Effect of informed consent on patient characteristics in a stroke thrombolysis trial
Identifieur interne : 002798 ( Pmc/Corpus ); précédent : 002797; suivant : 002799Effect of informed consent on patient characteristics in a stroke thrombolysis trial
Auteurs : Götz Thomalla ; Florent Boutitie ; Jochen B. Fiebach ; Claus Z. Simonsen ; Norbert Nighoghossian ; Salvador Pedraza ; Robin Lemmens ; Pascal Roy ; Keith W. Muir ; Christoph Heesen ; Martin Ebinger ; Ian Ford ; Bastian Cheng ; Tae-Hee Cho ; Josep Puig ; Vincent Thijs ; Matthias Endres ; Jens Fiehler ; Christian GerloffSource :
- Neurology [ 0028-3878 ] ; 2017.
Abstract
To determine whether the manner of consent, i.e., informed consent by patients themselves or informed consent by proxy, affects clinical characteristics of samples of acute stroke patients enrolled in clinical trials.
We analyzed the manner of obtaining informed consent in the first 1,005 patients from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset running in 6 European countries. Patients providing informed consent by themselves were compared with patients enrolled by proxy consent. Baseline clinical measures were compared between groups.
In 359 (35.7%) patients, informed consent was by proxy. Patients with proxy consent were older (median 71 vs 66 years,
Patients recruited by proxy consent were older, had more severe strokes, and had higher prevalence of aphasia than those with capacity to give personal consent. Variations in the manner of consent across countries may influence trial results.
NCT01525290 (
Url:
DOI: 10.1212/WNL.0000000000004414
PubMed: 28842449
PubMed Central: 5649757
Links to Exploration step
PMC:5649757Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effect of informed consent on patient characteristics in a stroke thrombolysis trial</title><author><name sortKey="Thomalla, Gotz" sort="Thomalla, Gotz" uniqKey="Thomalla G" first="Götz" last="Thomalla">Götz Thomalla</name></author><author><name sortKey="Boutitie, Florent" sort="Boutitie, Florent" uniqKey="Boutitie F" first="Florent" last="Boutitie">Florent Boutitie</name></author><author><name sortKey="Fiebach, Jochen B" sort="Fiebach, Jochen B" uniqKey="Fiebach J" first="Jochen B." last="Fiebach">Jochen B. Fiebach</name></author><author><name sortKey="Simonsen, Claus Z" sort="Simonsen, Claus Z" uniqKey="Simonsen C" first="Claus Z." last="Simonsen">Claus Z. Simonsen</name></author><author><name sortKey="Nighoghossian, Norbert" sort="Nighoghossian, Norbert" uniqKey="Nighoghossian N" first="Norbert" last="Nighoghossian">Norbert Nighoghossian</name></author><author><name sortKey="Pedraza, Salvador" sort="Pedraza, Salvador" uniqKey="Pedraza S" first="Salvador" last="Pedraza">Salvador Pedraza</name></author><author><name sortKey="Lemmens, Robin" sort="Lemmens, Robin" uniqKey="Lemmens R" first="Robin" last="Lemmens">Robin Lemmens</name></author><author><name sortKey="Roy, Pascal" sort="Roy, Pascal" uniqKey="Roy P" first="Pascal" last="Roy">Pascal Roy</name></author><author><name sortKey="Muir, Keith W" sort="Muir, Keith W" uniqKey="Muir K" first="Keith W." last="Muir">Keith W. Muir</name></author><author><name sortKey="Heesen, Christoph" sort="Heesen, Christoph" uniqKey="Heesen C" first="Christoph" last="Heesen">Christoph Heesen</name></author><author><name sortKey="Ebinger, Martin" sort="Ebinger, Martin" uniqKey="Ebinger M" first="Martin" last="Ebinger">Martin Ebinger</name></author><author><name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name></author><author><name sortKey="Cheng, Bastian" sort="Cheng, Bastian" uniqKey="Cheng B" first="Bastian" last="Cheng">Bastian Cheng</name></author><author><name sortKey="Cho, Tae Hee" sort="Cho, Tae Hee" uniqKey="Cho T" first="Tae-Hee" last="Cho">Tae-Hee Cho</name></author><author><name sortKey="Puig, Josep" sort="Puig, Josep" uniqKey="Puig J" first="Josep" last="Puig">Josep Puig</name></author><author><name sortKey="Thijs, Vincent" sort="Thijs, Vincent" uniqKey="Thijs V" first="Vincent" last="Thijs">Vincent Thijs</name></author><author><name sortKey="Endres, Matthias" sort="Endres, Matthias" uniqKey="Endres M" first="Matthias" last="Endres">Matthias Endres</name></author><author><name sortKey="Fiehler, Jens" sort="Fiehler, Jens" uniqKey="Fiehler J" first="Jens" last="Fiehler">Jens Fiehler</name></author><author><name sortKey="Gerloff, Christian" sort="Gerloff, Christian" uniqKey="Gerloff C" first="Christian" last="Gerloff">Christian Gerloff</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28842449</idno><idno type="pmc">5649757</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5649757</idno><idno type="RBID">PMC:5649757</idno><idno type="doi">10.1212/WNL.0000000000004414</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">002798</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002798</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effect of informed consent on patient characteristics in a stroke thrombolysis trial</title><author><name sortKey="Thomalla, Gotz" sort="Thomalla, Gotz" uniqKey="Thomalla G" first="Götz" last="Thomalla">Götz Thomalla</name></author><author><name sortKey="Boutitie, Florent" sort="Boutitie, Florent" uniqKey="Boutitie F" first="Florent" last="Boutitie">Florent Boutitie</name></author><author><name sortKey="Fiebach, Jochen B" sort="Fiebach, Jochen B" uniqKey="Fiebach J" first="Jochen B." last="Fiebach">Jochen B. Fiebach</name></author><author><name sortKey="Simonsen, Claus Z" sort="Simonsen, Claus Z" uniqKey="Simonsen C" first="Claus Z." last="Simonsen">Claus Z. Simonsen</name></author><author><name sortKey="Nighoghossian, Norbert" sort="Nighoghossian, Norbert" uniqKey="Nighoghossian N" first="Norbert" last="Nighoghossian">Norbert Nighoghossian</name></author><author><name sortKey="Pedraza, Salvador" sort="Pedraza, Salvador" uniqKey="Pedraza S" first="Salvador" last="Pedraza">Salvador Pedraza</name></author><author><name sortKey="Lemmens, Robin" sort="Lemmens, Robin" uniqKey="Lemmens R" first="Robin" last="Lemmens">Robin Lemmens</name></author><author><name sortKey="Roy, Pascal" sort="Roy, Pascal" uniqKey="Roy P" first="Pascal" last="Roy">Pascal Roy</name></author><author><name sortKey="Muir, Keith W" sort="Muir, Keith W" uniqKey="Muir K" first="Keith W." last="Muir">Keith W. Muir</name></author><author><name sortKey="Heesen, Christoph" sort="Heesen, Christoph" uniqKey="Heesen C" first="Christoph" last="Heesen">Christoph Heesen</name></author><author><name sortKey="Ebinger, Martin" sort="Ebinger, Martin" uniqKey="Ebinger M" first="Martin" last="Ebinger">Martin Ebinger</name></author><author><name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name></author><author><name sortKey="Cheng, Bastian" sort="Cheng, Bastian" uniqKey="Cheng B" first="Bastian" last="Cheng">Bastian Cheng</name></author><author><name sortKey="Cho, Tae Hee" sort="Cho, Tae Hee" uniqKey="Cho T" first="Tae-Hee" last="Cho">Tae-Hee Cho</name></author><author><name sortKey="Puig, Josep" sort="Puig, Josep" uniqKey="Puig J" first="Josep" last="Puig">Josep Puig</name></author><author><name sortKey="Thijs, Vincent" sort="Thijs, Vincent" uniqKey="Thijs V" first="Vincent" last="Thijs">Vincent Thijs</name></author><author><name sortKey="Endres, Matthias" sort="Endres, Matthias" uniqKey="Endres M" first="Matthias" last="Endres">Matthias Endres</name></author><author><name sortKey="Fiehler, Jens" sort="Fiehler, Jens" uniqKey="Fiehler J" first="Jens" last="Fiehler">Jens Fiehler</name></author><author><name sortKey="Gerloff, Christian" sort="Gerloff, Christian" uniqKey="Gerloff C" first="Christian" last="Gerloff">Christian Gerloff</name></author></analytic><series><title level="j">Neurology</title><idno type="ISSN">0028-3878</idno><idno type="eISSN">1526-632X</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objective:</title><p>To determine whether the manner of consent, i.e., informed consent by patients themselves or informed consent by proxy, affects clinical characteristics of samples of acute stroke patients enrolled in clinical trials.</p></sec><sec><title>Methods:</title><p>We analyzed the manner of obtaining informed consent in the first 1,005 patients from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset running in 6 European countries. Patients providing informed consent by themselves were compared with patients enrolled by proxy consent. Baseline clinical measures were compared between groups.</p></sec><sec><title>Results:</title><p>In 359 (35.7%) patients, informed consent was by proxy. Patients with proxy consent were older (median 71 vs 66 years, <italic>p</italic> < 0.0001) and had a higher frequency of arterial hypertension (58.2% vs 43.4%, <italic>p</italic> < 0.0001). They showed higher scores on the NIH Stroke Scale (median 11 vs 5, <italic>p</italic> < 0.0001) and more frequently aphasia (73.7% vs 20.0%, <italic>p</italic> < 0.0001). The rate of proxy consent varied among countries (<italic>p</italic> < 0.0001), ranging from 77.1% in Spain to 1.2% in Denmark.</p></sec><sec><title>Conclusions:</title><p>Patients recruited by proxy consent were older, had more severe strokes, and had higher prevalence of aphasia than those with capacity to give personal consent. Variations in the manner of consent across countries may influence trial results.</p></sec><sec><title>Clinicaltrials.gov and Clinicaltrialsregister.eu identifiers:</title><p>NCT01525290 (<ext-link ext-link-type="uri" xlink:href="http://clinicaltrials.gov">clinicaltrials.gov</ext-link>); 2011-005906-32 (<ext-link ext-link-type="uri" xlink:href="http://clinicaltrialsregister.eu">clinicaltrialsregister.eu</ext-link>).