Informed Consent Documents from Psychedelic Clinical Trials: A Descriptive Ethical Analysis

Katherine Cheung, Caleigh Propes, Marianna Graziosi, Kyle Patch, David B. Yaden

AJOB Empirical Bioethics, May 2025

Abstract

Background

Classic psychedelics, such as psilocybin and LSD, evoke certain kinds of altered states of consciousness. Specific features of the experience, such as its allegedly ineffable nature, have been discussed as posing challenges to the informed consent process. A growing call for tailored informed consent documents (ICDs) in the psychedelic bioethics literature raises the question of how closely ICDs used in contemporary psychedelic trials reflect the concrete suggestions and proposals offered by psychedelic bioethicists.

Methods

In this article, we review ICDs from psilocybin clinical trials in the United States. Using a content analysis approach, we provide a systematic qualitative description of the ICDs which comprise our final sample (N=28; 28 clinical trials across 13 unique sites). Coders demonstrated good reliability (κ=.683).

Results

Qualitative analyses revealed that most of the coding aligned with expectations based upon the psychedelics bioethics literature, such as the emphasis on Mental Health Risks and Physical Risks in ICDs. Notably, psychedelic-specific codes (e.g., Inef ability, Therapeutic Touch) did not appear as frequently in ICDs.

Conclusions

Scholars in psychedelic bioethics have called for the inclusion of a variety of potential risks and benefits in ICDs. It will be important to continue debating which elements are worth including in ICDs such that potential research participants are presented with the most salient factors relevant to their decision about joining a study. We provide a table of best practices applied by our sample of ICDs.

Disentangling informing participants from obtaining their consent
Experience Report
Patricia Pearl O’Rourke, Joseph Ali, Judith Carrithers, David Magnus, Benjamin S. Wilfond, Sheana Bull, Laura M. Dember, Gail D’Onofrio, Julie Goldman, P. Michael Ho, Edward R. Melnick, Karen L. Staman, James A. Tulsky, Miguel A. Vazquez, Angelo Volandes, David Wendler
Learning Health Systems, 21 April 2025
Open Access
Abstract
Introduction
Pragmatic clinical trials conducted in the context of routine care frequently satisfy the regulatory criteria for a waiver of research consent. When they do, investigators and Institutional Review Boards might assume that there is no reason to communicate any information regarding the study to participants. Yet, this approach ignores the possibility that there may be value in providing information to participants, even when the study does not pose significant risks and researchers are not obtaining their consent.
Methods
Members of the NIH Collaboratory Ethics and Regulatory Core working group used ethical analysis to determine whether there are reasons to provide information to research participants, other than notifying them of significant risks or obtaining their consent. Study team members then provided examples of trials which illustrate the feasibility and different options for providing information to participants in the context of trials conducted with a waiver of research consent.
Results
Communicating information to participants can promote one or more of six goals: respect for persons, participant understanding of the research, participant understanding of their contributions, participant ability to voice any concerns, participant engagement, and trust and trustworthiness. Providing information can also raise potential concerns about feasibility and cost, which need to be balanced against these reasons to inform participants. Depending on the study, a variety of methods can be used to communicate information; for example, letters, email, flyers, posters, as well as brief conversations with clinicians.
Conclusion
Even when researchers are not obtaining participants’ consent, communicating information can promote one or more of six important goals. Providing information to participants should thus be the default for trials conducted under a waiver of research consent.

Human artificial placenta technology-trials: counselling and informed consent using healthcare professionals’ and parental perspectives
Basic Science Article
Angret de Boer, André Krom, Rania Kalaai, Marieke de Vries, Marije Hogeveen, Sylvia A. Obermann-Borst, Marijn Vermeulen, Juliette S. van Haren, Peter Andriessen, Martine C. de Vries, E. J. T. Verweij, Rosa Geurtzen
Pediatric Research, 16 April 2025
Abstract
Background
The Artificial Amnion and Placenta Technology (AAPT) is developed to improve outcomes of extremely premature birth, with first in-human trials expected in the coming years. Empirical research with key stakeholders is essential for responsibly designing these trials. This study aims to discuss considerations for counselling and informed consent for the first in-human trials of the AAPT, discussing legal and ethical considerations.
Methods
A qualitative study using both individual and focus group interviews with healthcare professionals (HCPs) and parents was performed. Interviews were thematically analysed.
Results
Fifteen parents and 46 HCPs were interviewed. The results are represented into key themes reflecting participants’ perspectives on: (I) the moral and legal status of the subject treated in AAPT trials, (II) the first participant: the pregnant person, and (III) the terminology used to describe the technology. Furthermore, considerations around the informed consent process and counselling, including parental hope, are described. The findings suggest these factors are interconnected, as the moral and legal context surrounding AAPT trials influences the approach to counselling and informed consent.
Conclusion
Resolving key ethical and legal issues important for counselling and informed consent is essential for establishing parental right and the development of a responsible, ethically sound informed consent process.

