EAB: Randomised Controlled Trials Flashcards
what is an RCT
a planned experiment in humans
designed to assess efficacy of treatment or intervention
What are RCTs used to evaluate?
- drugs
- methods of diagnosis eg MRI scanner
- methods of organising care
- methods of screening for disease
- methods for disease prevention
- health care policies
What is the PICO framework for basic RCT design questions?
- What is the question?
- Who is the population of interest? (P)
- What is the intervention? (I)
- What is comparison? (C)
- How will the outcome be assessed? (O)
What are some examples of eligibility criteria?
- Condition e.g. diagnosis
- Age
- Sex
- Other conditions present (co-morbidity)
- Severity of illness
- Where recruited eg hospital or primary care
What is the range of outcome measures (5 Ds)?
- Death
- Disease activity or recurrence
- Disability
- Distress
- Discomfort (pain)
What is the primary outcome measure?
the primary outcome measure is the main variable of interest that the study is designed to investigate
- Clinically relevant
- Objective (not subjective)
- Easy and accurate to measure
- Independent of treatment
What is blinding in a RCT?
Protects against bias in performance of trial and assessment of
outcomes
- ‘Open label’ - no blinding
- ‘Single blind’ - usually the patient is masked to the treatment allocated
- ‘Double blind’ - both the patient and their doctor* are masked to the allocated treatment
- or technician making the measurement
How do you determine how many subjects should be used in a trial?
Sample size calculation: must obtain statistical advice
Depends on four measures
- Size of expected effect
- Variability of the outcome measure
- ‘Power’ and ‘significance’
How do you calculate the absolute and relative risk reduction?
How do you calculate the ‘number needed to treat’ (NNT)?
Number of patients who would have to receive treatment of interest in order to prevent adverse event in one patient.
What is the intention to treat analysis? and what does it avoid?
- All individuals who were randomised should be included in the analysis
Avoids bias from drop outs, loss to follow-up and non-compliance
How do RCTs offer strong protections against bias (internal validity)?
Trials offer strong protections against bias:
- Random allocation
- Blinding
- Intention to treat analysis
- Pre-specified protocol to guide analysis and reporting
What is external validity?
- It is essentially generalisability
- Are the subjects typical of patients usually seen
- Is the treatment typical of treatment delivered in most practices
- Pragmatic and explanatory trials
what are 3 trial types
- multi arms trials
- cross over trial
- adaptive trial
what is a mutli arm trial and why is it used?
multi-arm trials have 3 or more groups
ie: control, experimental treatment 1 and experimental treatment 2 groups
multi arm trials are more efficient
what is a cross over trial
patients randomised to intervention/control and then after a wash-out period, they swap groups
What the trial protocol?
The protocol is a document that describes exactly how a clinical trial will be conducted
what does a trial protocol specify in advance
- the objectives
- study design,
- methodology,
- statistical considerations and
- organization of a clinical trial
what is trial protocol supplemented by?
Supplemented by a statistical analysis plan (SAP)
what is a case report form?
- collect patient data, usually electronic, has info for the specific
measures.- standard CRF preserves study data and maintains quality (reliable, valid, few missing values) and integrity
What is a Clinical Trials Unit (CTU)?
specialist units which have been set up with a specific remit to design, conduct, analyse and publish clinical trials
How can we be confident with the reporting of trials?
The CONSORT Statement
- 25 item checklist
- offers a standard way for authors to prepare reports of trial findings
- facilitates complete and transparent reporting
- reduces the influence of bias on their results
- aids critical appraisal and interpretation.
What is the risk of bias assessment tool (RoB 2 tool)?
Five domains:
- Bias arising from the randomisation process
- Bias due to deviations from intended interventions
- Bias due to missing outcome data
- Bias in measurement of the outcome
- Bias in selection of the reported result
