{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T10:32:09Z","timestamp":1792751529451,"version":"4.5.0"},"reference-count":80,"publisher":"American Society of Hematology","issue":"24","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,12,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>As most patients with sickle cell disease (SCD) do not have access to curative therapies, the availability of drug therapies that can modify disease severity remains highly desirable. Despite an increased understanding of the pathophysiology of SCD, only 4 drugs are approved by the US Food and Drugs Administration. Most drug trials in SCD have involved the use of acute pain episodes as the primary clinical end point. These studies have typically been to prevent or shorten the duration of such episodes. To date, no drug has received regulatory approval for shortening the duration of acute vaso-occlusive complications, likely highlighting the complex pathophysiology of acute pain episodes. Trials to prevent acute pain episodes have largely evaluated those episodes requiring health care use as a surrogate end point. However, with differences in culture and health care practices among countries, health care use may not reliably predict clinically important effects on acute pain episodes. This article discusses issues related to the use of health care use as the primary end point for prevention trials of acute pain episodes and highlights the importance of evaluating patient-reported outcomes as well as other SCD-related complications as outcome measures.<\/jats:p>","DOI":"10.1182\/blood.2023021220","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T16:21:44Z","timestamp":1698423704000},"page":"2047-2054","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":18,"title":["The challenge of clinical end points in sickle cell disease"],"prefix":"10.1182","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4501-9982","authenticated-orcid":false,"given":"Kenneth I.","family":"Ataga","sequence":"first","affiliation":[{"name":"Center for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"9757","key":"2023121416231085800_bib1","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/S0140-6736(10)61029-X","article-title":"Sickle-cell disease","volume":"376","author":"Rees","year":"2010","journal-title":"Lancet"},{"issue":"7","key":"2023121416231085800_bib2","doi-asserted-by":"crossref","first-page":"e1001484","DOI":"10.1371\/journal.pmed.1001484","article-title":"Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions","volume":"10","author":"Piel","year":"2013","journal-title":"PLoS Med"},{"issue":"7","key":"2023121416231085800_bib3","doi-asserted-by":"crossref","first-page":"905","DOI":"10.3324\/haematol.10937","article-title":"Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London","volume":"92","author":"Telfer","year":"2007","journal-title":"Haematologica"},{"issue":"17","key":"2023121416231085800_bib4","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1182\/blood-2009-07-233700","article-title":"Improved survival of children and adolescents with sickle cell disease","volume":"115","author":"Quinn","year":"2010","journal-title":"Blood"},{"issue":"6","key":"2023121416231085800_bib5","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1111\/bjh.14015","article-title":"Improvement of medical care in a cohort of newborns with sickle-cell disease in North Paris: impact of national guidelines","volume":"173","author":"Couque","year":"2016","journal-title":"Br J Haematol"},{"issue":"3","key":"2023121416231085800_bib6","doi-asserted-by":"crossref","first-page":"e208","DOI":"10.1016\/S2352-3026(22)00004-7","article-title":"Estimating the risk of child mortality attributable to sickle cell anaemia in sub-Saharan Africa: a retrospective, multicentre, case-control study","volume":"9","author":"Ranque","year":"2022","journal-title":"Lancet Haematol"},{"issue":"23","key":"2023121416231085800_bib7","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1056\/NEJM199406093302303","article-title":"Mortality in sickle cell disease. 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