Penelitian Epidemiologi Kohort

Anisa Catur Wijayanti, SKM., M.Epid.

Prodi Kesehatan Masyarakat
FIK_UMS
2019
Cohort in epidemiology:

sekelompok orang yang mempunyai atau mengalami

pengalaman yang sama
 Experimental vs. Cohort

 Studi eksperimen:
 subyek dimasukan kedalam kelompok dan pajanan diberikan
kepada subyek oleh peneliti

 Studi kohort:
 Pajanan terjadi secara alamiah (karena pilihan subyek atau
karena kebetulan misal adanya kebocoran radiasi), bukan
diberikan oleh peneliti. Pengelompokan subyek bukan oleh
peneliti
Definisi kohort
- Berdasarkan geografis tempat tinggal yang sama
- Berdasarkan tempat kerja yang sama
- Berdasarkan pekerjaan yang sama tetapi pada industri
yang berbeda
- Anggota organisasi profesi
Definisi kohort
 Kebaikan kohort menurut geografis atau pada suatu
tempat kerja adalah karakteristik pajanan lebih konsisten
dan tidak bervariasi

 Kelebihan kohort yang berasal dari tempat yang berbeda

adalah meningkatnya jumlah studi populasi
Objective of cohort study
 to compare:

 an incidence rate in an exposed population

to the rate that would have been observed
in the same population, at the same time
if it had not been exposed
Recipe: Cohort study
Recipe: Cohort study

 Identify group of
 exposed subjects
 unexposed subjects
 Follow up for disease occurrence
 Measure incidence of disease
 Compare incidence between exposed and unexposed
group
  TIME

Disease
Exposed

People No disease
Population
Without
disease
Disease
Not exposed

No disease
follow-up period
 Calculate
measure of frequency:

 Cumulative incidence
- Incidence proportion
- Attack rate (outbreak)

 Incidence density

end of follow-up
Cumulative incidence

 CI is a population-based estimate of individual risk

 CI is always a proportion (0 – 1, or %)
 CI needs the follow-up period over which the risk is
estimated
 CI = I/N I = # of new cases during follow-up
N= # of disease-free subjects at start
COHORT
 Schematic:

Outcome
Expose
No Outcome
Free of
Outcome
Outcome

Non Expose No Outcome

 Cohort studies
exposed

unexposed
 Cohort studies
exposed

Incidence among
exposed

unexposed

Incidence among
unexposed
Closed vs. Dynamic
 Closed cohort
Subyek diobservasi dari saat penelitian dimulai sampai
dengan akhir penelitian. Diasumsikan tidak ada subyek
yang masuk atau keluar dari penelitian setelah penelitian
berjalan.
 Dynamic (open population)
Subyek diperbolehkan masuk ataupun keluar dari
penelitian.
 Closed Cohort and Open Cohort

Closed Cohort

PRESENT FUTURE

D+
E+ • Anggota kelompok E+ and E-
difolow-up dalam periode waktu
D- yang sama
• Insidens outcome (D) diukur
D+ dgn ukuran Cummulative
Incidence
E-

D-

Fixed cohort
 Cumulative Incidence
Incidence proportion
CI assumes that entire population at risk
followed up for specified time period

x
x
x
x
x
CI = 7/12 per year

x = 0.58 per year

x
x disease onset
Month 1 Month12
Incidence density
 Measures how rapidly a new event are developing
 It is a rate, not a risk  It is always measured in units of
time
 The denominator is the sum of follow-up time for all
subject in the observed group (cohort)
 IR = I/PT I = # new cases during the follow-up
PT = person time of observation
 90 91 92 93 94 95 96 97 98 99 00 Time at risk

A 6.0
B x 6.0
C 11.0
D 9.5
E x 5.0

Total years at risk 37.5

-- time followed
x disease onset
ID = 2 / 37.5 person- years
= 0.053 person-year
 Open Cohort
Awal studi Akhir studi
P o
?
E
X
R ?
E+ S X
?
O X
N ?
? !
O = meninggal
TIME krn kausa lain
X = outcome +
? = drop-out
P o
?
E
?
E- R X
S ?
O o
N !
?

TIME Insidens diukur dengan

Incidence Density
 Pengelompokan subyek berdasarkan ada atau tidak ada
pajanan
 Subyek tidak menpunyai sakit yang diteliti pada saat
penelitian dimulai.
 Subyek diikuti untuk mengetahui status penyakit
Types of Cohort Study
 Retrospective cohort
 Baik pajanan maupun outcome sudah terjadi

 Prospective cohort
 Pajanan dapat sudah ada atau belum, tetapi outcome belum
terjadi
 Prospective Cohort
Exposure Disease
x ?
o ?

