The motivations, barriers, and sociodemographic characteristics of healthy Chinese volunteers in phase I research.

PURPOSE: To describe the motivations, barriers, and sociodemographic characteristics of healthy Chinese volunteers in phase I research and to demonstrate the factors influencing their willingness to participate in subsequent trials. METHODS: Healthy subjects who participated in seven phase I trials at two centres were invited to participate in the cross-sectional survey at discharge by anonymously and voluntarily completing the self-administered questionnaire. RESULTS: From 442 subjects asked to complete the questionnaire, a response rate of 94.8% (419) was obtained, and 72.8% of the respondents had participated in a mean of 2.0 ± 1.3 previous studies. Over 90% of the subjects indicated that the main motivations to participate trials were to help more people, to contribute to scientific research, and to obtain money. The top 5 barriers were time inconvenience, advertisement sources, potential risks associated with the drug, privacy, and the route of drug administration. Nearly half (49.6%) of the subjects were willing to participate in the next trial. The factors impacting the willingness of the subjects to participate in subsequent trials were gender, screening frequency, enrolment frequency, level of understanding of the research, two motivating factors (to make money and receive a free check-up), and ten barriers (e.g. risk, distance, living conditions, and trust). CONCLUSIONS: The majority of healthy Chinese subjects were young, were less well educated, had low income levels, and had poor medical insurance coverage. Given the multiple sources of motivation and complex barriers to trial participation, investigators and recruitment staff should consider ethics aspects to guarantee volunteer safety and well-being.

Healthy volunteer profile: Levels of anxiety, depression, socioeconomic aspects and candidates' motivations of participation in phase I clinical trials / Perfil del voluntario sano: niveles de ansiedad, depresión, aspectos socioeconómicos y motivaciones de participación de candidatos a ensayos clínicos en fase

INTRODUCTION: Healthy volunteers participate in phase I clinical trials mainly in search of an economic compensation; their economic instability may constitute a vulnerability factor for anxiety/depression. OBJECTIVES: To select suitable and rapid screening tests for anxiety and depression in healthy volunteers, to know their socioeconomic situation and to identify the main reason for their participation. METHODS: Cross-sectional study, under a nonparametric statistical analysis and ROC curve analysis. Goldberg's Anxiety and Depression Scale (GADS) (fast test) and the Beck Depression (BDI-II) and Anxiety (BAI) Inventories (standard tests) were applied to all participants. RESULTS: One hundred and thirty-nine potential candidates were recruited; the average age was 32 years (SD = 8.8); 53.9% were students, 43.9% employers and 2.2% were unemployed; 85.6% had university studies, 13.7% secondary education and .7% primary studies. GADS, BDI-II and BAI results were: 24.5% volunteered with anxiety and 15.8% with depression (GADS); anxiety levels (BAI): 60.4% had null, 25.9% mild, 11.5% moderate and 2.2% severe; depression (BDI-II): 87.8% had null, 5.8% mild, 5.8% moderate and .7% severe. Socioeconomic characteristics: 48.2% low stratum, 43.2% medium, 5.7% medium high and 2.8% high. Motivations: 46.1% for economic compensation, 35.9% contribution to science, 14.4% for curiosity and 3.6% access to health. CONCLUSIONS: GADS shows insufficient capacity to discriminate between anxiety/depression and the use of BAI and BDI-II is suggested; anxiety and depression levels were higher in healthy volunteers than the prevalence in the general population but lower when compared to university population; employment status was mostly composed of university students with low socioeconomic characteristics and a high economic motivation

