W12 Flashcards
what was the most voted answer for what do you think the best reason to participate in research is?
may benefit from the experimental treatment
what are therapeutic misconceptions?
- 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
what is the most voted answer for what do you think the biggest obstacle is to participating in research?
possibility of side effects
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”:
discussing with research coordinator
what type of info from placemat survey was the highest and lowest?
blood
family history
has trust changed between academia and industry?
yes now more overlap
- building therapeutic treatment plan
what is the most voted answer for “if you were Pat, would you want to know the results from the tests for research purposes?
yes from all the tests
what is the most voted answer for which of the issues Pat faced do you think is the most important?
finding ways to maximize research participation
what are the benefits of engagement?
- better patient experience
- better health outcomes
- higher quality research
- lower costs
what are the challenges of dementia?
- verbal communication impairment
- memory loss
- decision-making capacity
- emotional dispostion
what are the strategies for dementia?
- personalized methodology
- greater flexibility
- preliminary meetings with person and carer
- research training
what are the benefits to digital biomakrers?
- track progression and trends
- feel empowered
- monitor symptoms
- optimize treatments
- analyze precise data sets about disease and response
what are the 2 things for biomarkers?
to capture and disclosure
what is active data collection?
user prompted to perform an assessment or enter a value
what is passive data collection?
values are acquired unobtrusively and sometimes without knowledge of user
what are the 5 components of data collection?
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
attributes towards digital biomarkers
- growing acceptance
+: increased efficiency and accuracy, mitigation of human error, more frequent data capture - : neg emotions (self-blame, anxiety)
what are the considerations for research design?
- study group allocation and exclusion (interpretation)
- behavioral changes and influence on study findings (emotional impact)
- impact on research experience for participants (decision-making)
proactively addressing ethics and literacy through engagement
advisory
consultation
co-creation
eval
research
what is the clinical trial phase pipeline?
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
trial vs phase
number of trials can be performed in phase
what is the duration of a trial
length of time for recruitment and treatment period
- recruitment difficult
what is the duration of phase
trials + analysis + decision making
is progression sequential?
no
what are repurposed drugs?
drugs tested for other diseases or conditions tested in alternate order or skip phases
what is a mechanism associated with AD therapies?
disease-modifying: patient experience clinical response and there is impact on disease process
- small molecule
- immunotherapies
what is small molecule?
AB production, aggregation, clearance
tau phosphorylation and assembly
BACE inhibition
neuroprotective strategies
what is immunotherapies?
active: stimulation immune sys to target AB and tau-related pathology
passive: does not invoke immune sys, required reg injection of antibodies
what is involved in symptomatic therapies?
- cognitive enhancing agents
- behavior agents
what are cognitive-enhancing agents?
patients experiences cog improvement above baseline, but compound does not alter underlying disease process
what are behavior agents?
patients experiences behavioral improvemeent above baseline but compound does not alter underlying disease process
- depression, agitation, sleep disorders, aggression
what are the 8 currently approved treatments?
tacrine
donepezil
ricastigmine
galantamine
memantine - symptomatic releif
aducanunab
lecanemab
what is aducanumab?
anti-amyloid reducing drug
- 1st clinical trial drug that treats the neuropathology of ad
- discontinued now
why was aducanumab discontinued?
biogen: reprioritizes resources
side effect: amyloid related imaging abnormalities
- brain swelling and microhemorrages
- confusion, dizziness, delirium, vision abnormality, altered mental status
what does Lecanemab do to AD?
stick to amyloid protein
antibody attracts immune cells to break down protein
less protein around neuron
what does Donanemab do?
attacks the amyloid plaques later on in stages
- removes amyloid
- slows the progression
- modifies disease
what is the most common form of candidate treatments in pipeline?
disease-modifying
what is phase 1 for disease-modifying?
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
how are stem cells used for AD?
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
what is the amyloid cascade hypothesis?
amyloid B causes synaptic and neuron function dysregulation
creates intercellular conditions for the formation of tau pathology
neuronal loss and compromised nt fxn
what are add-on trials?
new drug compared with placebo in patients who already receiving treatment with background therapy
what are combination trials?
- 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
placebo-controlled 2x2 design
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
3-arm design
a
b
a + b
+ : no patient untreated, small trial with easier recruitment
- : hard to discriminate effects, less appropriate for late stages
adaptive trial deisgn
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
