Research project design

international collaborative epidemiological studies

Conference on Global Health and Vaccination Research

Tromsø, June 8th 2010

Elisabete Weiderpass
Cancer Registry of Norway
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I. Introduction
1. Epidemiology & epidemiological studies
2. Types of study design
II. Experimental (interventional) studies
1. General characteristics of experimental studies
2. Types of experimental studies
III. Observational studies
1. General characteristics of observational studies
2. Types of observational studies
IV. International collaborative epidemiological studies
1. Reasonable of collaborative research
2. Types of studies mostly used in international collaborative
research
3. Examples
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Overview of study designs

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Epidemiology & epidemiological studies

• Epidemiology is concerned with events that occur

in groups of people, not separate individuals

• Epidemiological studies are concerned not only

with people who get a disease, but with
those who do not, and in particular how these
two groups may differ
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What is interesting for an epidemiologist

to measure?

• Occurrence of disease or other health related events

Incidence, prevalence and clearance of HPV infection

among young girls in Kampala (Uganda)

• Whether an exposure is associated with particular disease

Does HPV infection cause squamous cell carcinoma of the

conjunctiva
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How to approaches?

Decide which
Draft the idea Define the study design
& define the exposures & will be most
study hypothesis outcomes of appropriate
the study to test the
hypothesis
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Types of study design

• Experimental approach
▫ Clinical trials, field trials

▫ Example: vaccination trials for HPV in

Norway

• Observational studies
▫ Observation of occurrence of disease in
people
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Types, overview of study design, randomization

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Experimental studies: characteristics

Experimental studies = interventional studies

• Study subjects are allocated to the different study

groups through the use of randomization

• Randomization ensures that the assignment of subjects

to various groups is determined by chance alone, and is
not subjectively influenced by the investigators or the
participants
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Outline of an intervention trial

Outcome
Intervention group
No outcome

Study population allocation implemented by the investigator

Outcome
Control group
No outcome

Direction of inquiry
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Types of experimental studies:

Clinical trials; objectives

▫ To evaluate new forms of treatment of a disease or

condition

▫ Carried out in hospitals or clinics among people who

have already developed the disease
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Types of experimental studies:

Field trials; objectives
▫ To evaluate whether an agent or procedure reduces the
risk of developing disease among those free from the
condition at enrolment

▫ Deal with subjects who are disease-free

▫ Have to be conducted in the field than in hospitals or

clinics
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Types confounding & overview of study design

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Observational studies: characteristics

• Observation of occurrence of disease in people who are
already segregated into groups

• The role of investigator is to observe what happens, noting

who is exposed or unexposed and who has or has not
developed the outcome of interest

• Confounders and unmeasurable factors make it difficult to

establish the exactly role of an exposure factor; i.e. studying
occupational exposure, people may differ not only in
exposure to occupational hazards but also in other lifestyle
factors such as socioeconomic background, health status,
smoking and alcohol habits. These are confounders.
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Types of observational studies:

Cohort studies
• Selection of a study population (cohort)

• Determination of which cohort members are exposed to

the factor of interest (or different degrees of exposure).
Allocation of subjects to the exposure is not controlled
by the investigator

• Follow-up over time of entire population

• Incidence of disease in the exposed individuals is

compared with the incidence in those not exposed
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Outline of a cohort study

Outcome
Exposed group
No outcome
Study population

allocation is not implemented by the investigator

“cohort”

Outcome
Unexposed group
No outcome

Direction of inquiry
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Types of observational studies:

Case-control studies
• Identification of cases of the disease or condition of
interest and suitable controls without this disease or
condition

• Comparison of cases and controls to assess whether there

were any differences in their past exposure to putative
risk factors

• This design is suitable for investigating rare diseases such

as cancer
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Outline of a case-control study

Exposed
Cases

Unexposed Study population

Exposed

Controls

Unexposed

Direction of inquiry
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Cross-sectional studies
• A sample of individuals is selected from a previously
defined population and contacted at a particular point in
time to obtain simultaneously information on both the
exposure and outcome of interest

• For this design it is crucial to ensure that the sample of

subjects is representative of whole population to whom
the results will be extrapolated. To avoid selection bias:
use of random sampling methods is appropriate
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Routine-data-based studies
(ecological studies)

• Data on exposure and outcome of interest for this type of study

are obtained from routine data-collection-systems without
contacting any of the study subjects

• Can be carried out at an individual or at an aggregated level

• Major limitation is that few variables are usually available

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Purposes, planning, design, performing, advantages &

disadvantages
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International collaborations are strategic

instruments to:
• Strengthen research quality, relevance and significance

• Make use of knowledge and technology developed

abroad

• Researchers developing resulting in being attractive to

leading research communities

• Attract international research funds

• Contribute to knowledge and capacity development in

developing countries
Source: The Research Council of Norway
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Norway’s and the other Nordic countries

basic research characteristics
Research sources Population
• Norway and the Nordic • Norway and Nordic countries
countries have the best data characterises homogeny
available population
• Many high quality registry and • We have the least inhabited
hospital records region of all European
• Unique personal identification countries
number making possible to
compare data from different
sources
• Provide high quality research
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Why to strengthen the research quality?

