ABSTRACT
Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document.
Subject(s)
Antirheumatic Agents/therapeutic use , Drug Approval/legislation & jurisprudence , Drug and Narcotic Control/trends , Health Planning Guidelines , Rheumatic Fever/drug therapy , Clinical Trials, Phase III as Topic , Drug and Narcotic Control/legislation & jurisprudence , Europe , Humans , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Placebos , Practice Guidelines as Topic , Time FactorsSubject(s)
Anticonvulsants/pharmacokinetics , Anticonvulsants/standards , Drug and Narcotic Control/legislation & jurisprudence , Drugs, Generic/pharmacokinetics , Drugs, Generic/standards , Epilepsy/drug therapy , Anticonvulsants/adverse effects , Clinical Trials as Topic/standards , Contraindications , Drug Substitution/adverse effects , Drug Substitution/standards , Drug and Narcotic Control/trends , Drugs, Generic/adverse effects , Epilepsy/prevention & control , European Union , Humans , Patient Compliance/psychology , Therapeutic EquivalencyABSTRACT
OBJECTIVE: Antidepressants use in paediatric patients has been linked with risk of suicidal behaviours. The aim of this paper, therefore, is to examine whether all antidepressants are associated with such risk. METHOD: All 22 paediatric short-term placebo-controlled trials of SSRIs and NSRIs that were submitted to European registration authorities by pharmaceutical companies were identified and examined for events related to suicidality, which were defined as suicide, suicide attempts or suicidal thoughts. Random effect meta-analysis was used to combine the information from all trials. RESULTS: No completed suicides were reported. However, for each compound there was at least one study with an increased risk for events related to suicidality in the active compound group. The overall OR for these events in the depression studies was 1.67 (95% CI: 1.05-2.65) and for anxiety 1.33 (95% CI: 0.33-5.35). CONCLUSIONS: Caution is called for in the use of all SSRIs and NSRIs in the paediatric population. Furthermore, in the absence of contradictory information, caution in the use of other antidepressants in this population should be exercised as well (e.g. tricyclic antidepressants).
