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Disc laimer: The contents of this presentation are the views of the author and do not necessarily represent an offic ial position of the European C ommission. © European Union, 2013
Study design
Theodora Mouratidou
Public Health Policy Support Unit
Institute for Health and Consumer Protection
(JRC-IHCP)
2 GRADE Workshop – Ispra– 11-12 December 2013
GRADE Workshop: Agenda
9:00 - 10:15 Introduction. Guideline development process and the GRADE approach
10:15-11:00 Types of questions. Framing a question: PICO question. Exercise
11:00-11:15 Coffee
11:15-12:00 Choosing outcomes. Relative importance of outcomes. Exercise
12:00-12:45 Study designs. Exercise
12:45-13:30 Lunch
13:30-14:30 Search of the literature. Exercise
14:30-15:00 Determinants of quality of evidence: What can lower the evidence? (I)
15:00-15:15 Coffee
15:15-17:00 Determinants of quality of evidence: What can lower the evidence? (II) Exercise
9:00-11:15 Determinants of quality of evidence: What can lower the evidence? (III)Determinants of quality of evidence: What can upgrade evidence?
11:15-11:30 Coffee
11:30-13:00 Going from the evidence to the recommendation. Exercise
13:00-13:45 Lunch
13:45-16:00 Using the Guideline Development Tool (GDT) software. ExerciseFeedback and conclusions
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a. Introduction to study design
a. Experimental design
b. Observational design
c. Levels of evidence
d. Group exercise
Outline
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Linking exposure and outcome
• What is the exposure and who are the exposed?
• Which are the potential confounders?
• What are the potential health effects?
• What approach to take to study the relationship between exposure and
effect?
Are exposure and outcome linked?
Exposure OutcomeConfounder
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• Define the hypothesis to be tested by including a precise definition of the
exposure and outcome under study
• Decide which study design will be the most appropriate to test that
specific study hypothesis
• Study design is the procedure under which a study is been carried out:
• experimental (intervention) studies split into clinical
(subjects have already developed the disease) and field
(individual and aggregated level of subjects who are
disease-free) trials
• observational studies include cohort and case-control
studies amongst others
Study design
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Figure 2. Algorithm for classification of types of clinical research
Taken from Grimes and Shulz, Lancet 2002;359:57-61
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• Experimental studies; we actively attempt to change something to see
what effect this has on disease occurrence. We control who is exposed
and who is not, who is allocated to a new treatment regime and who is
not etc.
• We do intervene
• Observational studies; we measure the occurrence of a disease or other
health outcomes or compare patterns or exposure and disease to identify
particular exposures or risk factors associated with the disease
• We do not intervene in any way
• A number of questions, aside the question the study want to address,
should be answered before making a choice such as
• Experimental unit
• Measures of clinical benefit and/or risk
• Availability of a comparator
• Ethics
Classification of types of clinical research
Grimes and Shulz, Lancet 2002;359:57-61
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• Characterized by the fact that the study subjects are allocated by the
investigator to the different study groups through the use of
randomization
Randomised controlled trials (RCTs)
http://www.iarc.fr/en/publications/pdfs-online/epi/cancerepi/CancerEpi.pdf
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• Quasi-experimental study designs, sometimes called non-randomized,
pre-post-intervention study designs
• Aim:
• to evaluate interventions but that do not use
randomization
• to demonstrate causality between an intervention and an
outcome
• Frequently used when it is not logistically feasible or not ethical to
conduct an RCTs
• interventions often cannot be randomized to individual
patients or locations
• the clinical and ethical necessity of intervening quickly
makes it difficult or impossible to undertake the lengthy
process of implementing a randomized study
Non-randomised controlled trials
Eliopoulos G M et al. Clin Infect Dis. 2004;38:1586-1591
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Hierarchy of the 8 quasi-experimental study designs
Eliopoulos G M et al. Clin Infect Dis. 2004;38:1586-1591© 2004 by the Infectious Diseases Society of America
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Figure 3. Schematic diagram showing temporal direction of three observational research designs
Taken from Grimes and Shulz, Lancet 2002;359:57-61
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Cohort studies
http://www.iarc.fr/en/publications/pdfs-online/epi/cancerepi/CancerEpi.pdf
• Starting point: selection of a study population, or cohort where
information is obtained to determine members exposed to the factor of
interest
• The entire population is then followed up over time. Disease incidence in
the exposed vs. not exposed individuals
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Case-control studies
http://www.iarc.fr/en/publications/pdfs-online/epi/cancerepi/CancerEpi.pdf
• Starting point is the identification of ‘cases’ of the disease and of suitable
‘controls’ without that disease
• Cases vs. controls to assess whether differences in their past exposure to
putative risk factors
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• Selection of study subjects
• cohort study: subjects are are initially free of disease and
are then followed over time
• case–control studies: subjects are selected on the basis
of the presence or absence of a disease
• Cohort studies: most closely resemble intervention studies
• Case–control studies: suitable for investigating rare diseases as a cohort
study would require the follow-up of a large number of individuals for a
long period (time to elapse between an exposure and the manifestation
of disease)
The major differences between cohort and case–control studies
http://www.iarc.fr/en/publications/pdfs-online/epi/cancerepi/CancerEpi.pdf
http://www.iarc.fr/en/publications/pdfs-online/epi/cancerepi/CancerEpi.pdf
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• Case–control studies: number of subjects necessary is much smaller
than the number required for cohort studies making them relative
inexpensive to carry out
• Results from case–control studies are more difficult to interpret but
danger of:
• selection bias
• exposure might be a consequence rather than a cause of
disease
Conti.
