 |
|
Potential for Conflict of Interest in the Evaluation of Suspected Adverse Drug Reactions
Use of Cerivastatin and Risk of Rhabdomyolysis
Bruce M. Psaty, MD, PhD;
Curt D. Furberg, MD, PhD;
Wayne A. Ray, PhD;
Noel S. Weiss, MD, DrPH
JAMA. 2004;292:(doi:10.1001/jama.292.21.2622).
Context In recent years, US patients have increasingly been the first to receive new medications, some of which are subsequently discovered to have suspected adverse drug reactions (SADRs). As a result, the challenge of early detection has largely shifted to the US postmarketing systems.
Objective To review the association between the use of cerivastatin sodium and the risk of rhabdomyolysis in an effort to illustrate the operation and limitations of the current US postmarketing safety-surveillance system.
Data Sources and Selection For the published literature, we used previous reviews and MEDLINE searches from all years through 2003. For the unpublished literature, we used internal company documents that have become part of the public record during a trial in Nueces County, Texas.
Data Synthesis In the published literature, cerivastatin was associated with much larger risks of rhabdomyolysis than other statins. Although only a small percentage of cerivastatin users also took gemfibrozil, approximately half of the case reports of rhabdomyolysis occurred in users of this combination therapy, and a cerivastatin-gemfibrozil interaction was supported by the results of a 3-day pharmacokinetic study. In internal company documents, multiple case reports suggested a drug-drug interaction within approximately 100 days of the launch in 1998; however, the company did not add a contraindication about the concomitant use of cerivastatin and gemfibrozil to the package insert for more than 18 months. Unpublished data available in July 1999 also suggested an increased risk of rhabdomyolysis associated with high doses of cerivastatin monotherapy. In late 1999 and early 2000, company scientists conducted high-quality analyses of the US Food and Drug Administration adverse event reporting system data. These analyses suggested that compared with atorvastatin calcium, cerivastatin monotherapy substantially increased the risk of rhabdomyolysis. To our knowledge, these findings were not disseminated or published. The company continued to conduct safety studies, some of them inadequately designed to assess the risk of rhabdomyolysis, until cerivastatin was removed from the market in August 2001.
Conclusions Despite limitations of the available data, the asymmetry between the information available to the company and the information available to patients and physicians seems striking. A subjective element is present in the effort to infer whether or not the occurrence of untoward outcomes in users of a particular drug was actually the consequence of the use of that drug, and, under the current system, a pharmaceutical company’s appraisal of SADRs may be influenced by economic considerations. Such an appraisal would best be made by an independent group. The US Congress should mandate and provide adequate support for independent reviews and analysis of postmarketing data.
Author Affiliations: Cardiovascular Health Research Unit, Departments of Medicine (Dr Psaty), Epidemiology (Drs Psaty and Weiss), and Health Services (Dr Psaty), University of Washington, Seattle; Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (Dr Furberg); and Vanderbilt University School of Medicine and the Geriatric Research, Education, and Clinical Center, Nashville Veteran’s Administration Medical Center, Nashville, Tenn (Dr Ray).
RELATED ARTICLES
Incidence of Hospitalized Rhabdomyolysis in Patients Treated With Lipid-Lowering Drugs
David J. Graham, Judy A. Staffa, Deborah Shatin, Susan E. Andrade, Stephanie D. Schech, Lois La Grenade, Jerry H. Gurwitz, K. Arnold Chan, Michael J. Goodman, and Richard Platt
JAMA. 2004;292(21):2585-2590.
ABSTRACT
| FULL TEXT
Potential for Conflict of Interest in the Evaluation of Suspected Adverse Drug Reactions: A Counterpoint
Brian L. Strom
JAMA. 2004;292(21):2643-2646.
EXTRACT
| FULL TEXT
Postmarketing Surveillance—Lack of Vigilance, Lack of Trust
Phil B. Fontanarosa, Drummond Rennie, and Catherine D. DeAngelis
JAMA. 2004;292(21):2647-2650.