</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Lees, Kr" uniqKey="Lees K">KR Lees</name></author><author><name sortKey="Emberson, J" uniqKey="Emberson J">J Emberson</name></author><author><name sortKey="Blackwell, L" uniqKey="Blackwell L">L Blackwell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ribo, M" uniqKey="Ribo M">M Ribo</name></author><author><name sortKey="Molina, Ca" uniqKey="Molina C">CA Molina</name></author><author><name sortKey="Cobo, E" uniqKey="Cobo E">E Cobo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Demarquay, G" uniqKey="Demarquay G">G Demarquay</name></author><author><name sortKey="Derex, L" uniqKey="Derex L">L Derex</name></author><author><name sortKey="Nighoghossian, N" uniqKey="Nighoghossian N">N Nighoghossian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mangset, M" uniqKey="Mangset M">M Mangset</name></author><author><name sortKey="Forde, R" uniqKey="Forde R">R Forde</name></author><author><name sortKey="Nessa, J" uniqKey="Nessa J">J Nessa</name></author><author><name sortKey="Berge, E" uniqKey="Berge E">E Berge</name></author><author><name sortKey="Wyller, Tb" uniqKey="Wyller T">TB Wyller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bateman, Bt" uniqKey="Bateman B">BT Bateman</name></author><author><name sortKey="Meyers, Pm" uniqKey="Meyers P">PM Meyers</name></author><author><name sortKey="Schumacher, Hc" uniqKey="Schumacher H">HC Schumacher</name></author><author><name sortKey="Mangla, S" uniqKey="Mangla S">S Mangla</name></author><author><name sortKey="Pile Spellman, J" uniqKey="Pile Spellman J">J Pile-Spellman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Slyter, H" uniqKey="Slyter H">H Slyter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brady, Mc" uniqKey="Brady M">MC Brady</name></author><author><name sortKey="Fredrick, A" uniqKey="Fredrick A">A Fredrick</name></author><author><name sortKey="Williams, B" uniqKey="Williams B">B Williams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flaherty, Ml" uniqKey="Flaherty M">ML Flaherty</name></author><author><name sortKey="Karlawish, J" uniqKey="Karlawish J">J Karlawish</name></author><author><name sortKey="Khoury, Jc" uniqKey="Khoury J">JC Khoury</name></author><author><name sortKey="Kleindorfer, D" uniqKey="Kleindorfer D">D Kleindorfer</name></author><author><name sortKey="Woo, D" uniqKey="Woo D">D Woo</name></author><author><name sortKey="Broderick, Jp" uniqKey="Broderick J">JP Broderick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kane, I" uniqKey="Kane I">I Kane</name></author><author><name sortKey="Lindley, R" uniqKey="Lindley R">R Lindley</name></author><author><name sortKey="Lewis, S" uniqKey="Lewis S">S Lewis</name></author><author><name sortKey="Sandercock, P" uniqKey="Sandercock P">P Sandercock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thomalla, G" uniqKey="Thomalla G">G Thomalla</name></author><author><name sortKey="Fiebach, Jb" uniqKey="Fiebach J">JB Fiebach</name></author><author><name sortKey="Ostergaard, L" uniqKey="Ostergaard L">L Ostergaard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thomalla, G" uniqKey="Thomalla G">G Thomalla</name></author><author><name sortKey="Cheng, B" uniqKey="Cheng B">B Cheng</name></author><author><name sortKey="Ebinger, M" uniqKey="Ebinger M">M Ebinger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brott, T" uniqKey="Brott T">T Brott</name></author><author><name sortKey="Adams, Hp" uniqKey="Adams H">HP Adams</name></author><author><name sortKey="Olinger, Cp" uniqKey="Olinger C">CP Olinger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dani, Ka" uniqKey="Dani K">KA Dani</name></author><author><name sortKey="Mccormick, Mt" uniqKey="Mccormick M">MT McCormick</name></author><author><name sortKey="Muir, Kw" uniqKey="Muir K">KW Muir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mendyk, Am" uniqKey="Mendyk A">AM Mendyk</name></author><author><name sortKey="Labreuche, J" uniqKey="Labreuche J">J Labreuche</name></author><author><name sortKey="Henon, H" uniqKey="Henon H">H Henon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, J" uniqKey="Smith J">J Smith</name></author><author><name sortKey="Forster, A" uniqKey="Forster A">A Forster</name></author><author><name sortKey="Young, J" uniqKey="Young J">J Young</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hotter, B" uniqKey="Hotter B">B Hotter</name></author><author><name sortKey="Jegzentis, K" uniqKey="Jegzentis K">K Jegzentis</name></author><author><name sortKey="Steinbrink, J" uniqKey="Steinbrink J">J Steinbrink</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leira, Ec" uniqKey="Leira E">EC Leira</name></author><author><name sortKey="Kaldjian, Lc" uniqKey="Kaldjian L">LC Kaldjian</name></author><author><name sortKey="Ludwig, Br" uniqKey="Ludwig B">BR Ludwig</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Lemaire, F" uniqKey="Lemaire F">F Lemaire</name></author><author><name sortKey="Bion, J" uniqKey="Bion J">J Bion</name></author><author><name sortKey="Blanco, J" uniqKey="Blanco J">J Blanco</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yusuf, S" uniqKey="Yusuf S">S Yusuf</name></author><author><name sortKey="Wittes, J" uniqKey="Wittes J">J Wittes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feaster, Dj" uniqKey="Feaster D">DJ Feaster</name></author><author><name sortKey="Mikulich Gilbertson, S" uniqKey="Mikulich Gilbertson S">S Mikulich-Gilbertson</name></author><author><name sortKey="Brincks, Am" uniqKey="Brincks A">AM Brincks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iwanowski, P" uniqKey="Iwanowski P">P Iwanowski</name></author><author><name sortKey="Budaj, A" uniqKey="Budaj A">A Budaj</name></author><author><name sortKey="Czlonkowska, A" uniqKey="Czlonkowska A">A Czlonkowska</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qureshi, Ai" uniqKey="Qureshi A">AI Qureshi</name></author><author><name sortKey="Gilani, S" uniqKey="Gilani S">S Gilani</name></author><author><name sortKey="Adil, Mm" uniqKey="Adil M">MM Adil</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kleindorfer, D" uniqKey="Kleindorfer D">D Kleindorfer</name></author><author><name sortKey="Lindsell, Cj" uniqKey="Lindsell C">CJ Lindsell</name></author><author><name sortKey="Alwell, K" uniqKey="Alwell K">K Alwell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goldstein, Jn" uniqKey="Goldstein J">JN Goldstein</name></author><author><name sortKey="Espinola, Ja" uniqKey="Espinola J">JA Espinola</name></author><author><name sortKey="Fisher, J" uniqKey="Fisher J">J Fisher</name></author><author><name sortKey="Pallin, Dj" uniqKey="Pallin D">DJ Pallin</name></author><author><name sortKey="Camargo, Ca" uniqKey="Camargo C">CA Camargo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kasner, Se" uniqKey="Kasner S">SE Kasner</name></author><author><name sortKey="Baren, Jm" uniqKey="Baren J">JM Baren</name></author><author><name sortKey="Le Roux, Pd" uniqKey="Le Roux P">PD Le Roux</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Neurology</journal-id><journal-id journal-id-type="iso-abbrev">Neurology</journal-id><journal-id journal-id-type="hwp">neurology</journal-id><journal-id journal-id-type="publisher-id">neur</journal-id><journal-id journal-id-type="pmc">neurology</journal-id><journal-id journal-id-type="publisher-id">NEUROLOGY</journal-id><journal-title-group><journal-title>Neurology</journal-title></journal-title-group><issn pub-type="ppub">0028-3878</issn><issn pub-type="epub">1526-632X</issn><publisher><publisher-name>Lippincott Williams & Wilkins</publisher-name><publisher-loc>Hagerstown, MD</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28842449</article-id><article-id pub-id-type="pmc">5649757</article-id><article-id pub-id-type="publisher-id">NEUROLOGY2016791053</article-id><article-id pub-id-type="doi">10.1212/WNL.0000000000004414</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>2</subject><subject>19</subject><subject>21</subject><subject>84</subject><subject>120</subject></subj-group><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Effect of informed consent on patient characteristics in a stroke thrombolysis trial</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Thomalla</surname><given-names>Götz</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>(1) DSMB for the TEA Stroke Trial</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>(1) Bayer, speaker honoraria (2) Boheringer Ingelheim, speaker honoraria, travel (3) Daichii Sankyo, speaker honoraria (4) Bristol Myer Squibb/Pfizer, speaker honoraria, travel</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>(1) Acandis, consultant (2) GlaxoSmithKline, consultant</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>(1) Bayer</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>(1) European Union, Grant No. 278276 (WAKE-UP)</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>(1) Deutsche Forschungsgesellschaft, Grant SFB936, Project C2 (2) Corona Foundation, CONTEST study</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Boutitie</surname><given-names>Florent</given-names></name><degrees>PhD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Fiebach</surname><given-names>Jochen B.</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>Steering committee WAKE-UP trial (non-pofit entity), imaging committee DIAS trials (commercial)</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>Neuroradiologist cultant to Perceptive (commercial), BioClinica (commercial),</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>Boehringer Ingelheim(commercial)</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Simonsen</surname><given-names>Claus Z.</given-names></name><degrees>MD, PhD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for travel or speaker honoraria:</title><list-item><p>Compensated for a talk, Boehringer-Ingelheim. Compensated for a talk, Bayer.</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Nighoghossian</surname><given-names>Norbert</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Pedraza</surname><given-names>Salvador</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>Stroke Journal</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Lemmens</surname><given-names>Robin</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>FWO Flanders: Senior Clinical Investigator, 2012-2017, 1841913N FWO Flanders: Research Grant 2015-2019: basic science grant G070015N HORIZON 2020: PROOF 2017-2019 no role in this study</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Roy</surname><given-names>Pascal</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Muir</surname><given-names>Keith W.</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>ReNeuron Ltd.</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for travel or speaker honoraria:</title><list-item><p>Honorarium for speaking at meeting sponsored by Boehringer-Ingelheim 2015. Honorarium for chairing a sponsored symposium by Bayer at the European Stroke Organisation Conference 2015.</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>Editorial boards of Stroke and International Journal of Stroke.