title: What is the value of conducting a trial of r-tPA for the treatment of mild stroke patients?
abstract: Background The Phase IIIb, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS) trial will assess r-tPA in ischemic stroke patients who present with mild deficits (i.e. mild stroke). Aims To assess PRISMS's societal value in clarifying the optimal care for patients with mild ischemic stroke. Methods A value of information (VOI) decision model was developed to compare the outcomes of mild stroke patients treated vs. not treated with r-tPA. Model inputs were derived from a subset of Third International Stroke Trial patients, a recent meta-analysis of r-tPA trials, expert opinion, and other published sources. VOI analyses were also used to assess the expected US societal value of the PRISMS trial and the expected value of reducing uncertainty in key trial estimates. Results The expected net societal value of the PRISMS trial was approximately $210 million ($160 m-$260 m), representing a six-fold return on investment. The value of reducing uncertainty in r-tPA efficacy was approximately $150 million ($100 m-$200 m), while reducing uncertainty in r-tPA safety (increased risk for symptomatic intracranial hemorrhage) did not add additional value in comparison. Conclusions Developing a better understanding of the outcomes of r-tPA treatment in patients with mild ischemic stroke will provide tremendous societal value by clarifying current uncertainty around treatment effectiveness. Enrollment in the PRISMS trial for patients presenting with mild ischemic stroke within 0-3 h of symptom onset should be highly encouraged.
authors.affiliation: 1 Pharmaceutical Outcomes Research and Policy Program, Department of Pharmacy, University of Washington, Seattle, WA, USA.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Guzauskas
authors.affiliation: 2 Genentech, Inc., San Francisco, CA, USA.
authors.forename: Er
authors.initials: E
authors.lastname: Chen
authors.affiliation: 2 Genentech, Inc., San Francisco, CA, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Lalla
authors.affiliation: 2 Genentech, Inc., San Francisco, CA, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Yu
authors.affiliation: 2 Genentech, Inc., San Francisco, CA, USA.
authors.forename: Darren
authors.initials: D
authors.lastname: Tayama
authors.affiliation: 1 Pharmaceutical Outcomes Research and Policy Program, Department of Pharmacy, University of Washington, Seattle, WA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Veenstra
mesh_terms: D002545:Brain Ischemia / Q000188:drug therapy; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008962:Models, Theoretical; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy*; D013997:Time Factors; D061665:Time-to-Treatment; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator
keywords: PRISMS; Tissue plasminogen activator; decision model; mild stroke; randomized controlled trial; value of information