EXTRACT
| FULL TEXT
Bayer’s Response to "Potential for Conflict of Interest in the Evaluation of Suspected Adverse Drug Reactions: Use of Cerivastatin and Risk of Rhabdomyolysis"
Joseph D. Piorkowski, Jr
JAMA. 2004;292(21):2655-2657.
EXTRACT
| FULL TEXT
Authors’ Reply to Bayer’s Response to "Potential for Conflict of Interest in the Evaluation of Suspected Adverse Drug Reactions: Use of Cerivastatin and Risk of Rhabdomyolysis"
Bruce M. Psaty, Curt D. Furberg, Wayne A. Ray, and Noel S. Weiss
JAMA. 2004;292(21):2658-2659.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Congress Responds to the IOM Drug Safety Report In Full
Psaty and Korn
JAMA 2007;298:2185-2187.
FULL TEXT
FDA Responds to Institute of Medicine Drug Safety Recommendations--In Part
Psaty and Charo
JAMA 2007;297:1917-1920.
FULL TEXT
Risks Associated With Statin Therapy: A Systematic Overview of Randomized Clinical Trials
Kashani et al.
Circulation 2006;114:2788-2797.
ABSTRACT
| FULL TEXT
The FDA and drug safety: a proposal for sweeping changes.
Furberg et al.
Arch Intern Med 2006;166:1938-1942.
ABSTRACT
| FULL TEXT
An educational intervention to improve physician reporting of adverse drug reactions: a cluster-randomized controlled trial.
Figueiras et al.
JAMA 2006;296:1086-1093.
ABSTRACT
| FULL TEXT
Statin-Induced Myopathy: The Two Faces of Janus
Arora et al.
J CARDIOVASC PHARMACOL THER 2006;11:105-112.
ABSTRACT
Evaluating Drug Effects in the Post-Vioxx World: There Must Be a Better Way
Avorn
Circulation 2006;113:2173-2176.
FULL TEXT
Spending on postapproval drug safety.
Ridley et al.
Health Aff (Millwood) 2006;25:429-436.
ABSTRACT
| FULL TEXT
Medication-Attributed Adverse Effects in Placebo Groups: Implications for Assessment of Adverse Effects
Rief et al.
Arch Intern Med 2006;166:155-160.
ABSTRACT
| FULL TEXT
Reform of Drug Regulation -- Beyond an Independent Drug-Safety Board
Ray and Stein
NEJM 2006;354:194-201.
FULL TEXT
The Food and Drug Administration's Deliberations on Antidepressant Use in Pediatric Patients
Leslie et al.
Pediatrics 2005;116:195-204.
ABSTRACT
| FULL TEXT
Challenges in Systematic Reviews That Assess Treatment Harms
Chou and Helfand
ANN INTERN MED 2005;142:1090-1099.
ABSTRACT
| FULL TEXT
Could It Happen Again?: The Bjork-Shiley Convexo-Concave Heart Valve Story
Blackstone
Circulation 2005;111:2717-2719.
FULL TEXT
The Research on Adverse Drug Events and Reports (RADAR) Project
Bennett et al.
JAMA 2005;293:2131-2140.
ABSTRACT
| FULL TEXT
Safety in Numbers -- Monitoring Risk in Approved Drugs
Okie
NEJM 2005;352:1173-1176.
FULL TEXT
Post-Marketing Drug Safety: Keep Patients Your Priority
Dugdale
DOC News 2005;2:3-3.
FULL TEXT
An Underrecognized Challenge in Evaluating Postmarketing Drug Safety
Roden
Circulation 2005;111:246-248.
FULL TEXT
Statins and Rhabdomyolysis -- Clinical Data, Health Policy, and Politics
JWatch General 2005;2005:2-2.
FULL TEXT
Potential for Conflict of Interest in the Evaluation of Suspected Adverse Drug Reactions: A Counterpoint
Strom
JAMA 2004;292:2643-2646.
FULL TEXT
Postmarketing Surveillance--Lack of Vigilance, Lack of Trust
Fontanarosa et al.
JAMA 2004;292:2647-2650.
FULL TEXT
|
