Ethics Archives - Page 5 of 13

A peer-reviewed article recently published in JAMA Network Open details CTTI work to get stakeholder feedback on informed consent language for hospital-acquired and/or ventilator-associated bacterial pneumonia (HABP/VABP) studies. The article describes the process of gathering feedback from 52 stakeholders to identify the most important elements to include in the informed consent process.

Previous CTTI research suggested that an early enrollment strategy using advance consent in pneumonia antibiotic trials is acceptable to key stakeholders. As part of that research, CTTI also engaged these stakeholders to identify, describe, and reach consensus on essential concepts that should be included in an advance consent form for a HABP/VABP clinical trial. Concepts were:

Reassurances on patient health and treatment
Reasons for advance consent and enrolling early
Explanation of non-inferiority

The proposed consent language developed in this process, in combination with a strategy for enrolling patients at highest risk for pneumonia before infection onset, may help potential participants make informed decisions about their involvement in clinical research. It may also improve enrollment rates in trials from which data are urgently needed to evaluate new treatments and improve patient care.

Learn more about past CTTI work on HABP/VABP.

Webinar Recording Now Available: CTTI’s Framework for Evaluating the NIH Single IRB Policy

Posted on January 22, 2020March 5, 2025 by Hannah Faulkner

A recording is now available of a CTTI webinar held on Thurs., Jan. 16, which provided a recap of resources available to help implement a sIRB model, as well as an overview of a recent project CTTI undertook to develop a framework that could help in evaluation of the NIH’s single IRB (sIRB) policy. The webinar was led by Cynthia Hahn (Integrated Research Strategy), Stephen Rosenfeld (Secretary’s Advisory Committee on Human Research Protections), and Heather Pierce (Association of American Medical Colleges).

CTTI has been involved in driving adoption of sIRBs for over a decade, but its recent work with the NIH is especially critical this month as changes to the Common Rule take effect, requiring all multi-site research studies to use a sIRB for review.

To develop its evaluation framework, CTTI conducted a literature review and interviews with a diverse set of stakeholders engaged in the process of sIRB adoption.

The webinar outlined the framework’s recommendations for measuring and continuously improving the sIRB model, including:

Creating a database of organizations that are implementing the sIRB model, as well as which organizations are serving as an sIRB.
Developing and testing a survey instrument to help evaluate sIRB function and collect metrics.
Establishing, defining, and routinely collecting and sharing metrics, such as sIRB review time and time spent performing other sIRB-related activities. The team pointed out that although many metrics are quantitative, it is also important to have qualitative metrics to assess the overall quality of the sIRB process. Routine sharing of these metrics would serve to encourage improvement and eliminate unnecessary duplication.

Explore CTTI’s existing resources and recommendations for sIRB adoption on the CTTI website.

CTTI Webinar Will Highlight sIRB Adoption Resources & Evaluation Considerations

Posted on January 8, 2020March 5, 2025 by Hannah Faulkner

As more single institutional review board (sIRB) requirements from the Common Rule go into effect this month, CTTI can help organizations navigate the change. A webinar on Thurs., Jan. 16 at noon ET will provide an overview of existing CTTI sIRB work, as well as suggestions for sIRB evaluation.

CTTI has been at the forefront of the sIRB movement for nearly a decade, championing the thoughtful implementation of sIRBs for multicenter clinical trials to enhance patient safety, accelerate study start-up, and improve trial conduct.

The webinar will highlight CTTI’s suite of recommendations and resources, as well as discuss outcomes from a recent collaboration between CTTI and a NIH sIRB policy workgroup. Speakers will include:

Cynthia Hahn, President, Integrated Research Strategy
Heather Pierce, Senior Director for Science Policy and Regulatory Counsel, Association of American Medical Colleges
Stephen Rosenfeld, Chair, Secretary’s Advisory Committee on Human Research Protections

Add the webinar to your calendar today.