</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>Institutional support for the Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial from 1) Covidien (Medtronic) and 2) Codman Institutional support for the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST-2) study from Boehringer-Ingelheim</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>I am Chief Investigator for the PISTE trial. This was funded by research grants to my institution from the Stroke Association (TSA 2011-06) and the National Institute for Health Research Health Technology Assessment board (HTA 14/08/47). Chief Investigator for ATTEST-2, 2015-20, funded by the Stroke Association and British Heart Foundation (TSA-BHF 2015-01).</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Heesen</surname><given-names>Christoph</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for travel or speaker honoraria:</title><list-item><p>Received speaker honoraries from Biogen, Merck, Genyzme, Novartis</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>International Journal of MS Care, 2014 until now</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other activities:</title><list-item><p>Received Research grants from Genzyme, Biogen, Roche, Novartis, Merck, Roche.</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>Genzyme Sanofi Aventis Biogen Novartis Roche</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>German Minstery of Research, PI 2012-2016 Hertie Foundation, PI 2014-2016</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NMSS</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Ebinger</surname><given-names>Martin</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Ford</surname><given-names>Ian</given-names></name><degrees>PhD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>Member of study Executive Committees for Servier. Member of DSMBs for GSK, RESMED, Medtronic, Quintiles, Astra Zeneca, Shire, Boston Scientific, Medimmune, Novartis</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for travel or speaker honoraria:</title><list-item><p>Funding for travel to conference and study meetings from Servier.</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>Deputy Editor of Clinical Trials</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>Research grants from Servier, GSK, Actamax, Biotronik, Stealth.</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>Various grants from Chief Scientist Office Scotland and Medical Research Council EME NIHR HTA EU FP7 EU IMI</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>Wellcome Trust Arthritis Research UK British Heart Foundation Diabetes UK Juvenile Diabetes Research Foundation Stroke Association Kidney Research UK</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Bastian</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Cho</surname><given-names>Tae-Hee</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Puig</surname><given-names>Josep</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for Travel or Speaker Honoraria:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Thijs</surname><given-names>Vincent</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>(1) Boehringer Ingelheim Belgium advisory board (2) Boehringer Ingelheim international advisory board (3) Medtronic steering committee of the REACT-AF and DIAGNOSE AF trial</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for travel or speaker honoraria:</title><list-item><p>(1) Medtronic (2) Boehringer Ingelheim (3) Pfizer (4) Bayer (5) Astra Zeneca</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>Acta Neurologica Belgica, Associate Editor, ongoing Stroke Editorial board member, ongoing European Journal of Emergency Medicine, Editorial Board member, ongoing European Stroke Journal, Editorial Board member, ongoing International Journal of Stroke, Editorial board member, ongoing</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>(1) Boehringer Ingelheim (2) Pfizer (3) Bayer (4) Astra Zeneca (5) Medtronic</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>Pfizer Inc Boehringer Ingelheim Medtronic</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>SYGNIS AG, Medtronic, Inc., Pfizer Inc., AstraZeneca, Boehringer Ingelheim, Astra Zeneca</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>VIB Flanders Research Fund (FWO) NHMRC</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>Flanders Research Fund (FWO)</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Endres</surname><given-names>Matthias</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>(1) non profit entity: safety monitoring board of STEMO study at the Center of Stroke research Berlin, no compensation (2) commercial entity: scientific advisory board Boehringer Ingelheim, honoraria paid to institution (3) commercial entity: scientific advisory board Bayer, honoraria paid to institution; (4) commercial entity: scientific advisory board Amgen, honoraria paid to institution; (5) commercial entity: scientific advisory board Covidien; honoraria paid to institution</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for travel or speaker honoraria:</title><list-item><p>(1) Boehringer Ingelheim, speaker honoraria paid to institution (2) Pfizer, speaker honoraria paid to institution(3) Sanofi, speaker honoraria paid to institution (4) Bayer, speaker honoraria paid to institution,(5) BMS, speaker honoraria paid to institution (6) Ever, speaker honoraria paid to institution (7) GSK, speaker honoraria paid to institution (8) Amgen, speaker honoraria paid to institution</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>(1) Stroke, Editorial Board , no compensation, (2) Journal of Molecular Medicine, Editorial Board, no compensation (3) Neuropsychopharmacology, Editorial Board, compensation; (4) Aktuelle Neurologie, Editorial Board, compensation (modest); (5) Journal of the European Stroke Organization, Editorial board, no compenstaion</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>non profit entity: German Center for Neurodegenerative Diseases (DZNE), employment, compensation (modest)</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>(1) Commercial entity Roche, unrestricted grant support to Dept Neurolgy Charite (2) Commercial entity Bayer, unrestricted grant support to the Dept Neurology and Center for Stroke Research Charite for Mondafis Trial (investigator initiated trial) and Berlin AF Registry (investigator initiated trial)</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>(1) German Ministry of Education and Science (BMBF) grant support (Center for Stroke Research Berlin, (2) Deutsche Forschungsgemeinschaft, grant support (ExcellenceCluster NeuroCure. SFB TR-43; KFO 247,KFO 213) (3) European Union (EUstroke, ARISE, Wake-Up) (4) German Center for Cardiovascular Research (DZHK) (5) Berlin site, German Center for Neurodegenerative Diseases (DZNE), Berlin site (6) Berlin Institute of Health (BiH)</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>German Center for Cardiovascular Research (DZHK), Berlin site, German Center for Neurodegenerative Diseases (DZNE), Berlin site,(6) Berlin Institute of Health (BiH)</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>(1) VolkswagenFoundation (Lichtenberg Professorship), (2) CoronaFoundation, (3) Fondation Leducq Transatlantic Network</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Fiehler</surname><given-names>Jens</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>Acandis, Penumbra, Microvention, Stryker, Codman, Medtronic, Sequent</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for travel or speaker honoraria:</title><list-item><p>Honoraria and funding for travel from commercial companies Acandis, Penumbra, Microvention, Stryker, Codman, Medtronic, Sequent</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>Neuroradioloy, Section editor Interventional Neuroradiology 2008-2015, Clinical Neuroradiology 2015-today</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>BMBF, BMWi</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><contrib contrib-type="author"><name><surname>Gerloff</surname><given-names>Christian</given-names></name><degrees>MD</degrees><author-comment content-type="disclosure"><p><list list-type="order"><title>Scientific Advisory Boards:</title><list-item><p>(1) Bayer Vital (2) Boehringer Ingelheim (3) Acticor Biotech, (4) Amgene, (5) Prediction Bioscience</p></list-item></list></p><p><list list-type="order"><title>Gifts:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Funding for travel or speaker honoraria:</title><list-item><p>(1) Bayer Vital, travel and speaker honoraria, (2) Boehringer Ingelheim, travel and speaker honoraria, (3) Sanofi Aventis, speaker honoraria</p></list-item></list></p><p><list list-type="order"><title>Editorial Boards:</title><list-item><p>(1) INFO Neurology Psychatrie (2) Aktuelle Neurologie (3) Editor of Textbook</p></list-item></list></p><p><list list-type="order"><title>Patents:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Publishing Royalties:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Employment, Commercial Entity:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Consultancies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Speakers' Bureaus:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Other Activities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Clinical Procedures or Imaging Studies:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Commercial Entities:</title><list-item><p>(1) Merz Pharmaceuticals*, (2) Allergan*, (3) Novartis*, (4) NeuroConn* *all grants were supporting employees/scientists of my clinic (no direct support of myself)</p></list-item></list></p><p><list list-type="order"><title>Research Support, Government Entities:</title><list-item><p>(1) DFG: SFB 936, since 2011, ongoing, (2) BMBF/DFG NETS Trial, ongoing, (3) EU FP7: project grant WAKE-UP stroke trial, since 2011, ongoing, (4) DFG: TRR 169, since 2016, ongoing</p></list-item></list></p><p><list list-type="order"><title>Research Support, Academic Entities:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Research Support, Foundations and Societies:</title><list-item><p>(1) Wegener Foundation / Movement Disorders Science, (2) Schilling Foundation, translational stroke research, since 2016, ongoing Program for two of my employees, (3) Werner-Otto-Foundation, (4) Wegener- Foundation</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options/Board of Directors Compensation:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>License Fee Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Royalty Payments, Technology or Inventions:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Research Sponsor:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Stock/Stock Options, Medical Equipment & Materials:</title><list-item><p>NONE</p></list-item></list></p><p><list list-type="order"><title>Legal Proceedings:</title><list-item><p>NONE</p></list-item></list></p></author-comment></contrib><aff>From Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum (G.T., C.H., B.C., C.G.), and Klinik und Poliklinik für Neuroradiologische Diagnostik und Intervention, Diagnostikzentrum (J.F.), Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; Service de Biostatistique (F.B., P.R.) and Department of Neurology (N.N., T.