Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009 Study Design and Measures of...
-
Upload
britton-bishop -
Category
Documents
-
view
218 -
download
0
Transcript of Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009 Study Design and Measures of...
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Study Design and Measures of Association
Dr Danilo Lo Fo Wong
Study Design and Measures of Association
Dr Danilo Lo Fo Wong
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Outline Outline
Study objectives
Types of study design
Measures of association
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Study objectivesStudy objectives
Investigate an outbreak
Measure disease frequency
Assess risk factors
Investigate trends
Hypothesis generating
Hypothesis testing
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Main types of studiesMain types of studies
Experimental Experimental studiesstudies
Observational studiesObservational studies
Cross-sectional studiesCross-sectional studies
Longitudinal studiesLongitudinal studies
Case-control studiesCase-control studiesCohort studiesCohort studies
Clinical trialsClinical trials
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Observational studiesObservational studies
Evaluate the association between exposure (E) and disease outcome (D)
No random allocation of exposure or intervention
Harmonise groups as much as possible except for the exposures under investigation
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Observational studiesObservational studies
TimeTime
D+D+
D-D-
DiseasedDiseased
Non-diseasedNon-diseased
E+E+
E-E-
ExposedExposed
Non-exposedNon-exposed
Study onsetStudy onset
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Cohort study (prospective)Cohort study (prospective)
E+E+
E-E-
D+D+
D-D-
D+D+
D-D-
TimeTime
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Cohort study (retrospective)Cohort study (retrospective)
E+E+
E-E-
D+D+
D-D-
D+D+
D-D-
TimeTime
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Cohort studyCohort study
Applications:
(Foodborne) disease outbreak
Usually high attack rates
Identifiable & manageable setting– Single event (wedding, picnic, etc.)– Single location (cafeteria, restaurant, etc.)
Assess (foodborne) disease incidence
Assess risk factors
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Cohort studyCohort study
Advantages
Clear temporal relationship
Least susceptible to some forms of bias
Possibility to examine multiple diseases
Disadvantages
No control over exposure
Not suitable for rare or long-latent diseases
Loss to follow-up threatens validity
More expensive than other observational designs
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Case-control studyCase-control study
D+D+
D-D-
E+E+
E-E-
E+E+
E-E-
TimeTime
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Case-control studyCase-control study
Applications:
(Foodborne) disease outbreak
Unclear setting of exposure– Spread out over time and space– Large cohort and/or rare disease
Increase in reported cases
Assess risk factors for sporadic illness
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Case-control studyCase-control study
Advantages
Efficient use of time and resources
Well-suited for rare diseases
Examine multiple exposures
Relatively inexpensive
Best when cohort study is not feasible
Disadvantages
Not suited for rare exposures
Difficult to identify appropriate controls
Ascertaining historic exposure often difficult
Sensitive to some forms of bias
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Cross-sectional studyCross-sectional study
TimeTime
D+D+
D-D-
E+E+
E-E-
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Cross-sectional studyCross-sectional study
Applications:
Prevalence estimate
Screening
Risk factor studies
Hypothesis generating
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Cross-sectional studyCross-sectional study
Advantages
One stop, one time
Least expensive
Based on sample of general population
– not restricted to people seeking medical care
Disadvantages
Not suitable if disease is rare or of short duration
Not possible to determine temporal relationship
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Steps to develop a studySteps to develop a study
Hypothesis generation
Develop study objectives
Decide which type of study works best
Study methods– Design survey tool/questionnaire– Identify subjects ((non)diseased or (non)exposed)– Determine sample size
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Steps to develop a studySteps to develop a study
Data gathering– Actively acquired data– Registered data– Published data
Statistical analysis– Descriptive– Analytic
• Univariate• Multivariate
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
2 x 2 Table2 x 2 Table
a. No. of subjects that are exposed and have the diseasea. No. of subjects that are exposed and have the disease
b. No. of subjects that are exposed and do not have the diseaseb. No. of subjects that are exposed and do not have the disease
c. No. of subjects that are not exposed and have the diseasec. No. of subjects that are not exposed and have the disease
d. No. of subjects that are not exposed and do not have the diseased. No. of subjects that are not exposed and do not have the disease
aa bb
cc ddNoNo
YesYesExposureExposure
YesYes NoNo
DiseaseDisease
a+ba+b
c+dc+d
a+ca+c b+db+d nn
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Measures of associationMeasures of association
Disease frequency (absolute)– Attack rate
Strength of association (relative)– Relative risk (RR)– Odds ratio (OR)
Significance of association– Chi-squared– P-values– Confidence intervals (CI)
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Disease frequencyDisease frequency
Attack rate: – the proportion of subjects at risk that develop disease (i.e.
