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June 7, 2000

Improving the Conduct and Reporting of Clinical Trials

Author Affiliations

Phil B.FontanarosaMD, Deputy EditorIndividualAuthorStephen J.LurieMD, PhD, Contributing EditorIndividualAuthor

JAMA. 2000;283(21):2787-2790. doi:10.1001/jama.283.21.2787

To the Editor: In attempting to perform a meta-analysis comparing fluconazole with amphotericin B in neutropenic cancer patients, Drs Johansen and Gøtzsche1 encounted several issues in the drug development process. I wish to comment on 3 of their concerns.

First, the authors question the effectiveness of oral amphotericin B and nystatin as antifungal agents. We agree with their assessment that these agents do not have a role in the treatment of serious systemic fungal infections. In the prophylactic studies described, the intent was to prevent fungal colonization and subsequent infections in high-risk, neutropenic patients with cancer. At the time these studies were conducted in the 1980s and early 1990s, recognized prophylactic antifungal regimens for selective bowel decontamination were oral amphotericin B or nystatin.2 As a result, the medical community deemed a trial of the oral polyenes against the new antifungal agent fluconazole worthwhile and scientifically relevant. Data supporting the use of fluconazole for treatment of systemic fungal infections are based on well-designed treatment studies,3 not the prophylactic studies included in the meta-analysis.

Second, the authors question the clinical trial process. Pfizer is committed to the principles of the International Conference on Harmonisation's (ICH's) 1997 Guideline for Good Clinical Practice4 that ensure the rights of patients in clinical research, and we observe these principles as part of our core values. Pfizer continues to introduce new drugs that benefit patients with serious illnesses. As part of an evolution of the conduct and reporting of clinical trials, Pfizer now requests investigators to report the results of multicenter studies as a group and not by individual sites. Pfizer agrees with the authors' concerns about study data retention, and requires that investigators retain their data from clinical trials according to the ICH Guideline for Good Clinical Practice.

Third, meta-analyses are useful if they are done using well-matched clinical trial designs. Without such defined entry criteria, meta-analyses cannot adequately synthesize complex underlying clinical issues, and thus should not be used to indict research hypotheses.

Johansen  HKGøtzsche  PC Problems in the design and reporting of trials of antifungal agents encountered during meta-analysis.  JAMA. 1999;282:1752-1759.Google Scholar
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