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STUDY DESIGNS – WHICH ONE IS BEST?
David Nunan, PhDResearch Fellow and Tutor
Nuffield Department of Primary Care Health Sciences and
Oxford Centre for Evidence Based Medicine
University of Oxford
Exercise
• What is the best study design?
• Why?
• Compare with your neighbour
Does thalidomide cause phocomelia?
You should be happy if when you leave today, you understand…
• Observational studies• Descriptive studies
• Case studies, case series
• Analytic studies
• Cohort, case-control, cross-sectional
• Experimental studies (randomised trials)
• Qualitative studies
Basic
principles of
study design
THE LANCET 2002;359:57- 61
Bias in study design
Randomised controlled trials
Cohort studies
Case-control studies
Cross-sectional studies
Clinical observation (case
reports, case-series)
Least biased
Most biased
Experimental
Observational
Practicing EBM – the 4 A’s
Ask a
clinical
question
Acquire
the best
evidence
Appraise
the
evidence
Apply
the
evidence
Step 1
Step 2
Step 4
Step 3
Clinical questions:
Interventions
Aetiology and risk factors
Diagnosis
Prognosis
Frequency and rate
What study designs should you be looking for?
Question Question type Best study design
What should I do about
this condition or
problem?
INTERVENTION RANDOMISED
CONTROLLED TRIAL
(RCT) > cohort
What causes the
problem?
AETIOLOGY AND RISK
FACTORS
RCT (?) > cohort > case
control
Does this person have
the condition or problem?
DIAGNOSIS CROSS-SECTIONAL
(random or consecutive
sample)
What will happen with
this problem?
PROGNOSIS AND
PREDICTION
COHORT (survival) >
case control > case
series
How common is the
problem?
FREQUENCY AND
RATE
CROSS SECTIONAL
(prevalence)
COHORT (incidence)
CASE REPORT/SERIES
Case reports
Conclusions – case reports/seriesAdvantages• Can help identify new trends or diseases• Can have significant influence on subsequent literature and
possibly on clinical practice• Often, report rare conditions for which trials may not be feasible.
Disadvantages• Generally short term• Investigator selection bias• Generally no controls
Design pitfalls to look out for• Patient(s) should be described in detail• Carefully reported, unbiased observations• Explore and infer, not confirm, deduce or prove
Overview
• Observational studies
• Descriptive studies• Case studies, case series
• Analytic studies• Cohort, case-control, cross-sectional
• Experimental studies (randomized trials)
• Qualitative studies
Analytical Studies
What is the study design?
Analytical Studies
Lowest = furthest from base station
Highest = nearest to base station
Is there a better study design to answer the question –
Mobile phone masts and childhood cancer?
Advantages• Good for studying rare conditions or diseases• Useful as initial studies to establish association• Can answer questions that can’t be answered by other designs
Disadvantages• Retrospective studies have more problems with data quality
(recall bias)• Limited to examining one outcome• Not good for study of rare exposures• It can be difficult to find a suitable control group
Design pitfalls to look out for• Confounding – exposure and outcome related to third variable
Conclusions – case control studies
What is the study design?
Analytical Studies
Bias in cross-sectional studies
Risk of ASthma in Poultry breeders
The RASP study – a cross sectional survey
How might risk be underestimated?
Bias in cross-sectional studies
Peptic Ulcers and milK ingEstion
The PUKE study – a cross sectional
study
R² = 0,9713
0
1
2
3
4
5
6
7
8
9
0 2 4 6 8
# o
f p
ep
tic
ulc
er
ca
se
s (
we
ek
ly)
Milk consumption (litres/day)Does milk cause peptic
ulcers?