-H.C.), Hospices Civils de Lyon; Université Lyon 1 (F.B., P.R.), Villeurbanne; CNRS, UMR 5558 (F.B., P.R.), Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France; Centrum für Schlaganfallforschung Berlin (CSB) (J.B.F., M. Ebinger, M. Endres) and Klinik und Hochschulambulanz für Neurologie (M. Ebinger, M. Endres), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (C.Z.S.), Aarhus University Hospital, Denmark; Department of Radiology (S.P., J.P.), Institut de Diagnostic per la Image (IDI), Hospital Dr Josep Trueta, Institut d’Investgació Biomèdica de Girona (IDIBGI), Girona, Spain; Department of Neurosciences, Experimental Neurology, and Leuven Research Institute for Neuroscience and Disease (LIND) (R.L.), KU Leuven-University of Leuven; VIB, Laboratory of Neurobiology (R.L.), Center for Brain & Disease Research, Leuven; Department of Neurology (R.L.), University Hospitals Leuven, Belgium; Institute of Neuroscience & Psychology (K.W.M.) and Robertson Centre for Biostatistics (I.F.), University of Glasgow, UK; Stroke Division (V.T.), Florey Institute of Neuroscience and Mental Health; and Department of Neurology (V.T.), Austin Health, Heidelberg, Australia.</aff></contrib-group><author-notes><corresp>Correspondence to Dr. Thomalla: <email>thomalla@uke.de</email></corresp><fn fn-type="financial-disclosure"><p>Go to <ext-link ext-link-type="uri" xlink:href="http://neurology.org/lookup/doi/10.1212/WNL.0000000000004414">Neurology.org</ext-link> for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was funded by the European Commission.</p></fn></author-notes><pub-date pub-type="ppub"><day>26</day><month>9</month><year>2017</year></pub-date><pub-date pub-type="pmc-release"><day>26</day><month>9</month><year>2017</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>89</volume><issue>13</issue><fpage>1400</fpage><lpage>1407</lpage><history><date date-type="received"><day>21</day><month>12</month><year>2016</year></date><date date-type="accepted"><day>19</day><month>6</month><year>2017</year></date></history><permissions><copyright-statement>Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>American Academy of Neurology</copyright-holder><license license-type="open-access"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/">Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND)</ext-link>, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:href="NEUROLOGY2016791053.pdf"></self-uri><abstract><sec><title>Objective:</title><p>To determine whether the manner of consent, i.e., informed consent by patients themselves or informed consent by proxy, affects clinical characteristics of samples of acute stroke patients enrolled in clinical trials.</p></sec><sec><title>Methods:</title><p>We analyzed the manner of obtaining informed consent in the first 1,005 patients from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset running in 6 European countries. Patients providing informed consent by themselves were compared with patients enrolled by proxy consent. Baseline clinical measures were compared between groups.</p></sec><sec><title>Results:</title><p>In 359 (35.7%) patients, informed consent was by proxy. Patients with proxy consent were older (median 71 vs 66 years, <italic>p</italic> < 0.0001) and had a higher frequency of arterial hypertension (58.2% vs 43.4%, <italic>p</italic> < 0.0001). They showed higher scores on the NIH Stroke Scale (median 11 vs 5, <italic>p</italic> < 0.0001) and more frequently aphasia (73.7% vs 20.0%, <italic>p</italic> < 0.0001). The rate of proxy consent varied among countries (<italic>p</italic> < 0.0001), ranging from 77.1% in Spain to 1.2% in Denmark.</p></sec><sec><title>Conclusions:</title><p>Patients recruited by proxy consent were older, had more severe strokes, and had higher prevalence of aphasia than those with capacity to give personal consent. Variations in the manner of consent across countries may influence trial results.</p></sec><sec><title>Clinicaltrials.gov and Clinicaltrialsregister.eu identifiers:</title><p>NCT01525290 (<ext-link ext-link-type="uri" xlink:href="http://clinicaltrials.gov">clinicaltrials.gov</ext-link>); 2011-005906-32 (<ext-link ext-link-type="uri" xlink:href="http://clinicaltrialsregister.eu">clinicaltrialsregister.eu</ext-link>).</p></sec></abstract><custom-meta-group><custom-meta><meta-name>OPEN-ACCESS</meta-name><meta-value>TRUE</meta-value></custom-meta></custom-meta-group></article-meta></front><body><p>As a general principle, any research involving humans requires voluntary participation based on informed consent.<sup><xref rid="R1" ref-type="bibr">1</xref></sup> This also applies to enrollment in clinical trials und usually requires participants to give written informed consent after having received detailed information about potential benefits and risks as well as alternative treatment options, and after having had adequate time for consideration. Trials in acute stroke, however, present several challenges to this approach. Reperfusion therapies in acute stroke show a clear time-dependent effect, being more effective the earlier treatment is started, or reperfusion achieved.<sup><xref rid="R2" ref-type="bibr">2</xref>,<xref rid="R3" ref-type="bibr">3</xref></sup> Both routine care and clinical trials in acute stroke are carried out under pressure of time. Thus, time available for consideration is very short. In addition, the brain injury commonly compromises language function, awareness of neurologic deficits, conscious level, and physical abilities, including vision and writing, relevant to the usual consent process. Since most stroke patients lack capacity to provide consent,<sup><xref rid="R4" ref-type="bibr">4</xref>,<xref rid="R5" ref-type="bibr">5</xref></sup> alternative approaches are needed,<sup><xref rid="R6" ref-type="bibr">6</xref>,<xref rid="R7" ref-type="bibr">7</xref></sup> and the bias introduced by systematic exclusion of certain subgroups of stroke patients, e.g., those with aphasia, has been reviewed critically.<sup><xref rid="R8" ref-type="bibr">8</xref></sup></p><p>Previous stroke trials point towards possible meaningful differences between patients able to give consent by themselves and those enrolled by proxy consent, with patients enrolled by proxy consent being more severely affected.<sup><xref rid="R9" ref-type="bibr">9</xref>,<xref rid="R10" ref-type="bibr">10</xref></sup> However, the number of studies addressing this research question is small, and it is uncertain how the manner of obtaining consent affects further characteristics of stroke patients enrolled in clinical trials and how this might affect the generalizability of trial results. To address this question, we analyzed data of the first 1,005 patients enrolled in WAKE-UP, a European multicenter randomized controlled clinical trial of IV thrombolysis in acute stroke patients with unknown time of symptom onset based on MRI.<sup><xref rid="R11" ref-type="bibr">11</xref></sup> We study the effect of the manner of consent on the clinical characteristics of patients enrolled. Moreover, we also describe national variations in the manner of obtaining informed consent, an issue that has not yet been studied for acute stroke trials.</p><sec sec-type="methods" id="s1"><title>METHODS</title><sec id="s1-1"><title>Study population.</title><p>WAKE-UP (Efficacy and safety of MRI-based thrombolysis in wake-up stroke: a randomised, double-blind, placebo-controlled trial) is an investigator-initiated, randomized, double-blind, placebo-controlled trial designed to test the efficacy and safety of IV thrombolysis in patients with unknown time of symptom onset selected by MRI.<sup><xref rid="R11" ref-type="bibr">11</xref></sup> Patients are screened with MRI including diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR), and the presence of a DWI–FLAIR mismatch indicating ischemic stroke lesion <4.5 hours<sup><xref rid="R12" ref-type="bibr">12</xref></sup> represents the main imaging criterion for randomization to treatment with either IV tissue plasminogen activator or placebo. The trial was started in September 2012. The present analysis includes baseline data of patients enrolled until April 1, 2016. Only information recorded at baseline was analyzed, and only data of patients with at least information concerning informed consent, symptom onset, age, and sex were included.</p></sec><sec id="s1-2"><title>Standard protocol approvals, registrations, and patient consents.</title><p>WAKE-UP was approved by the national competent authorities and ethics committees in all participating countries. WAKE-UP was registered at <ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov/">clinicaltrials.gov</ext-link> (NCT01525290) and <ext-link ext-link-type="uri" xlink:href="https://www.clinicaltrialsregister.eu/">clinicaltrialsregister.eu</ext-link> (2011-005906-32).</p><p>Informed consent has to be obtained prior to enrollment of patients in the trial. Options for proxy consent are given in accordance with the following European and national regulations (<xref ref-type="fig" rid="F1">figure 1</xref>):</p><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label><caption><title>Approaches to informed consent in WAKE-UP</title><p>The different means of obtaining informed consent in WAKE-UP depending on the ability of the patient to give informed consent and on the availability of a legal guardian. The means of informed consent allowed for patient enrollment differed by country according to national regulations and the approval of national and regional ethics committees.</p></caption><graphic xlink:href="NEUROLOGY2016791053FF1"></graphic></fig><p>A: The patient is judged to have capacity to give informed consent and able to provide written consent: the patient provides written consent.