introduction to statistics lesson 1

Lesson 1Lesson 1Lesson 1Lesson 1The Cycle of ResearchThe Cycle of Researchyy

Definitions of TermsDefinitions of TermsStudy DesignStudy Designy gy g

Measurement ScalesMeasurement Scales

Understanding the ResearchUnderstanding the ResearchUnderstanding the ResearchUnderstanding the Research

The description of any medical or health research study The description of any medical or health research study p y yp y yshould provide answers to the following:should provide answers to the following: How were the data collected?How were the data collected?

What was the sampling method?What was the sampling method?gg What is the study design?What is the study design?

In addition to understanding how the data were In addition to understanding how the data were collected, the measurement scale of the data needs to collected, the measurement scale of the data needs to ,,be consideredbe considered

Both the type of data collected (measurement scale) and Both the type of data collected (measurement scale) and how the data were collected determine the appropriatehow the data were collected determine the appropriatehow the data were collected determine the appropriate how the data were collected determine the appropriate descriptive statistics, graphs, and analysis methods to descriptive statistics, graphs, and analysis methods to use. use.

2PubH 6414 Lesson 1

Cycle of ResearchCycle of ResearchCycle of ResearchCycle of Research

3PubH 6414 Lesson 1

Samples and PopulationsSamples and PopulationsSamples and PopulationsSamples and Populations PopulationPopulation:: complete set of individuals that complete set of individuals that

share some common characteristic(s)share some common characteristic(s)share some common characteristic(s). share some common characteristic(s). the group we are interested in learning aboutthe group we are interested in learning about..

Sample:Sample: A subset of the defined population. A subset of the defined population. the group that is actually studied and from which data the group that is actually studied and from which data

are collected. are collected.

4PubH 6414 Lesson 1

Why study samples?Why study samples?Why study samples?Why study samples? If the goal is to make some conclusion(s) about If the goal is to make some conclusion(s) about

the population why not just collect data on thethe population why not just collect data on thethe population, why not just collect data on the the population, why not just collect data on the entire population?entire population?

ItIt b t i d/ tib t i d/ ti i t ll ti t ll t It It can be too expensive and/or timecan be too expensive and/or time--consuming to collect consuming to collect data for the data for the populationpopulation

St d f th l ti bSt d f th l ti b i ibli ibl Study of the population may be Study of the population may be impossibleimpossible

Measurements Measurements from a sample may be more accurate from a sample may be more accurate p yp ythan measurements from the populationthan measurements from the population

5PubH 6414 Lesson 1


6PubH 6414 Lesson 1

Samples and PopulationsSamples and PopulationsSamples and PopulationsSamples and Populations Statistic:Statistic: A value obtained from a sample. A value obtained from a sample.

i i ht f 1 000 b l d f thi i ht f 1 000 b l d f th i.e. average weight of 1,000 boys sampled from the i.e. average weight of 1,000 boys sampled from the U.S. U.S.

Parameter:Parameter: A A population variable, whose value population variable, whose value i ki kis unknown. is unknown. i.e. average weight of ALL 10 year old boys in the i.e. average weight of ALL 10 year old boys in the

U.S. U.S.

7PubH 6414 Lesson 1

Random SamplingRandom SamplingRandom SamplingRandom Sampling

Generalization of studyGeneralization of study results is only valid if theresults is only valid if the Generalization of study Generalization of study results is only valid if the results is only valid if the sample is sample is representativerepresentative of the larger population of the larger population that it is drawn from.that it is drawn from.

Random samplesRandom samples tend to be representative of tend to be representative of the population from which the sample is drawn.the population from which the sample is drawn.

Random samples are also called Random samples are also called Probability Probability samplessamples because the probability of each subject because the probability of each subject ( i ) b i i l d d i h l i k( i ) b i i l d d i h l i k(or unit) being included in the sample is known. (or unit) being included in the sample is known.

8PubH 6414 Lesson 1

Simple Random Sample (SRS)Simple Random Sample (SRS)Simple Random Sample (SRS)Simple Random Sample (SRS)

Basic idea: Select a sample from the population Basic idea: Select a sample from the population p p pp p pso that:so that: Each subject in the population has equal probability of Each subject in the population has equal probability of

being selectedbeing selectedbeing selectedbeing selected Selection of one subject does not influence the Selection of one subject does not influence the

probability of selecting another subjectprobability of selecting another subject Formal definition: A sample of size Formal definition: A sample of size nn selected by selected by

a procedure that gives every sample of size a procedure that gives every sample of size nnthe same probability of being selectedthe same probability of being selectedthe same probability of being selectedthe same probability of being selected

SRS removes selection bias and results in a SRS removes selection bias and results in a representative samplerepresentative sample

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representative samplerepresentative sample

Selection BiasSelection BiasSelection BiasSelection Bias

Selection Bias: “A systematic tendency to favor Selection Bias: “A systematic tendency to favor y yy ythe inclusion in a sample of selected subjects the inclusion in a sample of selected subjects with particular characteristics while excluding with particular characteristics while excluding those with other characteristics.”those with other characteristics.”

Pocket Dictionary of StatisticsPocket Dictionary of Statistics

Garbage in Garbage in Garbage outGarbage out

Bias (in general): a systematic deviation from the Bias (in general): a systematic deviation from the

10PubH 6414 Lesson 1

truthtruth

How to obtain a Simple Random How to obtain a Simple Random Sample (SRS):Sample (SRS):

Obtaining a simple random sample requires that allObtaining a simple random sample requires that allObtaining a simple random sample requires that all Obtaining a simple random sample requires that all possible subjects are identified. possible subjects are identified.

