Innovations In Clinical Neuroscience

SEP-OCT 2014

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

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[ V O L U M E 1 1 , N U M B E R 9 – 1 0 , S E P T E M B E R – O C T O B E R 2 0 1 4 ] Innovations in CLINICAL NEUROSCIENCE 21 two surveys suggest there is a persistent problem in this area. Given the critical importance of the baseline assessment in determining t he emergence of new or worsening SIB during the course of a treatment study, further research is urgently needed to better understand the accuracy of baseline SIB assessments being acquired in clinical studies and, if necessary, to identify methods to improve the accuracy of the information being collected and reported. More consistent use of multiple sources of information may be one means of improving the validity of baseline SIB assessments. Overall the survey results suggest that the FDA guidance does appear to be working as it was intended: respondents indicated that subjects experiencing SIB during an ongoing study are being identified and are receiving follow-up evaluation, whether they continue in the trial or not, and prospective data on the occurrence of SIB in clinical trials are being collected for further study. Challenges were identified, however, with reports that some study sites are ill prepared to handle subjects experiencing SIB, as well as obtaining referrals for mental health assessments. Although these challenges were reported by a minority of respondents (<20%), they are important to note, as they potentially impact patient safety. The major limitations of this study include the relatively low response rate and the possibility of variability in response conditions (e.g., in some cases, respondents may have consulted with colleagues as encouraged by the survey instructions, but in other cases they may have not done so). Taken together, these factors may have resulted in unrecognized bias, which could limit the generalizability of the results. Although the survey instructions encouraged respondents to discuss the questions with colleagues at their company and provide a single representative response to the survey, on average there were about two responses for each company represented in the survey sample (with a range of 1 to 6). The study results did not d ifferentiate respondents who obtained broader input from those who did not. Issues of this nature may be inevitable, however, in surveys of large companies where different business units and functional lines may be independently involved with SIB assessments, and there may or may not be a standardized approach to how SIB assessments are conducted and the data analyzed. An additional limitation of this online study is its reliance on self- reported data, which cannot be objectively verified. Finally, in asking about SIB assessment instruments and practices used by the companies, the survey did not distinguish between current and past practices; doing so would have provided additional useful background on the evolution of company choices in both these areas. CONCLUSION In summary, the results of the present survey support the view that many pharmaceutical sponsors have attempted to implement FDA recommendations for inclusion of prospective SIB assessments in clinical trials. However, sponsors continue to face numerous challenges, especially in global studies, which could impact data quality. Consistent with the findings of the previous survey of study sites, 3 site difficulty in obtaining an adequate baseline SIB history is a continuing challenge. There also are continuing important questions regarding standardization of retrospective assessment timeframes and differing approaches to summarizing and analyzing SIB- related study data. Taken together, these results suggest that inconsistent reports of SIB within study datasets may occur and that integration of data across studies and development programs remains a concern. Likewise, some sites would benefit from assistance in developing appropriate patient evaluation and treatment referral n etworks to respond to reported SIB during trial participation. In the years since the appearance of the initial FDA guidance for industry on prospective assessment of SIB in clinical trials, 1 pharmaceutical companies have made significant efforts to comply with the FDA's recommendations. 3 ,18 Results of the current survey show these efforts have identified a number of operational, technical, and statistical challenges that may impact the quality of SIB-related clinical trial data and compromise the goals of the FDA guidance. Based on this experience, we believe re-convening key stakeholders from academia, industry, and the FDA to review what has been learned about implementation of prospective SIB assessments in clinical trials would be beneficial. Such a meeting could help identify potential solutions to persistent challenges. Such a meeting could also help build an informed consensus regarding standardization of the information and risk factors affecting SIB that need to be collected, as well as operational standards regarding the methods for collecting, analyzing, interpreting, managing, and reporting SIB-related study data. *SUPPLEMENT DOCUMENT AND TABLES Access the following supplement materials online: • Supplemental Document 1: http://innovationscns.com/wp- content/uploads/Chappell_Survey. pdf. • Supplemental Tables 1–4: http://innovationscns.com/wp- content/uploads/Chappell_Supple mental_Tables.pdf ACKNOWLEDGMENTS The authors gratefully acknowledge the assistance of Dr.

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