Single IRB

Topics Included: Safety

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For over a decade, CTTI has championed the adoption of single IRBs (sIRBs) for multicenter clinical trials in an effort to streamline and optimize study execution.

Use the following resources to adopt an sIRB model:

Recommendations and resources to address barriers to using sIRBs for multicenter clinical trials and for driving sIRB implementation
Resources for determining institutional engagement
A case study of the IMPACT-AFib trial's successfully implementation of an sIRB framework

CTTI also collaborated with an NIH workgroup to develop a comprehensive plan for assessing the NIH's sIRB policy. The final evaluation framework report describes suggested next steps and key elements to be included in a future evaluation of the sIRB model.

What is the issue?

Before a clinical trial begins, the study protocol needs to be reviewed by an impartial third party (usually an IRB) to ensure ethical rigor and to determine that the study provides potential benefits and prevents unnecessary harm to participants. In a multicenter trial (i.e., a study that investigates a single research question at several different sites/locations), each site’s IRB (often referred to as a local IRB) usually reviews the protocol separately. This can take a long time, cause duplicate work, and even result in the protocol being changed by individual sites so that it is no longer the same across all sites.

One solution is for all sites in a multicenter trial to use the same IRB (a single IRB of record). Although single IRB (sIRB) review is supported by the FDA, the Office of Human Research Protections (OHRP), and the NIH, the willingness of institutions to defer full local IRB review and approval to an sIRB in multicenter trials continued to vary (Sources: FDA & OHRP).

However, as of January 25, 2018, the NIH mandates the use of an sIRB for multisite, nonexempt NIH-funded clinical studies. U.S. institutions engaged in cooperative federally funded research must rely on an sIRB for the portion of the research conducted in the U.S. since the sIRB provision of the revised Common Rule took effect in January 2020. In addition, the FDA is revising its human subjects protection regulations and guidance because the 21st Century Cures Act required harmonization of human subjects protection regulations between the FDA and the rest of the federal government and modified the Federal Food, Drug, and Cosmetic Act to remove the requirement for review by local institutional review committees for device studies.

Since 2010, CTTI has worked to address challenges of adopting sIRB review. In 2018, this work evolved to focus on supporting adoption of sIRB models.

What CTTI project has been initiated to address the issue?

What are the objectives of CTTI's work on single IRBs?

What is the anticipated impact of CTTI's work on single IRBs?

Using an sIRB for a multicenter trial will improve trial efficiency and consistency.
Use of the Considerations Document will help delineate the legal and ethical responsibilities of institutions and IRBs in overseeing the conduct of clinical trials and can support communication between institutions and sIRBs.
Use of the CTTI-developed tools (including the Considerations Document, an Evaluation Checklist, and a Template IRB Authorization Agreement will make it easier for sponsors, IRBs, and institutions to implement the sIRB model for multisite research.
With widespread use of the sIRB model for multisite trials, study start-up will be accelerated and trial conduct will be improved, allowing treatments to reach patients faster.

How was evidence gathered to support our findings?

What are the findings from this project?

As part of driving adoption activities, CTTI continues to engage stakeholders and investigate ways to ease the transition to sIRBs. In November 2017, CTTI convened an expert meeting to discuss further actions that CTTI, the FDA, the OHRP, and the NIH can take to help the research community adopt sIRB review. In 2018, the NIH selected CTTI to support a workgroup that will develop a comprehensive plan for assessing the effectiveness of the NIH’s new sIRB policy. In September 2019, a CTTI driving adoption committee developed a set of new resources, including an Engagement Overview, Engagement Flowchart, Engagement Scenarios Guide, Engagement Definitions, and a Resource of Resources library.

