In The Name Of God Topic: COHORT Studies Armin Hirbod-Mobarakeh In The Name Of God Topic: COHORT Studies Presenter: Armin Hirbod-Mobarakeh

Targets Definition of cohort study Methodology Measures in cohort studies Advantages in cohort study Disadvantages in cohort study Types of cohort studies Biases in cohort studies Subgroups of cohort study A paradigm Armin Hirbod-Mobarakeh

Definition of cohort study Definition of term Term in research studies Armin Hirbod-Mobarakeh

Methodology Start with persons having the presumed cause (exposure). BUT free from the outcome (disease), and then wait for them to develop the effect Comparison group - also free from disease, but who, also DO NOT have the presumed cause Armin Hirbod-Mobarakeh

Cohort Study Design Exposed Not Exposed Disease People Population Without Disease No Disease Not Exposed Disease No Disease Armin Hirbod-Mobarakeh

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Advantages of Cohort Studies Can assess several outcomes Prospective control over exposure and outcome measurement possible (in prospective studies) Somewhat less potential for bias than case-control studies, but equal potential for confounding We can learn about prognosis and etiology of the disease Armin Hirbod-Mobarakeh

Disadvantages of Cohort Studies Not useful for rare outcomes As an observational study can never be assumed to be free of confounding and bias Expensive Time needed to conduct these studies Why we can not do one follow up Armin Hirbod-Mobarakeh

Types Of Cohort Studies Timing • Prospective • retrospective Open and closed cohorts • Open - people moving in and out • Closed - fixed population Armin Hirbod-Mobarakeh

Prospective cohort study Disease occurrence Exposure Study starts time time Exposure Study starts Disease occurrence Armin Hirbod-Mobarakeh

Retrospective cohort studies Disease occurrence Study starts Exposure time Armin Hirbod-Mobarakeh

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Measures in Cohort Studies Cumulative incidence Incidence density Risk ratio Odds ratio Armin Hirbod-Mobarakeh

Cumulative Incidence Cumulative incidence (CI) =is the proportion of people in a population who became diseased or ill or experienced an event during the specified period of time. CI = No. new cases of disease or events during time period Total population at risk at the beginning of the time period Armin Hirbod-Mobarakeh

Cumulative Incidence Example 818 women had in vitro fertilization in NSW during 2000 80 developed a clinical pregnancy within one month of follow-up after the first embryo transfer procedure. The CI of pregnancy was?? CI= 80/818 9.8 cases per hundred women on the program Armin Hirbod-Mobarakeh

Incidence Density The incidence rate or incidence density is the number of new cases in a population divided by the total time units each individual in the population at risk was observed. Incidence Rate= No new cases of disease/events during the specified time period Sum of the length of time during which each person in the population is at risk Armin Hirbod-Mobarakeh

Incidence Rate - Example (Incidence Density) In investigating the incidence of duodenal ulcer following the use of a specific drug in 14 subjects. 4 subjects started the study in Jan 1990 and all finished the study in Dec 1999. Ten subjects joined the study in Dec1995 and finished the study in November 1996. During the period of observation: 5 people developed duodenal ulcer while taking the drug. Armin Hirbod-Mobarakeh

Incidence Density What is total length of time that persons were in the population is at risk (denominator)? 4 X 10 years = 40 years 10 x 1 year = 10 years Total = 50 person-years New cases = 5 What is the incidence rate of duodenal ulcers after taking the drug? Incidence rate = 5 / 50 = 10 cases per 100 person-years Armin Hirbod-Mobarakeh

Risk ratio The relative risk is simply the ratio of the two conditional probabilities. Cases Non-cases Totals Exposed A B A+B Not Exposed C D C+D A+C B+D Cohort Analysis: RR = A/[A+B] C/[C+D] Armin Hirbod-Mobarakeh

ODDS RATIO It is defined as the ratio of the odds of an event occurring in one group to the odds of it occurring in another group, or to a sample-based estimate of that ratio. Armin Hirbod-Mobarakeh

You can understand the odds ratio by first noticing what the odds are in each row of the table. The odds for row Y- are a/b. The odds for row Y+ are c/d. The odds ratio (OR) is simply the ratio of the two odds. Cases Non-cases Totals Exposed A B A+B Not Exposed C D C+D A+C B+D Armin Hirbod-Mobarakeh

Comparing Odds Ratio and Relative Risk Outcome cancer no cancer Exposure Exposed (smoke) 70 300 Not Exposed (non smoke) 30 700 100 1000 RR = A/[A+B] C/[C+D]= 4.41 OR = ad/bc = 5.44 Armin Hirbod-Mobarakeh

