Signal detection poses important challenges in central nervous system (CNS) clinical trials.
The growth and globalization of multicenter CNS clinical trials —involving more and more countries, clinical sites, patients, and research professionals— have increased the difficulty for ensuring scoring consistency and trustworthy endpoint data quality.
Factors affecting signal detection and potentially causing the failure of CNS studies include poor subject selection, rating scale selection, rater training, and quality of scale administration. Moreover, rater-related subjectivity, variability, and bias can make signal detection almost an infeasible task.
Therefore, ensuring accurate and reliable endpoint data in CNS clinical trials is of utmost importance, yet this remains as a very challenging endeavor.
The Challenge of Poor Patient Selection and Subjectivity
Assessment subjectivity can be improved by the standardization of enrolled patients.
An important strategy to reduce assessment subjectivity is to ensure that every patient qualifies for the study and meets enrollment eligibility. Wrongly categorized patients can have a very negative impact on signal detection.
Many sponsors utilize a pre-enrollment form that ensures that ratings of medications, medical history, illness severity, demographics, and other patient variables are standardized.
It is also important to ensure that clinical trial subjects understand the scale being administered, including patient reported outcomes (PROs), and that their own responses to scale questions do not drift over time.
This can be accomplished via training, not only through trainings of the raters administering the scales, but also via training of the patients themselves.
The Difficulty of Rater Subjectivity and Bias
Rater subjectivity and bias is a major difficulty in CNS trials, since some endpoints may highly depend on human judgement. Rater bias, rater errors and rater variability put the quality of clinical data —and the entire trial— at risk.
Strategies to improve assessment subjectivity from the rater’s side are focused on the standardization of raters at clinical trial sites. Evaluations of inter- and intra-rater reliability at the start and during the entire duration of the clinical trial are useful to avoid rater drifts.
Rater Training and Qualification
Raters must be appropriately trained and qualified to ensure they adhere to scale administration guidelines and score in a consistent manner. The rater’s performance must be adequately assessed, and constant retraining and recalibration should be performed during the study to avoid mistakes.
Raters need to be carefully trained, and that training needs to continue through the life of the trial. Effective rater training can dramatically reduce rater errors, rater drift and inconsistency across raters.
In addition, independent central reviewers can improve quality control through monitoring of study data and the detection of quality problems.
How Can Sofpromed Help?
Sofpromed provides a team of clinicians who are experts in the main CNS clinical trial indications such as mood disorders (bipolar disorder, major depressive disorder), anxiety disorders (generalized anxiety disorder, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), social anxiety disorder), and psychotic disorders (schizophrenia, schizoaffective disorder).
Our team develops customized rater training programs to maximize data quality, standardize assessments, and improve signal detection.
These rater training programs are customized for each clinical trial and include rater qualification, scale-specific training and calibration, and rater certification on key instruments.
We provide rater training services for primary and secondary outcome measures in CNS clinical trials, conduct in-study review assessment for potential discrepancies and, if needed, rater remediation to improve the quality of the assessment.
We tailor investigator training for the specific study needs and rater experiences.
Our group of statisticians and clinicians facilitate the creation of the data quality metrics that give information regarding specificity and quality of study progress.
We have specialists with more than 20 years of experience in CNS clinical trials including tasks such as participant assessment, protocol review and recommendations, Principal Investigator, and Sub-Investigator roles.
Our clinicians are affiliated with and/or collaborate with major scientific, clinical, and academic mental health institutions.
Our capabilities include:
- CNS studies including centralized rating and training for psychedelic trials
- Study-specific rater training/certification/calibration
- Scale management/selection
- Centralized/remote ratings
- Study subject eligibility reviews
- In-study data monitoring
- In-study raters’ remediation/calibration
- Electronic clinical outcome assessment (eCOA)
- Video/audio recording of the assessments
We are specialized in the following CNS rating scales:
- Positive and Negative Syndrome Scale (PANSS)
- Brief Psychiatric Rating Scale (BPRS)
- Montgomery-Asberg Depression Scale (MADRS)
- Hamilton Depression Rating Scale (HAM-D)
- Hamilton Anxiety Rating Scale (HAM-A)
- Young Mania Rating Scale (YMRS)
- Clinical Global Impression Severity/Improvement (CGI-S/I)
Sofpromed’s services are particularly oriented and customized for small biotech and academic clients at affordable pricing.