Basics of Scientific Research

Class #4

Observational studies:
How to calculate disease frequencies

Ekaterine Karkashadze, MD, MS

Research Study Designs
Experimental
• Researchers intervene (study is
conducted in experimental
environment)
• Randomized control trial
Observational
• Researchers just observe (study is
conducted in natural environment)
• Cohort study
• Case-control study
• Cross-sectional study

They represent different ways of harvesting information on the relationship

between the exposure and the outcome – identify cause, prevention and
treatment
Research Study Designs
Experimental
• Derives highest quality of evidence
• Not always feasible to conduct
experimental studies because of
ethical considerations: not acceptable
to expose subjects deliberately to
potentially serious hazards
Observational
• Can be used to study the effects of
wide range of exposures, including
effects of hazardous agents
• Helpful to study disease frequency
(incidence, prevalence) and
determinants of disease progression,
to predict future healthcare needs
 Experimental vs. Observational
Experimental (randomized control trial) Follow-up Assessing outcomes

Exposed group: people receiving Outcome

Random new vaccine No outcome
Eligible subjects Assignment
Unexposed group: People Outcome
Researcher intervenes receiving old vaccine No outcome

Follow-up Assessing outcomes

Observational (cohort
study)
Exposed group: people receiving Outcome
new vaccine No outcome
Eligible subjects Regular
care Outcome
No intervention Unexposed group: People
receiving old vaccine No outcome
Examples
1) Study evaluates effectiveness of new vaccine in 1000 persons. Researchers randomly
assigned new vaccine to 500 people, the other half received old vaccine. Participants were
followed for 12 months to compare the outcomes between the two groups
a) Experimental
b) Observational

2) Study evaluates effectiveness of new vaccine in 1000 persons. Researchers enroll people
who received either new vaccine (300 people) or old vaccine (700 people) within the
national vaccination program. Participants were followed for 12 months to compare the
outcomes between the two groups
a) Experimental
b) Observational
Measures of Diseases Frequency in
Observational Studies
• Cohort study
• Cumulative incidence (calculated in closed cohort studies, when follow-up
time is the same for all)
• Incidence rate (calculated in open cohort studies, when follow-up time is the
different for each person)

• Cross-section study
• Prevalence

• Case-control study
• Disease frequency is not calculated in case-control study
2 X 2 Table
Outcome No outcome TOTAL
Exposed a c a+c
Not exposed b d b+d
TOTAL a+b c+d a+b+c+d
2 X 2 Table
Outcome No outcome TOTAL
Exposed a c a+c
Not exposed b d b+d
TOTAL a+b c+d a+b+c+d

a = number of exposed persons who developed outcome (disease)

c = number of exposed persons who did not develop outcome (disease)
a+c = total number of exposed persons
2 X 2 Table
Outcome No outcome TOTAL
Exposed a c a+c
Unexposed b d b+d
TOTAL a+b c+d a+b+c+d

b = number of unexposed persons who developed outcome (disease)

d = number of unexposed persons who did not develop outcome (disease)
b+d = total number of unexposed persons
 Cumulative Incidence in Cohort Studies
Outcome No outcome TOTAL
Exposed a c a+c
Not exposed b d b+d
TOTAL a+b c+d a+b+c+d

Number of new cases (outcome)

Cumulative incidence (CI) = X 100%
Total population
CI is expressed as %, range 0% to 100%

CI(exposed) = a X 100% CI(unexposed) = b X 100% CI(total) = a+b X 100%

a+c b+d a+b+c+d
 Example
• 570 young persons engaging in high risk behavior and 240 young persons
not engaging in high risk behavior were followed and clinically monitored
from 2014 to 2016 to evaluate association between high risk behavior and
new cases of sexually transmitted infection (STI).
• New cases of STI were documented in 46 persons engaged in high risk
behavior in 6 persons not engaged in high risk behavior.

Outcome No outcome TOTAL

Exposed a c a+c
Not exposed b d b+d
TOTAL a+b c+d a+b+c+d
 Example – Let’s fill this table together
• 570 young persons engaging in high risk behavior and 240 young persons
not engaging in high risk behavior were followed and clinically monitored
from 2014 to 2016 to evaluate association between high risk behavior and
new cases of sexually transmitted infection (STI).
• New cases of STI were documented in 46 persons engaged in high risk
behavior in 6 persons not engaged in high risk behavior.

