Patients who chose to participate in a phase I oncology study experienced less decisional conflict and perceived experimental therapy as more beneficial than patients who declined participation. In particular, accepters reported feeling more informed, having greater clarity about their values, and feeling more support and less pressure from others in the decision-making process. Accepters also reported feeling more certain about their decision and feeling that they had made a more effective decision.
DCS scores of similar level are associated with other difficult medical decisions. For example, the distribution of DCS scores in our study was similar to the distribution of scores among patients with severe chronic obstructive pulmonary disease who had decided with the help of a decision aid whether to receive mechanical ventilation (Dales et al. 1999
), a decision that involves substantial tradeoffs of quantity and quality of life. Similar scores were also found among postmenopausal women who had decided with the help of a decision aid whether to take hormone replacement therapy (Clark et al. 2003
) at a time when conflicting evidence about the risks of hormone replacement was attracting considerable attention. In contrast, patients facing less complex, less risky medical decisions have lower DCS scores than participants in our study. For example, patients who had decided with the help of a decision aid whether to pre-donate autologous blood before heart surgery had lower DCS scores than patients in the present study (Laupacis et al. 2006
). Here the risks and benefits are well described and the tradeoffs are not so difficult. Similarly, men who had decided to undergo vasectomy, a procedure with well-characterized risks and benefits, had lower DCS scores than patients in our study (Balde et al. 2006
). These comparisons suggest that the complexity of the decision and outcome uncertainties, rather than the severity of disease, create decisional conflict.
There has been limited research involving patients' decisions to enroll in phase I oncology clinical trials. Previous research found that patients who agreed to enroll in phase I trials reported being well-informed about their alternatives, understanding the risks and benefits of participation, and not experiencing coercive pressure to enroll in a trial (Agrawal et al. 2006
). However, this report only included patients who agreed to enroll in a phase I trial. In the present study, which included both accepters and decliners, we found that patients who declined to enroll in a phase I trial felt less informed and less clear in their personal values than did patients who agreed to enroll. Decliners reported having less support in the decision-making process and feeling greater pressure to make a decision. Furthermore, decliners perceived more risk than benefit from experimental therapy, whereas accepters reported the opposite perception.
Although we would expect personal uncertainty about the decision to participate in experimental therapy to be related to perceptions of risk and benefit about therapies, the correlations between the Uncertainty subscale and participants' perceived risk-benefit ratios were weak. This finding cannot be explained by a lack of variation in the measures, both of which show adequate variability, or by a lack of reliability in the Uncertainty subscale, because its reliability is also acceptable.
Better understanding of the differences between accepters and decliners would help to inform the bioethical significance of our findings. One possible interpretation is that decliners had higher DCS scores because they lacked understanding about the benefits and risks of participation and had less clarity about their personal values, whereas accepters had lower scores because they understood the risks and benefits and had greater clarity. In this scenario, there might be an ethical concern about decliners, because they may not have had appropriate decision-making support.
However, a different interpretation would stem from the observation that for phase I studies there is often no reliable information about benefits and risks, especially for studies of agents never before used in humans. From this perspective, an alternative interpretation of our findings is that decliners had higher DCS scores (particularly on the Informed and Values Clarity subscales) because they appreciated the real uncertainty about risks and benefits in phase I trials. In contrast, accepters reported understanding the potential risks and benefits of something for which risks and benefits are uncertain. This interpretation would indicate a problem with the quality of informed consent for patients who agree to enroll in phase I studies.
It is also possible that accepters understand the uncertainties inherent in phase I studies but agree to participate because of the high value they place on the chance of benefit (Agrawal et al. 2006
; Rasiel et al. 2005
; Weinfurt 2007
). Indeed, the absolute value of the difference between the perceived chance of benefit for standard and experimental therapies was nearly twice as high for accepters compared to decliners (p
< 0.001) (). Admitting uncertainty about a choice just made would generate cognitive dissonance (Festinger 1957
), so people may adjust their beliefs after making a decision to be more consistent with the decision they made. For example, voters leaving a polling place speak more positively about their favored candidate than do voters waiting in line to vote (Frenkel and Doob 1976
). In the case of patients enrolling in phase I trials, the fact of having made the decision might influence accepters to downplay doubts about how well they were informed and how clear were their values. Accepters' lower DCS scores would result, therefore, from an effort to minimize inconsistencies between beliefs (“I have great uncertainty regarding possible side effects, and this experimental therapy is unlikely to help me.”) and actions (enrolling in the study). If lower reported decisional conflict is a product of patients' efforts to reduce cognitive dissonance, it is not clear that this scenario would present an ethical concern. This interpretation of the findings would simply mean that we do not have direct access to patients' perceptions at the time their decisions are made, but only to the possibly modified beliefs of patients who are motivated to maintain consistency between past actions and present beliefs.
Our study has several limitations. First, although we found moderate differences in decisional conflict between patients who did and did not decide to enroll in a phase I trial, whether these differences reflect a problem with the informed consent process is not clear, because there are multiple possible reasons for our findings. Second, our measures of perceived chance of benefit and risk from standard and experimental therapies have not been formally validated, though they were pilot-tested and have been used previously (Meropol et al. 2003
). Third, recall bias may have been an issue, because the participants reported on their decisional conflict and perceived chance of benefits and risks of the therapies after their decision had been made. However, this type of bias, if present, would likely be systematic and should not affect our results. Finally, since patients uninterested in trial participation may seek care outside the types of academic medical centers where this study was conducted, the participation rate may be higher for accepters than decliners.