors, and only academics tend to use recognized frameworks for cultural adaptations. This highlights a gap between scientific knowledge and practice. To make prevention programs more effective and sustainable, it is crucial to involve local communities, foster cross-sector collaboration, and apply systematic methods that prioritize cultural relevance. This study lays the groundwork for a more structured, practice-based approach to cultural adaptation.
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