TYPES OF EPIDEMOLOGICAL STUDIES :

-There 2 main objective for epidemological studies; descriptive and analytic .

** Descriptive epidemiology deals with rates, ratios and distributions, it explain the
determinant's of the disease in the form of time place and person
** Analytical epidemological tests consist of observational studies and experimental
studies .
Observational studies include: .
-Case-Control, - Cohort & - cross-sectional studies

-The movement is from the effect to the disease .

-The researcher begins with a population with a certain outcome, and subjects are
classified into either "cases" or "controls" based on the outcome status
-The cases and controls are assessed retrospectively to for the presence of risk factor
(Information is collected about exposure to risk factors).
-Is very popular in exploring an exposure - disease assossiation .
- Selection of control subjects based on exposure status (exposed diseased or even non
exposed non diseased) is inappropriate ,
because comparing the frequency of exposure between the case and control groups is an
important part of case-control study.
-Optimal selection of control group is to provide an acurrate estimation of exposure
frequency among non diseased general population (bothh exposed and non exposed ).
- Independent variables (age, sex,...) are often selected to be the same (matched) between
the case and control groups to decrease the effect of confounding.
- Subjects with the disease of interest (case group) are comapred with an otherwise similar
group that is disease free (control group).

- It is retrospective study aiming at determining the association between risk factors and
disease occurance
The main measure of association is exposure Odds ratio can be calculated in the case
.control study but incidence of the disease can't
One of the drawbacks of case control study is that the risk can not be drived directly from
it's results.
**It is more cheap and easy than cohort study**

:.N.B.
- Incidence measures ( e.g. relative risk or relative rate) can't be directly measured in
case-control study,
Because the people being studied are those who have already developed the disease
- Relative risk and relative rate are calculated in cohort studies, where people are
followed over time for the occurance of the disease.
- prevalence odds ratio is calculated in cross-sectional studies to compare the prevalence
.of the disease in different populations

------------------------------------------------------------------------

- Divides the study group into "exposed" and "non exposed" to the risk factors
-Each subject is then follow prospectively till the presence of the disease .
-Is a prospective observational study in which groups are chosen based upon the presence
or absence of one or more risk factors
-All subjects are then observed over time for the development of the disease of interest
-Thus allowing estimation of the incidence within the total population and comparison of
incidences between subgroups.
-It is best for determining the incidence of the disease & comparing the incidence of the
,disease in 2 populations.
-one with and one without agiven risk) allows for calculation of a relative risk .
-It is stronger than case-control study and cross sectional study .

- Loss to follow-up in a prospective studies creates a potential for selection bias (selective
loss of high risk or low risk subjects)
e.g. if a substanial number of subjects are lost to follow-up in exposed and/or unexposed
,groups
- It is possible that the lost subjects differ in their risk of developing the outcome from the
remaining,
Such loss may result in either overestimation or underestimation of the association
.between exposure and the disease

Example: if 30% of subjects were lost to follow-up in a prospective study for the relation
of alcohol and breast cancer
-There is no information available on whether these subjects develop breast cancer or not
-The number (30%) is substanial and will influence the outcome if heterogeneity in
.developing breast cancer exists between the lost subjects and the remaining subjects
for example if the subjects lost in the exposed group experienced more breast cancer than
those with follow-up (selective loss of high risk subjects).
* As a result, the measure of association might be underestimated .
# To reduce the potential for selection bias in prospective studies, investigators try to
acheive high rats of follow-up

:.N.B.
-- Median survival: used to compare the median survival times in two or more groups of
patients (e.g. receiving new treatment or placebo).
--Median survival is calculated in cohort study or clinical studies
:.N.B.
** Prevalence odds ratio: is calculated in cross-sectional studies to compare the
prevalence of the disease between two different peoples .

-It is the frequency of new cases of a disease arising in a population at risk over a specified
time period .
It is the measure of the appearance of new cases- .

.
-is the measure of those with the disease in the population at a particular point in time
the relation between them in a stable population (little migration) can be demonstrated by:
Prevalence = (incidence) (time (
# So if the incidence is fixed in a stabe population, the prevalence is increased if there are
factors that prolong survival (i.e. disease duration) e.g. improved quality of care
** Prevalence of disease in a population = incidence of the disease / population

-Starts at some point between the exposure and the outcome .

- The researcher reviews the past records and classify subjects into "exposed" and "non
exposed" and then follow them untill the outcome
-In a cohort study, the study subjects are free of the outcome at the time a study begins .

- Both the exposure and the outcome are studied at one point of time
(at one cross section of time)
- Since both exposure and outcome are present for sometime before the study,
it is not possible to
determine the temporal association between the exposure and outcome from
cross-sectional study
-Takes a sample of individual from a population at one point in time
- It allows determination of a disease prevelance
(the total number of cases in a population at a given time).

# Disease incidence can't be determined .

.A study involving only patients already diagnosed with the condition of interest .
.It is helpful in determining the natural history of uncommon conditions .
.* But provids no information about the disease incidence .

- Compare the therapeutic benefit of different interventions in patient already diagnosed

with a particular disease
- Usually subjects are randomly arranged into exposed (treatment group) & placebo and
then followed to detect the development of the outcome of interest
- Can't be used to determine disease incidence .

.
.Type of expermental study .
It is considered as the gold standard for studying the effecacy of a treatment or
a procedure.
-Compare two or more treatments .
Subjects are randomly assigned to an expermental (experienced a specific exposure
) e.g medication) and a control group (non exposed i.e placebo).
- This type of study has the least bias and helps to show a strong causal relationship .

.
-Is the grouping of differeny data point into similar categories .
- Usually involves randomization at the level of groups rather than at the level of individuals

- In which a group of participants is randomized to one treatment for a period of time

and the other group is given analternate treatment for the same period of time
)(interchanging the treatment))
with a washout (no ttt) period inbetween the treatment intervals to limit the confounding
.effect of the prior treatment
** At the end of the time period, the two groups then switch treatment for another set
period of time .

-Randomizes one treatment to one group and another treatment to the other group .
.Such as treatment drug to one group versus a palcebo to the other group .
** There are usually no other variables are measured

.
-Occurs when the effect a main exposure on an outcome is modified by another variable
-It is not a bias .
- It is a natural phenomenon that shoud be described not corrected as it is not a bias or
confoundation
Example: the effect of oral contraceptives on breast cancer is modified by he family
.history
i.e. women with +ve family history have an increased risk, while women without +ve
family history don't have an increased risk .

** Other examples: .
-- studying the effect of estrogen on the risk of venous thrombosis (modified by smoking)
-- Also studying of the risk of lung cancer in people exposed to asbestos (greatly depends .
on / modified by smoking)

:For exampl .
the effect of a new estrogen receptors agonist drug on the incidence of DVT is modified by
smoking status :
- Smokers taking the drug have an increased risk of developing DVT, while nonsmokers
taking the drug don't
- It may be confused with confounding, both can be diffrentiated by dividing the whole
.)cohort into subgroups (stratified analysis
Imagin that smoking is a confounding that, by itself is associated with a higher risk of DVT,
,so if more smokers are taking the drug
- it might appear that the drug causes DVT, but when stratified analysis is performed by
,analyzing smokers and nonsmokers separately
-it will appear that the drug is no longer associated with DVT
.
- Is a time period required for an exposure to start the effect i.e the time require from
getting exposed to outcome
In infectious diseases it is relatively short, while in chronic diseases (e.g. cancer or CAD (
-- it may be very long and extended period of exposure may be required to affect the
outcome
-- Latent period also can be applied to the exposure to risk modifier, as it may need to be
continous over a certain period of time before influencing the outcome
**Latent period is a natural phenomenon not a bias

-It is defined as an extreme and unusual observed in a dataset .

-It may be the result of a recording error, a measurement error or a natural phenomenon .
- It affects the measures of centeral tendency as well as measures of dispersion
for example:
# The mean: is extremely sensetive to the outliers and easily shifts towards them
- The standard deviation is sensetive to outliers because it is the measure of dispersion
within the data set and outliers significantly increase the dispersion
(SD = deviation of values around the mean).
The rang = maximum value - minimal value (so it is definitely changed ( .

** The mode is not changed by outliers as they dont change the most frequent value
observed .
## The median is much more resistant to the outliers as is located in the middle of the
dataset where the observations usually dont differ much from each other .

.
--Is used as ameasure for association in a cohort studies .
--It is the ratio of the risk in an exposed group to that of the unexposed group .
The NULL value of RR is 1.0 .
**A RR of 1 means that there is no association between the risk factor and the disease .
A relative risk > 1 means that there is a positive association between the risk factor and .
.the outcome
A relative risk < 1 means that there is a negative association between the risk factor and .
.the association
--The farther the the value of the RR from 1, the stronger the association .
Example: the RR of bronchogenic cancer in smokers is greater than 2 --> indicates :
a strong association between smoking (risk factor) and bronchogenic carcinoma
(outcome).
## When exposure is measured on a continous scale (Number of smoked cigarettes per
day or PPD).
** The classification into two or more ordinal categories enable the risk to be assessed as a
function of exposure .
--And the DOSE RESPONCE EFFECT can be calculated from the exposure and the outcome
** The present example illustrates a dose responce relationship between smoking and
bronchogenic cancer
)the RR of bronchgenic lung cancer increases as the number of smoked PPD increases( .

-- One weakness of the RR is that it gives no clue whether such finding can be explained by .
chance alone.
The confidence interval and the "P" value can help strengthen the finding of the study .

For the study to be statistically significant .

1- The confidence intrval must not contain null value.
2- The "p" value should be less than 0.05 (i.e < 5% chance the result obtained were due to
chance alone).
3- The RR is not Null value

## The "p" value is used to strengthen the results of the study, it is defined as the
propability of obtaining the result by chance alone.
e.g. "P" value is 0.01 means that :
(the probability of obtaining the result by chance alone is 1%)
**Ther commonly accepted upper limit (cut-off point) of the "P" value for the study
to be considered statisically significant is 0.05 (i.e. less than 5% (.
## The "P" value deals with random variability, not bias.
** If the "P" value less than 0.05 (i.e the study is statistically significant), the 95%
confidence interval doesn't contain 1.0 (the null value for RR).
@@ A relative risk of 0.71 shows that the drug decreased the risk of mortality by 29% the null value for RR is 1).
e.g.: Acase of RR 1.6 (greater than 1) & the confidence interval 1.02-2.15
(doesn't contain the null value 1).
**so for the study to be statistically significant the "P" value must be less than 0.05

:N.B: Verrrrrry important to know how to calculate relative risk fron the 22 table

Relative risk = {a/(a+b)} / { c/(c+d) }

N.B.: Absolute Risk Reduction (ARR).
RR = event rate for the drug or test i.e = +ve cases/ total nuber examined by the test or
drug

** In case of 2 drugs or interventions study one drug reduce the relative risk (RR) than the
other .
--Absolute risk Reuction (ARR) = RR of first drug(placebo) - RR of second drug (under test (.
** Number needed to treat (NNT): is the number of people that should receive
a treatment to prevent one defined event .
$$ Is calculated by inverse the absolute risk reduction $$

** NNT = 1/ARR **

:.N.B.
- The power of a study is the ability to detect a difference between two groups (treated
versus non treated, exposed versus non exposed ).
- Increasing the sample size --> increases the power of the studyand consequently makes
-the confidence interval of the point of estimate (e.g. relative risk) tighter
** If the sample size is small --> low power of study to detect the difference between
& exposed and non exposed subjects
this makes the confidence interval of the study wide (e.g. 0.8-3.1) and makes the study
statistically insignificant.
And if we increase the sample size --> the confidence interval will be tighter and the study
will be statistically significant.

