1
Q
What is the Independent variables (IV)
A
- Variable that is manipulated in a study
- E.g., amount of drug administered/ type of drug administered
2
Q
What is the Dependent variables
A
- Variable that is measured in a study (to observe effect of IV)
- E.g., behaviour/mood/cognition/motor performance
3
Q
What is a between-subject designs (independent groups)
A
- Experiments are conducted with 2 (or more) different
groups - (IV is operationalised as different groups)
- E.g., Group A given a new drug; Group B given CBT
- Usually interested in the difference between the means of
these groups.
4
Q
What are the advantages of a between subject design?
A
- Easier & more time efficient to run
- Allows observation of variables that are not stable (i.e., habituation, practice effects, etc.)
5
Q
What are the disadvantages of a between subject design?
A
- Many variables are unable to be controlled (e.g., systematic
differences between the groups)
–> need more participants so these effects average out - Results are presented in terms of group differences; masks changes within the individual
- Method of allocating to groups (randomised controlled trial; consecutive case design?)
6
Q
What is a Within-subject designs (repeated measures)?
A
- Same participants involved in every level of the experiment
- IV is operationalised as different levels/testing occasions that all participant receive
- E.g., same participants are tested for attention span before
& after taking a drug - Usually interested in difference in the mean of the 2(+)
testing occasions
7
Q
What are the advantages of Within-subject design?
A
- Requires fewer participants
- Each participant acts as their own control
8
Q
What are the disadvantages of a Within-subject design?
A
- Not amenable to measurement of unstable variables
- Time & money
- May need alternate forms to assess DV to counteract practice effects
- May need to counteract cross-over effects (Landauer, 1975)
9
Q
WHat are Control groups/conditions
A
- Used to ensure the effect observed is due to the variable wemanipulated & not some other variable
- Especially important in between-subject designs
- A control group will be identical to the groups being tested, except for the manipulation
For example:
Group A: has depression & given new antidepressant (exp. group)
Group B: has depression but receives no treatment (control group) - participants with same symptoms/severity, demographics etc. as experimental group
- If no difference is observed between the 2 groups, then it appears the new antidepressant did not work
10
Q
What are Placebo controls
A
- sometimes in drug research a placebo condition will be used
- A placebo control condition will be similar to the experimental condition, except rather than receiving the drug (or no drug) they receive a substance containing no active ingredients (a placebo)
E.g., Group A: has depression, receives new antidepressant
Group B: has depression, & receives sugar pill
- Placebo controls are extremely useful for investigating whether any benefits derived from a drug are due to placebo effects
11
Q
What are Three-groups designs
A
3 groups may be used
1. Given a new drug
2. Given a proven drug
3. Given a placebo
- Allows comparison between new drug & placebo
- Allows comparison between new & established drugs
- Allows experimenter to see if measures are sensitive enough to detect change (i.e., compare proven drug & placebo)
12
Q
What are specificity of drug effects:
A
- e.g., include groups comprising people with different mental illnesses → does the drug work in depression exclusively?
13
Q
What is longitudinal design
A
ffects may also be assessed over time (multiple measurements)
14
Q
What is cross-sectional design
A
once of design
15
Q
What is bias
A
- Bias results in systematic errors in measurement or prediction
- Bias can enter an experiment from many different sources
- Experimenter & participant expectations/bias (double blind
studies)
16
Q
WHat are selction biases
A
- Demographic differences (age/gender)
- Cultural differences
- Personality differences
- Education etc. etc. etc
17
Q
Rate which forms of study has the most control (1) to least control (7)
A
- experiment
- correlation
- Test
- survey
- case history
- Naturalistic observation
- Introspection
18
Q
What are Ethical & legal constraints on drug research
A
In most drug studies there are severe ethical & legal constraints
* E.g., alcohol studies: legal constraints are relatively few (except min. age), but there are still ethical problems (e.g., how do people get home after experiment?)
- administering alcohol (& other legal drugs) to participants to participants can be costly (time & money)
- retrospective consumption questionnaires are often used (or daily consumption questions (diaries))
19
Q
What are the potential varibles or domains we look for effects in during drug research?
A
changes to
* Arousal
* Cognition
* Perception
* Motor function
* Mood
* We might also want to measure side effects / biochemical or physiological drug effects
20
Q
How/why do we measure perfomrence within a drug test
A
- The more measures we use:
- the more comprehensive our assessment
- the more costly our experiment (financial & time)
- the greater the need to consider experimental controls &
logistics (e.g., order we administer measures). - Assessing change/differences in performance across performance domains (e.g., arousal, cognition, perception, motor function) tells us something about how the drug works, & the effects it produces (primary & side effects)
21
Q
Measuring arousal
A
- Arousal level changes naturally throughout the day, but can also be affected by a number of things – including drug use
- Most drugs are thought of as either ‘ stimulants’ or ‘depressants’, when given in large doses (at low doses this categorization does not hold)
- ‘uppers’ & ‘downers’ imply a relationship between arousal & mood
– not necessarily that clear - High arousal does not high activity
22
Q
How is arousal measured?
A
- Since various drugs have an effect on arousal how we measure arousal is important
- Electroencephalograph (EEG): a measure of arousal/ detects potential differences between points on the scalp & neutral points on the body
- Other ways to measure arousal:
- Introspection?
- Unstructured Introspection
- Systematic Introspection – e.g., self-report scales (e.g., VAS)
- Ask an observer?
23
Q
What are the levels of arsoual
A
Death
Coma
Sleep
Drowsy
Normal
Aroused
Highly excited
Mania
Convulsions
Death
24
Q
Measuring mood
A
- Drugs can impact significantly on mood
- Can be studied experimentally (e.g., we can test drug effects by inducing mood states) or using a between-groups design (e.g., depressed vs. non- depressed patients)
- Measurements could be by self-report, doctor’s assessment, informant report, questionnaire, tests of biological markers of depression etc.
- Consider the advantages & disadvantages of these ways of
assessing drug effects on mood
25
Measuring perception
* Refers to the detection & integration of external stimuli
* Visual & auditory perception are most often studied
* Perception research often investigates the changes in the sensitivity of a person’s perception brought about by changes in the internal or external environment (e.g., drug use)
* These changes in sensitivity = thresholds (two types)
* Absolute Threshold --> Lowest value of stimulus detectable by an organ (e.g., eyes)
* Difference Thresholds --> Organ detects a change in level of stimulation
26
What are absoloute thresholds?
The lowest value of a stimulus that can be
accurately detected 50% of the time. Example:
* Vision: candle flame on a dark, straight road, at 60km
* Smell: 1 drop of perfume in a 6-room apartment
* Hearing: watch tick 6 m away
* Taste: 1 tsp sugar in 8 L water
* Touch: wing of a fly falling on your cheek from 1cm
27
What is difference thresholds?
* measure the ability of an individual to detect a
change in a stimulus
* E.g., when can you tell the light is brighter than it was before?
* Critical frequency at fusion (CFF) – sensitive to drug effects
28
Measuring cognitive performance
* Ability to process, store & retrieve information (e.g., attention, memory, learning, etc.); can also include higher-level processes such as planning, set-shifting & response inhibition
* Often manipulated experimentally
--> Effect of drug at different stages of cognitive process can be assessed (e.g., may affect storage of information, or earlier attention processes)
29
Measuring motor performance
* Drugs can have a significant impact on motor tasks like coordination (e.g., alcohol)
* How might we measure these?
* ? simple or choice reaction time, tapping, pursuit rotor, etc.
30
Measuring side effects/physiological effects
Some methods of assessing side effects:
* Questionnaire (e.g., yes/no questions; rating scale etc.)
* Biochemical assay
* Doctor's check-up/ physical examination
* Informant report
* Strengths & weaknesses of these methods
Some methods of assessing physiological effects: biochemical assays, MRI scans, PET scans
31
How do you identify a good research design?
What is the research question: does the chosen design allow that question to be answered?
* What are the strengths & limitations of the measures used to assess effects?
--> How sensitive/ appropriate are the measures?
--> How precisely can measurements be made?
* What experimental controls have been put in place?
* Effect size: how meaningful is the change observed in terms ofeveryday functioning?
32
What are some special factors to consider with drug studies when trying to identify a good research design?
* Washout effects (esp. in w/g designs)
* Deprivation study designs (withdrawal)
* Level of drug administered
* Dose of drug used (e.g., compliance with instructions)
* Inclusion of biochemical assays
* Controls for routine / habitual or other drug use
* Non-specific treatment effects
* Special group selection factors (mild, moderate, & severe
depression?)
* Timeframe for assessing effect
* Reporting of adverse events/non-compliance / attrition
* If in-vitro cellular trials are used: how generalizable are results to intact living systems?
* If animal trials are used: how similar is the species, apparatus, domain of function being tested?
33
What are the Major considerations in drug development?