</p><p>B: The patient is judged to have capacity to give informed consent but unable to provide written consent due to a physical barrier: the patient provides witnessed oral consent and provides later written consent as soon as possible.</p><p>C: The patient lacks capacity to give informed consent, legal guardian is available: the legal guardian acts on behalf of the patient and provides written consent.</p><p>D: The patient lacks capacity to give informed consent, legal guardian is not available, informed consent by next of kin: next acts on behalf of the patient following the patient's presumed will and provides written consent; patient or legal guardian provides later written consent as soon as possible.</p><p>E: The patient lacks capacity to give informed consent, legal guardian is not available, enrollment of patient by consensus between investigator and independent physician: the patient may be enrolled by consensus between the investigator and an independent physician; if possible, patient's next of kin should be contacted to appraise the patient's presumed will; the patient or legal guardian provides later written consent as soon as possible.</p><p>F: The patient lacks capacity to give informed consent, legal guardian is not available, enrollment of patient by investigator: the patient may be enrolled by the investigator acting on behalf of the patient following the patient's presumed will; if possible, the patient's next of kin should be contacted to appraise the patient's presumed will; the patient or legal guardian provides later written consent as soon as possible.</p></sec><sec id="s1-3"><title>Clinical examinations and MRI at baseline.</title><p>Neurologic examination was performed by certified investigators using the NIH Stroke Scale (NIHSS).<sup><xref rid="R13" ref-type="bibr">13</xref></sup> Information on time of symptom recognition and of the time point last seen well was obtained from patients or caregivers, and the reason why exact symptom onset was unknown was recorded according to 5 categories: night sleep, day sleep, unwitnessed stroke with aphasia, unwitnessed stroke with confusion, other. Time of admission to hospital was obtained from the medical records.</p><p>MRI including DWI and FLAIR was performed according to the trial protocol. Local investigators judged DWI–FLAIR mismatch according to standards provided together with the study protocol and after completion of a computer-based image judgement training and certification. Presence of a visible acute ischemic lesion on DWI, DWI–FLAIR mismatch, and any signs of intracranial haemorrhage were recorded.</p></sec><sec id="s1-4"><title>Statistical analysis.</title><p>Demographic and clinical characteristics as well as imaging findings at baseline are described and compared between groups. The following delays were calculated: time between last seen well and symptom recognition, time between symptom recognition and hospital admission, time between hospital admission and informed consent, and time between hospital admission and administration of the study drug. In addition to the NIHSS sum score, presence of aphasia as assessed by item 9 of the NIHSS and disturbance of level of consciousness as assessed by item 1a of the NIHSS were analyzed separately as categorical variables.</p><p>Descriptive statistics are provided including median (interquartile range [IQR]) and percentages for continuous and categorical data, respectively. For group comparison, the manner of informed consent was dichotomized into informed consent by the patient personally (written or oral: A, B) or informed consent by proxy (legal guardian, next of kin, consultant, or investigator: C, D, E, F). The manner of obtaining informed consent was also compared among countries for the 6 countries enrolling patients at the time of database export (Belgium, Denmark, France, Germany, Spain, United Kingdom). Fisher exact test or χ<sup>2</sup> test was used to compare groups for categorical variables, and the Kruskal-Wallis test was used for continuous variables. In order to account for heterogeneity among countries, group comparisons were repeated by fitting a logistic regression model of the odds of informed consent given by proxy according to each factor adjusted for country. All analyses are considered exploratory. SAS software, version 9.3 (SAS Institute Inc., Cary, NC) was used for all analyses.</p></sec></sec><sec sec-type="results" id="s2"><title>RESULTS</title><p>Of 1,039 patients enrolled in the trial, 1,005 patients met the inclusion criteria and were included in the analysis. Median age was 68 years (IQR 58–75 years); 38.8% of patients were women. In 646 (64.3%) patients, informed consent was given by the patients themselves, while in 359 (35.7%), informed consent was by proxy (see <xref ref-type="table" rid="T1">table 1</xref> for distribution of means of informed consent).</p><table-wrap id="T1" orientation="portrait" position="float"><label>Table 1</label><caption><p>Means of informed consent used for enrollment</p></caption><graphic xlink:href="NEUROLOGY2016791053TT1"></graphic></table-wrap><p>Patients enrolled via informed consent by proxy were older (median 71 vs 66 years, <italic>p</italic> < 0.0001) and were more frequently female (49.9% vs 32.7%, <italic>p</italic> < 0.0001; <xref ref-type="table" rid="T2">table 2</xref>). They also had a longer delay between the time point last seen normal and the time of symptom recognition (8.9 vs 7.3 hours, <italic>p</italic> < 0.0001). In contrast, the delay between symptom recognition and hospital arrival was shorter (1.5 vs 1 hour, <italic>p</italic> < 0.0001). Regarding trial-related activities, the delays between hospital admission and informed consent and between admission to hospital and the start of study drug, respectively, were longer for patients with informed consent by proxy, but in the additional analysis adjusted for country, no significant association was found.</p><table-wrap id="T2" orientation="portrait" position="float"><label>Table 2</label><caption><p>Clinical characteristics by means of informed consent</p></caption><graphic xlink:href="NEUROLOGY2016791053TT2"></graphic></table-wrap><p>Arterial hypertension was observed more frequently in patients with informed consent by proxy (58.2% vs 43.4%, <italic>p</italic> = 0.0022). Diabetes mellitus, hypercholesterolemia, and atrial fibrillation also were observed more frequently in patients with proxy consent, but the difference was not significant after adjustment for country. Patients enrolled via informed consent by proxy presented with a more severe neurologic deficit on admission, reflected by higher values on the NIHSS (median 11 vs 5, <italic>p</italic> < 0.0001). They also showed more frequently aphasia (73.7% vs 20.0%, <italic>p</italic> < 0.0001) and disturbed level of consciousness (17.0% vs 3.4%, <italic>p</italic> < 0.0001). Of note, MRI findings (i.e., findings of intracranial haemorrhage, acute DWI lesions, and DWI–FLAIR mismatch) did not differ between groups.</p><p>The relative frequency of the manner of informed consent used for enrollment varied among countries (<italic>p</italic> < 0.001; <xref ref-type="table" rid="T1">table 1</xref>). Written consent by patients themselves was the most frequent manner of informed consent in all countries apart from Spain (ranging from 86.0% in Denmark to 19.6% in Spain). Informed consent by next of kin ranged from 67.4% in Spain to not being used at all in Denmark. Enrollment by independent physician was used in 21.2% of cases in Germany but was only rarely used in other countries. In contrast, enrollment by investigator was common in France (35.5%), less frequent in Belgium (8.2%), but only used in single cases in the other countries. Overall, the proportion of informed consent by proxy ranged from 77.1% in Spain to 1.2% in Denmark (<xref ref-type="fig" rid="F2">figure 2</xref>).</p><fig id="F2" orientation="portrait" position="float"><label>Figure 2</label><caption><title>Manner of obtaining informed consent by country</title><p>The distribution of the different means of informed consent obtained in WAKE-UP, i.e., either by patients themselves or by proxy, for the 6 countries participating in the trial at the time of database extraction for the current analysis.</p></caption><graphic xlink:href="NEUROLOGY2016791053FF2"></graphic></fig></sec><sec sec-type="discussion" id="s3"><title>DISCUSSION</title><p>In this analysis of baseline data of the first 1,005 patients enrolled in the WAKE-UP trial, about 1 in 3 patients were enrolled by proxy consent. In these cases, consent was provided by the legal guardian, by next of kin, by an independent consultant, or by the investigator based on an emergency clause. There were marked differences in clinical characteristics between patients depending on how informed consent was obtained. Patients enrolled by proxy consent were older, more frequently hypertensive, and had more severe stroke symptoms reflected by higher NIHSS scores. Patients enrolled by proxy consent were also about 3.5 times more likely to be aphasic and 5 times more likely to have a disturbed level of consciousness. These observations are consistent with previous observations.<sup><xref rid="R4" ref-type="bibr">4</xref>,<xref rid="R8" ref-type="bibr">8</xref></sup> Both prestroke conditions (i.e., higher age, more severe comorbidity) and stroke-related factors (i.e., more severe neurologic symptoms including higher rate of aphasia) contribute to lack of capacity to give informed consent.</p><p>Our findings are consistent with observations from 2 other trials of IV thrombolysis. In the National Institute of Neurological Disorders and Stroke trial, 439 of 624 (70%) patients were enrolled by proxy consent, and these patients were older and more severely affected.<sup><xref rid="R9" ref-type="bibr">9</xref></sup> In the first 300 patients enrolled in the third International Stroke Trial (IST-3), patients with nonlacunar hemispheric stroke syndromes and those with a more severe neurologic deficit were more likely to have been enrolled by proxy consent.<sup><xref rid="R10" ref-type="bibr">10</xref></sup> Observations of imaging characteristics have noted smaller DWI volumes and absence of large artery occlusion among patients without capacity to consent.