INTRODUCCIÓN: El motivo principal para participar como voluntario sano en un ensayo clínico fase I responde generalmente a aspectos de compensación económica, por tanto, su inestabilidad económica podría configurar un factor de vulnerabilidad a la ansiedad/depresión. Consecuentemente, sería conveniente utilizar test para valorar su estado mental. OBJETIVOS: Evaluar los niveles de ansiedad y depresión mediante test óptimos y confiables, conocer las características socioeconómicas y los motivos de participación de voluntarios sanos en ensayos clínicos en fase I. MÉTODOS: Estudio transversal, bajo un análisis estadístico no paramétrico y metodología de análisis de curvas ROC. RESULTADOS: Se encuestaron a 139 candidatos con media de edad de 32 años (DE: 8.8); el 53.9% estudiantes, el 43.9% trabajadores y el 2.2% desempleados; formación: el 85.6% universitaria, el 13.7% secundaria y el 0.7% primaria. Se seleccionó la Escala de Ansiedad-Depresión de Goldberg (EADG), el Inventario de Depresión (BDI-II) y el Inventario de Ansiedad de Beck (BAI); registrando: el 24.5% ansiedad y el 15.8% depresión (EADG); ansiedad (BAI): el 60.4% nula, el 25.9% leve, el 11.5% moderada y el 2.2% severa; depresión (BDI-II): el 87.8% nula, el 5.8% leve, el 5.8% moderada y el 0.7% severa. Las características socioeconómicas: el 48.2% estrato bajo, el 43.2% medio, el 5.7% medio alto y el 2.8% alto. Motivaciones: el 46.1% económicas, el 35.9% contribución a la ciencia, el 14.4% curiosidad y el 3.6% por acceso a salud. CONCLUSIONES: Los niveles de ansiedad y depresión encontrados superan la prevalencia en la población general, pero son inferiores a la población universitaria; EADG muestra insuficiente capacidad para distinguir entre ansiedad y depresión, se sugiere el uso de BAI y BDI-II; predominan características socioeconómicas bajas y motivaciones de participación económicas

Screening for Phase 1 Clinical Trials: An Opportunity to Evaluate Psychological States and Reeducate Patients on Prognosis?

Disease progression or recurrence after a period of remission can be a challenging event for individuals seeking cancer treatment. Those referred for possible phase 1 trial enrollment are often motivated to participate in these studies with hope for a cure despite approximately 5% response rates in this setting. Addressing such commonly held misunderstandings during the initial evaluation for phase 1 trial eligibility could provide a valuable opportunity to improve physician communication by identifying signs of distress or psychiatric conditions, addressing underlying psychological biases, and encouraging adaptive coping strategies.

Expectations and anxieties of Duchenne muscular dystrophy patients and their families during the first-in-human clinical trial of NS-065/NCNP-01.

Duchenne muscular dystrophy (DMD) is a recessive X-linked genetic disease caused by a mutation in the dystrophin gene. The new drug NS-065/NCNP-01 utilizing exon-skipping therapy targeting specific deletions has been used in a first-in-human trial for the treatment of DMD. We surveyed 10 pairs of DMD participants and their parents within this clinical trial via an iPad survey form and through interviews regarding their understanding of the trial, expectations, anxieties, and reasons for participating in the trial. Approximately half of the participants actively decided to participate of their own volition, and none considered quitting the trial. This indicates that participants participated more positively in this clinical trial than previously expected. However, some potential concerns were also revealed, with one being that the desire to please those around them might be more important to the DMD participants than the effects of the drug. Another issue is the possibility of biased information originating from the study subjects' parents; while seven out of 10 of the parents told their children that the study drug might work, only four of these parents also explained that it might not work. Only two study participants received an explanation concerning the drug's side effects from their parents. This result implies that caution should be taken when family expectations are high, and there is a possibility that subjects will be given biased information from their parents.

Phase I cancer trials: a qualitative study of specialist palliative care.

