The Tendril Plot-a novel visual summary of the incidence, significance and temporal aspects of adverse events in clinical trials

Abstract

Background: In contrast to efficacy, safety hypotheses of clinical trials are not always pre-specified, and therefore, the safety interpretation work of a trial tends to be more exploratory, often reactive, and the analysis more statistically and graphically challenging.

Methods: We introduce a new means of visualizing the adverse event data across an entire clinical trial.

Results: The approach overcomes some of the current limitations of adverse event analysis and streamlines the way safety data can be explored, interpreted and analyzed. Using a phase II study, we describe and exemplify how the tendril plot effectively summarizes the time-resolved safety profile of two treatment arms in a single plot and how that can provide scientists with a trial safety overview that can support medical decision making.

Conclusion: To our knowledge, the tendril plot is the only way to graphically show important treatment differences with preserved temporal information, across an entire clinical trial, in a single view.

Trial registration: ClinicalTrials.gov NCT01443845.

Figures

Figure 1.

The Tendril plot algorithm concept illustrated on a portion of a single preferred term: Back pain. The inset zooms in on the first 3 events to demonstrate how events on placebo tilt the tendril to the right and events on active tilt the tendril to the left. To emphasize this step in the algorithm, in this plot, the events are colored by treatment arm; yellow and brown circles for placebo and active arm, respectively. The distance between points are proportional to time between events. Point size is not linked to any information.

Figure 2.

A tendril plot of all AEs in the RE2SPOND trial. Each MedDRA PT is represented by a line (tendril) and each point is an event. Since time runs along each tendril, it is the shape that carries the important information, rather than the x and y coordinates. An event on the roflumilast treatment arm will tilt tendril direction to the left, and an event on the placebo arm will tilt tendril direction to the right. Point size is indicative of the total number of events for the type of AE in both treatment arms in the trial. The FDR adjusted Pearson’s chi-squared P-value in each point is mapped onto a continuous color gradient.

Figure 3.

Panel showing examples of interactivity. For example (A) hovering over an event gives detailed information about type of AE, AE frequency, etc.; selecting a specific PT in (B); filtering to a subset of PTs with a total event frequency ≥100 in (C); linking selected events to additional information in (D); and recasting into a trellis configuration, for assessment by SOC, in (E).