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CPPS 337 > CPPS 337 > Flashcards

CPPS 337 Flashcards

1
Q

Objective

A

Every experiment starts with a research question, which is stated as the study objective - the objective is whatever is going to be assessed or measured

  • primary (efficacy of drug) and secondary objectives (safety of drug)

Example:
- Experiment: test new drug for migraine prophylaxis (prevention)
- Primary Objective: does drug A reduce frequency of migraines

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2
Q

Outcomes

A

specific assessments designed to help inform a study objective

(outcomes get you to objective - help you answer the research question)

1 or 2 primary outcomes that decide the success of your study

Examples:
- Change from baseline to week 24 in monthly migraine days (primary)
- Number of patients with a migraine 1 day after their dose
of Drug A

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3
Q

Enrollment

A

Patients that are recruited for study

  • inclusion criteria
  • exclusion criterai
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4
Q

Intervention group

A

Gets treatment

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5
Q

Control group

A

Does not get treatment

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6
Q

Randomization

A

Random allocation of participants to treatment and control group

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7
Q

Stratification factors

A

Want to keep t and c groups balanced for baseline characteristics - helps randomization be balanced

  • Tell computer to make groups with equal number of moderate/severe asthma, and high/low dose corticosteroids
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8
Q

Allocation concealment

A

Concealing which group the patient has been allocated to

  • make the allocation process automated and conducted by a third party
  • can use interactive voice/web response system
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9
Q

Blinding

A

Matching control to treatment

  • can use doubly dummy for different dosage forms: One group gets tablet and placebo shot, other gets placebo tablet and shot
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10
Q

Parallel control group

A

treatment and control groups observed at same time

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11
Q

Historical control group

A

control group taken from old study

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12
Q

Active treatment

A

active established drug thats given to control group

  • active controlled vs plavebo controlled trials
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13
Q

Prospective study

A

looks forward - watches for outcomes like the development of a disease
- relates the outcome to suspected risk or protection factors

  • clinical trials (testing new drug) always prospective - go forward in time
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14
Q

Retrospective study

A

looks backward - outcome established at the start of the study; examines past exposures to suspected risk or protection factors

  • figuring out about AIDS: looked at patient history and found virus)
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15
Q

Historical control

A

the outcomes of the intervention group are compared to results from a comparable group of patients whose data is retrieved from a database from the past

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16
Q

Reasons to choose a historical control

A
  • there is no active control
  • use of placebo considered unethical (patients would suffer)
  • intervention is so good that all patients should be given access
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17
Q

Reasons not to use historical control

A
  • results depend on choice of control
  • subject to bias
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18
Q

Crossover designs

A

all participants are exposed to all controls and interventions in the trial - patients serve as their own control - takes individual variability out of the eqn

  • start on a and switch to b after a period of time
  • assuming order does not matter
  • washout period between switch so no lingering effects of one drug (hard to do cuz some effect may stay)
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19
Q

Withdrawal studies

A

participants on a particular treatment are taken off therapy or have their dosage reduced

  • objective is to asses response to discontinuation or dose reduction
  • evaluating duration of benefit of an intervention already known to be useful
  • checking for rebound effect (making condition worse after discontinuation)
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20
Q

Cohort study

A

observing a group/cohort over time

  • participants selected based on characteristic/exposure that may cause disease
  • incidence of the disease in the exposed individuals is compared with the incidence in those not exposed
  • example: Framingham study (tracking cardiovascular outcomes and risk factors for CV disease)
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21
Q

Cohort studies advantages

A
  • can study multiple outcomes for a given exposure
  • good for investigating rare exposures
  • can calculate rates of disease in exposed and unexposed individuals over time
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22
Q

Cohort studies disadvantages

A
  • Large numbers of subjects are required to study rare exposures

Prospective Cohort Studies

  • Expensive
  • Long
  • Maintaining follow-up is difficult
  • Loss to follow-up or withdrawals

Retrospective Cohort Studies

  • Susceptible to selection bias
  • Susceptible to recall bias
  • Less control over what information is available
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23
Q

Case-control studies

A

compare patients with a disease/outcome of interest (case) with patients who dont have it (control)

  • look back retrospectively to see how often a risk factor was present in each group to determine the relationship between risk factor and disease
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24
Q

Difference between case-control studies and cohort studies

A

Case-control studies identify subjects by outcome status at the outset of the investigation

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25
Q

Advantages of case-control studies

A
  • quick to conduct
  • when a condition is uncommon - a lot of info can be revealed from few subjects
  • relatively inexpensive
  • can use existing records
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26
Q

Disadvantages of case-control studies

A
  • recall bias
  • hard to validate info
  • selection of control group used to be hard
  • individual pairing with control used to be hard
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27
Q

Case series

A

Bunch of case reports of patients who were given similar treatment

  • when you see something odd - drug makes skin blue - look for other reports where this has happened, put them into series, publish that (b/c more evidence than case report)
  • linking together case reports
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28
Q

case series disadvantage

A

no control group

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29
Q

reasons to use case series

A

Can provide:

  • initial indication of treatment efficacy
  • description of a novel clinical problem/complication.
  • valuable in describing the natural history of a condition
  • valuable in describing recovery and complication rates after a treatment/procedure
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30
Q

Characteristics of good case series

A
  • Clearly defined question
  • Well-described study population
  • Well-described intervention
  • validated outcome measures
  • Appropriate statistical analyses
  • Well-described results
  • Discussion/conclusions supported by data
  • Funding source acknowledged
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31
Q

median

A

middle number of a data set

  • line up numbers from least to greatest - middle number with equal data points above and below
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32
Q

mode

A

most frequently reported data value in a data set

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33
Q

variance/ standard deviation

A

show the dispersion of data from the average value in a data set

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34
Q

skewness

A

deviations from a symmetrical bell curve - asymmetry from the mean

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35
Q

outliers

A

values much larger or smaller than others within a data set

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36
Q

validity (accuracy)

A

how close a measurement is to the true value (target/reference)

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37
Q

reliability (precision)

A

how close several measurements are to each other

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38
Q

how can you improve validity of an experiment

A
  • mitigate bias
  • use randomization
  • blinding
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39
Q

how can you improve reliability of an experiment

A
  • increase sample size
  • control potential confounding variables
  • increase number of measurements
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40
Q

internal validity

A

the extent to which a study’s design accurately measures the truth without influence from other variables

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41
Q

external validity

A

the extent to which the research results reflect what happens outside of a research setting (in the real world)

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42
Q

null hypothesis

A

states there is no difference between a treatment and control

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43
Q

alternative hypothesis

A

states there is a difference between a treatment and control

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44
Q

p value

A

denotes how probable it is that the results of an experiment are due to chance

  • conventionally, p < 0.05 denotes significance (arbitrary cuz if studying effects of a drug on mortality, don’t want a 5% chance the person will die)
  • if p is higher than 0.05 maybe you just don’t have a big enough sample size to discern statistically significant result)
  • higher p values suggest weaker evidence against the null hypothesis
  • lower p values suggest stronger evidence against the null hypothesis
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45
Q

inclusion criteria

A

who should you include in the study and why (based on research question)

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46
Q

exclusion criteria

A

who should you exclude in the study and why

  • studying a drug that causes anxiety - exclude ppl with defects in amygdala
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47
Q

what if you include everyone and exclude no one

A

outliers skew results

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48
Q

what if you exclude certain people/ measurements but not others

A

introduces bias

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49
Q

confounding

A

extraneous variables that may influence the measurement of a relationship between other variables

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50
Q

nocebo effect

A

informing patient they will experience negative symptoms from a drug and they do

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51
Q

selection bias

A

issues in sampling

  • studying anxiety and you recruit patients from a psychiatric hospital - more likely to display what you want them to display
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52
Q

recall bias

A

issues in remembering details

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53
Q

interviewer bias

A

issues in how a researcher may present themselves to an interviewee

  • priming participants through leading questions, stereotyping (threat or boost effect on performance), influence by expectations or opinions
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54
Q

Hawthorne effect

A

people modify their own behavior because they know they are being observed/assessed

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55
Q

Pygmalion/Rosenthal effect

A

expectations may drive performance

  • self fulfiiling prophecy
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56
Q

type I error
(false Positive)

A

inaccurately rejecting the null hypothesis when it is true

  • related to the significance level (p)
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57
Q

type II error
(false Negative)

A

inaccurately accepting the null hypothesis when it is false

  • depends on power (sample size)
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58
Q

selection/sampling bias

A

cherry picking people (need random selection instead)

