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Environmental Health

Lecture 2Lecture 2

Cluster InvestigationCluster InvestigationDr. Bartlett and Dr. Geary Olsen Dr. Bartlett and Dr. Geary Olsen

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Elizabeth Lyons – MSU Graduate

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Environmental Health: Cluster Investigation

A lot of what health departments A lot of what health departments do is respond to citizen do is respond to citizen complaints regarding clusters. complaints regarding clusters. Usually cancer clusters.Usually cancer clusters.

They also participate in long-They also participate in long-term studies.term studies.

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Environmental Health: Cluster Investigation

Somebody calls the health department:Somebody calls the health department: Three kids at our school have childhood Three kids at our school have childhood

leukemialeukemia Your vet clinic is right next to the Your vet clinic is right next to the

playground, and we can smell pesticide playground, and we can smell pesticide coming from your clinic.coming from your clinic.

We think the pesticide fumes are causing We think the pesticide fumes are causing our kids to get leukemia.our kids to get leukemia.

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Cluster Investigation Epidemiology Cluster - A number of persons, animals, or things Cluster - A number of persons, animals, or things

gathered or situated close together.gathered or situated close together. A cluster is a closely grouped series of events or A cluster is a closely grouped series of events or

cases of a disease, with well-defined distribution cases of a disease, with well-defined distribution patterns, in relation to time or place (or both). patterns, in relation to time or place (or both). Time cluster, space cluster, time-space clusterTime cluster, space cluster, time-space cluster

Random = happening by chance.Random = happening by chance. P= probability. A P-value of .01 would mean that P= probability. A P-value of .01 would mean that

the probability of a event occurring by chance the probability of a event occurring by chance would be 1 in 100. (NO!)would be 1 in 100. (NO!)

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Cluster Investigation Epidemiology

If the null hypothesis is trueIf the null hypothesis is true, then P = .01 , then P = .01 represents the probability that a difference represents the probability that a difference as extreme as that observed (or more as extreme as that observed (or more extreme) would occur (just by chance).extreme) would occur (just by chance).

With regards to clusters of disease, a With regards to clusters of disease, a P-value or P-value or Significance LevelSignificance Level is meaningful is meaningful and interpretable as a probability statement and interpretable as a probability statement only if the observations were drawn at only if the observations were drawn at random from a defined population.random from a defined population.

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Time-Space Cluster investigation

Why it is hard to use P values to Why it is hard to use P values to determine if you have a cluster.determine if you have a cluster.

The problem is that sometimes clusters The problem is that sometimes clusters happen “naturally” just by chance.happen “naturally” just by chance. Is your cluster due to something Is your cluster due to something

causing an increase rate of disease?causing an increase rate of disease? Or is it one of these “chance” clusters?Or is it one of these “chance” clusters?

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What can cause a cluster?

““Statistical” Clusters:Statistical” Clusters: - Given - Given enough time and enough potential enough time and enough potential groupings, eventually there will be groupings, eventually there will be subsets of the data (a particular town, subsets of the data (a particular town, month, farm, sector, county, etc.) that month, farm, sector, county, etc.) that may (by chance alone) have a higher rate may (by chance alone) have a higher rate of a disease than the entire population.of a disease than the entire population. Illinois SubdivisionIllinois Subdivision

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A posteriori vs. A priori ““After the fact” vs. “before the fact”After the fact” vs. “before the fact” What is the probability that, through the eons of What is the probability that, through the eons of

time, I would be standing here before you with two time, I would be standing here before you with two arms, two eyes, 10 fingers and only one nose? arms, two eyes, 10 fingers and only one nose? The probability is 1.000…. (It has already The probability is 1.000…. (It has already

happened!) But that’s not the point. happened!) But that’s not the point. The question was posed after observing the data. If I The question was posed after observing the data. If I

had 8 fingers, I would have asked had 8 fingers, I would have asked a different a different question. question.

When the question is posed based on what you When the question is posed based on what you observe in the data, then p values from statistical observe in the data, then p values from statistical tests of association are no longer valid.tests of association are no longer valid.

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Random is a process, not a result.

Consider the tables of random Consider the tables of random numbers. numbers.

Look at about 100 of them Look at about 100 of them until you see one that somehow until you see one that somehow doesn’t look random.doesn’t look random.

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Statistical test of association

Chi-square goodness of fit testChi-square goodness of fit test Expect 10% of the numbers to be “7”Expect 10% of the numbers to be “7” 110 number in the cluster110 number in the cluster

Would expect 11 to be “7”Would expect 11 to be “7”Observed 25 to be “7”Observed 25 to be “7”

P = .01 – but is it valid?P = .01 – but is it valid?

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Texas sharpshooter Texas sharpshooter who shoots at the side of Texas sharpshooter who shoots at the side of

a barn and then draws a bull’s eye around a barn and then draws a bull’s eye around the bullet hole. the bullet hole.