proportion of exposed subjects that become ill)
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
2 x 2 Table2 x 2 Table
aa bb
cc dd
YesYes
NoNo
YesYes
NoNo
ExposureExposure
DiseaseDisease
Attack rateAttack rateexposedexposed: (diseased|exposed)/exposed = a/(a+b): (diseased|exposed)/exposed = a/(a+b)
a+ba+b
c+dc+d
a+ca+c b+db+d nn
Attack rateAttack rateunexposedunexposed: (diseased|unexposed)/unexposed = c/(c+d): (diseased|unexposed)/unexposed = c/(c+d)
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
ExampleExample
4040 400400
2020 420420
YesYes
NoNo
YesYes
NoNo
Eating Eating product Xproduct X
SalmonellosisSalmonellosis
440440
440440
6060 820820 880880
Attack rateAttack rateexposedexposed: 40/440 = 0.09 = 9%: 40/440 = 0.09 = 9%
Attack rateAttack rateunexposedunexposed: 20/440 = 0.05 = 5%: 20/440 = 0.05 = 5%
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Strength of associationStrength of association
Relative Risk (RR)– Risk of disease for exposed vs. non-exposed– Cohort and cross-sectional studies
Odds ratio (OR)– Odds of exposure for diseased vs. non-diseased – Case-control, cross-sectional and cohort studies
OR ~ RR when:– Cases and controls representative for population– Disease not frequent
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
2 x 2 Table2 x 2 Table
aa bb
cc dd
YesYes
NoNo
YesYes
NoNo
ExposureExposure
DiseaseDisease
a+ba+b
c+dc+d
a+ca+c b+db+d nn
OR = odds exposureOR = odds exposurediseaseddiseased/odds exposure/odds exposurenon-diseased non-diseased = (a:c)/(b:d) = ad/bc= (a:c)/(b:d) = ad/bc
RR = RiskRR = Riskexposedexposed/Risk/Riskunexposed unexposed = [a/a+b)]/[c/c+d)]= [a/a+b)]/[c/c+d)]
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
ExampleExample
4040 400400
2020 420420
YesYes
NoNo
YesYes
NoNo
Eating Eating product Xproduct X
SalmonellosisSalmonellosis
440440
440440
6060 820820 880880
OR = (40*420)/(20*400) = 2.1OR = (40*420)/(20*400) = 2.1
RR = (40/440)/(20/440) = 2.0RR = (40/440)/(20/440) = 2.0
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Significance of associationSignificance of association
Chi-squared– Test association between exposure and disease
P-value– probability that an association at least as strong as that observed
might have arisen by chance alone– P < 0.05: significant
Confidence interval (CI)– range within which in 95% of times the true value of the
estimated association lies (i.e. 95% CI)– Indication of confidence in the point-estimate
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
2 x 2 Table2 x 2 Table
aa bb
cc dd
YesYes
NoNo
YesYes
NoNo
ExposureExposure
DiseaseDisease
a+ba+b
c+dc+d
a+ca+c b+db+d nn
Chi-squared:Chi-squared:(a+b)(c+d)(a+c)(b+d)(a+b)(c+d)(a+c)(b+d)
n(|ad-bc| - n/2)n(|ad-bc| - n/2)22
P-value = P-value = Percentiles of Chi-square distributionPercentiles of Chi-square distribution
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
ExampleExample
4040 400400
2020 420420
YesYes
NoNo
YesYes
NoNo
Eating Eating product Xproduct X
SalmonellosisSalmonellosis
440440
440440
6060 820820 880880
Chi-squared: 7.15Chi-squared: 7.15
P-value < 0.05P-value < 0.05
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Confidence IntervalConfidence Interval
Lower border = ln(OR) – Z*(var ln(OR))Lower border = ln(OR) – Z*(var ln(OR))½½ = L = L
95% Confidence Interval for OR: e95% Confidence Interval for OR: eLL to e to eUU = X to Y = X to Y
Upper border = ln(OR) + Z*(var ln(OR))Upper border = ln(OR) + Z*(var ln(OR))½½ = U = U
aa bb
cc dd
YesYes
NoNo
YesYes
NoNo
ExposureExposure
DiseaseDisease
a+ba+b
c+dc+d
a+ca+c b+db+d nn
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
ExampleExample
4040 400400
2020 420420
YesYes
NoNo
YesYes
NoNo
Eating Eating product Xproduct X
SalmonellosisSalmonellosis
440440
440440
6060 820820 880880
Lower border = 0.74 – 1.96*(0.08)Lower border = 0.74 – 1.96*(0.08)½½ = 0.2 = 0.2
95% Confidence Interval for OR: e95% Confidence Interval for OR: e0.20.2 to e to e1.31.3 = 1.2 to 3.7 = 1.2 to 3.7
Upper border = 0.74 + 1.96*(0.08)Upper border = 0.74 + 1.96*(0.08)½½ = 1.3 = 1.3
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Interpretation RR and CIInterpretation RR and CI
RR > 1 : risk of disease among exposed greater than among unexposed
RR = 1 : risk of disease the same among exposed and unexposed
RR < 1 : risk of disease among exposed less than among unexposed (i.e. protective)
CIlower< 1 < CIupper : no significant association
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Interpretation OR and CIInterpretation OR and CI
OR > 1 : odds of exposure among diseased greater than among non-diseased
OR = 1 : odds of exposure the same among diseased and non-diseased
OR < 1 : odds of exposure among diseased less than among non-diseased (i.e. protective)
CIlower< 1 < CIupper : no significant association
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
ExamplesExamples
OR = 2.3; 95% CI 1.2 – 28.5OR = 2.3; 95% CI 1.2 – 28.5
RR = 3.6; 95% CI 0.8 – 4.7RR = 3.6; 95% CI 0.8 – 4.7
OR = 0.4; 95% CI 0.2 – 0.7OR = 0.4; 95% CI 0.2 – 0.7
RR = 5.6; 95% CI 5.3 – 5.9RR = 5.6; 95% CI 5.3 – 5.9
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Epi InfoEpi Info
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Hypothesis testingHypothesis testing
Which study to design?