Additional Resources

Project Team Members

Role	Name	Affiliation	Project
Social Science Lead	Amy Cornelli	Clinical Trials Transformation Initiative	Single IRB Driving Adoption
Team Member	Andy Womack	Genentech - a member of the Roche Group	Single IRB Advancement
Team Member	Cami Gearhart	Quorum Review Inc	Single IRB Advancement
Team Member	Carol Pech	University of Wisconsin	Single IRB Driving Adoption
Team Member	Carrie Dombeck	Duke University	Single IRB
Team Member	Cheryl Grandinetti	Food and Drug Administration	Single IRB
Team Leader	Colleen Gorman	Pfizer Inc	Single IRB
Team Leader	Cynthia Hahn	Feinstein Institute for Medical Research	Single IRB Advancement
Team Member	Deneill Harney	University of Michigan	Single IRB Driving Adoption
Team Member	Devon Check	Duke University	Single IRB
Team Leader	Felix Gyi	Chesapeake IRB	Single IRB
Team Member	Hallie Kassan	Feinstein Institute for Medical Research	Single IRB Advancement/Driving Adoption
Team Member	James Riddle	Advarra Consulting	Single IRB Driving Adoption
Team Member	Jane Perlmutter	Individual Patient/Caregiver	Single IRB & Central IRB Advancement
Team Leader	Jennifer Li	Duke University	Single IRB
Team Member	Jennifer Peterson	Syneos Health	Single IRB Driving Adoption
Team Member	John Buse	NC TraCS, University of North Carolina at Chapel Hill	Single IRB Advancement
Team Member	Judith Kramer	Clinical Trials Transformation Initiative	Single IRB
Team Leader	Kathryn Flynn	Duke University	Single IRB
Team Leader	Kevin Weinfurt	Duke University	Single IRB
Team Member	Lawrence Muhlbaier	Duke University	Single IRB
Team Member	Margaret Rankovic	CITI Program, a Division of BRANY	Single IRB Driving Adoption
Team Member	Michele Russell-Einhorn	Advarra	Single IRB Driving Adoption
Team Member	Nichelle Cobb	University of Wisconsin	Single IRB Driving Adoption
EC Champion	Pat Furlong	Parent Project Muscular Dystrophy	Single IRB Driving Adoption
Team Member	Patrick Archdeacon	Food and Drug Administration	Single IRB
Team Member	Patrick McNeilly	Food and Drug Administration	Single IRB Advancement
Team Leader	Petra Kaufmann	National Institutes of Health	Single IRB Advancement
Team Member	Robert Silbergleit	University of Michigan	Single IRB Driving Adoption
Project Manager	Sara Calvert	Clinical Trials Transformation Initiative	Single IRB & Central IRB Advancement
Team Leader	Soo Bang	Celgene	Single IRB Advancement
Team Member	Yvonne Higgins	WIRB-Copernicus Group	Single IRB Advancement
Team Member	Cynthia Hahn	Feinstein Institute for Medical Research	Single IRB
Team Member	Michael Link	Department of Veterans Affairs	Single IRB Driving Adoption

Organization affiliations are listed as active affiliations during the project.

*Indicates former project manager, team leader, or team member.

Resources

Safety | Recommendations

Recommendations for Data Monitoring Committees

Recommendations for Use of Data Monitoring Committees in Clinical Trials

Safety | Publications

Stakeholder Experiences with the Single IRB Review Process and Recommendations for Food and Drug Administration Guidance

Safety | Case Studies

ASCO Improves the Accuracy and Attribution of Serious Adverse Event Reporting in its Clinical Trials

Safety | Case Studies

Genentech Overhauls its Informed Consent Form to Minimize Patient and Site Burden

Safety | Case Studies

Northwell Health Establishes Single IRB to Improve Trial Oversight and Execution

Safety | CTTI News

New CTTI Publication Highlights Stakeholder Preferences for Informed Consent Language in HABP/VABP Studies

A peer-reviewed article recently published in JAMA Network Open details CTTI work to get stakeholder feedback on informed consent language for hospital-acquired and/or ventilator-associated bacterial pneumonia (HABP/VABP) studies. The article describes the process of...