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Biases Selection bias Information bias Confounding bias This classification is by Miettinen OS in 1970s See for example Miettinen & Cook, 1981 Armin Hirbod-Mobarakeh

Selection Bias Front-End Bias(can be reduced by screening tests) Non-response bias(can be reduced by analyze) Migration bias(can be reduced by analyze) Consider a study of the effects of exercise on all-cause mortality in persons who are thought to be completely healthy at baseline. Now consider what would happen if some participants with undiagnosed cardiovascular disease (CAD) were indeed enrolled in the study and indeed it turns out that they exercise less (say because they get out of breath more easily). Selection bias occurs when those persons lost to follow up have a different probability of the outcome than those persons who remain in the analysis Armin Hirbod-Mobarakeh

Information bias Surveillance bias diagnostic bias Analytic bias can be reduced by blinding Armin Hirbod-Mobarakeh

confounding bias Example of Confounding can be reduced by matching Night Light and myopia in Quinn's study Heavy coffee drinking and myocardial infarction can be reduced by matching Armin Hirbod-Mobarakeh

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Subgroups of cohort study Historical cohort Armin Hirbod-Mobarakeh

Historical Cohort Studies Cohort formed in the past with period of follow-up ending also in the past Example: Atomic bomb blast survivors While the Historical Cohort Study is the most well-known type of cohort study, there are other types of cohort studies. The Incidence Cohort Study assesses the incidence of disease and seeks to identify risk factors for disease onset. It answers the question, “Is the incidence greater in those exposed than in those who are non-exposed?” The Prognostic Cohort Study follows a diseased cohort to assess factors associated with the outcome. The outcome may be either recovery or death. The primary purpose is to identify all the explanatory factors for the outcome. Such explanatory factors are also known as prognostic factors. The Randomized Controlled Trial (RCT) can also be considered a special type of cohort studies. Armin Hirbod-Mobarakeh

Advantages of Historical Cohort Studies Easier to create the cohort Follow-up has already occurred Less costly and time consuming Armin Hirbod-Mobarakeh

Disadvantages of Historical Cohort Studies Incomplete data sets No control over the quality of the measurements that are available Incomplete control of confounding Armin Hirbod-Mobarakeh

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Paradigm Fereidoon azizi TLGS(Tehran Lipid and Glucose Study) Sample:The study cohort consists of more than 15,000 individuals who are older than 3 yr at study entry The sampling frame is chosen from urban district 13 of Tehran The reasons for choosing district 13 as the sample The population that resides in that district is relatively stable compared with the other districts of Tehran the medical and health facilities in this district are under the supervision of Shahid Beheshti University of Medical Sciences, which also hosts the Endocrine Research Center, in which the study is designed and managed; the health centers of district 13 enjoy a well-developed network of experienced volunteers, who play a critical role in the recruitment of individuals for the study the age distribution of the population of district 13 are representative of the overall population of Tehran and Iran Armin Hirbod-Mobarakeh

samples were selected as follows: Phase 1 : population survey baseline health examinations The primary objectives: measure the population prevalence of known cardiovascular risk factors, including dyslipoproteinemia, hyperglycemia, obesity, smoking, and hypertension. samples were selected as follows: A list of all households under coverage by three health centers in east of Tehran was prepared households were specified according to each health center the proportion of households under coverage by each health center to the total number of households in the three health centers was determined lists of all households selected were prepared, and their addresses were determined. Samples were selected using the stratified sampling method. Armin Hirbod-Mobarakeh

actions Sending invitations :The crude response rate was approximately 57.5%. there was no significant difference between responders and nonresponders . interview and medical examination.:Participants were first familiarized with the study objectives and were asked to sign a written consent baseline medical examinations: In this section, trained physicians collected data on the medical history, BP, peripheral pulse, and thyroid examination. Trained technicians obtained anthropometric data such as height, weight, and hip and waist sizes. ECG was taken from those aged 30 yr. Blood samples were drawn after 10 to 12 h of fasting. Laboratory measurements included lipid profiles, fasting blood sugar, thyroid profile, and serum creatinine. After baseline medical examinations, study participants are being contacted annually by telephone about Medical events. After identification of events, confirmatory data are being collected by study physicians by abstracting hospital records and performing in-home physical examinations. Armin Hirbod-Mobarakeh

Oh!!!!!!! Finally it’s over Armin Hirbod-Mobarakeh