Innovations In Clinical Neuroscience

Summit 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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trial. Jandira Ramos, Denise Carter, L aura Farfel and William Martin are currently employed by Alkermes. Patient selection for CNS clinical trials: findings from an eligibility review d atabase with a focus on Alzheimer disease trials Presenters: Hilsabeck RC, Murphy J, Yakovleva N, Reinhold CK, Miloslavich K, and Nations KR Affiliations: INC Research/inVentiv Health Background/Objective: The purpose of this analysis was to examine key areas of vulnerability in patient selection for CNS trials and specifically in Alzheimer's disease (AD) trials. Design: A contract research organization (CRO)-based team of physicians and clinical scientists reviewed key screening diagnostic and medical data prior to subject randomization. Resulting eligibility concerns were thereafter discussed with sites, leaving final decisions on randomization in the hands of investigators. Results: A total of 29,266 patients, all submitted by investigators as qualified, were reviewed in 36 trials (psychiatry, neurology, and analgesia). Of these, 2,605 (9%) were not eligible to randomize. Despite significant variability between indications (range 4.8–16.1%), findings did not significantly differ between general therapeutic areas (c 2 (2)=3.10, p=0.212). In AD trials, 16.1 percent of patients were considered unsuitable for participation, which is significantly higher than all other indications combined (c 2 (1)=56.54, p<0.001). Reasons AD patients were considered ineligible were broad, including, but not limited to cardiovascular disease risk (22%) and dementia not due to probable AD (20%). Additional data, including regional differences and most common findings, are presented. Conclusion: This analysis demonstrates that CNS trials are susceptible to penetration by unqualified/unsuitable patients, and that AD trials are among the most vulnerable. High rates of AD patient selection error, 85 percent higher than the rate for all other indications c ombined, might shed some light on how protocol and patient complexity increases risk, and ways in which trial designers and managers can focus their efforts to protect trial quality and patient s afety. Disclosures/funding: All authors are employees of INC Research/inVentiv Health, the Contract Research Organization responsible for execution of all trials included in this analysis. You show me your (I/E) and I'll show you my (diagnosis): professional subjects changing indications Presenters: Shiovitz TM 1,2 , Steinmetz CB 1 , Fox BL 1 , Rickers SL 2 , and Schoneberg SH 1 Affiliations: 1 CTSdatabase LLC, Sherman Oaks, CA; 2 California Neuroscience Research, Sherman Oaks, CA Background/Objective: Professional subjects are individuals who participate in multiple, and often concurrent, studies in order to collect stipends. They might change their presentation to satisfy inclusion or exclusion criteria of each study. Professional subjects are a substantial problem in clinical trials and might contribute to study failure. We seek to understand how professional subjects might change their indications/diagnoses in order to qualify for disparate studies. Design: We performed a search of matching subjects in CTSdatabase on August 11, 2017. Subject data was sorted to determine how frequently there was a change in prescreening indication or screening diagnosis. Only matches that occurred at unique sites were included in the data set. Results: Of 11,969 matches that have occurred since subjects were first entered in October 2011, 16.1 percent (1,925) involved a change of indication or diagnosis between sites. The most frequent cross-indication pairs were schizophrenia and depression (3.06%), schizophrenia and bipolar (1.96%), depression and bipolar (1.62%). Conclusion: Professional subjects participate in multiple studies and might change their presentation when appearing at different sites. This might be unintentional or purposefully d eceptive. Changing indications might be appropriate, such as depression co- occurring with anxiety or migraine, or inappropriate, such as participating in an opioid-induced constipation study c oncurrently with a study of opioid augmentation of treatment-resistant depression. In any case, multiple changes of diagnosis or indication should raise the suspicion of a professional subject. Disclosures/funding: A subject registry, such as CTSdatabase, can detect these subjects and provide a history of previous study participation, including screening diagnoses. PLACEBO RESPONSE Mitigating placebo response in CNS clinical trials: a site based pilot program Presenters: Tireman E, Templeton K, and Kakar R Affiliations: All authors are from Segal Trials in Fort Lauderdale, Florida Background/Objective: It is a widely known that just receiving treatment can improve a patient's symptoms. Due to this phenomenon, a majority of clinical trials are randomized and have a placebo arm. The placebo effect is a response to this inactive treatment arm; however, it is not only just a response to the treatment itself, but also rather a response to the entire experience. It is well known among the CNS drug development scientists that the placebo effect is a significant hindrance to the progression of new drug development. There are many factors that combine to create this placebo effect. The receiving of treatment of any kind, whether it is the investigational product or intervention or placebo, is just the start of it. Things such as psychosocial factors, expectations, and even how the placebo is administered have all been shown to be factors in response. The major problem with the placebo effect is that the bigger the placebo response, the harder it is to show that an experimental treatment is effective. This leads to an overwhelming number of failed clinical trials, wasted money by the pharmaceutical companies, and a large ICNS Innovations in Clinical Neuroscience • November–December 2017 • Volume 14 • Number 11–12 • Supplement S15

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