Any of the following methods will result in a random Any of the following methods will result in a random y gy gsample of size sample of size nn

Place an ID for each subject in a hat and Place an ID for each subject in a hat and jjrandomly select a sample of size randomly select a sample of size nn

Use a table of random numbers to select a Use a table of random numbers to select a sample of size sample of size nn from the list from the list

Use a computer program to select a random Use a computer program to select a random


sample of size sample of size nn from the listfrom the list

Sampling with and without Sampling with and without replacementreplacement

Sampling with replacement:Sampling with replacement: Sampling with replacement: Sampling with replacement: After a subject is selected, return the ID to the listAfter a subject is selected, return the ID to the list Possible for a single subject to be selected twicePossible for a single subject to be selected twiceg jg j

Sampling without replacementSampling without replacement Once selected the subject is not available for future Once selected the subject is not available for future

selectionselection Most often, sampling without replacement is usedMost often, sampling without replacement is used

F l l ti th diff b tF l l ti th diff b t For large populations, the difference between For large populations, the difference between these is negligiblethese is negligible


Stratified Random SamplingStratified Random Samplingp gp g For stratified random sampling the population is For stratified random sampling the population is

divided into groups with similar characteristics. divided into groups with similar characteristics. These groups are called ‘strata’. A simple These groups are called ‘strata’. A simple random sample is selected from each stratarandom sample is selected from each strataPossible stratification variables arePossible stratification variables are Possible stratification variables arePossible stratification variables are GenderGender ClinicClinicClinicClinic Age groupsAge groups

This is a useful method when the subgroups This is a useful method when the subgroups vary in the study measurementsvary in the study measurements

Requires that information about the stratification Requires that information about the stratification variable(s) is available for all subjectsvariable(s) is available for all subjects


variable(s) is available for all subjectsvariable(s) is available for all subjects

Consider the sampling MethodConsider the sampling MethodConsider the sampling MethodConsider the sampling Method

When reading the medical literature consider theWhen reading the medical literature consider the When reading the medical literature consider the When reading the medical literature consider the following:following: Is the study sample representative of the population Is the study sample representative of the population

of interest?of interest? What was the sampling method? If a random sample What was the sampling method? If a random sample

was used the statistical inference is validwas used the statistical inference is validwas used, the statistical inference is validwas used, the statistical inference is valid If complete population data were collected, no If complete population data were collected, no

inference is necessary. Descriptive statistics inference is necessary. Descriptive statistics y py pcompletely represent the population when complete completely represent the population when complete population data are available.population data are available.


Study DesignStudy DesignStudy DesignStudy Design

Twelve 18Twelve 18--24 year old males in a jogging24 year old males in a jogging Twelve 18Twelve 18 24 year old males in a jogging 24 year old males in a jogging club participated in a study of brain club participated in a study of brain gycogengycogen among physically fit individualsamong physically fit individualsgycogengycogen among physically fit individuals. among physically fit individuals. The The populationpopulation of interest is (potentially) of interest is (potentially)

1818 24 year24 year oldold malesmales1818--24 year24 year--old old males.males.The The samplesample is this group of twelve is this group of twelve

jjjoggers.joggers.The The sample design sample design is how these twelve is how these twelve


where selected and studied. where selected and studied.

CalculationCalculationCalculationCalculation

Th t l l i h d ltiTh t l l i h d lti The twelve males were weighed, resulting The twelve males were weighed, resulting in weights in pounds of :in weights in pounds of :

{129,134,136,140,141,142,144,155,158,162,{129,134,136,140,141,142,144,155,158,162,165,191}165,191}The The statistics statistics how obtained were the how obtained were the

average and standard deviation of the average and standard deviation of the


ggweights. weights.

EstimationEstimationEstimationEstimation

The sample statistics are our estimates of The sample statistics are our estimates of the population values:the population values:the population values:the population values:

Average: 149.75 poundsAverage: 149.75 pounds Standard Deviation: 17.35 poundsStandard Deviation: 17.35 pounds


InferenceInferenceInferenceInference

B i ith ti l h lth d tB i ith ti l h lth d t By comparison with national health data By comparison with national health data from the CDC, we conclude that young from the CDC, we conclude that young thl ti l h l i htthl ti l h l i htathletic males have lower average weights athletic males have lower average weights

than young males overall, and thus their than young males overall, and thus their b i l lt t bb i l lt t bbrain glycogen results may not be brain glycogen results may not be generalizable to young males overall.generalizable to young males overall.


SamplePopulation

study cyclestudy cyclestudy cyclestudy cycle

StatisticParameter

Consider This StudyConsider This StudyConsider This StudyConsider This Study Two thousand AfricanTwo thousand African--American women, ages 35 to 55 years, American women, ages 35 to 55 years,

were surveyed to determine their adherence to recommendedwere surveyed to determine their adherence to recommendedwere surveyed to determine their adherence to recommended were surveyed to determine their adherence to recommended breast and cervical cancer screening schedules. At the time of breast and cervical cancer screening schedules. At the time of the survey, each woman lived in the inner city of a southern the survey, each woman lived in the inner city of a southern metropolitan areametropolitan areametropolitan area. metropolitan area.

Status Household income<$5000

Education>high school

Not married or

Employed

Had Papsmear

had mammography<$5000 school or

separatedsmear hy

Yes 27% 68% 68% 80% 48% 35%No 73% 32% 32% 20% 52% 65%No 73% 32% 32% 20% 52% 65%

The investigators concluded that African-American women in this age group who live in the inner city do not adhere tothis age group who live in the inner city do not adhere to suggested screening schedules.

Question 1: Question 1:

“___” corresponds to the SamplePopulationpprocedure highlighted in

this picture?this picture? StatisticParameter

1.1. The investigators made the conclusion The investigators made the conclusion whether Africanwhether African--American women in American women in this age group who live in the inner city this age group who live in the inner city adhere to suggested screening adhere to suggested screening schedules.schedules.

ff2.2. The health and socialThe health and social--economic data of economic data of those women were recorded.those women were recorded.