Relative risk reduction (RRR)=

ARR(control group) - ARR (treatment group)/ ARR (control group)

- It is the number of people that must be treated for one adverse event to occur .
(similar to number needed to treat )

**.NNH = 1/ Attributable risk .

Attributable risk = .
Adverse event rate (treatment group) - Adverse event rate (control group).
.Adverse event rate = Number of deaths / total number of the group .

For example: drug X (deaths=60 & living=20) placebo drug (deaths=38 & living=38( .

Adverse event rate in treatment group = 60/80= 0.75 .

Adverse event rate in placebo group = 38/76= 0.50 .
Attributable risk = 0.75 - 0.50 = 0.25 .
NNH = 1/0.25 = 4 .

- Results from the manner in which the subjects are selected for the study, from the
selective losses from the follow-up .

It is a selection bias that can be created by selecting a hospitalized patients as the cotrol
group.

-Due to a nonrandom sampling of a population .

- It can lead to a study population having characteristics that differ from the target
population
* A common example; is that severely ill patients are most likely to enroll in cancer trials
leading to:
results that are not applicable to patients with less advanced cancer
i.e. the study sample isn't represntative of the target population with respect to the joint .
distribution of exposure and outcome .

- Occurs due to imperfect assessment of the association between the exposure and
outcome .
-As a result of erorrs in the measurements of exposure and outcome status
* It can be minimized by using standarized techniques for surveillance and measurement of
outcomes .
- as well as trained observers to measure the exposure and outcome

- Occurs from poor data collection with inaccurate results .

:
- Lead-time bias should be considered while evaluating any screening test .
* It happens when two interventions are compared to diagnose a disease
and one of them diagnose the disease earlier than the other without an effect on the
outcome (survival).
## What actually happens is that detection of the disease was made at an earlier point of
time
- But the disease course itself or the prognosis did not change .
>> So the screened patients appeared to live longer from the time of diagnosis till the time
of death.

:N.B.: IN USMLE
Think of LEAD BIAS when you see " a new screening test" for poor prognosis diseases like
lung cancer or pancreatic cancer

- when the observer maybe influenced by prior knowledge or details of the study that can
affect the results
-Referrs to misclassification of an outcome and /or exposure .
.e.g.: labeling diseased subjects as non diseased and vice versa .
* Blinded studies usually avoid this bias by preventing the observer from knowing which
treatment or intervention the participants are receiving .
*Blinding can involve patients exclusively or both patients and physicians (double blinding(
and are related to the design of the study (the scenario will describe how the study was .
desgined).

- Occurs when a study participant is affected by prior knowledge to answer a question

* Result from inaccurate recall of past exposure by people in the study and applies mostly
to retrospective studies as case-control study .
# People who have suffered an advirse event (such as having a child with congenital
anomalies) are more likely to recall previous risk factors than
# people who have not experienced a poor outcome
** This is more common in case-control studies than in randomized clinical trials .

.
- Occure when the case and control populations differ due to admission or referral
practices .
For example: a study involving cancer risk factors performed at a hospital specialized in
cancer research ,
* may enroll cases referred from all over the nation, however hospitalized control subjects
without cancer may come from only the local area .

- Refers to the fact that a risk factor itself may lead to extensive diagnostic investigations and
increase the probability that a disease is identified.
For example: patients who smoke may undergo increased imaging surveillance due to
their smoking status, which would detect more cases of cancer in general .

- Occurs when the outcome of the test is obtained by the patient's response not by
objective diagnostic methods (e.g. migrane headache ).

- Is a type of selection bias where a treatment regimen is selected for a patient based on the
severity of their condition.
.with out taking into account other possible confounding variables
.Offline case 20 .

- It may result fro the way that treatment and control groups are assembled .
- It may occur if the subjects are assigned to the study groups of a clinical trial in
a non random fashion .
For example in a study group comparing oral NSAIDs and intra-articular corticosteroid
injections for the treatment of osteoarthritis
* obese patients may be pereferentially assigned to the corticosteroid group (affect the
outcome ).

- Reffer to a conclusion that there is no difference between the groups studied when
a difference truely existing .
- It is a random erorr not a systemic erorr (i.e bias ).

- Occurs when at least part of the exposure-disease relation ship can be explained by
another variable (confounding).
>> Due to presence of one or more variables associated independently with both the
exposure and the outcome .
For example: cigarette smoking can be a aconfounding factor in studying the association
between maternal alcohol drinking and low birth weight babies .
As cigarette smoking is independently associated with alcohol consumption and low borth
weight babies.

- It is the tendency of a study population to affect the outcome because these people are
aware that they are being studied .
- This awareness leads to consequent change in behaviour while under observation -->
seriously affecting the validity of the study .
- It is usually seen in studies that concern behavioral outcomes or outcomes that can be
influenced by behavioral changes .
** In order to minimize the Hawthorne effect, the studied subjects can be kept unaware
that they are being studied .

- It describes researcher's beleifs in the efficacy of treatment that can potentially affect the
outcome .

.N.B. all bias are considered as a threat to the validity of a study.

