A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience
Issue link: http://innovationscns.epubxp.com/i/631092
[ V O L U M E 1 2 , N U M B E R 1 1 – 1 2 , N O V E M B E R – D E C E M B E R 2 0 1 5 , S U P P L E M E N T C ] Innovations in CLINICAL NEUROSCIENCE 15 elucidate the extent and nature of eligibility decision errors in CNS clinical trials. Methods: Eligibility review is a p rocess conducted in select trials by a global team of physicians and doctoral-level clinical scientists who review all key screening data before subject are randomized. The reviewers discuss questions/concerns with the investigator, after which the investigator either provides additional clinical history that supports confidence in subject eligibility or the subject is screen failed by the site. Results: As of August 2015, 16,414 subjects were reviewed for eligibility, covering 38 trials over a five-year period. All subjects were considered qualified by investigators before submission; however, 1,468 (8.9%) were found to be ineligible after review. The rate of findings did not differ significantly between therapeutic areas (psychiatry: 8.4%; neurology: 11.4%; analgesia: 10.4%; F(2,35)=3.13, p=0.06), but did differ between specific indications [F(8,29)=2.43, p=0.04]. However, study-level variability within therapeutic area, and even within indication, suggest that these differences are not meaningful and cannot necessarily predict rate of findings in future trials (all trials range: 0–25.0%). Further, there was no relationship between rate of findings and study size, as measured by number of sites (R 2 =0.01, p=0.25) and number of subjects (R 2 =0.03, p=0.99). Additional data will be presented to describe country-level performance, clinical category of findings, and the impact of site experience on patient selection. Conclusion: This analysis demonstrates that CNS trials are highly susceptible to penetration by unqualified subjects, regardless of therapeutic area and trial size. Light intervention at screening, before inappropriate subjects are randomized, can maximize data interpretability and protect patient safety in clinical trials. Disclosures: The authors are employees of INC Research, the contract research organization responsible for execution of all trials i ncluded in this analysis. Predicting placebo responders through frame of reference shifts Presenter: Pashko S Affiliations: Steven Pashko, LLC Background: Within dual human information-processing systems theory, two views have been characterized: the rational-cognitive relies on conceptual information and the experiential relies on perceptual information. Self-reports of psychological status vary significantly depending on which dominates; shifting between these views may cause the placebo effect. Objective: Construct an empirically testable method for the a-priori identification of placebo responders Methods: The shift can be provoked experimentally through the self-identity/ body swap paradox. In all study subjects, conflicting perceptual inputs cause the unlikely perception that a person's body has been swapped with a mannequin's. The shift occurs when conviction in one's perceptual view overrides their conceptual one. The method was used in a study of pain. Results: Using this conflict procedure, pain tolerance increased in subjects whose self-identity was shifted. Shifting between reporting: A) perceptual experience plus attendant conceptualizations (e.g., pain + thoughts about it) to B) only the perceptual experience (e.g., pain alone) may be the causal mechanism. Proposed here is that the placebo effect occurs in people who 1) have a higher degree of flexibility in shifting between conceptual and perceptual reporting and 2) initially report from the rational-cognitive (conceptual) view and then from the experiential (perceptual) one. Conclusion: Determining a person's propensity (e.g., increased speed and/or completeness) to shift using a "challenge test" (i.e., making the shift stimulus unlike a human form) may yield a method for the a- p riori prediction of placebo responders. Key factors for proactive study start-up and site activation in neuroscience studies Presenters: Armstrong K, Zarro J Affiliations: Premier Research Objective: In the demanding arena of clinical research where deadline and economic pressures are felt by all those who are involved in study execution, it is critically important to ensure rapid, yet thorough, study start-up so that the maximal number of sites are able to begin enrolling at the earliest possible date. Methods: A suite of neuroscience studies were reviewed to identify and outline the lessons learned and best practices for efficient and effective study start-up. Results: Key success factors were identified including rapid site identification of those with direct and related neuroscience experience. Rater training can often impact study start-up both on the study level in regards to establishing the requirements for scales management and rater training, as well as on a site activation level with the need for sites to complete the training requirements to start screening. Further, submission deadlines and requirements, both locally and nationally, are critical to meeting planned timelines. Additional factors included the contracting process which is aided by established confidentiality agreements and working experience with the contracting institution requirements of lead sites. Conclusion: Thorough planning of the key success factors identified is directly related to rapid and efficient study start-up leading to meeting or beating timelines.