Grady C, Bedarida G, Sinaii N, Gregorio MA, Emanuel EJ.
Clinical Trials, October 2017.
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.
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.
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.
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.
Chen SC, Sinaii N, Bedarida G, Gregorio MA, Emanuel E, Grady C.
Clinical Trial, October 2017
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.
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.
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).
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.
Persad GC, Emanuel EJ.
Hastings Center Report, September 2017.
When Dr. Hortense screens her patients in Chicago for cervical dysplasia and cancer, she conducts a pelvic exam, takes a sample of cervical cells, and sends them for Pap cytology and human papilloma virus DNA co-testing. But when she conducts cervical cancer screening in Botswana, she employs a much simpler diagnostic strategy. She applies acetic acid to highlight precancerous lesions and visually inspects the cervix-a technique known as the VIA (visual inspection with acetic acid) method. She treats suspicious lesions with cryotherapy. There are multiple reasons that Dr. Hortense uses VIA in developing countries. It requires no specialized laboratory facilities or highly trained personnel. With immediate results, there is no delay in diagnosis and treatment, ensuring that patients are not lost to follow-up. Most importantly, VIA is considerably cheaper than Pap and HPV co-testing. This difference in care between Chicago and Botswana presents an ethical dilemma in global health: is it ethically acceptable to provide some patients cheaper treatments that are less effective or more toxic than the treatments other patients receive? We argue that it is ethical to consider local resource constraints when deciding what interventions to provide. The provision of cheaper, less effective health care is frequently the most effective way of promoting health and realizing the ethical values of utility, equality, and priority to the worst off.
Navathe AS, Song Z, Emanuel EJ.
JAMA, June 2017.
This Viewpoint discusses bundled payment models and suggests ways in which the next generation of episode-based payments can better align with population health.
McCoy MS, Emanuel EJ.
JAMA, May 2017
This Viewpoint argues that “potential” conflicts of interest (COIs) are actual COIs that are effectively managed, and calls for clear terminology to describe the severity of COIs and how they are identified and managed.
Medical Journal of Australia, May 2017
We should aim at improving the care of dying patients
Modern debates about legalising euthanasia and physician-assisted suicide (PAS) in Great Britain and the United States began in the late 19th century.1Legislation was periodically proposed only to be defeated until, in 1942, Switzerland decriminalised assistance in suicide for cases when there were no “selfish motives”.2 In 2002, euthanasia was legalised in the Netherlands and Belgium, then in Luxembourg in 2009, and most recently, in 2015 in Colombia and in 2016 in Canada.3 PAS, but not euthanasia, has been legalised in five US states. In Oregon, PAS was legalised by popular referendum in 1997. In addition, in 2009, Washington State legalised PAS by referendum and Montana by court ruling; Vermont in 2013 and California in 2015 also legalised PAS by legislation.4
Grady C, Touloumi G, Walker AS, Smolskis M, Sharma S, Babiker AG, Pantazis N, Tavel J, Florence E, Sanchez A, Hudson F, Papadopoulos A, Emanuel E, Clewett M, Munroe D, Denning E; INSIGHT START Informed Consent Substudy Group.
Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed.
We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin).
77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups.
An easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient.
Informed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008-006439-12