1- Slection bias can be cotrolled by choosing a representative sample of the population for
the study & acheiving a high rate of follow up
2-Observer's bias can be cotrolled by blinding technique .
3- Ascertainment bias can be cotrolled by selecting a strict protocol of case ascertainment
4- Confounders: can be avoided by 3 methods in the design stage of the study; matching
restriction and randomization
** Matching is used in case control study in which select variables that could be
confounders (age, race,..) then
- cases and controls are selected based on the matching variables
- Randomization is commonly empolyed in clinical trials its purpose is to balance various
factors (confounders) that can influence the estimate of association between the
treatment and placebo groups so that the unconfounded effect of the exposure can be
isolated .
** A very important advantage of randomizatio when compared to other methods is the
possibility to control .
the known risk factors(as; Age, severity of the disease) as well as unknown & difficult to
measure confounders as level of stress, socioeconomic status) and make all confounders (
evenly distributed between the treatment group and the placebo
-- In clinical trials, randomization is said to be successful, when there is similarity in the
distribution of the baseline charachteristics (age, race, prevalence...) between the
treatment and placebo groups
i.e the confounders are evenly distributed between the treatment and the placebo
.groups

- It is the ratio of the chance of an event occuring in the treatment arm (drug or group of
interest ).
compared to the chance of that event occuring in the control arm (the other drug or
group) during a set period of time

Hazard ratio = event occuring in the test group / event occuring in the control group .

So; the lower the hazaed ratio, the less likely the event will occur in the treatment arm .
-The higher the ratio, the more likely the event will occur in the treatment arm .
-A ratio close to 1 indicates no significant difference between the 2 groups .
Example: Hazard ratio of 2 drugs A & B in bleeding complications .
** Hazard ratio for major bleeding = 0.93 i.e. close to 1 means that both groups are similar
to each others in this event .
** Hazard ratio for intracranial bleeding = 0.41 (indicates the lower chance of drug "A" to
cause intracranial bleeding than drug "B" ).
** Hazard ratio for GIT bleeding = 1.50 (indicates that drug "A" has a higher chance to
cause GIT than drug "B" ).
** Hazard ratio for life threating bleeding = 0.80 (indicates the lower chance of drug "A" to
cause intracranial bleeding than drug "B" ).
** Hazard ratio for total bleeding = 0.91 (indicates the slight lower chance of drug "A" to
cause intracranial bleeding than drug "B" ).
## In case number (11 ofline) you should focus on the baseline value in the case in take
the corresponding hazard ratio in the study
then
decide, which one of them has the greater hazard of hyperkalemia
(N.B. Ca channel blockersaffects GFR ).

$$ You should learn case 19 in offline 2013 .

- In any randomized clinical study, the goal of successful randamization is .

1- to eliminate bias in treatment assignments
2- Blind the inestigators from the identity of the patients who receive the treatment arm
3- Minimize the confounding variables

Ideal randomization allows for adequate statistical power and should include :
1- equal patient group sizes
2- Low selection bias
3- Low propability of confounding variables
-- A listing of the base line characteristics of the patients in each arm would demonstrate
if the two arms had patients with similar characteristics and would insure the proper
randomization occured in the study

** It is commonly used to compare two means not proportions .

** The basic requirements needed to perform this test are :
-the two mean values - the sample variances - the sample size >>
T test" is then done to obtain the "P" value" .
If the "P" value is less than 0.005 --> the null hypothesis
(that there is no difference between the two groups) is rejected
and the two means are assumed to be statistically different
If the "P" value is large --> the Null hypothesis is retained .

- Also can be used to compare two means, but

Population (not sample) variances are employed in the calculations .
- Because the population variances are not usually known --> this test has limited
applicability .

-I.e. Analysis of variances (ANOVA( .

* Used to compare two or more means (determine whether there are significant
differences between the means of 2 or more independent groups.
e.g. ANOVA can be used to assess for difference in mean blood pressure among three
samples of populations.
Grouped by exercis status (never exercis, exercis occasionally and exercis frequently( .

- Used to test the association between two categoral variables .

- By compare proportions (of categorized outcome, e.g. high or low ) then presented with
the exposure (present or not present ).
A 22 table may be used (high or low outcome) and (exposed & non exposed) to compare
the observed values to the expected values .
** If the difference between the observed and expected values is large, this means there is
association between the exposure and the outcome
For example: it is used to determine if the distribution of gender and smoking status is
random or if there is difference between the sexes regarding smoking status .

- Is an epidemiologic meathod for pooling of the data from several studies to do an analysis
having a relatively big statistical power.
For example: individual studies assessing the effects of aspirin on certain cardiovascular
events may be inconclusive
However analysis of data compiled from multiple clinical trials may reveale a significant
benefite.

- Is a method used to model the linear relationship between a dependent variable and 2 or
more non dependent variables .
For example this test could be used to quantify the effects of alcohol use, tobacco,
smoking and charred food consumption on the incidence of gastric ulcer .

-It is a measure of the strength and direction of a linear relationship between 2 variables .
For example, a study may report a correlation coefficient describing the association .
.between hemoglobin A1c level and average blood glucose level

- Involves two or more expermintal intervensions, each with two or more variables that are
studied independtly .
For example .
A study uses 3 different interventions
beta blocker (metoprolol), calc. channel blocker (amlodipine) or ACEIs (ramipril)
with to two different variable bl pr. endpoints (102-107 mmHg or < 92 mmHg (.

1- ACEIs
-Lower bp goal

-higher bp goal

2-Beta blocker
-Lower bp goal

-higher bp goal

3- Ca channel blocker
-Lower bp goal

-higher bp goal

-The normal distribution is symetrical and bell shaped .