• To extend the number of cases and controls or

exposed/non-exposed population

• To bring new scientists or students to the group

• To have better chance to receive funds

• To develop knowledge that can be applicable

everywhere in the Europe or in the World
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Study plan
Initial feasibility
studies

Planning process
(concept phase) Entire study

Small scale
pilot investigations
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Up to date knowledge To be familiar with the The ethics need to be

about the disease and experts and their research evaluated during the entire
Idea specific conditions in
the country
on the specific topic in that
country and in the World
planning phase

Hypothesis
Study design

Aims/Objectives

To identify collaborators

To identify funding body

Ethics considerations

Conducting a pilot project

Writing a protocol

Preparing Grant Application

Conducting the study

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Study hypothesis

• What are the main and secondary hypotheses ?

• What are the expected exposures and outcomes
of interest ?
• What is the magnitude of the anticipated
effect(s) ?
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Objectives
• What is known about the topic
• Need of the proposed study; originality and
potential significance of its findings
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Study population and methods of

recruitment

• Geographical location and the demographic

characteristics of the study population
• How the study subjects will be recruited
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Ethical considerations

• Impinge on many aspects of the design and

conduct of intervention studies

• The submission for ethics committee review

must make clear that the ethical implications of
all aspects of the study have been given full
consideration by the investigators
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Study design
Depends on:
• What is the aim of the study
• Where the study will be conducted
• What kind of investigations is proposed
• Who is going to be included
• For how long the study will vary
• Are the sources available
• Approves the ethical committee such designed study?
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The common study types in collaborative

epidemiological research

• Controlled randomised trials

• Collaborative cohort studies

• Consortium:

▫ Meta-analysis of trials, cohort or case-control studies

▫ Pooled analysis of trials, cohort or case-control studies

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Randomised trials
NordICC: The Northern-European Initiative on Colorectal Cancer

To investigate the effect of colonoscopy on CRC incidence and

mortality

Countries: Nordic countries + Poland & the Netherlands

Participants: 66 000 individuals, both sexes, age
Arms: intervention- colonoscopy/ controls- no intervention (1:2)
Follow-up: 15 years

Challenges:
- To obtain ethical considerations in all countries for this kind of study
- To achieve the appropriate number of interventions
- To follow the same procedures for colorectal screening in all centers
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Collaborative cohort studies

Women’s Lifestyle and Health cohort parallel study in Sweden & Norway

orway weden

 
o study the relationship o study the relationship
between internal and between lifestyle factors*
external hormones and and cancer,
female cancer with focus cardiovascular diseases
on breast cancer and chronic diseases in
young women
*OC, HRT, dietary habits, ect.
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The joined study

Women’s Lifestyle and Health study (WLH)

 Participants: Overall 104 000 women

- 47 000 women from the Swedish WLH cohort and
- 57 000 women from the Norwegian NOWAC cohort

 Age of participants: born 1943-1962, 30-49 years;

 Enrolment: 1991/1992

 Challenges: To obtain ethical consent

To collect comparable data
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Consortional studies
• Association of two or more projects/studies on the
same outcomes
• Often cohort and case-control studies
• Designed mainly to study rare diseases
• Methods: pooled analysis or meta-analysis

• Advantages: enlarged power of the study

• Disadvantages:
▫ Many different variables: need to be strict with
inclusion of variables; they should be comparable
▫ Outcomes (disease codes) should be checked and exact
in all projects
▫ Complicated administration if many projects included
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Pooled & meta-analysis

• Pooled analysis is a method frequently used in
epidemiology when individual studies are too
small to allow any definite conclusion, then all
basic data are combined and analysed

• Meta-analysis combines the results of several

studies that address a set of related research
hypotheses. This is normally done by
identification of a common measure of effect
size, which is modeled using a form of meta-
regression
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Consortional study at NCI I

Study on breast cancer in males:
to identify risk factors of the disease

• Study requirements: cohort & case- control studies with at

least 20 incidental cases
• Sources of data:
- questionnaires ( about 24 variables)
- biological samples (hormonal and DNA analysis): 75-100
cases
• Participating studies: 12 case-controls (2060 cases), 8
cohorts (540 cases)
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Consortional study at NCI II

Study on breast cancer in males: example of pooled analysis

• Number of cases: 2 600

• cases/controls ratio: 1:2
• Statistical analysis (study specific):
▫ for non biologic data:
 case-control: logistic regression
 cohorts: Cox proportional hazards models
▫ for biologic risk factors:
 logistic regression
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What to expect from an international

collaboration?
Advantages Disadvantages
• Enlarged knowledge • Time-consuming
• Greater experience • Complicated
administration and
• Enlarged data
management
• Better technology
• Large author lists
• More funds
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Thank you