SMHS IntroEpi

Scientific Methods for Health Sciences - Introduction to Epidemiology

Overview

Epidemiology is the study of the distribution and determinants of disease frequency in human populations. It serves as an important area in the scientific field: it is the only scientific discipline that is concerned with the occurrence of disease in human populations and how it changes over time. The introduction to Epidemiology aims to introduce the filed of Epidemiology and study the basic concepts and methodologies we are going to apply later. It also aims to help students solve and analyze Epidemiological problems and introduce students to various Epidemiological studies.

Motivation

To get an introduction to Epidemiology, we want to:

• study on the basis of the language of epidemiology and identify key sources of data for epidemiologic purposes
• be able to calculate and interpret measures of disease frequency
• recognize and evaluate epidemiological study designs and their limitations
• be an informed consumer of epidemiological sources of information (journals, websites, government agencies).

Five main goals of epidemiology

• To identify the cause of disease and its risk factors
• To determine the extent of disease found in the community
• To study the natural history and prognosis of disease
• To evaluate new preventative and therapeutic measures
• To provide a foundation for developing public policy.

Distinguishing between Endemic, Epidemic, and Pandemic

• Endemic: The habitual presence (or usual occurrence) of a disease within a given geographic area;
• Epidemic: The occurrence of a disease clearly in excess of normal expectancy in a given geographic area;
• Pandemic: A worldwide epidemic affecting an exceptionally high proportion of the global population.

Modes of Disease Transmission

• Direct contact: transmission occurs when the pathogen is transferred by contact from an infected person to contaminated intermediate object such as sneeze, touch or sexual intercourse.
• Indirect contact: transmission involves the transfer of pathogen by contact with a contaminated intermediate inanimate object or vector. (1) Inanimate object vehicle), examples may be toy, food or water; (2) Vector-borne (animal or insect), examples include mosquito, tick and mice.

Attack Rates and Ratios (ARR)

Attack rates and ratios use statistics to develop and evaluate hypotheses in an outbreak involves: starting with the big picture and big risk factors for disease such as “How many people at the event got ill?”; refining the big picture into smaller questions of “Did they eat the salad? Chicken? Or ice cream?”; formulating a hypothesis such as “Among those who eat at the buffet, are the people who ate the Caesar salad at greater risk than those who did not?”

• Attack Rates (AR): $AR=\frac{Number\,of\,people\,at\,risk\,who\,develop\,a\,certain\, illness} {Total\,number\,of\,people\,at\,risk}.$

• Attack Rate Ratio (ARR): $ARR=\frac{Attack\,rate\,in\,those\,exposed} {Attack\,rate\,in\,those\,unexposed}.$

• $H_{0}:ARR=1$,and 95% confidence intervals can be used to see whether estimated ARR interval includes the null value of 1. If ARR is much greater than 1, then people exposed are more likely to develop the illness compared to those unexposed.

Measuring Disease

To name and calculate two measures of incidence and describe differences in interpreting these measures as well as to understand the difference of the difference between proportion and a true rate.

• Incidence: number of new cases of a disease occurring in the population during a special period of time divided by the number of persons at risk of developing the disease during that period of time. For example: if there are 2000 persons at risk during the year and 20 develop disease over that period. The incidence rate would be 20⁄2000=1%.

• • Cumulative incidence: $ \frac{Number\,of\,new\,cases}{Total\,population\,at\,risk}. $
  • Incidence rate: $\frac{Number\,of\,new\,cases}{Total\,person-time\,contributed\,by\,the\,persons\,followed}.$

Person time is a way to measure the amount of time all individuals in a study spend at risk. For example, if subject A is followed for 3 days, subject B is followed for 5 days and C for 8 days then person-days = 3 + 5 + 8 = 16.

• Prevalence $\frac{Number\,of\,cases\,of\,a\,disease\,in\,the\,population\,at\,a\,specified\,time}{Number\,of\,persons\,in\,the\,population\,at\,that\,time}.$
  • The specified time can be a period or a point, so we can measure the prevalence during a short period in January of 2013 or on January 3$^{rd}$, 2013.

Measuring Mortality Rates

• To calculate and interpret all-cause mortality rates, group-specific mortality rates and cause-specific mortality rates.

• All cause mortality rates=$\frac{Number\,of\,deaths\,in\,a\,specified\,time\,period}{Number\,in\,population\,in\,the\,middle\,of\,the\,year}$.

• Cause-specific mortality rate=$\frac{Total\,number\,of\,deaths\,in\,1\,year\,from\,lung\,cancer\,in\,US}{Population\,of\,the\,US\,in\,the\,middle\,of\,the\,year}$.

