scholarly journals Appraising Harm in Phase I Trials: Healthy Volunteers' Accounts of Adverse Events

2019 ◽  
Vol 47 (2) ◽  
pp. 323-333 ◽  
Author(s):  
Lisa McManus ◽  
Arlene Davis ◽  
Rebecca L. Forcier ◽  
Jill A. Fisher
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Adverse Events ◽  
Phase I ◽  
Healthy Volunteers ◽  
Trial Participation ◽  
Trial Participant ◽  
Phase I Trials ◽  
Investigational Drugs ◽  
Motivation To Participate

While risk of harm is an important focus for whether clinical research on humans can and should proceed, there is uncertainty about what constitutes harm to a trial participant. In Phase I trials on healthy volunteers, the purpose of the research is to document and measure safety concerns associated with investigational drugs, and participants are financially compensated for their enrollment in these studies. In this article, we investigate how characterizations of harm are narrated by healthy volunteers in the context of the adverse events (AEs) they experience during clinical trials. Drawing upon qualitative research, we find that participants largely minimize, deny, or re-attribute the cause of these AEs. We illustrate how participants' interpretations of AEs may be shaped both by the clinical trial environment and their economic motivation to participate. While these narratives are emblematic of the larger ambiguity surrounding harm in the context of clinical trial participation, we argue that these interpretations also problematically maintain the narrative of the safety of clinical trials, the ethics of testing investigational drugs on healthy people, and the rigor of data collected in the specter of such ambiguity.

scholarly journals Healthy Volunteers’ Perceptions of the Benefits of Their Participation in Phase I Clinical Trials

2018 ◽  
Vol 13 (5) ◽  
pp. 494-510 ◽  
Author(s):  
Jill A. Fisher ◽  
Lisa McManus ◽  
Megan M. Wood ◽  
Marci D. Cottingham ◽  
Julianne M. Kalbaugh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Healthy Volunteers ◽  
Employment Status ◽  
Qualitative Interviews ◽  
Trial Participation ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Financial Compensation ◽  
Trial History

Other than the financial motivations for enrolling in Phase I trials, research on how healthy volunteers perceive the benefits of their trial participation is scant. Using qualitative interviews conducted with 178 U.S. healthy volunteers enrolled in Phase I trials, we investigated how participants described the benefits of their study involvement, including, but not limited to, the financial compensation, and we analyzed how these perceptions varied based on participants’ sociodemographic characteristics and clinical trial history. We found that participants detailed economic, societal, and noneconomic personal benefits. We also found differences in participants’ perceived benefits based on gender, age, ethnicity, educational attainment, employment status, and number of clinical trials completed. Our study indicates that many healthy volunteers believe they gain more than just the financial compensation when they accept the risks of Phase I participation.

A Study on the Characteristics of Healthy Volunteers who Participate in Phase I Clinical Trials in Korea

2021 ◽  
pp. 155626462110342
Author(s):  
Ji-Hye Seo ◽  
Ock-Joo Kim ◽  
Sang-Ho Yoo ◽  
Eun Kyung Choi ◽  
Ji-Eun Park
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Healthy Volunteers ◽  
Health Science ◽  
Trial Participation ◽  
Phase I Clinical Trials ◽  
Financial Reward ◽  
Therapeutic Purpose ◽  
The Republic

The phase I trial is the first step in administering a drug to humans, but it has no therapeutic purpose. Under the absence of therapeutic purpose, healthy volunteers demonstrated different motivations, unlike the actual patients participating in trials. There were many reported motivations, such as financial motivation, contributing to the health science, accessing ancillary health care benefits, scientific interest or interest in the goals of the study, meeting people, and general curiosity. The aim of this study was to identify the motivation and characteristics of healthy volunteers participating in phase I trials in the Republic of Korea. We gave surveys to 121 healthy volunteers to study their demographic characteristics and the reasons of participation. We identified whether the decision to participate in the research was influenced by demographic factors and whether the perception and attitudes toward the research were influenced by the characteristics of the healthy volunteers. After completion of the first survey, 12 healthy volunteers who had participated in a phase I clinical trial were selected to answer the second interview. According to our survey, most healthy volunteers were unmarried men and economically dependent. Most of them participated in the study because of financial reward. The most important factor to measure financial reward was the research period. Also, 43% of the volunteers were university students, 42% answered “university graduation” and 55% were residing in family-owned houses. Many healthy volunteers were found to be living in family homes and to have a student status or lack of economic independence. Results of the survey showed that 64% of respondents indicated having more than one clinical trial participation. In-depth interviews showed that healthy volunteers had diverse motivation to participate in research and that healthy volunteer perceive the clinical trial positively. The main motivation for healthy volunteers’ participation in research was “financial reward.” Healthy volunteers also considered research schedules, processes, and safety, and had a positive perception of clinical trials, but they thought that the public has a negative perception.

