The International Society for Central Nervous System Clinical Trials and Methodology (ISCTM) partnered with the Michael J. Fox Foundation for Parkinson’s Research to hold a joint session on innovation in Parkinson’s disease research at the ISCTM 14th Annual Scientific Meeting held February 20 to 22, 2018 in Washington, D.C. The session focused on (1) biomarkers and outcomes measures in Parkinson’s disease clinical trials; 2) clinical trial designs, outcomes, and statistical approaches; and 3) the path forward. This paper aims to summarize key takeaways from the session presenters, panelists, and audience members.

Individuals from academia, the pharmaceutical industry, and regulators reevaluated earlier recommendations for the design of clinical trials for negative symptoms based on data from recent large trials. A session in February, 2018 at the International Society of CNS Clinical Trails and Methodology (ISCTM) annual meeting reviewed results from selected trials that reported findings between 2013 and 2018. The group reached a consensus on prior recommendations that should be reconsidered in future trials which included: (1) How can placebo effects be minimized? (2) Should global measures of negative symptoms be included? (3) Should a new drug targeting negative symptoms be tested in a monotherapy design or in an add-on design? (4) Can new information from negative symptom trials inform the selection of clinical outcome assessments (COA’s) for future trials? For each of these issues new data was evaluated, discussed by the group, and in some cases the earlier recommendations were revised.

International Society for CNS Clinical Trials and Methodology convened an expert Working Group that assembled consistency/inconsistency flags for the Montgomery-Asberg Depression Rating Scale (MADRS). Twenty-two flags were identified. Seven flags are believed to be strong flags that suggest that a thorough review of rating is warranted. The flags were applied to assessments derived from the NEWMEDS data repository. Almost 65% of ratings had at least one inconsistency flag raised and 22% had two or more. Application of flags to clinical ratings may improve reliability of ratings and validity of trials.