<sup><xref rid="R14" ref-type="bibr">14</xref></sup> These results underline that restricting enrollment to patients with capacity for consent will systematically exclude specific subgroups of stroke patients and result in populations that are not representative of acute stroke patients in general.<sup><xref rid="R15" ref-type="bibr">15</xref></sup> In a Cochrane review on information provision to stroke patients and caregivers, only 10 of 14 randomized controlled trials included in the review excluded patients with aphasia due to incapacity to consent.<sup><xref rid="R16" ref-type="bibr">16</xref></sup> In a single-center interventional stroke trial, inability to consent applied as exclusion criterion to 330 of 1,194 (28%) patients.<sup><xref rid="R17" ref-type="bibr">17</xref></sup> The effects of such restrictions include systematic exclusion of patients with some types of neurologic deficit (e.g., aphasia) from acute stroke research,<sup><xref rid="R8" ref-type="bibr">8</xref></sup> loss of generalizability, and slower recruitment rates. Many imaging endpoint biomarkers are likely to be uninformative with such restrictions.</p><p>We focused on a comparison of clinical data between patients capable of consent and those not capable without further detailed comparison of the subgroups of patients enrolled with different approaches to proxy consent. However, from an ethics perspective, there is a fundamental difference between surrogate consent (category C/D), considered to represent meaningful patient-centered consent, and physician consent in the absence of direct or surrogate consent (category E/F). We performed additional analyses subdividing the group of patients enrolled by proxy consent into patient-centered surrogate consent (C/D) and physician consent (E/F). This comparison revealed only slight differences in presenting symptoms, with disturbed level of consciousness and aphasia being slightly more frequent for physician consent (20.4% and 79.6%) as compared to patient-centered surrogate consent (14.9% and 70.1%), while age, sex distribution, and median NIHSS were comparable for the 2 subgroups of proxy consent.</p><p>Informed consent is considered a fundamental ethical principle of any research involving humans as described in the Declaration of Helsinki.<sup><xref rid="R1" ref-type="bibr">1</xref></sup> However, the Declaration of Helsinki also recognizes the problem of obtaining informed consent from patients in critical conditions and suggests different approaches to informed consent. The Food and Drug Administration as well as competent authorities in most European countries allow emergency research without informed consent under strictly defined circumstances. Only limited guidance is provided on how to regulate clinical research in patients incapable of giving informed consent, and as a consequence very different approaches for obtaining informed consent are used in different stroke trials and, within trials, among countries or trial sites.<sup><xref rid="R18" ref-type="bibr">18</xref></sup></p><p>At the time of database extraction for the current analysis, WAKE-UP was running in 6 European countries: Belgium, Denmark, France, Germany, Spain, and the United Kingdom. In principle, the EU directive on clinical trials (EC) No. 2001/20/EC<sup><xref rid="R19" ref-type="bibr">19</xref></sup> applies to all of these countries, providing rules for trials in emergency situations. However, the regulations provided in the directive are ambiguous and require interpretation. As a consequence, national regulations and interpretation of these regulations by institutional review boards and ethics committees are implemented with heterogeneous results, leading to a great diversity of national practice with regards to enrollment of incapable patients in Europe.<sup><xref rid="R20" ref-type="bibr">20</xref></sup> Within the WAKE-UP trial, we assured that multiple options for informed consent were available. The use of the 5 available approaches differed among the 6 countries. Of note, the proportion of proxy consent varied largely among countries, being hardly used at all in Denmark (1.2%) but in more than 2-thirds of patients in Spain (77.1%). Differences in approval of informed consent for the trial between countries may partly explain this variation (i.e., no approval for proxy consent beyond consent by a legal guardian in Denmark, no approval for consent by investigator in Germany and the United Kingdom). With regards to further reasons for the observed variation, we may only speculate. Differences in the attitude towards and in experience with different manners of informed consent among countries may also play a role. Independent from underlying reasons, these findings may inform the conduct of multinational stroke trials in the future as well as in other disease areas where proxy consent is likely to be used.</p><p>Country effects in clinical trials are generally assumed to be largely due to chance and small patient numbers in the individual countries.<sup><xref rid="R21" ref-type="bibr">21</xref></sup> However, there may be effects that reflect differences in populations or the clinical setting among countries, resulting in differences in patient characteristics or arguably treatment effect. We observed a confounding effect of country on the association between the manner of informed consent and clinical characteristics that appears plausible in reflecting country-specific aspects of the trial setting. The observed shorter time delay between hospital admission and treatment initiation in patients providing informed consent themselves appeared to be largely driven by a shorter mean delay between hospital admission and treatment initiation in Denmark as compared to all other countries, together with the fact that in Denmark virtually all patients were enrolled based on self-consent. These observations have to be interpreted with caution, as we cannot rule out potential center-level effects. However, given this limitation, our observations suggest that the choice of countries in which a trial should be run may modify the characteristics of the study population and hence may also influence the effects of the treatment under investigation.</p><p>There are statistical approaches to managing site differences in clinical trials, which broadly enclose the options of ignoring possible site effects, or of modeling them as either fixed effects or random effects.<sup><xref rid="R22" ref-type="bibr">22</xref></sup> There is, however, no standard solution for this problem, but the best strategy for controlling site effects depends on the expected effects, including confounding and site-by-treatment interaction. In WAKE-UP, randomization is stratified by site in order to avoid imbalances between sites concerning treatment allocation, and site and country will be addressed as confounding factors in the final statistical analysis.</p><p>The time-critical nature of interventions, the high prevalence of incapacity in acute stroke, and the demonstrable effect of proxy consent on trial conduct and populations call for considering approaches that might expedite proxy consent procedures for stroke clinical research, as has been considered in other emergency conditions.<sup><xref rid="R23" ref-type="bibr">23</xref>,<xref rid="R24" ref-type="bibr">24</xref></sup> The Council for International Organizations of Medical Sciences has recently proposed new international ethical guidelines for health-related research involving humans that, among other issues, address research in emergency settings and in patients incapable of providing informed consent.<sup><xref rid="R25" ref-type="bibr">25</xref></sup> There is an urgent need for clearer, more homogeneous, and more pragmatic regulations for enrollment of incapable patients into clinical trials. The opinions of stroke patients and caregivers should also be considered. In prospective interview studies, a majority of patients agreed to participate in acute stroke trials without conventional informed consent.<sup><xref rid="R26" ref-type="bibr">26</xref>,<xref rid="R27" ref-type="bibr">27</xref></sup> The concept of exception from informed consent for clinical research in neurologic emergency conditions like stroke was also generally accepted and deemed appropriate given approval of institutional review boards in a qualitative study of several focus groups including stroke patients, their families, and healthy young individuals.<sup><xref rid="R28" ref-type="bibr">28</xref></sup></p><p>In a large population of patients enrolled in a randomized controlled trial of IV thrombolysis in stroke, we demonstrate that the manner of informed consent affects the clinical characteristics of patients. In addition, the manner of informed consent differed significantly among countries. These findings illustrate the importance of identifying strategies for the inclusion of incapable patients in acute stroke trials. As of yet, reperfusion treatment is the only effective treatment strategy for acute stroke, and it is still only available for a limited subgroup of stroke patients. Further clinical trials improving treatment of acute stroke and testing new treatment approaches are urgently needed. Currently, differences in national regulations and diverging practice to informed consent may hamper trial success. More harmonized interpretation and implementation of international regulations into national practice is required to enable comparable practice including all different manners of consent in an emergency setting among different countries.