Month: December 2023

New Regulatory Guidance Referencing Consent

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FDA: Institutional Review Board Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations
FDA – Final rule.
Summary
The Food and Drug Administration (FDA, the Agency, or we) is issuing a final rule to amend its regulations to implement a provision of the 21st Century Cures Act (Cures Act). This final rule allows an exception from the requirement to obtain informed consent when a clinical investigation poses no more than minimal risk to the human subject and includes appropriate safeguards to protect the rights, safety, and welfare of human subjects. The final rule permits an institutional review board (IRB) to waive or alter certain informed consent elements or to waive the requirement to obtain informed consent, under limited conditions, for certain FDA-regulated minimal risk clinical investigations.
…Summary of the Major Provisions of the Final Rule
The final rule amends FDA’s regulations to allow IRBs responsible for the review, approval, and continuing review of clinical investigations to approve an informed consent procedure that does not include or that alters certain informed consent elements, or to waive the requirement to obtain informed consent, for certain minimal risk clinical investigations. For an IRB to approve a waiver or alteration of informed consent requirements for minimal risk clinical investigations, the rule requires an IRB to find and document five criteria that are consistent with the revised rule entitled “Federal Policy for the Protection of Human Subjects” (the revised Common Rule (January 19, 2017)). FDA believes the amendment provides appropriate safeguards to protect the rights, safety, and welfare of the human subjects participating in such clinical investigations. We are also making conforming amendments to FDA’s regulations.

Digital Health Technologies for Remote Data Acquisition in Clinical Investigations; Guidance for Industry, Investigators, and Other Stakeholders; Availability
Food and Drug Administration, HHS.
Final guidance. Scheduled Pub. Date: 12/22/2023  FR Document: 2023-28262
PDF: https://downloads.regulations.gov/FDA-2021-D-1128-0066/attachment_1.pdf     8 Pages (112 KB)
Summary
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry, investigators, and other stakeholders entitled “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations.” This guidance provides recommendations on the use of digital health technologies (DHTs) to acquire data remotely from participants in clinical investigations that evaluate medical products. DHTs for remote data acquisition in clinical investigations can include hardware and/or software to perform one or more functions. Use of DHTs as recommended in this guidance may improve the efficiency of clinical trials for sponsors, investigators, and other stakeholders and may increase the opportunities for individuals to participate in research and make participation more convenient. This guidance finalizes the draft guidance of the same title issued on December 23, 2021.
Consent
Risk Considerations When Using Digital Health Technologies
p.19 …3. Informed Consent
   FDA regulations at 21 CFR part 50 set forth the requirements for obtaining the informed consent of participants59 in clinical investigations. DHTs can be used to obtain electronic informed consent in a clinical investigation.60
   Some considerations for what information to include in the informed consent process regarding the DHT being used in a clinical investigation include but are not limited to the following:

  • The informed consent process must describe any reasonably foreseeable risks or discomforts to participants (see sections IV.F.1 and IV.F.2 of this guidance), including reasonably foreseeable risks or discomforts related to the use of the DHT in the clinical investigation.61 Information regarding what may be done to mitigate serious risks, and risks and discomforts more likely to occur, should also be considered for inclusion.
  • When appropriate, a statement must be included indicating that use of the DHT during the clinical investigation may involve risks to the participant (or to the embryo or fetus if the participant is or may become pregnant) which are currently unforeseeable.62
  • The informed consent process should explain the type of information that will be collected by the DHT and how that information will be used and monitored. When relevant, participants should be informed of what action to take in case of any concerning sign, symptom, or abnormal clinical event (e.g., hypoglycemia or abnormal cardiac rhythm) detected by a DHT, such as seeking emergency medical attention, if appropriate.
  • The informed consent process should specify who may have access to data collected through the DHT during or after the clinical investigation (e.g., sponsors, investigators, participants, DHT manufacturers, other specified third parties) and during what time frame.63
  • An explanation of measures to protect participant privacy and data, and limitations to those measures, when DHTs are used should be included.
  • If participants may incur additional expense because they are taking part in the clinical investigation, the consent process must explain the added costs,64 which could include costs for the participants that may result from using the DHT during the clinical investigation (e.g., data use charges).
  • DHTs or other technologies may be covered by end-user license agreements or terms of service as a condition of use, which may, among other things, allow DHT or other technology manufacturers and other parties to gain access to personal information and data collected by the DHT or other technology. When applicable, sponsors and investigators should ensure that the informed consent process explains to participants that their data may be shared outside of the clinical investigation, according to the end-user license agreement or terms of service. End-user license agreements and terms of service typically are lengthy and use complex terminology. Sponsors and investigators proposing use of DHTs for data collection should understand how such agreements or terms of service may affect trial participants and address this information when developing informed consent documents.65

61 See 21 CFR 50.25(a)(2).
62 See 21 CFR 50.25(b)(1).
63 In addition, the informed consent process must note the possibility that FDA will inspect records identifying the participants (21 CFR 50.25(a)(5)).
64 21 CFR 50.25(b)(3).
65 For further information, see the Secretary’s Advisory Committee on Human Research Protections webpage “Attachment B-Clarifying Requirements in Digital Health Technologies Research,” available athttps://www.hhs.gov/ohrp/sachrp-committee/recommendations/april-7-2020-attachment-b/index.html.
66 See 21 CFR 312.57,312.58,312.62, and 312.68.
67 See 21 CFR 812.2(b)(1)(v)and(vi), 812.140, 812.145, and 812.150.
68 See FDA Study Data Standards Resources, available athttps://www.fda.gov/industry/fda-data-standards-advisory-board/study-data-standards-resources,and the Data Standards Catalog, available athttps://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-standards-catalog.

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Informed Consent: A Monthly Review
_________________

December 2023 :: Issue 60

This digest aggregates and distills key content addressing informed consent from a broad spectrum of peer-reviewed journals and grey literature, and from various practice domains and organization types including international agencies, INGOs, governments, academic and research institutions, consortiums and collaborations, foundations, and commercial organizations. We acknowledge that this scope yields an indicative and not an exhaustive digest product.

Informed Consent: A Monthly Review is a service of the Center for Informed Consent Integrity, a program of the GE2P2 Global Foundation. The Foundation is solely responsible for its content. Comments and suggestions should be directed to:

Editor
Paige Fitzsimmons, MA
Associate Director, Center for Informed Consent Integrity
GE2P2 Global Foundation
paige.fitzsimmons@ge2p2global.org

PDF Version: Center for Informed Consent Integrity – A Monthly Review_December 2023 Continue reading →

Spotlight Article

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This month we are spotlighting The Lived Experience of Pediatric Gene Therapy – A Scoping Review by Kimberly et al. In this Human Gene Therapy article the authors assess empirical research examining the lived experience of both patients and caregivers participating in pediatric gene therapy trials. Their scoping review underscores a serious gap in the literature leading to an examination of narrative accounts from trial participants and their families, and areas where further research in necessary. The authors note that:

[p. 4]
“…When making a decision about whether to enroll a child in a GT clinical trial, caregivers must weigh factors such as: the inability for most treatments to be repeated or re-dosed; uncertainty around the durability, efficacy, and safety of an experimental treatment; risk of a child’s disease progressing if they wait for an approved treatment or more safety data; and efficacy of existing approved alternative treatments… The confluence of these factors within a high-stakes decision-making framework creates a unique ethical context for pediatric rare disease patients and their parents and caregivers. The progressive nature of many of these diseases also adds a time constraint to participation…

[p. 16]
The field of pediatric GT research… has an important and timely opportunity to better understand how patients and their parents/caregivers choose whether or not to consider GT, and their lived experience of participating in clinical trials. Pediatric patients’ own perspectives are almost completely absent from the literature, marking an important area for future research efforts. Such insights from further research will inform more patient- and family-centered clinical trial design and can help to ensure that clinical trial design and implementation reflect patients’ and families’ values, their priorities, and their goals for care. This scoping review lays a foundation for future research in this space.”