http://www.iarc.fr/en/publications/pdfs-online/epi/cancerepi/CancerEpi.pdf
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• A sample of individuals is selected from a defined population and
contacted at a particular point in time to obtain simultaneously
information on both the exposure(s) and outcome(s) of interest
• Must ensure that the sample of subjects who participate in the study is
representative of the whole population to whom the results will be
extrapolated
• Are generally used to estimate the prevalence of common conditions of
reasonably long duration
• Are relatively simple to conduct and short in duration because they do not
require follow-up
Cross-sectional studies
http://www.iarc.fr/en/publications/pdfs-online/epi/cancerepi/CancerEpi.pdf
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• As with case–control studies, it is not possible to know whether the
outcome followed the exposure in time or the exposure resulted from the
outcome
• This is because information on both exposure and outcome is collected at
the same single point in time e.g. H. pylori infection preceded or followed
chronic atrophic gastritis
• not a concern for exposures that do not change over time
such like gender, ethnicity or genetically determined traits
Cross-sectional studies-disadvantages
http://www.iarc.fr/en/publications/pdfs-online/epi/cancerepi/CancerEpi.pdf
22 GRADE Workshop – Ispra– 11-12 December 2013
23 GRADE Workshop – Ispra– 11-12 December 2013
Decisions, decisions, decisions….. Evidence about treatmentbenefits and harms! which box would you open first?
Jeremy Howick, Iain Chalmers, Paul Glasziou, Trish Greenhalgh, Carl Heneghan, Alessandro Liberati, Ivan Moschetti, Bob
Phillips, and Hazel Thornton. "The 2011 Oxford CEBM Evidence Levels of Evidence (Introductory Document)". Oxford Centrefor Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653
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• A hierarchy of the likely best evidence
'are rules of thumb that helps us make a decision in real environments
quickly and without resorting to pre-appraised sources and are often as
accurate as a more complicated decision process'
The 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence (1-5)
Jeremy Howick, Iain Chalmers, Paul Glasziou, Trish Greenhalgh, Carl Heneghan, Alessandro Liberati, Ivan Moschetti, Bob
Phillips, and Hazel Thornton. "Explanation of the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) Levels ofEvidence (Background Document)". Oxford Centre for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653
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• Grimes and Shulz, Lancet 2002;359:57-61
• http://www.iarc.fr/en/publications/pdfs-online/epi/cancerepi/CancerEpi.pdf
• Eliopoulos G M et al. Clin Infect Dis. 2004;38:1586-1591
• Jeremy Howick, Iain Chalmers, Paul Glasziou, Trish Greenhalgh, Carl Heneghan,
Alessandro Liberati, Ivan Moschetti, Bob Phillips, and Hazel Thornton. "The 2011Oxford CEBM Evidence Levels of Evidence (Introductory Document)". Oxford Centre
for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653
• Jeremy Howick, Iain Chalmers, Paul Glasziou, Trish Greenhalgh, Carl Heneghan,
Alessandro Liberati, Ivan Moschetti, Bob Phillips, and Hazel Thornton. "Explanationof the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence
(Background Document)". Oxford Centre for Evidence-Based Medicine.http://www.cebm.net/index.aspx?o=5653
• OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence".
Oxford Centre for Evidence-Based Medicine.
http://www.cebm.net/index.aspx?o=5653 * OCEBM Table of Evidence WorkingGroup = Jeremy Howick, Iain Chalmers (James Lind Library), Paul Glasziou, Trish
Greenhalgh, Carl Heneghan, Alessandro Liberati, Ivan Moschetti, Bob Phillips, HazelThornton, Olive Goddard and Mary Hodgkinson
List of references
Any questions
Next:Exercise
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JRC xxxxx – © European Union, 2013Disc laimer: The contents of this presentation are the views of the author and do not necessarily represent an offic ial position of the European C ommission.