CHEM 392 EXAM STUDY GUIDE WITH
COMPLETE SOLUTIONS
2017, 2015, 2013: List three reasons that new migraine drugs are required - ANSWER 1.
chronic migraine is a debilitating disorder affecting 1 in 7 people (22% NZ woman suffer
from migraine)
2.it is costly as leading cause of visits to emergency department (as difficult to
differentiate between internal bleeding in brain)
3. there are very few, low adherence (give side effects worse than migraine)
medications available
2017: Some small molecule Calcitonin gene-related peptide (CGRP) receptor
antagonists have been discontinued or withdrawn from clinical development. List 2
reasons why these molecules have been discontinued or withdrawn - ANSWER
Olcegepant was discontinued because it was not bioavaliable
Telcagepant was withdrawn because caused liver damage when taken daily
2016, 2014: Small molecule CGRP receptor antagonists are being developed as
potential migraine treatments. List 5 challenges that have been encountered during
their development - ANSWER 1. CGRP is a complex 37AA molecule, difficult to find small
molecule analogue
2. Don't know what receptors CGRP bind to (but activity looked like GPCR)
3. SK-N-MC cell line is an unstable screening model (as when gets older loses ability to
bind CGRP)
4. CGRP receptors are not typical GPCRs (RAMP1 essential for activity)
5. How do we know if mice are experiencing a migraine?
2015: Blocking CGRP activity in migraine is a promising therapuetic approach. List the
two different antibody-based approaches that are being investigated - ANSWER
erenumab targeting CGRP receptor, monthly SC injection, approved
ALD403 targeting CGRP itself, IV injection, phase 3
,2013: List two approaches for blocking CGRP activity to treat migraine - ANSWER block
CGRP receptor (antagonist or antibody) or bind CGRP itself (antibody)
2017, 2016, 2015, 2014, 2013, 2012, 2011, 2010: Describe the phases of clinical trials
with focus on purpose and numbers likely to be enrolled - ANSWER Phase 1 - toxicity
and dose, typically not randomised 10-100 healthy volunteers
Phase 2a - safety and dose ranging and "surrogate" efficiency, sometimes randomised
100-300 patients with disease
Phase 2b - surrogate and target outcome, randomised 100-300 patients with disease
Phase 3 - efficacy and safety, always randomised, long term 300-3,000 patients with
disease
Phase 4 - post marketing surveillance (non-randomised) those taking treatment
2017, 2014: Define intention-to-treat and per-protocol analyses - ANSWER intention to
treat: participants analysed in the group assigned to them whether or not they
completed or received treatment
per-protocol: only participants who completed treatment assigned to them are analysed
2014: Is intention-to-treat or per-protocol analysis preferable? - ANSWER
intention-to-treat is preferable because is avoids bias, preserves randomisation and
models the real world
2017: Why is allocation concealment important in a rightly designed clinical trial? What
are the common methods used as part of allocation concealment? - ANSWER allocation
concealment protects random sequence, prevents selection bias. methods: assignment
by 24hr hotline, prenumbered/coded containers, onsite computer allocation,
sequentially number, sealed, opaque envelops
2016,2015, 2010: List four good design elements desirable in a clinical trial - ANSWER
randomisation,
allocation concealment,
blinding,complete follow up, right analysis
, 2016, 2015: Discuss the importance of two good design elements desirable in a clinical
trial - ANSWER Randomisation - creates equal groups, prevents confounding
allocation concealment - protects random sequence, prevents selection bias
blinding -masks assigned intervention during whole trial, reduces influence of
subjectivity, minimises observer bias
complete follow up - ??
right analysis - intention to treat preserves randomisation, models real world
2017, 2015, 2014, 2012, 2010: A central principle of research on human beings requires
the informed consent be obtained before individuals participate. Explain why informed
consent is important and the process the researchers typically follow to obtain this
consent - ANSWER informed consent to be given is crucial to prevent invasion of
subject's privacy and breaching of confidentiality. When researches recruit,
participants are given all relevant information to understand what will be done with the
data and how confidentiality will be handled so they can give informed and voluntary
consent.
