The Ethical considerations of Placebo Study design in NMO EMA view - PowerPoint PPT Presentation

The Ethical considerations of Placebo Study design in NMO EMA view Regulatory Workshop on Clinical Trials Designs in Neuromyelitis Optica London, October 2014

Ethics • Deontology • Teleology – Clinicians – Final outcome of development – Investigators • Need to compare to approved agents • Virtue • Easiness of investigation • Short time to market the – Patients and society final product • Investigator integrity • Clinician integrity

EMA view Aspects to consider Study population Benefit over present best • • – NMO / NMOSD standard of care – AQP4-IgG positive / negative Risk over present best • – Previously immunosuppression standard of care / Ongoing / Naïve Risk of withholding treatment – Post Immunosuppressant • failure Comparator availability • Risk of uncertainty in • – Which active comparators are knowledge of benefit / risk available for best care balance when establishing Commitment • comparison to best care – – Patient external validity – Clinician / Investigator – Sponsor

Schizophrenia EMA view • Similar risk for • Placebo arm not withholding treatment accepted – Increased acute risk • Pseudoplacebo (low – Increased disability if dose antipsychotic) non treated accepted in some • FDA demand for circumstances placebo arm, in spite of other approved treatments

EMA view • Placebo controlled trial hardly acceptable for clinically confirmed NMO / NMOSD pts who are responding to immunossupressant tx: – Reasonable diagnostic certainty – Recognised efficacious therapeutic options with known risks

EMA view • Placebo controlled trial also hardly acceptable for: – AQP4-IgG negative with NMO criteria – NMOSD if previously identified neurological impairment

EMA view • Placebo controlled trial might be acceptable – In NMO / NMOSD patients who failed previous treatments (failure definition) – As add-on to ongoing immunosuppressant tx