Yuki Yunanda

(no medical intervention)

Natural history of diseases

Recovery
Biologic Clinical Disability
Outcome
onset Diagnosis Death
etc

Clinical courses
(medical intervention)
 3

Critical Appraisal : Prognosis

1. Are the results of the study valid?

2. Are the results of this study important?

3. Can I apply this valid, important

evidence about prognosis to my patient?
 4

1. Are the results of the study valid?

a) Was a defined, representative sample of patients

assembled at a common (usually early) point in the course
of their disease?

b) Was the follow-up of the study patients sufficiently long

and complete?

c) Were objective outcome criteria applied in a „blind‟

fashion?

d) If subgroups with different prognoses are identified, was

there adjustment for important prognostic factors and
validation in an independent “test set” patients?
 6

1.(a) Was a defined, representative sample of

patients assembled at a common (usually early)
point in the course of their disease?

• It is preferable if study patients are enrolled at a

uniformly early time in the disease, usually when the
disease first becomes manifest.
• Patients should also be representative of the underlying
population
• The Methods section should describe the stage at which
patients entered the study
Yes, (Methods pg.24, col.
2 Patients)
 8

1.(b) Was follow-up sufficiently long and complete?

• Length of follow-up should be long enough to detect the
outcome of interest (e.g., for pregnancy outcomes, nine
months; for cancer, many years).

• All patients should be followed from the beginning of the

study until the outcome of interest or death occurs

• Reasons for non follow-up should be provided (e.g., death,

change address, etc)

• Most evidence-based journals require at least 80% follow-up

for a prognosis study to be considered valid.
• The Results section should state the median or mean length of
follow-up.
(See Methods pg.24, col.2 Study
Design and Oversight, end points)
 10

1.(c) Were objective outcome criteria applied in a

blind fashion?

• A clear definition of all outcomes should be provided

• Investigators making judgments about clinical outcomes

are kept “blind” to subjects’ clinical characteristics and
prognostic factors. Minimize bias.

• The Methods section should provide a clear definition or

explicit criteria for each outcome, and whether
determination is blinded to prognostic factors will be
found in either the Methods or Results sections.
• To minimize the effects of bias in measuring the outcome,
investigators should established specific criteria to define
each important outcome and then used them throughout
patient follow-up.*
• In valid studies, investigators making judgments about
clinical outcomes are kept “blind” to these patients clinical
characteristics & prognostic factors.*

*(Straus, SE, Richardson, SE, Glasziou, P, Haynes, RB. Evidenced-Based

Medicine: How to Practice and Teach EBM)
• In administrative databases, those who record outcome
data will always be unblinded, (and those who record
predictor data, always blinded) but will be unaware of the
hypotheses of future investigators making use of
database.**

• One relatively easy safeguard that you can use is to leave

data collection personel unaware of study hypotheses.**

• **(Guyatt, G. Determining Prognosis and Creating Clinical Rule

Decision in Clinical Epidemiology: How to Do Clinical Practice
Research, 3rd edition, 2006. p338-339).
“Were objective & unbiased outcome criteria used?”
• Investigators should clearly specify and define their target
outcome before the study and, whenever possible, they
should base their criteria on objective measure.***

• As the subjectivity of the outcome definition increases, it

becomes more important that individuals determining the
outcomes are blinded to the presence of prognostic
factors.***

***(Randolph, A, Bucher, H, Richardson, WS, Wells, G, Tugwell, P, Guyatt, G.

Prognosis in JAMA User’s Guide)
Can not tell, but in the
‘Methods’ it said
‘Investigators were
unaware of overall
outcome data’ (pg.24
col.2 Study Design and
Oversight
 15

1.(d) 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
• The Results section should identify any prognostic factors and
whether or not these have been adjusted for in the analysis.
There’s no different
prognostic factor between two
group on this study
(see result pg.26 Table 1
‘Baseline and Operative
Characteristics of the Patients’
 17

2. Are the results of this study important?

a) How likely are the outcomes over time?

b) How precise is this prognostic estimate?
 18

2.(a) How likely are the outcome over time?

• % of outcome of interest at a particular point in

time (1, 5, 10 etc. survival rates,
• Mean, Median time (length of the follow-up by
which 50% of patients have died) of the outcome
• Event curves
• Effect size (Hazard ratio, Rate ratio, Odds ratio,
etc.)
 19

2.(b) How precise is this prognostic

estimate?

• Precision  95% confidence interval (CI)

• The narrower the confidence interval, the more precise is the
estimate.

• Precision of the estimates depends on number of observations

on which the estimate is based  shorter follow-up periods
results in more precision.
2. Are the results of this study important?
 21

3. Can I apply this valid, important evidence

about prognosis to my patient?
a) Is my patient so different from those in the study that its
results cannot apply?

b) Will this evidence make a clinically important impact on my

conclusions about what to offer or tell my patient?
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3.(a) 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.
 23

3.(b) Will this evidence make a clinically

important impact on our conclusions about what
to offer or tell our patient?

• 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.
• Communicating to patients their likely fate
• Guiding treatment decisions
• Comparing outcomes to make inferences about quality of care
Glasser, SP, Cutter,G. Association, Cause and Correlation in Essential
Clinical Research. Springer. 2008.
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