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  • Writer's pictureN-of-1 Hub

Personalised Clinical Trials (N-of-1) for Children with Fetal Alcohol Spectrum Disorder (FASD)

N-of-1 Hub is collaborating with Monash University and Monash Health on a series of N-of-1 trials to see whether stimulants improve Attention Deficit Hyperactivity Disorder (ADHD) symptoms in children diagnosed with Fetal Alcohol Spectrum Disorder.



What is the clinical problem?

Fetal Alcohol Spectrum Disorder (FASD) is a neuro-developmental disorder caused by alcohol exposure during pregnancy. Children with FASD experience disruption to their neurodevelopment, and 50-94 % of children with FASD meet DSM-5 diagnostic criteria for ADHD difficulties. There is a paucity of evidence on whether stimulant medication is effective in treating ADHD symptoms in children with FASD. The limited evidence available suggests there is a wide variation in treatment response to stimulant medication in children with FASD.


What are N-of-1 trials?

N-of-1 trials use the patient as their own control to determine whether a treatment is effective for them. These study designs are often mistaken for “qualitative” or “descriptive” case studies, but they are prospectively designed quantitative studies designed to rigorously collect and analyse data from an individual. They provide more reliable conclusions than the “trial and error” approach that is commonly used to determine the best treatment for a patient in clinical practice.


N-of-1 trials provide the opportunity for the highest level of evidence to be obtained about what works for an individual. Results can be used to inform shared decision-making about future management.


N-of-1 trials to test stimulants in children with FASD

Associate Professor Jane Nikles, Director of N-of-1 Hub, explains,

“Further value can be obtained through pooling the data from a series of N-of-1 trials. Pooled N-of-1 trials are well suited to clinical trials where it is difficult to recruit, such as in children, because they can provide rigorous information with a small number of patients. Pooled N-of-1 trials often require smaller numbers of patients to participate than standard clinical trials, because they involve collecting multiple outcome measurements per participant, which increases statistical power."

Dr Ali Crichton adds: 

"N-of-1 trials have been successfully conducted in other paediatric populations to establish ADHD medication efficacy but are yet to be used in the FASD population. Large inter-individual variability in attention profiles in children with FASD and ADHD, mean standard clinical trials may fail to identify individual treatment response differences because they focus on aggregated group outcomes. Additionally, stimulants show substantial inter-individual variability in response, such that dose must be titrated in the individual to achieve clinical response on the lowest possible dose. Data from our group highlights this clinical variability and also shows frequent polypharmacy for treatment of ADHD in children with FASD. Approximately 25% of patients are routinely prescribed stimulants and non-stimulants for ADHD symptoms. This points to a critical need to conduct high quality research to inform individual treatment choices for ADHD in FASD."

For each child, we are conducting an N-of-1 trial design with four pairs of 2 week periods, each comparing randomly ordered stimulant and placebo. Feasibility and tolerability will be assessed by examining the level of completion of questionnaires, medication compliance with individual dosing schedule, and trial completion rates, alongside adverse events and parent ratings of the children’s side effects. N-of-1 trial data will be aggregated for analysis of the primary outcome  (ADHD behaviours measured using the Conners 3 Short form (S) (for children age 6 to18 years), and the Conners Early Childhood (for children 2 to 6 years), teacher rated versions) to provide an estimate of the group treatment effect as well as individual-level treatment effects. Potential mediating factors will be explored to identify variables that might be associated with variability of the response between individuals. Dr Crichton and other members of the team, including K. Harris, J. McGree,  P.J. Anderson, and K. Williams, co-designed the N-of-1 trials with N-of-1 Hub. 


This trial is funded by the Thrasher Research Fund.

 

N-of-1 Hub is a consulting company that specialises in designing, conducting and analysing personalised clinical studies using single-case designs. N-of-1 Hub also offers customised training workshops and data management and analysis services.

 


For further information about N-of-1 Hub, and to discuss your study needs, please contact us through the above form.







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