TY - JOUR
T1 - Use of case reports and the Adverse Event Reporting System in systematic reviews
T2 - overcoming barriers to assess the link between Crohn's disease medications and hepatosplenic T-cell lymphoma.
AU - Selvaraj, Saranya A.
AU - Chairez, Elizabeth
AU - Wilson, Lisa M.
AU - Lazarev, Mark
AU - Bass, Eric B.
AU - Hutfless, Susan
N1 - Funding Information:
This project was funded under contract number HHSA 290-2007-10061-I from the AHRQ, US Department of Health and Human Services. The authors of this article are responsible for its content, including any clinical treatment recommendations. No statement in this article should be construed as an official position of the AHRQ or of the US Department of Health and Human Services. SS was supported by the Johns Hopkins Predoctoral Clinical Research Training Program grant number 1TL1RR-025007 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). This article’s contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Publication of this article was funded in part by the Open Access Promotion Fund of the Johns Hopkins University Libraries.
PY - 2013
Y1 - 2013
N2 - To identify demographic and clinical characteristics associated with cases of hepatosplenic T-cell lymphoma (HSTCL) in patients with Crohn's disease, and to assess strength of evidence for a causal relationship between medications and HSTCL in Crohn's disease. We identified cases of HSTCL in Crohn's disease in studies included in a comparative effectiveness review of Crohn's disease medications, through a separate search of PubMed and Embase for published case reports, and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS). We used three causality assessment tools to evaluate the relationship between medication exposure and HSTCL. We found 37 unique cases of HSTCL in patients with Crohn's disease. Six cases were unique to the published literature and nine were unique to AERS. Cases were typically young (<40 years of age) and male (86%). The most commonly reported medications were anti-metabolites (97%) and anti-tumor necrosis factor alpha (anti-TNFa) medications (76%). Dose and duration of therapy were not consistently reported. Use of aminosalicylates and corticosteroids were rarely reported, despite the high prevalence of these medications in routine treatment. Using the causality assessment tools, it could only be determined that anti-metabolite and anti-TNFa therapies were possible causes of HSTCL in Crohn's disease based on the data contained in the case reports. Systematic reviews that incorporate case reports of rare lethal events should search both published literature and AERS, but consideration should be given to the limitations of case reports. In this study, establishing a causative effect other than 'possible' between anti-metabolite or anti-TNFa therapies and HSTCL was not feasible because case reports lacked data required by the causality assessments, and because of the limited applicability of causality assessment tools for rare irreversible events. We recommend minimum reporting requirements for case reports to improve causality assessment and routine reporting of rare life-threatening events, including their absence, in clinical trials to help clinicians determine whether rare adverse events are causally related to a medication.
AB - To identify demographic and clinical characteristics associated with cases of hepatosplenic T-cell lymphoma (HSTCL) in patients with Crohn's disease, and to assess strength of evidence for a causal relationship between medications and HSTCL in Crohn's disease. We identified cases of HSTCL in Crohn's disease in studies included in a comparative effectiveness review of Crohn's disease medications, through a separate search of PubMed and Embase for published case reports, and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS). We used three causality assessment tools to evaluate the relationship between medication exposure and HSTCL. We found 37 unique cases of HSTCL in patients with Crohn's disease. Six cases were unique to the published literature and nine were unique to AERS. Cases were typically young (<40 years of age) and male (86%). The most commonly reported medications were anti-metabolites (97%) and anti-tumor necrosis factor alpha (anti-TNFa) medications (76%). Dose and duration of therapy were not consistently reported. Use of aminosalicylates and corticosteroids were rarely reported, despite the high prevalence of these medications in routine treatment. Using the causality assessment tools, it could only be determined that anti-metabolite and anti-TNFa therapies were possible causes of HSTCL in Crohn's disease based on the data contained in the case reports. Systematic reviews that incorporate case reports of rare lethal events should search both published literature and AERS, but consideration should be given to the limitations of case reports. In this study, establishing a causative effect other than 'possible' between anti-metabolite or anti-TNFa therapies and HSTCL was not feasible because case reports lacked data required by the causality assessments, and because of the limited applicability of causality assessment tools for rare irreversible events. We recommend minimum reporting requirements for case reports to improve causality assessment and routine reporting of rare life-threatening events, including their absence, in clinical trials to help clinicians determine whether rare adverse events are causally related to a medication.
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U2 - 10.1186/2046-4053-2-53
DO - 10.1186/2046-4053-2-53
M3 - Article
C2 - 23826928
AN - SCOPUS:84886555418
SN - 0309-1708
VL - 2
SP - 53
JO - Unknown Journal
JF - Unknown Journal
M1 - 53
ER -