A 23-year-old man presents to his psychiatrist for treatment-resistant depression. He reports decreased mood, decreased energy, feelings of guilt, and suicidal ideation the past 2 weeks. Past medical history is significant for major depressive disorder (MDD), which has previously been treated with adequate trials of various selective serotonin reuptake inhibitors (SSRIs). He states previous treatment “worked for a while, but eventually stopped working.” Prior to this current episode, his most recent depressive symptoms occurred 6 months ago. He does not use any illicit substances, and screening laboratory tests are unremarkable. He recently saw a commercial advertising a new antidepressant and asks how adding this new drug would affect his chances of a future MDD relapse. The data from a randomized controlled trial in which this drug was used as an adjunctive treatment demonstrated that 15 percent of patients relapsed within 1 year, compared to 30 percent of patients in the placebo group.
Which of the following statements is the most appropriate answer to the patient's question?
E) The risk of another MDD relapse is halved by adding the new drug to his current regimen
Relative to his current treatment regimen, the risk of another MDD relapse by adding the drug in the trial is 0.5, or one-half. The relative risk (RR) is the risk of an event in the experimental/treatment group compared to the risk in the control/placebo group. If RR <1, the event is less likely in the experimental group. If RR = 1, the event is equally likely in the experimental and control group. If RR>1, the event is more likely in the experimental group. In this vignette, an event is defined as a relapse of major depressive disorder. USMLE Step 1 questions may present a 2 by 2 table and expect one to calculate risk in the experimental and control groups. However, this question already provides the risk for each group. The risk of MDD relapse is 15% in the group receiving the new drug. The risk of MDD relapse in the placebo arm is s 30%. Thus, the relative risk is 15/30 = 0.5, which could be described in patient-friendly terms as “one-half” the risk of relapse compared to his current regimen.
Answer choice A: For every 7 patients who take the new drug, MDD relapse will be prevented in one patient, is incorrect. This is a true statement, but it addresses the number needed to treat (NNT). NNT reflects groups of patients in aggregate rather than directly addressing the risk in an individual patient. The rate of relapse in the placebo group is 30%. The rate of relapse is the treatment group is 15%. The difference is 30-15=15%. NNT = 100/15 = 6.67, ≈7
Answer choice B: More data must be collected before the physician may answer the patient’s question, is incorrect. In general, it is good practice for clinical studies to be replicated to validate results. One must be cautious to not over-generalize the results of early studies. However, there is sufficient data in this trial to answer the patient’s question.
Answer choice C: The chance of another MDD relapse if the patient takes the new drug is 15%, is incorrect. In the study, 15% of patients taking the new drug experienced MDD relapse. However, one may not generalize this statistic to state that any patient who takes the new drug has a 15% chance of MDD relapse. This is due to the profile of unique demographic, genetic, medical, and other traits of those recruited for any given study. These traits might be very different in the study compared to the patient populations encountered in any randomly-selected clinic.
Answer choice D: The chance of another MDD relapse if the patient takes the new drug is 30%, is incorrect. This is risk of MDD relapse in the placebo group.
Key Learning Point
Conceptually, relative risk answers the question “what is the risk of an adverse outcome in the trial group/exposed group compared to the reference group (placebo/no exposure)?” It is calculated by:
- Finding the risk of adverse outcome in the trial group
- Finding the risk of adverse outcome in the placebo group
- Dividing the answer from step 1 by the answer in step 2
Often such data are presented in a two-by-two table. In the context of this problem, such a table might look as follows, with each cell of the table customarily labeled a through d. Beware, though, as USMLE test questions may switch the order of rows/or columns, requiring them to be re-formatted if one is to successfully apply the memorized formula.
When a 2 x 2 table is formatted as shown, the formula for relative risk is a/(a+b) / c/(c+d)
RR = 15/(15+85) / 30+(30/70) = 15/100 / 30/100 = 15/30 = 0.5
