Strand B Flashcards
What is a clinical trial?
A research study in which one or more human subjects are prospectively assigned to one or more interventions to evaluate those interventions on health-related biomedical or behavioural outcomes
What is a clinical study?
A study involving using human volunteers that is intended to add medical knowledge, interventional and observational
What is the difference between a clinical trial and study?
Study - interventional and observational
Trial - interventional only
What is the history of clinical trials?
562 BCE - ‘first’ clinical trial
1537 - first trial of 2 medical treatments
1747 - one of the earliest controlled clinical trials
1940s - first double blind clinical trial
1948 - first ‘true’ randomised control trial
What are the different types of clinical trials?
Mechanistic
Exploratory/development
Pilot/feasibility
Other interventional
Behavioural
Basic experimental (BESH)
What are the differences between experimental and observational studies?
Experimental - Randomised control trials (RCTs)
Non-randomised control trials (nRCTs)
Observational - Cohort studies
Case-control studies
Cross-sectional studies
Ecological studies
What are randomised control studies (RCTs)?
Used to find effectiveness of new treatment while eliminating as many biases as possible
Randomised to one of two or more groups to test specific drug, treatment, etc (e.g. intervention used vs placebo)
Groups are followed up to see how effective
Outcomes measured at specific times and different responses are assessed statistically
What are non-randomised control studies (nRCTs)?
People allocated to different interventions using methods that are not random
Purely observational, non-randomised interventional studies, and single-arm trials with external control
What are cohort studies?
Observational study using defined groups while being followed over time
People with similar characteristics
Why are cohort studies used?
Examine associations between different interventions received and subsequent outcomes
What is the difference between a prospective and retrospective cohort study?
Prospective - recruits participants before
Retrospective - subjects from past records describing interventions received
What are case-control studies?
Observational study to find the possible cause of a disease/condition
Researcher looks for aspects of lives that differ to see what has caused the condition
Why are case-controlled studies used?
Compares groups of patients who have the disease with a group of people without but with similar characteristics (unrelated from condition)
What is a cross-sectional study?
A ‘snap-shot’ observation of a set of people at 1 time
Describe a variable not measuring it
Why are cross-sectional studies used?
Public health research uses this to assess exposure and a disease and compare the rates of disease and symptoms of an exposed and unexposed group
What are the advantages and disadvantages of cross-sectional studies?
Advantages: cheap, quick, minimal room for error
Disadvantages: Doesn’t help determine cause and effect, report bias is probable (surveys)
What are ecological studies?
Used to understand relationship between outcome and exposure at a population level (population with shared characteristics)
Characteristics include geography, ethnicity, socio-economic status of employment
Why are ecological studies used?
Ecological vs other studies is the group is the unit analysis studied no assumptions about individual study participants
What are the phases of a clinical trial?
Laboratory studies - cell/animal studies
Phase I - Safety of medication on people
Phase II - Safety and effectiveness
Phase III - Safety, effectiveness and dosing
Phase IV - long-term effectiveness vs new treatment to standard treatment
What happens during the laboratory stage of clinical trials?
Basic research, accurately model desired biological effect of a drug predicting treatment outcome in patients and predict ant adverse reactions
Testing: in vitro, in vivo and drug profiling using computer models
What happens during phase I of clinical trials?
Drug/treatment on small group of people for first time
Safety and side effects
Several months
Success around 52%
What happens during phase II of clinical trials?
Larger group of people
Emphasis on effectiveness
Preliminary data whether drug works in people with disease/condition
Last several years (~1-4)
Success around 30%
What happens during phase III of clinical trials?
Large groups of people
More information of safety and effectiveness, different populations and dosages and drug-drug interaction
Information for the drug to be used safely
Success around 58%
What is the FDA approval stage during clinical trials?
New Drug Application (NDA) for treatment to an organisation e.g. FDA
Review results to determine if approves the drug and allow marketing to public
Continue to monitor effects
Success around 25-30%
What happens during phase IV of clinical trials?
After approved by FDA - post-marketing monitoring stage
Available to public
Monitored in large diverse populations
More information of treatment’s benefits and optimal use
What are things to consider when setting up and running a clinical trial?
Ethics
Consent
Controls
Randomisation
Binding
Sample size
Statistics
What is ethics?
It is moral principles that govern a persons behaviour or the conducting of an activty
What are examples of different ethical considerations in research?
Voluntary participation
Confidentiality
Consent
Anonymity
Potential for harm
What is consent?