A Tale of Three Cultures

2020 ◽  
pp. 75-99
Author(s):  
Jill A. Fisher
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Healthy Volunteers ◽  
West Coast ◽  
East Coast ◽  
Trial Participation ◽  
Phase I Trials ◽  
Hybrid Culture ◽  
Active Pursuit

Despite similar financial goals among healthy volunteers, there are regional differences in the culture of Phase I participation. Chapter 3 focuses on this theme to further unpack variations in how patterns of imbricated stigma influence healthy volunteers’ perceptions of Phase I trials, particularly with respect to the longevity of their study involvement. Specifically, East Coast participants tend to be well-networked as part of their long-term, active pursuit of clinical trials, but they often also express anti-capitalist critiques of the industry. In comparison, Midwesterners tend to be more passive about their trial participation, thinking of it as a short-term financial opportunity to counterbalance a temporary setback. West Coast participants occupy a hybrid culture between those of the East Coast and Midwest participants, actively seeking out new studies but expressing a distrust in the clinics and wanting to limit their study involvement. These regional cultures act as a prism for healthy volunteers’ perceptions of Phase I trials, shaping whether and how they adopt identities as research participants.

Adverse Events

2020 ◽  
Author(s):  
Jill A. Fisher
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Healthy Volunteers ◽  
Social Inequalities ◽  
New Drugs ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Racial Inequalities ◽  
Investigational Drugs ◽  
The Social

Phase I clinical trials test the safety and tolerability of new pharmaceuticals and typically pay healthy people to enroll as research participants. In addition to being exposed to the risks of taking investigational drugs, healthy volunteers are confined to residential research facilities for some portion of the clinical trial. Most healthy volunteers are African American and Hispanic men in their late twenties to early forties. Motivated by pervasive economic insecurity and racial discrimination, these individuals often enroll serially in Phase I trials to stay afloat or to get ahead. This book reveals not only the social inequalities on which Phase I trials rest, but also depicts the important validity concerns inherent in this mode of testing new pharmaceuticals. Healthy volunteers are enrolled in highly controlled studies that bear little resemblance to real-world conditions. Moreover, in these studies everyone—from the pharmaceutical companies sponsoring the studies, to the clinics conducting them, and the healthy volunteers paid to participate—is incentivized to game the system, with the effect that new drugs appear safer than they really are. Providing an unprecedented view of the intersection of US racial inequalities with pharmaceutical testing, Adverse Events calls attention to the dangers of this research enterprise to social justice and public health.

scholarly journals Phase I trial compensation: How much do healthy volunteers actually earn from clinical trial enrollment?

2021 ◽  
pp. 174077452110110
Author(s):  
Jill A Fisher ◽  
Lisa McManus ◽  
Julianne M Kalbaugh ◽  
Rebecca L Walker
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Healthy Volunteers ◽  
Low Income ◽  
Research Participation ◽  
Therapeutic Area ◽  
Phase I Trials ◽  
Full Time ◽  
Subject Recruitment

