PMID- 37907282
OWN - NLM
STAT- Publisher
LR  - 20231031
IS  - 1759-8486 (Electronic)
IS  - 1759-8478 (Linking)
DP  - 2023 Oct 31
TI  - Clinically important effect sizes for clinical trials using infarct growth 
      reduction as the primary outcome: a systematic review.
LID - jnis-2023-020850 [pii]
LID - 10.1136/jnis-2023-020850 [doi]
AB  - BACKGROUND: Infarct growth on multimodal imaging is a common lead outcome in 
      phase 2 proof-of-concept and dose-optimization neuroprotective agent stroke 
      trials. However, the effect size in infarct growth reduction that correlates with 
      clinically meaningful differences in clinical global disability outcomes has not 
      been well delineated. METHODS: A systematic literature search identified all 
      endovascular thrombectomy randomized trials reporting magnitude of treatment 
      effect on both infarct growth reduction and increase in functional independence 
      (modified Rankin Scale (mRS) 0-2). Data aggregation determined the size of 
      infarct growth reductions salient to four types of clinically meaningful effect 
      sizes of increase in functional independence: (1) the minimal clinically 
      important difference (MCID)-outcome specific; (2) the MCID-practice changing; (3) 
      the realistic target difference; and (4) the reasonable comparability effect 
      size. RESULTS: A systematic search identified four trials enrolling 612 imaged 
      participants. Across the trials, the amount of functional independence (mRS 0-2) 
      increase associated with each 1 mL reduction in infarct growth was mean 2.3+/-0.6%. 
      An infarct growth reduction of 0.57 mL correlated with the mRS 0-2 increase MCID 
      of 1.3%. Infarct growth reductions of 2.27 mL, 4.35 mL, and 6.53 mL correlated 
      with realistic effect and reasonable comparability effects sizes of mRS 0-2 
      increases of 5%, 10%, and 15%, respectively. CONCLUSION: In formal meta-analysis 
      of randomized treatment trials, every 1 mL reduction in infarct growth was 
      associated with a 2.3% increase in functional independence (mRS 0-2) at 3 months. 
      This conversion factor can inform selection of infarct growth effect size targets 
      for phase 2 trials of neuroprotective agents.
CI  - (c) Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and 
      permissions. Published by BMJ.
FAU - Liao, Nien-Chen
AU  - Liao NC
AUID- ORCID: 0000-0002-1332-7614
AD  - Neurology, Taichung Veterans General Hospital, Taichung, Taiwan.
AD  - Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung 
      University - Yangming Campus, Taipei, Taiwan.
FAU - Bahr Hosseini, Mersedeh
AU  - Bahr Hosseini M
AD  - Comprehensive Stroke Center and Neurology, Reed Neurologic Research Center, 
      University of California Los Angeles, Los Angeles, California, USA.
FAU - Saver, Jeffrey L
AU  - Saver JL
AUID- ORCID: 0000-0001-9141-2251
AD  - Comprehensive Stroke Center and Neurology, Reed Neurologic Research Center, 
      University of California Los Angeles, Los Angeles, California, USA 
      JSaver@mednet.ucla.edu.
LA  - eng
PT  - Journal Article
DEP - 20231031
PL  - England
TA  - J Neurointerv Surg
JT  - Journal of neurointerventional surgery
JID - 101517079
SB  - IM
OTO - NOTNLM
OT  - CT perfusion
OT  - MR perfusion
OT  - Statistics
OT  - Stroke
OT  - Thrombectomy
COIS- Competing interests: JLS has received, for service on clinical trial steering 
      committees and DSMBs advising on rigorous study design and conduct, contracted 
      hourly payments from Medtronic, Abbott, NeuroVasc, Phillips Medical, Bayer, 
      Biogen, Roche, BrainsGate, BrainQ, and Occlutech, and stock options from Rapid 
      Medical and QuantalX.
EDAT- 2023/11/01 00:42
MHDA- 2023/11/01 00:42
CRDT- 2023/10/31 21:13
PHST- 2023/07/23 00:00 [received]
PHST- 2023/09/20 00:00 [accepted]
PHST- 2023/11/01 00:42 [medline]
PHST- 2023/11/01 00:42 [pubmed]
PHST- 2023/10/31 21:13 [entrez]
AID - jnis-2023-020850 [pii]
AID - 10.1136/jnis-2023-020850 [doi]
PST - aheadofprint
SO  - J Neurointerv Surg. 2023 Oct 31:jnis-2023-020850. doi: 10.1136/jnis-2023-020850.