Outcome No outcome TOTAL

Exposed a c a+c
Not exposed b d b+d
TOTAL a+b c+d a+b+c+d
 Example
STI No STI TOTAL
High risk behavior 46 (a) 524 (c) 570 (a + c)
No high risk 6 (b) 234 (d) 240 (b+d)
52 758 810
TOTAL (a+b) (c+d) (a+b+c+d)

CI(exposed) = a X 100% =
46/570=8% a+c
CI(unexposed) = b X 100% =
6/240=2.5% b+d
CI(total) = a+b X 100% =
52/810=6.4% a+b+c+d
Incidence rate (IR) in cohort study
No. Person-
Years
A (Diagnosed with disease) Accrued
8

B (Died) 12

C (Lost) 6

D 20

E 14
Total population (A- 60
E)
1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014
Observation period

IR look at occurrence of diseases within the total time spent at risk

5 Patients (A-E) were at risk for 60 person-years and 1 person developed disease
Incidence rate (IR) in cohort study

• Incidence rate (IR) is (1) the number of people in a population who

developed disease divided by (2) the sum of "time at risk" each member of
the population contributed while in the study
• 1 case/ 60 person-years (PY) = 0.02 cases per 1 person-year of follow-up
• Usually this is multiplied by 100 (or 1 000, 100 000)
• 1 case / 60 PY *100 = 2 cases per 100 PY of follow-up
• IR of 2 / 100 PY means that if we follow 100 persons for 1 year period 2
persons will develop disease
 Prevalence
• Proportion of individuals in a population with disease or condition at a
specific point of time
• Expressed in %

No. of observed cases at time t

Prevalence
Total no. of individuals at time t

EXAMPLE: Researchers decided to evaluate prevalence of chronic Hepatitis C in a region

X with 8 458 adult residents. Anti-HCV test was used to determine Hepatitis C status. The
test was positive in 169 persons. Calculate the prevalence.

Prevalence of Hepatitis C among adult population of region X:

169 / 8 458 * 100% = 1.99 % (About 2%) 16

 Homework Exercise
• 300 persons aged 40-50 years old were followed for 5 years to determine
association between regular alcohol consumption and hip fracture. 100
persons reported daily consumption of alcohol and 200 persons reported
that they do not consume alcohol on regular basis. At the end of follow-up
10 persons who consumed alcohol daily had hip fracture. Among persons
who did not consume alcohol on daily basis also 10 persons had hip
fracture.

• Fill out 2 X 2 table

• What is Cumulative Incidence (CI) of hip fracture in exposed population?
• What is Cumulative Incidence (CI) of hip fracture in unexposed population?
• What is Cumulative Incidence (CI) of hip fracture in total population?
This exercise will be discussed in the next class
Quiz
Quiz 2
1. Read carefully an extract from the abstract Cleaning Staff's Attitudes about Hand Hygiene in a
Metropolitan Hospital in Australia” and define the type of research

Objective: To explore the attitudes of hospital cleaning staff regarding hand hygiene
Methods: Focus groups were conducted with 12 cleaning staff at a large Australian hospital
Results: Hospital cleaners recognize the importance of hand hygiene in preventing healthcare-
associated infections. Cleaners cite peer support, leadership, and the recognition and reward of
those excelling in hand hygiene as strong motivators. Barriers to optimal hand hygiene practice
include the presence of multiple conflicting guidelines, hand hygiene "overload" and a lack of
contextualized education programs.

a) Basic research
b) Fundamental research
c) Quantitative research
d) Qualitative research X
Quiz 2
2. Which of the following is an example of basic research:

a) The study of drug Clopidegrel for the reduction of risk of cardiovascular diseases
b) The study on impact of regular consumption of fast food on health status among adults aged
40 or greater
c) Discovery of reverse transcriptase – an enzyme that plays a crucial role in pathogenesis of
some infectious diseases and cancers X
d) Comparison of treatment strategies for effective reduction of anxiety
Quiz 2
3. Read carefully an extract from the abstract: “Reduction in the Incidence of Type 2 Diabetes
With Lifestyle Intervention or Metformin” and define the type of research
Background: Vitamin D metabolites support innate immune responses to Mycobacterium tuberculosis.
Methods: We randomly assigned children who had negative results for tuberculosis infection to receive a weekly oral dose
of either vitamin D or placebo for 3 years. The primary outcome was a positive result for tuberculosis test at the 3-year
follow-up.
Results: A total of 8851 children underwent randomization: 4418 were assigned to the vitamin D group, and 4433 to the
placebo group. At the end of the trial, the percentage with a positive tuberculosis test result was 3.6% (147 of 4074
children) in the vitamin D group and 3.3% (134 of 4043) in the placebo group (adjusted risk ratio, 1.10; 95% CI, 0.87=1.38;
p=0.42). The incidence of adverse events did not differ significantly between the two groups.
Conclusions: Vitamin D supplementation did not result in a lower risk of tuberculosis infection.

a) Fundamental research
b) Applied research X
c) Basic research
d) Pure research
Quiz 3
• Based on Lecture 3: Research designs
• You have 15 minutes to complete the quiz
• Send back short answers via Goni