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Phil B.FontanarosaMD, Deputy EditorIndividualAuthorStephen J.LurieMD, PhD, Contributing EditorIndividualAuthor
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
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.
Panzer H. Improving the Conduct and Reporting of Clinical Trials. JAMA. 2000;283(21):2787–2790. doi:10.1001/jama.283.21.2787
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