• Group-specific mortality rate=$\frac{Total\,number\,of\,deaths\,in\,1\,year\,among\,women\,in\,US} {Female\,population\,of\,the\,US\,in\,the\,middle\,of\,the\,year}$.

Additional Measures of Mortality

• • Infant mortality: $\frac{Number\,of\,deaths\,in\,children\,under\,1\,year\,of\,age\,in\,2011} {(Number\,of\,live\,births\,in\,2011}$.

• • Proportionate mortality: measures proportion of all deaths occurring in a given place over a given time that is due to a given cause.

• • Case fatality: Of all people diagnosed with a given disease, the proportion of persons die of a case over a certain period.

• • Underlying cause of death.

Direct and Indirect Adjustment of Rates

Direct and indirect adjustment of rates are used to compare two populations or one population at different time periods with different age distributions by adjust for age to compare the mortality rates in two populations if they both have the same age distribution.

• Direct age-adjustment: expected rate (or standardized rate) can be compared to the crude rate or to any other similarly standardized rate.

For each population:

1. Calculate age-specific rates

2. Multiply age-specific rates by the # of people in corresponding age range in standard population

3. Sum expected # of deaths across age groups

4. Divide total # of expected deaths by total standard population

Age-adjusted mortality rate for each population of interest.

• Indirect age-adjustment: expected number of deaths can be compared to the number of actual deaths with the standardized mortality rate (SMR). It is especially useful when I don’t trust the group-specific rates (i.e. if the population is too small).

1. Acquire age-specific mortality rates for standard population

2. Multiply standard population’s age-specific rates by # of people in age range in study population

3. Sum expected # of deaths across age groups in study population

4. Divide observed # of deaths by expected # of deaths in study population

Result: SMR (>1 more than expected, =1 as expected, <1 less than expected)

Screening

Screening is the use of testing to sort out apparently well persons (asymptomatic) who probably have disease from those who probably do not and allows to detect the disease early. Examples of screening include: fasting blood sugar for diabetes, bone densitometry for osteoporosis and Otoacoustic emissions testing for hearing loss new borns. It is done during the preclinical phase and is a secondary prevention strategy. Screening increases lead time, thereby allows us to detect disease early, initiate treatment sooner and provide better outcomes. However, it is critical that screening programs must be warranted and there must be a critical point that can be preceded by screening.

A. Clinical utility predictive value & reliability: clinical utility of positive tests. If a patient is tested positive, the likelihood they actually have the disease is called Positive Predictive Value (PPV), if a patient tests negative, the likelihood they actually do not have the disease is called Negative Predictive Value (NPV). PPV and NPV are affected by prevalence of disease, specificity and sensitivity of the test.

		Disease Status
		Disease	No Disease
Screening Test	Positive	a (True positives)	b (False positives)
	Negative	c (False negatives)	d (True negatives)

$PPV=\frac{a}{a+b},NPV=\frac{d}{c+d}$

PPV interpretation: Given a positive result on the disease, the likelihood that an individual is positive in the screening test is PPV.

NPV interpretation: Given a negative result on the disease, the likelihood that an individual is negative in the screening test is NPV.

B. Factors influence predictive values:

• Disease prevalence: increasing disease prevalence increases PPV (or decreases NPV). Screening program most productive and efficient in high-risk populations; screening for infrequent disease may waste resources; need to present PPV in context of disease prevalence.
• Test specificity (ability of a test to correctly identify those who have the disease $=\frac{d}{b+d}$): higher test specificity increases PPV.
• Test sensitivity (ability of a test to correctly identify those who do not have the disease =$\frac{a}{a+c}).$

Note: the cutoff of a disease will influence test sensitivity and specificity: lowering the cutpoint will increase true positive hence increases sensitivity; decreases true negative hence decreases specificity. Similarly, raising the cutpoint will decrease true positives hence decreases sensitivity; increase true negatives hence increases specificity.

C. Validity: validity is the ability of a test to distinguish between who has disease and who does not; reliability is the ability to replicate results on same sample if test if repeated. The following charts shows the three possible outcomes: (from left to right) valid not reliable, reliable not valid and valid and reliable.

D. Reliability(repeatability) of tests:

Can the results be replicated if the test is redone? The results may be influenced by three factors:

• Intrasubject variation: variation within individual subjects
• Intraobserver variation: variation in reading of results by the same reader
• Interobserver variation: variation between those reading results

E. How do multiple testing improve screening programs?

Using multiple tests:

(1) sequential tests(2-stage) is less expensive, less invasive, less uncomfortable test first; if positive on first test, then follow-up with additional testing.

(2) simultaneous tests (parallel) conduct multiple screening tests at the same time; to be considered positive, the person can test positive on either test, to be considered negative, the person must test negative on all tests.

