L10- randomised controlled trials Flashcards
What does ‘scientifically proven to work’ mean?
That it has been compared against another treatment and is better e.g. relative risk
What study is analogous to a RCT, except that treatment/exposure is not allocated unlike a RCT?
Cohort study, therefore it is an analytical study not an experimental study like a RCT
Define a clinical trial
Any form of PLANNED EXPERIMENT which involves patients and is designed to elucidate the most appropriate method of treatment of FUTURE PATIENTS with a given medical condition
What is the purpose of a clinical trial?
To provide reliable evidence of treatment efficacy and safety
Outline the major steps involved in a RCT
- Definition of factors
- Conduct of trial
- Comparison of outcomes
What are the reasons for pre-defining outcomes for clinical trials?
Define what,when and how before trial:
- Prevent ‘data dredging’ & ‘repeated analyses’
- Protocol for data collection
- Agreed criteria for measurement and assessment of outcomes
What are the advantages of random allocation?
- Minimal allocation bias - equal chance of each treatm’
- Minimal confounding - in the long run, randomisation leads to treatment groups that are likely to be similar in size and characteristics by chance (unknown and known confounding factors)
What are the advantages of blinding?
Knowledge of which participant is receiving which treatment may introduce bias e.g.
(i) patients may alter their behaviour, other treatment, pr expectation of outcome
(ii) Clinician may alter their treatment, care and interest in the patient (non-treatment effect)
(iii) Investigator may alter their approach when making measurements and assessing outcomes (measurement bias)
Randomisation without blinding does not avoid allocation bias.
What is the ‘placebo effect’?
Even if the therapy is irrelevant to the patient’s condition, the patient’s attitude to his or her illness and indeed the illness itself may be improved by a feeling that something is being done about it
What is a placebo?
An inert substance made to appear identical in every way to the active formulation with which it is to be compared, e.g. appearence, taste, texture, dosage regime, warning etc….
The aim of a placebo is to be able to cancel out any ‘placebo effect’ that may exist in active treatment.
Total effect = active treatment effect + placebo effect
How can you minimise ‘losses to follow-up’?
- Make the follow-up practical and minimise inconvenience
- Be honest about the commitment required from participants
- Avoid coercion or inducements
- Maintain contact with participants
What are the differences between ‘explanatory’ and ‘pragmatic’ trials?
a
What is the meaning of an ‘intention-to-treat’ analysis?
a
What are the ethical principles involved in medical research involving human subjects?
a
What issues need to be considered for a clinical trial to be considered ethical?
- placebos only used when no standard treatment available
- placebos are a form of deception therefore participants must know that they may receive one
What is the role and function of a research ethics committee?
a
How does a clinical trial compare to other epidemiological studies?
A clinical trial is like a cohort study except that it is not observational - exposures are allocated by trial investigators
Define efficacy
The ability of a heath care intervention to improve the health of a defined group under specific conditions
Define safety
The ability of a health care intervention not to harm a define group under specific conditions
What are the three things that a clinical trial needs to be in order to give a fair comparison of effect and safety?
- Reproducible - in experimental conditions
- Controlled - comparison of interventions
- Fair - unbiased without confounding
What are the differences in small clinical trials (
random variation caused by chance
Which stage of drug development and monitoring is clinical trials (comparison with a standard treatment)?
Phase III
What are the disadvantages of using historical controls?
- Selection often less well defined, less vigorous
- Treated differently form ‘new treatment’ group
- Less information about potential bias/confounders
- Unable to control for confounders
What is involved in the first step of a RCT: ‘definition of factors’?
Defining:
- The disease of interest
- The treatments to be compared
- The outcomes to be measured
- Possible bias and confounding
- The patients eligible for the trial
- The patients to be excluded from the trial - appropiate to exclude?
What is involved in the second step of a RCT: ‘conduct of trial’?
- Identify a source of eligible patients
- Invite eligible patients to be involved in trial
- Consent patients willing to be in trial
- Allocate participants to the treatments fairly i.e. without bias or confounding
- Follow-up participants in identical ways
- Minimise losses to follow-up
- Maximise compliance with treatments
What is involved in the third step of a RCT: ‘comparison of outcomes’?
- Is there an observed difference in outcome between the treatment groups?
- Could the observed difference have arisen by chance, i.e. is it statistically significant (chance, bias, confounding)?
- How big is the observed difference between the treatment groups. i.e. is it clinically significant?
- Is the observed difference attributable to the treatments compared to the trial?
What are primary and secondary outcome measures for clinical trials?
Primary outcome
- preferably one primary outcome
- used in sample size calculation
Secondary outcome (not main focus, specified pre-trial)
- other outcomes of interest
- often includes occurrence of side-effects
List three broad types of outcomes that can be measure in a clinical trial
- Patho-physiological e.g. tumour size, ECG changes etc..
- Clinically defined e.g. mortality, morbidity, disability
- Patient-focussed e.g. quality of life, psychological well-being, social well-being, satisfaction (more subjective)
What are the features of an ideal outcome?
- Appropriate and relevant
- Valid & attributable
- Sensitive & specific
- Reliable & robust
- Simple & sustainable
- Cheap & timely
Describe how an ideal outcome is appropriate and relevant
Relevant to the patient, clinician, society etc… will the results either way actually improve things?
Describe how an ideal outcome is valid and attributable
Can any observed effect be reasonably linked to the treatments being compared?
Describe how an ideal outcome is sensitive and specific?
Can the chosen method of measurement detect changed accurately?
Describe how an ideal outcome is reliable and robust?
Can the outcome be measurable by different people in various settings with similar results?
Describe how an ideal outcome is simple and sustainable
Is the method of measurement easy to carry out repeatedly?
Describe how an ideal outcome is cheap and timely
Is the outcome excessively expensive to measure
When are measurements taken during the clinical trial?
- Baseline measurement -
- Monitoring outcomes during trial:
(i) possible effect - one group being disadvantaged?
(ii) adverse effects - individuals being harmed? - Final measurement of outcomes - final treatment effects
