Informed Consent, Therapeutic Misconception, and Unrealistic Optimism
Lynn A. Jansen
Perspectives in Biology and Medicine, Spring 2020; 63 (2) pp 359-373
Abstract
The Belmont Report attested to the cardinal importance of informed consent for ethical research on human subjects. Important challenges to securing informed consent have emerged since its publication more than 40 years ago. Among some of the most significant of these challenges are those that highlight social psychological factors that have the potential to impair the appreciation of relevant information disclosed in the informed consent process. Responding to these challenges requires us to think harder about the content of the principle of informed consent and the demands that it imposes on investigators. This article focuses on two challenges in particular, that presented by the so-called therapeutic misconception, and that presented by the psychological bias of unrealistic optimism. After outlining an account of the principle of informed consent as it applies to the research context, the article briefly reviews the empirical literature on the therapeutic misconception and the bias of unrealistic optimism. It then relates these phenomena to the principle of informed consent, paying special attention to the ethical demands they impose on investigators. The article concludes by considering how recent trends to integrate research and clinical care affect the main points it has advanced.

Improving knowledge and decision readiness to participate in cancer clinical trials: Effects of a plain language decision aid for minority cancer survivors
Short Communication
Aisha Langford, Jamie L. Studts, Margaret M. Byrne
Patient Education and Counseling, 7 July 2020
Abstract
Objective
To evaluate the impact of a web-based, plain language decision aid (CHOICES DA) on minority cancer survivors’ knowledge of cancer clinical trials (CCTs), readiness for making decisions about clinical trial participation, and willingness to participate in a clinical trial.
Methods
Participants were 64 Black and Hispanic cancer survivors from Miami, Florida. In a single arm intervention study, participants completed self-report assessments of CCT knowledge, decision readiness regarding clinical trial participation, and willingness to participate at three time points.
Results
Black and Hispanic participants did not differ on demographic characteristics. Post-test and follow-up measures of CCT knowledge and decision readiness were significantly greater than pre-test measures for the sample overall, and for Black and Hispanic participants separately. Few significant differences were observed between Black and Hispanic participant outcomes at each survey time point, and willingness to participate did not change overall and for either group independently.
Conclusions
Reviewing the CHOICES DA was associated with significantly improved knowledge and decision readiness to participate in a CCT immediately and at 2-week follow-up.
Practical Implications
These findings suggest that CHOICES DA may support informed decision making about CCT participation within an acute, yet clinically relevant window of time for minority cancer patients who are substantially under-represented in cancer research.

Informed consent for HIV phylogenetic research: a case study of individuals living with HIV in an urban area who were contacted for participation in an HIV study
Abby E. Rudolph, Omar Martinez, Robin Davison, Chineye Brenda Amuchi
Ehquidad International Welfare Policies and Social Work Journal, 4 July 2020; 14
Open Access
Summary
Introduction: Phylogenetic analyzes can provide information on the dynamics of HIV transmission. National and state differences in HIV criminalization and disclosure laws and advances in next-generation sequencing could affect the study’s perceived risks. Methods: We present the study opt-out rates and the reasons provided during enrollment for a study conducted in Boston (6 / 2017-8 / 2018). Results: Of the 90 patients who came to participate, 45 did not consent to participate. Reasons for not participating included an unwillingness to discuss their HIV status, privacy and confidentiality concerns, disinterest and lack of time. Conclusions: Given the low participation rates and concerns related to HIV status disclosure, privacy and confidentiality, these questions remain (1) should informed consent be required for all phylogenetic analyzes, including anonymous information and surveillance data? (2) What additional steps can investigators take to protect people’s privacy, particularly in contexts where HIV is criminalized or there have been civil / criminal cases investigating HIV transmission? And (3) what role can community members play to minimize potential risks, particularly for the most marginalized? These questions require input from both researchers and community members living with HIV / AIDS.