OBJECTIVE: In recent years, a simultaneous care model for advanced cancer patients has been recommended meaning that palliative care services are offered throughout their cancer journey. To inform the successful adoption of this model in a phase I trial context, the study aimed to explore patients' care needs and their perceptions of specialist palliative care. METHODS: Semi-structured interviews were conducted with 10 advanced cancer patients referred to the Experimental Cancer Medicine team. Interviews were transcribed verbatim and thematically analysed with a framework approach to data organisation. RESULTS: Despite reporting considerable physical and psychological impacts from cancer and cancer treatment, participants did not recognise a need for specialist palliative care support. Understanding of the role of specialist palliative care was largely limited to end of life care. There was perceived conflict between considering a phase I trial and receiving specialist palliative care. Participants felt specialist palliative care should be introduced earlier and educational resources developed to increase patient acceptability of palliative care services. SIGNIFICANCE OF RESULTS: Patients with advanced cancer referred for phase I trials are likely to benefit from specialist palliative care. However, this study suggests patients may not recognise a need for support nor accept this support due to misperceptions about the role of palliative care. Developing a specific educational resource about specialist palliative care for this population would help overcome barriers to engaging with a simultaneous care model.

Picking and Choosing Among Phase I Trials : A Qualitative Examination of How Healthy Volunteers Understand Study Risks.

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others' experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials.

Participant perspectives on a phase I/II ocular gene therapy trial (NCT02077361).

Background: To learn from the experiences of potential clinical trial participants, participants in a Phase 1 ocular gene therapy trial, and their partners to improve communications and trial conduct. Materials and methods: Primary and secondary qualitative analysis of semi-structured interviews of potential participants (n = 20), clinical trial participants (n = 2) and their partners (n = 2) in a gene therapy clinical trial for choroideremia (NCT02077361). Analysis included: 1) thematic analysis of transcribed entrance and exit semi-structured interviews with trial participants and their partners; and 2) secondary qualitative analysis of interviews with potential trial participants, conducted prior to the initiation of the clinical trial. Results: Participants and partners who had received information during the consent process had a better understanding of the risks and benefits of participation in a Phase 1 gene therapy clinical trial than potential trial participants. However, participants and partners reported deficiencies in communication throughout the trial. Results highlight additional opportunities for trial staff to reinforce initial information about the trial, communicate logistical information and individual outcome data, and express appreciation for participation. Conclusions: Our study enabled clinical trial participants to describe their experiences in a clinical trial for a novel gene therapy. We provide practical recommendations to future clinical trial staff on communications and conduct participant perspectives. Communications strategies should address changing information needs over the course of the trial, express appreciation for participation and enable feedback from participants and their supporting family members, friends, or caregivers.

Three randomized controlled trials evaluating the impact of "spin" in health news stories reporting studies of pharmacologic treatments on patients'/caregivers' interpretation of treatment benefit.

BACKGROUND: News stories represent an important source of information. We aimed to evaluate the impact of "spin" (i.e., misrepresentation of study results) in health news stories reporting studies of pharmacologic treatments on patients'/caregivers' interpretation of treatment benefit. METHODS: We conducted three two-arm, parallel-group, Internet-based randomized trials (RCTs) comparing the interpretation of news stories reported with or without spin. Each RCT considered news stories reporting a different type of study: (1) pre-clinical study, (2) phase I/II non-RCT, and (3) phase III/IV RCT. For each type of study, we identified news stories reported with spin that had earned mention in the press. Two versions of the news stories were used: the version with spin and a version rewritten without spin. Participants were patients/caregivers involved in Inspire, a large online community of more than one million patients/caregivers. The primary outcome was participants' interpretation assessed by one specific question "What do you think is the probability that 'treatment X' would be beneficial to patients?" (scale, 0 [very unlikely] to 10 [very likely]). RESULTS: For each RCT, 300 participants were randomly assigned to assess a news story with spin (n = 150) or without spin (n = 150), and 900 participants assessed a news story. Participants were more likely to consider that the treatment would be beneficial to patients when the news story was reported with spin. The mean (SD) score for the primary outcome for abstracts reported with and without spin for pre-clinical studies was 7.5 (2.2) versus 5.8 (2.8) (mean difference [95% CI] 1.7 [1.0-2.3], p < 0.001); for phase I/II non-randomized trials, 7.6 (2.2) versus 5.8 (2.7) (mean difference 1.8 [1.0-2.5], p < 0.001); and for phase III/IV RCTs, 7.2 (2.3) versus 4.9 (2.8) (mean difference 2.3 [1.4-3.2], p < 0.001). CONCLUSIONS: Spin in health news stories reporting studies of pharmacologic treatments affects patients'/caregivers' interpretation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03094078 , NCT03094104 , NCT03095586.

