This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (50)  • Contact me when this article is cited  Related Content  • Related letter  • Related article  • Similar articles in JAMA  Topic Collections  • Drug Therapy  • Adverse Effects  • Gastroenterology  • Liver/ Biliary Tract/ Pancreatic Diseases  • Alert me on articles by topic  Social Bookmarking   What's this?

David J. Graham, MD,MPH; Carol R. Drinkard, MPH,PhD; Deborah Shatin, PhD; Yi Tsong, PhD; Margaret J. Burgess

JAMA. 2001;286:831-833.

Context  Soon after initial marketing in March 1997, troglitazone, the first thiazolidinedione antidiabetic agent, was found to cause life-threatening acute liver failure. The drug was removed from the market in March 2000.

Objective  To evaluate the effect of US Food and Drug Administration (FDA) risk management efforts, including repeated labeling changes and "Dear Healthcare Professional" letters, on periodic liver enzyme monitoring of patients taking troglitazone.

Design, Setting, and Participants  Claims data from a large, multistate managed care organization were used to establish 4 cohorts of patients (N = 7603) with at least 90 days of health plan enrollment before first troglitazone prescription during 4 consecutive periods spanning April 1997 to September 1999 and representing 4 progressively stringent liver monitoring recommendations.

Main Outcome Measures  Percentage of eligible troglitazone users in each cohort with baseline, monthly (for up to 6 months of continuous use), and complete (baseline and monthly) enzyme monitoring, based on computerized records of laboratory claims.

Results  Baseline testing increased from 15% before any FDA monitoring recommendations (cohort 1) to 44.6% following 4 separate FDA interventions (cohort 4; P<.001). In cohort 4, 33.4% of users had follow-up testing after 1 month of therapy, falling to 13% after 5 months of continuous use. In all cohorts, less than 5% received all recommended liver enzyme tests by the third month of continuous use.

Conclusions  The FDA risk management efforts did not achieve meaningful or sustained improvement in liver enzyme testing. Evaluation of the impact of regulatory actions is needed before such actions can be regarded as effective or sufficient.

Author Affiliations: Office of Postmarketing Drug Risk Assessment (Dr Graham) and Office of Biostatistics (Dr Tsong), Center for Drug Evaluation and Research, US Food and Drug Administration, Rockville, Md; and Center for Health Care Policy and Evaluation, UnitedHealth Group, Minneapolis, Minn (Drs Drinkard and Shatin and Ms Burgess).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

RELATED LETTER

Sweeping Changes to Food and Drug Administration and Drug Safety Regulations
James T. Cross
Arch Intern Med. 2007;167(7):732.
EXTRACT | FULL TEXT  

RELATED ARTICLE

August 15, 2001
JAMA. 2001;286(7):863-864.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

A Randomized Trial of Electronic Clinical Reminders to Improve Medication Laboratory Monitoring
Matheny et al.
J. Am. Med. Inform. Assoc. 2008;15:424-429.
ABSTRACT | FULL TEXT  

Using population-based routine data for evidence-based health policy decisions: lessons from three examples of setting and evaluating national health policy in Australia, the UK and the USA
Morrato et al.
J Public Health (Oxf) 2007;29:463-471.
ABSTRACT | FULL TEXT  

Drug Safety Proposals And The Intrusion Of Federal Regulation Into Patient Freedom And Medical Practice
Gottlieb
Health Aff (Millwood) 2007;26:664-677.
ABSTRACT | FULL TEXT  

Sweeping Changes to Food and Drug Administration and Drug Safety Regulations
Cross
Arch Intern Med 2007;167:732-732.
FULL TEXT  

Improved therapeutic monitoring with several interventions: a randomized trial.
Feldstein et al.
Arch Intern Med 2006;166:1848-1854.
ABSTRACT | FULL TEXT  

Adherence to black box warnings for prescription medications in outpatients.
Lasser et al.
Arch Intern Med 2006;166:338-344.
ABSTRACT | FULL TEXT  

Reform of Drug Regulation -- Beyond an Independent Drug-Safety Board
Ray and Stein
NEJM 2006;354:194-201.
FULL TEXT  

Improving Laboratory Monitoring at Initiation of Drug Therapy in Ambulatory Care: A Randomized Trial
Raebel et al.
Arch Intern Med 2005;165:2395-2401.
ABSTRACT | FULL TEXT  

Missed Hypothyroidism Diagnosis Uncovered by Linking Laboratory and Pharmacy Data
Schiff et al.
Arch Intern Med 2005;165:574-577.
ABSTRACT | FULL TEXT  

Linking Laboratory and Pharmacy: Opportunities for Reducing Errors and Improving Care
Schiff et al.
Arch Intern Med 2003;163:893-900.
ABSTRACT | FULL TEXT