3.3. 2000 African2000 African--American women, ages American women, ages 35 55 d li i h i i35 55 d li i h i i35 to 55 years and lives in the inner city 35 to 55 years and lives in the inner city , were surveyed in this study., were surveyed in this study.

Question 2:Question 2:select the correct picture for the

following procedure.following procedure.“Twenty-seven percent of the women had a household income under $5000.”

1. 2.

3. 4.

Question 3:Question 3:

“Forty-eight percent had their most y g precent Pap smear” is ___?

1.1. ParameterParameter22 Statistic used toStatistic used to2.2. Statistic, used to Statistic, used to

estimate estimate parameterparameterparameterparameter

3.3. Statistic, also the Statistic, also the ttparameterparameter

Question 4:Question 4:l h i di hselect the picture corresponding to the

following statement.g“The investigators concluded that African-American women in this age group who live in the inner city do not adhere to suggested screening schedules ”adhere to suggested screening schedules.”1. 2.

4.3.

More on “How More on “How was the was the Data CollectedData Collected?”?”

Study DesignStudy DesignStudy DesignStudy Design

Classification of Study DesignsClassification of Study DesignsClassification of Study DesignsClassification of Study DesignsStudy designs can be classified as either Observational or Study designs can be classified as either Observational or

ExperimentalExperimentalExperimentalExperimentalObservational Studies: Observational Studies: subjects are observed subjects are observed withoutwithout any any

interventionintervention by the investigatorby the investigator Case seriesCase series CrossCross--Sectional Sectional CaseCase ControlControl CaseCase--Control Control Cohort Cohort Experimental Studies: Experimental Studies: a comparative study a comparative study involving an involving an

interventionintervention by the investigatorby the investigator Controlled studiesControlled studies Uncontrolled studiesUncontrolled studies


Uncontrolled studiesUncontrolled studies

Case SeriesCase SeriesCase SeriesCase Series

A case series is observationalA case series is observational Subjects are observed and the outcomes or Subjects are observed and the outcomes or

characteristics of the observation are describedcharacteristics of the observation are described Case series typically have a small number of Case series typically have a small number of subjectssubjects

These are not planned studies so they are not These are not planned studies so they are not always considered ‘studies’always considered ‘studies’

Observations from a case series may lead to Observations from a case series may lead to research questions for more rigorously designed research questions for more rigorously designed studiesstudies


CaseCase--Series ExampleSeries ExampleCaseCase Series ExampleSeries Example

In 1981, Gottlieb et al. reported a rare form of In 1981, Gottlieb et al. reported a rare form of , p, ppneumonia and unusual infections in 5 young pneumonia and unusual infections in 5 young menmen

G ttli b t lG ttli b t l P ti i iiP ti i ii i di d Gottlieb, et al. Gottlieb, et al. Pneumocystis cariniiPneumocystis carinii pneumonia and pneumonia and mucosal candidisasismucosal candidisasis in previously healthy in previously healthy homosexual men: Evidence of a new acquired cellular homosexual men: Evidence of a new acquired cellular i d fi ii d fi i N E l d J l f M di iN E l d J l f M di iimmunodeficiency.immunodeficiency. New England Journal of Medicine, New England Journal of Medicine, 1981; 305(24): 14251981; 305(24): 1425--14311431

Other similar case series were reportedOther similar case series were reportedOther similar case series were reportedOther similar case series were reported By 1982 this condition was named: Acquired By 1982 this condition was named: Acquired

Immune Deficiency Syndrome (AIDS)Immune Deficiency Syndrome (AIDS)


CrossCross--Sectional DesignSectional DesignCrossCross Sectional DesignSectional Design

CrossCross--sectional studies collect data from a sectional studies collect data from a sample of subjects at one point in time. sample of subjects at one point in time. Provides a ‘snapshot’ of the characteristics of interest Provides a ‘snapshot’ of the characteristics of interest Often large number of subjectsOften large number of subjects Often large number of subjectsOften large number of subjects

Collected Collected data can be used to explore data can be used to explore relationships between variables at a point in timerelationships between variables at a point in time Possible outcome variables: Disease, Death, EventPossible outcome variables: Disease, Death, Event Explanatory variables: Exposure to some Risk FactorExplanatory variables: Exposure to some Risk FactorExplanatory variables: Exposure to some Risk FactorExplanatory variables: Exposure to some Risk Factor Demographic characteristics: age gender, ethnicity, Demographic characteristics: age gender, ethnicity,

etc.etc.


CrossCross--sectional Design: Conssectional Design: ConsCrossCross sectional Design: Conssectional Design: Cons

Cross sectional studies are not useful for Cross sectional studies are not useful for identifying the ‘causeidentifying the ‘cause--effect’ relationship effect’ relationship between variablesbetween variables

There There is potential for bias in data collected by is potential for bias in data collected by surveyssurveyssurveyssurveys Volunteer biasVolunteer bias

NonNon--response biasresponse bias


CaseCase--Control DesignControl DesignCaseCase Control DesignControl Design CaseCase--Control studies are useful for exploring the Control studies are useful for exploring the

relationship between disease (or some other outcome)relationship between disease (or some other outcome)relationship between disease (or some other outcome) relationship between disease (or some other outcome) and possible risk factorsand possible risk factors

Subjects are selected based on the outcomeSubjects are selected based on the outcome‘‘CC ’’ l d h th dil d h th di ‘‘CasesCases’ ’ –– already have the disease already have the disease

‘‘ControlsControls’ ’ –– individuals from a similar population who do not have individuals from a similar population who do not have the disease the disease

D t iD t i tt t t d i k f t ( ) ft t d i k f t ( ) f Determine Determine pastpast exposure to suspected risk factor(s) for exposure to suspected risk factor(s) for the disease or condition fromthe disease or condition from Interviews with subjects or family membersInterviews with subjects or family members Medical recordsMedical records

These are often called Retrospective studies because These are often called Retrospective studies because the outcome already occurred prior to inclusion in the the outcome already occurred prior to inclusion in the


y py pstudy. study.

