A graphic reanalysis of the NINDS Trial.
OBJECTIVE
Reports of clinical trials typically present only a fraction of the available data, at times hampering interpretation of their meaning. The initial report of the National Institute of Neurologic Diseases and Stroke (NINDS) trials of tissue plasminogen activator in acute ischemic stroke is an example of this phenomenon.


METHODS
We used the original data from the NINDS trials to create graphs showing the effect of treatment on neurologic function in all 624 individual patients in the trial. Our goal was to show detailed graphics of the 90-day outcomes, stratified on relevant confounders and effect modifiers.


RESULTS
Final outcomes were highly dependent on stroke severity. In many graphs, the small difference between groups favored tissue plasminogen activator, particularly when baseline NIHSS score was between roughly 5 and 22. These differences diminish or disappear when 90-day change in NIHSS is graphed. Our graphs fail to support the time-is-brain hypothesis.


CONCLUSIONS
Our graphical method of presenting the NINDS trial results provides more detail than was conveyed in the original report and empowers readers to reach their own conclusions about the trial's meaning. Outcomes for placebo and treatment limbs are sufficiently similar that larger trials, conducted under the same conditions as the NINDS trial, are needed to determine which patients benefit from this therapy.
Hoffman
Jerome R
JR
Department of Emergency Medicine, University of California School of Medicine, Los Angeles, CA, USA. jrh@ucla.edu
Schriger
David L
DL
D000208:Acute Disease; D000367:Age Factors; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003196:Computer Graphics; D015986:Confounding Factors, Epidemiologic; D003626:Data Display; D003627:Data Interpretation, Statistical; D015987:Effect Modifier, Epidemiologic; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D012720:Severity of Illness Index; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator