Number needed to treat to benefit and to harm for intravenous tissue plasminogen activator therapy in the 3- to 4.5-hour window: joint outcome table analysis of the ECASS 3 trial.
OBJECTIVE
Measures of a therapy's effect size are important guides to clinicians, patients, and policy-makers on treatment decisions in clinical practice. The ECASS 3 trial demonstrated a statistically significant benefit of intravenous tissue plasminogen activator for acute cerebral ischemia in the 3- to 4.5-hour window, but an effect size estimate incorporating benefit and harm across all levels of poststroke disability has not previously been derived.


METHODS
Joint outcome table specification was used to derive number needed to treat to benefit (NNTB) and number needed to treat to harm (NNTH) values summarizing treatment impact over the entire outcome range on the modified Rankin scale of global disability, including both expert-dependent and expert-independent (algorithmic and repeated random sampling) array generation.


RESULTS
For the full 7-category modified Rankin scale, algorithmic analysis demonstrated that the NNTB for 1 additional patient to have a better outcome by >or=1 grades than with placebo must lie between 4.0 and 13.0. In bootstrap simulations, the mean NNTB was 7.1. Expert joint outcome table analyses indicated that the NNTB for improved final outcome was 6.1 (95% CI, 5.6-6.7) and the NNTH 37.5 (95% CI, 34.6-40.5). Benefit per 100 patients treated was 16.3 and harm per 100 was 2.7. The likelihood of help to harm ratio was 6.0.


CONCLUSIONS
Treatment with tissue plasminogen activator in the 3- to 4.5-hour window confers benefit on approximately half as many patients as treatment <3 hours, with no increase in the conferral of harm. Approximately 1 in 6 patients has a better and 1 in 35 has a worse outcome as a result of therapy.
Saver
Jeffrey L
JL
UCLA Stroke Center, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, USA. jsaver@ucla.edu
Gornbein
Jeffrey
J
Grotta
James
J
Liebeskind
David
D
Lutsep
Helmi
H
Schwamm
Lee
L
Scott
Phillip
P
Starkman
Sidney
S
D000465:Algorithms; D002986:Clinical Trials as Topic; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator