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Everyone is hurling content over the pay-wall. In a time when we should be diffusing knowledge, the monetization beckons and many move deeper into their echo chamber.
That is why my favorite read has been QuantaMagazine. Light-Triggered Genes Reveal the Hidden Workings of Memory saved my morning. 
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I am a big Systems Thinker and you should be too. The cost of being a one-dimensional thinker plays out in the latest R&D efforts in Alzheimer's disease. Believe it or not--we are still funding the failed hypotheses of decades earlier.
Adaptive Phase II Study of BAN2401 in Early Alzheimer’s Disease Continues toward 18-Month EndpointCriteria for Success at 12-Month Analysis of ADCOMS Not Met
Study to Remain Blinded Per Protocol until Final Readout of Comprehensive 18-Month Data
Adaptive Phase II Study of BAN2401 in Early Alzheimer’s Disease Continues toward 18-Month EndpointCriteria for Success at 12-Month Analysis of ADCOMS Not Met
Study to Remain Blinded Per Protocol until Final Readout of Comprehensive 18-Month Data
Study 201 (ClinicalTrials.gov identifier NCT01767311) is a placebo-controlled, double-blind, parallel-group, randomized study in patients with prodromal or mild Alzheimer’s disease (collectively known as early Alzheimer’s disease) and with positive biomarkers for brain amyloid pathology.
Indulge me in a brief tangent. A recent podcast shuffled my thinking. Debbie Millman is a powerhouse design expert with a broad range of interests and talents. Design Matters is a juggernaut source of creativity and ideas but underneath the hood are powerful conversations and observations about words, artistry, and engagement.
I thoroughly enjoyed a recent interview with Richard Saul Wurman--the founder of TED. Let me clarify. I enjoyed the banter as I ran 6 miles on a trail--I would not have wanted to be interviewing him. A tad bit belligerent and fussy but a riveting partner on a crisp fall morning. He talks about questions. We don't ask the right questions. He wants more from the media. For example, to just report the magnitude of an earthquake tells us nothing. If we know nothing of the depth, infrastructure, or a host of other variables we are unable to contextualize. I believe him. I lived in California and experienced both the Loma Prieta in 1989 and Northridge in 1994. Weaker magnitude earthquakes can have far more devastating consequences depending on building codes, tidal surges, and a host of other characteristics.
Here are a few questions for what is listed in Clinical Trials.gov for the latest clinical trial report from NCT01767311. I do research and data analytics for a living but the website is intended for patients, family members, health care professionals, and other members of the public easy access to information on clinical studies on a wide range of diseases and conditions. Again, there isn't any data available yet that I can find.
ADAPTIVE PHASE II STUDY OF BAN2401 IN EARLY ALZHEIMER’S DISEASE CONTINUES TOWARD 18-MONTH ENDPOINT
1.Criteria for success at 12-month analysis of The Alzheimer's disease Composite Score (ADCOMS) not met but study is still continuing. I am curious about the in-house developed endpoint ADCOMS to measure efficacy.
Assessment of safety reasons for stopping were not met--but what were the safety signals? Amyloid related imaging abnormalities (ARIA)? What were the interoperability scores for results?
2. Original primary outcomes was a 12-month time frame and now the current status 18 months (submitted 9.17.2015)
3. Secondary outcomes include hippocampal volume, composite clinical score (ADCOMS), and brain amyloid measured by amyloid PET.
4. The Bayesian design is a responsive design allowing "automatic changes to the design during the study, including adaptively changing the subject allocation ratio to treatment arms with higher probabilities based on the results of interim analyses in order to more efficiently identify the effectiveness and optimal dose regimen of BAN2401."
ADAPTIVE PHASE II STUDY OF BAN2401 IN EARLY ALZHEIMER’S DISEASE CONTINUES TOWARD 18-MONTH ENDPOINT
1.Criteria for success at 12-month analysis of The Alzheimer's disease Composite Score (ADCOMS) not met but study is still continuing. I am curious about the in-house developed endpoint ADCOMS to measure efficacy.
Assessment of safety reasons for stopping were not met--but what were the safety signals? Amyloid related imaging abnormalities (ARIA)? What were the interoperability scores for results?
2. Original primary outcomes was a 12-month time frame and now the current status 18 months (submitted 9.17.2015)
3. Secondary outcomes include hippocampal volume, composite clinical score (ADCOMS), and brain amyloid measured by amyloid PET.
4. The Bayesian design is a responsive design allowing "automatic changes to the design during the study, including adaptively changing the subject allocation ratio to treatment arms with higher probabilities based on the results of interim analyses in order to more efficiently identify the effectiveness and optimal dose regimen of BAN2401."
What do we really know about "diagnosing" patients for participation? What is the inter-operator variability for different assessments of cognition? If we are using PET scan and other imaging to define AD or dementia we are making a BIG leap that this is the causative agent. Given the history of evidence, Bayesian priors should point in a different direction, no?
The ADCOMS measures what investigators want it to measure. Composite study end points should focus separately on safety and effectiveness outcomes, and design separate composite end points to match these different clinical goals. Instead ADCOMS includes 4 Alzheimer's Disease Assessment Scale–cognitive subscale items, 2 Mini-Mental State Examination items, and all 6 Clinical Dementia Rating—Sum of Boxes items (memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care)
The ADCOMS measures what investigators want it to measure. Composite study end points should focus separately on safety and effectiveness outcomes, and design separate composite end points to match these different clinical goals. Instead ADCOMS includes 4 Alzheimer's Disease Assessment Scale–cognitive subscale items, 2 Mini-Mental State Examination items, and all 6 Clinical Dementia Rating—Sum of Boxes items (memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care)
Now if we return to Nobel laureate Dr Tonegawa we see research findings that red areas of hippocampus are essential for creating new memories but the short-term recall depends on a specialized area in green called the subiculum. This generates new ideas and what we might learn from measures of hippocampal volume as secondary endpoints.
How memories are indeed formed would be a smart place to start. How do we know what actually is responsible for cognitive decline of the scale observed in Alzheimer's disease and other dementias? Metabolic derangement definitely has a role but the solutions are bigger and need a system thinking approach...the brain demands it.