-All measures of central tendancy are equal i.e mean = median = mode .
# The degree of dispersion from the mean is determined by the standard deviation
* of data --> within 1 Standard deviation from the mean ( mean +/- 1 SD %68 (.
* of data --> within 2 standard deviation from the mean (mean +/- 2 SD %95( .
* of data --> within 3 standard deviation from the mean (mean +/- 3 SD %99.7) .

:.N.B

In contrary to normal distribution curve, most of data in real

world statistical analysis have asymeterical distributions:

1- Positivel skewed curve

-Smaller numbers predominate in the dataset
-The long slop of the curve "the tail" extends in the positive direction
- The mean is the most shifted to the positive direction followed be the median then the
mode .

So the mean is greater than the median

In strongly skewed distributions, the median is a better measure for centeral tendency
than the mean.

2-Negatively sekewed curve

- Larger numbers predominate in the dataset -The long slop of the curve "the tail" extends in the negative direction
- The mean is the most shifted to the negative direction followed by the median then the
mode.
** So the mode > the median > the mean (i.e the mean is the smallest (.
** In strongly skewed distributions, the median is a better measure for centeral tendency .than the mean

- Sensitivity --> the proportion of true +ve cases among all diseased cases .
(Sensitivity = true +ve by the test/all patients that are actually diseased).
-Indicates the ability of a test to detect those patient with disease .
- A higher sensitivity --> the higher the test detect patient with the disease --> decrease
false negatives.
- Screening tests (especially for diseases with severe sequally) should have a high sensitivity

- Specificity --> the proportion of true -ve cases among all non diseased cases .
(Specificity = true -ve by the test/all patients that are actully free)
- Is a measure of the true negative rate and indicates how will a test can rule out a given
condition (exclude those without the disease).
- The higher the specificity the more likely that most healthy patients will have a -ve test
results
** The higher the specificity --> the less likely the false +ves .

-- They are fixed values that are not vary with the pre-test probability of a disease or with
the prevalence of the disease.
-- The ideal diagnostic test should have high sensitivity and specificity .

:.N.B
- Raising the cutoff point of a diagnostic test --> decrease it's sensitivity but increase it's
specificity.
- Lowering the cutoff point of a diagnostic test --> increase it's sensitivity but decrease it's
specificity.

(.
## draw the 22 table (a,b,c,d). ##
-- Is the measure of association in case control study .
-- It compares the odds of exposure in cases to the odds of exposure in control
OR = (ad)/(bc) .
** It is not the same as relative risk .
RR can be calculated in follow up studies by comparing the risk of exposed individuals to .
.the risk of unexposed individuals

RR = [a/(a+b)] / [c/(c=d( [ .

- Direct calculation of RR in case-control study is not possible, because the study design
doesn't include following peoples overtime .
But sometimes the RR canbe approximately equal to the odd's ratio .
- If the prevelance of the disease is low --> the odd's ratio approximates the Relative risk
** This is called ( the rare disease assumption) .
- Increasing the sample size will decrease the "P" value of the odd's ratio and make the
confidence interval tighter .

:N.B.
- Attributable risk percent (ARP): represents the excess risk in a population that can be
attributed to the exposure to a particular risk factor .
- It can be calculated by subtracting the risk in the unexposed population (basline risk)
from the risk from the exposed population
and dividing the results by the risk in the exposed population

ARP = (Risk in exposed - Risk in nonexposed)/Risk in exposed .

or
- ARP can be calculated from the relative risk as follow .

ARP = (RR-1)/RR .

Pre and post-test Probabilities (+ve perdictive value (PPV) & -ve predictive value .

- Describes the probability of having the disease if the test result is +ve .
)if the patient has a +ve test result, what is the liklehood that he actually has a disease(
- The post-test probability of having the disease is directly related to the PPv .
- If the PPV is 25% i.e low, consequently if the test result is positive, then the post-test
probability of having the disease is low
- The post-test probability is also dependent on the sensitivity, specificty and pre-test .
probability of having the disease .

- describes the probability of not having the disease if the test result is ve .
NPV will vary with the pre-test probability of a disease (important)
i.e A patient with high probability of having a disease will have a low NPV .
-And a patient with a low probability of having a disease will have a high NPV .
** If the NPV is 96 % this means that if the test result is -ve, the chances of the patient to .
not have the disease is high (96%).
And the chances of the patient to have the disease is low (100 - 96 = 4%( .

##Example##

1- BREAST CANCER & FNA test results

-- a patient of a high pre-test probability for having the disease (1st degree relative having .
breast cancer or age > 40 ys), has a low NPV.
-- a patient of a low pre-test probability for having breast cancer (less than 40 ys old), has a .
high NPV.

2- HIV & ELISA test results

- A patient who belongs to a high risk group e.g. (multiple sexual partners, use no .
condoms, IV drug abuse)
has a high pre-test probability of having AIDS --> so he will have a low NPV >>
-- On the other hand a patient who belongs to a low risk group (one sexual partner, using .
condom and no IV drug abuse)
has a low pre-test probability of having AIDS --> so has a high NPV

NOTE
- The prevalence of the disease is directly related to the pre-test probability of having the
disease (PPV) & inversely related to the pre-test probability of not having the disease
(NPV), so increased prevalence --> low NPV but high PPV and vice versa.
-- Sensitivity and specificity are not affected by the prevalence of the disease and so the
likehood ratio positive i.e sensitivity (1-specificity)
as it depends on sensitivity and specificity

:.N.B
-If the test result is -ve , the probability of the patient to have the disease = 1 NPV .