The Lived Experience of Pediatric Gene Therapy – A Scoping Review
Laura Kimberly, Cara Hunt, Katherine Beaverson, Emma James, Alison Bateman-House, Richard McGowan, Jennifer DeSante-Bertkau
Human Gene Therapy, 15 November 2023
Abstract
Little is known about patients’ and families’ lived experience of participating in pediatric gene therapy (GT) clinical trials. Currently, pediatric GT research targets a broad range of indications––including rare and ultra-rare diseases––which vary in severity and in the availability of alternative therapies. Pediatric GT differs meaningfully from adult GT because the decision to participate involves a dyad of both the child and parent or caregiver/s. It is critical to understand patients’ and caregivers’ perceptions and experiences of the social, emotional, physical, and logistical burdens or benefits of participating in such trials, and how they weigh and prioritize these factors when deciding whether to participate. We conducted a scoping review of the current literature in this subject area with objectives to a) provide an overview of existing literature, b) identify gaps and areas for further research, and c) better understand the lived impact of pediatric GT research on patients and their parents/caregivers. , Four themes emerged, including 1) weighing risks and benefits 2) timing of GT trial participation 3) value of clear communication, and 4) potential impact on quality of life. Notably, our sample surfaced articles about how patients/parents/caregivers were thinking about GT – their understanding of its safety, efficacy, and risks – rather than accounts of their experiences, which was our initial intention. Nevertheless, our findings offer useful insights to improve the informed consent process and promote a more patient- and family-centered approach. Moreover, our findings can contribute to patient advocacy organizations’ efforts to develop educational materials tailored to patients’ and families’ expressed informational needs and perspectives, and can inform more patient- and family-centered policies from GT clinical trial sponsors.

Navigating Informed Consent Requirements and Expectations in Cluster Randomized Trials: Research Ethics Board Members’ and Researchers’ Views

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Navigating Informed Consent Requirements and Expectations in Cluster Randomized Trials: Research Ethics Board Members’ and Researchers’ Views
Anita Ho, Soodabeh Joolaee, Michael McDonald, Don Grant, Michel M White, Holly Longstaff, Eirikur Palsson
Ethics of Human Research, November-December 2023
Abstract
Informed consent is a cornerstone of ethical human research. However, as cluster randomized trials (CRTs) are increasingly popular to evaluate health service interventions, especially as health systems aspire toward the learning health system, questions abound how research teams and research ethics boards (REBs) should navigate intertwining consent and data-use considerations. Methodological and ethical questions include who constitute the participants, whose and what types of consent are necessary, and how data from people who have not consented to participation should be managed to optimize the balance of trust in the research enterprise, respect for persons, the promotion of data integrity, and the pursuit of the public good in the research arena. In this paper, we report the findings and lessons learned from a qualitative study examining how researchers and REB members consider the ethical dimensions of when data can be collected and used in CRTs in the evolving research landscape.

Altered stakes: Identifying gaps in the informed consent process for psychedelic-assisted therapy trials

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Altered stakes: Identifying gaps in the informed consent process for psychedelic-assisted therapy trials
Tahlia R. Harrison
Journal of Psychedelic Studies, 20 November 2023
Abstract
Background and aims
Psychedelic-assisted therapy (P-AT) has been shown to reduce post-traumatic stress disorder (PTSD), depression, and anxiety symptoms, and is likely to be approved in the United States (US) in the coming years. However, concerns about participant safety in these early trials have surfaced, including allegations of sexual misconduct. This paper aims to illuminate how potential risks have been communicated to P-AT participants via informed consent documents and to suggest how existing policy might be modified given the unique risks involved in P-AT trials.
Methods
Publicly available informed consent forms (ICFs) were gathered by searching clinicaltrials.gov. Queries were applied to filter trials involving the use of a classical psychedelic (psilocybin, LSD) or psychedelic-adjacent substance (MDMA, ketamine) in tandem with psychotherapeutic intervention and those with a status of “completed,” “recruiting,” or “active.”
Results
Nineteen ICFs met inclusion criteria and were reviewed to determine what risks, benefits, and safety protocols were communicated to participants in their respective trials. The primary finding from this review of ICFs from P-AT trials revealed that studies were in compliance with federal regulation. However, there were missing elements related to the vulnerability experienced while under the effects of psychedelics that warrant inclusion in future ICFs in P-AT trials.
Conclusion
Although the ICFs for P-AT trials examined in this study covered several important areas related to risk, benefits, safety, and accountability as required by federal regulations in the US, future research should consider ways to expand this content in order to assure that consent is truly informed prior to enrolling subjects.

