EVIDENCE BASED

MEDICINE
PROGNOSIS
 WHAT HAPPEN ?

Diagnostic test
and
Diagnosis

PROGNOSIS ?
TREATMENT?

Complaints
Measurements
Abnormality
 WHAT IS PROGNOSIS ?

 Important phase of a disease  progression

of a disease.
 Patient’s, doctor’s, insurance’s concern
 Prognosis: the prediction of the future course
of events following the onset of disease.
 can include death, complications,
remission/recurrence, morbidity, disability
and social or occupational function.
 PROGNOSIS

 How my ilness will

affect me?
 Is it dangerous?
 Could I die of it ?
 Will there be pain?
 How long will I be
able to continue my
present activities?
 Can I be cure at all?
 PROGNOSIS

Diagnosing what is wrong

with them
 Administering treatment that
does more good than harm
 Giving them an indication of
what the future is likely to
hold (prognosis)
 PROGNOSIS

Considering :
A qualitative aspect
(which outcomes could happen?)
A quantitative aspect
(how likely are they to happen?)
A temporal aspect
(over what time period?)

“expert opinion”
• consulting the
appropriate specialist
• looking it up in a
textbook
“clinical experience”
“read up”
 WHAT IS PROGNOSIS ?

 Possible outcomes of a disease and the

frequency with which they can be expected
to occur.
 Natural history: the evolution of disease
without medical intervention.
 Clinical course: the evolution of disease in
response to medical intervention.
 STUDIES OF NATURAL HISTORY

 Degree to which natural history can be

studied depends on the medical system and
the type of disease (rare,high risk).
 The natural history of some diseases can be
studied because:
 remain unrecognized (i.e., asymptomatic)
e.g., anemia, hypertension.
 considered “normal” discomforts e.g.,
arthritis, mild depression.
 STUDIES OF NATURAL HISTORY

 Natural history studies permit the

development of rational strategies for:
 early detection of disease
 e.g., Invasive Cervical CA.
 treatment of disease
 e.g. Ptyriasis versicolor
 Diabetes
Prognosis Suffer target
outcome

Patients at risk Prognostic

Time
of target event factor

Do not suffer
target outcome

?
 A. ARE THE RESULTS OF THIS PROGNOSIS
STUDY VALID?
1. Was a defined, representative sample of patients
assembled at a common (usually early) point in
the course of their disease?
2. Was the follow-up of the study patients
sufficiently long and complete?
3. Were objective outcome criteria applied in a
blind fashion?
4. If subgroups with different prognoses are
identified, was there adjustment for important
prognostic factors and validation in an
independent “test set” patients?
 A.1. Was a defined, representative sample of
patients assembled at a common (usually early)
point in the course of their disease?
 How well defined the individuals in the study
– criteria - representative of the underlying
population.
 inclusion, exclusion
 Sampling method
 similar, well-defined point in the course of
their disease  cohort
COHORT STUDY

Inception cohort: A point in time when cohorts are started to be observed;

should be specified clearly and be the same
 Prognostic factor Outcomes

Yes

Population of Present No
people with Sample
TIME
the disease
Yes

Absent No
Selection
Potential Sampling Measurement
biases

Location of potential bias in cohort studies

 A.2. Was follow-up sufficiently long and
complete?

 Ideal follow-up period

 Until EVERY patient recovers or has one of
the other outcomes of interest,
 Until the elapsed time of observation is of
clinical interest to clinicians or patients.
 Short follow up time  too few study
patients with outcome of interest  little
information of use to a patient.
 A.2. Was follow-up sufficiently long and
complete?

 Loss to follow up  influence the estimate of

the risk of the outcome  validity?.
 Patients are too ill (or too well)
 Die
 Change address etc ,
 Most evidence-based journals require at least
80% follow-up for a prognosis study to be
considered valid.
 Best and worst case scenario!
A.3. Were objective outcome criteria applied in
a blind fashion?

 Investigators making judgments about

clinical outcomes are kept “blind” to subjects’
clinical characteristics and prognostic factors.
 Minimize measurement BIAS; minimized by:
 Blinding
 Fined criteria for all outcome events.
 apply equally efforts to ascertain all events
in both exposure groups.
 A.4. If subgroups with different prognoses are
identified, was there adjustment for important
prognostic factors and validation in an
independent “test set” patients?
 Prognostic factors:
conditions that, when present in persons
already known to have disease, are
associated with an outcome of the disease
 Risk factors:
condition that can be identified in well
persons and, when present, are associated
with an increased risk of acquiring disease
 RISK AND PROGNOSTIC FACTORS
DISABILITY

Increase
d risk of
acquirin
disease

FACTO
RISK
R
g

Biologic onset Diagnosis

PROGNOST

with disease
associated
FACTORS

outcomes
PROBABILITY?
IC

DEATH
 RISK AND PROGNOSTIC FACTORS

Increased
FACTOR
acquiring
disease

risk of

RISK
LOW PROBABILITY OF EVENT

EVENT: ONSET OF DISEASES

QUITE FREQUENT EVENT(HIGH PROBABILITY)

EVENT:SUFFERING, COMPLICATION, DISABILITY, DEATH, etc.