 Retrospective Cohort
Exposure Disease
x ?
o ?
Prospective cohort study
Disease
Exposure Study starts occurrence

time

Disease
Study starts Exposure occurrence

time
 Retrospective cohort studies

Disease
Exposure occurrence Study starts

time

Case study
Salmonella in Belfast
Planning a Cohort Study
 Apakah populasi studi cukup besar untuk menghasilkan
data yg reliable secara statistik?
 Apakah jangka waktu penelitian cukup panjang untuk
meneliti efek yang lama atau penyakit yg jarang terjadi?
 Apakah data pajanan dapat menjelaskan hubungan pajanan
dengan terjadinya outcome?
Choice of Study Population
1. General Population
 Risk factors is generally found in the general population
 Able to study several risk factors and outcomes
 Able to generalize, providing high validity
 No acceptable record
 High mobility  expensive and difficult to monitor
 Potentially low cooperativeness & high loss to follow-up
 Chose a high risk sub-population (Framingham Heart Study,
1951: only persons 30+)
Choice of Study Population
2. Specific population
 Population having very different exposure from the general
population (very high or very low).
 This population is very beneficial to verify certain risk
factors, more efficient especially for very rare
 Population of workers has low probability to loss to follow-
up
 Relatively low mobility  cheaper and easier to follow-up
 Some population is more valid and reliable
 Difficult to generalize
Principles in Choosing Exposed Population
 Availability
1. Available record
2. Available method and instrument to measure
exposure
3. Available mechanism to follow-up (reporting-
recording, monitoring system, surveillance etc)
 Population with low mobility
 High risk
 Population able to produce accurate information on
exposure and outcome.
Seleksi Populasi terpajan
 Apakah pajanan umum atau jarang ada di populasi?

 Apakah dapat memberikan informasi yg akurat tentang

pajanan dan outcome pada seluruh populasi studi?
 Populasi khusus
 Tinggal dekat lingkungan yg berbahaya.
 Ada pada waktu kejadian (hiroshima population,
veteran of vietnam’s war)
 Industrial-based (Occupational)

 Kelompok yg memberikan informasi yg adekuat

 Anggota asuransi kesehatan, organisasi, murid

 Populasi pada geografis tertentu.

Selection of unexposed group
 Unexposed may means:
 Totally unexposed to certain risk factor
 Unexposed to one risk factor (study of multiple risk factors)
 Low grade exposure
 Some members are exposed and some are not (such as in general
population).

  unexposed group is more apt to be called comparison

or reference group)
Comparison group
1. Internal comparison group
 From the same population as the exposed, but
“unexposed”
 Has the same probility of detected if he/she develop
the outcome due to the same procedures
 Example: Framingham heart study, studying risk
factors such as smoking, drinking, diet, blood pressure,
cholesterol level, behavior, diabetes, obesity etc.
Comparison group
2. External population
Group that differ from the exposed population and assumed not
to be Chosen due to difficulty in getting an internal
comparison
 Example: cotton textil workers as a comparison group for
asbestos textil
 The unexposed assumption might be inaccurate so that the
result is underestimated
 The confounder distribution might be very different from
those in the exposed group. If the information on confounding
was available the effect can be analyzed
 Follow-up procedures might differ among the two groups
 Smaller healthy worker effect compared to using the general
population
Comparison group
3. General population. Chosen due to difficulty in getting internal
and external comparison. The outcome was compared to
the outcome in general population
 Incomplete exposure. Some of the population members are
exposed. If the exposed population was high 
underestimate
 Might have a healthy worker effect.
 Might differ in the distribution of confounding compared to
the exposed group. Information on confounding is difficult
to assessed
 The follow-up procedure and accuracy of outcome
information might differ
Selection of comparison population

 Groups being compared should be as similar as possible

in terms of
Other risk factors of outcome
 Exposure assessment
 Outcome assessment
Pengukuran Pajanan
 Wawancara, kuesioner, catatan harian
 Data external, dari catatan yg ada
 Pengukuran konsentrasi agen fisik, kimia atau biologi pada
individu atau lingkungan
Sumber Data Outcome

 Catatan RS, klinik

 Sertifikat kematian
 Pemeriksaan fisik secara periodik
 Kwesioner, wawancara
Follow-up of the Cohort
 Update interview, resend questionnaire, update physical
exam, exposure measurement, outcome
 Sketch diagram on how to follow-up the subjects
 Develop a guide on how to search losses of follow-up. It
should not be related to exposure or outcome.
Result from cohort study
 Rate & Risk (measures of frequency)
 Rate/Risk difference (measures of impact)
 Rate Ratio (strength of association)
Effect measures in cohort studies

 Absolute measures
 Risk difference (RD) Ie - Iue

 Relative measures
 Relative risk (RR)
Ie
 Rate ratio Iue
 Risk ratio

Ie = incidence in exposed
Iue= incidence in unexposed
Measure of association
 Absolute measure
 Risk difference (RD) = Ie - Iue

 Relative measure
 Risk ratio
 Rate ratio
Incidence exposed
Incidence unexposed
Result from cohort study (1)
Measures of frequency
Population Cases CI
(f/u 2 years) (2 years)
HIV + 215 8 0.037
HIV - 281 1 0.003
(Source: Epiet)