Optimizing treatment expectations and decision making through informed consent for psychotherapy: A randomized controlled trial

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Optimizing treatment expectations and decision making through informed consent for psychotherapy: A randomized controlled trial
Leonie Gerke, Franz Pauls, Sönke Ladwig, Sarah Liebherz, Klaus Michael Reininger, Levente Kriston, Manuel Trachsel, Martin Härter, Yvonne Nestoriuc
Journal of Consulting and Clinical Psychology, 16 November 2023
Abstract
Objective
The objective of this research was to determine the efficacy and safety of an optimized informed consent (OIC) consultation for psychotherapy.
Method
We performed a randomized controlled superiority online trial involving 2 weeks of treatment and 3 months of follow-up. One hundred twenty-two adults with mental disorders confirmed by structured interview currently neither in out- nor inpatient psychotherapy (mean age: 32, gender identity: 51.6% female, 1.6% diverse), were randomized. Participants received an information brochure about psychotherapy for self-study (treatment as usual [TAU]; n = 61) or TAU plus a one-session OIC utilizing expectation management, contextualization, framing, and shared decision making (n = 61). The primary outcome was treatment expectations at 2-week follow-up.
Results
At 2-week follow-up, participants receiving OIC showed more positive treatment expectations compared to those receiving TAU only (mean difference: 0.70, 95% CI [0.36, 1.04]) with a medium effect size (d = 0.73). Likewise, OIC positively influenced motivation (d = 0.74) and adherence intention (d = 0.46). OIC entailed large effects on reduction of decisional conflict (d = 0.91) and increase of knowledge (d = 0.93). Participants receiving OIC showed higher capacity to consent to treatment (d = 0.63) and higher satisfaction with received information (d = 1.34) compared to TAU. No statistically significant group differences resulted for expected adverse effects of psychotherapy. Results were maintained at 3-month follow-up. Data sets for n = 10 cases (8.2%) were missing (postassessment n = 4, 2-week n = 6, 3-month follow-up n = 8).
Conclusions
Explaining to patients how psychotherapy works via a short consultation was effective in strengthening treatment expectations and decision making in a nonharmful way. Further trials clarifying whether this effectively translates to better treatment outcomes are required. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Informed Consent among Clinical Trial Participants with Different Cancer Diagnoses

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Informed Consent among Clinical Trial Participants with Different Cancer Diagnoses
Research Article
Connie M. Ulrich, Sarah J. Ratcliffe, Camille J. Hochheimer, Qiuping Zhou, Liming Huang, Thomas Gordon, Kathleen Knafl, Therese Richmond, Marilyn M. Schapira, Victoria Miller, Jun J. Mao, Mary Naylor, Christine Grady
AJOB Empirical Bioethics, 3 November 2023
Abstract
Importance
Informed consent is essential to ethical, rigorous research and is important to recruitment and retention in cancer trials.
Objective
To examine cancer clinical trial (CCT) participants’ perceptions of informed consent processes and variations in perceptions by cancer type.
Design and Setting and Participants
Cross-sectional survey from mixed-methods study at National Cancer Institute–designated Northeast comprehensive cancer center. Open-ended and forced-choice items addressed: (1) enrollment and informed consent experiences and (2) decision-making processes, including risk-benefit assessment. Eligibility: CCT participant with gastro-intestinal or genitourinary, hematologic-lymphatic malignancies, lung cancer, and breast or gynecological cancer (N = 334).
Main Outcome Measures
Percentages satisfied with consent process and information provided; and assessing participation’s perceptions of risks/benefits. Multivariable logistic or ordinal regression examined differences by cancer type.
Results
Most patient-participants felt well informed by the consent process (more than 90% overall and by cancer type) and. most (87.4%) reported that the consent form provided all the information they wanted, although nearly half (44.8%) reported that they read the form somewhat carefully or less. More than half (57.9%) said that talking to research staff (i.e., the consent process) had a greater impact on participation decisions than reading the consent form (2.1%). A third (31.1%) were very sure of joining in research studies before the informed consent process (almost half of lung cancer patients did—47.1%). Most patients personally assessed the risks and benefits before consenting. However, trust in physicians played an important role in the decision to enroll in CCT.
Conclusions and Relevance
Cancer patients rely less on written features of the informed consent process than on information obtained from the research staff and their own physicians. Research should focus on information and communication strategies that support informed consent from referring physicians, researchers, and others to improve patient risk-benefit assessment and decision-making.

