Non-randomised studies
Methodologies for a new era summer school
School of Applied Social Studies, University
College Cork
22 June 2011
Dr Paul Montgomery
Jennifer Burton
Why bother?
The data from a good study can be analysed in
many ways, but no amount of clever analysis
can compensate for the problems with the
design of a study.
(Altman, 1991)
Introduction
It is sometimes impossible or undesirable to
influence events in a human sample


You may not be able to control group allocation
It may be unethical to expose or withhold an
intervention
An appreciation of the varieties of study
designs available can reduce the need
to reinvent the wheel and to rediscover
the mistakes of others. It can also help
to end the “scandal of research”’
(Altman, 1993)
Aims
Identify types of questions that can be answered
using non-randomised methods
Describe several non-randomised designs
Highlight the strengths and weaknesses of
common non-randomised designs
Question to design
Prevalence/ incidence
Risk and protective factors
Prognosis
Harm
Effectiveness
Nature,
prevalence of
social problem
Systematic
Reviews and
Meta-Analyses
Intervention
Trials:
Efficacy
Risk,
protective
factors
Intervention
Trials :
Effectiveness
Practice
Guidelines
Evidence Based Practice:
Judicious application of
research to individual
clients and organisations
The Hierarchy of Evidence
For Intervention Studies
Meta-Analysis of Randomised Trials
Randomised Trials
Internally
Valid
Evidence of
Effectiveness
Non-randomised studies
Cohort studies
Case-Control studies
Non-comparative studies
Illustrative examples,
hypothesis generating studies
Case Series (open trial)
Case reports
Expert opinion
Question to Design
In practice, methods tend to be
complementary in answering questions
Each method may be used to answer
several types of questions
Several studies may help tease apart a
question
Prevalence
How many people have mental health disorders?
Surveys
Census (one-time full population)

Ideal but expensive, difficult, likely to miss people
from marginal groups
Cross section (one-time sample)

Must consider many potential biases due to
geography, time, etc.
Cross-Sectional Survey
Identify a sample of adults
representative of the population
Measure symptoms of mental health
problems
Calculate the number of people above a
given threshold
Surveys
Usefully estimate prevalence or incidence and
associations
Comparisons may be made between different
subgroups to identify associations
Risk and Protection
Does smoking cause cancer?
Risk and Protection
What factors
can predict
falls in the
elderly?
Retrospective Cohort
Take all elderly people in Oxford
Look at



Characteristics of their homes
Individual factors (e.g. medication use)
Other predictors?
Look for association between these
factors and falls
Retrospective Cohort
Backward looking survey
Relatively inexpensive and practical
Good for detecting latent outcomes
Prone to several sources of bias (selection,
participant recall, etc.)
Risk and Protection
What are the factors that contribute to chronic
fatigue syndrome?
Prospective Cohort
Take all babies born in a given period in
1970
Survey them regularly
Look for correlations between variables
(e.g. maternal depression) and
outcomes (e.g. chronic fatigue)
Prospective Cohort
 Identifies temporal relationships
 Can examine multiple effects of exposure
 Loss-to-follow-up can be a problem
 Inefficient for the evaluation of rare problems
unless the attributable risk is high
 e.g. 1970 British Cohort Study (ongoing)
http://www.cls.ioe.ac.uk/
Risk and Protection
Is fish oil good for my mental health?
Ecological Studies
Compare countries’ consumption of
fish oil to their rates of depression
Increased consumption of fish oil
lowers a nation’s rate of depression
(Hibbeln 2001), but eating fish is not
the only difference among countries
Ecological Studies
Large unit of analysis (e.g. countries)
May identify population-level risk and protective
factors
Because the unit of observation is not the
individual subject, they are subject to the
ecological fallacy when they overlook important
sources of variance
Risk and Protection
Is running bad for my knees?
Case Control
Identify a group of runners
Then find a group of people who don’t
run matched for age, sex, weight and
other variables
Test for associations between knee
problems and being a runner
Case Control
Inexpensive and practical
Good for generating hypotheses
Lacks a temporal dimension
Unless data come from a population-based
survey, cannot give incidence and prevalence
data
Prognosis
My husband has just
taken 4 times the
recommended dose
of purple pills.
What’s going to
happen?
Case Report
An otherwise healthy 60 year old man was prescribed 10 mg of vardenafil
(Levitra, Bayer) for sexual dysfunction. Because this was ineffective,
he increased the dose to 40 mg. Three hours later, he had a tonicclonic seizure, seen by his relatives.
On admission to hospital, neurological examination, brain magnetic
resonance imaging, and electroencephalography after sleep
deprivation were normal. Stress electrocardiography,
echocardiography, and cardiac scan with dipyridamole test as well as
carotid doppler ultrasonography did not show concomitant cardiac
diseases. The man was told to stop using vardenafil.
Two months later he had a new tonic-clonic seizure, four hours after
taking 30 mg of vardenafil. At eight months' follow-up he is seizurefree without treatment.
Pasquale Striano, Federico Zara, Carlo Minetti (professor of paediatrics), Salvatore Striano
(2006). Epileptic seizures can follow high doses of oral vardenafil. BMJ;333:785.
Case Report
Inexpensive and quick
May draw attention to important clinical
and research issues
In rich detail, describes conditions and
outcomes
May not be representative, does not
usually provide evidence of causation
Case Series
Several case studies
Draws attention to patterns in client populations
Common in aetiological research
Break
Effectiveness
Does abstinence education reduce the
likelihood of premarital sex?
Pre-post (single group)
Take a class of kids
Ask them if they will have sex before marriage
They attend an abstinence-based education
programme
Ask them if they will have sex before marriage
Pre-post (single group)
Inexpensive, generally easier than controlled
studies
Provides some evidence of temporal
relationships
Usually lacks a plausible counterfactual (i.e.
what would have happened in the absence of
intervention)
Effectiveness
Does Head Start
improve IQ?
Between Group
Look at all the kids in New York born in
1980 who were eligible for Head Start
Compare those who attended to those
who did not attend
If possible, collect measures before and
after attendance
Between Group
Provides a counterfactual scenario,
can give evidence of temporal
relationships.
Groups may differ on both measured
and unmeasured variables, observed
differences may be attributable to
factors other than the intervention.
Effectiveness
Does having regular contact with a social
worker improve outcomes for fostered
children?
Historical Control
Compare children in foster care since
the 1944 education act to children in
foster care before then.
If possible, include measures before
and after enrolment for children in each
group.
Historical Control
Provides a counterfactual scenario
Groups may differ on both measured
and unmeasured variables, observed
differences may be attributable to
factors other than the intervention
Effectiveness
Do intensive
police
crackdowns
reduce gun
violence?
Time-Series
Identify areas with high levels of gun crime and
identify peak times
Repeatedly use crackdowns during periods of
high crime
Compare times with the intervention to periods
without the intervention
Time-Series
Provides a counterfactual scenario
Times may be different
Often requires complicated statistical
analyses to control for differences in
baseline variables, time trends, etc.
Conclusion
What is your question?
What types of study design might
contribute to an answer?
Think ‘Horses for Courses’
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Wed am non-randomised stud