If you define a cluster (draw the bull’s eye) If you define a cluster (draw the bull’s eye) based on what you observe in the data (the based on what you observe in the data (the bullet hole), then statistical tests can not be bullet hole), then statistical tests can not be used to confirm the existence of the cluster used to confirm the existence of the cluster (time-space association with a particular (time-space association with a particular risk factor). risk factor). Why are you studying “7” disease? Why are you studying “7” disease?

Why are you studying it here?Why are you studying it here?

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“Statistical” Clusters:

Given the large number of diseases and Given the large number of diseases and risk factors (employment, organizations, risk factors (employment, organizations, housing location, etc), some will appear housing location, etc), some will appear to be associated with disease just by to be associated with disease just by chance alone.chance alone.

““Given enough time, it is probable for the Given enough time, it is probable for the improbable to happen.”improbable to happen.”

Albert EinsteinAlbert Einstein

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Other causes for clusters

Biological clustersBiological clusters - - are clusters of are clusters of disease which have a biological basis. disease which have a biological basis. This is what we are looking for!This is what we are looking for!

Confounding (and time-space clusters)Confounding (and time-space clusters) Legionnaire’s Disease in MichiganLegionnaire’s Disease in Michigan

Reporting Bias (and time-space clusters)Reporting Bias (and time-space clusters) Rabies hysteria or apathyRabies hysteria or apathy

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Example: www.RUSick2.msu.edu For foodborne outbreaks: For foodborne outbreaks:

Statistical Clusters: Statistical Clusters: Given enough food items and enough time, Given enough food items and enough time,

clusters of foodborne disease will occur which clusters of foodborne disease will occur which do not have a biological basis and do not do not have a biological basis and do not represent common-source foodborne outbreaks.represent common-source foodborne outbreaks.

Pranksters or malicious intentPranksters or malicious intent ConfoundingConfounding

Strawberries every springStrawberries every springRestaurant next to “an event”Restaurant next to “an event”

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Cluster Investigation Cancer clustersCancer clusters- - these cannot be investigated like these cannot be investigated like

acute infectious disease clusters.acute infectious disease clusters. 1. Long and indefinite incubation/induction period for 1. Long and indefinite incubation/induction period for

the disease.the disease. 2. Routes of the cancer causing agents are usually 2. Routes of the cancer causing agents are usually

through the environment not through personal through the environment not through personal contact, or consumption of food or beverage.contact, or consumption of food or beverage.

““Hot pursuit” case control studies usually done in acute Hot pursuit” case control studies usually done in acute infectious disease outbreaks are not useful in cancer infectious disease outbreaks are not useful in cancer cluster analysis.cluster analysis.

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Cluster Investigation The following list of characteristics can help to The following list of characteristics can help to

identify a situation where a case-control study or a identify a situation where a case-control study or a multicommunity investigation multicommunity investigation mightmight be useful. be useful.

1.1. There must be at least five cases to a cluster and There must be at least five cases to a cluster and they must have a high relative risk (RR).they must have a high relative risk (RR).

1.1. What is high? 2.0? 10.0?What is high? 2.0? 10.0?2.2. A unique and well known etiological agent is A unique and well known etiological agent is

known to be the cause and the pathophysiologic known to be the cause and the pathophysiologic mechanism for that agent is known.mechanism for that agent is known.

3.3. The agent is in the environment and can be The agent is in the environment and can be measured there.measured there.

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4. The agent is persistent in the infected/exposed 4. The agent is persistent in the infected/exposed people but rare in normal populations and its people but rare in normal populations and its unique physiologic response in the exposed can unique physiologic response in the exposed can be measured.be measured.5. There is a heterogeneity of exposure (range 5. There is a heterogeneity of exposure (range from high to low) within the neighborhood so from high to low) within the neighborhood so effects can be easily measured.effects can be easily measured.6. The route of exposure can be easily recalled.6. The route of exposure can be easily recalled.7. Multi-community studies can be done by 7. Multi-community studies can be done by looking at (otherwise) similar exposed and looking at (otherwise) similar exposed and unexposed communities.unexposed communities.8. Endemic space cluster, not a space-time cluster 8. Endemic space cluster, not a space-time cluster that exists for a while then vanishes.that exists for a while then vanishes.

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Cluster InvestigationMinnesota Cluster Analysis Track Record

1. Information and education- 95%1. Information and education- 95% 2. Public initiated surveys- 4%2. Public initiated surveys- 4% 3. Validation, evaluation, feasibility 3. Validation, evaluation, feasibility

and education- 1%and education- 1% 4. In-depth study- <1%4. In-depth study- <1%

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Cluster Investigation Evaluation of false positive reports is the price Evaluation of false positive reports is the price

we must pay in order to identify the true we must pay in order to identify the true biological cluster. biological cluster.

Examples:Examples: The first few AIDS casesThe first few AIDS cases Foodborne outbreaks of Foodborne outbreaks of E.coliE.coli 0157:H7 0157:H7 Most foodborne outbreaksMost foodborne outbreaks (Note: These are all infectious agents!)(Note: These are all infectious agents!) Bitter Harvest (PBB)Bitter Harvest (PBB)