Informed consent is one of the founding principles of research ethics, so human participants can enter research freely with full information about what it mean for them to take part
Give consent before they enter
How can a researcher ensure the participants are fully informed?
By understanding what the research is and what they are consenting to
Researcher giving sufficient and appropriate information about the trial (information sheets)
Researchers ensures no coercion
Time given for the participant to consider choice and discuss if appropriate
Participant has the right to withdraw at any time
What is bias?
Systematic errors that encourage one outcome over others
Investigators then come to wrong conclusions about the beneficial and harmful effects of interventions
What is the result of bias?
Over-estimation of the effect of treatments
Treatment look better than they really are
Make ineffective treatments look as if they work
What is a control group?
The standard to which comparisons are made in an experiment
Composed of participants who do not receive the experimental treatment
Why are controls used?
To effectively test a treatment in the absence of some absolute or relative measure of success
What are the parameters of control groups?
Ideally they are identical in every way except that the experimental groups are subjected to treatments or interventions with effect
What is randomisation?
It is the process by which treatments are assigned to participants by chance rather than by choice
Avoids bias in assigning volunteers to get one treatment or another
What are the different types of randomisation?
Simple
Block
Stratified
What is simple randomisation?
Based on a single sequence of random assignments
Maintains complete randomness of the assignment of a subject to a particular group
Most common and basic
What are the advantages and disadvantages of simple randomisation?
Advantages: Simple
Easy to implement
Disadvantages: Could result in unequal number amongst groups
What is block randomisation?
Randomise subjects into groups that result in equal sample sizes
Block size decided by researcher, all possible balanced combinations must be calculated
Blocks randomly chosen to determine patients’ assignment into the groups
What are the advantages and disadvantages of block randomisation?
Advantages: Balance in sample size
Disadvantages: Can predict blocks
Groups may not be comparable in terms of covariates
What is stratified randomisation?
Control and balance covariates
Generates separate block for each combination of covariates subjects assigned appropriate one
After all subjects identified and assigned, simple randomisation is performed within block to assign subjects to group
What are the advantages and disadvantages of stratified randomisation?
Advantages: Simple for small trials
Takes covariates into consideration
Disadvantages: Complicated if many covariates
Subjects have to be identified before assignment (bias)
What is blinding?
Studies designed to prevent members of research team and study participants from influencing results
Allows collection of scientifically accurate data
What are single-blinded studies?
Only the researcher knows treatment or intervention the participant is receiving until the trial is over
What are double-blind studies?
Neither participants or researcher knows which treatment or intervention participants are receiving until clinical trial is over
How can blinding help influence the behaviour of the researchers?
Influence patient management
Decision to withdraw patient from trial
Decision to adjust drug dose
Decision about intensity of therapy
Decision about adjacent therapy
Decision to discharge patient
How can blinding help influence the behaviour of the trial subjects?
Influence compliance with the trial
Influence expectations
Influence assessment of patient reported outcome
Knowledge of treatment group can influence behaviour outcome assessor
Influence assessment of outcome
What is a placebo?
Treatments that look like the real thing but contain no active ingredient
What is the aim of a placebo?
To achieve blinding
What is the placebo effect?
When a persons physical or mental health appears to improve after taking a placebo or dummy treatment
Why are statistics important in clinical trials?
For design, conduct, analysis and reporting
Researchers form reasonable and accurate inference from collected information
No uncertainty
Prevent errors and biases in medical research
What is a hypothesis?
A proposed assumption for a phenomenon that may or may not be true
What is hypothesis testing?
An evaluation done by a researcher to confirm or disprove a hypothesis
What are the different types of hypothesis tests?
T-test
Chi^2
Z-test
What are the 2 different hypothesis the researcher has?
Null and alternative hypothesis
What is the null hypothesis (H0)?
Captures what the current situation is
What is the alternative hypothesis (H1)?
Captures what we want to show by doing the trial
What does hypothesis testing do?
It tests if the hypothesises more probable than the existing hypothesis and assumes the null hypothesis is true until proven that the alternative hypothesis is instead true
What happens if there are too little participants?
Real effect may be missed - indistinguishable from chance variation
If study does not yield useful results, time and money wasted
What happens if there are too many participants?
Smaller trials could reach firm conclusions so no need for participants beyond this
Cost implications
What is the true endpoint of a clinical trial?
A clinically meaningful endpoint that directly measures patients (has treatment worked?)