1. Reporting How do we present data in a way that is more helpful for patients/clinicians/regulators/industry to make more informed decisions? –Presentations that are interpretable for non-researchers Provide absolute risk AND relative risk summaries Provide reference or “baseline” risk to aid decision-makers –Provide risk for alternative therapy or without therapy Provide summaries for each important outcome (benefits AND harms) Group information by outcome severity Visual summaries Measures of variation Heterogeneity of effects

2. Expected Number in 100 Treated Patients ABNNT Responders >30% improvement XX >50% improvement XX Adverse Reactions Life-threateningXX SevereXX OtherXX 01 Confidence Intervals for: Risk Difference Relative Risk

3. Proportion of responders 0100 Response Magnitude Big Winner Loser A B 50 = Boxplot

4. % Pain Change 0 100 Difference in proportions NNT Relative Risk 0 1 050 Cumulative Distribution Functions Plot risk difference, RR, and NNT (w/ confidence bands) as a function of % pain change (on a common horizontal axis)

5. Scatterplot Approach w/ Distance Metric Assume benefit and risk each can be measured on a continuous (e.g., 0-10) scale or can be transformed as such Create a scatterplot (benefit vs. risk) based on patient results Fit a smooth “tolerability boundary” through 2 or more points –All points on the boundary have equivalent benefit:risk Reduce to one-dimensional analyses by defining a distance function –Use the tolerability boundary to standardize the distance –Closer to (risk =0, benefit=10) → Benefit:risk ↑

6. Patient Level Measures Patients rate their overall experience with respect to perceived benefit and risk Possibly useful for therapies to treat symptoms (e.g., pain) when “risks” are recognizable to the participant Problematic when symptoms do not equate with risk –i.e., silent risk of abnormal labs (e.g., LFTs, bilirubin)

7. Example: Scatterplot Approach: ACTG A5252 A5252: Study evaluating therapies for neuropathic pain Benefit: Pain (measured 0-10) Risk: “how bothersome were the side effects?” (0-10) Define tolerability boundary based on 3 points: Minimum tolerable benefit when risk = 0 (b1) Maximum tolerable risk when benefit = 10 (r1) Minimum tolerable benefit when risk = r1/2 (b2)

8. Partition plane into regions of interest and summarize the proportion that fall into these regions LOSER WINNER ? ? May be acceptable with a very serious disease with no known cure ? May not be acceptable with a disease that is not life-threatening and other effective and safe treatment options are available BENEFIT  RISK 

9. Group#Event/#Subj.Prop. A1/5000.2% B3/5000.6% MeasurePoint est & 95%CI Risk Diff.(B-A)0.4% [-0.4%, 1.2%] Relative Risk (B/A)3.0 [0.3, 158] Group#Event/#Subj.Prop. A1/5,0000.02% B3/5,0000.06% MeasurePoint est & 95%CI Risk Diff.(B-A)0.04% [-0.04%, 0.12%] Relative Risk (B/A)3.0 [0.3, 158] Absolute vs. Relative Risk Implications for safety NI trials and rare event trials Do both as interpretation depends on both. Excellent discussion: Wei et.al. Food and Drug Law: Regulation and Education Update. January/February 2011