CaseCase--Control Design ExampleControl Design ExampleCaseCase Control Design ExampleControl Design Example

Inskip, PD et al. Cellular telephone use and brain Inskip, PD et al. Cellular telephone use and brain tt N E l d J l f M di iN E l d J l f M di i (2001)(2001)tumors. tumors. New England Journal of MedicineNew England Journal of Medicine (2001), (2001), 344(2), 79344(2), 79--8686

Cases and Controls were identifiedCases and Controls were identified 782 cases with various types of brain tumors 782 cases with various types of brain tumors 799 controls with nonmalignant conditions799 controls with nonmalignant conditions

Exposure to cell phone use was evaluated by subject Exposure to cell phone use was evaluated by subject i t ii t iinterview interview

Study conclusion: “There was no indication of higher Study conclusion: “There was no indication of higher brain tumor risk among persons who had used handbrain tumor risk among persons who had used hand--held cellular phones compared to those who had notheld cellular phones compared to those who had notheld cellular phones compared to those who had not held cellular phones compared to those who had not used them.” used them.”

htt // / t i /f t h t/b ihtt // / t i /f t h t/b i tt


http://www.cancer.gov/cancertopics/factsheet/brainhttp://www.cancer.gov/cancertopics/factsheet/brain--tumorstumors--cellcell--phonesphones

CaseCase--Control DesignControl Design

Drawbacks of caseDrawbacks of case--control studies: control studies: Misclassification Bias: It isn’t always easy to determineMisclassification Bias: It isn’t always easy to determine Misclassification Bias: It isn t always easy to determine Misclassification Bias: It isn t always easy to determine

disease statusdisease status Recall Bias: Subjects don’t always accurately remember Recall Bias: Subjects don’t always accurately remember

hihiexposure historyexposure history Cannot be used to estimate the prevalence of a condition.Cannot be used to estimate the prevalence of a condition. SelectionSelection of appropriate controls can be difficultof appropriate controls can be difficult Selection Selection of appropriate controls can be difficult of appropriate controls can be difficult

Advantages of caseAdvantages of case--control studies: control studies: Can obtain an adequate number of cases for studies ofCan obtain an adequate number of cases for studies of Can obtain an adequate number of cases for studies of Can obtain an adequate number of cases for studies of

rare diseasesrare diseases Economical and quick compared to prospective studiesEconomical and quick compared to prospective studies


Cohort DesignCohort DesignCohort DesignCohort Design Cohort studies follow a group of subjects (cohort) Cohort studies follow a group of subjects (cohort)

over timeover time to determine disease or mortality statusto determine disease or mortality statusover timeover time to determine disease or mortality status.to determine disease or mortality status. Sometimes called followSometimes called follow--up or longitudinal studiesup or longitudinal studies

Members of the cohort can be classified as Members of the cohort can be classified as ‘exposed’ or ‘not exposed’ to one or more risk ‘exposed’ or ‘not exposed’ to one or more risk factors at the beginning of the study. For example:factors at the beginning of the study. For example:

k dk d kk smokers and nonsmokers and non--smokers smokers overweight and normal weightoverweight and normal weight

The study follows the cohort over time toThe study follows the cohort over time to The study follows the cohort over time to The study follows the cohort over time to investigate the association between exposures investigate the association between exposures and outcomes.and outcomes.


Cohort Study DesignCohort Study DesignCohort Study DesignCohort Study Design MostMost cohort studies are cohort studies are prospectiveprospective

Ri k f t i d t i d i thRi k f t i d t i d i th Risk factor exposure is determined in the Risk factor exposure is determined in the present and information about the outcome is present and information about the outcome is collected at a future timecollected at a future timeco ected at a utu e t eco ected at a utu e t e

Cohort studies can also be Cohort studies can also be retrospectiveretrospective Exposure and outcome have already occurredExposure and outcome have already occurred Exposure and outcome have already occurredExposure and outcome have already occurred Requires having complete and accurate Requires having complete and accurate

records to “follow” subjects from exposure to records to “follow” subjects from exposure to outcomeoutcome

These are also called ‘historical cohort studies’These are also called ‘historical cohort studies’


Cohort Study ExampleCohort Study ExampleCohort Study ExampleCohort Study Example

NIH: Division of Epidemiology, Statistics & NIH: Division of Epidemiology, Statistics & P ti R h (DESPR) N ti l ChildP ti R h (DESPR) N ti l ChildPrevention Research (DESPR): National Childrens Prevention Research (DESPR): National Childrens StudyStudy

The The National Children's StudyNational Children's Study is the largest and longest is the largest and longest study of environmental effects on children’s health ever study of environmental effects on children’s health ever conducted in the United States. The Study will follow conducted in the United States. The Study will follow 100 000 children from before birth to age 21 to examine100 000 children from before birth to age 21 to examine100,000 children from before birth to age 21 to examine 100,000 children from before birth to age 21 to examine the effects of environmental influences on their health the effects of environmental influences on their health and development. and development.

For more information about the Study and its progress, For more information about the Study and its progress, visit the Study Web site at visit the Study Web site at http://www nationalchildrensstudy govhttp://www nationalchildrensstudy gov


http://www.nationalchildrensstudy.govhttp://www.nationalchildrensstudy.gov..

Cohort DesignCohort DesignCohort DesignCohort Design Drawbacks of cohort studies: Drawbacks of cohort studies:

TimeTime consumingconsuming andand costlycostly TimeTime--consuming consuming and and costlycostly..

