Table 1 Risk of bias arising from the randomization process

Was the allocation sequence random?

Probably Yes

Lower risk of Bias

“A permuted-block design with blocks of various sizes was used for randomization, with patients stratified according to clinical center and time from the onset of stroke to the start of treatment (0-90 or 91-180 min)” [2].

No information on method used for random sequence generation.

Was the allocation sequence concealed until participants were enrolled and assigned to interventions?

Probably No

Higher Risk of Bias

“The randomization process was decentralized” [3].

Randomization was done at treatment centers (N = 39) but required coordination by clinical centers (N = 8) and a coordinating center.

“There are 16 patients of the total 624 reported as having been unblinded during the study. This includes 12 patients in the Activase group, and 4 in the placebo group” [3].

Reasons for unblinding envelopes available for 8/16 participants.

“Blinding was incorporated into the studies by using blind labeled vials and identical administration regiments for the treatment arms” [3].

Contents of matched placebo used to generate foaming reaction unreported.

Did baseline differences between intervention groups suggest a problem with the randomization process?

Yes

Higher Risk of Bias

N/A

4 Baseline imbalances identified between groups prognostically favoring alteplase in the 91-180 min stratum were consistent with a larger treatment effect compared to the 0-90 min stratum.