W12

Question 1

what was the most voted answer for what do you think the best reason to participate in research is?

Answer 1

may benefit from the experimental treatment

Question 2

what are therapeutic misconceptions?

Answer 2

• majority of research is non-therapeutic,, despite the intention
• no difference in long-term outcomes between AD patients who participate in clinical trials and those who don’t

Question 3

what is the most voted answer for what do you think the biggest obstacle is to participating in research?

Answer 3

possibility of side effects

Question 4

what is the most voted answer for “if you were Pat, would you prefer to learn about risks and the benefits of the study by”:

Answer 4

discussing with research coordinator

Question 5

what type of info from placemat survey was the highest and lowest?

Answer 5

blood
family history

Question 6

has trust changed between academia and industry?

Answer 6

yes now more overlap
- building therapeutic treatment plan

Question 7

what is the most voted answer for “if you were Pat, would you want to know the results from the tests for research purposes?

Answer 7

yes from all the tests

Question 8

what is the most voted answer for which of the issues Pat faced do you think is the most important?

Answer 8

finding ways to maximize research participation

Question 9

what are the benefits of engagement?

Answer 9

• better patient experience
• better health outcomes
• higher quality research
• lower costs

Question 10

what are the challenges of dementia?

Answer 10

• verbal communication impairment
• memory loss
• decision-making capacity
• emotional dispostion

Question 11

what are the strategies for dementia?

Answer 11

• personalized methodology
• greater flexibility
• preliminary meetings with person and carer
• research training

Question 12

what are the benefits to digital biomakrers?

Answer 12

• track progression and trends
• feel empowered
• monitor symptoms
• optimize treatments
• analyze precise data sets about disease and response

Question 13

what are the 2 things for biomarkers?

Answer 13

to capture and disclosure

Question 14

what is active data collection?

Answer 14

user prompted to perform an assessment or enter a value

Question 15

what is passive data collection?

Answer 15

values are acquired unobtrusively and sometimes without knowledge of user

Question 16

what are the 5 components of data collection?

Answer 16

consent - esp important for passive collection, ask for consent in intervals
privacy
conflict of interest - 3rd party use of data
complementarity - active data collection, don’t want to jeopardize data
emotional impact

Question 17

attributes towards digital biomarkers

Answer 17

• growing acceptance
  +: increased efficiency and accuracy, mitigation of human error, more frequent data capture
• : neg emotions (self-blame, anxiety)

Question 18

what are the considerations for research design?

Answer 18

• study group allocation and exclusion (interpretation)
• behavioral changes and influence on study findings (emotional impact)
• impact on research experience for participants (decision-making)

Question 19

proactively addressing ethics and literacy through engagement

Answer 19

advisory
consultation
co-creation
eval
research

Question 20

what is the clinical trial phase pipeline?

Answer 20

P1: test new treat in healthy, determine effects, 20-80, clinical researcher, months (side effects)

P2: test new treatment on patients, eval safety and efficacy, 100-300, clinical researcher, 2 yrs

P3: test new treatment, eval efficacy, safety, effectiveness, 300+, researcher and physician, several years

FDA review and approval

Question 21

trial vs phase

Answer 21

number of trials can be performed in phase

Question 22

what is the duration of a trial

Answer 22

length of time for recruitment and treatment period
- recruitment difficult

Question 23

what is the duration of phase

Answer 23

trials + analysis + decision making

Question 24

is progression sequential?

Answer 24

no

Question 25

what are repurposed drugs?

Answer 25

drugs tested for other diseases or conditions tested in alternate order or skip phases

Question 26

what is a mechanism associated with AD therapies?

Answer 26

disease-modifying: patient experience clinical response and there is impact on disease process - small molecule - immunotherapies

Question 27

what is small molecule?

Answer 27

AB production, aggregation, clearance tau phosphorylation and assembly BACE inhibition neuroprotective strategies

Question 28

what is immunotherapies?

Answer 28

active: stimulation immune sys to target AB and tau-related pathology passive: does not invoke immune sys, required reg injection of antibodies

Question 29

what is involved in symptomatic therapies?

Answer 29

- cognitive enhancing agents - behavior agents

Question 30

what are cognitive-enhancing agents?

Answer 30

patients experiences cog improvement above baseline, but compound does not alter underlying disease process

Question 31

what are behavior agents?

Answer 31

patients experiences behavioral improvemeent above baseline but compound does not alter underlying disease process - depression, agitation, sleep disorders, aggression

Question 32

what are the 8 currently approved treatments?

Answer 32

tacrine donepezil ricastigmine galantamine memantine - symptomatic releif aducanunab lecanemab

Question 33

what is aducanumab?

Answer 33

anti-amyloid reducing drug - 1st clinical trial drug that treats the neuropathology of ad - discontinued now

Question 34

why was aducanumab discontinued?

Answer 34

biogen: reprioritizes resources side effect: amyloid related imaging abnormalities - brain swelling and microhemorrages - confusion, dizziness, delirium, vision abnormality, altered mental status

Question 35

what does Lecanemab do to AD?

Answer 35

stick to amyloid protein antibody attracts immune cells to break down protein less protein around neuron

Question 36

what does Donanemab do?

Answer 36

attacks the amyloid plaques later on in stages - removes amyloid - slows the progression - modifies disease

Question 37

what is the most common form of candidate treatments in pipeline?

Answer 37

disease-modifying

Question 38

what is phase 1 for disease-modifying?

Answer 38

52% biologics 29% small molecule - mechanisms: amyloid, inflammation, transmitter receptors, tau, metabolism and bioenergetics - 23% of P1 agents repurposed treatments approved for use in another indication

Question 39

how are stem cells used for AD?

Answer 39

8 trials developing - allogenic human mesenchymal stem cells : P2 - amniotic and umbilical cord tissue : P1 - autologous adipose tissue derived mesenchymal stem cells : P2 - lomocel-B mesenchymal stem cells derived from bone marrow : P2

Question 40

what is the amyloid cascade hypothesis?

Answer 40

amyloid B causes synaptic and neuron function dysregulation creates intercellular conditions for the formation of tau pathology neuronal loss and compromised nt fxn

Question 41

what are add-on trials?

Answer 41

new drug compared with placebo in patients who already receiving treatment with background therapy

Question 42

what are combination trials?

Answer 42

- two drugs tested 2x2 - alone, combo, compared to placebo - tests 2 targets - tests two therapies on one target - test delivery modes - sequential combo - multifunctional agent targeting 1 or more activity or target

Question 43

placebo-controlled 2x2 design

Answer 43

a + P b + P a + b P +P add-on: standard of care + b standard + P no standard + B no standard + P - well controlled - compare effects of each drug and synergistic effects of both

Question 44

3-arm design

Answer 44

a b a + b + : no patient untreated, small trial with easier recruitment - : hard to discriminate effects, less appropriate for late stages

Question 45

adaptive trial deisgn

Answer 45

I - SPY - umbrella trial: many agents tested in parallel with placebo - basket: patients grouped by genotype and other disease features + : compare effects on biomarkers, adaptive dosed, shared placebo and trial, continuous comparison -: hard to assess effects, treatment baskets harder to determine, no established intermediate endpoints