Understanding voluntariness of consent in first-in-human cell therapy trials
Perspective
Kristina Hug
Regenerative Medicine, 1 July 2020
Abstract
Consensus about contents of voluntariness in informed consent is lacking. Core criteria for voluntary consent are needed to ensure voluntariness. This article outlines the multidimensionality of voluntariness and identifies what could reduce voluntariness, especially in first-in-human clinical trials involving cell therapies. In such trials, truly voluntary consent is especially important because: such trials may involve risk of serious harm, while in case of some diseases, eligible patients often have potentially effective therapeutic alternatives; patients considering participation in high-risk first-in-human trials may feel more desperate and some may be dependent on their caregivers, including those in the family; implanted cells cannot be taken out of the patient’s body if the patient wants to withdraw.

Assessment of the quality of Patient Information Sheets and Informed Consent Forms for clinical trials at a Hospital Neurology Service
Andrea G Jaramillo Vélez, Margarita Aguas Compaired, Montserrat Granados Plaza, Eduardo L. Mariño, Pilar Modamio
European Journal of Neurology, 28 June 2020
Abstract
Background and purpose
Clinical trials (CTs) aimed at vulnerable groups such as patients with mental disorders create ethical complexity. The Patient Information Sheet (PIS) should provide all the information about the CT that is relevant to the subject’s decision to participate. After being informed, the subject will decide freely whether to take part in the CT and will read and sign the Informed Consent Form (ICF). The objective was to assess the quality of PIS/ICFs from a Hospital Neurology Service (NS). The assessment was made using validated and reliable checklists of the information included in the PIS/ICFs of CTs with medicinal products.
Methods
Analyses of the compliance with the checklists of 21 PIS and ICFs reviewed/approved during 2016‐2017 by a medicinal Research Ethics Committee.
Results
All PIS/ICFs were from multicenter CTs sponsored by pharmaceutical companies in different therapeutic areas, mainly Parkinson’s (52.4%) and Alzheimer’s (38.1%) diseases. The PISs from the NS demonstrated good compliance (≥ 80%) with the checklist, while ICFs should be improved. Sponsors omitted some relevant information such as study title or that the participant be informed of any information arising from the research that may be relevant to the subject’s health, although this information may be in the PIS.
Conclusions
The PIS/ICFs of CTs of medicinal products currently used need improvement. PISs and ICFs should be separate documents for each CT. The PIS/ICFs should consider, in particular, those criteria related to the decision of participants, protect their rights and ensure that the information received is complete.

How Health Literacy Can Enhance the Design and Conduct of Clinical Trials From Consent to Conclusion
Catina O’Leary, Chris Casey, Diane Webb, Deborah Collyar, Andrew Pleasant
Studies in Health Technology and Informatics, 25 Jun 2020; 269 pp 275-284
Abstract
Health literacy research and interventions have provided multiple tools to improve communication between professionals and patients in clinical contexts for many years. Despite the reality that many patients participate in clinical trials in conjunction with standard medical care, only recently have efforts extended to address and improve the health literacy of both clinical trial researchers and participants. To date, the primary focus of health literacy activities in clinical trials has centered on communicating trial results to trial participants. This report describes the opportunities and strategies necessary to layer health literacy activities across the clinical trial process from consent to conclusion.

Clinical correlates of the ability to consent to research participation in brain metastasis
Adam Gerstenecker, Meredith Gammon, Dario Marotta, John Fiveash, Burt Nabors, Kyler Mulhauser, Kristen Triebel
Psycho-Oncology, 20 July 2020
Abstract
Objective
Impairment in the ability to provide informed consent is common in persons with brain metastasis. However, little is known about what factors contribute to this impairment in the patient group. Our objective is to determine if the associations between demographic, cognitive, and clinical variables correlate with the ability to provide informed consent in persons with brain metastasis.
Methods
We administered a comprehensive neuropsychological battery to a group of 61 persons with brain metastasis. Demographic and clinical information was also collected. All diagnoses were made by board‐certified oncologists and were verified histologically. Statistical analyses included Pearson’s product‐moment correlations, point biserial correlations, and linear regression.
Results
Results indicated that combinations of education, verbal memory, executive function, whole brain radiation therapy, and chemotherapy affected various aspects of the ability to provide informed consent. Subsequent regression models demonstrated that these variables contributed a significant amount of shared variance to the ability to provide informed consent.
Conclusion
We found that the ability of persons with brain metastasis to provide informed consent is a cognitively-complex ability that is also affected by education and treatment variables. This information can help clinical researchers in identifying persons with brain metastasis at risk of an impaired ability to provide informed consent and aid in the consenting process.