Impact

• Addressing ethical and legal issues surrounding counseling and informed consent is essential to safeguard a responsible and ethically sound consent process for future human artificial amnion and placenta technology (AAPT)-trials.
• This is the first study exploring stakeholder perspectives on the AAPT, highlighting the complexities in counselling and informed consent, such as the moral status of participants and the rights of all parties, which must be carefully navigated before trial designs can progress.
• The article underscores the importance of establishing consensus and maintaining open dialogue among all stakeholders to create a robust, ethically grounded framework for informed consent in future trials.

Towards Excellence: Virtue and the Principle of Autonomy in Informed Consent for Clinical Trials
Alexander Montes
The Journal of Medicine and Philosophy, 1 April 2025
Abstract
In this article, I argue that approximating virtues such as care and respectfulness are necessary to conduct an informed consent discussion for clinical trials adequately. I argue against Beauchamp and Childress’ principlism insofar as it claims that virtues do not have “advantages” over the principle of respecting autonomy. When we elaborate what it means to facilitate autonomy in a consent discussion adequately, we find we are describing the virtues. This is because virtues do have an advantage over principles insofar as virtues provide us with rich descriptions of not only what we should do (respect autonomy), but how to do so (with the virtues of respectfulness, care, etc.). Thus, the principle of respecting autonomy points back to the virtues. I conclude by showing how cultivation of these virtues can help rectify well-known shortcomings in the informed consent process.

The Second Legacy of Henrietta Lacks
Viewpoint
Jerry Menikoff
JAMA, 17 February 2025
Abstract
Henrietta Lacks has already provided the world with one extraordinary legacy: her cells were used to create the first cell line, which has produced uncountable medical breakthroughs since 1951. But history also puts her at the center of another important issue: determining the extent to which it is ethical to conduct secondary research on a nonidentified biospecimen without that person’s consent. Recent developments create an opportunity for the research community to take an important step forward in clarifying that issue.

Consent to recontact for future research using linked primary healthcare data: Outcomes and general practice perceptions from the ATHENA COVID-19 study
Research Article
Kim Greaves, Amanda King, Zoltan Bourne, Jennifer Welsh, Mark Morgan, Maria Ximena Tolosa, Trisha Johnston, Carissa Bonner, Tony Stanton, Rosemary Korda
Clinical Trials, 29 December 2024
Abstract
Background
The ATHENA COVID-19 study was set up to recruit a cohort of patients with linked health information willing to be recontacted in future to participate in clinical trials and also to investigate the outcomes of people with COVID-19 in Queensland, Australia, using consent. This report describes how patients were recruited, their primary care data extracted, proportions consenting, outcomes of using the recontact method to recruit to a study, and experiences interacting with general practices requested to release the primary care data.
Methods
Patients diagnosed with COVID-19 from 1 January 2020 to 31 December 2020 were systematically approached to gain consent to have their primary healthcare data extracted from their general practice into a Queensland Health database and linked to other datasets for ethically approved research. Patients were also asked to consent to allow future recontact to discuss participation in clinical trials and other research studies. Patients who consented to recontact were later approached to recruit to a long-COVID study. Patients’ general practices were contacted to export the patient files. All patient and general practice interactions were recorded. Outcome measures were proportions of patients consenting to data extraction and research, permission to recontact, proportions of general practices agreeing to participate. A thematic analysis was conducted to assess attitudes regarding export of healthcare data, and the proportions consenting to participate in the long-COVID study were also reported.
Results
Of 1212 patients with COVID-19, contact details were available for 1155; 995 (86%) were successfully approached, and 842 (85%) reached a consent decision. Of those who reached a decision, 581 (69%), 615 (73%) and 629 (75%) patients consented to data extraction, recontact, and both, respectively. In all, 382 general practices were contacted, of whom 347 (91%) had an electronic medical record compatible for file export. Of these, 335 (88%) practices agreed to participate, and 12 (3%) declined. In total, 526 patient files were exported. The majority of general practices supported the study and accepted electronic patient consent as legitimate. For the long-COVID study, 376 (90%) of those patients recontacted agreed to have their contact details passed onto the long-COVID study team and 192 (53%) consented to take part in their study.
Conclusion
This report describes how primary care data were successfully extracted using consent, and that the majority of patients approached gave permission for their healthcare information to be used for research and be recontacted. The consent-to-recontact concept demonstrated its effectiveness to recruit to new research studies. The majority of general practices were willing to export identifiable patient healthcare data for linkage provided consent had been obtained.

