Study Designs for HealthStudy Designs for HealthProfessionalsProfessionals

Ashry Gad Mohamed, Ashry Gad Mohamed, MB.ChB, MPH, DrPHMB.ChB, MPH, DrPH

Professor of EpidemiologyProfessor of EpidemiologyCollege of Medicine & KKUHCollege of Medicine & KKUH

ObjectivesObjectives

At the end of the presentation each participant should be able to:

1-know main designs for biomedical researches.

2-Select the proper design for each research question.

3-list areas of strength and weakness of each design.

4-interpret the parameters of expression of study results.

Descriptive Analytical

Case report

Case series

Cross section

Ecological

Case control

Cohort

Observational Experimental

Study Designs

Animal Experiment

HumanInterventionClinical trial

Case ReportCase Report

• Detailed presentation of a single case Generally report a new or unique finding

• Previous unknown disease

• Unexpected link between diseases

• Unexpected new therapeutic effect

• Adverse events

Case SeriesCase Series• Experience of a group of patients with a

similar diagnosis• Cases may be identified from a single

or multiple sources• Generally report on new/unique

condition• May be only realistic design for rare

disorders

Case SeriesCase Series

• Advantages• Useful for hypothesis generation• Informative for very rare diseases with few

established risk factors

• Disadvantages• Cannot study cause and effect

relationships• Cannot assess disease frequency

Cross-sectional StudyCross-sectional Study

• Data collected at a single point in time

• Describes associations

• Prevalence

Cross-sectional StudiesCross-sectional Studies

• Frequent conditions with long duration of expression (nonfatal, chronic conditions)

• It measures prevalence, not incidence of disease

• Not suitable for studying rare or highly fatal diseases or a disease with short duration of expression

Prevalence vs. IncidencePrevalence vs. Incidence

• Prevalence

– The total number of cases at a point in time

– Includes both new and old cases

• Incidence– The number of new cases over time

Cross-sectional StudyCross-sectional Study

Sample of Population

Physically active life style

Sedentary life

style

Prevalence of IHD

Prevalence of IHD

Time Frame = Present

Cross-sectional studiesCross-sectional studies• Disadvantages

• Weakest observational design, (it measures prevalence, not incidence of disease).

• The temporal sequence of exposure and effect may be difficult or impossible to determine

• Usually don’t know when disease occurred• Rare events a problem. Quickly emerging

diseases a problem

Case-Control StudyCase-Control Study

Patients with CAD

Patients w/o CAD

PresentPast

High fish Diet

High fish Diet

Low fish Diet

Low fish Diet

Cases

Controls

Case-Control Studies: Case-Control Studies: StrengthsStrengths

• Good for rare outcomes: cancer

• Can examine many exposures

• Useful to generate hypothesis

• Fast

• Cheap

Case-Control Studies: Case-Control Studies: WeaknessesWeaknesses

• Cannot measure– Incidence

– Prevalence

– Relative Risk

• Can only study one outcome

• High susceptibility to bias

Analysis of case control studyAnalysis of case control study

• Because population at risk is absent we can not calculate relative risk as it is based on incidence, however it can be estimated by means of odds ratio (OR) which is the ratio of odds of exposure among diseased to the odds of exposure among controls.

Exposure for each case and controlExposure for each case and control

Disease status

Cases Controls

Exposure Yes

NO

A B

C D

A+C B+D

• Calculating Odds (number exposed number unexposed)

Odds (Cases) = A/C

Odds (controls) = B/D

Odds Ratio = (A/C) / (B/D) = AD/BC

Disease Status

CHD

(Cases)

No CHD

(Controls)

88 224

112 176

200 400

Fish diet

No fish

Total

Odds Ratio=

AD

BC

= 176 X 88

112 X 224

= 0.62

Example

Cohort StudyCohort Study

• Begin with disease-free patients

• Classify patients as exposed/unexposed

• Record outcomes in both groups

• Compare outcomes using relative risk

Cohort Study: StrengthsCohort Study: Strengths

• Provides incidence data

• Establishes time sequence for causality

• Eliminates recall bias

• Allows for accurate measurement of exposure variables

Cohort Study: WeaknessesCohort Study: Weaknesses

• Exposure may change over time

• Disease may have a long pre-clinical

phase

• Attrition of study population

Measuring the effect of risk factorMeasuring the effect of risk factor

Relative RiskRelative Risk = (a/a+b) / (c/c+d) = (a/a+b) / (c/c+d)

Risk factor

Outcome Total

present absent

Present a b a +b

Absent c d c +d

Total a +c b+d N

Obesity & DiabetesObesity & Diabetes

Obesity Diabetes Total

present absent

Present 43 369 412

Absent 29 601 630

Total 72 b+d 1042

RR= (43/412) / (29/630) =0.104 / 0.046 =2.26RR= (43/412) / (29/630) =0.104 / 0.046 =2.26

Clinical trialClinical trial

Definition

a planned experiment on humans.

