Week 3 - Research Methods in Behavioural Pharmacology Flashcards
What is a between-subjects design?
• Experiments conducted with 2 (or more) different groups
o IV operationalized as different groups
• Usually interested in the difference between the means of these groups
What are the advantages of a BS Design?
- Easier and more time efficient to run
* Allows observation of variables that are not stable (i.e. habituation, practice effects)
What are the disadvantages of BS design?
• Many variables are unable to be controlled (e.g. systematic differences between the groups_)
o Need more participants so these effects average out
• Results are presented in terms of group differences; masks change within the individual
• Method of allocating to groups (randomized controlled trial; consecutive case design?)
What is a within subjects design (repeated measures)?
• Same participant involved in every level of the experiment
o IV is operationalized as different levels/testing occasions that all participant receive
What are the advantages of a WS design?
- Requires fewer participants
* Each participants acts as their own control
What are the disadvantages of a WS design?
- Not amenable to measurement of unstable variables
- Time and money
- May need alternate forms to assess DV to counteract practice effects
- May need to counteract cross-over effects
What are control groups, and what are they used for?
- Used to ensure the effect observed is due to the variable we manipulated and not some other variable
- Especially important in between-subjects designs
- A control group will be identical to the groups being tested, except for the manipulation
What is a placebo and what are they useful for?
- A placebo control conditions similar to experimental condition, except rather than receiving the drug (or no drug) they receive a substance containing no active ingredients (a placebo)
- Placebo controls are extremely useful for investigating whether any benefits derived from a drug are due to placebo effects
What is the Nocebo Effect?
if the side effects told to be negative then can start to actually experience them
What is the expectation mechanism hypothesis?
hypothesized that you need the priming of pain reduction to actually experience pain reduction
What is a three groups design?
- Given a new drug
- Given a proven drug
- Given a placebo
What does a three groups design allow?
- allows a comparison between new drug and placebo
- allows comparison between new and established drugs
- allows experimenter to see if measures are sensitive enough to detect change (i.e. compare proven drug and placebo)
What are alternative combinations of groups used to answer questions of?
o Effectiveness of drugs vs. non-pharmacological interventions
E.g. CBT group vs. drug-treated and placebo-groups
o Specificity of drug effects:
E.g. include groups comprising people with different mental illnesses
• Does the drug work in depression exclusively?
How else may effects be assessed?
over time (multiple measurements (longitudinal design) or once-off (cross-sectional design)) Sources of Bias
What are some sources of bias
o Experimenter and participants expectations/bias (double blind studies) o Selection bias: experimental controls Demographic differences (age/gender) Cultural differences Personality differences Education ect
What is the level of control for experimental designs from low to high?
Introspection -> Naturalistic Observation -> Case History -> Survey -> Test -> Correlation -> Experiment
What are potential variables?
• Depending on the drug and its action, some of the domains in which we may look for effects are:
o Arousal
o Cognition
o Perception
o Motor function
o Mood
• We might also want to measure side effects/biochemical or physiological drug effects
What is the outcome of more performance measures?
• The more measures we use:
o The more comprehensive our assessment
o The more costly our experiment (financial and time)
o The greater the need to consider experimental controls and logistics (e.g. order we administer measures)
What does assessing change in performance across domains tell us?
tells us something about how the drug works, and the effects it produces (primary and side effects)
What are the levels of arousal from low to high?
Death -> Coma -> Sleep -> Drowsy -> Normal -> Aroused -> Highly excited -> mania -> convulsions -> death
What is one brain scanning way to measure arousal?
• EEG: a measure of arousal/detects potential differences between points on the scalp and neutral points on the body
What are other ways to measure arousal?
o Introspection?
Unstructured introspection
Systemic introspection
o Ask an observer?
How to measure mood?