1. Medical need
2. Commercial potential
3. Feasibility for mass production
* “Orphan drugs”
34
What is the FDA approval processes: 4 stages
1. Preclinical investigation (basic science; tests on cells &
animals; effects of drugs noted for side effects, toxic effects,
addictions, cancerous tumors, fetal deformities,
pharmacodynamics)
2. Clinical investigation (human testing, 4 phases, incl. 3 phases of clinical trials)
3. Review of NDA (New Drug Application)
4. Postmarketing studies
35
What are some Specific limitations of animal studies,
* Cats: markedly different sleep-wake cycles (e.g., sleep 65-80% of the time)
* Monkeys: develop obvious behavioural abnormalities from
confinement
* Rabbits: different enzymes from humans (e.g., can eat some plants that would be poisonous to humans)
Despite limitations, animals studies generally provide a valid
indication of the likely drug effect in humans
36
In the drug development & animal testing (Stage
1:step 1) what is the first step of the process
Step 1. Determining toxicity
* Acute toxicity (for single doses)
* Subacute toxicity (short term use of drug)
* Chronic toxicity (longer-term drug use)
* Special toxicity (carcinogenic? teratogenic?)
37
In the drug development & animal testing (Stage
1:step 2) what is the second step of the process
Step 2. Pharmacological studies (direct & indirect)
* Direct:
– to locate direct measures of changes induced by drugs via tools such as:
* rating scales, objective measures (e.g., “jiggle-cage”/ “tail
suspension test”), conditioning studies (see next slides), sites- of-action studies
* Indirect:
- to identify markers or signs of effects rather than evidence of the effect itself or - to observe effects on behaviours that are induced in animals
38
What are the general principles of Direct pharmacological studies- conditioning
* Stimulant substances: rapid learning/acquisition of conditioned response, poor discrimination / ready generalisation, slow termination/extinction
* Depressant substance: slow acquisition/learning, poor
generalisation/easy discrimination, rapid extinction
39
Measuring conditioned behavior in nonhuman (what are the Schedules of Reinforcement)
* Schedules of Reinforcement: pattern that determines when
reinforcements are to be given
* Ratio Schedules
- Fixed ratio (FR)
- Variable ratio (VR)
* Interval Schedules
- Fixed Interval (FI)
- Variable Interval (VI)
* Avoidance-Escape Task
* Punishment
* Stimulus Properties of Drugs
- stimulus properties
- ability to act as a discriminative stimulus in a discrimination learning task.
40
Measuring conditioned behavior in nonhuman (what are the Reinforcing properties of drugs)
* Rate of Responding
* Progressive Ratio
- Breaking point (organism will stop responding)
* Choice
- 2 levers; one has consequences. Exposure to 2 drugs over
separate sessions; then observe animal’s choice of drug A or B.
* Conditioned Place Preference
- Animal will spend time in area of reinforcement
41
FDA approval processes
* Stage 1 Pre-clinical (animal studies to determine suitability as therapeutic agent; measurement of ED50 , LD50 & therapeutic index) – i.e., toxicity & pharmacological studies
* Stage 2 Clinical investigation (human volunteers):
* Phase 1: Pharmacokinetic & Safety Testing - human testing to determine toxicity & side effects in healthy human (paid) volunteers
* Phase 2: Small-scale Effectiveness Testing - human testing in clinical samples (i.e., patient groups) to assess potential therapeutic effects (+adverse)
* Phase 3: Large-scale Effectiveness Testing - expanded clinical trials using basic 3-group design
--> approval or rejection of new drug for licensing & marketing
* Phase 4: accumulation of data on drug effects
42
In the Phases of human testing (clinical trials) what is phase one?
* Phase 1
* 20-100 healthy volunteers
* Informed consent mandatory
* evaluate side effects
* establish final, correct dosage
* pharmacokinetics studied
* generally takes 2 years
43
In the Phases of human testing (clinical trials) what is phase two?
Phase 2
* 100-300 patients who have disease drug intended to treat
* drug given on experimental basis
* determines therapeutic effect
* usually takes 2 years
44
In the Phases of human testing (clinical trials) what is phase three?
Phase 3
* 1000-3000 ill patient volunteers
* administered same way that it will be used on the market
* performance vs. other drugs currently on the market (3-group design with placebo; single or double-blind)
* usually lasts 2-4 years
Completion of Phase 3
* drug company submits all documentation to FDA in a New Drug Application (NDA)
* waits for final FDA decision → approval or denial
* only 20% NDAs receive final FDA approval for marketing
45
In the Phases of human testing (clinical trials) what is phase four? (postmarking study)
* After NDA review completed & approved
* Lasts on average, 15 years
* New drug placed on the market
* Surveillance: check for new harmful effects in larger group of humans
* Drug removed from market if serious problems occur
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