We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review |

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(21):2622-2631. doi:10.1001/jama.292.21.2622.
Text Size: A A A
Published online

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 For the unpublished literature, we used internal company documents that have become part of the public record during a trial in Nueces County, Texas.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 Unpublished data available in July 1999 also suggested an increased risk of rhabdomyolysis associated with high doses of cerivastatin monotherapy.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.

Conclusions Published online November 22, 2004 (doi:10.1001/jama.292.21.2622).

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

103 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
What are the Results?

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
What Are the Overall Quality and Limitations of the Evidence?