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Study Design Objectives By the end of this session candidates should be able to: ď †1. Review the fundamental study designs ď † 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


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


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


PRESENT Risk factor present

Case Risk factor absent

Compare Risk factor present

Control Risk factor absent

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

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:


 Provides incidence data  Establishes time sequence for causality  Eliminates recall bias  Allows for accurate measurement of exposure


Cohort Study:


 Can measure multiple outcomes  Can adjust for confounding variables  Can calculate relative risk

Cohort Study:


 Expensive  Time consuming  Cannot study rare outcomes  Confounding variables

Cohort Study:


 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), 25892600.  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.


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



Intervention no outcome Study population outcome Control no outcome baseline future


Study begins here (baseline point)

Types of trials Trial




Not controlled

Not randomised

Not blinded

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.

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.


Systematic Reviews  Comprehensive survey  All relevant studies of highest level of

evidence  Rigorous analysis  Systematic review

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


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..


What are the risk factors for the development of sarcoidosis?


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?


final study design (2)