** Cases and diagnostic tests tha are high yield USMLE questions in probabilities :
-coronary artery disease and ECG stress test
-Pulmonary embolism and ventilation-perfusion scanning
-Prostate cancer and serum PSA level

- Represents the appropriatness of the test (i.e. the test ability to measures what is
supposed to be measured).
- In order to determine the validity of a test, the results are compared to those obtained
from the gold standerd test.
It doesn't depend on the pre-test probability of the disease .

N.B.: Also sensitivity and specificity of a test compare its results to the results obtained by
the gold standard test

.Test-retest reliability .
-A reliable test is reproducible; gives similar or very close results on repeat measurements
-Reliability is quantified in terms of Coefficient of variation (CV)
-COefficient of variation; is the standar deviation of the set of repeated measurements
divided by their mean & expressed as a percentage.
-Reliabilty is maximal when random error is minimal

- It emphasizes the importance of choosing the apropriate cutoff value, although

overlapping of normal & abnormal resultes make it difficult.
-Any cutoff point demonstrates a trade-off between SENSITIVITY and 1-SPECIFICITY
- Sensitivity (positivity in disease) --> is the proportion of subjects who have the target
condition and gives positive results
Sensitivity = TP/(TP + FN).CLINICALLY
- Specificity (Negativity in health) --> is the proportion of subjects without the target .
condition and gives negative results
Specificity = TN/(TN + FP).CLINICALLY .
Sensitivity --> ++ true +ve & -- false -ve (diagnosed as normal but he is diseased ++( .
Sensitivity --> allaw not to miss any diseased patient (not to miss any true +ve ++ (.
Specificity --> ++ true -ve & -- false +ve (diagnosed as diseased but he is normal ++( .
** ROC --> Aiming at decrease false -ve and false +ve results .
(i.e increase sensitivity and specificity).

- In ROC curve: sensitivity = true positive while (1-specificity) = false positive

- Positive predictive value (ppv) --> is the probability of having the disease if the test results
are +ve .
PPV = TP/(TP + FP) .
Negative predictive value (NPV) --> is the probability of not having the disease if the test .
.result is -ve
NPV = TN/(TN + FN (.

Positive likelihood ratio (LR+) = sensitivity/(1-specificity( .

LR+) --> is the ratio of the proportion of patients who have the target condition & test ( .
positive to
the proportion of patients without the target condition & who also test positive .

Negative likelihood ratio (LR-) = (1-specificity)/sensitivity

LR-) --> is the ratio of the proportion of patients who have the target condition who test ( .
negative to
the proportion of patients without the target condition who also test negative
ROC curve has 2 lines; vertical line (Y) for sensitivity and horizontal line (X) for specificity .
.* Large Y values --> Indicates High sensitivity .
.* Small X values --> Indicates High specificity .
Low cutoff --> Increase sensitivity (better ability to identify patients with the disease i.e
)increase true positive
Although this causes decrease specificity (the test falsely identifies more subjects as
.diseased also they are not) and vice versa
.High cutoff --> Decrease sensitivity and Increase specificity .
Low cutoff --> High Sensitivity --> higher negative predictive value (NPV) --> decrease false
-ve results (Ruling out probability).
High cutoff --> Higher Specificity --> higher positive predictive value (PPV) --> decrease false
+ve results (Ruling in probability).

:N.B: Draw the overlap curve

-- A shift of the ROC curve upwards for a given cutoff indicates increased sensitivity and
vice versa.
-- A shift of the curve to the right for a given cutoff (higher value)indicates decreased
sensitivity and vice versa .
--The curve usually shows that an increase in sensitivity is offset by decrease in specificity
As mentioned before .
sensitivity= TP/(TP+FN) & specificity= TN/(TN+FP), so decreased overlap between the
healthy and diseased population curves >>
decrease both the number of FP & FN (i.e decreses the dominator) --> thus increase >>
both sensitivity and specificity
(i.e allow for a test with both higher sensitivity and specificity).

-- In overlap curve: moving the cutoff vlaue to the right (higher value) would increase
specificity at the expense of sensitivity, while
moving the cutoff to the left (lower value) would increase sensitivity at the expense of
specificity.
A cutoff value just outside the overlapping portion would maximize the sensitivity
(if to the left) or specificity (if to the right) at 100% .

Both sensitivity and specificity depend on the cutoff value of a given test for example : .
- Raising the cutoff value makes it more difficult to diagnose the condition .
-- i.e
it makes it harder to obtain +ve results and easier to obtain -ve results --> this will increase
specificity but decrease sensitivity .
-- Lowering the cutoff value makes it easier to obtain +ve results and harder to obtain -ve
results .
.i.e increase sensitivity and decrease specificity

Increase sensitivity --> increase -ve predictive value (NPV) .

due to (decrease false -ve results).
Increase specificity --> increase +ve predictive value (PPV) .
due to (decrease false +ve results).

- Is the proportion of the true +ve results out of the total number of the true results of the
test (-ve results are not taken into account ).
- Percision is equvalent to +ve predictive value i.e. true +ve/all true
- It is the measure of the random error in the study
- The study is percised if the results are not scaterred widely, this is reflected by a tight
confidence interval .
So, if the first study has a wider confidence interval than the second study --> the second .
.study is more percised

- Is the proportion of the true results (true +ve and true -ve) out of all results that are
predicted by the test .
- The closer the ploted curve approaches the left and top borders of the ROC curve, the
more accurate the test .
** Accuracy can also be measured by the total area under the plotted curve on ROC curve
Increase of the total area under the curve --> increases the accuracy of the test .

:N.B.
-- Both accuracy and percision depend upon sensitivity and specificity of the test as well as
the prevalence of the condition in the population tested .
** Validity and accuracy are measures of systematic errors (bias ) .
** Accuracy is reduced if the sample doesn't reflect the true value of the parameter .
measured.
Increasing the sample size --> increases the percision of the study, but doesn't affect the .
.accuracy

-- It assesses a linear relationship between two variables .