Effects of same-day consent vs delayed consent on the recruitment and retention of trial participants—an observational SWAT

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Effects of same-day consent vs delayed consent on the recruitment and retention of trial participants—an observational SWAT
Methodology
Elfghi, F. Jordan, S. Sultan, W. Tawfick
Trials, 25 October 2023
Open access
Abstract
Background and aim
The recruitment process in a randomized trial can be challenging. Poor recruitment can have a negative impact on the allocated budget and estimated completion date of the study and may result in an underpowered study. We aimed to perform a Study Within A Trial (SWAT) to evaluate the impact of same-day consent or delayed consent on recruitment and retention in the host trial.
Methods
This SWAT is designed as a prospective cohort design. The host trial was a randomized controlled trial evaluating the effectiveness of an intensive lifestyle modification programme in participants with peripheral arterial disease. Researchers screened the participants for inclusion and exclusion criteria. Informed consents were obtained from the participants who were willing to participate in the study on a standardized consent form. Participants were given the option to consent on the same day or to delay their consent. Following the consent, the participants were allocated to two groups (same-day consent vs. delayed consent) based on pre-determined criteria for SWAT. One hundred sixteen participants were consented to take part in the host trial. Seventy-five participants were randomized to the host trial. The primary outcome was the proportion of participants who withdrew consent at the recruitment phase. Secondary outcomes were reasons for consent withdrawal and dropout, attrition rate, and adherence with the host trial intervention.
Results
There was a significantly lower consent-withdrawal rate in same-day consent (17.4%, n = 8/46), compared to the delayed consent group (47.1%, n = 33/70), p = 0.001. There was a significantly lower dropout rate in participants randomized following same-day consent (10.5%, n = 4/38), compared to those randomized after delayed consent (29.7%, n = 11/37), p = 0.038. Transport was the main reason mentioned for consent withdrawal and dropout. In participants randomized to the host trial intervention arm, there was a significant difference in adherence (percentage of the 12-week programme completed) between same-day consent (96.7% ± 4.9) and delayed consent participants (86.4% ± 11.2), p = 0.003, as well as number of weeks completed (mean difference =  − 1.547, 95% confidence intervals (− 2.237 to − 0.85)), p = 0.02.
Conclusion
This SWAT found evidence that participants who gave consent on the same day seemed to have better adherence and fewer-withdrawal and dropout rates.

Editor’s note: A SWAT is a “study within a trial”.

A Systems Approach to Improving Clinical Trial Informed Consent Forms in Lung Cancer Clinical Trials

