HANAN ABBAS ASSISTANT PROFESSOR

OF FAMILY MEDICINE

STUDY DESIGN

Study Design

Objectives By the end of this session candidates should be

able to: 1. Review the fundamental study designs 2. Discuss Studies -Uses -Strengths/weaknesses

Research Design

• Most problems in studies are due to poor design (not poor analysis)

• The research design is the master plan specifying the methods and procedures for collecting and analyzing the needed information.

Study Design

Experimental

• Randomized

controlled trials

• Quasi

Observational

Analytic • Cross sectional

• Case-control

• Cohort studies

Descriptive

• Case report

• Case series

• Survey

Analytical Studies

Observational

Experimental

Observational Studies

Cross-sectional

Case-control

Cohort

Epidemiologic Study Designs

Grimes & Schulz, 2002 (www)

Hierarchy of Epidemiologic Study Design

Tower & Spector, 2007 (www)

Case reports

It describes the medical history or adverse

treatment effect for a patient .

advantages : generating ideas, save time.

Not expensive.

Disadvantages; weak evidence.

Cross-sectional Study

Data collected at a single point in time

Describes associations

Prevalence

A “Snapshot”

Example of a Cross-Sectional Study

Association between garlic consumption

and CAD in the Family Practice Clinic

Cross-Sectional Study

Strengths

Quick

Cheap

Weaknesses

Cannot establish cause-effect

Observational Studies

Case-Control Study

Start with people who have disease

Match them with controls that do not

Look back and assess exposures * case-control

(retrospective ): Begins with outcome (cancer cases and healthy controls

CASE CONTROL STUDY

Risk factor absent

Risk factor present

Risk factor absent

Risk factor present

Taking into consideration the confounding variables e.g. age, sex, education, etc.

PRESENT PAST

Control

Case

Compare

Example of a Case-Control Study

Are those with CAD less likely to have

consumed garlic?

Advantages of Case-Control Studies

- Cheap, easy and quick studies

- Multiple exposures can be examined

- Rare diseases and diseases with long latency can be studied

- Suitable when randomization is unethical

(alcohol and pregnancy outcome)

Disadvantages of Case-Control Studies

- Case and control selection troublesome

- Subject to bias (selection, recall, misclassification)

- Direct incidence estimation is not possible

- Temporal relationship is not clear

- Multiple outcomes cannot be studied

- If the incidence of exposure is high, it is difficult to show the difference between cases and controls

- Not easy to estimate attributable fraction

- Reverse causation is a problem in interpretation - especially in molecular epidemiology studies

Case-Control Studies: Strengths

Good for rare outcomes: cancer

Can examine many exposures

Useful to generate hypothesis

Fast

Cheap

Provides Odds Ratio

Case-Control Studies: Weaknesses

Cannot measure

Incidence

Prevalence

Relative Risk

Can only study one outcome

High susceptibility to bias

Design pitfalls to look out for

Is the control group appropriate for the population?

Does the study use matching or pairing appropriately to avoid the effects of a confounding variable?

Does it use appropriate inclusion and exclusion criteria?

Real-life Examples

Smedby, K. E., Hjalgrim, H., Askling, J., Chang, E. T., Gregersen, H., & Porwit-MacDonald, A. et al. (2006). Autoimmune and chronic inflammatory disorders and risk of non-hodgkin lymphoma by subtype. Journal of the National Cancer Institute, 98(1), 51-60.

This study matched patients with non-Hodgkin lymphoma (NHL) with control subjects and compared their history of autoimmune and chronic inflammatory disorders, markers of severity, and treatment. It found that the risk of NHL was increased in association with rheumatoid arthritis, primary Sjögren syndrome, systemic lupus erythematosus, and celiac disease.T

Cohort Study

Begin with disease-free patients

Classify patients as exposed/unexposed

Record outcomes in both groups

Compare outcomes using relative risk

Example of a Cohort Study

To see the effects of garlic use on CAD

mortality in a population

cohort (prospective): Begins with an exposure (smokers and non-smokers)

Examples of Cohort Studies

* Framingham Heart Study (www)

* NHANES Studies (www)

* MACS (www)

* Physicians' Health Study (www)

* Nurses' Health Study (www)

* ALSPAC (www)

Advantages of Cohort Studies

- Can establish population-based incidence

- Accurate relative risk (risk ratio) estimation

- Can examine rare exposures (asbestos > lung cancer)

- Temporal relationship can be inferred (prospective design)

- Time-to-event analysis is possible

- Can be used where randomization is not possible

- Magnitude of a risk factor’s effect can be quantified

- Selection and information biases are decreased

- Multiple outcomes can be studied

(smoking > lung cancer, COPD, larynx cancer)

Disadvantages of Cohort Studies

- Lengthy and expensive

- May require very large samples

- Not suitable for rare diseases

- Not suitable for diseases with long-latency

- Unexpected environmental changes may influence the association

- Non-response, migration and loss-to-follow-up biases

- Sampling, ascertainment and observer biases are still possible

Cohort Study: Strengths

Provides incidence data

Establishes time sequence for causality

Eliminates recall bias

Allows for accurate measurement of exposure

variables

Cohort Study: Strengths

Can measure multiple outcomes

Can adjust for confounding variables

Can calculate relative risk

Cohort Study: Weaknesses

Expensive

Time consuming

Cannot study rare outcomes

Confounding variables

Cohort Study: Weaknesses

Exposure may change over time

Disease may have a long pre-clinical phase

Attrition of study population

Design pitfalls to look out for

Design pitfalls to look out for

The cohorts need to be chosen from separate, but similar, populations.

How many differences are there between the control cohort and the experiment cohort?

Will those differences cloud the study outcomes?

