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Although these designs share the advantages and limitations of within\u2010individual comparison, they also have design\u2010specific assumptions. It is not known to what extent the differences in assumptions lead to different results in RWE DDI analyses. Using a nationwide US commercial healthcare insurance database (2006\u20132016), we compared the CCO and SCCS designs, as they are implemented in DDI studies, within five DDI\u2010outcome examples: (1) simvastatin\u00a0+\u00a0clarithromycin and muscle\u2010related toxicity; (2) atorvastatin\u00a0+\u00a0valsartan, and muscle\u2010related toxicity; and (3\u20135) dabigatran\u00a0+\u00a0P\u2010glycoprotein inhibitor (clarithromycin, amiodarone, and verapamil) and bleeding. Analyses were conducted within person\u2010time exposed to the object drug (statins and dabigatran) and adjusted for bias associated with the inhibiting drugs via control groups of individuals unexposed to the object drug. The designs yielded similar estimates in most examples, with SCCS displaying better statistical efficiency. With both designs, results varied across sensitivity analyses, particularly in CCO analyses with small number of exposed individuals. Analyses in controls revealed substantial bias that may be differential across DDI\u2010exposed and control individuals. Thus, both designs showed no association between amiodarone or verapamil and bleeding in dabigatran\u2010exposed but revealed strong positive associations in controls. Overall, bias adjustment via a control group had a larger impact on results than the choice of a design, highlighting the importance and challenges of appropriate control group selection for adequate bias control in self\u2010controlled analyses of DDIs.<\/jats:p>","DOI":"10.1002\/cpt.2119","type":"journal-article","created":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T18:47:16Z","timestamp":1606502836000},"page":"1353-1360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Drug\u2010Drug Interaction Surveillance Study: Comparing Self\u2010Controlled Designs in Five Empirical Examples in Real\u2010World Data"],"prefix":"10.1111","volume":"109","author":[{"given":"Katsiaryna","family":"Bykov","sequence":"first","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics Department of Medicine Brigham and Women\u2019s Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Li","sequence":"additional","affiliation":[{"name":"Global Patient Safety Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangmi","family":"Kim","sequence":"additional","affiliation":[{"name":"Global Patient Safety Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seanna M.","family":"Vine","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics Department of Medicine Brigham and Women\u2019s Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Vincent","family":"Lo Re","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine and Center for Pharmacoepidemiology Research and Training Department of Biostatistics, Epidemiology, and Informatics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J.","family":"Gagne","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics Department of Medicine Brigham and Women\u2019s Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1507"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i5014"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2016.03.006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.857"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0597-x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.277"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1376"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000638"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280208092342"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.2330"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280208092346"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.100702"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.150"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001087"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-016-0349-y"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2012.04453.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12055"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.01.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13343"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04498.x"},{"key":"e_1_2_9_21_1","unstructured":"US Food and Drug Administration.FDA Drug Safety Communication: New restrictions contraindications and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury<https:\/\/www.fda.gov\/drugs\/drug\u2010safety\u2010and\u2010availability\/fda\u2010drug\u2010safety\u2010communication\u2010new\u2010restrictions\u2010contraindications\u2010and\u2010dose\u2010limitations\u2010zocor> (2011). 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