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59
Q

statistically significant

A

gray area - causes rejection of null hypothesis

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60
Q

avoiding Type II error

A

increase statistical power

  • increase sample size –> reduce variability (spread) –> reduce overlap
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61
Q

power

A

probability of correctly rejecting a false null hypothesis (avoiding type II error) - probability that sample means will be found statistically different when there is a true difference

  • increasing sample size
  • correctly reject the null hypothesis 80% of the time
  • 80% of the curve is to the right of the cut off
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62
Q

confidence interval

A

if p value is 0.05, the confidence interval is 95%

  • we are 95% sure that the true difference lies within the 95% confidence interval (confidence interval contains the true difference between the treatment groups)
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63
Q

statistical significance

A

indicates reliability of study results

64
Q

clinical significance

A

reflects impact on clinical importance

65
Q

how to avoid type 1 error

A

decrease p value

66
Q

how to avoid type 2 error

A

increase sample size (power)

67
Q

Therapeutic Products Directorate

TPD

A

pharmaceutical drugs and medical devices

  • ensures their safety, efficacy, and high quality
68
Q

Biologics and Genetics Therapies Directorate

BGTD

A

biological (drugs that come from animals) or radiopharmaceutical drug and medical device combinations

  • adeno associate viral affectors
69
Q

Natural and Non-prescription Health Products Directorate

NNHPD

A

non-prescription drugs, disinfectant drugs, herbal compounds

  • homeopathic
  • ayurvedic
  • aspirin
70
Q

Nutraceutical

A

product isolated from foods and sold in medicinal forms

  • dietary supplements
  • probiotics
71
Q

research

A

systematic investigation and study of materials and sources to establish facts and reach new conclusions

72
Q

research in humans

A

research involving humans or their biological materials

73
Q

TCPS-2

Tri-Council Policy Statement (2nd Edition)

A

Tells you ethical conduct for research involving humans

Joint policy of Canada’s three federal research agencies:
- CIHR
- NSERC
- SSHRC

74
Q

REB

Research Ethics Board

A

independent committee of medical and non-medical professionals that ensure that a clinical trial is ethical

75
Q

Research requiring REB

A
  • research involving human participants
  • involving human biological materials
  • materials derived from living and deceased individuals
76
Q

Article 2.2
REB

A

REB review not required when research relies exclusively on information that is in the public domain

77
Q

Article 2.3
REB

A

REB review not required for research involving observation of ppl in public spaces

as long as there is:
- no intervention
- no expectation of privacy
- no identification of specific individuals

78
Q

Article 2.4
REB

A

REB review not required for research relying on secondary use of anonymous information or anonymous human biological materials

79
Q

Article 2.5
REB

A

Quality assurance and quality improvement studies, program evaluation activities, performance reviews do not constitute research for the purposes of TCPS2

80
Q

Article 2.6
REB

A

creative practice activities do not require REB review

81
Q

3 core principles of ethics (TCPS2)

A
  • Respect for persons
  • Concern for Welfare
  • Justice
82
Q

Respect for persons

A

participant autonomy and informed consent

autonomy: free (without interference), informed, and on-going consent - know about the purpose, benefits and risks of research

  • can seek consent from authorized third party while involving participant in the decision making progress
83
Q

concern for welfare

A

concern for privacy, for minimizing harm, seeking a favorable balance between benefits and risks

84
Q

justice

A
  • fair and equitable treatment
  • equitable distribution of benefits and risks
  • awareness of vulnerable populations
  • justified inclusion/exclusion criteria

(randomization)

85
Q

Article 4.1

TCPS2

A

culture, spoken language, religion, race, sexual orientation, ethnicity, disability, gender, age or linguistic proficiency should NOT be grounds for exclusion

86
Q

Article 4.2

TCPS2

A

women should not be excluded based solely on gender or sex

87
Q

Article 4.3

A

a woman’s reproductive capacity or pregnancy status is not a vlid reason for exclusion in itself

88
Q

Article 4.4

A

children should not be excluded due to their age or developmental stage, unless the research could impair their development/cause trauma

89
Q

Article 4.5

A

advanced age is not a valid reason for exclusion

90
Q

Article 4.6

A

a lack of decision-making capacity is not valid grounds for exclusion

91
Q

Article 4.7

A

individuals whose circumstances (poverty/health status) may make them vulnerable should not be inappropriately included nor automatically excluded on the basis of their circumstances

