0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
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 ......
Special Communication |

Problems in the Design and Reporting of Trials of Antifungal Agents Encountered During Meta-analysis

Helle Krogh Johansen, MD, DMSc; Peter C. Gøtzsche, MD, DMSc
JAMA. 1999;282(18):1752-1759. doi:10.1001/jama.282.18.1752.
Text Size: A A A
Published online

Meta-analyses may become biased if the reported data in the individual trials are biased and if overlap among trials cannot be identified. We describe the unanticipated problems we encountered in collecting data for a meta-analysis comparing a new antifungal agent, fluconazole, with amphotericin B in patients with cancer complicated by neutropenia. In 3 large trials that comprised 43% of the patients identified for the meta-analysis, results for amphotericin B were combined with results for nystatin in a "polyene" group. Because nystatin is recognized as an ineffective drug in these circumstances, this approach creates a bias in favor of fluconazole. Furthermore, 79% of the patients were randomized to receive oral amphotericin B, which is poorly absorbed and not an established treatment, in contrast to intravenous amphotericin B, which was administered in 4 of 5 placebo-controlled trials, or 86% of patients. It was unclear whether there was overlap among the "polyene" trials, and it is possible that results from single-center trials were included in multicenter trial reports. We were unable to obtain information to clarify these issues from the trial authors or the manufacturer of fluconazole. Two of 11 responding authors replied that the data were with the drug manufacturer and two indicated that they did not have access to their data because of change of affiliation. In the meta-analyses, fluconazole and amphotericin B (mostly given orally) had similar effects (13 trials), whereas nystatin was no better than placebo (3 trials). Since individual trials are rarely conclusive, investigators, institutions, and pharmaceutical companies should provide essential details about their work to ensure that meta-analyses can accurately reflect the studies conducted and that patients will realize maximum benefits from treatments. We recommend that investigators keep copies of their trial data to help facilitate accurate and unbiased meta-analyses.

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

First Page Preview

View Large
First page PDF preview

Figures

Tables

References

CME
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.

Multimedia

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

Web of Science® Times Cited: 85

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

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

Articles Related By Topic
Related Collections
PubMed Articles
Jobs
brightcove.createExperiences();