Clinical Viewpoints

Pediatric clinical trials offer unique challenges. They are often associated with the highest placebo response rates.  Clinical outcome assessments are complicated by different age-appropriate versions and observer versions. And obtaining consent and assent is a more complex process. Dr. Joan Busner, chair of ISCTM Orphan Diseases Working Group, provides insights from her considerable experience in designing and supporting pediatric and rare disease clinical trials. 

Mood disorder clinical trials rely upon clinician ratings for key measures of efficacy.  Ensuring the eligibility of patients is a critical success factor, and when ratings are also used as eligibility criteria this can present challenges.  Gary Sachs, MD, Clinical Vice President, Bipolar Disease and Mood Disorders, discusses how to measure diagnostic confidence, and leverage this to improve the ability to detect treatment-related effects in mood disorder trials.  

The draft FDA guidelines on patient-reported outcomes in cancer trials, changes the way we design and implement COA measurement strategies in oncology trials. Todd Everhart, MD, our Clinical VP of Internal Medicine, provides insights for good measurement strategy in oncology designs, and how to leverage decentralized methods to optimize the trial participation experience for patients and sites.  

David Daniel, MD, our Head of CNS medicine, applies his years of in-depth knowledge and experience of the design and conduct of schizophrenia clinical trials to discuss the challenges and solutions in detecting treatment effects for positive and negative symptoms.  

Many CNS clinical trials use clinician ratings to support important study endpoints. When ratings are also used as eligibility criteria, this can lead to greater apparent placebo response due to baseline score inflation, and this increases the difficulty in detecting treatment-related effects. Gary Sachs, MD, Clinical Vice President, Bipolar Disease and Mood Disorders, and Alan Kott, MUDr, Practice Lead, Data Analytics, explore approaches on how to detect and how to mitigate baseline score inflation in CNS trials.

In this episode of Clinical Viewpoints, Dr. Steve Targum,  an experienced CNS researcher, discusses the complexities of placebo responses in clinical trials. Highlighting the challenges of signal detection amidst higher-than-anticipated placebo effects, he explores the efficacy of double-blind placebo run-in designs. Dr. Targum emphasizes the need for systematic approaches to manage placebo responses, citing examples from his research. He underscores the design's potential to enhance trial outcomes by identifying and managing early responders effectively, despite industry hesitations due to conservatism and cost concerns.

There are several well-established clinician ratings that are used in Parkinson’s clinical trials such as the UPDRS which have led to successful drug approvals. However, with increasing research and development into new wearable sensors, artificial intelligence, and remote assessment, there is increasing interest and activity in the development and validation of novel endpoints. Lew Fredane, Clinical Vice President and Therapeutic Area Leader for neurology at Signant, discusses novel endpoints in PD trials.