Not suitable for very rare Not suitable for very rare outcomesoutcomes

Historical cohort design requires complete and Historical cohort design requires complete and accurate medical recordsaccurate medical recordsaccurate medical recordsaccurate medical records..

Long followLong follow--up time required can result in up time required can result in loss to loss to followfollow--up (or drop out) up (or drop out) of some subjects in the studyof some subjects in the study


Experimental StudiesExperimental Studies Experimental Studies involve an Experimental Studies involve an interventionintervention by by

the investigator. Some examples of interventions the investigator. Some examples of interventions areare::

New drugNew drug New surgical procedureNew surgical procedure

Ed cation / co nseling programEd cation / co nseling program Education / counseling programEducation / counseling program Exercise Exercise programprogram


Experimental StudiesExperimental Studies Clinical Clinical Trials Trials are experimental studies of a are experimental studies of a

medical treatment or procedure that involve medical treatment or procedure that involve human subjects. human subjects.

Two types of clinical trials: those with control Two types of clinical trials: those with control subjects and those without control subjects. subjects and those without control subjects.


Controlled Clinical TrialsControlled Clinical TrialsControlled Clinical TrialsControlled Clinical Trials

Control subjects in a clinical trial provide aControl subjects in a clinical trial provide a Control subjects in a clinical trial provide a Control subjects in a clinical trial provide a comparison group for the subjects who comparison group for the subjects who receive the interventionreceive the intervention

Control subjects receive one of the Control subjects receive one of the followingfollowinggg No interventionNo intervention Placebo Placebo Standard treatment (if one exists)Standard treatment (if one exists) Intervention at a later timeIntervention at a later time


Types of Controlled TrialsTypes of Controlled Trials Concurrently assign study subjects to two groups: an Concurrently assign study subjects to two groups: an

intervention group and a control group and follow both over intervention group and a control group and follow both over the same period of time to observe the same period of time to observe outcomesoutcomespp

SelfSelf--controlled study design: Each study subject is controlled study design: Each study subject is observed before and after the intervention so each subjectobserved before and after the intervention so each subjectobserved before and after the intervention so each subject observed before and after the intervention so each subject is their own controlis their own control..

CrossCross--over study design: subjects are assigned to one of over study design: subjects are assigned to one of two groupstwo groups Intervention first followed by the placeboIntervention first followed by the placebo Intervention first followed by the placeboIntervention first followed by the placebo Placebo first followed by the interventionPlacebo first followed by the intervention


Randomized Controlled Clinical Trials Randomized Controlled Clinical Trials (RCCT)(RCCT)(RCCT)(RCCT)

In a RCCT Subjects are In a RCCT Subjects are randomlyrandomly assigned to the assigned to the jj yy ggintervention group or the control group intervention group or the control group Each subject has equal probability of being in control or Each subject has equal probability of being in control or

treatment grouptreatment group Reduce selection bias and produce groups that have Reduce selection bias and produce groups that have

comparable baseline characteristics.comparable baseline characteristics. These trials provide the strongest evidence for a These trials provide the strongest evidence for a p gp g

causecause--effect relationship between the intervention and effect relationship between the intervention and the outcome. the outcome.

Drawbacks of randomized controlled clinical trialsDrawbacks of randomized controlled clinical trials Drawbacks of randomized controlled clinical trials Drawbacks of randomized controlled clinical trials TimeTime--consuming consuming ExpensiveExpensive


Randomized Controlled Clinical Randomized Controlled Clinical TTTrial ExampleTrial Example

MRFIT: Multiple Risk Factor Intervention TrialMRFIT: Multiple Risk Factor Intervention Trialpp 12,866 men with RF for CHD randomly assigned to12,866 men with RF for CHD randomly assigned to

Intervention: counseling to reduce risk factorsIntervention: counseling to reduce risk factors Control: usual physician careControl: usual physician care Control: usual physician careControl: usual physician care

Endpoint: death from CHDEndpoint: death from CHD 66--8 years of follow8 years of follow--upup66 8 years of follow8 years of follow upup Study resultsStudy results

Risk factor levels declined in both groups but slightly Risk factor levels declined in both groups but slightly more in the special intervention groupmore in the special intervention groupmore in the special intervention group.more in the special intervention group.

Mortality from CHD and from all causes was not Mortality from CHD and from all causes was not significantly different between the two groups. (JAMA, significantly different between the two groups. (JAMA, 1982; 248:14651982; 248:1465--77)77)


1982; 248:14651982; 248:1465--77) 77)

Blinded studiesBlinded studiesBlinded studiesBlinded studies

SingleSingle--blindblindgg Subjects do not know whether they are in treatment Subjects do not know whether they are in treatment

or control groupor control group DoubleDouble--blindblind DoubleDouble blindblind

Subjects Subjects andand investigators are not aware of treatment investigators are not aware of treatment assignmentassignment

TripleTriple blindblind TripleTriple--blindblind Subjects, investigators Subjects, investigators andand statistician do not know statistician do not know

treatment assignmenttreatment assignment Goals of blinding: to promote objective Goals of blinding: to promote objective

assessment of study results and reduce biasassessment of study results and reduce bias Placebos are used to keep the study blindedPlacebos are used to keep the study blinded


Placebos are used to keep the study blindedPlacebos are used to keep the study blinded

Random AssignmentRandom AssignmentRandom AssignmentRandom AssignmentObservational studies use random Observational studies use random samplingsampling but but

controlled clinical trials use randomcontrolled clinical trials use random assignmentassignmentcontrolled clinical trials use random controlled clinical trials use random assignmentassignment In a randomized clinical trial, subjects are In a randomized clinical trial, subjects are

selectedselected based on inclusion and exclusion based on inclusion and exclusion criteriacriteria The selection process is not necessarily randomThe selection process is not necessarily random

