Post on 04-Apr-2018
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CLINICAL DECISIONSUSING AN ARTICLE
ABOUT PROGNOSIS
NOEL L. ESPALLARDO, MD, MSc
Department of Clinical Epidemiology
UP College of Medicine and Philippine General Hospital
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Natural History of Disease
No With disease With disease Death
disease no symptom with symptoms
Risk Diagnosis Prognosis
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Definition of Prognosis
Prediction of the course of disease following its onset
Prognostic factorsconditions associated with theoutcome of disease
Difference with risk factors
risk factors prognostic factors
well patients diseased patients
outcome is diagnosis outcome is complication/death
rates in 1,000 or 10,000 rates 100
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A Cohort Study of Patients
with Acute MI
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Natural History of Disease
No heart With heart With AMI Death
disease disease
Risk
Age
Male
Smoking
HypertensionHypercholesterolemia
Diagnosis Prognosis
Age
Female
Smoking
HypotensionAnterior infarct
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Elements of Prognostic Studies
Start of study
Zero timepoint in time in the course of disease
Inception cohortgroup of patients assembled at the onset oinception of their disease
Follow-up of study
Long enough to observe the desired outcome
End of study Five Ds death, discomfort, disease, disability and
dissatisfaction
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Natural History of Disease
No heart With heart With AMI Death
disease disease
Risk Diagnosis Prognosis
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Cohort Study
With AMI Death
Start of study
Zero point
Inception cohort
Follow-up
Long enough
End
Death
Disease
Disability
DiscomfortDissatisfaction
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False Cohort
Cohort is assembled based on their availability at thetime the outcome is observed
Also termed survival cohort or available patientcohort
Presented in literature as case-series
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False Cohort Study
(Case Control)
With AMI Death
Prognostic factors Start of study
Dropout
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Potential Biases
in Cohort Studies
Sampling bias
Groups being assembled are not at similar point in time of disease
Susceptibility bias
Groups assembled are not similarly susceptible to outcome of disease
Migration bias
Some members of the group dropout of the original group
Cross-over, dropouts
Measurement
One group have less chance of determining the exact outcome
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Cohort Study
With AMI Death
Sampling bias
No clear diagnosis
Some with repeat
MI
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Effect of Sampling Bias
No With disease With disease Death
disease no symptom with symptoms
Survival A
Survival B
Test A
Test B
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Cohort Study
With AMI Death
Sampling bias
No clear diagnosis
Some with repeat
MI
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Cohort Study
With AMI Death
Sampling bias
No clear diagnosis
Some with repeat
MI
Susceptibility bias Migration bias
More with repeat MI DropoutsCrossover
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Cohort Study
With AMI Death
Sampling bias
No clear diagnosis
Some with repeat
MI
Susceptibility bias Migration bias
More with repeat MI DropoutsCrossover
Measurem
Specific ca
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Controlling Bias in Cohort
Random selection
Randomly select patients or randomly assign them to groups
Restriction
Limit the range of patient characteristics i.e. age group,residence etc.
Matching
For each patient in one group select one or more patients witthe same characteristics (except for the factor under study) tothe other group
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Controlling Bias in Cohort
Stratification
Compare rates within subgroups
Simple adjustment
Adjust crude rate by assigning weight for one or fewcharacteristics
Multivariate
Adjust for difference in multiple factors using statisticalmodeling techniques
Sensitivity analysis
Best case/worst case
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In the end
Biased?
Perhaps. Does it matter?
Do you have better data?
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Survival Curve Analysis
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A 43 year old male with dyspnea consulted at PGH. Hewas initially diagnosed to have PTB and treated as suchwith no relief. He came to the ER in respiratory distress.Chest x-ray showed pulmonary mass with extrathoracicextension.
Impression: Bronchogenic carcinoma, T4, N3 with bonemetastasis highly considered
The patients wife asked Doctor, will my husband be ableto go home?
The Patient
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EBM practitioner
Among patients who have bronchogenic cancer who
have extensive involvement, nodal metastasis and
probable bone metastasis, what is the probability ofsurvival at 5 years?
The physician-in-charge
Until when will the physician strive for the utmost
welfare of a patient succumbing to his terminal illness?
The Clinical Question
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MEDLINE search
bronchogenic carcinoma
prognostic factors (extensive involvement,
nodal or bone metastasis)
5 year survival
The EBM Practitioner
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Lassen et al.
Long-term survival in lung cancer: Post-treatmentcharacteristics in patients surviving 5 to 18 years -
An analysis of 1,714 consecutive patients
Journal of Clinical Oncology, 1995; 13: 1215-1220.
The Article
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Was there a well defined sample of patients at a similarpoint in the course of the disease.
YES 1,714 consecutive patients who wereadmitted in a hospital for treatment andincluded in clinical trials were included. Allpatients underwent pre-treatment stagingprocedures.
Are the Results Valid
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Was follow-up sufficiently long and complete?
YES Follow-up was done for 5 years or more.
Are the Results Valid
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Were objective and unbiased outcome criteria used?
YES Main outcome was survival or mortality.Outcome is measured as alive or dead.
Are the Results Valid
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Was there adjustment for important prognostic factors?
YES Logistic regression analysis, adjustmentwas done for other prognostic factor.
Are the Results Valid
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How large is the likelihood of the outcome event in a specified period of
time?
For extensive stage, bone metastasis is a significant prognostic factor
survival rate with bone metastasis = 2.2%
survival rate without bone metastasis = 4.5%
survival with chest irradiation = 3.2%
survival rate with no chest irradiation = 3.6%
presence of metastasis decreases probability of survival by 50%
What are the Results
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How precise are the estimates of the likelihood?
P value = 0.01 for bone metastasis
What are the Results
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Were the study patients similar to my own?
YES Subjects included in this study were patients
admitted to a hospital for treatment.
Will the Results Help Me
in Caring for My Patient
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Will the results lead directly to selecting or avoiding therapy?
YES Radiation treatment can be avoided.
Will the Results Help Me
in Caring for My Patient
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Are results useful for reassuring or counseling patients?
YES With extensive lesion and presence of metastasis
probability of survival is low. Radiation therapy is nothelpful.
Will the Results Help Me
in Caring for My Patient
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The clinical question
Among patients who have bronchogenic cancer who haveextensive involvement, nodal metastasis and probablebone metastasis, what is the probability of survival at 5years?
The EBM practitioners answer
The probability of the patient surviving in 5 years is verylow (2.2%). Radiation therapy does not offer anyadvantage. The money to be spent for radiationtreatment can be used for other purpose.
The EBM Practitioner
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The question of the physician-in-charge
Until when will the physician strive for the
utmost welfare of a patient succumbing to his
terminal illness?
The answer
Until the patient holds on to life.
The Decision in the Old Paradigm
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The patient was admitted to the wards for antibiotictreatment (clindamycin) for the pneumonia
Radiation therapy was done
On the 27th hospital day culture of tracheal aspiraterevealed Pseudomonas infection and antibiotic was shifted
to imipenem. Five days later the patient went home against medical
advice
THE FAMILY HAD NO MORE FUNDS TO SUSTAIN
TREATMENT !
The Rest of the Story
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Bronchogenic carcinoma, T4, N3 with bone metastasis
highly considered
P 100,000.00 Palliation
P 100,000.00 Start a sari-sari store
Two year computer scienceSend three overseas worker
What is the Price of a Life
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Keep on Asking
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