CLINICAL DECISIONS USING AN ARTICLE ABOUT PROGNOSIS

NOEL L. ESPALLARDO, MD, MSc

Department of Clinical Epidemiology UP College of Medicine and Philippine General Hospital

Natural History of Disease

No disease With disease no symptom With disease with symptoms Death

Risk

Diagnosis

Prognosis

Definition of Prognosis
Prediction of the course of disease following its onset Prognostic factors conditions associated with the outcome of disease
Difference with risk factors
risk factors
well patients outcome is diagnosis rates in 1,000 or 10,000

prognostic factors
diseased patients outcome is complication/death rates 100

A Cohort Study of Patients with Acute MI

Natural History of Disease

No heart disease With heart disease With AMI Death

Risk

Diagnosis

Prognosis Age Female Smoking Hypotension Anterior infarct

Age Male Smoking Hypertension Hypercholesterolemia

Elements of Prognostic Studies

Start of study
Zero time point in time in the course of disease Inception cohort group of patients assembled at the onset or

inception 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

Natural History of Disease

No heart disease With heart disease With AMI Death

Risk

Diagnosis

Prognosis

Cohort Study
With AMI Death

Start of study Zero point Inception cohort

Follow-up Long enough

End Death Disease Disability Discomfort Dissatisfaction

False Cohort
Cohort is assembled based on their availability at the time the outcome is observed
Also termed survival cohort or available patient cohort Presented in literature as case-series

False Cohort Study (Case Control)

With AMI
Dropout

Death

Prognostic factors

Start of study

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

Cohort Study
With AMI Death

Sampling bias No clear diagnosis Some with repeat MI

Effect of Sampling Bias

No disease With disease no symptom With disease with symptoms Death

Test A

Survival A

Test B

Survival B

Cohort Study
With AMI Death

Sampling bias No clear diagnosis Some with repeat MI

Cohort Study
With AMI Death

Sampling bias

Susceptibility bias

Migration bias Dropouts Crossover

No clear diagnosis More with repeat MI Some with repeat MI

Cohort Study
With AMI Death

Sampling bias

Susceptibility bias

Migration bias Dropouts Crossover

Measurement Specific cause

No clear diagnosis More with repeat MI Some with repeat MI

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 with the same characteristics (except for the factor under study) to the other group

Controlling Bias in Cohort

Stratification Compare rates within subgroups
Simple adjustment Adjust crude rate by assigning weight for one or few characteristics Multivariate Adjust for difference in multiple factors using statistical modeling techniques Sensitivity analysis Best case/worst case

In the end
Biased?
Perhaps. Does it matter? Do you have better data?

Survival Curve Analysis

The Patient
A 43 year old male with dyspnea consulted at PGH. He was initially diagnosed to have PTB and treated as such with no relief. He came to the ER in respiratory distress. Chest x-ray showed pulmonary mass with extrathoracic extension.
Impression: Bronchogenic carcinoma, T4, N3 with bone metastasis highly considered The patients wife asked Doctor, will my husband be able to go home?

The Clinical Question

EBM practitioner Among patients who have bronchogenic cancer who have extensive involvement, nodal metastasis and probable bone metastasis, what is the probability of survival 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 EBM Practitioner

MEDLINE search
bronchogenic carcinoma prognostic factors (extensive involvement,

nodal or bone metastasis) 5 year survival

The Article
Lassen et al. Long-term survival in lung cancer: Post-treatment characteristics in patients surviving 5 to 18 years An analysis of 1,714 consecutive patients Journal of Clinical Oncology, 1995; 13: 12151220.

Are the Results Valid

Was there a well defined sample of patients at a similar point in the course of the disease.

YES

1,714 consecutive patients who were admitted in a hospital for treatment and included in clinical trials were included. All patients underwent pre-treatment staging procedures.

Are the Results Valid

Was follow-up sufficiently long and complete?
YES

Follow-up was done for 5 years or more.

Are the Results Valid

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

Was there adjustment for important prognostic factors?
YES

Logistic regression analysis, adjustment was done for other prognostic factor.

What are the Results

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

How precise are the estimates of the likelihood?
P value = 0.01 for bone metastasis

Will the Results Help Me in Caring for My Patient

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

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

Are results useful for reassuring or counseling patients?
YES

With extensive lesion and presence of metastasis probability of survival is low. Radiation therapy is not helpful.

The EBM Practitioner

The clinical question Among patients who have bronchogenic cancer who have extensive involvement, nodal metastasis and probable bone metastasis, what is the probability of survival at 5 years?
The EBM practitioners answer The probability of the patient surviving in 5 years is very low (2.2%). Radiation therapy does not offer any advantage. The money to be spent for radiation treatment can be used for other purpose.

The Decision in the Old Paradigm

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 Rest of the Story

The patient was admitted to the wards for antibiotic treatment (clindamycin) for the pneumonia Radiation therapy was done On the 27th hospital day culture of tracheal aspirate revealed 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 !

What is the Price of a Life

Bronchogenic carcinoma, T4, N3 with bone metastasis highly considered P 100,000.00 P 100,000.00 Palliation Start a sari-sari store Two year computer science Send three overseas worker

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