In July 2009 FDA Issues Updated Guidance For Industry Document Concerning DILI In Premarketing Clinical Evaluation
(Posted by Tom Lamb at DrugInjuryWatch.com)
In July 2009 the FDA issued a Guidance for Industry document intended for pharmaceutical companies developing new prescription drugs which explains how certain laboratory measurements obtained in clinical trials can be used to assess the new drug's potential to cause severe drug-induced liver injury (DILI). Further, this FDA document describes how these measurements can be evaluated so as to distinguish whether or not the new drug is "sending" so-called signals of potential severe liver injury.
Liver damage is the most frequent safety-related cause for pulling drugs from the market, according to this July 2009 Guidance for Industry document, "Drug-Induced Liver Injury: Premarketing Clinical Evaluation" from the FDA, which updates a draft version which was issued in 2007.
From the Introduction part of this Guidance document:
This guidance is intended to assist the pharmaceutical industry and other investigators who are conducting new drug development in assessing the potential for a drug to cause severe liver injury (i.e., irreversible liver failure that is fatal or requires liver transplantation). In particular, the guidance addresses how laboratory measurements that signal the potential for such drug-induced liver injury (DILI) can be obtained and evaluated during drug development. This evaluation is important because most drugs that cause severe DILI do so infrequently; typical drug development databases with up to a few thousand subjects exposed to a new drug will not show any cases. Databases may, however, show evidence or signals of a drug’s potential for severe DILI if the clinical and laboratory data are properly evaluated for evidence of lesser injury that may not be severe, but may predict the ability to cause more severe injuries. This guidance describes an approach that can be used to distinguish signals of DILI that identify drugs likely to cause severe liver injury from signals that do not suggest such a potential. This guidance does not address issues of preclinical evaluation for signals of DILI, nor the detection and assessment of DILI after drug approval and marketing. [footnote omitted]
This July 2009 Guidance for Industry document concludes with "Appendix A: Illustrative Examples of DILI", which includes a brief discussion about the regulatory history of Duract (bromfenac), Rezulin (troglitazone), and Exanta (ximelagatran), each of which were associated with drug-induced liver injury (DILI).