However selected subjects areHowever selected subjects are randomlyrandomly However, selected subjects are However, selected subjects are randomly randomly assigned to either a treatment or control groupassigned to either a treatment or control group Goal is to have comparable groups in all Goal is to have comparable groups in all

characteristicscharacteristics exceptexcept the treatmentthe treatmentcharacteristics characteristics exceptexcept the treatmentthe treatment With large enough sample size, random assignment With large enough sample size, random assignment

usually results in comparable groupsusually results in comparable groups


Bias in Clinical TrialsBias in Clinical TrialsBias in Clinical TrialsBias in Clinical Trials

The following describe possible sources of bias in The following describe possible sources of bias in g pg pa Clinical Triala Clinical Trial

Procedure BiasProcedure Bias Treatment group receives more attention than control Treatment group receives more attention than control

groupgroup Recall biasRecall bias Recall biasRecall bias

Subjects in one group are more likely to remember Subjects in one group are more likely to remember events than subjects in another groupevents than subjects in another group

Compliance biasCompliance bias Patients comply with one treatment more than Patients comply with one treatment more than

anotheranother


anotheranother

Consider when reading medical Consider when reading medical literature:literature:

For an observational studyFor an observational study For an observational studyFor an observational study Is the study sample representative of the population Is the study sample representative of the population

of interest?of interest? What was the sampling method? If random sampling What was the sampling method? If random sampling

was used, statistical inference is valid.was used, statistical inference is valid. What are potential sources of bias?What are potential sources of bias? What are potential sources of bias?What are potential sources of bias?

For a clinical trialFor a clinical trial What are inclusion / exclusion criteria?What are inclusion / exclusion criteria? What are inclusion / exclusion criteria?What are inclusion / exclusion criteria? How were random assignments made?How were random assignments made? What are potential sources of bias?What are potential sources of bias?


What are potential sources of bias?What are potential sources of bias?

Problem 1Problem 1Problem 1Problem 1

TwentyTwenty--five male volunteers, ages 18 to 24five male volunteers, ages 18 to 24TwentyTwenty five male volunteers, ages 18 to 24 five male volunteers, ages 18 to 24 years, participated in a study to compare years, participated in a study to compare effects of small doses of melatonin and a effects of small doses of melatonin and a l b i d l b d il b i d l b d iplacebo to induce sleep at bedtime. placebo to induce sleep at bedtime.

Subjects who took melatonin fell asleep in 5 Subjects who took melatonin fell asleep in 5 6 i t l t h i d th6 i t l t h i d thor 6 minutes; volunteers who received the or 6 minutes; volunteers who received the

placebo took 15 minutes or more to fall placebo took 15 minutes or more to fall asleep The researchers concluded thatasleep The researchers concluded thatasleep. The researchers concluded that asleep. The researchers concluded that melatonin in small doses may be an effective melatonin in small doses may be an effective sleep aid. sleep aid.

Eberly and Telke 52PubH 6450

1. What is the sample?p

1.1. TwentyTwenty--five male five male volunteersvolunteers

2.2. Male who ages 18 Male who ages 18 ggto 24 yearsto 24 years

33 All malesAll males3.3. All malesAll males

53PubH 6450 Eberly and Telke

2. The interested population is ____?p p

1.1. TwentyTwenty--five male five male volunteersvolunteers

2.2. Male who ages 18 Male who ages 18 ggto 24 yearsto 24 years

33 All malesAll males3.3. All malesAll males


3. What is the outcome of interest?

11 The age ofThe age of1.1. The age of The age of volunteersvolunteers

22 The time to fallThe time to fall2.2. The time to fall The time to fall asleepasleepTh d fTh d f3.3. The doses of The doses of melatoninmelatonin

4.4. The doses of a The doses of a placeboplacebo


4. What is the study design?y g

1.1. CrossCross--sectionalsectional2.2. CaseCase--controlcontrol33 CohortCohort3.3. CohortCohort4.4. Clinical trialClinical trial


Problem 2Problem 2Problem 2Problem 2 Oncologists at the National Cancer Center Institute Oncologists at the National Cancer Center Institute

studied the effects of interleukinstudied the effects of interleukin--2 (IL2 (IL--2) an immune2) an immunestudied the effects of interleukinstudied the effects of interleukin--2 (IL2 (IL--2), an immune 2), an immune system protein, in patients with spreading melanoma or system protein, in patients with spreading melanoma or unresponsive, spreading kidney cell cancer. Their goal unresponsive, spreading kidney cell cancer. Their goal was to determine if the use of ILwas to determine if the use of IL--2 spurs the patient’s2 spurs the patient’swas to determine if the use of ILwas to determine if the use of IL 2 spurs the patient s 2 spurs the patient s immune system to fight the cancer and halt its spread. immune system to fight the cancer and halt its spread.

300 patients are randomized to treatment or placebo, 20 300 patients are randomized to treatment or placebo, 20 in the treatment group experienced total remission andin the treatment group experienced total remission andin the treatment group experienced total remission and in the treatment group experienced total remission and remained in remission for at least 8 years. 5 in the remained in remission for at least 8 years. 5 in the placebo group experienced total remission and remained placebo group experienced total remission and remained in remission for at least 8 years.. The investigators in remission for at least 8 years.. The investigators y gy gconcluded the use of ILconcluded the use of IL--2 marks a significant advance in 2 marks a significant advance in the treatment of these two types of cancer. the treatment of these two types of cancer.