The setting is in health institutions

environment. It usually involves

patients.

Rationale Before a new treatment method is made available to the public it must be studied

and tested for safety and effectiveness.

Clinical trials provide the “gold standard”

of determining the relationship between

garlic and cardiovascular disease

prevention.

Clinical TrialClinical Trial

Study sample

Treatment Group

Control Group

Outcomes

Outcomes

R a n d om i z e

Allocation of regimensAllocation of regimens

Intervention versus Placebo

Current treatment

Nothing

Randomization

Aim

Methods

BlindingBlinding

One or more of the people involved in the trial is unaware of the intervention.

1- Open trial

2- Single- blind trial

3- Double blind trial

4-Double blind double dummy trial

5- Triple and quadruple blind

Follow up• Quantity

• Quality

• Compliance

AnalysisAnalysis

60 45

15

Intension to treat analysis.

15/ 60 =0.25 =25%

Protocol analysis.

15/45 = 0.33 =33%

Relative RiskRelative RiskGroup outcome Total

positive Negative

Intervention a b a +b

Control c d c +d

Measures of effect size 1-Relative risk (RR)

–Is the ratio of the risk of a given event in one group of subjects compared to another group

Experimental Event Rate (EER) ----------------------------------------------- Control Event Rate (CER )

EER: The percentage of intervention group who experienced outcome in question. ( a/(a + b))

CER: The percentage of control group who experienced outcome in question. (c /( c + d))

2-Relative risk reduction (RRR)

–The proportion of the initial or baseline risk which was eliminated by a given treatment/intervention or by avoidance of exposure to a risk factor

RRR= (CER – EER) / CER

3-Absolute risk reduction (ARR)

–The difference in risk of a given event, between

two groups

ARR= CER - EER

4-Number Needed to Treat (NNT)

It is defined as the number needed to treat in order to prevent one additional adverse event (e.g. death)

NNT = 1/ ARR

–Its clinical importance depends on Initial probability of the outcome.

RR=(18/64) / (29/65) = 0.281/0.446 =0.63 =63%RR=(18/64) / (29/65) = 0.281/0.446 =0.63 =63%

95% CI= 0.39 – 1.0195% CI= 0.39 – 1.01 Source: N Engl J Med 1992; 326: 1527-1532.Source: N Engl J Med 1992; 326: 1527-1532.

Intervention Outcome Total

Death survival

Ligation 18 46 64

sclerotherapy 29 36 65

22--Absolute Risk Reduction (ARR): Absolute Risk Reduction (ARR): ARR= CER - EERARR= CER - EER =(29/65) – (18/64) ==(29/65) – (18/64) =0.446 – 0.281 = 0.165 = 16.5%0.446 – 0.281 = 0.165 = 16.5% 3-Relative Risk Reduction (RRR) 3-Relative Risk Reduction (RRR)

RRR= (CER – EER) / CERRRR= (CER – EER) / CER =(0.446 – 0.281) / 0.446 =(0.446 – 0.281) / 0.446 =0.165 / 0.446 = 0.37 = 37% =0.165 / 0.446 = 0.37 = 37% i.e. Legation decreases the risk i.e. Legation decreases the risk of death by 37% of death by 37%

4-N4-Number Needed to Treat (NNT):umber Needed to Treat (NNT):

NNT = 1/ ARRNNT = 1/ ARR = 1 / 0.165 = 1 / 0.165 = 6.06 = 6.06 =6 patients =6 patients You have to treat 6 patients by ligation to You have to treat 6 patients by ligation to save one life save one life

Ethical issues

• Informed consent

• Confidentiality

• Stopping rules

Independent monitoring group

Clear existence of benefits

Clear existence of harm

Clinical TrialsClinical 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

What is the best study design?What is the best study design?

• A young patient who had ventricular tachycardia after an sports activity

• Hypersensitivity reactions associated with exposure to naproxen and ibuprofen.

• Thromboembolic Stroke in Young Women and use of oral Contraceptives.

• Exposure to benzene and non-Hodgkin lymphoma.

• SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon alpha-2b for genotype 1 nonresponders.

• Risk factors among young women with endometrial cancer.

• The annual incidence and course of neck pain in the general population.

• The prevalence of pressure ulcers in hospitalised patients in The Netherlands.

• Strangulated hernia with ileal perforation due to abdominal trauma in a paediatric patient.

• Valsartan in a Japanese population with hypertension and other cardiovascular disease.

• The effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with functional Class I or II Heart Failure.

• lymphoblastoid interferon-α for chronic hepatitis C.

• Efficacy of interferon-gamma1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis.