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Effects of Drug-Induced Liver Injury on Hepatology and the ... Effects of Drug-Induced Liver Injury on Hepatology and the ... Document Transcript

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  • Effects of Drug-Induced Liver Injury on Hepatology and the Practice of Medicine 3/28/01 Click here to start Table of Contents Author: William M. Lee, MD Effects of Drug-Induced Liver Injury on Hepatology and the Practice of Medicine Impact of Drug-Induced Liver Injury on the Public Where Drugs Fit In The Liver Works Very Well Too Well? Why Is Rarity a Problem? Hard to study/hard to define Is anything wrong with approval process? The Doctor’s Dilemma Physician’s Information Sources What Clinicians Face PPT Slide Possible solutions Ways of improving surveillance DILI Study (pilot phase)
  • PPT SlideDILI Study (phase 2)SummarySummary II
  • Effects of Drug-Induced Liver Injury on Hepatology and thePractice of Medicine William M. Lee, MD Department of Internal Medicine University of Texas Southwestern Medical Center at Dallas Next slide Back to first slide View graphic version
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  • Impact of Drug-Induced Liver Injury on the Public ● Rare reactions but severe, often fatal ● Little data available re: true incidence ● Who is to blame? ● What do clinicians want? ● What does the public deserve?Previous slide Next slide Back to first slide View graphic version
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  • Summary II Education of physicians is vital ● CME offerings ● Availability of information: Epocrates, Medline ● Other uses of technology possible ● Allows physicians to get back to “Do no harm” ● ● ●Previous slide Back to first slide View graphic version
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  • Where Drugs Fit In Main thrust of current medical care is prescribing ● 200 billion dollar industry annually ● Pharmacotherapy impacts lives incrementally ● Rare reactions impact lives more dramaticallyPrevious slide Next slide Back to first slide View graphic version
  • Summary Physicians share responsibility with pharmaceutical companies and FDA for drug reactions ● Clinicians want no trouble (do no harm to themselves) ● But they don’t help by providing the information they themselves need (case reports the exception) ● Improved surveillance will not come from physicians ● Academic physicians have the intrinsic motivation ● Nationwide surveillance system should be consideredPrevious slide Next slide Back to first slide View graphic version
  • The Liver Works Very Well Too Well? ● We trust the liver implicitly ● Metabolizes many drugs simultaneously ● So we are doubly surprised when it acts up! ● The rarity of drug reactions and their severity is the problem ● Physicians trust the liver as patients doPrevious slide Next slide Back to first slide View graphic version
  • Why Is Rarity a Problem? Hard to study/hard to define ● Cannot plan for it ● Cannot recognize it when it comes ● It is catastrophic, like an aneurysm ● Compares to other natural disasters ● But drug-reactions are iatrogenic!Previous slide Next slide Back to first slide View graphic version
  • Is anything wrong with approval process? ● FDA under pressure to approve drugs ● Approval process has been under attack (7 drugs withdrawn since ‘93) ● Patients apply pressure (for approval) as well ● FDA must serve as gatekeeper/wise fatherPrevious slide Next slide Back to first slide View graphic version
  • The Doctor’s Dilemma “First, do no harm” ● Be very cautious and not use new drugs ● Be more bold and try new agents without waiting ● Read as much as you can, the data is still not there!Previous slide Next slide Back to first slide View graphic version
  • Physician’s Information Sources ● Medical school/residency teaching ● Practice experience ● PDR ● Drug Ads/Reps ● Reading the literature--case reports! ● News mediaPrevious slide Next slide Back to first slide View graphic version
  • What Clinicians Face Loss of independence/time & financial pressure ● Much pressure to prescribe new drugs ● No physician can keep up with all rare reactions/interactions (PDR is hard to read) ● Current surveillance system is inadequate ● But physicians rarely contribute to MedWatch!Previous slide Next slide Back to first slide View graphic version
  • PPT Slide Why post-marketing surveillance fails ● Failure to recognize ‘hepatitis’ as drug-induced ● If drug is stopped, why report? ● Concern about malpractice/adverse outcome ● Withdrawal with increase ALT’s=assumed trivial ● Meant to, just ran out of time/energy/forgot ● Inadequate clinical information/timing/ concomitant drug use/exclusion of other etiologiesPrevious slide Next slide Back to first slide View graphic version
  • Possible solutions Do we need legislation to make it happen? ● More stringent drug testing before release ● Active post-marketing surveillance ● Post-marketing studies ? ● More readily accessible drug information ● Better physician post-graduate educationPrevious slide Next slide Back to first slide View graphic version
  • Ways of improving surveillance ● Monitor actively at academic medical centers ● Monitor through HMO databases ● Continue passive system with incentives ● Revise notification (black box) system ● Technology should help (e.g., Epocrates)Previous slide Next slide Back to first slide View graphic version
  • DILI Study (pilot phase) Retrospective analysis of 300 cases of severe liver injury (SLI) at 6 academic centers ● Cases accrued through medical records analysis/coding/abnormal lab values ● Case report forms developed ● Criteria for SLI (Bili > 10, INR > 1.5) less strict than for acute liver failure ● Case control format vs. panel of expertsPrevious slide Next slide Back to first slide View graphic version
  • PPT Slide Severe Liver Injury Cases DILI study; n = 230Previous slide Next slide Back to first slide View graphic version
  • DILI Study (phase 2) Prospective analysis of severe liver injury at a larger number of academic centers ● Provide data on all forms of hepatitis ● Attribution an issue: causality assessment methods are not foolproof ● Would serve as an early warning system ● Limitation: academic centers onlyPrevious slide Next slide Back to first slide View graphic version