</p></sec><sec sec-type="supplementary-material"><title>Supplementary Material</title><supplementary-material id="PMC_1" content-type="local-data"><caption><title>Accompanying Comment</title></caption><media mimetype="text" mime-subtype="html" xlink:href="supp_89_13_1400__index.html"></media><media xlink:role="associated-file" mimetype="application" mime-subtype="pdf" xlink:href="supp_WNL.0000000000004414_WNL.0000000000004429.pdf"></media></supplementary-material></sec></body><back><sec sec-type="contributions"><title>AUTHOR CONTRIBUTIONS</title><p content-type="contributions">Götz Thomalla: study concept and design, acquisition of data, analysis and interpretation of data, study supervision, drafting/revising the manuscript for content. Florent Boutitie: analysis and interpretation of data, drafting/revising the manuscript for content. Jochen B. Fiebach: study concept and design, acquisition of data, drafting/revising the manuscript for content. Claus Z. Simonsen: study concept and design, acquisition of data, drafting/revising the manuscript for content. Norbert Nighoghossian: study concept and design, acquisition of data, drafting/revising the manuscript for content. Salvador Pedraza: study concept and design, acquisition of data, drafting/revising the manuscript for content. Robin Lemmens: acquisition of data, drafting/revising the manuscript for content. Pascal Roy: analysis and interpretation of data, study supervision. Keith W. Muir: study concept and design, acquisition of data, drafting/revising the manuscript for content. Chistoph Heesen: drafting/revising the manuscript for content. Martin Ebinger: study concept and design, acquisition of data, drafting/revising the manuscript for content. Ian Ford: drafting/revising the manuscript for content. Bastian Cheng: study concept and design, acquisition of data. Tae-Hee Cho: acquisition of data, drafting/revising the manuscript for content. Josep Puig: acquisition of data, drafting/revising the manuscript for content. Vincent Thijs: study concept and design, acquisition of data, drafting/revising the manuscript for content. Matthias Endres: acquisition of data, study supervision, drafting/revising the manuscript for content. Jens Fiehler: study concept and design, acquisition of data, drafting/revising the manuscript for content. Christian Gerloff: study concept and design, analysis and interpretation of data, study supervision, drafting/revising the manuscript for content.</p></sec><sec sec-type="funding"><title>STUDY FUNDING</title><p content-type="funding">WAKE-UP receives funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 278276 (WAKE-UP).</p></sec><sec sec-type="disclosure"><title>DISCLOSURE</title><p content-type="disclosure">G. Thomalla received fees as a consultant or lecture fees from Acandis, Bayer Vital, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Daichii Sankyo, GlaxoSmithKline, and Stryker. F. Boutitie reports no disclosures relevant to the manuscript. J. Fiebach received consulting, lecture, and advisory board fees from Perceptive, BioClinica, Boehringer Ingelheim, Cerevast, Brainomix, and Lundbeck. C. Simonsen received lecture fees from Boehringer-Ingelheim. N. Nighoghossian reports no disclosures relevant to the manuscript. S. Pedraza received fees as a board member, consultant, or lecturer from Lundbeck and Synarc. R. Lemmens is a senior clinical investigator of FWO Flanders. P. Roy reports no disclosures relevant to the manuscript. K. Muir has received honoraria for speaking from Boehringer Ingelheim and Bayer and has received consultancy fees from ReNeuron Ltd. C. Heesen received grants or speaker honoraria from Bayer, Biogen, Genzyme, and Novartis. M. Ebinger, I. Ford, B. Cheng, T. Cho, and J. Puig report no disclosures relevant to the manuscript. V. Thijs received honoraria from Astra Zeneca, Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, and Pfizer for participation in advisory board meetings. M. Endres received fees from Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Ever, Glaxo Smith Kline, MSD, Pfizer, Novartis, and Sanofi. J. Fiehler received fees as a consultant or lecture fees from Codman, Covidien, Siemens, and Stryker. C. Gerloff received fees as a consultant or lecture fees from Bayer Vital, Boehringer Ingelheim, EBS Technologies, Glaxo Smith Kline, Lundbeck, Pfizer, Sanofi Aventis, Silk Road Medical, and UCB. Go to <ext-link ext-link-type="uri" xlink:href="http://neurology.org/lookup/doi/10.1212/WNL.0000000000004414">Neurology.org</ext-link> for full disclosures.</p></sec><glossary><title>GLOSSARY</title><def-list><def-item><term id="G1">DWI</term><def><p>diffusion-weighted imaging</p></def></def-item><def-item><term id="G2">FLAIR</term><def><p>fluid-attenuated inversion recovery</p></def></def-item><def-item><term id="G3">IQR</term><def><p>interquartile range</p></def></def-item><def-item><term id="G4">NIHSS</term><def><p>NIH Stroke Scale</p></def></def-item></def-list></glossary><ref-list><title>REFERENCES</title><ref id="R1"><label>1.</label><mixed-citation publication-type="journal"><article-title>World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects</article-title>. <source>JAMA</source><year>2013</year>;<volume>310</volume>:<fpage>2191</fpage>–<lpage>2194</lpage>.<pub-id pub-id-type="pmid">24141714</pub-id></mixed-citation></ref><ref id="R2"><label>2.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lees</surname><given-names>KR</given-names></name>, <name name-style="western"><surname>Emberson</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Blackwell</surname><given-names>L</given-names></name>, <etal>et al</etal></person-group><article-title>Effects of alteplase for acute stroke on the distribution of functional outcomes: a pooled analysis of 9 trials</article-title>. <source>Stroke</source><year>2016</year>;<volume>47</volume>:<fpage>2373</fpage>–<lpage>2379</lpage>.<pub-id pub-id-type="pmid">27507856</pub-id></mixed-citation></ref><ref id="R3"><label>3.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Ribo</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Molina</surname><given-names>CA</given-names></name>, <name name-style="western"><surname>Cobo</surname><given-names>E</given-names></name>, <etal>et al</etal></person-group><article-title>Association between time to reperfusion and outcome is primarily driven by the time from imaging to reperfusion</article-title>. <source>Stroke</source><year>2016</year>;<volume>47</volume>:<fpage>999</fpage>–<lpage>1004</lpage>.<pub-id pub-id-type="pmid">26956258</pub-id></mixed-citation></ref><ref id="R4"><label>4.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Demarquay</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Derex</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Nighoghossian</surname><given-names>N</given-names></name>, <etal>et al</etal></person-group><article-title>Ethical issues of informed consent in acute stroke: analysis of the modalities of consent in 56 patients enrolled in urgent therapeutic trials</article-title>. <source>Cerebrovasc Dis</source><year>2005</year>;<volume>19</volume>:<fpage>65</fpage>–<lpage>68</lpage>.<pub-id pub-id-type="pmid">15644623</pub-id></mixed-citation></ref><ref id="R5"><label>5.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mangset</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Forde</surname><given-names>R</given-names></name>, <name name-style="western"><surname>Nessa</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Berge</surname><given-names>E</given-names></name>, <name name-style="western"><surname>Wyller</surname><given-names>TB</given-names></name></person-group><article-title>I don't like that, it's tricking people too much…: acute informed consent to participation in a trial of thrombolysis for stroke</article-title>. <source>J Med Ethics</source><year>2008</year>;<volume>34</volume>:<fpage>751</fpage>–<lpage>756</lpage>.<pub-id pub-id-type="pmid">18827109</pub-id></mixed-citation></ref><ref id="R6"><label>6.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Bateman</surname><given-names>BT</given-names></name>, <name name-style="western"><surname>Meyers</surname><given-names>PM</given-names></name>, <name name-style="western"><surname>Schumacher</surname><given-names>HC</given-names></name>, <name name-style="western"><surname>Mangla</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Pile-Spellman</surname><given-names>J</given-names></name></person-group><article-title>Conducting stroke research with an exception from the requirement for informed consent</article-title>. <source>Stroke</source><year>2003</year>;<volume>34</volume>:<fpage>1317</fpage>–<lpage>1323</lpage>.<pub-id pub-id-type="pmid">12663878</pub-id></mixed-citation></ref><ref id="R7"><label>7.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Slyter</surname><given-names>H</given-names></name></person-group><article-title>Ethical challenges in stroke research</article-title>. <source>Stroke</source><year>1998</year>;<volume>29</volume>:<fpage>1725</fpage>–<lpage>1729</lpage>.<pub-id pub-id-type="pmid">9707218</pub-id></mixed-citation></ref><ref id="R8"><label>8.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Brady</surname><given-names>MC</given-names></name>, <name name-style="western"><surname>Fredrick</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Williams</surname><given-names>B</given-names></name></person-group><article-title>People with aphasia: capacity to consent, research participation and intervention inequalities</article-title>. <source>Int J Stroke</source><year>2013</year>;<volume>8</volume>:<fpage>193</fpage>–<lpage>196</lpage>.<pub-id pub-id-type="pmid">23130972</pub-id></mixed-citation></ref><ref id="R9"><label>9.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Flaherty</surname><given-names>ML</given-names></name>, <name name-style="western"><surname>Karlawish</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Khoury</surname><given-names>JC</given-names></name>, <name name-style="western"><surname>Kleindorfer</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Woo</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Broderick</surname><given-names>JP</given-names></name></person-group><article-title>How important is surrogate consent for stroke research?</article-title><source>Neurology</source><year>2008</year>;<volume>71</volume>:<fpage>1566</fpage>–<lpage>1571</lpage>.<pub-id pub-id-type="pmid">18753472</pub-id></mixed-citation></ref><ref id="R10"><label>10.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kane</surname><given-names>I</given-names></name>, <name name-style="western"><surname>Lindley</surname><given-names>R</given-names></name>, <name name-style="western"><surname>Lewis</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Sandercock</surname><given-names>P</given-names></name></person-group><article-title>Impact of stroke syndrome and stroke severity on the process of consent in the Third International Stroke Trial</article-title>. <source>Cerebrovasc Dis</source><year>2006</year>;<volume>21</volume>:<fpage>348</fpage>–<lpage>352</lpage>.<pub-id pub-id-type="pmid">16490945</pub-id></mixed-citation></ref><ref id="R11"><label>11.