ID/1000
Person-years Cases person-year
Smoke 102,600 133 1.30
Do not smoke 42,800 3 0.07
Result from cohort study (2)
Measures of association

Relative risk (RR) Ie / Iue

1. Risk ratio (CIR) CIe / CIue
2. Rate ratio (IDR) IDe/ IDue
Examples
Population TB CI
(f/u 2 years) cases (2 years)
HIV + 215 8 0.037
HIV - 281 1 0.003
CIR 12.3

Lung Ca ID/1000
Person-years cases person-year
Smoke 102,600 133 1.30
Do not 42,800 3 0.07
IDR 18.6
Result from cohort study (2)
Impact measure

 Risk difference (RD) Ie – Iue

= Attributable risk (AR)

 Attributable risk % (AR%) Ie – Iue

-------------
Ie
Kekuatan Studi kohort
 Pilihan desain untuk studi dimana pajanan jarang
 Dapat mempelajari asosiasi antara satu pajanan dgn
outcome lebih dari satu
 Dapat memperlihatkan hubungan temporal antara
pajanan dan outcome
 Bias pengukuran pajanan dapat diperkecil
 Dapat mengukur incidence
Keterbatasan Studi Kohort
 Tidak efisien untuk meneliti penyakit yg jarang terjadi
 Jika prospective, biaya besar dan waktu lama
 Jika retrospective, perlu catatan yg adekuat
 Kemungkinan losses to follow-up besar dan merupakan
ancaman validitas hasil penelitian
 Prospective Cohort Study
Examples:

• Framingham Heart Study

• Nurses Health Study

 Prospective Cohort Study
Framingham Heart Study:
• Framingham, MA (1948):  5,000 of the 30,000
town residents ages 30 to 59 years of age
without established coronary disease
participated.
• “Exposures” include smoking, obesity, elevated
blood pressure, high cholesterol, physical
activity, and others.
• “Outcomes” include development of coronary
heart disease, stroke, gout, and others.
 Prospective Cohort Study

Framingham Heart Study:

• Outcome events were identified by examining
the study population every 2 years, and by
daily surveillance of hospitalizations in the only
hospital in Framingham, MA.
• Participants followed for more than 30 years.
• Study has made fundamental contributions to
our understanding of the epidemiology of
cardiovascular disease.
 Prospective Cohort Study

Framingham Heart Study:

• More than 200 published reports.
• Unfortunately, Framingham, MA is almost
exclusively Caucasian.
 Prospective Cohort Study
Nurses Health Study:
• In 1976, > 120,000 married female nurses ages
30 to 55 in one of 11 U.S. states participated.
• At 2-year intervals, follow-up questionnaires
were completed on development of
outcomes and exposure information.
• “Exposures” include use of oral contraceptives,
post-menopausal hormones, hair dyes,
dietary fat consumption, age at first birth, and
others.
 Prospective Cohort Study

Nurses Health Study:

• “Outcomes” include heart disease, various types
of cancer, and others.
• Many new “exposures” have been added to the
biennial questionnaires (e.g. electric blanket use,
selenium levels, etc.).
 Prospective Cohort Study
Follow-up Issues:
• Major challenge is to collect follow-up data
on every study subject.
• Loss to follow-up is a major source of bias
and is related to:
--- Length of follow-up
--- Monitoring methods used in the study
• Multiple sources of information can be
used to obtain complete follow-up information.
 The cohort study
is
the gold-standard
Alain Moren of analytical epidemiology

CASE-CONTROL STUDIES HAVE THEIR PLACE

IN EPIDEMIOLOGY but if cohort study possible,
do not settle for second best
Referensi
 2. Bonita, R., Beaglehole, R., Kjellstrom, T. 2006. Basic
Epidemiology 2ed edition. Geneva : WHO.
 3. Bustan, N. 2012. Pengantar Epidemiologi. Jakarta :
Rineka Cipta.
 6. Ryadi, S., dan Wijayanti, T. 2011. Dasar-Dasar
Epidemiologi. Jakarta : Salemba Medika.
 7. Zheng, T. 1998. Principles of Epidemiology. Connecticut :
Yale University.
-end-
 Sebuah penelitian kepada 100 orang dilakukan untuk
membuktikan bahwa pernikahan dini dapat terjadi karena
ketidaktahuan orangtua mengenai bahaya yang dapat
diakibatkan dari pernikahan dini pada anaknya. Penelitian
dengan cara membandingkan kelompok yang melakukan
pernikahan dini dan pada kelompok yang tidak melakukan
pernikahan dini. Diketahui dari 50 orang yang mengalami
pernikahan dini 30 responden memiliki orangtuanya yang
berpendidikan rendah dan dari 50 orang tidak melakukan
pernikahan dini 30 responden memiliki orangtua yang
berpendidikan tinggi.
 Tentukan :
 Jenis penelitian apa? Alasannya?
 Buat tabel 2 x 2
 Hitung kekuatan hubungannya
 Interpretasi