Innovations In Clinical Neuroscience

Summit 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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organizations, and regulatory agencies [ RAs] [e.g., FDA and European Medicines Agency (EMA)]). Health outcomes measurement in RCTs is an area of high interaction between several disciplines and different stakeholders. W hile stakeholders such as RAs advise on clinical endpoints to include in study protocols and provide approval for specific clinical endpoint measurements, others like private and public institutions create comprehensive libraries of instruments for COA measurements with description of their original psychometric properties obtained at validation stages. RAs are the main drivers for the final COAs and COA instrument selection, which guide the clinical endpoints required to claim a New Drug Application (NDA), followed by field experts on the therapeutic area. However, the definition of COAs provided by RAs is often not specific enough. Therefore, the disease- specific guidance issued is open to discussion, and consequently COA instrument selection requires a more interdisciplinary methodology. Design: We review the strategies used by different stakeholders for COA selection. In this context, we defined stakeholders as A) pharma industry, B) independent researchers, C) expert consultants, D) vendors, and E) alliances among stakeholders. As for selection strategies, we defined the use of A) RA guidance, B) results from published meta-analysis, C) literature reviews, D) libraries of COAs, E) libraries of instruments, F) authors of the specific instruments, G) key opinion leaders for specific diseases, H) new COAs v alidation set for specific drug development plans, and I) initiatives to systematize the selection as decision tools (i.e., checklists for COAs selection and for COAs instrument selection). E xamples of each one of the listed were provided, and strengths and weaknesses were analyzed for each one. We review the use of an efficacy-based selection approach within existing COA selection strategies. Results: Different examples for each above specified strategies and stakeholders' categories were identified based on specific searches on public databases and authors' experience in the field. Examples of identified strategies are systematic reviews (e.g., Core Outcome Measures in Effectiveness Trials [COMET] initiative), checklists for patient-reported outcome (PRO) selection (e.g., Consensus-based Standards for the Selection of health Measurement Instruments [COSMIN]), Evaluating the Measurement of Patient- Reported Outcomes [EMPRO]), or even a PRO dimensional approach, such as the Patient Reported Outcomes Measurement Information System (PROMIS). Furthermore, other strategies exist coming from alliances, such as pharma, academia, patients, and public health bodies, promoting COA identification, selection, and validation, as is sometimes the case with Innovative Medicines Initiative (IMI), National Institute of Mental Health Research Domain Criteria (NIMH–RDoC), specific funding actions, such as foundations and university chairs, and task force groups w ithin scientific societies, such as European College of Neuropsychopharmacology Targeted Network Meetings (ECNP-TNM) and The International Society for CNS Clinical T rials and Methodology (ISCTM). Conclusion: The number of trial failures in the neurosciences makes COAs and COA instrument selection especially critical. A review of the state of the art regarding all initiatives to improve COA and COA selection process is presented. Overall innovative approaches on endpoint selection will require an approach focused on efficacy based COA selection requiring pre-competitive actions in order to 1) confirm the psychometric features of COAs completed in clinical trials (global and by country-language), 2) explore potential derived composite scores as clinical surrogates or endpoints, 3) confirm efficiency of COAs used in past trials at global and by country-language level, 4) explore feasibility of core outcome set (COS) specific for indications, based on qualitative and as well as quantitative methods. Initiatives do exist in the European Union and United States, but there is a need to describe the state of the art, to set a framework for all this activity, and to highlight the weaknesses and strengths of the existing ones, ideally those available to drug developers, and end users (i.e., clinical trial designers and scientists). Within the existing initiatives a more efficacy-based approach for COAs needs to be explored. ICNS ICNS Innovations in Clinical Neuroscience • November–December 2017 • Volume 14 • Number 11–12 • Supplement S18

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