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Thomalla</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Fiebach</surname><given-names>JB</given-names></name>, <name name-style="western"><surname>Ostergaard</surname><given-names>L</given-names></name>, <etal>et al</etal></person-group><article-title>A multicenter, randomized, double-blind, placebo-controlled trial to test efficacy and safety of magnetic resonance imaging-based thrombolysis in wake-up stroke (WAKE-UP)</article-title>. <source>Int J Stroke</source><year>2014</year>;<volume>9</volume>:<fpage>829</fpage>–<lpage>836</lpage>.<pub-id pub-id-type="pmid">23490032</pub-id></mixed-citation></ref><ref id="R12"><label>12.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Thomalla</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Cheng</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Ebinger</surname><given-names>M</given-names></name>, <etal>et al</etal></person-group><article-title>DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4.5 h of symptom onset (PRE-FLAIR): a multicentre observational study</article-title>. <source>Lancet Neurol</source><year>2011</year>;<volume>10</volume>:<fpage>978</fpage>–<lpage>986</lpage>.<pub-id pub-id-type="pmid">21978972</pub-id></mixed-citation></ref><ref id="R13"><label>13.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Brott</surname><given-names>T</given-names></name>, <name name-style="western"><surname>Adams</surname><given-names>HP</given-names><suffix>Jr</suffix></name>, <name name-style="western"><surname>Olinger</surname><given-names>CP</given-names></name>, <etal>et al</etal></person-group><article-title>Measurements of acute cerebral infarction: a clinical examination scale</article-title>. <source>Stroke</source><year>1989</year>;<volume>20</volume>:<fpage>864</fpage>–<lpage>870</lpage>.<pub-id pub-id-type="pmid">2749846</pub-id></mixed-citation></ref><ref id="R14"><label>14.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Dani</surname><given-names>KA</given-names></name>, <name name-style="western"><surname>McCormick</surname><given-names>MT</given-names></name>, <name name-style="western"><surname>Muir</surname><given-names>KW</given-names></name></person-group><article-title>Brain lesion volume and capacity for consent in stroke trials: potential regulatory barriers to the use of surrogate markers</article-title>. <source>Stroke</source><year>2008</year>;<volume>39</volume>:<fpage>2336</fpage>–<lpage>2340</lpage>.<pub-id pub-id-type="pmid">18535280</pub-id></mixed-citation></ref><ref id="R15"><label>15.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mendyk</surname><given-names>AM</given-names></name>, <name name-style="western"><surname>Labreuche</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Henon</surname><given-names>H</given-names></name>, <etal>et al</etal></person-group><article-title>Which factors influence the resort to surrogate consent in stroke trials, and what are the patient outcomes in this context?</article-title><source>BMC Med Ethics</source><year>2015</year>;<volume>16</volume>:<fpage>26</fpage>.<pub-id pub-id-type="pmid">25903471</pub-id></mixed-citation></ref><ref id="R16"><label>16.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Smith</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Forster</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Young</surname><given-names>J</given-names></name></person-group><article-title>Cochrane review: information provision for stroke patients and their caregivers</article-title>. <source>Clin Rehabil</source><year>2009</year>;<volume>23</volume>:<fpage>195</fpage>–<lpage>206</lpage>.<pub-id pub-id-type="pmid">19218295</pub-id></mixed-citation></ref><ref id="R17"><label>17.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Hotter</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Jegzentis</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Steinbrink</surname><given-names>J</given-names></name>, <etal>et al</etal></person-group><article-title>Impact of selection criteria on recruitment in an interventional stroke trial</article-title>. <source>Cerebrovasc Dis</source><year>2013</year>;<volume>36</volume>:<fpage>344</fpage>–<lpage>350</lpage>.<pub-id pub-id-type="pmid">24192450</pub-id></mixed-citation></ref><ref id="R18"><label>18.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Leira</surname><given-names>EC</given-names></name>, <name name-style="western"><surname>Kaldjian</surname><given-names>LC</given-names></name>, <name name-style="western"><surname>Ludwig</surname><given-names>BR</given-names></name>, <etal>et al</etal></person-group><article-title>Lack of international consensus on ethical aspects of acute stroke trials</article-title>. <source>J Stroke Cerebrovasc Dis</source><year>2012</year>;<volume>21</volume>:<fpage>200</fpage>–<lpage>204</lpage>.<pub-id pub-id-type="pmid">20719537</pub-id></mixed-citation></ref><ref id="R19"><label>19.</label><mixed-citation publication-type="journal">Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. OJ <year>2001</year>;<volume>L121</volume>:<fpage>34</fpage>–<lpage>44</lpage>.</mixed-citation></ref><ref id="R20"><label>20.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lemaire</surname><given-names>F</given-names></name>, <name name-style="western"><surname>Bion</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Blanco</surname><given-names>J</given-names></name>, <etal>et al</etal></person-group><article-title>The European Union Directive on Clinical Research: present status of implementation in EU member states' legislations with regard to the incompetent patient</article-title>. <source>Intens Care Med</source><year>2005</year>;<volume>31</volume>:<fpage>476</fpage>–<lpage>479</lpage>.</mixed-citation></ref><ref id="R21"><label>21.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yusuf</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Wittes</surname><given-names>J</given-names></name></person-group><article-title>Interpreting geographic variations in results of randomized, controlled trials</article-title>. <source>N Engl J Med</source><year>2016</year>;<volume>375</volume>:<fpage>2263</fpage>–<lpage>2271</lpage>.<pub-id pub-id-type="pmid">27959693</pub-id></mixed-citation></ref><ref id="R22"><label>22.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Feaster</surname><given-names>DJ</given-names></name>, <name name-style="western"><surname>Mikulich-Gilbertson</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Brincks</surname><given-names>AM</given-names></name></person-group><article-title>Modeling site effects in the design and analysis of multi-site trials</article-title>. <source>Am J Drug Alcohol Abuse</source><year>2011</year>;<volume>37</volume>:<fpage>383</fpage>–<lpage>391</lpage>.<pub-id pub-id-type="pmid">21854281</pub-id></mixed-citation></ref><ref id="R23"><label>23.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Iwanowski</surname><given-names>P</given-names></name>, <name name-style="western"><surname>Budaj</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Czlonkowska</surname><given-names>A</given-names></name>, <etal>et al</etal></person-group><article-title>Informed consent for clinical trials in acute coronary syndromes and stroke following the European Clinical Trials Directive: investigators' experiences and attitudes</article-title>. <source>Trials</source><year>2008</year>;<volume>9</volume>:<fpage>45</fpage>.<pub-id pub-id-type="pmid">18644120</pub-id></mixed-citation></ref><ref id="R24"><label>24.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Qureshi</surname><given-names>AI</given-names></name>, <name name-style="western"><surname>Gilani</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Adil</surname><given-names>MM</given-names></name>, <etal>et al</etal></person-group><article-title>Pattern of informed consent acquisition in patients undergoing emergent endovascular treatment for acute ischemic stroke</article-title>. <source>J Vasc Interv Neurol</source><year>2014</year>;<volume>7</volume>:<fpage>21</fpage>–<lpage>25</lpage>.</mixed-citation></ref><ref id="R25"><label>25.</label><mixed-citation publication-type="book"><collab>Sciences CfIOoM</collab>. <source>International Ethical Guidelines for Health-Related Research Involving Humans</source>. <publisher-loc>Geneva</publisher-loc>: <publisher-name>Council for International Organizations of Medical Sciences</publisher-name>; <year>2016</year>.</mixed-citation></ref><ref id="R26"><label>26.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kleindorfer</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Lindsell</surname><given-names>CJ</given-names></name>, <name name-style="western"><surname>Alwell</surname><given-names>K</given-names></name>, <etal>et al</etal></person-group><article-title>Ischemic stroke survivors' opinion regarding research utilizing exception from informed consent</article-title>. <source>Cerebrovasc Dis</source><year>2011</year>;<volume>32</volume>:<fpage>321</fpage>–<lpage>326</lpage>.<pub-id pub-id-type="pmid">21921594</pub-id></mixed-citation></ref><ref id="R27"><label>27.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Goldstein</surname><given-names>JN</given-names></name>, <name name-style="western"><surname>Espinola</surname><given-names>JA</given-names></name>, <name name-style="western"><surname>Fisher</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Pallin</surname><given-names>DJ</given-names></name>, <name name-style="western"><surname>Camargo</surname><given-names>CA</given-names></name></person-group><article-title>Public opinion of a stroke clinical trial using exception from informed consent</article-title>. <source>Int J Emerg Med</source><year>2010</year>;<volume>3</volume>:<fpage>385</fpage>–<lpage>389</lpage>.<pub-id pub-id-type="pmid">21373310</pub-id></mixed-citation></ref><ref id="R28"><label>28.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kasner</surname><given-names>SE</given-names></name>, <name name-style="western"><surname>Baren</surname><given-names>JM</given-names></name>, <name name-style="western"><surname>Le Roux</surname><given-names>PD</given-names></name>, <etal>et al</etal></person-group><article-title>Community views on neurologic emergency treatment trials</article-title>. <source>Ann Emerg Med</source><year>2011</year>;<volume>57</volume>:<fpage>346</fpage>–<lpage>354 e6</lpage>.<pub-id pub-id-type="pmid">20875693</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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