Exposure Outcome Confounder - European Commission · Public Health Policy Support Unit Institute for Health and Consumer Protection (JRC-IHCP) 2 GRADE Workshop –Ispra–11-12 December

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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


a. Introduction to study design

a. Experimental design

b. Observational design

c. Levels of evidence

d. Group exercise

Outline


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


• 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


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


• 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

9 GRADE Workshop – Ispra– 11-12 December 2013 10 GRADE Workshop – Ispra– 11-12 December 2013

• 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


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


Cohort studies


• 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


Case-control studies


• 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


• 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



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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.



• 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



• 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




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


• 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

.

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.

Documents

Exposure Outcome Confounder - European Commission · Public Health Policy Support Unit Institute for Health and Consumer Protection (JRC-IHCP) 2 GRADE Workshop –Ispra–11-12 December