Realities of Phase I Clinical Trials May Not Match Patient Expectations

More than 80% of patients referred for consideration in a phase I clinical trial were still willing to participate after a consultation where they learned more about trial participation, according to the results of a single-center prospective study. However, almost one-half of patients predicted tumor shrinkage as a result of participating in the phase I clinical trial, a much higher percentage than what is typically seen in these trials. The results of this study were published in Cancer.

“These rates conflict with the typical phase I response rates of 4% to 20%, and this discrepancy demonstrates the challenges facing patients and healthcare professionals during their interactions in phase I studies,” wrote Saoirse O. Dolly, MBBS, PhD, of Royal Marsden NHS Foundation Trust in London, and colleagues.

Phase I trials are designed to determine a recommended drug dose and schedule, and to discover more about a drug’s potential toxicity. According to the study, in order to determine the best dose, patients participating in these phase I trials often receive subtherapeutic doses of the drug with little chance of efficacy, or high doses of the drug with excess toxicity. For these reasons, phase I trials are often restricted to patients with advanced disease and few other treatment options.

With this study, Dolly and colleagues explored patients’ motivations and perceptions related to phase I trial participation. Participants completed a questionnaire before (n = 396) and after (n = 301) a trial participation consultation.

Eighty-four percent of participants ranked the possibility of tumor shrinkage as the most important motivation for trial participation; 56% listed the fact that there were no alternative treatments, 44% listed physician recommendations, 38% listed the fact that the research might benefit others, and 24.4% listed family wishes.

“This highlights the fact that patients view phase I studies as an extension of previous conventional anticancer treatment,” the researchers wrote. “Phase I candidates tend to have better physical health and quality of life than those receiving best supportive care, and this may reflect on the higher expectation of a therapeutic benefit, as seen previously.”

When participants were asked about the potential for personal benefit from participation, 42.7% predicted tumor shrinkage. However, this number increased to 46.8% after the consultation. Fourteen percent of participants expected a cure from the phase I trial.

“It is tempting to interpret this as patient misinterpretation of previous discussions with healthcare professionals or a lack of information provided to patients throughout their cancer journey and to conclude that as a result we should inform our patients better,” the researchers wrote. “An alternative explanation is that this subset of patients, despite having been exposed to this information, have chosen to maintain unrealistic hope.”

Looking at the potential risks of participating in a phase I trial, 70.7% of participants expected moderate side effects and 49.7% of participants did not anticipate the need for weekly visits. However, after the consultation, significantly more participants (93%) understood that weekly visits would be necessary as part of the phase I trial participation.

Compared with before the consultation, significantly more participants wanted to enter a phase I trial after the consultation (71.5% vs 84.3%; P < .001).