To report or not to report: Exploring healthy volunteers' rationales for disclosing adverse events in Phase I drug trials

Abstract

Background: Phase I trials test the safety and tolerability of investigational drugs and often use healthy volunteers as research participants. Adverse events (AEs) are collected in part through participants' self-reports of any symptoms they experience during the trial. In some cases, experiencing AEs can result in trial participation being terminated. Because of the economic incentives underlying their motivation to participate, there is concern that healthy volunteers routinely fail to report AEs and thereby jeopardize the validity of the trial results. Methods: We interviewed 131 U.S. healthy volunteers about their experiences with AEs, including their rationales for reporting or failing to report symptoms. Results: We found that participants have three primary rationales for their AE reporting behavior: economic, health-oriented, and data integrity. Participants often make decisions about whether to report AEs on a case-by-case basis, evaluating what effects reporting or not reporting might have on the compensation they receive from the trial, the risk to their health, and the results of the particular clinical trial. Participants' interpretations of clinic policies, staff behaviors, and personal or vicarious experiences with reporting AEs also shape reporting decisions. Conclusions: Our findings demonstrate that participants' reporting behavior is more complex than previous portraits of healthy volunteers have suggested. Rather than finding participants who were so focused on the financial compensation that they were willing to subvert trial results, our study indicates that participants are willing in most cases to forgo their full compensation if they believe not reporting their symptoms jeopardizes their own safety or the validity of the research.

KEYWORDS:

• clinical trials
• healthy volunteers
• adverse event reporting
• scientific validity
• financial motivation

Conflicts of interest

None.

Acknowledgments

Additional members of the HealthyVOICES research team made this article possible by conducting interviews, verifying the accuracy of the transcripts, and coding the transcripts.

Ethical approval

This study was approved by the Biomedical Institutional Review Board at the University of North Carolina at Chapel Hill.

Author contributions

JAF conceived of and designed the larger longitudinal study. JAF (and other non-author research team members) conducted the interviews. JAF and LM (and other non-author research team members) coded the transcripts. JAF and LM conceived of article topic. LM analyzed the data. LM wrote the first draft of the article. Both authors contributed to article editing and revision.

Notes

¹ In total, 180 participants were recruited to the larger study. As part of the design of this study, 20% of participants were randomized to a control group so that we could assess whether involvement in our study affected healthy volunteers' perceptions of or participation in Phase I trials. Participants in the control group were interviewed only at recruitment and 3 years after enrollment. After randomization, 34 participants were in the control group and 146 were in the full-participation group. At the time of the 1-year interviews (the data used in this article), we had removed one participant from the study, three participants voluntarily withdrew, and 11 were lost to follow-up, leaving 131 (90% retention) in the full-participation group.

² Based on the qualitative data obtained through the semistructured interviews, it became apparent that participants appeared to vary in how they accounted for household income, with some participants only accounting for their personal income (regardless of household configuration) while others included income of spouses/partners, roommates, or parents.

³ All participant names used in this article are pseudonyms.