{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:41:47Z","timestamp":1792035707120,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutical Statistics"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The assumption of \u201cno unmeasured confounders\u201d is a critical but unverifiable assumption required for causal inference yet quantitative sensitivity analyses to assess robustness of real\u2010world evidence remains under\u2010utilized. The lack of use is likely in part due to complexity of implementation and often specific and restrictive data requirements for application of each method. With the advent of methods that are broadly applicable in that they do not require identification of a specific unmeasured confounder\u2014along with publicly available code for implementation\u2014roadblocks toward broader use of sensitivity analyses are decreasing. To spur greater application, here we offer a good practice guidance to address the potential for unmeasured confounding at both the design and analysis stages, including framing questions and an analytic toolbox for researchers. The questions at the design stage guide the researcher through steps evaluating the potential robustness of the design while encouraging gathering of additional data to reduce uncertainty due to potential confounding. At the analysis stage, the questions guide quantifying the robustness of the observed result and providing researchers with a clearer indication of the strength of their conclusions. We demonstrate the application of this guidance using simulated data based on an observational fibromyalgia study, applying multiple methods from our analytic toolbox for illustration purposes.<\/jats:p>","DOI":"10.1002\/pst.2457","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T12:25:14Z","timestamp":1733315114000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Real Effect or Bias? Good Practices for Evaluating the Robustness of Evidence From Comparative Observational Studies Through Quantitative Sensitivity Analysis for Unmeasured Confounding"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8952-7738","authenticated-orcid":false,"given":"Douglas","family":"Faries","sequence":"first","affiliation":[{"name":"Real\u2010World Access and Analytics Eli Lilly &amp; Company  Indianapolis USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Statistics North Carolina State University  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Affairs Biostatistics CSL Behring  King of Prussia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Hazlett","sequence":"additional","affiliation":[{"name":"Departments of Statistics &amp; Data Science and Political Science University of California at Los Angeles  Los Angeles USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Stamey","sequence":"additional","affiliation":[{"name":"Department of Statistical Science Baylor University  Waco USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7703-707X","authenticated-orcid":false,"given":"Shu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Statistics North Carolina State University  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Statistics University of California Berkeley  Berkeley USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7131-562X","authenticated-orcid":false,"given":"Mingyang","family":"Shan","sequence":"additional","affiliation":[{"name":"Real\u2010World Access and Analytics Eli Lilly &amp; Company  Indianapolis USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Sheffield","sequence":"additional","affiliation":[{"name":"Value, Economics, and Outcomes Eli Lilly &amp; Company  Indianapolis USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0153-8286","authenticated-orcid":false,"given":"Nancy","family":"Dreyer","sequence":"additional","affiliation":[{"name":"Dreyer Strategies  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.7741"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-0069"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/19466315.2021.1883473"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.14960"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181f74493"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4053"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2017.08.3019"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz261"},{"issue":"6","key":"e_1_2_7_10_1","first-page":"467","article-title":"GRACE Principles: Recognizing High\u2010Quality Observational Studies of Comparative Effectiveness","volume":"16","author":"Dreyer N. A.","year":"2010","journal-title":"American Journal of Managed Care"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2013.12.011"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2016.22.10.1107"},{"key":"e_1_2_7_13_1","unstructured":"P.Velentgas N. A.Dreyer P.Nourjah S. R.Smith andM. M.Torchia \u201cDeveloping a Protocol for Observational Comparative Effectiveness Research: A User's Guide. Conducted Under Contract No. 290\u20102005\u20100035\u2010I. AHRQ Publication No. 12(13)\u2010EHC099. Rockville MD: Agency for Healthcare Research and Quality \u201d(2013)."},{"issue":"3","key":"e_1_2_7_14_1","first-page":"1","article-title":"Methods to Control for Unmeasured Confounding in Pharmacoepidemiology: An Overview","volume":"38","author":"Uddin M. J.","year":"2016","journal-title":"International Journal of Clinical Pharmacy"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2017.04.022"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4394"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-87959-8"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.7326\/M16-2607"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5117"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/rssb.12348"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyaa094"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2012.01475.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1515\/jci-2018-0007"},{"key":"e_1_2_7_24_1","unstructured":"M. B.Mathur L. H.Smith P.Ding andT. J.Van der Weele \u201cEvalue Package \u201d(2021) https:\/\/cran.r\u2010project.org\/web\/packages\/EValue\/index.html."},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/1536867X20909696"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6973"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/19345747.2015.1078862"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1604"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2012.10.012"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1996.10476713"},{"key":"e_1_2_7_31_1","unstructured":"R.Hebdon J.Stamey D.Kahle andX.Zhang \u201cUnmconf: Modeling With Unmeasured Confounding \u201dhttps:\/\/cran.r\u2010project.org\/web\/packages\/unmconf\/index.html."},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2019.1609973"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.2217\/cer.14.16"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyaa213"},{"issue":"6","key":"e_1_2_7_35_1","first-page":"1887","article-title":"Robust Causal Inference Using Directed Acyclic Graphs: The R Package \u2018Dagitty","volume":"45","author":"Textor J.","year":"2016","journal-title":"International Journal of Epidemiology"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2021.08.001"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz150"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2022.10.005"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.2064"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1200"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.03.37"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5925"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001528"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470316696"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0000000000000079"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/19466315.2021.1883475"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v051.i13"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-82673-4"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12561-022-09334-w"}],"container-title":["Pharmaceutical Statistics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pst.2457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T07:06:44Z","timestamp":1742713604000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pst.2457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,4]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/pst.2457"],"URL":"https:\/\/doi.org\/10.1002\/pst.2457","archive":["Portico"],"relation":{},"ISSN":["1539-1604","1539-1612"],"issn-type":[{"value":"1539-1604","type":"print"},{"value":"1539-1612","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,4]]},"assertion":[{"value":"2023-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2457"}}