92
Q

regulations and standards for consent are outlined in ____

A
  • TCPS2 - Canada
  • Common Rule (45 CFR 46) - US
93
Q

undue influence

A

physical, psychological, or financial control exerted by an authority figure

94
Q

coercion

A

more extreme form of undue influence that involves threat of harm or punishment for failure to participate

95
Q

8 requirements of consent

A

(1) freely given by participant/proxy (without undue influence or coercion)
(2) informed
(3) on-going
(4) must precede data collection
(5) undue influence or coercion negate consent
(6) use of incentives must not be coercive (too much money)
(7) can include participants that lack the capacity to decide for themselves if: participant is involved in decision making as much as possible; consent from an authorized third party is attained; third party is not researcher or part of the research team; research will directly benefit participant or others in the same category
8) consent is documented

96
Q

factors that influence level of understanding

A
  • level of understanding/education
  • knowledge of subject matter
  • age (eg. children)
  • language spoken
  • emotional and psychological condition (affects ability to comprehend risks involved)
  • time pressure (eg. forced to sign the form quickly)
97
Q

consent can be waived in research if

A
  • research involves no more than minimal risk to subjects
  • research could not be carried out practicably without the waiver
  • waiver wont adversely affect the rights and welfare of subjects
  • where appropriate, subjects will be provided with additional information about their participation
98
Q

consent can be waived in individual medical emergencies if

A

1) serious threat to participant that requires immediate intervention
2) there is no standard effective treatment or the research offers a realistic possibility of direct benefit in comparison with standard care
3) risk involved is not greater than the standard of care (currently employed treatment options) and is justified by the prospect of direct benefit to the participant beyond what would be expected from the standard treatment option
4) participant is unconscious or lacks capacity
5) authorization by a third party cannot be secured in time

99
Q

14 required elements of a consent form

A

(1) info that the individual is INVITED to participate in the research project (at their own volition)

(2) stating the RESEARCH PURPOSE in plain language

(3) identity of the RESEARCHER and the FUNDER+SPONSOR

(4) expected DURATION of study, nature of participation, description of the research procedures, participant responsibilities

(5) foreseeable RISKS/BENEFITS description

(6) assurance that participant is under NO OBLIGATION to participate, free to withdraw WITHOUT PENALTY, will be given info throughout the process to inform their decision to stay/withdraw (on-going process), info on their right to WITHDRAW their DATA or human biological materials

(7) info on any CONFLICTS OF INTERESTS on the part of the researchers

(8) measures to be undertaken for DISSEMINATION OF RESEARCH RESULTS and whether participants will be identified

(9) IDENTITY AND CONTACT INFO of a qualified representative who can explain the SCIENTIFIC/scholarly aspects of the research to them

(10) IDENTITY AND CONTACT INFO of ppl outside the research team that participants can contact with any questions about ETHICAL ISSUES in the research (someone who can talk to them about their rights within the study)

(11) WHAT INFO is being COLLECTED about participants and for what purposes

(12) info on PAYMENT OF INCENTIVES for participation or REIMBURSEMENT for participation related expenses/injury

(13) statements that participants have NOT WAIVED ANY LEGAL RIGHTS

(14) info on STOPPING RULES and when researchers may remove participants from the trial

100
Q

TGN1412

A
  • humanized monoclonal antibody
  • intended to treat B-cell lymphocytic leukemia and rheumatoid arthritis
  • agonistic anti-CD28 antibody
  • directly triggers T-cell activation and proliferation without need of antigen presenting cell
  • ppl in phase 1 trial suffered severe allergy like reactions caused by a cytokine storm
  • differences in T-cell reactivity between humans and non-human primates contributed to ineffective pre-clinical toxicity screening (interspecies differences)
101
Q

problems with the TGN1412 consent form

A
  • oversold safety and participants not informed that 75% would receive the drug
  • did not disclose the degree of uncertainty in phase 1 trials
  • financial incentive may have been coercive
  • participants reported not being well educated on nature of study or mechanism of action of drug
102
Q

4 lessons learned from the TGN1412 study

A
  • animal data doesn’t always accurately predict human responses
  • European guidelines for phase 1 clinical trials for biopharmaceuticals were revised: implemented MTD establishment methods and MABEL as the starting dose instead of NOAEL
  • a rigorous, fair, and transparent consent process is of the utmost importance
  • incentivization must not unduly influence the decision making of the participant
103
Q

