{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:41:00Z","timestamp":1780584060330,"version":"3.54.1"},"reference-count":20,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2016,1,14]],"date-time":"2016-01-14T00:00:00Z","timestamp":1452729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>The Ebola virus disease outbreak in 2014\u20132015 led to a huge caseload with a high case fatality rate. No specific treatments were available beyond supportive care for conditions such as dehydration and shock. Evaluation of treatment with convalescent plasma from Ebola survivors was identified as a priority. We evaluated this intervention in an emergency setting, where randomization was unacceptable. The original trial design was an open-label study comparing patients receiving convalescent plasma and supportive care to patients receiving supportive care alone. The comparison group comprised patients recruited at the start of the trial before convalescent plasma became available, as well as patients presenting during the trial for whom there was insufficient blood group\u2013compatible plasma or no staffing capacity to provide additional transfusions. However, during the trial, convalescent plasma was available to treat all new patients. The design was changed to use a comparator group comprising patients previously treated at the same Ebola treatment center prior to the start of the trial. In the analysis, it was planned to adjust for any differences in prognostic variables between intervention and comparison groups, specifically baseline polymerase chain reaction cycle threshold and age. In addition, adjustment was planned for other potential confounders, identified in the analysis, such as patient presenting symptoms and time to treatment seeking. Because plasma treatment started up to 3\u2009days after diagnosis and we could not define a similar time-point for the comparator group, patients who died before the third day after confirmation of diagnosis were excluded from both intervention and comparison groups in a per-protocol analysis. Some patients received additional experimental treatments soon after plasma treatment, and these were excluded. We also analyzed mortality including all patients from the time of confirmed diagnosis, irrespective of whether those in the trial series actually received plasma, as an intention-to-treat analysis. Per-protocol and intention-to-treat approaches gave similar conclusions. An important caveat in the interpretation of the findings is that it is unlikely that all potential sources of confounding, such as any variation in supportive care over time, were eliminated. Protocols and electronic data capture systems have now been extensively field-tested for emergency evaluation of treatment with convalescent plasma. Ongoing studies seek to quantify the level of neutralizing antibodies in different plasma donations to determine whether this influences the response and survival of treated patients.<\/jats:p>","DOI":"10.1177\/1740774515621056","type":"journal-article","created":{"date-parts":[[2016,1,15]],"date-time":"2016-01-15T07:02:37Z","timestamp":1452841357000},"page":"13-21","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Design and analysis considerations in the Ebola_Tx trial evaluating convalescent plasma in the treatment of Ebola virus disease in Guinea during the 2014\u20132015 outbreak"],"prefix":"10.1177","volume":"13","author":[{"given":"Tansy","family":"Edwards","sequence":"first","affiliation":[{"name":"MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm G","family":"Semple","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"De Weggheleire","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Claeys","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike","family":"De Crop","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"Menten","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Ravinetto","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Temmerman","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutgarde","family":"Lynen","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elhadj Ibrahima","family":"Bah","sequence":"additional","affiliation":[{"name":"Service des maladies infectieuses et tropicales, de L\u2019H\u00f4pital National Donka, Conakry, Guinea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G","family":"Smith","sequence":"additional","affiliation":[{"name":"MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"van Griensven","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Ebola_Tx Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,1,14]]},"reference":[{"key":"bibr1-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro974"},{"key":"bibr2-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu396"},{"key":"bibr3-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1086\/514298"},{"key":"bibr4-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g5539"},{"key":"bibr5-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61411-2"},{"key":"bibr6-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv042"},{"key":"bibr7-1740774515621056","first-page":"1208","volume":"211","author":"Colebunders RL","year":"2015","journal-title":"J Infect Dis"},{"key":"bibr8-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1411100"},{"key":"bibr9-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60193-3"},{"key":"bibr10-1740774515621056","unstructured":"World Health Organization (WHO). Ebola response roadmap update, http:\/\/apps.who.int\/iris\/bitstream\/10665\/135029\/1\/roadmapupdate26sept14_eng.pdf?ua=1 (2014, accessed 11 November 2015)."},{"key":"bibr11-1740774515621056","unstructured":"World Health Organization. Ethical issues related to study design for trials on therapeutics for Ebola Virus Disease. In: WHO ethics working group meeting (summary of discussion), 20\u201321 October 2014, http:\/\/apps.who.int\/iris\/bitstream\/10665\/137509\/1\/WHO_HIS_KER_GHE_14.2_eng.pdf (accessed 5 November 2015)."},{"key":"bibr12-1740774515621056","unstructured":"World Health Organization. Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks. Interim Guidance for National Health Authorities and Blood Transfusion Services, http:\/\/apps.who.int\/iris\/bitstream\/10665\/135591\/1\/WHO_HIS_SDS_2014.8_eng.pdf?ua=1 (2014, accessed 5 November 2015)."},{"key":"bibr13-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)62392-8"},{"key":"bibr14-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ680"},{"key":"bibr15-1740774515621056","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.13-0630"},{"key":"bibr16-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61734-7"},{"key":"bibr17-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1177\/1740774515620145"},{"key":"bibr18-1740774515621056","first-page":"1","volume-title":"Abstracts of the 9th European congress on tropical medicine and international health","volume":"20","author":"Claeys Y","year":"2015"},{"key":"bibr19-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00144-9"},{"key":"bibr20-1740774515621056","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00221-2"}],"container-title":["Clinical Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1740774515621056","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1740774515621056","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1740774515621056","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:29:21Z","timestamp":1777397361000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1740774515621056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,14]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1177\/1740774515621056"],"URL":"https:\/\/doi.org\/10.1177\/1740774515621056","relation":{},"ISSN":["1740-7745","1740-7753"],"issn-type":[{"value":"1740-7745","type":"print"},{"value":"1740-7753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,14]]}}}