Comprehension and recall from the informed consent process by phase I healthy volunteers before dose administration.

AIMS/BACKGROUND: A fundamental part of all clinical trials is informed consent, reflecting the respect for the volunteer's autonomy. Research participation is voluntary; therefore, certain aspects of the proposed study must be disclosed so that volunteers can make an informed decision. In this study, we aimed to examine the level of comprehension and recall of healthy volunteers from the informed consent process. METHODS: The study was carried out at a single phase I clinical trials unit. A questionnaire was administered to each volunteer to assess recall of important aspects of the study at the day-1 visit following the informed consent process. The questionnaire contained seven questions regarding study objectives, route, frequency and type of drug administration, adverse effects, number of subjects previously exposed and remuneration. One point was awarded for each correct answer. RESULTS: A total of 266 volunteers were administered the questionnaire. The mean total score (±standard deviation) for all volunteers was 4.5 ± 1.1 points out of 7, with a range of 0.8-6.7. For all 10 studies, 91% of volunteers responded correctly when answering about the route of administration, and 90% were able to accurately state the correct payment amount. Only 7% were able to repeat the aims of the study correctly. CONCLUSION: The poor performance of our study volunteers raises concerns about recall of information prior to study drug administration. This has implications for the volunteer's safety and ability to provide true informed consent. Interventions to improve recall prior to dosing should be undertaken.

Parental Experiences of Child Participation in a Phase I Pediatric Oncology Clinical Trial: "We Don't Have Time to Waste".

Children with cancer are only eligible for phase I clinical trials (P1Ts) when no known curative therapy remains. However, the primary aims of P1Ts are not focused on directly benefiting participants. This raises ethical concerns that can be best evaluated by exploring the experiences of participants. An empirical phenomenology study, using an adapted Colaizzi method, was conducted of 11 parents' lived experiences of their child's participation in a pediatric oncology P1T. Study findings were that parents' experiences reflected what it meant to have a child fighting to survive high-risk cancer. Although elements specific to P1T participation were identified, more pervasive was parents' sense of running out of time to find an effective treatment and needing to use time they had with their child well. Even though some problems were identified, overall parents did not regret their child's P1T participation and would recommend P1Ts to other parents of children with cancer.

Well-Being of Child and Family Participants in Phase 1 Pediatric Oncology Clinical Trials.

PROBLEM IDENTIFICATION: Pediatric oncology phase 1 clinical trials (P1Ts) are essential to developing new anticancer therapies; however, they raise complex ethical concerns about balancing the need for this research with the well-being of participating children. The purpose of this integrative review was to synthesize and appraise the evidence of how P1T participation, which begins with consent and ends with the transition off the P1T, can affect the well-being (either positively or negatively) of children with cancer. The Resilience in Individuals and Families Affected by Cancer Framework, which has an outcome of well-being, was used to synthesize findings. LITERATURE SEARCH: Articles on the experiences of child (n = 21) and adult (n = 31) P1T participants were identified through systematic searches. DATA EVALUATION: Articles were evaluated on rigor and relevance to P1T participant experiences as high, medium, or low. SYNTHESIS: Minimal empirical evidence was found regarding the effect of P1T participation on the well-being of children with cancer. Adult P1T participant experiences provide insights that could also be important to children's P1T experiences. IMPLICATIONS FOR PRACTICE: To achieve a balanced approach in P1T consent discussions, nurses and healthcare providers who work with children considering participation in a P1T should share the potential effect of participation on participants' well-being.

Psychological Status of Volunteers in a Phase I Clinical Trial Assessed by Symptom Checklist 90 (SCL-90) and Eysenck Personality Questionnaire (EPQ).

