Prospective StudyProspective Study Cohort Study Cohort Study

Assis.Prof.Dr Diaa MarzoukAssis.Prof.Dr Diaa MarzoukCommunity MedicineCommunity Medicine

What is a cohort?What is a cohort?

A cohort is a group of persons A cohort is a group of persons who share a common who share a common experience within a defined experience within a defined time period.time period.

Healthy cohorts are followed up Healthy cohorts are followed up forward in time for the forward in time for the development of a diseasedevelopment of a disease

Examples of cohorts:Examples of cohorts:

Birth cohort:Birth cohort:All persons born within a given All persons born within a given period of time.period of time.Marriage cohort:Marriage cohort:All persons married within a All persons married within a given period of timegiven period of timeOccupational cohort:Occupational cohort:

Selection of cohorts:Selection of cohorts:

Volunteers:Volunteers:Because it is acssesableBecause it is acssesableFrom armed forces:From armed forces:Because its medical records are Because its medical records are availableavailableHave particular exposue:Have particular exposue:At workAt work

Prospective StudyProspective StudyCohort StudyCohort Study

It starts with a group of people / It starts with a group of people / cohort: cohort: All considered to be All considered to be free of a free of a given disease.given disease.But But vary in exposurevary in exposure to a to a supposed risk factor.supposed risk factor.

Information is gathered about Information is gathered about their exposure to the suspected their exposure to the suspected risk factorrisk factorThe individuals are divided into The individuals are divided into exposed and not exposedexposed and not exposed

To the factor of interestTo the factor of interest

The cohort is followed over The cohort is followed over time in order to determine time in order to determine differences in differences in the rate at which the rate at which disease developsdisease develops in relation to in relation to exposure to the factorexposure to the factor

Retrospective StudiesRetrospective StudiesCase Control St.Case Control St.

Diseased and nondiseased Diseased and nondiseased groups (cases and controls) are groups (cases and controls) are selected and compared for selected and compared for presence or absence of presence or absence of antecedent factor (risk factor)antecedent factor (risk factor)

Advantages of Advantages of Prospective StudyProspective Study

1.1. The cohort is classified in The cohort is classified in relation to exposure to the relation to exposure to the factor before the disease factor before the disease developsdevelops

This classification cannot be This classification cannot be influenced by the knowledge influenced by the knowledge that disease exists.that disease exists.

2. It permits calculation of 2. It permits calculation of Incidence rates among Incidence rates among exposed and not exposed.exposed and not exposed.

3. Theabsolute difference 3. Theabsolute difference between both is the between both is the attributable risk.attributable risk.

3. The relative risk.3. The relative risk.

4. 4. Permits observation of many Permits observation of many outcomesoutcomes, , e.g smoking and lung cancer, e.g smoking and lung cancer, showed that smoking is associated showed that smoking is associated with other otcomes as emphysema, with other otcomes as emphysema, CHD, peptic ulcer, cancer larynx, CHD, peptic ulcer, cancer larynx, oral cavity, oesopphagus and oral cavity, oesopphagus and urinary bladder. urinary bladder.

Disadvantages of Disadvantages of Prospective studiesProspective studies

1.1. Long, expensive and large Long, expensive and large scale undertaking.scale undertaking.

2.2. The problem of attrition: loss The problem of attrition: loss of patients due to lack of of patients due to lack of interest, migration or death interest, migration or death from other causes.from other causes.

3. Changes in diagnostic criteria 3. Changes in diagnostic criteria and methods over timeand methods over time

4. Administrative problems as 4. Administrative problems as loss of staff, loss of funding, and loss of staff, loss of funding, and the high costs of record keepingthe high costs of record keeping

Analysis of ResultsAnalysis of Results

Anlytic studies are designed to Anlytic studies are designed to determine whether an determine whether an association exsists between a association exsists between a factor or exposure and a disease factor or exposure and a disease and to determine the strength of and to determine the strength of the association.the association.

Relative RiskRelative Risk

It is an important measure of It is an important measure of association that relates the association that relates the incidence rates of the disease incidence rates of the disease under study among those with under study among those with and without the factor or and without the factor or exposure. exposure.

Relative RiskRelative Risk

It is defined as the ratio of the It is defined as the ratio of the incidence rate for persons incidence rate for persons exposed to the incidence rate exposed to the incidence rate for those not exposed.for those not exposed.

Relative Risk (RR)=Relative Risk (RR)=

Incidence among exposedIncidence among exposed

Incidence among unexposedIncidence among unexposed

Diseased Not DiseasedDiseased Not Diseased

Exposed a bExposed a b

Not Exposed c dNot Exposed c d

RR= RR= a a ÷ ÷ c c = = adad

a+b c+d bca+b c+d bc

Historical Prospective Historical Prospective StudiesStudies

It combines the advantages of It combines the advantages of both retrospective and both retrospective and prospective study desgins.prospective study desgins.It involves following healthy It involves following healthy exposed and unexposed cohorts exposed and unexposed cohorts for the development of the for the development of the disease.disease.