-- )The nul value for the correlation coefficient is 0 (no association( .
>> And the range of plausible values is from -1 to 1 .
** The sign (mark) of crrelation coefficient indicates a positive or negative association .
The closer the value to its margins (-1 or 1), the stronger the association .
-- The correlation coefficient shows the strength of association but does not necessarily .
imply causality (cause of it).
--.The association is statistically significant if P value is low .

-It measures the incidence of the disease .

- It is calculated by divide the number of diseased subjects by the number of people at risk
or of interest .
-No of diseased/people at risk

Prevalence of disease in a population = incidence of the disease / population .

.
- Mean --> is the sum of observations divided by the number of observations .
-.Mean (X') = E X/N. i.e = sum of obs./ N. of obs .

- Median --> is the middle observation in a series of observations after arranging them in an
ascending or descending manner .
** If number of observations is odd --> Median = (n+1)/2 .
** If the number of oservations is even --> Median = n/2 .

.Mode --> is the most frequent occuring value in the data .

EXAMPLE: 5,6,7,5,10,3 .
.Mean = (5+6+7+5+10+3)/5 = 36/6 = 6 .
.Mode --> 5 .
.EX2: 5,6,8,9,11.
Median = (5+1)/2 = 3. so Median is the 3rd observation --> .
.median = 8
EX3: 5,6,8,9 .
.Median = 4/2 = 2. so median is the 2nd obsrvation .
.Median will be the mean of observations 2&3 --> (6+8)/2 = 7 .

:.N.B.
Range: is a measure of variation (dispersion) .
Range: is the difference between the largest and the smallest values .
Range = lagest value - smallest value .
.e.g.Range = 9-5 = 4

:.N.B.
- Average: it is the summation of the total number of observations divided by the
sample size .
e.g. in random sample of children the number of episods of UTIs are as follow (50 child (0),
)30 child (1), 10 child (2), 10 child (3).
The average number of UTIs episods per year in a child is:
the number of UTIs episods per years is: . (500) + (301) + (102) + (103) = 80 UTIs episod per year
** The average number of UTIs episods per year in a child = 80/100 = 0.8 (between 0 and 1(
.i.e the child experiences less than one attack of UTIs per year

- A 95% confidence interval is the range of values in which we can be 95% confident that the
true mean of the underlying population falls in
- In order to calculate the confidence interval we need to know the (mean, SD, Z- score and
sample size).
Standard error of the mean
.(SEM)= is calculated using the formulab

SEM = SD//n

.Notice that the sample size (n) is a part of the calculation .

.*Thus the confidence interval (CI) will tighten as the sample size increases .
.*The next step is to multiply the SEM with the corresponding z-score .
For 95% CI, the Z-score is 1.96 (for 99% CI the Z-score is 2.58) .
The final step is
to obtain the confidence limit as shown: Mean +_ 1.96*SD//n

-They are useful for crude analysis of data .

- They can demonstrate the type of association (linear or non linear( .
. *If a linear association is oresent, the correlation coefficient can be calculated .
The association is positive (if the outcome increases with the increase in the exposure) ->
+ve correlation coefficient while
the association is negative (if outcome decreases with the increase in exposure) ->

-ve correlation coefficient .

. *the correlation coefficient in an almost perfect linear association is close to 1 .
-- Crude analysis of association using the scatter plots doesn't account for possible
confounders.

:N.B.
1- It is very important to consider the natural history of a disease when evaluating the
effectiveness of a druge in a trial .
e.g. common cold --> natural esolution within one week should be taken in consideration
while evaluatingan anti-viral drug used in treatment of common cold.
2- It is difficult to comment on a druge effectiveness, unless a comparison is made with the
control group and statisical significance is made to know the power of the study

NULL HYPOTHESIS AND ALTERNATIVE HYPOTHESIS.

-Is always the statement of NO relationship between the exposure and the outcome
- To state the null hypothesis correctly you should recognize the study design first
- In cross-sectional study: the 2 variables (CRP & cancer colon) are studied at the same
point of time so
the temporal relationship between the 2 variable can't be evaluated
So you can't measure the relationship between the 2 variables --> Null hypothesis is better
.considered

- It Opposes the Null hypothesis .

-It States that there is a relationship between the exposure and the outcome .
- It is better for studies in which a relationship between the 2 variables is existing to
consider the Alternative hypothesis .

- It is the applicability of the obtained results beyond the cohort that was studied .
- External validity answer the question "how the generalizabe are the results of a study to
other populations .
For example: if the cohort is restricted to middle aged women, the results of the study are .
.applicable only to middle aged women & not applicable to eldery men

================================================================

1- Smoking cessation the single most effective preventive intervention in almost every
patient or most effective modifier of mortality including aspirin and tight glucose control) (
in nearly every disease .

2- How to calculate:
Sensitivity = true +ve by the test / (true +ve + false -ve)
all patients that are actually diseased .

True positive = sensitivity (true +ve + false -ve) .

i.e(N. of patients actually with the disease ).
True negative = (1- sensitivity) (true +ve + false -ve) .
i.e. (N. of patiets actually with the disease).