BACKGROUND The psychological status of volunteers was investigated to provide a theoretical method for Phase I clinical trial management and result analysis. MATERIAL AND METHODS The Symptom Checklist 90 (SCL-90) and Eysenck Personality Questionnaire (EPQ) were used to assess the psychological status 200 healthy Chinese volunteers. RESULTS SCL-90 results indicate that the average value of positive factors is 10.32±14.26 by self-assessment of healthy volunteers, somatization factor is 1.13±0.13, compulsive symptom factor is 1.29±0.27, interpersonal sensitivity factor is 1.31±0.21, depression factor is 1.26±0.33, anxiety factor is 1.21±0.21, hostility factor is 1.08±0.26, phobia factor is 1.05±0.18, paranoid factor is 1.12±0.23, and psychotic symptom factor is 1.17±0.26. CONCLUSIONS Compared to the norm in China, the score of each factor of healthy volunteers was relatively low, with a statistically significant difference (P<0.001). EPQ results show that P score was 4.59±2.33, E score is 13.13±4.32, N score was 6.89±5.26, and L score was 13.21±4.25 for the 200 healthy volunteers. Compared to the norm in China, the P and N scores were lower, and the E and L scores were higher, with a statistically significant difference (P<0.001).

Do Patients With Advanced Cancer Have the Ability to Make Informed Decisions for Participation in Phase I Clinical Trials?

Purpose Patients with advanced cancer (ACPs) participating in phase I clinical trials inadequately understand many elements of informed consent (IC); however, the prevalence and impact of cognitive impairment has not been described. Patients and Methods ACPs enrolled onto phase I trials underwent neuropsychological assessment to evaluate cognitive functioning (CF) covering the following domains: memory (Hopkins Verbal Learning Test), executive functioning (Trail Making Test B), language (Boston Naming Test-Short Version and Controlled Oral Word Association Test), attention (Trail Making Test A and Wechsler Adult Intelligenence Scale-IV Digit Span), comprehension (Wechsler Adult Intelligence Scale-IV), and quality of life (Functional Assessment of Cancer Therapy-Cognitive Function). Structured interviews evaluated IC and decisional capacity. Psychological measures included distress (Hospital Anxiety Depression Scale) and depression (Beck Depression Inventory-II). Results One hundred eighteen ACPs on phase I trials were evaluated, with CF ranging from mild impairment to superior performance. Only 45% of ACPs recalled physician disclosure of the phase I trial purpose. The 50% of ACPs who correctly identified the phase I research purpose had greater CF compared with ACPs who did not, as revealed by the mean T scores for memory (37.2 ± 5.6 v 32.5 ± 5.1, respectively; P = .001), attention (29 ± 2.7 v 26.9 ± 2.4, respectively; P < .001), visual attention (35.2 ± 6.6 v 31.5 ± 6.2, respectively; P = .001), and executive function (38.9 ± 7.5 v 34 ± 7.1, respectively; P < .001). Older ACPs (≥ 60 years) were less likely to recall physician disclosure of phase I purpose than younger ACPs (30% v 70%, respectively; P = .02) and had measurable deficits in total memory (34.2 ± 5.0 v 37.3 ± 5.6, respectively; P = .002), attention (24.5 ± 2.6 v 28 ± 2.8, respectively; P < .001), and executive function (32.8 ± 7.3 v 36.4 ± 7.6, respectively; P = .01). Older ACPs, compared with younger ACPs, also had greater depression scores (10.6 ± 9.2 v 8.1 ± 5.2, respectively; P = .03) and lower quality-of-life scores (152 ± 29.6 v 167 ± 20, respectively; P = .03). After adjustment by age, no psychological or neuropsychological variable was further significantly associated with likelihood of purpose identification. Conclusion CF seems to play a role in ACP recall and comprehension of IC for early-phase clinical trials, especially among older ACPs.

Understanding how coping strategies and quality of life maintain hope in patients deliberating phase I trial participation.

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.

Motivations, enrollment decisions, and socio-demographic characteristics of healthy volunteers in phase 1 research.