Safety | CTTI News

Webinar Recording Now Available: CTTI’s Framework for Evaluating the NIH Single IRB Policy

A recording is now available of a CTTI webinar held on Thurs., Jan. 16, which provided a recap of resources available to help implement a sIRB model, as well as an overview...

Safety | CTTI News

CTTI Webinar Will Highlight sIRB Adoption Resources & Evaluation Considerations

As more single institutional review board (sIRB) requirements from the Common Rule go into effect this month, CTTI can help organizations navigate the change. A webinar on Thurs., Jan. 16...

Safety

Single IRB

For nearly a decade, CTTI has championed the adoption of single IRBs (sIRBs) for multicenter clinical trials in an effort to streamline and optimize study execution.

Safety

Informed Consent

The informed consent process can often be burdensome and lacks giving prospective trial participants the information they need to aid in their decision to participate.

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Formats

Stage of Trial

Informed Consent

Topics Included: Recruitment, Safety

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The informed consent process can often be burdensome and lacks giving prospective trial participants the information they need to aid in their decision to participate.

Use CTTI’s recommendations and resources – an informed consent discussion tool and tiered informed consent document – to optimize your informed consent process and provide participants with clear, accurate information about trial specifics, risks, and benefits.

What is the issue?

In accordance with medical ethics regarding research on human subjects and federal regulatory requirements, it is necessary to obtain informed consent (IC) from prospective clinical trial participants. Required elements of IC in health research governed by U.S. Federal Regulations, including FDA regulations and the Common Rule, are clearly described, yet the current IC process is often not meeting the needs of research participants. Informed consent documents (ICDs) are lengthy and may be difficult for patients to comprehend. Institutionally-required legal language is often inserted into ICDs, creating confusion about whether the ICD’s purpose is to clearly inform the patient or to serve institutional needs. Various groups have taken measures to address these concerns, but deficiencies with the process still exist. Issues surrounding re-consent of research participants, as well as when consent is required in a learning system of health care, are related issues but are outside the scope of this project.

What CTTI project has been initiated to address the issue?

What are the objectives of CTTI's work on informed consent?

Identify previous and current efforts to improve ICDs and the IC process, including alternatives to the traditional paper ICD
Describe barriers and propose potential remedies to concisely communicating the required elements of IC
Propose a more effective process, including IC documentation, for ensuring research participants’ understanding of critical IC elements, taking into account variability among research settings and participants

What is the anticipated impact of CTTI's work on informed consent?

Completion of the CTTI Informed Consent project will lead to a higher quality IC process. Application of the corresponding recommendations may lead to the following improvements:

The IC process may be more interactive, customized, and transparent to meet the needs of individual study participants.
Trial staff can benefit from better training tailored to their needs and learning styles, and patients can benefit from more emotionally responsive trial staff.
The ICD can be restructured to increase readability, enhance trial participant understanding of the study, and provide additional information that is easily accessible.
Electronic consent systems may be considered to facilitate use of the improved ICD and consent participants.

How was evidence gathered to support our findings?

What were the findings from this project?

Evidence from the literature review suggests that IRB-, sponsor-, and site-related operational barriers exist, along with an inadequate understanding of what patients want from the IC process. No single proven tool for measuring the quality of IC or effectiveness of consent interventions was cited in the literature. Limited, available evidence suggests that the current consent process has direct consequences on the ability to conduct clinical trials. The analysis of the literature review was published in May 2016. The published results from the expert interviews supported these literature review findings and expanded on identified barriers.

All interviewees agreed that IC is essential to the protection of research participants; however, most acknowledged that the IC process in the United States has evolved into a rigid and cumbersome process that requires immediate attention and reform. Interviewees expressed consensus on three major themes: a new approach to the ICD, enhancing participant understanding of the clinical research, and modification of IRB review.

