{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T08:21:56Z","timestamp":1784794916250,"version":"3.55.0"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T00:00:00Z","timestamp":1595635200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T00:00:00Z","timestamp":1595635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1172544"],"award-info":[{"award-number":["OPP1172544"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>An effective drug to treat cryptosporidial diarrhea in HIV-infected individuals is a global health priority. Promising drugs need to be evaluated in endemic areas which may be challenged by both lack of resources and experience to conduct International Committee of Harmonisation-Good Clinical Practice (ICH-GCP)-compliant clinical trials.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We present the challenges and lessons learned in implementing a phase 2A, randomized, double-blind, placebo-controlled trial of clofazimine, in treatment of cryptosporidiosis among HIV-infected adults at a single site in Malawi.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Primary challenges are grouped under study initiation, study population, study implementation, and cultural issues. The lessons learned primarily deal with regulatory system and operational barriers, and recommendations can be applied to other human experimental trials in low- and middle-income countries, specifically in sub-Saharan Africa.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study demonstrated that initiating and implementing human experimental trials in sub-Saharan Africa can be challenging. However, solutions exist and successful execution requires careful planning, ongoing evaluation, responsiveness to new developments, and oversight of all trial operations.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13063-020-04620-8","type":"journal-article","created":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T12:02:34Z","timestamp":1595678554000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Conducting clinical trials in sub-Saharan Africa: challenges and lessons learned from the Malawi Cryptosporidium study"],"prefix":"10.1186","volume":"21","author":[{"given":"Neema","family":"Toto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Douglas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Gmeiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn K.","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lindblad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lumbani","family":"Makhaza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred","family":"Nedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Phulusa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald V.","family":"Quinnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh A.","family":"Sawyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Thole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley C.","family":"Van Voorhis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3682-8892","authenticated-orcid":false,"given":"Pui-Ying","family":"Iroh Tam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,25]]},"reference":[{"issue":"2","key":"4620_CR1","first-page":"1","volume":"7","author":"N Singh","year":"2018","unstructured":"Singh N. 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Encycl Microbiol. 2009:444\u201354. https:\/\/doi.org\/10.1016\/B978-012373944-5.00185-1.","DOI":"10.1016\/B978-012373944-5.00185-1"},{"issue":"11","key":"4620_CR4","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-003616","volume":"3","author":"SR Franzen","year":"2013","unstructured":"Franzen SR, Chandler C, Enquselassie F, Siribaddana S, Atashili J, Angus B, Lang T. Understanding the investigators: a qualitative study investigating the barriers and enablers to the implementation of local investigator-initiated clinical trials in Ethiopia. BMJ Open. 2013;3(11):e003616.","journal-title":"BMJ Open"},{"issue":"6","key":"4620_CR5","doi-asserted-by":"publisher","first-page":"2174","DOI":"10.1093\/ije\/dyw313","volume":"45","author":"M Kelaher","year":"2016","unstructured":"Kelaher M, Ng L, Knight K, Rahadi A. Equity in global health research in the new millennium: trends in first-authorship for randomized controlled trials among low- and middle-income country researchers 1990-2013. Int J Epidemiol. 2016;45(6):2174\u201383.","journal-title":"Int J Epidemiol"},{"key":"4620_CR6","unstructured":"Studies on Map-Clinical Trials.gov [https:\/\/www.clinicaltrials.gov\/ct2\/search\/map]. Accessed 30 Apr 2019."},{"issue":"7","key":"4620_CR7","doi-asserted-by":"publisher","first-page":"e758","DOI":"10.1016\/S2214-109X(18)30283-3","volume":"6","author":"IA Khalil","year":"2018","unstructured":"Khalil IA, Troeger C, Rao PC, Blacker BF, Brown A, Brewer TG, Colombara DV, De Hostos EL, Engmann C, Guerrant RL, et al. Morbidity, mortality, and long-term consequences associated with diarrhoea from Cryptosporidium infection in children younger than 5 years: a meta-analyses study. Lancet Glob Health. 2018;6(7):e758\u201368.","journal-title":"Lancet Glob Health"},{"issue":"2","key":"4620_CR8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005373","volume":"11","author":"MS Love","year":"2017","unstructured":"Love MS, Beasley FC, Jumani RS, Wright TM, Chatterjee AK, Huston CD, Schultz PG, McNamara CW. A high-throughput phenotypic screen identifies clofazimine as a potential treatment for cryptosporidiosis. PLoS Negl Trop Dis. 2017;11(2):e0005373.","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"4620_CR9","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1186\/s13063-018-2846-6","volume":"19","author":"P Nachipo","year":"2018","unstructured":"Nachipo P, Hermann D, Quinnan G, Gordon MA, Van Voorhis WC, Iroh Tam PY. Evaluating the safety, tolerability, pharmacokinetics and efficacy of clofazimine in cryptosporidiosis (CRYPTOFAZ): study protocol for a randomized controlled trial. 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Accessed 30 Apr 2019."}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-04620-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-020-04620-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-04620-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,24]],"date-time":"2021-07-24T23:08:49Z","timestamp":1627168129000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-020-04620-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,25]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["4620"],"URL":"https:\/\/doi.org\/10.1186\/s13063-020-04620-8","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,25]]},"assertion":[{"value":"5 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This manuscript does not directly contain human data; however, its topic is a clinical trial in which all patients were appropriately consented and ethics approval was granted from the NHSRC (reference 17\/05\/1821) and by the Liverpool School of Tropical Medicine Research Ethics Committee (reference 17-031).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"There was no specific informed consent sought for this publication because it does not contain any patient data. However, as part of the Cryptofaz clinical trial, full informed consent was obtained before any patient started the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"PI and WVV have received grants from Bill & Melinda Gates Foundation (BMGF) outside of the submitted work. WVV has patents issued for bumped kinase inhibitors (BKIs) for the therapeutic treatment of cryptosporidiosis diarrhea and is a founder and has stock of ParaTheraTech LLC, a company that is developing BKIs for animal health indications. All other authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"680"}}