Trust in early phase research: therapeutic optimism and protective pessimism.
ABSTRACT Bioethicists have long been concerned that seriously ill patients entering early phase ('phase I') treatment trials are motivated by therapeutic benefit even though the likelihood of benefit is low. In spite of these concerns, consent forms for phase I studies involving seriously ill patients generally employ indeterminate benefit statements rather than unambiguous statements of unlikely benefit. This seeming mismatch between attitudes and actions suggests a need to better understand research ethics committee members' attitudes toward communication of potential benefits and risks of early phase studies to potential subjects. We surveyed the members of two U.S. research ethics committees using a phase I gene transfer study scenario, and compared the results to a previous survey of potential subjects' perceptions and attitudes toward benefit and risk for the same protocol. The results show that there is indeed a gap between the subjects' perceptions and the committee members' views on what is appropriate to be communicated to research subjects. This discrepancy is the product of both the commonly assumed optimism of the subjects and to a "protective pessimism" of the research ethics committee members. We discuss this discrepancy using "frameworks of trust" and demonstrate the need to incorporate these frameworks into the existing model of informed consent.
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ABSTRACT: Purpose:Ocular gene transfer clinical trials are raising patient hopes for the treatment of choroideremia - a blinding degenerative retinopathy. Phase I choroideremia gene transfer trials necessitate communicating about the risks of harm and potential benefits with patients while avoiding the sensationalism that has historically undermined this field of translational medicine.Methods:We conducted interviews between June 2011 and June 2012 with 6 choroideremia patient advocates, 20 patients, and 15 clinicians about their hopes for benefits, perceived risks of harm, and hopes for the time frame of clinical implementation of choroideremia gene transfer.Results:Despite the safety focus of phase I trials, participants hoped for direct visual benefits with evident discrepancies between stakeholder perspectives about the degree of visual benefit. Clinicians and patient advocates were concerned by limited patient attention to risks of harm. Interviews revealed confusion about the time frames for the clinical implementation of choroideremia gene transfer and patient urgency to access gene transfer within a limited therapeutic window.Conclusion:Differences in stakeholder perspectives about choroideremia gene transfer necessitate strategies that promote responsible communications about choroideremia gene transfer and aid in its translation. Strategies should counter historical sensationalism associated with gene transfer, promote informed consent, and honor patient hope while grounding communications in current clinical realities.Genet Med advance online publication 19 September 2013Genetics in Medicine (2013); doi:10.1038/gim.2013.148.Genetics in medicine: official journal of the American College of Medical Genetics 09/2013; DOI:10.1038/gim.2013.148 · 3.92 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.