Background/aims Financial compensation for research participation is a major focus of ethical concern regarding human subject recruitment. Phase I trials are sometimes considered to be a lucrative source of income for healthy volunteers, encouraging some people to become “professional guinea pigs.” Yet, little is known about how much these clinical trials actually pay and how much healthy volunteers earn from them. Methods As part of a mixed-methods, longitudinal study of healthy volunteers, we required participants to complete clinical trial diaries, or surveys that captured detailed information about screening and enrollment in Phase I trials. Over a 3-year period, participants provided information online or via telephone about each clinical trial for which they screened (e.g. the clinic name, the study’s therapeutic area, the length of the trial, the number of nights spent in the clinic, and the study compensation), and whether they qualified for trial inclusion. Clinical trial diaries generated data about whether participants continued to screen for and enroll in clinical trials and how much money they earned from their participation. Results 131 participants routinely completed clinical trial diaries or confirmed that they had not screened for any new clinical trials. Together, these participants screened for 1001 clinical trials at 73 research facilities during a 3-year period. Overall, the median clinical trial compensation was US$3070 (range = US$150–US$13,000). Participants seeking new healthy volunteer trials tended to screen for three studies per year, participate in one or two studies, and earn roughly US$4000 annually. Participants who were unemployed earned the most income from clinical trials compared to those with full-time or part-time jobs, and those individuals whom we label “occupational” participants because of their persistent pursuit of clinical trials earned more than people who screened occasionally. Notably, the median annual trial compensation was well below US$10,000 for all employment groups, and most occupational healthy volunteers also earned less than US$10,000 each year. The 10% of participants who earned the most had a median annual income of US$18,885 from clinical trials, and there was significant volatility in these individuals’ earnings from year to year. Conclusion Despite the perception that Phase I enrollment can generate significant earnings, it was exceedingly rare for anyone in this study to make more than US$20,000 in a single year, and unusual to earn even between US$10,000 and US$20,000. From an ethics perspective, individual trials might appear to unduly induce enrollment by offering significant sums of money, but given our findings, the larger problem for low-income participants may be the unrealistic perception that clinical trials alone could be a way of earning a living.

scholarly journals Healthy volunteers in US phase I clinical trials: Sociodemographic characteristics and participation over time

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256994
Author(s):  
Corey A. Kalbaugh ◽  
Julianne M. Kalbaugh ◽  
Lisa McManus ◽  
Jill A. Fisher
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Healthy Volunteers ◽  
New Drugs ◽  
Trial Participation ◽  
Sociodemographic Characteristics ◽  
Phase I Trials ◽  
Full Time ◽  
Phase I Clinical Trials ◽  
Over Time

Background Increasing the diversity of research participants is an important focus of clinical trials. However, little is known regarding who enrolls as healthy volunteers in Phase I clinical trials, which test the safety and tolerability of investigational new drugs. Despite the risk, healthy volunteers can derive no medical benefit from their participation, and they are financially compensated for enrolling. Objective This study’s purpose is to describe sociodemographic characteristics and clinical trial participation histories of healthy people who enroll in US Phase I trials. Methods The HealthyVOICES Project (HVP) is a longitudinal study of healthy individuals who have enrolled in Phase I trials. We describe self-reported sociodemographic information and Phase I trial history from HVP recruitment (May-December 2013) through the project’s end three years later (December 2016). Trial experiences are presented as medians and quartiles. Results The HVP included 178 participants. Nearly three-fourths of participants were male, and two-thirds were classified as racial and ethnic minorities. We found that some groups of participants were more likely to have completed a greater number of clinical trials over a longer timeframe than others. Those groups included participants who were male, Black, Hispanic, 30-39-years-old, unemployed, had received vocational training in a trade, or had annual household incomes of less than $25,000. Additionally, the greater the number of clinical trials participants had completed, the more likely they were to continue screening for new trials over the course of three years. Participants who pursued clinical trials as a full-time job participated in the greatest number of trials and were the most likely to continuing screening over time. Implications Participation as a healthy volunteer in US Phase I trials is driven by social inequalities. Disadvantaged groups tend to participate in a greater number of clinical trials and participate longer than more privileged groups.

scholarly journals Investigator Disclosure and Advanced Cancer Patient Understanding of Informed Consent and Prognosis in Phase I Clinical Trials

2018 ◽  
Vol 14 (6) ◽  
pp. e357-e367 ◽  
Author(s):  
Fay J. Hlubocky ◽  
Nancy E. Kass ◽  
Debra Roter ◽  
Susan Larson ◽  
Kristen E. Wroblewski ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Informed Consent ◽  
Phase I ◽  
Advanced Cancer ◽  
Interaction Analysis ◽  
Trial Participation ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Advanced Cancer Patients ◽  
Medical Benefits

