CAT 4: How to Read a Prognosis Article Maribeth Chitkara, MD Rachel Boykan, MD

You are on service on 11N and taking care of a 2 year old patient who was admitted with a first time febrile seizure. The parents are understandably shaken by the experience and have many questions for you. The thing they are most worried about, is whether or not their child will have any longstanding neurologic deficits. In other words, will this impair the child’s chances of getting into Harvard?

Prognosis Prognostic factors don’t necessarily cause the outcome, just have a strong enough association to predict the development of the outcome. Prognostic factors don’t necessarily cause the outcome, just have a strong enough association to predict the development of the outcome. Different from Risk Factors - patient characteristics associated with the development of the disease at all. Different from Risk Factors - patient characteristics associated with the development of the disease at all.

Prognostic Factors in ALL Gender Gender Ethnicity Ethnicity Age at diagnosis Age at diagnosis WBC count at diagnosis WBC count at diagnosis Cytogenetic markers Cytogenetic markers Presence or absences of CNS disease Presence or absences of CNS disease Response to initial treatment Response to initial treatment Genetic conditions (Down’s Syndrome ) Genetic conditions (Down’s Syndrome )

Prognosis: Study Designs Cohort (ideal) Cohort (ideal) Investigators follow one or more groups over time to look for specific outcome Investigators follow one or more groups over time to look for specific outcome Case Control Case Control “case” with outcome of interest, “control” without, retrospectively look back for prognostic factors “case” with outcome of interest, “control” without, retrospectively look back for prognostic factors Subject to recall bias Subject to recall bias Appropriate when outcome of interest is rare Appropriate when outcome of interest is rare

Prognosis - Validity Was there a representative and well-defined sample of patients at a similar point in the course of the disease? Was there a representative and well-defined sample of patients at a similar point in the course of the disease? Was follow-up sufficiently long and complete? Was follow-up sufficiently long and complete? Were objective and unbiased outcome criteria used? Were objective and unbiased outcome criteria used? Was there adjustment for important prognostic factors? Was there adjustment for important prognostic factors?

Prognosis - Results Quantitative results from studies of prognosis or risk are the number of events that occur over time How large is the likelihood of the outcome event in a specified period of time? How large is the likelihood of the outcome event in a specified period of time? How precise are the estimates of likelihood? (confidence intervals) How precise are the estimates of likelihood? (confidence intervals)

What are the Results? Outcome Present Outcome Absent Prognostic Factor Present ab Prognostic Factor Absent cd Relative Risk (a/a+b)/(c/c +d) Relative Risk (a/a+b)/(c/c +d) Absolute Risk Increase Absolute Risk Increase (a/a+b) – (c/c+d)

Survival Curves

Prognosis - Applicability Even when valid, a prognostic study provides only an estimate of the true risk. Even when valid, a prognostic study provides only an estimate of the true risk. Will the results help me in caring for my patients? Will the results help me in caring for my patients? Were the study patients similar to mine? Were the study patients similar to mine? Will the results lead directly to selecting or avoiding therapy Will the results lead directly to selecting or avoiding therapy Are the results useful for reassuring or counseling patients? Are the results useful for reassuring or counseling patients?