Specificity = true -ve by the test/ (true -ve + false +ve) .

all patients that are actully free

True negative = specificty (true -ve + false +ve) .

i.e all patients that are actully free

- is the probability of rejecting the null hypothesis when it is truly false

i.e. it is the probability of finding a true relationship (the probability of seeing difference .
when there is one truly existing).
-- So if the researchers need to find a difference between a tested drug and the standard .
of care if exists, they need to maximiz the power (1-B).
** Power depends on sample size and the difference in outcome between the 2 groups
being tested

- Occurs when the researchers fail to reject the null hypothesis when the null hypothesis .
is really false
)they say there is no difference when actually there is (one) difference(
- It causes the investigators to miss true relationships .
- An example: a study finding that doesn't affect platelet function when, in fact it does .
- Beta (B): is the probability of committing a type II erorr .
If (B) is set at 0.2 (20%) i.e there will be a 20% chance to accept the null hypothesis when it
is false >
the power (1-B) will be 0.8 (8o%) i.e there will be a 80% chance of rejecting the null
hypothesis when it is truly false

- Occurs when the researchers reject the null hypothesis when the null hypothesis is really
true .
..)they say there is difference when actually there is no difference(
i.e the study finds a statistically significant difference between 2 groups when it is actually .
.not existing
An example: If a study concluded that hard candy improves heart failure mortality, when
it doesn't
Alpha (a): is the maximum probability of making type I erorr a researcher is willing to .
.accept
-It corresponds with the 'P" value or the probability of making a type I error .
- The (a) is typically set at P= 0.05, meaning that the researchers accept a 5% possibility .
that the difference preceived as true is actually due to chance .

:N.B.: in a,b,c,d table

** type I erorr = b/(b+d ).

** type II erorr = c (a+c).

:N.B.
There are 4 basic payment methods that exist between health insurance and physicians :

1-Capitation
- Physicians are paid fixed amount of money per enrollee, not per service .
(i.e paid by capitation ).
So they have incentives to contain (decrease) costs per enrollee due to the fixed budget
allocated for them.
-If many enrollees seek care or there are enrollees need extensive care, physicians costs
.may be greater than their payments
So physicians are motivated to provied more preventive care to catch illness early so .
.patients stay healthier and need fewer tests and procedures as they age

2-Free for service (FFS(

-Physicians are paid fixed amount of money for every service and diagnostic test they
provide .
- They face little financial risk and they enticed (tend to) increase the number of service
they provide on each visit.
.as well as the number of visit per each patient
-There is no incentive to avoid costly tests or procedures .

3-Discounted fee for service

_______________________________
--Discounted FFS works smilarly to FFS except that physicians are reimbursed (repay)
a discounted amount .
So physicians paid under this model may be more conservative when ordering tests and .
,providing services compared to those paid by FFS
especially if expensive tests or services are greatly discounted .

4-Salary
- Physicians are paid a fixed amount and their pay is not tied to number of enrollees or
services rendered (provided ).
- Unless their contracts includ withholds or bonuses, salaried physicians face no financial
risk.
So they have no financial incentive to change their treatment patterns, either in service
.provided or number of follow up visits

** Capitation is often used in health maintenance organization insurance plans

** FFS and discount FFS are commonly used in preferred provider organization insurance
plans .

:.N.B
- A state with a population of 4,000,000 contains 20,000 people who have
, disease A, a fatal neurodegenerative condition. there are 7,000 new cases of the disease
a year and 1000 deaths attributable to disease A. there are 40,000 deaths per year from all
causes, what is the,,,,,,,, ?

** Incidence of the disease:

is the number of new cases of a disease per year divided by population at risk
- incidence = 7000 / (4,000,000 - 20,000 ( .

**The disease specific mortality:

is the number of deaths attributable to the disease per year divided by the total population
- The disease specific mortality = 1000/4,000,000

**The rate of increase of a disease:

is the number of new cases per year minus the number of deaths (or cures) per year divided
by the total popeolation.
- The rate of increase of a disease = (7000-1000)/4,000,000

The prevalence of a disease: is the number of persons with the disease divided by the total population at a specfic point
of time
-The prevalence of a disease = 20,000 / 4,000,000

The mortality rate: ** is the number of deaths per year divided by the total population
--The mortality rate = 40,000 / 4,000,000

:N.B.: when you see it as a graph.

1- An increase in lung cancer incidence and mortality has been observed in women over
the last four decades due to increased cigarette smoking .
2- Breast cancer is the most common non skin cancer among women in USA, but breast
,cancer mortality is comperatively low.
3-Mortality from breast cancer has stayed relatively stable overtime, where as colon cancer
.mortality decreased some what over the last decades
4-Stomach cancer is now uncommon, so it's incidence and mortality have been drastically
.decreased in the last decades
5-Mortality of ovarian cancer is stabe over time
6-A part from skin cancer, the most common women cancer are ordered in descending
.according to incidence: Breast cancer, Lung cancer then colon cancer
7-In order of mortality: Lung cancer followed by Breast cancer then colon cancer

:.N.B
- case-Fatality rate: is calculated by dividing the fatal cases by the total number of people
with the disease.
- Case-fatality = Number of fatal cases/total number of people with the disease-

:N.B
** If events are independent, the probability that all events will turn out the same
.(e.g. -ve) is the product of the separate probabilities for each event
** The probability of at least 1 event turnning out differently is given as: 1- (the probability of all events being the same).
For example
## A new seriological test for detecting prostate cancer is negative in 95% of patients who
dont have the disease, if the test is used on 8 blood samples
taken from patients with out prostate cancer, what is the probability of getting
at least 1 positive test .
- In this case a 0.95 (95%)probability of giving a true negative result and 0.05 (5%)
probability of giving false positive result .

8- To calculate the chance of all 8 tests being negative: probability (all negative)= (0.95(
you have to to know that the total probability is always equal to 1.0 (100%).
>> so
The probabilty that at least 1 test turns out positive is: Probability (at least 1 positive) = 1-probility (all negative) = 1- (0.95 )