Would a Large tPA Trial for Those 4.5 to 6.0 Hours from Stroke Onset Be Good Value for Information?

To quantify the potential value of new research in patients treated with thrombolytic treatment (tissue-type plasminogen activator [tPA]) in the 4.5- to 6.0-hour time window after stroke onset and to determine the optimal size of a future trial using value of information analysis.

Expected value of partial perfect and sample information (EVPPI and EVSI) analyses were conducted using a probabilistic Markov model. Data for modified Rankin Scale (mRS) distributions in patients 4.5 to 6.0 hours since stroke onset for tPA (n = 576) and placebo (n = 543) were obtained from pooled randomized controlled trials. EVSI was quantified with net monetary benefit (assuming willingness to pay for health as $100,000/QALY). We calculated discounted population-level EVSI by multiplying per-person EVSI by the annual number of eligible patients with stroke in the United States and assuming a 10-year time frame of treatment use. Study costs were based on administrative costs and the costs of tPA.

The base-case lifetime cost-effectiveness analysis showed that tPA was dominated by placebo in this patient group. EVPPI for mRS distributions was $1003 per person. On the basis of EVSI, the optimal sample size of a new trial collecting data on tPA efficacy in these patients would be 5600 across study arms with expected population-level societal returns (EVSI minus study costs) of $68.7 million.

Expanding research attention to the 4.5- to 6.0-hour time window for tPA treatment of patients with acute ischemic stroke is justified because the expected returns are substantial. Even a relatively large trial in which more information on treatment efficacy on the basis of mRS scores is collected would represent good value for information.