MTD

A

Maximum tolerated dose:

highest dose of a drug that does not cause unacceptable side effects

104
Q

MABEL

A

Minimal Anticipated Biological Effect Level

lowest animal dose required to produce pharmacological activity

105
Q

NOAEL

A

Non-observed adverse effects level

highest dose at which there is no observed adverse effect in animals

106
Q

safety monitoring plan (given to REB) should describe

A
  • how participant safety will be monitored
  • what actions will be taken if the safety of a participant is compromised
  • how the efficacy of the intervention will be monitored
  • what actions will be taken if the efficacy is greater than expected
  • criteria by which participants may be removed from the study
  • study wide stopping rules
107
Q

Stopping rules

A

stop all or part of the study if there are greater than expected harms or benefits in the study outcomes + remove individual participants from the study for their own safety (if drug is overly effective in one individual)

108
Q

stopping rules should be practiced when

A
  • a study condition is more or less efficacious than another
  • a study condition is more or less safe than another
  • study is futile because data is unreliable/ findings wont address research questions
109
Q

consent and study recruitment

A
  • consent process followed as dictated by the REB
  • proper consent form
  • appropriate inclusion and exclusion principles
  • recruitment not coercive
110
Q

BIA 10-2474 clinical trial

A

physicians continued to administer a high dose of the drug even after one participant was sent to the hospital - study not cancelled until he went into coma

  • participants not informed of the symptoms of the hospitalized patient (possibly could have withdrawn consent)
  • physicians did not wait to determine the full scope of the adverse effects suffered by the hospitalized patient - lack of adequate wait period and stopping rules

respect for persons (not informed about coma patient - consent) and concern for welfare (further harm done) core principles violated

111
Q

ethical considerations for phase 1 of clinical trials

A

1) there is little to no experience regarding the drug and its effects

  • regulated consent procedures ensure that participants are aware of the untested nature of the therapeutic (cant oversell safety)
  • regulated recruitment and consent process ensure participants do not accept risks they would otherwise refuse just for the financial incentives

2) clinical risk + uncertain clinical benefit raises safety concerns

  • small sample sizes must be employed
  • dosing must be increased in small, clearly defined increments and only after the participants’ response to the initial dose is known
112
Q

therapeutic misconception

A

occurs when participants fail to understand research is the goal not treatment

112
Q

ethical considerations for phase 2 trial

A

1) participants may be financially impacted by their health condition

  • incentives for study participation should not be coercive
  • participants should not be accepting risks they would otherwise refuse because of the incentives

2) circumstances such as chronic pain or cancer refractory to standard treatments may affect the patient’s perception of the balance between the risks and rewards of the trial

  • minimize possibility of therapeutic misconception (research is the goal not treatment)
113
Q

ethical considerations for phase 3 trials

A

1) the care of patients should not be compromised by the assignment to an experimental group

  • data must be analyzed at regular intervals to make sure not just one group is benefitting at the expense of the other
  • end the trial if new drug is more harmful or beneficial

2) new drug may provide additional benefit relative to the standard option

  • plan in place to ensure participants continue to receive adequate treatment following the conclusion of the study
  • if new drug is efficacious and safe, it must be made clear as to whether participants will continue to be provided with the treatment after the study is finished and under what conditions the drug will be offered to present and future patients
114
Q

phase 4 ethical concerns

A

commercial motivations:

financial terms between sponsors and investigators must be carefully examined to ensure that inappropriate prescription or billing practices for financial gain are avoided

115
Q

why are we so close to entering a ‘post-antibiotic era’ where completely resistant infections become routine

A
  • overprescribing antibiotics
  • bacteria evolving
  • last major antibiotic class discovered in 1962 - should bench a class
116
Q

discovery of penicillin

A

penicillin isolated from a mould that killed bacteria (staph)

  • didn’t know the mechanism of action behind it, but the structure was modified to gain advantage in pharmacokinetics to make drug last longer
117
Q

discovery of aspirin

A

isolated salicylic acid from willow bark, but it was very caustic - added an acetyl group to it to make acetylsalicylic acid (ASA)

  • used for pain/inflammation and fever
  • later discovered it had antiplatelet properties (causing bleeding and less clotting)
118
Q

discovery of anti-retrovirals

A

HIV (retrovirus) causes AIDS (acquired immune deficiency syndrome)