1. The 300 patients in this study are the ?the___?

1.1. PopulationPopulationS lS l2.2. SampleSample

3.3. Selected to Selected to treatment or treatment or placebo groups by placebo groups by someonesomeone


2. This study is ____?y

1.1. Retrospective and Retrospective and observationalobservational

2.2. Retrospective and Retrospective and experimentalexperimental

3.3. Prospective and Prospective and experimentalexperimentalexperimentalexperimental

4.4. Prospective and Prospective and observationalobservational

Eberly and Telke 59

observationalobservational

PubH 6450

Problem 3Problem 3Problem 3Problem 3

A study was conducted relating to the epidemiology A study was conducted relating to the epidemiology y g p gyy g p gyof breast cancer and the possible involvement of of breast cancer and the possible involvement of dietary fats, vitamins and other nutrients. dietary fats, vitamins and other nutrients.

It included 2024 breast cancer patients admitted toIt included 2024 breast cancer patients admitted to It included 2024 breast cancer patients admitted to It included 2024 breast cancer patients admitted to Roswell Park Memorial Institute, Erie County, New Roswell Park Memorial Institute, Erie County, New York, from 1958 to 1965. Another group of 1463 York, from 1958 to 1965. Another group of 1463 people was chosen from patients having no people was chosen from patients having no neoplasmsneoplasms and no pathology of gastrointestinal or and no pathology of gastrointestinal or reproductive systems The primary factors beingreproductive systems The primary factors beingreproductive systems. The primary factors being reproductive systems. The primary factors being investigated were vitamins A and E (measured in investigated were vitamins A and E (measured in international units per month). international units per month).


1. What is the exposure of this study?p

11 Vitamins A and EVitamins A and E1.1. Vitamins A and EVitamins A and E2.2. Whether patients Whether patients

get breast cancerget breast cancerget breast cancerget breast cancer3.3. Whether patients Whether patients

hh llhave have neoplasmsneoplasms or or pathology of pathology of

t i t ti lt i t ti lgastrointestinal or gastrointestinal or reproductive reproductive

ttsystemssystemsEberly and Telke 62PubH 6450

2. This study is ____?y

1.1. Retrospective and Retrospective and observationalobservational

2.2. Retrospective and Retrospective and experimentalexperimental

3.3. Prospective and Prospective and observationalobservationalobservationalobservational

4.4. Prospective and Prospective and experimentalexperimental


experimentalexperimental

What type of data wereWhat type of data wereWhat type of data were What type of data were collected?collected?

Measurement ScalesMeasurement Scales

Measurement ScalesMeasurement ScalesMeasurement ScalesMeasurement ScalesThe two broad categories of data are Categorical The two broad categories of data are Categorical

and Numericaland Numericaland Numericaland Numerical Categorical dataCategorical data

Also called ‘Qualitative’Also called ‘Qualitative’ Examples: gender, blood type, race, disease status, Examples: gender, blood type, race, disease status,

etc.etc. Data consist of the counts in each categoryData consist of the counts in each categoryData consist of the counts in each category Data consist of the counts in each category

Numerical dataNumerical data Also called ‘Quantitative’Also called ‘Quantitative’

Diff b t th b h iDiff b t th b h i Differences between the numbers have meaning on a Differences between the numbers have meaning on a numerical scalenumerical scale

Examples: weight, height, survival time, blood Examples: weight, height, survival time, blood pressurepressure


pressurepressure

Types of Categorical DataTypes of Categorical DataTypes of Categorical DataTypes of Categorical Data Nominal Nominal –– two or more categories with no natural two or more categories with no natural

ddorder order Examples: Gender, Race, Blood group Examples: Gender, Race, Blood group

O di lO di l t t i th t ht t i th t h OrdinalOrdinal –– two or more categories that have a two or more categories that have a natural ordernatural order Ex Apgar scores tumor stage Social classEx Apgar scores tumor stage Social class Ex. Apgar scores, tumor stage, Social classEx. Apgar scores, tumor stage, Social class Numerical assignments are relative (> or <) and do not Numerical assignments are relative (> or <) and do not

represent any interval relationship between categories represent any interval relationship between categories BinaryBinary –– a special case of either Ordinal or a special case of either Ordinal or

Nominal dataNominal data


Binary data is categorical data with only two categoriesBinary data is categorical data with only two categories

Contingency TablesContingency TablesContingency TablesContingency TablesData for two categorical characteristics are often Data for two categorical characteristics are often

displayed in contingency tables. The cell counts are displayed in contingency tables. The cell counts are p y g yp y g ythe number of subjects with each combination of the number of subjects with each combination of the characteristics.the characteristics.

Lung CancerLung Cancer No Lung No Lung CancerCancer

SmokerSmoker 8585 1515

ExEx--smokersmoker 1515 1010ExEx smokersmoker 1515 1010

NonNon--smokersmoker 00 7575


Numerical ScalesNumerical ScalesNumerical ScalesNumerical Scales

Continuous scaleContinuous scale –– data that can take on any data that can take on any real value on the measurement scalereal value on the measurement scale Blood pressure, temperature, age, weight, height etc. Blood pressure, temperature, age, weight, height etc.

can all be measured on a continuumcan all be measured on a continuumcan all be measured on a continuumcan all be measured on a continuum Discrete scalesDiscrete scales –– data that are only integersdata that are only integers

Number of children in a family number of births in aNumber of children in a family number of births in a Number of children in a family, number of births in a Number of children in a family, number of births in a year, number of accidents in a month etc. year, number of accidents in a month etc.

Arithmetic operations are meaningful forArithmetic operations are meaningful forArithmetic operations are meaningful for Arithmetic operations are meaningful for numerical data numerical data


Diagram of Measurement ScalesDiagram of Measurement ScalesDiagram of Measurement ScalesDiagram of Measurement Scales

Categorical Numerical

Ordinal Nominal Continuous DiscreteOrdinal Nominal Continuous Discrete

scale not ordered any value integerson the scale


Q i 1Question 1:Is this variable qualitative or quantitative?

