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Reply: REPLY: (effect modification) to avoid both problems described above. Observations of our results graphically (see Figs 1 and 4 in our e thank Johansson and Salzer for their response to our ar- article) suggest that there is evidence of benefit from intra-arterial Wticle. We agree that several considerations of our study are therapy versus controls in patients with a small baseline infarct limited by the small sample size. However, the main objection of core and good collateral circulation; however, we wanted to cau- the authors is with the statement in the conclusion of our article, tion our readers that they should not assume from our data that a “Overall, this report supports the selection of patients for intra- similar effect exists in patients with a large baseline core or poor arterial therapy on the basis of favorable patient characteristics collaterals. This is so because biologically, it is plausible that these (small core, good collateral circulation) and low likelihood of re- patients with large baseline infarcts or very poor collaterals may canalization with intravenous thrombolysis (large and proximal have poorer outcomes on average even with good treatment. clot burden).” They fail to mention the sentence that follows, Therefore, we suggested a cautionary last sentence, “Additional “Additional studies will be needed to further understand the con- studies will be needed to further understand the continued benefit tinued benefit of intra-arterial treatment for patients with larger of intra-arterial treatment for patients with larger infarct burden infarct burden or distal occlusions.” or distal occlusions,” instead of giving the readers a spurious mes- Any clinical trial is powered primarily to understand main sage that patients with low ASPECTS or poor collaterals are likely effects. This was the case even with the Solitaire With the Inten- to benefit to the same extent as patients with small core or good tion for Thrombectomy as Primary Endovascular Treatment collaterals. (SWIFT PRIME) trial. Subgroup analysis is to look for patterns We therefore agree with the authors that future clinical trials that might help physicians make more considered assessments on and analysis of larger pooled datasets will be helpful in building prognosis and effect modification. These analyses are therefore more evidence for refining selection of patients who may benefit not level 1 evidence but suggest the need for confirmatory studies from intra-arterial therapy. Our study is one small step in that within those subgroups. Some of these studies may be possible direction. while others may never happen. Physicians then draw reasonable conclusions based on the data presented, their own heuristics, and any other current evidence to inform their practice. They REFERENCES can decide to wait for further confirmatory studies. This is what 1. Saver JL, Goyal M, Bonafe A, et al; SWIFT PRIME Investigators. Stent- we suggested. retriever thrombectomy after intravenous t-PA vs. t-PA alone in We agree that the absence of statistically significant effect stroke. N Engl J Med 2015;372:2285–95 CrossRef Medline modification by a variable on the relationship between the treat- 2. Goyal M, Menon BK, van Zwam WH, et al; HERMES collaborators. ment and the outcome is not evidence for lack of effect modifica- Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. tion. Small sample size is a problem with tests of effect modifica- Lancet 2016;387:1723–31 CrossRef Medline tion in any clinical trial because the trial is invariably not powered X A.P. Jadhav to test for the presence or absence of such effect modification. We Department of Neurology and Neurological Surgery also agree that multiple testing within multiple subgroups in- University of Pittsburgh Medical Center Pittsburgh, Pennsylvania creases the likelihood of type I error (stating that there is signal X B.K. Menon when there is none). Given the small sample size in our study, we X M. Goyal therefore deliberately avoided looking for statistical interaction Department of Clinical Neurosciences and Radiology University of Calgary http://dx.doi.org/10.3174/ajnr.A5617 Calgary, Alberta, Canada E58 Letters May 2018 www.ajnr.org http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Neuroradiology American Journal of Neuroradiology

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Publisher
American Journal of Neuroradiology
ISSN
0195-6108
eISSN
1936-959X
DOI
10.3174/ajnr.A5617
Publisher site
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Abstract

REPLY: (effect modification) to avoid both problems described above. Observations of our results graphically (see Figs 1 and 4 in our e thank Johansson and Salzer for their response to our ar- article) suggest that there is evidence of benefit from intra-arterial Wticle. We agree that several considerations of our study are therapy versus controls in patients with a small baseline infarct limited by the small sample size. However, the main objection of core and good collateral circulation; however, we wanted to cau- the authors is with the statement in the conclusion of our article, tion our readers that they should not assume from our data that a “Overall, this report supports the selection of patients for intra- similar effect exists in patients with a large baseline core or poor arterial therapy on the basis of favorable patient characteristics collaterals. This is so because biologically, it is plausible that these (small core, good collateral circulation) and low likelihood of re- patients with large baseline infarcts or very poor collaterals may canalization with intravenous thrombolysis (large and proximal have poorer outcomes on average even with good treatment. clot burden).” They fail to mention the sentence that follows, Therefore, we suggested a cautionary last sentence, “Additional “Additional studies will be needed to further understand the con- studies will be needed to further understand the continued benefit tinued benefit of intra-arterial treatment for patients with larger of intra-arterial treatment for patients with larger infarct burden infarct burden or distal occlusions.” or distal occlusions,” instead of giving the readers a spurious mes- Any clinical trial is powered primarily to understand main sage that patients with low ASPECTS or poor collaterals are likely effects. This was the case even with the Solitaire With the Inten- to benefit to the same extent as patients with small core or good tion for Thrombectomy as Primary Endovascular Treatment collaterals. (SWIFT PRIME) trial. Subgroup analysis is to look for patterns We therefore agree with the authors that future clinical trials that might help physicians make more considered assessments on and analysis of larger pooled datasets will be helpful in building prognosis and effect modification. These analyses are therefore more evidence for refining selection of patients who may benefit not level 1 evidence but suggest the need for confirmatory studies from intra-arterial therapy. Our study is one small step in that within those subgroups. Some of these studies may be possible direction. while others may never happen. Physicians then draw reasonable conclusions based on the data presented, their own heuristics, and any other current evidence to inform their practice. They REFERENCES can decide to wait for further confirmatory studies. This is what 1. Saver JL, Goyal M, Bonafe A, et al; SWIFT PRIME Investigators. Stent- we suggested. retriever thrombectomy after intravenous t-PA vs. t-PA alone in We agree that the absence of statistically significant effect stroke. N Engl J Med 2015;372:2285–95 CrossRef Medline modification by a variable on the relationship between the treat- 2. Goyal M, Menon BK, van Zwam WH, et al; HERMES collaborators. ment and the outcome is not evidence for lack of effect modifica- Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. tion. Small sample size is a problem with tests of effect modifica- Lancet 2016;387:1723–31 CrossRef Medline tion in any clinical trial because the trial is invariably not powered X A.P. Jadhav to test for the presence or absence of such effect modification. We Department of Neurology and Neurological Surgery also agree that multiple testing within multiple subgroups in- University of Pittsburgh Medical Center Pittsburgh, Pennsylvania creases the likelihood of type I error (stating that there is signal X B.K. Menon when there is none). Given the small sample size in our study, we X M. Goyal therefore deliberately avoided looking for statistical interaction Department of Clinical Neurosciences and Radiology University of Calgary http://dx.doi.org/10.3174/ajnr.A5617 Calgary, Alberta, Canada E58 Letters May 2018 www.ajnr.org

Journal

American Journal of NeuroradiologyAmerican Journal of Neuroradiology

Published: May 1, 2018

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