  • key enzyme in the replication of HIV is a reverse transcriptase (need to inhibit it)
  • CCR5 inhibitors (attachment), Reverse transcriptase inhibitors (transcription), Integrase inhibitors (integration into genome), Protease inhibitors (assembly/maturation)
  • azidothymidine (AZT) - previously shelved anti-cancer drug found useful
  • needed two diff antivirals so that resistance would not develop - combination therapy
119
Q

2 approaches to drug discovery

A

Compound-centred (20th century): relied on luck, test promising compounds for pharmacologic activity (no understanding of target yet)

facilitated by technology: get compound from nature, get its chemical structure –> create diff modifications of the structure and then screen them by having your target receptor laying there and hit with compounds until something binds the receptor

  • combinatorial chemistry: allows for generation of large number of compounds from a small number of precursors
  • high throughput screening: automated system that allows for rapid screening of thousands of compounds (assay for receptor binding and biochemical/cellular targets)

sources of compounds:

  • natural products (penicillin), endogenous compounds (insulin), re-purposing

Target-centred (21st century):
identify/characterize target first, then design a drug that hits that target - rational drug design

  • we can characterize receptors now through techniques like protein crystallography
  • we have better understanding of disease mechanisms now
120
Q

combinatorial chemistry

A

allows for generation of a large number of compounds from a small number of precursors

121
Q

high-throughput screening

A

automated system that allows for teh rapid screening of thousands of compounds

assay for:

  • receptor binding
  • biochemical/cellular targets
122
Q

target-centred approach to cancer

A

Immunotherapy

cancer cells turn off T cells (could simply block the protein)

  • pembrolizumab targets programmed cell death protein (PD)-1 (found on activated T-cells)
  • tumours bind to PD1 and turn off T-cell response to the tumour
  • pembrolizumab blocks PD-1
123
Q

patenting

A

grants exclusivity for the marketing of the product - lasts 20 years (8 years exclusivity post-market approval) - after expiration other companies may copy the drug and sell it themselves (referred to as a generic version of the drug)

124
Q

argument for lowering patent protection

A

it will:
- lower costs (generic drugs are cheaper than originator drugs
- enhance access

125
Q

argument for increasing patent protection

A
  • rewarding innovation
  • encouraging research (pharmaceutical industry is gonna say screw you guys patent protection too short)
126
Q

key elements of preclinical testing

A
  • pharmacodynamics (how selective the drug is - if it hits other receptors too cuz that will lead to more side effects)
  • pharmacokinetics: t1/2 (half life of the drug) and routes of elimination (liver or kidney)
  • toxicology: therapeutic index ((want high therapeutic index (ratio of toxic dose to effective dose - want big gap between the toxicity of the drug and efficacy of the drug)
  • pharmaceutical development - what dosage form is preferred

afterwards, get approval from regulatory body to test in humans

127
Q

regulatory agencies

A
  • Canada: HEALTH CANADA
  • USA: Food and Drug Administration (FDA)
  • Europe: European Medicines Agency (EMA)

need their approval to market in that jurisdiction

128
Q

drug approval process

A

regulatory agencies

129
Q

health canada branch responsible for Rx drugs (prescription drugs)

A

Therapeutic Products Directorate (TPD)

130
Q

phase 1

A
  • small, open label (not blinded - everyone knows whose taking the drug) or uncontrolled (no control group)
  • healthy volunteers/ patients for whom conventional therapies have failed
  • focus: pharmacokinetics, dosing, safety
  • goals: hows the drug metabolized + what is the range of doses
131
Q

phase 2

A
  • medium size (100 to a few hundred)
  • open label, single blind or double blind
  • patients
  • focus: efficacy, safety and pharmacokinetics (wanna see if drug behaves differently in someone who acc has the disease)
132
Q

phase three

A
  • large (several hundred to 1000s)
  • double blind usually
  • patients
  • focus: efficacy and safety
  • Goals: is the drug more efficacious than placebo + as safe as placebo
  • if drug is more efficacious than placebo and has no safety issues you get a notice of compliance (NOC - free to market the drug)
133
Q

Notice of Compliance (NOC)

A

manufacturer has complied with all the requirements set forth by Health Canada in the Food and Drugs Regulations

  • free to market their drug in canada
134
Q

Notice of Compliance with conditions (NOC/c)