2016: List and explain the three ethical principles that resulted from the Belmont Report
- ANSWER respect for persons - participants must give informed and voluntary consent
before being studied
beneficence - the research must be beneficial to society, and this benefit must outweigh
the risks to the participants
justice - participants must be balanced and not be from vulnerable groups nor coerced
into participating
2016: Relate one of the ethical principles from the Belmont Report to the University of
Auckland Human Participants Ethics Committee guiding principles - ANSWER respect
for persons - autonomy (respect for persons capacity for self-determination)
beneficence - beneficence (acting in the public good and promoting the good of other
people)
justice - justice (treating others equitably and distributing burdens and benefits fairly)
COMPLETE SOLUTIONS
2017, 2015, 2013: List three reasons that new migraine drugs are required - ANSWER 1.
chronic migraine is a debilitating disorder affecting 1 in 7 people (22% NZ woman suffer
from migraine)
2.it is costly as leading cause of visits to emergency department (as difficult to
differentiate between internal bleeding in brain)
3. there are very few, low adherence (give side effects worse than migraine)
medications available
2017: Some small molecule Calcitonin gene-related peptide (CGRP) receptor
antagonists have been discontinued or withdrawn from clinical development. List 2
reasons why these molecules have been discontinued or withdrawn - ANSWER
Olcegepant was discontinued because it was not bioavaliable
Telcagepant was withdrawn because caused liver damage when taken daily
2016, 2014: Small molecule CGRP receptor antagonists are being developed as
potential migraine treatments. List 5 challenges that have been encountered during
their development - ANSWER 1. CGRP is a complex 37AA molecule, difficult to find small
molecule analogue
2. Don't know what receptors CGRP bind to (but activity looked like GPCR)
3. SK-N-MC cell line is an unstable screening model (as when gets older loses ability to
bind CGRP)
4. CGRP receptors are not typical GPCRs (RAMP1 essential for activity)
5. How do we know if mice are experiencing a migraine?
2015: Blocking CGRP activity in migraine is a promising therapuetic approach. List the
two different antibody-based approaches that are being investigated - ANSWER
erenumab targeting CGRP receptor, monthly SC injection, approved
ALD403 targeting CGRP itself, IV injection, phase 3
,2013: List two approaches for blocking CGRP activity to treat migraine - ANSWER block
CGRP receptor (antagonist or antibody) or bind CGRP itself (antibody)
2017, 2016, 2015, 2014, 2013, 2012, 2011, 2010: Describe the phases of clinical trials
with focus on purpose and numbers likely to be enrolled - ANSWER Phase 1 - toxicity
and dose, typically not randomised 10-100 healthy volunteers
Phase 2a - safety and dose ranging and "surrogate" efficiency, sometimes randomised
100-300 patients with disease
Phase 2b - surrogate and target outcome, randomised 100-300 patients with disease
Phase 3 - efficacy and safety, always randomised, long term 300-3,000 patients with
disease
Phase 4 - post marketing surveillance (non-randomised) those taking treatment
2017, 2014: Define intention-to-treat and per-protocol analyses - ANSWER intention to
treat: participants analysed in the group assigned to them whether or not they
completed or received treatment
per-protocol: only participants who completed treatment assigned to them are analysed
2014: Is intention-to-treat or per-protocol analysis preferable? - ANSWER
intention-to-treat is preferable because is avoids bias, preserves randomisation and
models the real world
2017: Why is allocation concealment important in a rightly designed clinical trial? What
are the common methods used as part of allocation concealment? - ANSWER allocation
concealment protects random sequence, prevents selection bias. methods: assignment
by 24hr hotline, prenumbered/coded containers, onsite computer allocation,
sequentially number, sealed, opaque envelops
2016,2015, 2010: List four good design elements desirable in a clinical trial - ANSWER
randomisation,
allocation concealment,
blinding,complete follow up, right analysis
, 2016, 2015: Discuss the importance of two good design elements desirable in a clinical
trial - ANSWER Randomisation - creates equal groups, prevents confounding
allocation concealment - protects random sequence, prevents selection bias
blinding -masks assigned intervention during whole trial, reduces influence of
subjectivity, minimises observer bias
complete follow up - ??
right analysis - intention to treat preserves randomisation, models real world
2017, 2015, 2014, 2012, 2010: A central principle of research on human beings requires
the informed consent be obtained before individuals participate. Explain why informed
consent is important and the process the researchers typically follow to obtain this
consent - ANSWER informed consent to be given is crucial to prevent invasion of
subject's privacy and breaching of confidentiality. When researches recruit,
participants are given all relevant information to understand what will be done with the
data and how confidentiality will be handled so they can give informed and voluntary
consent.
2016: List and explain the three ethical principles that resulted from the Belmont Report
- ANSWER respect for persons - participants must give informed and voluntary consent
before being studied
beneficence - the research must be beneficial to society, and this benefit must outweigh
the risks to the participants
justice - participants must be balanced and not be from vulnerable groups nor coerced
into participating
2016: Relate one of the ethical principles from the Belmont Report to the University of
Auckland Human Participants Ethics Committee guiding principles - ANSWER respect
for persons - autonomy (respect for persons capacity for self-determination)
beneficence - beneficence (acting in the public good and promoting the good of other
people)
justice - justice (treating others equitably and distributing burdens and benefits fairly)