• Can be studies experimentally (e.g. we can test drug effect by inducing mood states) or using a b-g design (e.g. depressed vs. non-depressed patients)
• Measurement could be by self-report, doctor’s assessment, informant report, questionnaire, tests of biological markers of depression etc.
o Consider the adv and dis of these ways of assessing drug effects on mood
What does perception research study?
- 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)
- Changes in sensitivity = thresholds (two types)
What are the two types of thresholds
Absolute and difference thresholds
What is critical frequency at fusion (CFF)
The sensitivity to drug effects
What is cognitive performance?
• Ability to process, store and retrieve information (e.g. attention, memory, learning etc); can also include higher-level processes such as planning, set-shifting and response inhibition
How is this manipulated experimentally?
o Effect of drug at different stages of cognitive process can be assessed (e.g. may affect storage of information, or earlier attention processes)
How to measure motor performance?
simple or choice reaction time, tapping, pursuit rotor, ect.
What are the methods to study side effects/physiological effects?
o Questionnaire (e.g. yes/no questions; rating scale etc)
o Biochemical assay
o Doctor’s check-up/physical examination
o Informant report
Strengths and weakness
• Some methods of assessing physiological effects: biochemical assays, MRI scans, PET scans
What are factors to be considered in drug studies?
o Wash out effects (esp. in w/g designs)
o Deprivation of drug administered
o Dose of drug used (e.g. P. compliance with instruction)
o Inclusion of biochemical assays
o Controls for routine/habitual or other drug use
o Non-specific treatment effects
o Special group selection factors (mild, moderate, and severe depression?)
o Time frame for assessing effect
o Reporting of adverse events/non-compliance/attrition
What are some major considerations in drug development?
- Medical need
- Commercial potential
- Feasibility for mass production
• “Orphan drugs”
What are the 4 stages for FDA approval?
- Preclinical investigations (basic science; tests on cells & animals; effects of drugs noted for side effects ,toxic effects, addiction, cancerous tumors, fetal deformities, pharmacodynamics)
- Clinical investigation (human testing, 4 phases, incl. 3 phases of clinical trials)
- Review of NDA (New Drug Application)
- Post marketing studies
What is step 1 of animal testing in drug development?
Step 1: Determining toxicity
• Acute toxicity (for single doses)
• Sub acute toxicity (short term use of drug)
• Chronic toxicity (longer-term drug use)
• Special toxicity (carcinogenic? Taratogenic?)
What is step two of animal testing in drug development?
Direct and indirect pharmacological studies?
What are direction pharmacological studies?
o To locate direct measures of changes induced by drugs via tools such as:
Rating scales. Objective measures (e.g. jiggle-case/tail suspension test), conditioning studies, sites of action studies
What are indirect pharmacological studies?
o To identify markers or signs of effects rather than evidence of the effect itself or
o To observe effects on behaviors that are induced in animals
How is conditioned behaviour measured in nonhumans?
• Schedules of Reinforcement: patterns that determines when reinforcement are to to be given
What are the different types of schedules and their subgroups?
o Ratio Schedules Fixed ratio (FR) Variable ratio (VR) o Interval Schedules Fixed Interval (FI) Variable Interval (VI)
What is the stimulus property of a drug?
Ability to act as a discriminate stimulus in a discrimination learning task
What are the processes for determining the reinforcing properties of drugs?
o Rate of Responding
o Progressive Ratio
Breaking point (organism will stop responding)
o Choice
2 levers; one has consequences. Exposure to 2 drugs over separate sessions; then observe animals’ choice of drug A or B
o Conditioned place Preference
Animal will spend time in area of reinforcement
What are the stages for clinical investigation (human volunteers?
o Phase 1: human testing to determine toxicity and side effects in healthy human (paid) volunteers
o ‘Phase 2: human testing in clinical samples (i.e. patient groups) to assess potential therapeutic effects (+adverse)
o Phase 3: expanded clinical trials using basic 3-group design
o > approval or rejection of new drug for licensing and marketing
o Phase 4: accumulation of data on drug effects
