sokol Thursday, 10/12/17 09:10:07 PM Re: None Post # of 134376 What benefit need be shown for FDA approval of an Alzheimer's drug? Can Anavex show a statistically meaningful benefit for (a) cognition and/or (b) function? See this article for a discussion of statistically meaningful benefits of endpoints for FDA approval of an Alzheimer's drug: http://www.usagainstalzheimers.org/sites/all/themes/alzheimers_networks/files/Researchers-Against-Alzheimer%27s-Endpoints-Analysis-FINAL-5-10-17.pdf Here are some excerpts: ''The Food and Drug Administration’s (FDA) approach to approving new medicines for Alzheimer’s disease since the 1990s has been to require a proven benefit on two independent primary endpoints of cognition and function, although this policy has not been formalized in the FDA rules or finalized FDA guidance. We argue that, in light of an improved scientific understanding of the continuous and progressive character of the disease and consistent with many recent oral expressions by agency leadership in public settings, the FDA should clarify for the field that a clinically meaningful benefit on a single primary endpoint of cognition or function is a sufficient basis for a New Drug Application filing. .....we would note that even if the FDA may be open to approving a safe and well-tolerated drug that demonstrates efficacy on a single primary endpoint of cognition or function,22 the agency might naturally wait for such a drug to be presented to the agency before articulating this position. We would strongly disagree with such an approach. If the FDA were to state that meaningful efficacy on a single endpoint is sufficient for approval, we believe that it would impact prospective investments in this therapeutic area as well as clinical trial design, including considerations of power and sample size, and possibly even reducing the costs and burden of trials to some degree. 18 Hong Liu-Seifert et al., “Function and clinical meaningfulness of treatments for mild Alzheimer's disease,” Alzheimers Dement (Amst), March 2016, p. 105–112, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879645/ (internal footnote omitted). See also footnotes 21 and 22: 21 There is an argument that the practice of classifying endpoints in terms of cognition and function is itself in need of conceptual re-examination. To a patient, a memory loss (cognition) that prevents normal social engagement or reading comprehension (function) could be viewed as either or both a cognitive endpoint or a functional endpoint. Regarding function as meaningful and cognition as not meaningful doesn’t make sense from a patient’s perspective. From a patient’s perspective, the critical inquiry is whether a drug candidate has a truly ‘clinically meaningful’ impact on an endpoint that matters to him or her, whether classified as cognition or function. A full explication of this argument is beyond the scope of this paper. 22 We recognize that with advances in our understanding of Alzheimer’s disease and other dementias, the categories of “cognition” and “function” have become less rigid and more confusing, as it has become increasingly clear that cognition is a surrogate for function, although not a substitute for it.''