Martha Carvour, MD, PhD March 2, 2017 IM EBM Boards Review Martha Carvour, MD, PhD March 2, 2017 No financial disclosures

Question 1 A new treatment for scleroderma is evaluated in a phase III randomized clinical trial. The treatment demonstrates a clinically and statistically significant improvement in symptoms over a 12-month course. Besides the effect of the treatment on disease symptoms, which of the following can be assessed with this phase III study? The likelihood that a patient with scleroderma will benefit from the treatment The effect of the treatment on disease symptoms in different patient populations affected by scleroderma The relative rates of serious adverse events in the treatment and placebo groups The 10-year risks of the treatment compared to the 10-year benefits of the treatment

Question 1 A new treatment for scleroderma is evaluated in a phase III randomized clinical trial. The treatment demonstrates a clinically and statistically significant improvement in symptoms over a 12-month course. Besides the effect of the treatment on disease symptoms, which of the following can be assessed with this phase III study? The likelihood that a patient with scleroderma will benefit from the treatment The effect of the treatment on disease symptoms in different patient populations affected by scleroderma The relative rates of serious adverse events in the treatment and placebo groups The 10-year risks of the treatment compared to the 10-year benefits of the treatment

Question 1 The main objective of this question is to distinguish between phases III and IV. Phase III assesses the effects (desired and adverse) in the population that was under study during the period of study. The relative rates of serious adverse events in the treatment and placebo groups  Phase III. Phase IV permits study over more diverse clinical populations and longer time periods. The effect of the treatment on disease symptoms in different patient populations affected by scleroderma  Phase IV. The 10-year risks of the treatment compared to the 10-year benefits of the treatment  Phase IV.

Question 2 A new treatment for scleroderma is evaluated in a phase III randomized clinical trial. During the study, some patients in the placebo group receive medications that are similar to the study drug. These are prescribed by their personal physicians. However, when the study is analyzed, these patients are classified as placebo recipients. What is this kind of analysis called? Post hoc analysis Intention-to-treat analysis Per-protocol analysis As-treated analysis

Question 2 A new treatment for scleroderma is evaluated in a phase III randomized clinical trial. During the course of the study, some patients in the placebo group received medications that were similar to the study drug. These were prescribed by their personal physicians. However, when the study is analyzed, these patients are classified as placebo recipients. What is this kind of analysis called? Post hoc analysis Intention-to-treat analysis Per-protocol analysis As-treated analysis

It’s The Thought (ITT) that counts. Question 2 The main objective of this question is to distinguish between common approaches to analyzing clinical trial data. Intention-to-treat (ITT): Analyze according to the treatment that was intended (by randomization) Per-protocol: Analyze those who actually received the treatment as intended (typically non-random) As-treated: Analyze according to what actually happened (typically non-random) It’s The Thought (ITT) that counts.