Advantages• Good for assessing prevalence/burden of disease• Quick and easy to conduct (no follow-up)• Multiple outcomes and exposures can be studied• Useful to identify hypothesis/relationships that can be followed
up in experimental studies
Disadvantages• Cannot measure change in variables over time• Inappropriate for demonstrating causal relationships• Not suitable for rare diseases or disease of short duration• Non-responder bias (surveys)
Conclusions – cross sectional studies
Analytical Studies
• Prospective or retrospective
• Controlled
• Can determine causes and incidence of diseases as well as identify risk factors
• Generally expensive and difficult to carry out (prospective)
• Cheaper and quicker = retrospective
Cohort studies
Cohort Design - Prospective
Time
Study begins here
Study
population
free of
disease
Exposure
present
Exposure
absent
Disease/outcome
No disease/outcome
Disease/outcome
No disease/outcome
present
future
Cohort Design - Retrospective
Time
Study begins here
Study
population
free of
disease
Exposure
present
Exposure
absent
Disease/outcome
No disease/outcome
Disease/outcome
No disease/outcome
present
future
• 2748 men and women, 50 – 79 years• HDL-C measured at baseline• Followed for 12 years• Death from all causes, CHD, and CVD• No loss to follow-up
• Low levels of HDL-C associated with increase mortality
• Risk of death from all-causes 2x higher in low HDL-C versus high HDL-C
• Risk of death from CVD and CHD 4x higher in low versus high HDL-C
Advantages• Subjects in cohorts can be matched, which limits the influence of
confounding• Standardisation of criteria/outcome is possible• Easier and cheaper than a RCT
Disadvantages• Cohorts can be difficult to identify due to confounding variables• No randomisation, which means that imbalances in patient
characteristics could exist• Blinding/masking difficult• Can take long time for outcome of interest to occur
Conclusions – cohort studies
Confounding
• Other patient features/causal factors, apart from the one being measured, that can affect the outcome of the study e.g..
Why random allocation?
Odds ratios were exaggerated by 41% for inadequately concealed
trials and by 30% for unclearly concealed trials (adjusted for other
aspects of quality).
Non-randomised controlled trials: • Can detect associations between an intervention and an
outcome
• But, they cannot rule out the possibility that the association was caused by a third factor linked to both intervention and outcome.
• Failure to conceal random allocation exaggerates estimates of treatment effects
Time
Study begins here
Study
population
free of
disease
Exposure
present
Exposure
absent
Disease/outcome
No disease/outcome
Disease/outcome
No disease/outcome
present
future
RANDOMISATION
Difference between randomized trials and non-randomized studies
Randomized trials
• Random (and hopefully concealed) procedure decides which participants go in which arm. (Rules out allocation bias)
• Placebo controls and double blinding possible.
Non-randomized/Cohort studies
• Participants ‘self-select’ or are selected to receive an intervention/exposure
• Placebo controls and double blinding not possible.
What study design(s) would you choose?
1. What is the importance of patient preferences in the choice of treatment for benign prostatic hyperplasia? (1 min)
2. How will you identify and describe misunderstandings between patients and doctors associated with prescribing decisions in general practice? (1 min)
3. How can you explore how men and women with cancer talk about using the internet? (1 min)
Overview
• Observational studies• Descriptive studies
• Case studies, case series
• Analytic studies
• Cohort, case-control, cross-sectional
• Experimental studies (randomized trials)
• Qualitative studies
What is qualitative research?
• Study of “things” (phenomena) in their natural settings
• Make sense of, or interpret, phenomena in terms of meanings people bring to them
• Aim to get a “deeper significance” of what study participants ascribe to the research topic
• Interpretive, naturalistic approach
• Priority is how participant(s) “experiences” contribute to the research question
What are some qualitative research methods?
• Participant observation – data on naturally occurring behaviours in their usual contexts
• Focus groups – effective in eliciting data on cultural norms of a group and generating broad overviews of issues in groups
• In-depth interviews – optimal for collecting data on individuals’ personal histories, perspectives, and experiences
You should be happy if when you leave today, you understand…
• Observational studies• Descriptive studies
• Case studies, case series
• Analytic studies
• Cohort, case-control, cross-sectional
• Experimental studies (randomised trials)
• Qualitative studies