Infant birth weight (grams)Infant birth weight (grams)

Q lit tiQ lit ti1.1. QualitativeQualitative2.2. QuantitativeQuantitative

Q estion 2:Question 2:Is this variable categorical or continuous?

Household income Household income (b l l l b l)(b l l l b l)(below normal, normal, above normal)(below normal, normal, above normal)

1.1. CategoricalCategorical22 ContinuousContinuous2.2. ContinuousContinuous

Q ti n 3Question 3:Is this variable qualitative or quantitative?

Number of children in the familyNumber of children in the family

1.1. QualitativeQualitative2.2. Quantitative (Discrete) Quantitative (Discrete) 3.3. Quantitative (Continuous)Quantitative (Continuous)( )( )4.4. None of these.None of these.

Question 4:Is this variable quantitative?

Social Security number

11 TrueTrue1.1. TrueTrue2.2. FalseFalse

Question 5:Question 5:Rate your instructor’s teaching ability.

1=Poor, 2=Fair, 3=Good, 4=Very Good, 5=Excellent

Is this variable categorical or continuous?Is this variable categorical or continuous?

11 CategoricalCategorical1.1. CategoricalCategorical2.2. ContinuousContinuous3.3. EitherEither4.4. NeitherNeither

Question 6Question 6Rate your instructor’s teaching ability.

1=Poor, 2=Fair, 3=Good, 4=Very Good, 5=Excellent

Is this variable Nominal Ordinal or Binary?Is this variable Nominal, Ordinal or Binary?

11 NominalNominal1.1. NominalNominal2.2. OrdinalOrdinal3.3. BinaryBinary4.4. None of these.None of these.

Question 7OUTCOME WHEN TOSSING AOUTCOME WHEN TOSSING A

COIN.Heads or tailsHeads or tails

Is this variable Nominal OrdinalIs this variable Nominal, Ordinal or Binary?

11 NominalNominal1.1. NominalNominal2.2. OrdinalOrdinal3.3. BinaryBinary4.4. None of these.None of these.

Question 8Number of heads when tossing a

coin 30 times.coin 30 times.

I hi i bl Bi ?Is this variable Binary?

11 NoNo1.1. NoNo2.2. YesYes

Question 8Number of heads when tossing a

coin 30 times.coin 30 times.

Wh i hi i bl ?What is this variable?

11 Quantitative (Discrete)Quantitative (Discrete)1.1. Quantitative (Discrete)Quantitative (Discrete)2.2. Quantitative (Continuous)Quantitative (Continuous)3.3. NominalNominal4.4. Categorical BinaryCategorical Binaryg yg y

Relationships between Numerical Relationships between Numerical and Categorical Dataand Categorical Data

Numerical data can be converted to categorical Numerical data can be converted to categorical ggdatadata For example, age is a numerical continuous variable For example, age is a numerical continuous variable

but it can be summarized as ‘age groups’: 0but it can be summarized as ‘age groups’: 0--5, 65, 6--10, 10, g g pg g p ,, ,,1111--19, 2019, 20--39, 4039, 40--59, 6059, 60--79, 80+79, 80+

When represented as ‘age groups’, age is a When represented as ‘age groups’, age is a categorical (ordinal) variablecategorical (ordinal) variableg ( )g ( )

Ordinal data can be coded numerically Ordinal data can be coded numerically The numerical coding of ordinal data does not mean The numerical coding of ordinal data does not mean

that the ordinal data are now numerical howeverthat the ordinal data are now numerical howeverthat the ordinal data are now numerical, howeverthat the ordinal data are now numerical, however The codes represent the The codes represent the order order of the categories, not of the categories, not

the interval relationship between categoriesthe interval relationship between categories


Next topics: Summary Statistics and Next topics: Summary Statistics and graphsgraphs

For Numerical DataFor Numerical Data Statistics: Mean, standard deviation, median, Statistics: Mean, standard deviation, median,

range, percentilerange, percentile Tables and graphs: frequency distribution, Tables and graphs: frequency distribution,

histograms, boxhistograms, box--plots, scatterplots, scatter--plotsplotsF C t i l D tF C t i l D t For Categorical DataFor Categorical Data Statistics: proportion, percent, rates, relative Statistics: proportion, percent, rates, relative

i k dd ii k dd irisk, odds ratiorisk, odds ratio Tables and graphs: bar charts, pie charts, Tables and graphs: bar charts, pie charts,

ti t blti t bl81PubH 6414 Lesson 1

contingency tablescontingency tables

Readings and AssignmentsReadings and AssignmentsReadings and AssignmentsReadings and Assignments

Readings:Readings: Chapter 2: Study Designs in Medical ResearchChapter 2: Study Designs in Medical Research Chapter 3: Scales of Measurement pgs 26Chapter 3: Scales of Measurement pgs 26--2727 Chapter 4: Pages 68Chapter 4: Pages 68--7272 Chapter 4: Pages 68Chapter 4: Pages 68--7272 Optional: Chapter 13 pgs 332 Optional: Chapter 13 pgs 332 -- 335335

Practice Exercises for Lesson 1Practice Exercises for Lesson 1 Try Intro to Excel Module on your own:Try Intro to Excel Module on your own:http://www.biostat.umn.edu/~http://www.biostat.umn.edu/~susant/FALL09PH6414LAB.htmlsusant/FALL09PH6414LAB.html

St t H k 1 P bl 1 d 2St t H k 1 P bl 1 d 2 Start Homework 1: Problems 1 and 2Start Homework 1: Problems 1 and 2 New vocabulary: look up any unfamiliar terms in New vocabulary: look up any unfamiliar terms in

thethe Pocket Dictionary of StatisticsPocket Dictionary of Statistics or the textor the text


the the Pocket Dictionary of Statistics Pocket Dictionary of Statistics or the text or the text glossaryglossary

introduction to statistics lesson 1

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