Informed consent for early-phase clinical trials: therapeutic misestimation, unrealistic optimism and appreciation
Original research
Jodi Halpern, David Paolo, Andrew Huang
BMJ, 12 June 2019
Abstract
Unrealistic therapeutic beliefs are very common—the majority of patient-subjects (up to 94%) enrol in phase 1 trials seeking and expecting significant medical benefit, even though the likelihood of such benefit has historically proven very low. The high prevalence of therapeutic misestimation and unrealistic optimism in particular has stimulated debate about whether unrealistic therapeutic beliefs in early-phase clinical trials preclude adequate informed consent. We seek here to help resolve this controversy by showing that a crucial determination of when such therapeutic beliefs are ethically problematic turns on whether they are causally linked and instrumental to the motivation to participate in the trial. Thus, in practice, it is ethically incumbent on researchers to determine which understanding and beliefs lead to the participant’s primary motivation for enrolling, not to simply assess understanding, beliefs and motivations independently. We further contend that assessing patient-subjects’ appreciation as a component of informed consent—it is already an established component of decision-making capacity assessments—can help elucidate the link between understanding-beliefs and motivation; appreciation refers to an individual’s understanding of the personal significance of both the medical facts and the experience of trial participation. Therefore, we recommend that: (1) in addition to the usual question, ‘Why do you want to participate in this trial?’, all potential participants should be asked the question: ‘What are you giving up by participating in this trial?’ and (2) researchers should consider the settings in which it may be possible and practical to obtain ‘two-point consent’.

Informed Consent Issues for Cell Donors
Methods in Molecular Biology book series
Insoo Hyun
Chimera Research, 8 June 2019; pp 67-74
Abstract
Stem cell-based chimera research depends on the free and voluntary provision of human biomaterials necessary for the derivation of pluripotent stem cell lines. Informed consent requirements for the procurement of human embryos, gametes, and somatic cells must take into account unique features of biomedical research involving the use of immortal cell lines that carry their donors’ genetic information. The extent and basis for donors’ rights, including the right to withdraw from research, are explored here in detail.

Parents’ and clinicians’ views on conducting paediatric diagnostic test accuracy studies without prior informed consent: qualitative insight from the Petechiae in Children study (PiC)
Original Article
Thomas Waterfield, Mark D Lyttle, Michael Shields, Derek Fairley, Damian Roland, James McKenna, Kerry Woolfall
BMJ, 7 June 2019
Abstract
Objective 
The Petechiae in Children (PiC) study assesses the utility of presenting features and rapid diagnostic tests in the diagnosis of serious bacterial infection in feverish children with non-blanching rashes. An embedded qualitative study explored parents’ and clinicians’ views on the acceptability of the PiC study, including the use of research without prior consent (RWPC) in studies of diagnostic test accuracy.
Design 
Semistructured qualitative interviews. Analysis was thematic and broadly interpretive, informed by the constant comparative approach.
Participants 
Fifteen parents were interviewed 55 (median) days since their child’s hospital attendance (range 13–95). Five clinicians involved in recruitment, and consent were interviewed.
Results 
Parents and clinicians supported RWPC for the PiC study and future emergency paediatric diagnostic test accuracy studies as long as there is no harm to the child and emergency care is not delayed. Parents and clinicians made recommendations around the timing and conduct of a consent discussion, which were in line with RWPC guidance. Parents enrolled in the PiC study preferred a design that included consent discussions with the research team over the alternative of ‘opt-out’ consent only.
Conclusions 
This embedded qualitative study demonstrates that RWPC is appropriate for use in paediatric emergency studies of diagnostic test accuracy and that the approach used in PiC was appropriate. Future diagnostic studies involving additional invasive procedures or an opt-out only approach to consent would benefit from exploring parent and clinician views on acceptability at the pretrial stage.