Nipah virus infection among abattoir workers across Malaysia
Cholera outbreak in Manila, Philippines
Foodborne salmonellosis in the Institute of Health Sciences hostel, Muscat, Oman
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Nipah virus infection:Cross-sectional study Nipah virus infection:Cross-sectional study
Objective: To assess the prevalence of Nipah infection among abattoir workers and the association with pigs
Serum sampling of workers from registered abattoirs in 11 of 13 states in Malaysia
Exposure: pigs
Outcome: antibodies (ab’s) against Nipah virus
Abattoirs (n=143)
Workers (n=435)– 7 out of 435 infected (1.6%) slaughtering pigs– 0 out of 233 infected (0%) slaughtered ruminants
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Nipah virus infection:Cross-sectional study Nipah virus infection:Cross-sectional study
7 workers carrying ab’s against Nipah virus from abattoirs in 3 states with clinical outbreak among pig farmers
Workers in these 3 states more likely to have Nipah antibody than those in other states
– 7/144 (4.9%) vs. 0/291 (0%), P < 0.001
Conclusion: – Nipah infection not widespread among abattoir workers in
Malaysia– Infection linked to exposure to pigs
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Vibrio cholerae: Case-control study
Vibrio cholerae: Case-control study
Objective: to investigate an increasing number of diarrhea cases from a district in Manila
List of diarrhea cases from 3 hospitals in 1 district
338 suspect cholera cases admitted
Rectal swabs, environmental survey, water samples
Spot map to identify extent of outbreak
Case control study in 4 areas with highest AR’s– 56 cases– 56 controls– Matched for age and gender
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Vibrio cholerae: Case-control study
Vibrio cholerae: Case-control study
2 protective factors– Boiling water prior to drinking
(OR = 0.08, 95% CI 0.02 – 0.4)– Washing drinking water containers with soap and water
(OR = 0.12, 95% CI 0.02 – 0.63)
Inspection showed leaking water pipes, numerous illegal connections and unsanitary toilet facilities
– 1 sample from household faucets positive for fecal coliforms
Conclusion: Cholera outbreak due to contaminated water
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Salmonellosis Outbreak: Cohort study
Salmonellosis Outbreak: Cohort study
Questionnaire to all students at IOHS– 123 cases identified among 158 who ate dinner (AR = 78%); 72
confirmed cases (S. Enteritidis)– 0 cases out of 91 who did not eat this meal (AR = 0%) – RR infinity, p < 0.001
Univariate analysis– Chicken (RR = 4.4; 95% CI 1.7 – 11)– Egg mousse (RR = 6.0; 95% CI 2.5 – 15)– Fried dal (RR = 1.2; 95% CI 1.0 – 1.4)– Omelet (RR = 1.3; 95% CI 1.2 – 1.4)– Chapati (RR = 6.0; 95% CI 1.7 – 11)
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Salmonellosis Outbreak: Cohort study
Salmonellosis Outbreak: Cohort study
Restricted analysis (n=158)– Chicken (RR = 14; 95% CI 2.0 – 96)– Egg mousse (RR = 19; 95% CI 2.8 – 128)– Chapati (RR = 19; 95% CI 2.8 – 128)
Interview of kitchen staff– Time- and temperature abuse of chicken– Cross-contamination of chapati dough with raw eggs– Mousse contained raw eggs and was not cooked
Conclusion: Outbreak due to cross-contamination and time-temperature abuse during preparation of three foods in the IOHS kitchen
Foodborne Outbreak Investigation, Hanoi, Vietnam 01 – 05 June 2009
Thank you for your attention
Thank you for your attention