BACKGROUND: Various explicit screening tools, developed mostly in central Europe and the USA, assist clinicians in optimizing medication use for older adults. The Turkish Inappropriate Medication use in oldEr adults (TIME) criteria set, primarily based on the STOPP/START criteria set, is a current explicit tool originally developed for Eastern Europe and subsequently validated for broader use in Central European settings. Reviewed every three months to align with the latest scientific literature, it is one of the most up-to-date tools available. The tool is accessible via a free mobile app and website platforms, ensuring convenience for clinicians and timely integration of updates as needed. Healthcare providers often prefer to use their native language in medical practice, highlighting the need for prescribing tools to be translated and adapted into multiple languages to promote optimal medication practices. OBJECTIVE: To describe the protocol for cross-cultural and language validation of the TIME criteria in various commonly used languages and to outline its protocol for clinical validation across different healthcare settings. METHODS: The TIME International Study Group comprised 24 geriatric pharmacotherapy experts from 12 countries. In selecting the framework for the study, we reviewed the steps and outcomes from previous research on cross-cultural adaptations and clinical validations of explicit tools. Assessment tools were selected based on both their validity in accurately addressing the relevant issues and their feasibility for practical implementation. The drafted methodology paper was circulated among the study group members for feedback and revisions leading to a final consensus. RESULTS: The research methodology consists of two phases. Cross-cultural adaptation/language validation phase follows the 8-step approach recommended by World Health Organization. This phase allows regions or countries to make modifications to existing criteria or introduce new adjustments based on local prescribing practices and available medications, as long as these adjustments are supported by current scientific evidence. The second phase involves the clinical validation, where participants will be randomized into two groups. The control group will receive standard care, while the intervention group will have their treatment evaluated by clinicians who will review the TIME criteria and consider its recommendations. A variety of patient outcomes (i.e., number of hospital admissions, quality of life, number of regular medications [including over the counter medications], geriatric syndromes and mortality) in different healthcare settings will be investigated. CONCLUSION: The outputs of this methodological report are expected to promote broader adoption of the TIME criteria. Studies building on this work are anticipated to enhance the identification and management of inappropriate medication use and contribute to improved patient outcomes.

Amsterdam Public Health Aging and Later Life Amsterdam The Netherlands

Center for Appropriate Medication Use Sheba Medical Center Tel Hashomer Ramat Gan Israel

Department of Anesthesiology Pharmacology and Therapeutics Faculty of Medicine University of British Columbia Vancouver BC Canada

Department of Clinical and Molecular Sciences Universita Politecnica delle Marche Ancona Italy

Department of Geriatric Medicine Hospital del Mar Barcelona Spain

Department of Geriatrics and Internal Medicine 1st Faculty of Medicine Charles University General Faculty Hospital Prague Czech Republic

Department of Internal Medicine and Gerontology Jagiellonian University Medical College University Hospital 2 Jakubowskiego St Building 1 5th Floor 30 688 Kraków Poland

Department of Internal Medicine and Paediatrics Faculty of Medicine and Health Sciences University of Ghent Ghent Belgium

Department of Medicine 4 LMU University Hospital LMU Munich Munich Germany

Division of Geriatrics Department of Internal Medicine Istanbul Medical Faculty Istanbul University Çapa 34093 Istanbul Turkey

Division of Geriatrics Department of Internal Medicine Liv Hospital Istanbul Turkey

Division of Geriatrics Department of Internal Medicine Marmara University Medical School Pendik Istanbul Turkey

Ehemals Institut für Klinische Pharmakologie Medizinische Fakultät Mannheim Universität Heidelberg Theodor Kutzer Ufer 1 3 68167 Mannheim Germany

European Geriatric Medicine Society Vienna Austria

Faculty of Health and Social Sciences South Bohemian University Ceske Budejovice Czech Republic

Fondazione Policlinico Gemelli IRCCS and Università Cattolica del Sacro Cuore Rome Italy

Geriatria Accettazione Geriatrica e Centro di Ricerca Per l'invecchiamento IRCCS INRCA Ancona Italy

Internal Medicine Section of Geriatric Medicine Amsterdam UMC Location University of Amsterdam Amsterdam The Netherlands

Leslie Dan Faculty of Pharmacy University of Toronto Toronto Canada

Pôle « Maladies du Vieillissement Gérontologie et Soins Palliatifs » and INSERM DCAC u1116 Université de Lorraine CHRU Nancy 54000 Nancy France

Pôle « Maladies du Vieillissement Gérontologie et Soins Palliatifs » Université de Lorraine CHRU Nancy Nancy France

Women's Age Lab and Women's College Research Institute Women's College Hospital Toronto ON Canada

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