Appraising

Prognostic Study
Introduction - Prognosis
Important phase of a disease progression
of a disease.
Patients, doctors, insurances 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.
Introduction - 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.

Natural History Studies
Degree to which natural history can be studied
depends on the medical system (Scandinavia)
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.
Natural History Studies
Natural history studies permit the
development of rational strategies for:
early detection of disease
e.g., Invasive Cervical CA.
treatment of disease
e.g. Diabetes

Prognosis
Patients at risk
of target event
Prognostic
factor
Time
Suffer target
outcome
Do not suffer
target outcome
?
?
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. ARE THE RESULTS OF THIS
PROGNOSIS STUDY VALID?
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
A.1. Was a defined, representative sample of
patients assembled at a common (usually early)
point in the course of their disease?
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 patient
Loss to follow up influence the estimate of the risk of the
outcome validity?.
Patients are too ill (or too well); Die; Move, etc
Most journals require at least 80% follow-up for a prognosis
study to be considered valid.
Best and worst case scenario (sensitivity analysis)
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!

Measurement bias
Measurement bias can be minimized by:
ensuring observers are blinded to the exposure
status of the patients.
using careful criteria (definitions) for all
outcome events.
apply equally rigorous efforts to ascertain all
events in both exposure groups.
Prognostic factors: factors associated with a
particular outcome among disease subjects. Can
predict good or bad outcome
Need not necessarily cause the outcome, just be
associated with them strongly enough to predict their
development
examples includes age, co-morbidities, tumor size, severity
of disease etc.
often different from disease risk factors e.g., BMI and pre-
menopausal breast CA.
A.4. If subgroups with different prognoses are
identified, was there adjustment for important
prognostic factors and validation in an independent
test set patients?
Risk factors
distinct from prognostic factors,
include lifestyle behaviors and environmental exposures
that are associated with the development of a target
disorder.
Ex: smoking = important risk factor for developing lung
cancer, but tumor stage is the most important prognostic
factor in individuals who have lung cancer.
A.4. If subgroups with different prognoses are
identified, was there adjustment for important
prognostic factors and validation in an independent
test set patients?
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.
asses extent of bias by using a best/worst case
analysis.
patients can also cross-over from one exposure group
to another
if cross-over occurs at random = non-differential
misclassification of exposure
Bias in Follow-up Studies
A. Selection or Confounding Bias
3. Generalizability bias
related to the selective referral of
patients to tertiary (academic) medical
centers.
highly selected patient pool have
different clinical spectrum of disease.
influences generalizability
Survival Cohorts
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 trt.
Not a true inception cohort e.g., retrospective case
series.
S
u
r
v
i
v
a
l

C
o
h
o
r
t
s

B
i
a
s

True Cohort
Survival Cohort
Observed
Improvement
True
Improvement
Assemble
Cohort
N=150
Measure Outcomes
Improved = 75
Not improved = 75
50% 50%
80%
50%
Measure Outcomes
Improved = 40
Not improved = 10
Assemble
patients
Begin
Follow-up
N = 50
Not
Observed
N = 100
Dropouts:
Improved = 35
Not improved = 65
II. 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?
B.1. How likely are the outcomes over time?
% 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.
Survival Rate

1 year survival
A. Good
B. 20%
C. 20%
D. 20%
Median survival
A. ?
B. 3 months
C. 9 months
D. 7.5 months
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 patients?
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?
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
Conclusion
Prognosis study beneficial
Communicating to patients their likely fate
Guiding treatment decisions
Comparing outcomes to make inferences
about quality of care