PROGNOST

with disease
associated
FACTORS

outcomes
IC

Prepared by.Putri Eyanoer,MD.,Ms.Epi.,Ph.D.

 Well Onset of acute Outcome:
myocardial infarction Death, reinfarction

RISK PROGNOSIS

1. Age >> 1. Age >>

2. Male 2. Male
3. LDL>/ HDL< 3. Anterior infarction
4. Cigarette smoking 4. Hypotension
5. Hypertension 5. Congestive heart failure
6. Inactivity 6. Ventricular arrythmia

Differences between risk and prognostic factors for acute myocardial infarction
 A.4. If subgroups with different prognoses are
identified, was there adjustment for important
prognostic factors and validation in an
independent “test set” patients?
 Prognostic factors:
conditions that, when present in persons
already known to have disease, are
associated with an outcome of the disease
 Risk factors:
condition that can be identified in well
persons and, when present, are associated
with an increased risk of acquiring disease
 Bias in Follow-up Studies

A. Selection or Confounding Bias

1. Assembly or susceptibility bias: when exposed and non-
exposed groups differ other than by the prognostic
factors under study, and the extraneous factor affects
the outcome of the study.
 Examples:
 differences in starting point of disease (survival
cohort)
 differences in stage or extent of disease, co-
morbidities, prior treatment, age, gender, or
race.
 Bias in Follow-up Studies

A. Selection or Confounding Bias

2. Migration bias:
 patients drop out of the study (lost-to-follow-up).
usually subjects drop out because of a valid reason
e.g., died, recovery, side effects or disinterest.
 these factors are often related to prognosis.
 patients can also cross-over from one exposure
group to another
 if cross-over occurs at random = non-differential
misclassification of exposure
 SURVIVAL COHORT

 Survival cohort (or available patient cohort) studies

can be very biased because:
 convenience sample of current patients are likely to be at
various stages in the course of their disease.
 individuals not accounted for have different experiences
from those included e.g., died soon after treatment.
 Not a true inception cohort e.g., retrospective case
series.
 SURVIVAL COHORT
Observed True
True Cohort Improvement Improvement
Assemble Measure Outcomes
Cohort
N=150
Improved = 75
Not improved = 75 50% 50%
Survival Cohort

Assemble
patients

Begin Measure Outcomes

Follow-up Improved = 40
N = 50
Not
Not improved = 10
Dropouts:
80% 50%
Observed Improved = 35
N = 100 Not improved = 65
 Bias in Follow-up Studies

B. Measurement bias
 Measurement (or assessment) bias occurs when one
group has a higher (or lower) probability of having
their outcome measured or detected.
 likely for softer outcomes
 side effects, mild disabilities, subclinical disease or
 the specific cause of death.
 B. ARE THE RESULTS OF THIS STUDY
IMPORTANT?
1. How likely are the outcomes over time?
2. How precise is this prognostic estimate?

 % of outcome of interest at a particular point in

time (1 or 5 year survival rates),
 Median time to the outcome (e.g. the length of
follow-up by which 50% of patients have died)
 Event curves (e.g. survival curves) that illustrate, at
each point in time, the proportion of the original
study sample who have not yet had a specified
outcome.
 B.2 How precise is this prognostic estimate?

 Precision  95% confidence interval

 The narrower the confidence interval, the
more precise is the estimate.
 If survival over time is the outcome of interest
 shorter follow-up periods results in more
precision  follow up period important to be
clinically important
C. CAN WE APPLY THIS VALID, IMPORTANT
EVIDENCE ABOUT PROGNOSIS TO OUR
PATIENT?
1. Is our patient so different from those in the
study that its results cannot apply?
2. Will this evidence make a clinically
important impact on our conclusions about
what to offer or tell our patient?
C.1. Is our patient so different from those in the
study that its results cannot apply?
 How well do the study results generalize to the
patients in your practice?
 Compare patients' important clinical
characteristics,
 Read the definitions thoroughly
 The closer the match between the patient before
you and those in the study, the more confident
you can be in applying the study results to that
patient.
 For most differences, the answer to this question is
“no”,  we can use the study results to inform our
prognostic conclusions.
 C.2 Will this evidence make a clinically
important impact on our conclusions about
what to offer or tell our patient?
 Useful for
 Initiating or not therapy,
 monitoring therapy that has been initiated,
 deciding which diagnostic tests to order.
 providing patients and families with the
information they want about what the
future is likely to hold for them and their
illness.
 C.2 Will this evidence make a clinically
important impact on our conclusions about
what to offer or tell our patient?
 Communicating to patients their likely fate
 Guiding treatment decisions
 Comparing outcomes to make inferences
about quality of care