Fictitious Example

A cohort study was designed to assess the impact of sun exposure on skin damage in beach volleyball players.

Comparisons of skin damage were then made based on the use of sunscreen.

The analysis showed a significant difference between the cohorts in terms of the skin damage.

Real-life Example

Ramchand, R., Ialongo, N. S., & Chilcoat, H. D.

(2007). The effect of working for pay on adolescent tobacco use. American Journal of Public Health, 97(11), 2056-2062.

This study uses data collected from high school students from Baltimore, Maryland, and studies the differences in initiation of tobacco use between a cohort of adolescents that started working for pay and a cohort of adolescents that did not work. The results suggest that adolescents who work for pay have a higher risk of initiating tobacco use.

Lindenauer, P. K., Rothberg, M. B., Pekow, P. S., Kenwood, C., Benjamin, E. M., & Auerbach, A. D. (2007). Outcomes of care by hospitalists, general internists, and family physicians. New England Journal of Medicine, 357(25), 2589-2600.

To study effects of hospitalists, general internists, and family physicians on patient care, patients that were hospitalized with certain conditions under the care of hospitalists, general internists, and family physicians were separated into three cohorts. The results showed that patients cared for by hospitalists had shorter hospital stays and lower costs than those cared for by general internists or family physicians.

INTERVENTION STUDIES

Experimental Studies

Clinical trials provide the “gold standard” of

determining the relationship between garlic

and cardiovascular disease prevention.

Characteristics of the Experimental

Study a- Intervention

b- Control

c- Randomization to eliminate the confounding variables

d- blindness.

Clinical Trials

Randomized

Double-blind

Placebo-controlled

Clinical Trials

Strengths:

Best measure of causal relationship

Best design for controlling bias

Can measure multiple outcomes

Weaknesses:

High cost

Ethical issues may be a problem

Compliance

time Study begins here (baseline point)

Study population

Intervention

Control

outcome

no outcome

outcome

no outcome

baseline

future

RANDOMIZATION

Types of trials

Blinded Not blinded

Randomised Not randomised

Controlled Not controlled

Trial

Double-blind design • Neither patient nor outcome evaluator knows Rx to which patient was assigned • Single-blind • Patient or evaluator is blinded as to Rx, but not both • Triple-blind • Patient, Physician, and Data analyst are blinded as to Rx identity

Design pitfalls to look out for

An RCT should be a study of one population only.

Was the randomization actually “random,” or are there really two populations being studied?

The variables being studied should be the only variables between the experimental group and the control group.

Real-life Examples

Ensrud, K. E., Stock, J. L., Barrett-Connor, E.,

Grady, D., Mosca, L., Khaw, K., et al. (2008). Effects of raloxifene on fracture risk in postmenopausal women: The raloxifene use for the heart trial. Journal of Bone and Mineral Research, 23(1), 112-120.

This research studied the effect of raloxifene on fracture risk in postmenopausal women, and found that the women who took raloxifene over the same five year period of time as the women who did not reduced their risk of clinical vertebrate fracture.

Krishna, S., Balas, E. A., Francisco, B. D., & König, P. (2006). Effective and sustainable multimedia education for children with asthma: A randomized controlled trial. Children's Health Care, 35(1), 75-90.

This article reports on the effect of multimedia education for children with asthma. A control group of pediatric patients with asthma was given standard asthma educational resources, while the experimental group of pediatric patients with asthma was given standard resources plus multimedia resources. The study found a reduction in daily symptoms, in emergency room visits, in school days missed, and in days of limited activity in the group given multimedia education resources.

Secondary studies

1-systematic reviews; which uses an explicit and reproducible method to review primary studies.

1-meta-analysis; which is a mathematical synthesis of the result of two or more primary studies.

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Meta-Analyses

Systematic objective way to combine data from many studies

Pooled estimate of treatment effectiveness

Statistical significance

Publication bias

Theoretical framework

Misleading results

All Rights Reserved @ 2009 Deryck Pattron, Ph.D. 47

Systematic Reviews

Comprehensive survey

All relevant studies of highest level of evidence

Rigorous analysis

Systematic review

Summary points;

Many papers published in medical journals have potentially serious methodological flaws.

When deciding whether a paper is valid and relevant ,first establish what specific question it address.

Question about therapy should be addressed by clinical trials.

Summary points;

Questions about prognosis require cohort study.

Diagnosis: demonstrating whether a new diagnostic test is valid and reliable. preferred study is cross sectional survey.

Conclusion (1)

Case-series is a coherent set of cases of a disease (or similar problem).

Cases are compared with reference group, we have a case control study

In a population studied at a specific time and place (a cross-section) the primary output is prevalence data, though association between risk factors and disease can be generated.

In cross-sectional studies, we are looking for both exposure and outcome

In case-control studies, we know the outcome, looking for the exposure

In cohort studies, we know the outcome, following up looking for the outcome in question

Conclusion (2)

If the population in a cross-sectional survey is followed up to measure health outcomes, this study design is a cohort study.

If the population of such a study are, at baseline, divided into two groups, and the investigators impose a health intervention upon one of the groups the design is that of a trial.

Studies based on aggregated data are commonly referred to as ecological studies.

RCTs represent the “gold standard” of research designs. They thus provide the most convincing evidence of relationship between exposure and effect..

SCENARIO 1

What are the risk factors for the development of sarcoidosis?

SCENARIO 2

What are the long-term effects of the daily use of topical minoxidil?

Scenario 3

Is there a difference between pediatricians and family

physicians in the practice of neonatal circumcision?

Scenario 4

Does cigarette smoking cause lung cancer?

THANKS FOR YOUR KIND ATTENTION AND LISTENING