Potential research participants’ use of information during the consent process: A qualitative pilot study of patients enrolled in a clinical trial
Research Article
Simon Paul Jenkins, Melanie J. Calvert, Heather Draper
PLOS One, 18 June 2020
Open Access
Abstract
There is increasing evidence that clinical trial participants are uninformed about the trials in which they participate, raising ethical concerns regarding informed consent. The aim of this pilot study was to explore clinical trial participants’ use of consent discussions and information sheets when considering participating in clinical trials research. A qualitative, interview-based pilot study was designed in order to elicit, through dialogue, details of the reasons for participants’ use of, and preferences regarding, different modes of information provision. Semi-structured interviews were undertaken with two different groups of patients who were participants in the Reinforcement of Closure of Stoma Site trial. The first group comprised newly-consented trial participants, who had been recruited up to 72 hours before our interview; the second group comprised patients attending a follow-up clinic 12 months after joining the trial. Thirteen participants were recruited in total: three newly-consented patients, and ten follow-up patients. The study found that participants’ use of consent discussions to gain information about clinical trials was varied, and that they only minimally used information sheets after providing initial consent for the trial. Participants demonstrated varying degrees of knowledge about the trial, with some having forgotten that they were still involved in the trial. Participants reported a high level of trust in medical staff as a reason for not seeking more information about the trial. Some participants reported dissatisfaction with the timing of information provision. Some were amenable to novel ways of receiving trial information, such as web-based methods. The pilot study demonstrated the feasibility of a larger study into the provision of information to prospective clinical trial participants. The results suggest that considering alternative ways of providing information and the appropriateness of existing information provision may be acceptable to and useful for potential trial participants.

Informed consent procedures in patients with an acute inability to provide informed consent: Policy and practice in the CENTER-TBI study
Roel P. J. van Wijk, Jeroen T. J. M. van Dijck, Marjolein Timmers, Ernest van Veen, Giuseppe Citerio, Hester F. Lingsma, Andrew I. R. Maas, David K. Menon, Wilco C. Peul, Nino Stocchetti, Erwin  J. O. Kompanje
Journal of Critical Care, October 2020, 59; 6-15
Abstract
Purpose
Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice.
Methods
Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries.
Results
Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N = 426;20%) and deferred consent (N = 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%).
Conclusions
Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers.

Advances and challenges in conducting ethical trials involving populations lacking capacity to consent: A decade in review
Victoria Shepherd
Contemporary Clinical Trials, August 2020; 95
Abstract
Informed consent is an essential requirement prior to clinical trial participation, however some ‘vulnerable’ groups, such as people with cognitive impairments and those in medical emergency situations, may lack decisional capacity to consent. This raises ethical and practical challenges when designing and conducting clinical trials involving these populations, who are frequently excluded as a result. Despite recent advances in improving informed consent processes, there has been far less attention paid to the enrolment of adults lacking capacity.

Exclusion criteria are an important determinant of the external validity of clinical trial results. The exclusion of these populations, and consent-based recruitment biases which arise from the challenges of identifying and involving surrogate decision-makers, leads to trials which are not representative of the clinical population.

This article discusses the involvement of adults who lack decisional capacity to consent in clinical trials and presents the advances over the previous decade and the remaining ethical challenges for the inclusion of this under-represented population in research.