Analytical Epidemiology clinical trials

ANALYTICAL STUDY DESIGN : 

ANALYTICAL STUDY DESIGN BY: DR. ARCHANA CHAVAN NEXUS CRI

EPIDEMIOLOGY : 

EPIDEMIOLOGY DEFINATION: The branch of medicine that deals with the study of the causes, distribution, and control of disease in populations. Analytical studies Observational studies Case-control studies Cohort studies Intervention studies Clinical trials

ANALYTICAL EPIDEMIOLOGY : 

ANALYTICAL EPIDEMIOLOGY IN ANALYTICAL STUDIES , THE SUBJECT OF INTEREST IS THE INDIVIDUAL WITHIN THE POPULATION. THE OBJECT IS NOT TO FORMULATE BUT TO TEST THE HYPOTHESES. ANALYTICAL STUDY COMPRISE TWO DISTINCT TYPES OF OBSERVATIONAL STUDIES A. Case control B. Cohort

CASE- CONTROL STUDIES : 

CASE- CONTROL STUDIES CASE CONTROL STUDIES, OFTEN CALLED “RETROSPECTIVE STUDY”. COMMON FIRST APPROACH TO TEST CAUSAL HYPOTHESES. DISTANCT FEATURE: a. Both exposure and outcome (disease) have occurred before the start of the study. b. The study proceeds backwards from effect to cause. c. It uses a control or comparison group to support or refute an inference.

Case Control : 

Case Control Basically comparision studies. Cases and controls must be comparable with respect to known confounding factors. Confounding factors viz: name, age, sex, occupation. Eg: cases – immunized childrens Vs Controls are all unimmunized look for factor of interest.

Basic Design : 

Basic Design Basic Design = 2x2

Analysis : 

Analysis Intention to test the Hypothesis: ‘Cigarette smoking causes lung cancer’ Therefore total No. of cases _ a + c Total no. of controls – b + d

BASIC STEPS : 

BASIC STEPS A. Selection of cases and controls. Matching. Measurement of exposure and Analysis and interpretation.

Selection of cases : 

Selection of cases Diagnostic Criteria: should be same throughout the patients. Eligibility criteria: eg: newly diagnosed cases within a specified period of time are eligible then old cases with advanced stages.

Sources of Cases : 

Sources of Cases Hospitals. General population.

Selection of Controls : 

Selection of Controls Controls must be free from th disease under study. Sources of controls: Hospital controls. Relatives. Neighborhood. General population.

Matching : 

Matching Controls may differ from the cases in No. of Factors eg. Age, sex, occupation, social status etc. Matching is defined as the process by which we select controls in such a way that they are similar to cases with regards to certain pertinent selected variables (eg. age) which are known to influence the outcome of the disease.

Confounding factors : 

Confounding factors Are defined as one which is associated both with exposure and disease and is distributed unequally in study and control groups. More specifically a confounding factor is one that although associated with exposure under investigation is itself independently of any such association a “risk factor”. Eg. Role of alcohol in aetiology of oseophageal cancer.

CONFOUNDING FACTOR : 

CONFOUNDING FACTOR Smoking is confounding factor because it is associated with the consumption of Alcohol and also independent risk factor for esophageal cancer. While matching it should be borne in mind that the suspected etiological factor or the variable we wish to measure should not be matched

Contd. : 

Contd. Eg: 50- year old mason with a particular disease, we will search 50- year old mason without that disease as a control.hus one can obtain pairs of patients and control of the same sex, age, duration and severity of illness.

MEASUREMENT OF THE EXPOSURE : 

MEASUREMENT OF THE EXPOSURE Information about the exposure should be obtained in precisely the same manner both for cases and controls. This may be obtained by the interviews, by questionnaires, or by studying past records of cases such as hospital records, employment records.

ANALYSIS : 

ANALYSIS The final step is Analysis: To find association between: Exposure rate among cases and controls to suspected factors. Estimation of the Disease risk associated with exposure (odds ratio).