Some barriers that result in lengthy, variable, and overly complicated ICDs include the following:

IRB-related:

Lack of accepted readability standards
Local IRB review of ICDs in multisite trials
Varying interpretations of regulations
Inadequate training in plain language practices for IRB staff

Sponsor-related:

Challenging legal language added to ICDs to reduce liability

Staff-related barriers to a successful IC process tend to more commonly result in participant dissatisfaction due to unmet emotional needs or lack of relevant trial information. These barriers include:

Disconnection between expectations and reality of IC discussions
Staff de-emphasizes importance of the information to the participant
Pressure to meet enrollment targets shifts focus away from participants and leads to rushed interactions

To address these barriers, experts explored new approaches to the IC process that focused on enhancing trial participant understanding. The most frequent recommendation for a single actionable change was to reform the ICD required for federally regulated research by making it simpler, shorter, and more understandable. Following this, interviewees proposed multiple strategies to create a more interactive and ongoing IC process to enhance research participant understanding. Some strategies include improving staff training on the conduct of an IC discussion, allowing adequate time and selecting the appropriate setting for the discussion, and providing an opportunity for prospective research participants to speak with other participants as a resource for information. Evaluating participants’ understanding was another topic that experts discussed during the interview. Several interviewees proposed that research participants’ comprehension about the clinical investigation be evaluated. A third consensus issue from the interviews was the need for modification of practices in IRB review of clinical research. Aligned with recommendations from the CTTI Single IRB projects, the most substantive expert recommendation was implementation of a single IRB of record for multisite clinical trials.

Additional Resources

Current Relevant FDA and DHHS Regulations:

FDA Regulations are detailed in 21 CFR, Part 50 (Informed Consent of Human Subjects). 50 Subpart B sections on informed consent of human subjects include:

50.20 - General requirements for informed consent
50.23 - Exception from general requirements
50.24 - Exception from informed consent requirements for emergency research
50.25 - Elements of informed consent
50.27 - Documentation of informed consent

DHHS regulations are detailed in 45 CFR, Part 46 (Protection of Human Research Subjects). 46 Subpart A sections on informed consent include:

46.116 - General requirements for informed consent
46.117 - Documentation of informed consent

NIH Collaboratory:

View the NIH Collaboratory's free resources on informed consent.
View a moderated discussion on the HHS Public Meeting Related to Protection of Human Subjects and Standard of Care Research.

Project Team Members

Role	Name	Affiliation
Project Manager	Annemarie Forrest	Clinical Trials Transformation Initiative
Team Leader	Michele Kennett	University of Missouri
Team Leader	Jennifer Lentz	Eli Lilly
Team Leader	Jane Perlmutter	Individual Patient/Caregiver
Team Member	Julia Gorey	Office for Human Research Protections
Team Member	Sheila Young	GlaxoSmithKline
Team Member	Cheryl Grandinetti	Food and Drug Administration
Team Member	Annick Anderson	CISCRP
Team Member	Fred Bloom	CDC
Team Member	Steve Cummings	University of California, San Francisco
Team Member	Molly Flannery	Food and Drug Administration
Team Member	Zachary Hallinan	CISCRP
Team Member	Karim Calis	Food and Drug Administration
Team Member	Jayvant Heera	Pfizer Inc
Team Member	Kevin Hudziak	Eli Lilly
Team Member	Hallie Kassan	Feinstein Institute for Medical Research
Team Member	Beverly Lorell	King & Spaulding
Team Member	Ross McKinney	Duke University
Team Member	Marsha Melvin	Food and Drug Administration
Team Member	Stephen Mikita	Individual Patient/Caregiver
Team Member	Linda Morgan	Individual Patient/Caregiver
Team Member	Seth Schulman	Pfizer Inc
Team Member	Rose Tiernan	Food and Drug Administration
Team Member	Kaveeta Vasisht	Food and Drug Administration
Team Member	Shelia Young	GlaxoSmithKline

Organization affiliations are listed as active affiliations during the project.