Challenges in conducting paediatric trials with off-patent drugs.

INTRODUCTION: For more than two decades several initiatives have emerged to increase recruitment of paediatric patients in drug trials. While trials of newly approved drugs have successfully included paediatric patients in their drug development plan, the collection of safety and efficacy data in paediatric patients treated with off-patent drugs poses a major challenge. AIM: This paper aims to draw attention to problems and solutions across countries in investigator-initiated trials with off-patent drugs and recommendations for improvement. DISCUSSION: Off-patent drugs represent a particular challenge when they are included in a paediatric trial; these trials are frequently investigator-initiated and have limited resources, off-patent drugs are used in clinical settings and the trial protocol must accommodate e.g. flexible dosing and specimen sampling schedules, off-patent drugs typically exist in few formulations and concentrations which necessitates special or imported formulations. Paediatric trials are in some countries confined by e.g. consent from both parents, regardless of whether the Investigational Medicinal Product (IMP) is a well-known drug or a new experimental drug. CONCLUSION: Facilitation of research in off-patent drugs can improve evidence-based and safe treatment for the paediatric population. The following supportive initiatives are recommended: Harmonised regulatory change that improves the consent process in low risk trials to prevent inadequate recruitment. Pharmaceutical expertise should be prioritized to secure the best choice of IMP and supply. Constant focus on flexibility in design to accommodate a multifaceted paediatric population and ensure that trial protocols fit in well with routine clinical care and family life.

Limited knowledge of Tourette syndrome causes delay in diagnosis.

OBJECTIVE: Tourette syndrome (TS) is characterized by the presence of tics and is often accompanied by other symptoms, like attention deficit hyperactive disorder (ADHD), obsessive-compulsive disorder. The presenting symptoms are supposed to be tics. Onset is usually around school age. Early diagnosis of TS is important in order to provide patients with the necessary support as early as possible. METHODS: We examined the diagnostic process via a systematic interview in 314 children with TS. RESULTS: Median age at onset of symptoms was 3.0 years. In 40.1%, tics were the presenting clinically meaningful symptoms; in the other cases it was an associated symptom, like ADHD symptoms, obsessive-compulsive behavior, or behavioral problems. Median age of tic onset was 5.5 years. If TS presented with an accompanying symptom, the median age of onset was earlier (0-3.5 years). The mean age at the time of diagnosis was 8.9 years. The median delay from onset of the presenting symptoms until diagnosis was 5.3 years and the delay from onset of tics until diagnosis 2.8 years. CONCLUSION: There is a lack of knowledge about the normal course of TS among professionals and the public. Consequently, diagnosis is delayed and so accordingly is the initiation of the necessary support.