A
  • reserved for certain drugs that show promise for life threatening conditions
  • manufacturers forego larger confirmatory trials in the approval process (have to complete them at a later date - condition)
  • provides faster access to life saving medications
135
Q

regulatory bodies responsibilities

A
  • conduct site visits (inspections) to ensure proper protocols are followed
  • oversee finalization of product monograph (official source of information of the drug)
136
Q

product monograph and its three sections

A

official source of information of the drug

137
Q

3 sections of the product monograph

A

Health professional information (label):

  • Indication (condition for which the drug is approved - general or specific)
  • Safety: Contraindications (when not to use the drug), warnings, adverse reactions, drug interactions
  • Dosing
  • Pharmacology: pharmacokinetics and pharmacodynamics

Scientific information:

  • Pharmaceutics: chemical name and properties
  • Clinical trials
  • Detailed pharmacology: includes pre-clinical data
  • Toxicology: includes pre-clinical data

Consumer information:

-

138
Q

Phase IV

A
  • post-marketing surveillance
  • not usually a controlled trial (unless required)
  • not usually a requirement
139
Q

problems with trial lengths

A

not large enough to uncover rare serious side effects + not long enough to uncover long-term toxicity issues

if you make them longer: delaying approval will harm patients too

140
Q

re-purposing

A

drug already previously approved is repurposed for a new indication

  • lets you skip phase 1
  • examples: AZT, Sildenafil
141
Q

Sildenafil

A
  • repurposed drug (initially developed as an antihypertensive)
    -PDE-5 inhibitor - inhibits breakdown of cGMP - causes vasodilation
142
Q

formulary

A

list of drugs

143
Q

CDA

A

considers both economic and clinical data - sees how well the drug works and if its cost effective (compare it to other drugs) - then makes drug coverage recommendations

  • Health canada only sees if drug works; CDA sees how well it works
144
Q

SK Rx Drug Plan

A

covers drugs in the Drug Plan Formulary

145
Q

Drug plans

A

Provincial Coverage:

  • max charge of $25 for senior and children under 14
  • coverage for low income families/ those with high drug costs relative to income

Private Insurers

  • main source of drug coverage - 3rd party coverage
  • small deductible and after that 80-100% coverage
  • list of drugs covered reflect provincial formularies

Other
- Non-Insured Health Benefits
- Veterans’ affairs
- Workman’s Compensation Board

146
Q

who decides which drugs make it onto formularies

A

each drug plan (decisions guided by CDA review)

147
Q

CDA

A
  • Canada’s Drug Agency
  • not-for-profit organization funded by federal, provincial, territorial governments
  • ensures the appropriate and effective UTILIZATION OF HEALTH TECHNOLOGIES in the Canadian healthcare system
  • give you a single process for conducting reviews of the clinical (works at least as well as the other options) and economic (cost-effective) evidence for drugs and providing formulary listing recommendations to the publicly funded drug plans in Canada (drug plans make formulary decisions based on CDA recommendation)
  • conduct evidence-based reviews to come up with CDEC (Common Listing recommendations)
148
Q

CDA core programs

A

HTA (health technology assessment): help people keep up with new technology

Reimbursement reviews: more formulary related decisions

idea of formulary reviews is to giev you this one process that gives you best possible reveiw of. adryug

149
Q

rationale for CDA

A
  • all provinces used to conduct their own drug reviews
  • First Ministers initiated the plan for a single review and listing process
150
Q

CDA objectives

A
  • consistent and rigorous approach
  • reduced duplication
  • maximized use of limited resources and expertise
  • equal access to evidence and advice
151
Q

what does CDA review

A
  • new drugs after they are approved by Health Canada
  • existing drugs with new indications
  • oncology drugs
152
Q

CDA review team

A
  • two clinical reviewers
  • two economic reviewers
  • clinical expert (specialist in the field - opinion leader)
  • informatics specialist
153
Q

writing a systematic review (CDA)

A

Develop protocol using PICOS:
define Population, drug you are studying (Intervention), drug you are comparing to (Comparator), outcomes you are looking for to assess the drug (outcomes) - type of study (randomized controlled trial ex.)
Then, search literature and select studies that match protocol

154
Q

who regulates rug prices in canada

A

PMPRB
patent medicines prices review board

155
Q

OECD

A

countries with similar economies

organization for economic cooperation and development

156
Q
A

CPPS 337 (1 decks)

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