Each test has own sensitivity and specificity. Utilization of multiple testing can improve net sensitivity (simultaneous testing) or net specificity (sequential testing), that is sequential testing decreases net sensitivity and increases net specificity while simultaneous testing increases net sensitivity and decreases net specificity.

Randomized Controlled Trials (RCT):

The investigator assigns exposure at random to study participants, investigator then observes if there are differences in health outcomes between people who were (treatment group) and were not (comparison group) exposed to the facto. Special care is taken in ensuring that the follow-up is done in an identical way in both groups. The essence of good comparison between “treatment” is that the compared groups are the same except for the “treatment”.

*Steps of a RCT: hypothesis formed; study participant recruited based on specific criteria and their informed consent is sought; eligible and willing participants randomly allocated to receive assignment to a particular study group; study groups are monitored for outcome under study; rates of outcome in the various groups are compared.

External and internal validity:

• External validity: Generalization of study to larger source population. Influenced by factors like: demographic differences between eligible and ineligible subgroups; intervention mirror what will happen in the community or source population.

• Internal validity: Ability to reach correct conclusion in study. Influenced by factors like: ability of subjects to provide valid and reliable data; expected compliance with a regimen; low probability of dropping out.

Measures of Association and Effect in RCT:

Ratio of two measures of disease incidence (relative measures) - Risk Ratio (Relative Risk), Rate Ratio. Difference between two measures of disease incidence: Risk difference, efficacy.

		Disease Status
		Disease	No Disease
Treatment	Drug A	a	b
	Placebo	c	d

$Relative\,Risk=\frac{Cumulative\,Incidence\,in\,exposed} {Cumulative\,Incidence\,in\,unexposed}=ratio\,of\,risks=Risk\,Ratio=\frac{a/(a+b)} {c/(c+d)}=\frac{CI_{drugA}}{CI_placebo}$

$Rate Ratio=\frac{Incidence\,rate\,in\,exposed} {Incidence\,rate\,in\,unexposed}$

Interpretation: RR>1, The risk of X is RR times more likely to occur in group A than in group B; RR=1, Null value (no difference between groups); RR<1, Either calculate the reduction in risk ratios (100%-xx%) or invert (1/RR) to be interpreted as “less likely” risk.

• Situations that favor the use of RCT:

(1) Exposure of interest is a modifiable factor over which individuals are willing to relinquish control;

(2) Legitimate uncertainty exists regarding the effect of interventions on outcome, but reasons exist to believe that the benefits of the intervention in question overweight the risks;

(3) Effect of intervention on outcome is of sufficient importance to justify a large study.

Cohort Study:

Population of exposed and unexposed individuals at risk of developing outcomes are followed over time to compare the development of disease in each group.

• Steps: Establish the study population. Identify a study population that is reflective of base population of interest and has a distribution of exposure; identify group of exposed and unexposed individuals. Study on the outcomes of exposed and not exposed groups.

• Types:

Prospective (concurrent) and Retrospective Cohort Studies (non-concurrent) based on when is the data collected. Retrospective has benefits: more cost effective; good for disease of long latency. Prospective has benefits: data quality presumably higher. Both designs need to be cautious of ascertainment biases if outcomes or exposure is known.

• Measures of Association in Cohort Study:

Ratio of two measures of disease incidence (relative measures): Risk Ratio (Relative Risk), Rate Ratio. Difference between two measures of disease incidence: Risk Difference, Rate Difference.

• Strengths and weakness of Cohort Design:

Strengths:

(1) Maintain temporal sequence – can estimate incidence of disease; exposure precedes development of disease; also explore time-varying information.

(2) Excellent for studying known adverse exposures or those that cannot practically be randomized.

(3) Like RCT, excellent for studying rare exposures. (4) Multiple outcomes and sometimes multiple exposures can be studied.

Disadvantages:

(1) Long-term follow-up required and expensive;

(2) Not effective at capturing rare outcomes and can be challenging to study disease that take a long time to develop;

(3) Loss to follow-up can be a problem;

(4) Changes over time in criteria and methods can lead to problems with inferences;

(5) People self-select exposures so exposed and unexposed may differ with respect to important characteristics.

• Situations favor a Cohort Study:

(1) When there is evidence of an association between the exposure and the disease from other studies;

(2) When the exposure is rare but incidence of disease among the exposure is high;|

(3) When time between exposure and development of the disease is relatively short or historical data is available;

(4) When good follow-up can be ensured.

Case Control Study:

A case control study compares cases and controls to see which group has greater exposure to the disease.

• Measures of Association: Odds Ratio.

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• SOCR Home page: http://www.socr.umich.edu

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