Case control studies of Smoking and lung cancer : 

Case control studies of Smoking and lung cancer

EXPOSURE RATE : 

EXPOSURE RATE Exposure rates: A. Cases a/a + b = 33/35 = 94.2%. B. Controls = b/b + c = 55/82 = 67.0% This shows frequency rate of lung cancer was definitely higher among smokers than among non-smokers.

ESTIMATION OF RISK : 

ESTIMATION OF RISK The second analytical step is estimation of disease association with exposure. Exposure rate is 94.2 % in study group that does not mean that 94.2% those smoked would develop lung cancer.

ESTIMATION OF RISK : 

ESTIMATION OF RISK The estimation of disease risk associated with exposure is obtained by an index known as “Relative Risk” or Risk ratio (RR) RR = incidence among exposed x 100 incidence among non- exposed = a/(a + b) + c/ (c + d)

RELATIVE RISK : 

RELATIVE RISK Case control Studies does not provide incidence rates from which relative risk can be calculated directly, because there is no appropriate denominator or population a risk. In General RR can be calculated only from a cohort Study.

ODDS RATIO : 

ODDS RATIO Measure of strength of association between risk factors and outcome. Odds ratio is closely related to Relative risk. Based on 3 assumption: Disease being investigated must be relatively rare. In fact majority of the chronic disease have a low incidence in the general population.

ODDS RATIO : 

ODDS RATIO 2. The cases must be representative of those with the disease. 3. The controls must be representative of those without the disease.

Odds Ratio : 

Odds Ratio Odds Ratio : ad/ bc 33 X 27/55 X 2 = 8.1 In above e.g. Smokers showed a risk of having lung cancer 8.1 times that of Non- smokers. Odds ratio is Key Parameter in the analysis of case control studies.

Bias in Case control studies : 

Bias in Case control studies Bias due to confounding factors. Memory or recall Bias. Selection Bias. Interviewers Bias.

ADVANTAGES OF CASE- CONTROL STUDIES : 

ADVANTAGES OF CASE- CONTROL STUDIES Relatively easy to carry out. Rapid and inexpensive. Require comparatively few subjects. Esp. to investigate rare Disease. No risk to subject. Allows the study of several different etiological factors. No attrition problems Ethical problems are minimal.

DISADVANTAGES : 

DISADVANTAGES Problem of Bias. Selection of an appropriate control group may be difficult. We cannot measure incidence and can only estimate the relative risk. Do not distinguish between causes and associated factors. Not suited to evaluation of Therapy. Major concern is the representativeness of cases and controls.

Cohort Study : 

Cohort Study Cohort study is usually undertaken to obtain additional evidence to refute or support the existence of an association between suspected cause and disease.

FEATURES OF COHORT : 

FEATURES OF COHORT Cohorts are identified prior to the appearance of the disease under investigation. Study groups are so defined are observed over a period of time to determine the frequency of Disease. Study proceed forward from Cause to effect (PROSPECTIVE).

COHORT : 

COHORT COHORT: Prospective Retrospective. In epidemiology the term cohort is defined as a group of people who share a common characteristic or experience within a defined period.

INDICATION FOR COHORT STUDIES : 

INDICATION FOR COHORT STUDIES Where there is good evidence of association between exposure and disease, as derived from clinical observation and supported by descriptive and case –control studies. When exposure is rare, but the incidence of disease is high among exposed. When attrition of study population can be minimized e. g. follow up is easy , cohort is stable. When ample funds are available.

BASIC FRAME WORK : 

BASIC FRAME WORK The studies proceed from “cause to effect”. In cohort study the exposure has occurred , but the disease has not.

GENERAL CONSIDERATION : 

GENERAL CONSIDERATION Cohorts must be free from the disease under study. Study and control group must be easily susceptible to the disease under study. Both the groups must be comparable in respect to all the possible variables which may influence the frequency of the disease. The Diagnostic and eligibility criteria of the disease must be defined before hand. Groups are then followed , under the same identical conditions, over a period of time to determine the outcome of the exposure

Design : 

Design In Table (a + b) - exposed to the factor under study ‘a’ of which developed the Disease. ( c + d)- not exposed to the factor under the study. ‘c’ of which became cases. If it is found that the incidence of Disease in the exposed group a/ (a + b )is significantly higher than in non exposed group c/ (c + d). It would suggest that the disease and suspected cause are associated.