Purpose: Advanced cancer patients (ACPs) who participate in phase I clinical trials often report a less-than-ideal understanding of the required elements of informed consent (IC) and unrealistic expectations for anticancer benefit and prognosis. We examined phase I clinical trial enrollment discussions and their associations with subsequent ACP understanding. Methods: Clinical encounters about enrollment in phase I trials between 101 ACPs and 29 oncologists (principal investigators [PIs] and fellows) at three US academic medical institutions were recorded. The Roter Interaction Analysis System was used for analysis. ACPs completed follow-up questionnaires to assess IC recall. Results: PIs disclosed the following phase I IC elements to ACPs in encounters: trial purpose in 40%; specific physical risks in 60%; potential specific medical benefits gained by trial participation (eg, disease stabilization) in 48.2%; and alternatives to phase I trial participation in 47.1%, with 1.1% of encounters containing palliative and 2.3% hospice information. PIs provided ACP-specific prognoses in 29.0% of encounters but used precise terms of death in only 4.7% and terminal in 1.2%. A significant association existed between PI disclosure of the trial purpose as dosage/toxicity, and ACPs subsequently correctly recalled trial purpose versus PIs who did not disclose it (85% v 13%; P < .05). Conclusion: Many oncologists provide incomplete disclosures about phase I trials to ACPs. When disclosure of certain elements of IC occurs, it seems to be associated with better recall, especially with regard to the research purpose of phase I trials.

A study of informed consent (IC), age, and cognitive function (CF) among advanced cancer patients (acp) in phase I trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6548-6548
Author(s):  
F. J. Hlubocky ◽  
E. Larson ◽  
G. Sachs ◽  
C. K. Daugherty
Keyword(s):  
Clinical Trials ◽  
Informed Consent ◽  
Phase I ◽  
Digit Span ◽  
Verbal Learning ◽  
Psychological Status ◽  
Trial Participation ◽  
Phase I Trials ◽  
Ethical Concerns ◽  
Trail Making

6548 Background: Ethical concerns exist about acps’ ability to provide adequate informed consent (IC) for phase I trials. While cognitive impairment (CI) among acp is well-recognized due to multiple factors, e.g., previous effects of chemotherapy, age, psychological status, the prevalence of CI among acp in phase I trials has never been described. Methods: Acp CF was assessed using a neuropsychological battery of instruments: Hopkins Verbal Learning (HVLT); Verbal Fluency; Mini-Cognitive Assessment; Trail-making (Parts A& B); Boston Naming (short); WAIS subtests (Comprehension and Digit Span). Acp underwent semi-structured interviews to evaluate elements of IC, and completed the FACT-COG and the Hospital Anxiety and Depression Scale (HADS). Results: To date, a total of 34 acp enrolling in Phase I trials have been studied. Median age: 63y (range: 38–81y); 77% male; 77% Caucasian; 67% > HS education. Regarding IC understanding: Only 20% of responding acp correctly identified the purpose of Phase I trials; all subjects could recall risks of side effects, correctly stated they could refuse trial participation, and stated they could withdraw at anytime; 53% believed the trial was their only option. Older acp (>age 55y) were less likely to correctly describe the research purpose of the trial (29% v. 71% p=0.02). Older acp had measurable deficits in CF: Boston Naming (14±0.9 v.15±0.3, p=0.09); HVLT Total Recall (14±2 v.26±6, p<0.00) and Discrimination Index (7.5±3 v.11±1, p=0.03); Digit Span-Backwards (4±2 v.7±2, p<0.00); Trail-making B (244±64 v.188±51, p=0.04). While there were no differences in perceived CI (95±18 v.101±19, p=0.5) or impact on quality of life (25±7 v. 27±5, p=0.5), both groups had scores well below prior reported means. Older acp tended to report depressive symptoms more than younger acp (8±2 v.6±1, p=0.07). Conclusions: Our data suggest that CF may play a role in acp understanding of IC for clinical trials, especially among the elderly. Further research is needed, given ethical concerns regarding elderly acp in clinical trials of experimental agents who may have CI. No significant financial relationships to disclose.

