Clinical impact of NXY-059 demonstrated in the SAINT I trial: derivation of number needed to treat for benefit over entire range of functional disability.
OBJECTIVE
The SAINT I trial demonstrated that the neuroprotective agent NXY-059 improves the distribution of acute stroke patient outcomes on the modified Rankin Scale (mRS) of global disability. Standard dichotomized number-needed-to-treat (NNT) analyses for the magnitude of treatment benefit range widely, from 22.7 to infinity, and each capture only a portion of the observed beneficial shift in outcomes. Derivation of an NNT value reflecting the treatment's benefit over the entire range of the mRS is required to describe the clinical import of the trial results.


METHODS
The minimum and maximum possible NNTs for benefit over the range of mRS global disability outcomes were calculated by completing a joint distribution outcome table for a model population of 1000 patients, shifting responders by the greatest and smallest possible increments, respectively. The biologically most plausible NNT within this range was derived by having 10 neurologist and emergency-physician acute stroke-care experts independently specify the joint distribution of outcomes in model samples of 1000 patients assigned to placebo and active therapy.


RESULTS
The minimum possible NNT for benefit incorporating all mRS state transitions is 7.9 and the maximum is 16.7. The biologically most plausible NNT for 1 additional patient to have a better outcome by 1 or more grades on the mRS outcomes is 9.8 (95% CI, 8.7 to 10.9).


CONCLUSIONS
Considering improvements in global disability over the entire outcome range, the SAINT I trial results indicate that for every 100 patients treated, approximately 10 will benefit and none be harmed as a result of treatment.
Saver
Jeffrey L
JL
Stroke Center and Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, USA. jsaver@ucla.edu
D001557:Benzenesulfonates / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D016001:Confidence Intervals; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018401:Sample Size; D020521:Stroke / Q000188:drug therapy*
D001557:Benzenesulfonates; D002317:Cardiovascular Agents; D018696:Neuroprotective Agents; C120851:disufenton sodium