Placebos and Principles: A Trial of Ondansetron

Special ethical concerns exist about the use of placebo controls. A placebo-controlled study must answer four questions: [1] Was any therapeutic intervention available that could be reasonably assumed to be less harmful than the placebo control? [2] Did the placebo control pose more than minimal risk to those patients? [3] Was the study designed in every way possible to minimize potential harm to the patients receiving placebo? [4] Were the patients fully and accurately informed of the additional risk of being in the placebo group?

By answering these questions, the author evaluates a study comparing oral ondansetron to placebo for cancer patients receiving emetogenic chemotherapy.

Nausea and vomiting caused by toxic chemotherapeutic agents may compromise effective therapy. Uncontrolled nausea and vomiting not only result in discomfort and distress but may also lead to dehydration and poor compliance with subsequent chemotherapy [1]. The introduction of ondansetron (Zofran; GR38032F) into medical practice marked a major advance in the management of chemotherapy-induced emesis. Ondansetron preferentially antagonizes the 5-hydroxytryptamine₃ (serotonin) receptor at peripheral and central sites [2]. Data from clinical trials support ondansetron as the antiemetic agent of choice in preventing acute cisplatin-induced emesis. Four previous studies have compared ondansetron to high-dose metoclopramide (Reglan) for emesis [3-6]. An analysis of these studies indicates that ondansetron provides better control of nausea and vomiting than metoclopramide during the first 24 hours after cisplatin therapy. Additionally, ondansetron has fewer and milder side effects than does metoclopramide.

In this issue of Annals, Beck and colleagues [7] report a randomized, double-blind study comparing 1 mg, 4 mg, and 8 mg of oral ondansetron to placebo in patients given cyclophosphamide (Cytoxan)-based chemotherapy for the first time. Of 349 patients, 174 also received ≥ 35 mg/m² of doxorubicin (Adriamycin), including 52 on …