Understanding Barriers and Facilitators for Ethnic Minority Groups to Audio Recording Recruitment Discussions in Clinical Trials: A Participatory Approach to Improving Informed Consent and Participation
Saba Faisal, Giles Birchley, Julia Wade, Athene Lane, Frida Malik, Tom Yardley, Shoba Dawson
Health Expectations, April 2025
Abstract
Introduction
Fully informed consent is essential for ethical trial conduct, yet gaps in participant comprehension and recall can occur, particularly among underserved groups, for example, ethnic minorities. This Patient and Public Involvement and Engagement (PPIE) project explored the engagement of ethnic minority communities in trial recruitment discussions, particularly their views about audio recording discussions with healthcare professionals.
Methods
This PPIE project engaged ethnic minority communities in Bristol [UK], collaborating with community partners to facilitate access to then foster dialogue among Somali, South Asian and Chinese groups. Separate workshops for men and women from these ethnic groups were held to introduce community members to clinical trial processes. Discussions, both audio recorded and not, simulated real recruitment scenarios. To ensure cultural relevance and accessibility, discussions were partly facilitated by our PPIE community partners in native languages.
Results
The insights gained during workshops were organised into key themes. Gaps in understanding regarding clinical trial participation were highlighted. A key finding was that trust played an important role and was facilitated by engaging community leaders and ensuring cultural and linguistic sensitivity during discussions. To address gaps in knowledge about trials and streamline the educational process, we developed storyboards and multilingual video resources. These explained the importance of clinical trials generally and the importance of recruiting diverse patient populations in particular. The materials were co-created with community partners and refined through iterative feedback to ensure accuracy and cultural appropriateness. The challenge of language barriers necessitated skilled interpreters, especially when discussions were audio recorded, to optimise understanding among people from diverse ethnic backgrounds. The video, available in English, Urdu, Mandarin, Cantonese and Bangla, facilitates understanding of trial purposes and processes, with the aim of widening trial participation in these groups.
Conclusion
Our PPIE activities highlighted gaps in understanding, the critical role of trust and the challenge of language barriers. The co-created resources have been made available for those wanting to address and overcome some of these issues. The initial feedback from the clinical trials community on the video resources has been promising, underscoring their potential to impact future recruitment efforts and PPIE activities.
Patient or public contribution
To foster a co-creation process, this project included the active involvement of our PPIE collaborators and co-applicants ‘Khaas’ for funding. They also helped us reach contributors from the South Asian community (mainly of Pakistani and Bangladeshi origin) and arrange workshops. Our two PPIE contributors from Somali Resource Centre and Barton Hill Activity Club helped us reach the Somali community at the Wellspring Settlement. Similarly, the Chinese Community Wellbeing Society helped us reach people from the Chinese community. These PPIE partners also helped us run the workshop by providing live translation of discussion. They also helped translate video scripts and do voiceovers in videos. Also, PPIE contributors Tom Yardley and Amanda Roberts helped with the script development.

Stakeholder Views on Novel Consent Forms for an Acute Stroke Trial
Candace D Speight, Opeolu M Adeoye, S Iris Davis, Michael J Linke, Andrea R Mitchell, Neal W Dickert
Ethics & Human Research, March-April 2025; 47(2) pp 16-25
Abstract
Lengthy consent forms are poorly suited for clinical trials in emergency contexts; however, innovations in consent processes are challenging to implement. A previously developed, context-sensitive consent form and information sheet were approved by a single institutional review board (sIRB) of record for use in a multisite stroke treatment clinical trial. This study sought views on using these materials by research teams and representatives from local institutional review boards (IRBs) and human research protection programs (HRPPs). Semistructured interviews were conducted with 22 local IRB/HRPP respondents and study team members from various study sites. Study teams appreciated the abbreviated length of the consent form and how the information tailored to help patients’ decisions was included while supplementary information was placed in an information sheet. They also described positive impacts on their interactions and processes; IRB/HRPP respondents valued the simplicity of the language, formatting, and attention to what was in the consent form versus what was on the information sheet. They supported the efforts and questioned whether local IRBs would have given approval. Some respondents were unsure of how to best use the information sheet. The consent forms were found to be patient-centered and implementable by study teams. Further experience is needed to identify optimal ways of incorporating supplemental written information. Since many of the IRB/HRPP respondents were uncertain whether their local IRBs would have approved the consent materials that were approved by the sIRB, these findings reinforce the potential for sIRB processes to facilitate the implementation of innovative approaches to consent.