These cohorts are constructed These cohorts are constructed retrospectively through existing retrospectively through existing records that permit correct records that permit correct classification of the exposure classification of the exposure status of individualsstatus of individuals

Study subjectd are traced to Study subjectd are traced to the present time or sometimes the present time or sometimes to the future as well.to the future as well.The analysis of this study is as The analysis of this study is as the prospective study.the prospective study.

Examples of Cohort StudiesExamples of Cohort StudiesI-I- OBJECTIVE: OBJECTIVE: To identify risk factors for breast To identify risk factors for breast cancer among female survivors of childhood cancer among female survivors of childhood cancer.cancer.

Exposure:Exposure:Survivors of childhood cancer are at risk for Survivors of childhood cancer are at risk for secondary breast cancer.secondary breast cancer. DESIGN:DESIGN: Retrospective cohort study. Retrospective cohort study.

SETTING:SETTING: The Childhood Cancer Survivor Study The Childhood Cancer Survivor Study (CCSS), a multicenter study of persons who (CCSS), a multicenter study of persons who survived more than 5 years after childhood cancer survived more than 5 years after childhood cancer diagnosed from 1970 to 1986. diagnosed from 1970 to 1986.

PARTICIPANTS: PARTICIPANTS: Among 6068 women in the Among 6068 women in the CCSS, 95 women had 111 confirmed cases of CCSS, 95 women had 111 confirmed cases of breast cancer. breast cancer.

MEASUREMENTS: MEASUREMENTS: Standardized incidence Standardized incidence ratios for breast cancer were calculated by using ratios for breast cancer were calculated by using age-specific incidence rates in the general age-specific incidence rates in the general population. population. Breast cancer incidence was evaluated Breast cancer incidence was evaluated with with respect to primary cancer diagnosisrespect to primary cancer diagnosis and therapy, and therapy, age at and time since primary diagnosis, menstrual age at and time since primary diagnosis, menstrual and reproductive history, and family history of and reproductive history, and family history of cancer. cancer.

RESULTS: RESULTS:

Breast cancer risk was increased in Breast cancer risk was increased in survivors who were treated with chest survivors who were treated with chest radiation therapy (standardized incidence radiation therapy (standardized incidence ratio, 24.7 [95% CI, 19.3 to 31.0]) and ratio, 24.7 [95% CI, 19.3 to 31.0]) and survivors of bone and soft-tissue sarcoma survivors of bone and soft-tissue sarcoma who were not treated with chest radiation who were not treated with chest radiation therapy (standardized incidence ratios, 6.7 therapy (standardized incidence ratios, 6.7 and 7.6, respectively). and 7.6, respectively).

CONCLUSION:CONCLUSION:

Survivors of childhood sarcomas and those Survivors of childhood sarcomas and those who received chest radiation therapy are at who received chest radiation therapy are at risk for secondary breast cancer. When risk for secondary breast cancer. When assessing a survivor's risk, clinicians assessing a survivor's risk, clinicians should consider primary diagnosis, should consider primary diagnosis, previous radiation therapy, family cancer previous radiation therapy, family cancer history, and history of thyroid disease.history, and history of thyroid disease.

II-II-Growth in prepubertal Growth in prepubertal

children with cystic fibrosischildren with cystic fibrosis In cystic fibrosis, growth and lung function In cystic fibrosis, growth and lung function have been identified as prognostic markers have been identified as prognostic markers of both severity of pulmonary disease and of both severity of pulmonary disease and survival. survival.

Objective:Objective:longitudinal design to determine whether longitudinal design to determine whether normalisation of growth could be found in normalisation of growth could be found in the genetic subgroup of prepubertal the genetic subgroup of prepubertal children with CFchildren with CF with the homozygous Delta with the homozygous Delta F508 mutation, which is one of the known F508 mutation, which is one of the known severe mutations. severe mutations.

METHODS: METHODS: Data of all children born after 1980 with the Data of all children born after 1980 with the homozygous Delta F508 mutation, homozygous Delta F508 mutation, diagnosed in early childhood at the diagnosed in early childhood at the specialised centre of the Children's Hospital specialised centre of the Children's Hospital of Berne were systematically assessed up of Berne were systematically assessed up to the age of 11 years and retrospectively to the age of 11 years and retrospectively analysed. Follow-up data of height, weight analysed. Follow-up data of height, weight and BMI were compared to the Swiss and BMI were compared to the Swiss reference population using z-scores. reference population using z-scores.

RESULTS:RESULTS: In the study, cohort growth (height, weight In the study, cohort growth (height, weight and BMI) was significantly below that of the and BMI) was significantly below that of the normal Swiss population. A significant normal Swiss population. A significant decline of lung function with age was also decline of lung function with age was also found, however, no association between found, however, no association between lung function and growth could be seen. lung function and growth could be seen. Compared to an earlier cohort, an improved Compared to an earlier cohort, an improved growth over the last decade could be shown growth over the last decade could be shown but no improvement on lung function could but no improvement on lung function could be detectedbe detected

CONCLUSION: CONCLUSION: In contrast to sequential cross-In contrast to sequential cross-sectional studies of children with CF, sectional studies of children with CF, the present longitudinal study of the present longitudinal study of children with homozygous for the children with homozygous for the Delta F508 mutation failed to confirm Delta F508 mutation failed to confirm normalisation of growth over time. normalisation of growth over time.