Patients involved in clinical research are more concerned about intrinsic and traditional research (“publish or perish”) conflicts of interests (COI) than potential financial conflicts: Results of interviews with advanced cancer patients enrolling in phase I trials

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6008-6008
Author(s):  
C. K. Daugherty ◽  
F. J. Hlubocky ◽  
S. Gray ◽  
M. J. Ratain
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Cancer Patients ◽  
Career Advancement ◽  
Trial Participation ◽  
Phase I Trials ◽  
Financial Benefit ◽  
Advanced Cancer Patients ◽  
Traditional Research ◽  
Financial Benefits

6008 Background: Concerns exist about the potential for financial COI to bias the design, conduct, analysis, and reporting of clinical trials. However, information is lacking about the perceptions of these COI among actual research subjects—both in general and relative to more intrinsic and traditional research COI. Methods: Using a standardized survey, cancer patients (pts) were asked closed-ended and semi-qualitative questions regarding their concerns about extrinsic, e.g., financial, and intrinsic, e.g. career advancement, COI. Results: To date, 120 pts either enrolled, or being evaluated for participation, in phase I trials have been approached for an interview with 96 completing the interview (80% response rate). Median age of respondents is 61 y (33–82); 55% male; 83% Ca, 10% AA, 2% AsA or HA; 38% college educated. 91%, 100%, and 94% thought that the involved investigators (MDs), drug companies, and hospitals benefited from a clinical trial respectively. The benefits cited for MDs was improvement in knowledge/ability to treat pts. The benefits cited for the hospital and drug company were described as prestige and financial. 38% would be concerned if an MD involved in a clinical trial receives financial benefit from the research, e.g., being a paid consultant or owning stock in company involved in a trial, and 43% thought that they should be informed of these potential benefits. 64% thought they should be concerned if an MD receives career advancement benefits from trial participation, and 69% thought they should be informed of this benefit. 45% thought that investigators might feel institutional pressure to enroll pts. Qualitative data revealed that pts’ lack of concern about financial COI related to their assumption that MDs already receive financial benefits-believing this to be acceptable-with some even encouraging it. Conclusions: Cancer pts were more concerned about intrinsic and traditional research COI than potential financial COI. As well, many assume that MDs receive financial benefits from research. These results may be helpful when considering COI management policies. No significant financial relationships to disclose.

A pilot study of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in a phase I clinical trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6587-6587 ◽  
Author(s):  
Rui Qin ◽  
Amylou C. Dueck ◽  
Daniel Satele ◽  
Julian R. Molina ◽  
Charles Erlichman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Pilot Study ◽  
Adverse Events ◽  
Phase I ◽  
Patient Reported Outcomes ◽  
Point Of View ◽  
Phase I Clinical Trial ◽  
Phase I Clinical Trials ◽  
Patient Reported

6587 Background: Recently the Patient-Reported Outcomes version of the CTCAE was developed to augment clinically graded adverse events with information reported directly by patients on clinical trials (Basch, 2009). The validation and potential application of PRO-CTCAE in phase I clinical trials are of great interest as toxicity is the primary endpoint. Methods: Selected PRO-CTCAE items (21 items measuring 12 symptomatic adverse events) corresponding to the major adverse events required to be graded clinically were collected in an ongoing phase I clinical trial of weekly cilengitide and paclitaxel in patients with advanced solid malignancies (NCT01276496). PRO-CTCAE was administered in a paper booklet by a clinical research associate prior to treatment on days 1, 8 and 15 of their regular visits. These PRO-CTCAE items were summarized descriptively in comparison to clinician-assessed CTCAE ver 4.0 (NCI, 2009) during the first cycle. As a pilot study to assess feasibility of PRO-CTCAE in phase I trials, PRO-CTCAE was not intended for determination of dose-limiting toxicity. Results: Twelve patients were accrued to two separate doses of cilengitide and paclitaxel. The median age was 56 (range 36—67) and half of patients were female. All patients had an ECOG performance score <= 1. Over 90% of patients had received prior surgery and chemotherapy. All but one patient completed weekly PRO-CTCAE during the first cycle, the only patient refused to complete weeks 2 and 3 did not give a reason. PRO-CTCAE captured most of the symptomatic adverse events reflected in clinician-assessed CTCAE. Some symptomatic adverse events were not reported clinically by CTCAE but were reported by patients by PRO-CTCAE. Overall, PRO-CTCAE items indicated slightly more severe degree of symptoms experienced by patients than those reported in CTCAE. Conclusions: This is the first study that PRO-CTCAE items were integrated within regular study visits in a phase I trial. The administration of PRO-CTCAE has been proved feasible and fruitful, providing consistent and enhanced symptomatic toxicity from the patient point of view. The addition of PRO-CTCAE did not significantly increase patient burden. Clinical trial information: NCT01276496.

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