Readability and complexity of written information presented to hospitalised patients for trial consent during the COVID-19 pandemic in the UK: a retrospective document analysis
Ewan Gourlay, Tim Felton, Mona Bafadhel, Christopher E Brightling, Jane C Davies, Rachael A Evans, Ling Pei Ho, Stefan J Marciniak, Nick A Maskell, Joanna Porter, Elizabeth Sapey, Salman Siddiqui, Samantha Walker, Tom Wilkinson, Alex Robert Horsley
BMJ Open, 21 March 2025; 15(3)
Abstract
Objectives
Patient information sheets (PISs) and informed consent forms (ICFs) are essential tools to communicate and document informed consent for clinical trial participation. These documents need to be easily understandable, especially when used to take informed consent from acutely unwell patients. Health literacy guidance recommends written information should be at a level between reading ages 9-11. We aimed to assess the readability and complexity of PISs/ICFs used for clinical trials of acute therapies during the COVID-19 pandemic.
Design
Retrospective document analysis.
Setting
PISs/ICFs used in trials involving pharmaceutical interventions recruiting hospitalised patients with COVID-19 during the first year of the pandemic were sourced from hospitals across the UK.
Primary and secondary outcome measures
PISs/ICFs were assessed for length, approximate reading time and subsection content. Readability and language complexity were assessed using Flesch-Kincaid Grade Level (FKGL) (range 1-18; higher is more complex), Gunning-Fog (GFOG) (range 1-20; higher is more complex) and Flesch Reading Ease Score (FRES) (range 0-100; below 60 is ‘difficult’ for comprehension).
Results
13 documents were analysed with a median length of 5139 words (range 1559-7026), equating to a median reading time of 21.4 min (range 6.5-29.3 min) at 240 words per minute. Median FKGL was 9.8 (9.1-10.8), GFOG 11.8 (10.4-13) and FRES was 54.6 (47.0-58.3). All documents were classified as ‘difficult’ for comprehension and had a reading age of 14 years old or higher.
Conclusions
All PISs/ICFs analysed contained literary complexity beyond both recommendations and the reading level of many in the UK population. Researchers should seek to improve communications to improve trial volunteer comprehension and recruitment.

Cancer Patient Perspectives on Clinical Trial Discussion and Informed Consent Through Telemedicine
Original Reports
Yasin Khadem Charvadeh, Sahil D. Doshi, Kenneth Seier, Erin M. Bange, Bobby Daly, Allison Lipitz-Snyderman, Fernanda C.G. Polubriaginof, Michael Buckley, Gilad Kuperman, Peter D. Stetson, Deb Schrag, Michael J. Morris, Katherine S. Panageas
JSO Oncology Practice, 18 March 2025
Abstract
Purpose
Clinical trials are integral for patients with cancer but remain inaccessible to many because of barriers including geographic and transportation challenges. This study aimed to evaluate cancer patients’ preferences for telemedicine versus in-person visits for clinical trial discussions and informed consent (IC).
Methods
An electronic survey was administered to first-time telemedicine users at Memorial Sloan Kettering Cancer Center from 2021 to 2023. The survey assessed patients’ preferences for telemedicine versus in-person visits for the IC process and their comfort with discussing clinical trials virtually. The primary outcome was the proportion of patients who indicated that they preferred a telemedicine visit for the IC process. Patient comfort and preference for discussing clinical trials through telemedicine versus an in-person visit was also explored. Structured responses provided quantitative data over the 2021-2023 observation period and demographic variations. To gain a more detailed understanding, unstructured free-text responses describing clinical trial discussions were also analyzed through language modeling.
Results
Overall, 57% of patients (540/955) preferred telemedicine, 26% (249/955) had no preference, and 17% (166/955) preferred in-person visits for the IC process. The preference for telemedicine remained consistent across the 2021-2023 observation period. Most patients reported no difference between a telemedicine versus in-person visit for clinical trial discussion, including asking questions, sharing concerns, declining participation, and asking for more time to make a decision. Language modeling analysis revealed areas for improvement.
Conclusion
A majority of patients at a comprehensive cancer center who participated in clinical trial discussions through telemedicine reported a preference for telemedicine to complete the IC process. Telemedicine thus represents a valuable tool for reducing barriers to clinical trial participation, particularly in reducing travel and time barriers.