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A Systems Approach to Improving Clinical Trial Informed Consent Forms in Lung Cancer Clinical Trials
Conference Paper
King-Kallimanis, T. Chihuri, A. Ferris, U. BasuRoy
Precision Language In Thoracic Oncology, 11 September 2023
Abstract
Introduction
The informed consent form (ICF) literature is filled with ideas about how to aid potential trial participants in making informed choices. Yet, ICFs continue to grow in length with increased trial complexity and remain dense documents. In our review of lung cancer ICFs presented at WCLC 2022, we reported that these ICFs did not meet the regulatory requirement of being written at an 8th grade reading level. Building on that work we explored, from a systems perspective, the barriers to implementing a patient-centric addendum summarizing key information to the ICF.
Methods
We solicited key stakeholder feedback in three stages to understand barriers and facilitators to creating an addendum. Three stages of work are described. 1. Industry roundtable; Presentation of our earlier work to eight companies followed by a discussion of potential barriers to implementing an addendum. 2. One-on-one research stakeholder interviews; 15 interviews including IRB chairs, legal/compliance advisors, regulators, bioethicists, research nurses and principal investigators. Each interview explored the stakeholder’s role in developing/using ICFs, information selection, and improving the ICF. 3. Patient/Caregiver online survey; open to patients and caregivers living with lung cancer. Participants were asked to read 13 regulatory requirements for ICFs and rank the six most important to them, and provide their preferences regarding the presentation of information.
Results
Industry stakeholders generally supported an addendum to the ICF. However, they raised concerns regarding how “key information” would be selected and not be perceived as “cherry picking”. This concern was raised because of internal efforts of attendees when creating summaries to accompany the ICF for their own trials. In the research stakeholder one-on-one interviews, participants involved in developing ICF language expressed a desire for a standardized form. There was no agreement on the creation of an addendum; some participants argued it is yet another document for review while others supported its creation. One participant succinctly described the addendum as analogous to the patient leaflet for prescribed medications. Surveyed patients and caregivers indicated a strong preference for information to be presented in bullet format (67%). Most participants ranked, as their first preference, the requirement of being told “What will happen during the study” (Figure).
Conclusions
Previous studies identifying methods to help with comprehension of ICFs have gone mostly ignored. By taking a systems approach through leveraging key stakeholder feedback to learn of hidden barriers, we want to ensure patients are making an informed choice to participate in clinical trials.

Proactively tailoring implementation: the case of shared decision-making for lung cancer screening across the VA New England Healthcare Network

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Proactively tailoring implementation: the case of shared decision-making for lung cancer screening across the VA New England Healthcare Network
Research
Abigail N. Herbst, Megan B. McCullough, Renda Soylemez Wiener, Anna M. Barker, Elizabeth M. Maguire, Gemmae M. Fix
BMC Health Services Research, 22 November 2023
Open Access
Abstract
Background
Shared Decision-Making to discuss how the benefits and harms of lung cancer screening align with patient values is required by the US Centers for Medicare and Medicaid and recommended by multiple organizations. Barriers at organizational, clinician, clinical encounter, and patient levels prevent SDM from meeting quality standards in routine practice. We developed an implementation plan, using the socio-ecological model, for Shared Decision-Making for lung cancer screening for the Department of Veterans Affairs (VA) New England Healthcare System. Because understanding the local context is critical to implementation success, we sought to proactively tailor our original implementation plan to address barriers to achieving guideline-concordant lung cancer screening.
Methods
We conducted a formative evaluation using an ethnographic approach to proactively identify barriers to Shared Decision-Making and tailor our implementation plan. Data consisted of qualitative interviews with leadership and clinicians from seven VA New England medical centers, regional meeting notes, and Shared Decision-Making scripts and documents used by providers. Tailoring was guided by the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS).
Results
We tailored the original implementation plan to address barriers we identified at the organizational, clinician, clinical encounter, and patient levels. Overall, we removed two implementation strategies, added five strategies, and modified the content of two strategies. For example, at the clinician level, we learned that past personal and clinical experiences predisposed clinicians to focus on the benefits of lung cancer screening. To address this barrier, we modified the content of our original implementation strategy Make Training Dynamic to prompt providers to self-reflect about their screening beliefs and values, encouraging them to discuss both the benefits and potential harms of lung cancer screening.
Conclusions
Formative evaluations can be used to proactively tailor implementation strategies to fit local contexts. We tailored our implementation plan to address unique barriers we identified, with the goal of improving implementation success. The FRAME-IS aided our team in thoughtfully addressing and modifying our original implementation plan. Others seeking to maximize the effectiveness of complex interventions may consider using a similar approach.