Cefepimeは死亡率を増やすか？(1)のつづきです。FDAから警告が出ています。
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Information for Healthcare Professionals: Cefepime (marketed as Maxipime)
FDA ALERT [06/17/2009]:
The purpose of this communication is to share information about the FDA’s continuing safety review about the potential increased mortality in patients treated with cefepime. Cefepime is a cephalosporin antibacterial and is a member of the β–lactam class of antibacterial drugs. Cefepime is currently approved for the treatment of a variety of infections due to susceptible strains of microorganisms.
FDA performed meta-analyses based on additional data beyond those included in the Yahav et al. publication. In the FDA analyses, no statistically significant increase in mortality was seen in cefepime-treated patients compared to comparator-treated patients.
Based on the results of FDA's meta-analyses, the FDA has determined that cefepime remains an appropriate therapy for its approved indications.
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FDAでデータを追加してメタ分析し直したところ、死亡率増加は有意ではなかったとのことです。Yahavらの38試験に加えて50の試験を追加して解析しています。
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FDA Analyses: The FDA performed meta-analyses based on both trial-1 and patient-level 2data. Data were derived from all available cefepime comparative clinical trials with evaluable data available to the FDA. In order to include trials in which there were no deaths in both treatment groups, the FDA used the Mantel-Haenszel risk difference method stratified by trial to estimate the risk of mortality in the trials—this is different from the risk ratio method used by Yahav et al.
Trial-level meta-analysis: The FDA’s trial-level meta-analysis included data from 88 clinical trials – the 38 trials that were included in the Yahav et al. meta-analysis, plus data from an additional 50 trials. These 88 trials included 9,467 cefepime-treated patients and 8,288 comparator-treated patients. No statistically significant difference in mortality was observed between cefepime and the comparators in the FDA trial-level meta-analysis.
All-cause mortality rates at 30-days post-therapy were 6.21% (588/9467) for cefepime-treated patients and 6.00% (497/8288) for comparator-treated patients with adjusted risk difference = 5.38 per 1000 population (95% C.I.: -1.53, 12.28).
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治療後30日以内の総死亡率はcefepime群6.21%、対照群6.00%で有意差なし、ということでした。
重大な副作用については安全性について自ら再検証し、迅速に発表するFDAの姿勢はすばらしいですね。
6月17日のFDA警告ではじめて、マキシピームで死亡率が増えるという論文が2007年に発表されていたことを知りました。製薬会社では情報を把握しているはずですが、ブリストル・マイヤーズのホームページにも情報が開示された形跡もありません。もちろん、死亡率に差がなかったという情報も、今日の時点で開示されていません。
このような害についての情報は、迅速に臨床医に届けられなければならなかったのではないでしょうか。これでいいのでしょうか。甚だ疑問です。