*Corresponding author email: michel.bourin@univ-nantes.fr Symbiosis Group Symbiosis www.symbiosisonline.org www.symbiosisonlinepublishing.com SOJ Pharmacy & Pharmaceutical Sciences Open Access Review Article Generally speaking, the primary outcome measure evaluates the efficacy of a given intervention on the main diagnostic criteria used to define the therapeutic indication (i.e. psychotic symptoms for schizophrenia; fast blood glucose and glycated hemoglobin for diabetes). Secondary outcome measures include individual components of the diagnostic criteria (specific symptoms, biomarkers and/or others), together with parameters evaluating quality of life, satisfaction, social and professional functioning, and burden for families and caregivers. “Safety studies” explore undesirable effects, particularly those related to mechanism of action. Taken into account the above elements, we describe here the rationale underlying the choice of evaluation criteria. This means, which outcome measurements (clinical symptom severity, changes in vital signs, biochemical markers and imaging) may be chosen to evaluate treatment as a function of the type of therapeutic indication. Evaluation criteria for symptomatic treatments Many therapeutic indications concern a given clinical symptomatology, including disorders in vital functions (clinical signs).Symptomatic treatment is also the rule for disorders where the physiopathological mechanisms are badly known, such as mental disorders. The primary outcome measurement of a symptomatic treatment is intended to evaluate the symptom severity and/or the functional disorders defining a therapeutic indication. Secondary outcome measurements may include single symptoms or signs, quality of life assessments and drug consumption (e.g., many evaluation methods are available to quantify drug consumption in chronic rheumatic diseases[6]). Many studies, expert meetings and manuals have been dedicated to define a “core” of symptoms and signs of different diseases [7] (for mental disorders see [8]). Questionnaires concerning “core symptoms” have been edited, together with scales evaluating symptom severity, e.g., the Hamilton Anxiety Rating Scale (HAM-A)[9] and the Positive and Negative Syndrome Scale (PANSS) for schizophrenia[10]. Scale scores are evaluated with categorical or continuous scales. A typical categorical clinical scale is based on the following symptom severities: 0 = normal or absent, 1 = mild, 2 = moderate, 3 = severe and 4 = extremely Choice of Evaluation Criteria in a Clinical Trial Michel Bourin 1 * and Ricardo P Garay 2,3 1 Neurobiology of Mood disorders, University of Nantes, Nantes, France. 2 Pharmacology and Therapeutics, Craven, Villemoisson-sur-Orge, France. 3 CNRS, National Centre of Scientific Research, Paris, France. Received: September 23, 2016; Accepted: October 5, 2016; Published: October 27, 2016 *Corresponding author: Michel Bourin, Neurobiology of Mood disorders, University of Nantes, 98 rue Joseph Blanchart, 44100 Nantes, France; E-mail: michel.bourin@univ-nantes.fr Abstract The choice of proper evaluation criteria is a key aspect of any clinical trial. The efficacy, tolerance and safety of symptomatic treatments can be evaluated by assessing clinical symptoms and/ or signs (vital functions). For life-threatening diseases, the relevant evaluation criterion is morbi-mortality. However, this criterion is rarely chosen because it requires very long-term studies and a large number of patients. Then, a biomarker or other intermediary criteria can be used as a substitute endpoint. The intermediary criterion should correlate well with morbi-mortality (clinical criterion).In these last years, the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have been publishing scientific guidelines defining efficacy and safety evaluation criteria for the phase I and II “proof of concept” Randomized Clinical Trials (RCTs) and the phase III “pivotal trials” which are required for marketing authorization. The present paper describes the rationale underlying the choice of evaluation criteria, together with the advantages and limitations of their application in some selected therapeutic indications. Keywords: Clinical trials; Evaluation criteria; Intermediary criteria; Judgment criteria; Introduction Evaluation criteria include outcome measurements and assessment tools designed to evaluate the efficacy, safety and tolerability of a new treatment. Classically, the choice of evaluation criteria in a clinical trial was left to the discretion of the investigator. In these last years, the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have been publishing scientific guidelines on how to interpret and apply the requirements for the demonstration of quality, safety and efficacy of health interventions in a large number of therapeutic indications [1, 2]. These regulatory guidelines define the efficacy outcomes and assessment tools for phase II “proof of concept” Randomized Clinical Trials (RCTs) and phase III “pivotal trials” which are required for marketing authorization (for definition of “proof of concept” studies see[3, 4], for “pivotal trials” see[5]). A “therapeutic indication” defines the symptom or disease and the population for which the health intervention is intended.