With Alzheimer’s disease increasing across the globe, the demand for preventative, disease-modifying, and curative treatments is mounting. However, there remain several obstacles, including a high failure rate in Alzheimer’s disease clinical trials.
Given the pressing need for Alzheimer advances, Covance recently surveyed 100 of the most experienced investigators (throughout 25 countries) involved in Alzheimer’s research to gain perspectives that may be critical in planning for successful trials in the future. The majority of investigators included were physicians from large academic institutions, hospitals, and clinics, including neurologists and psychiatrists. Also represented were physicians with a specific focus on Neurogeriatrics, Clinical Pharmacology, and other related specialties.Results of the survey were compiled into an Investigator Perspective Report − part of Covance’s Clinical OptimizationTM methodology Xcellerate − aimed at helping sponsors gain a better understanding of investigator and thought leader interest in a particular therapeutic area or indication.
One area of focus for this Investigator Perspective Report was to uncover some lessons learned from failed Alzheimer’s trials. Specifically, the investigators were asked: “What has contributed most significantly to past trial failures in Alzheimer’s disease?”
Following are the top 10 reasons the experts listed based on their own experience: 1. intrinsic efficacy of drug; 2. severity of patient population; 3. duration of treatment; 4. dose selection; 5. sensitivity of rating scales; 6. application of scales and instruments; 7. absence of biological markers; 8. inclusion/exclusion criteria; 9. protocol complexity, amendments, instruction and inability to manage placebo response; and 10. mixing patient populations.
In addition to identifying these challenges, the investigators were also asked to propose solutions for improvement. Five major areas of improvement for Alzheimer’s trials were defined, plus advice given on how to build in strategies for success in future trial planning.
For one, the investigators cited the importance of conducting real-time quality control through ‘live’ data review. Another area for improvement suggested was considering the placebo response. A small percentage (6%) of investigators reported knowing that their ratings separated active from placebo treatment, while 17% said their ratings did not separate due mainly to lack of efficacy, severity of the disease evolution, cognitive testing, and inter-subject variability.
Third, the investigators mentioned the importance of improving signal to noise in efficacy evaluations, including: using a single rate assessor, ensuring site training and educating all staff of minimizing placebo response, establishing the correct diagnostic according to the DSM-IV TR, minimizing too many scales and/or procedures per visit, and following all protocol instructions explicitly.
Achieving balance in site and patient numbers was another area of consideration for investigators, i.e. ways to avoid having too many sites with too few patients enrolled. And finally, the investigators offered some thought-provoking ideas on recruiting the “right” Alzheimer’s patients faster.
Overall, these investigator perspectives are critical for improving future Alzheimer’s trial designs. Yet, site performance remains the single most important factor that will affect the successful conduct of a study. Good site performance means that patient identification is timely and consistent with protocol requirements, study activities are executed per the study protocol, and good quality data are captured.
Covance has detailed operational performance information on more than 70 percent of the industry sponsored registered phase IIb/III trials conducted in Alzheimer’s over the past five years. By applying our proprietary Xcellerate methodology, Covance is able to implement best practices to help optimize site selection and help ensure a successful delivery strategy.
Please visit http://www.covance.com/epromo/xcellerate/xcellerate-report.php?cid=xcellerate-fierce-mar to access the entire Xcellerate Investigator Perspective Report on Alzheimer’s disease.