BACKGROUND/AIM: Phase 1 trials with healthy volunteers are an integral step in drug development. Commentators worry about the possible exploitation of healthy volunteers because they are assumed to be disadvantaged, marginalized, and inappropriately influenced by the offer of money for research for which they do not appreciate the inherent risks. Yet there are limited data to support or refute these concerns. This study aims to describe the socio-demographic characteristics, motivations, and enrollment decision-making of a large cohort of healthy volunteers. METHODS: We used a cross-sectional anonymous survey of 1194 healthy volunteers considering enrollment in phase 1 studies at Pfizer Clinical Research Units in New Haven, CT; Brussels, Belgium; and Singapore. Descriptive statistics describe motivations and socio-demographic characteristics. Comparisons between groups were examined. RESULTS: The majority rated consideration of risks as more important to their enrollment decision than the amount of money, despite reporting that their primary motivation was financial. Risk, time, money, the competence and friendliness of research staff, and contributing to medical research were important factors influencing enrollment decisions for most participants. The majority of healthy volunteers in this cohort were male, single, reported higher than high school education, and 70% had previous research experience. Many reported low annual incomes (50% below USD$25,000) and high rates of unemployment (33% overall). Nonetheless, risk as an important consideration, money, and other reported considerations and motivations, except for time, did not vary by income, employment, education, or previous experience. There were regional differences in both socio-demographic characteristics and factors important to participation decisions. CONCLUSION: Healthy volunteers in phase 1 studies consider risks as more important to their enrollment decisions than the amount of money offered, although most are motivated to participate by the offer of money. Healthy volunteers are indeed low income, disproportionately unemployed, and have significant prior research experience. Yet these factors do not appear to affect either their motivations for participation or factors important to their research enrollment decisions.

Informed Consent and Decision Making Among Participants in Novel-Design Phase I Oncology Trials.

BACKGROUND: Although phase I clinical trials are the gateway to progress in cancer therapies, this setting poses ethical challenges to ensure that patients provide consent free from misunderstandings of therapeutic intent or unrealistic expectations of benefit. The design of phase I oncology trials has evolved rapidly over time and today includes more targeted agents and combinations of experimental drugs with standard drugs, which may further complicate how patients understand phase I research participation. METHODS: We conducted semistructured interviews regarding motivations, decision making, and understanding of trial purpose nested within a phase I clinical trial of a novel PI3kinase inhibitor combined with a standard oral chemotherapy in 18 participants. RESULTS: Fewer than half of patients correctly identified the safety and dosing objectives. The inclusion of a targeted agent was attractive to participants and was perceived as an indicator of less toxic or more efficacious therapy, with less appreciation for added risks. The significance of a cellular drug target, without a known predictive biomarker of response, was unclear to patients. The inclusion of a standard drug in the regimen attracted patients with more treatment options than traditional first-in-human participants. Patients frequently expressed a realistic understanding of prognosis and uncertainty of benefit, but simultaneous hopes for extraordinary outcomes. CONCLUSION: Novel phase I oncology trial designs may attract patients with less constrained treatment options, but the inclusion of targeted drugs and combinations including standard chemotherapies is likely to complicate understanding of safety and dosing objectives and likelihood of personal benefit for purposes of informed consent.

Phase 1 healthy volunteer willingness to participate and enrollment preferences.