TYPES OF COHORT : 

TYPES OF COHORT PROSPECTIVE : (CURRENT) Outcome has not yet occurred at the time the investigation begins RETROSPECTIVE: (HISTORICAL) Outcome has occurred before the start of the investigation. The investigator goes back in time – 10-30 yrs back to select his study group from existing records of past employment, medical or other records and traces there forwards through time, from the past date fixed on the records usually up to the present.

COMBINATION OF BOTH : 

COMBINATION OF BOTH Both the prospective and retrospective elements are combined.

ELEMENT OF COHORT : 

ELEMENT OF COHORT SELECTION OF STUDY SUBJECT OBTAINING THE DATAON THE EXPOSURE. SELECTION OF THE COMPARISION GROUP. FOLLOW UP. ANALYSIS

SELECTION OF STUDY SUBJECT : 

SELECTION OF STUDY SUBJECT Sample of the general population: Geographically area, special age groups, birth cohorts (Framingham Study) A group that is easy to identify: Nurses health study Special population (often occupational epidemiology): Rare and special exposure Permits the evaluation of rare outcomes

OBTAINING DATA ON THE EXPOSURE : 

OBTAINING DATA ON THE EXPOSURE

Selection of the Comparison Population : 

Selection of the Comparison Population Internal Control Group Exposed and non-exposed in the same Study population (Framingham study, Nurses health study) Minimise the differences between exposed and non-exposed External Control Group Chosen in another group, another cohort (Occupational epidemiology: Asbestosis vs. cotton workers)

SELECTION : 

SELECTION General Population: If non- of the above comparison is available than the mortality experience of the exposed group is compared with the mortality experience of the general population in the same geographic area as the exposed people. E.g. comparison of frequency of cancer among asbestos workers with the rate in general population in same geographic area.

FOLLOW UP : 

FOLLOW UP One of the problem in cohort studies is the regular follow up of the participants. Therefore at the start of the study methods should be devised depending upon the outcome to be determined (morbidity or Death). To obtain the data for assessing the outcome.

FOLLOW UP PROCEDURE : 

FOLLOW UP PROCEDURE Periodic medical examination of each member of the cohort. Review physician and hospital records. Routine surveillance of death records. Mailed questionnaires, telephone calls, periodic home visits.

Percentages of loses : 

Percentages of loses Follow up are inevitable due to death. Change of residence. Migration. Withdrawal from occupation.

ANALYSIS : 

ANALYSIS DATA ARE ANALYSED IN TERMS OF Incidence rates of outcome among exposed and non- exposed. Estimation of risk.

Incidence Rates : 

Incidence Rates

Incidence rates : 

Incidence rates Among smokers = 70/ 7000- 10 per 1000. Among non- smokers = 3/3000 = 1 per 1000. Statistical significance : P < 0.001

Relative risk : 

Relative risk R. R = incidence of disease (or Death) among exposed incidence of disease (or Death) among non- exposed Therefore for Hypothetical situation ?????????

Attributable Risk : 

Attributable Risk Is the difference in incidence rates of disease (or death) between an exposed group and non- exposed group. Some authors use the term “ risk” AR= incidence of disease rate among exposed - incidence of disease rate among non- exposed X 100________________________________ incidence rate among exposed. Attributable risk in our example 10 – 1 X 100 = 90 % 10

ADVANTAGES : 

ADVANTAGES Incidence can be calculated Several possible outcomes related to exposure can be studied simultaneously. Cohort studies provide a direct estimate of R.R Dose – response ratio can also be calculated. Since comparison groups are formed before disease develops.

Disadvantage : 

Disadvantage Large No. of population. Very lengthy- takes very long time to complete. Certain administrative. Loss of experience staff. Loss of funding. Extensive record keeping. Selection of comparison group- limiting factor

Disadvantage : 

Disadvantage There may be changes in std methods or Diagnostic Criteria of the Disease over the prolonged period. Cohort studies are expensive. The study may itself alter the patients Behavior.

Difference between : 

Difference between Case control Cohort study

Slide 55: 

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