Objective: This study aimed to understand how hope and motivation of patients considering phase I trial participation are affected by psychological factors such as coping strategies and locus of control (LoC) and general well-being as measured by the quality of life (QoL).Methods: An exploratory cross-sectional study was performed in patients with incurable cancer (N = 135) referred to our phase I unit for the first time. Patients were potentially eligible for phase I trial participation and participated in our study while deliberating phase I trial participation. We used questionnaires on hope, motivation to participate, coping, LoC, and QoL. To investigate the nature and magnitude of the relationships between the scales, a structural equation modeling (SEM) was fitted to the data.Results: Hope significantly predicted the motivation to participate in phase I trials. Predictors of hope were a combination of flexible and tenacious goal pursuit (both P < .01), internal LoC (P < .01), and QoL (P < .01). The SEM showed an exact fit to the data, using a null hypothesis significance test: chi-square (8) = 9.30, P = .32. Conclusions:Patients considering phase I trial participation seem to use a pact of tenacious and flexible coping and control to stay hopeful. Furthermore, hope and QoL positively affected each other. The psychological pact may promote an adaptation enabling them to adjust to difficult circumstances by unconsciously ignoring information, called dissonance reduction. This mechanism may impair their ability to provide a valid informed consent. We suggest including a systematic exploration of patients' social context and values before proposing a phase I trial. Patients may struggle to decide whether to engage in a treatment with unknown efficacy, benefit, and side effects, or to opt solely for symptom-oriented palliative care.2 During this deliberation, their mindset may help them deal with this choice by setting goals. 3Mindset represents people's personal attitudes that influence their goals and behavior. 4 Equally, physicians face the difficult decision whether to offer a phase I trial to their patients and how to answer patients' questions, not knowing whether the experiment is worthwhile. Additionally, when treatment options are sparse or not available, considering phase I trial participation may represent a health crisis. 21This crisis, facing a life-threatening situation, can trigger 2 modes of coping: tenacious goal pursuit (tenacity) and flexible goal adjustment (flexibility). 21 Patients who use tenacity try to modify their circumstances to fulfill their personal preferences. In contrast, patients who use flexibility adapt their personal preferences to the new situation.In both coping strategies, another psychological factor, the sense of control, can play a role.Locus of control (LoC) refers to the extent to which people believe their lives can be controlled by external factors (such as doctors) or internal factors (themselves). 22 One may assume that palliative patients with cancer, wh...

For advanced cancer patients deliberating early clinical trial participation, adequate information about expected effect on quality of life (HRQoL) and hope, may support decision making. The aim was to assess the potential relation of HRQoL to eligibility for phase-I trial participation, and to observe the variations in patient-reported outcomes. Patients completed questionnaires at preconsent (n = 124), baseline (n = 96), and after first evaluation of a phase-I trial (n = 76). The Mann-Whitney U test was used to test differences between eligible and ineligible patients. Univariate logistic regression was performed for eligibility. Factorial repeated-measures ANOVA compared the outcomes of patients continuing vs. stopping participation after first evaluation over time. Eligibility is associated with significant better global health OR = 0.946, 95% CI [0.918, 0.975], p = 0.001, physical functioning OR = 0.959, 95% CI [0.933, 0.985], p = 0.002, role functioning OR = 0.974, 95% CI [0.957, 0.991] and better appetite OR = 1.114 95% CI [1.035, 1.192]. HRQoL outcomes like global health, social functioning and appetite decline in all patients and differ between patients continuing or having to end participation. Over time, hope and tenacity decline in all patients and coping strategies alter in patients stopping participation. Trial participation influences patient-reported outcomes. Global health may predict for eligibility and trial continuation. Informing patients could affect patients' decision making.

The cover image, by Diane A. van der Biessen et al., is based on the Paper Understanding how Coping Strategies and Quality of Life maintain Hope in Patients deliberating Phase‐I Trial Participation, DOI .