Week2 Flashcards
Why is the AAAA framework important
An essential professional and academic skill
Medical knowledge is continually evolving
The medical profession frequently fails to use effective treatments even when they are available
Keeping up to date is a lifelong commitment for every doctor
You need to develop and use the skills to find, appraise and act on research evidence
Steroids in acute head injury
Corticosteroids had been used to treat acute head injury for more than 30 years
MRC-CRASH randomised controlled trial aimed to solve remaining uncertainty of benefit
International trial n=20000 planned
Trial stopped early n=10000 evidence of harm
Mortality at 2 weeks
- 21.1% with steroids
-17.9% with placebo
Hundreds of thousands harmed (killed) internationally
Assess: what type of study design
Research question vs study design
Frequency of disease/ who is affected : ecological; cross-sectional
Aetiology & risk factors : case-control; cohort
Effectiveness (benefits& harms) : randomised controlled trial RCT
Assess: clinical components PICO
Population: those who are eligible for treatment with the intervention/comparator
Intervention: new treatment
Comparator: existing treatment/ usual care (may be no treatment)
Outcome: mortality/ morbidity/ physiological measure (BP)
Formulating PICO is important for: efficient searching for evidence in electronic bibliographic databases such as MEDLINE
Assessment of the applicability of research to your patients
Access: where to look for RCTs
The Cochrane library
Search bibliographic databases like medline, pubmed, embase
MEDLINE and embase have study design filters
Pubmed has a clinical queries facility
What does appraisal ask
Does the study address a research question which is relevant to my clinical problem
Did researchers use the study design most likely to provide a valid answer to the clinical question
(For effectiveness was it a RCT)
Was the study done well/ is the study trustworthy (were steps taken to reduce bias)
If the study was done well (valid) what were the results
( direction, size, precision, statistical significance of result)
Key features of the RCT that minimise bias
Random allocation of participants to intervention or comparator
Having a comparator
Why have a control or comparator group
Increases sample size
Gives patients a choice about which treatment they receive
Allows us to evaluate whether patients would get better anyway- the comparator treatment/ no treatment
Allocation concealment
Hides the allocation of trail participants from participants and those recruiting participants so that this knowledge cannot influence who actually receives which treatment. Minimises the chance of selection bias (allocation bias)
A computer generated random sequence should be performed distant to where the trial is being conducted
Where possible treatment allocation should be concealed until it’s administration (sealed envelopes, similar packaging etc)
Blinding is used to minimise measurement bias
Patients may have preconceived ideas about how effective a treatment is. This can influence their perception of subjectively measured outcomes such as pain, low mood or quality of life. The placebo effect
Patients may offer socially desirable responses if they know they’re in the intervention arm
Observers may have preconceived ideas about how effective a treatment is this can influence how they measure subjective outcomes
Placebo effect
‘ a beneficial effect produced by a placebo drug or treatment which cannot be attributed to the properties of the placebo itself and must therefore be due to the patients belief in that treatment’
Blinding used to minimise performance bias
Healthcare professionals may have preconceived ideas about how effective a treatment is. This can influence (consciously or subconsciously) how they deliver treatments and may lead to participants in either the intervention or comparator arm receiving ‘extra’
Study participants may be disappointed about which arm they are randomised to which may lead to them behaving differently for example not engaging with the treatment
Blinding can take place at several levels
Participants
Clinicians delivering treatment
Researchers measuring outcomes
Statisticians undertaking analysis
Single blind, double blind, triple blind
Follow up should be complete to minimise attrition bias
Patients may be lost to follow up at different points in a trial
Patients may be available for outcome measurement but are not adhering to the trial protocol (not taking/ receiving allocated treatment)
Intention to treat ITT minimises attrition bias from loss to follow up and deviation from trial protocol
Interpreting results
Direction of effect: do we want more or less of the outcome
Size of effect estimate
Precision of effect estimate
Statistical significance of effect estimate- is any difference between groups likely to be real or due to chance
Clinical significance of effect- if the difference is statistically significant is it large enough to be clinically important