BACKGROUND/AIMS: Healthy volunteers in phase 1 clinical trials contribute to the development of safe drugs and other biologics and accept risks and burdens without anticipated health benefits from participation. Although emerging data have shown that healthy volunteers are influenced by risk, some still worry that financial incentives lead them to take on unreasonable risk. Yet little is known about healthy volunteers' preferences and how they make choices about enrolling in research studies. METHODS: We surveyed 654 healthy volunteers at the end of their participation in a phase 1 Pfizer trial in the United States, Belgium, and Singapore to examine their reported willingness to enroll in studies of different types, with various procedures, and with possible side-effects. RESULTS: The majority of respondents were willing to join many kinds of studies, but fewer were willing to participate in first-in-human vaccine studies or studies of psychiatric drugs than in other study types. With regard to procedures, a substantial proportion were unwilling to participate in studies that involved invasive procedures, such as a lumbar puncture (45.4%) and bone marrow biopsy (42.3%), but willing to participate in studies with less invasive procedures such as a computed tomography scan of the heart (86.8%), magnetic resonance imaging (87.4%), and skin allergy testing (86.8%). Although there was some variation by gender and region, the majority were willing to participate in studies with side-effects like pain (80%) or nausea and vomiting (64%), but only a minority were willing to join if the research drug would result in their having a one in a million chance of death (34.4%), a small chance of kidney damage (16.7%), or influence how their mind works (23.2%; Figure 4). CONCLUSION: Our results suggest that healthy volunteers are willing to participate in a wide range of types of phase 1 clinical trials, and express preferences for low risk and familiar studies and study procedures, preferences which are partially affected by offers of payment.

Adolescent and Parent Willingness to Participate in Microbicide Safety Studies.

STUDY OBJECTIVE: To understand adolescents' and parents' willingness to participate (WTP) in a hypothetical phase I prevention study of sexually transmitted infections, discordance within adolescent-parent dyads, and expectations of each other during decision-making. DESIGN AND SETTING: Adolescent-parent dyads were recruited to participate in a longitudinal study about research participation attitudes. PARTICIPANTS: Adolescents (14-17 years old) and their parents (n = 301 dyads) participated. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Individual interviews at baseline assessed WTP on a 6-level Likert scale. WTP was dichotomized (willing/unwilling) to assess discordance. RESULTS: WTP was reported by 60% (182 of 301) of adolescents and 52% (156 of 300) of parents. In bivariate analyses, older adolescent age, sexual experience, and less involvement of parents in research processes were associated with higher level of WTP for adolescents; only sexual experience remained in the multivariable analysis. For parents, older adolescent age, perceived adolescent sexual experience, and conversations about sexual health were significant; only conversations remained. Dyadic discordance (44%, 132 of 300) was more likely in dyads in which the parent reported previous research experience, and less likely when parents reported higher family expressiveness. Adolescents (83%, 248 of 299) and parents (88%, 263 of 300) thought that the other would have similar views, influence their decision (adolescents 66%, 199 of 300; parents 75%, 224 of 300), and listen (adolescents 90%, 270 of 300; parents 96%, 287 of 300). There were no relationships between these perceptions and discordance. CONCLUSION: Inclusion of adolescents in phase I clinical trials is necessary to ensure that new methods are safe, effective, and acceptable for them. Because these trials currently require parental consent, strategies that manage adolescent-parent discordance and support adolescent independence and parental guidance are critically needed.

Patients' perceived tolerance of side effects in phase I cancer clinical trials: A qualitative study.

This qualitative study aimed to explore cancer patients' perceived tolerance of side effects in phase I drug trials. Patients with solid tumours receiving molecularly targeted agents with/without chemotherapy were eligible for inclusion. In-depth semi-structured interviews were carried out with 17 patients with a median [range] age of 63 [41-72] years. Treatment was discontinued in seven patients. Verbatim transcripts of the audio-taped interviews were analysed using a constructivist grounded theory approach. Four conceptual categories emerged from data analysis, labelled "suffering from side effects" comprising a range of symptoms, psychosocial or role disturbances; "striving to cope with side effects" reflecting psychological strategies for managing side effects; "hoping" reflecting expectations about treatment efficacy and relief from side effects; and "appraisal of care." Among patients remaining in the trial, treatment was currently perceived as fairly tolerable. For most respondents, whether still in a trial or not, treatment discontinuation could not be justified by the non-tolerance of treatment side effects. These results question the adequacy of patient-perceived tolerance reports to determine an optimal drug dose for phase II trials. Confronted with patients' hopes and inappropriate beliefs, communication is challenging in phase I trials and could benefit from facilitating psychosocial interventions.