Statement on ICF [Informed Consent form] Posting for Clinical Trials Involving Gene Editing/Gene Therapies

GE2P2 Global :: Informed Consent for Genomic Medicine Initiative

Current - May 2022

Context

Ethically responsible conduct of clinical trials requires putting participants/patients at the center  ̶  ensuring safety, securing meaningful informed consent (IC), and proceeding in alignment with relevant national and international ethical guidelines, such as the Declaration of Helsinki [1], the ICH Guideline for Good Clinical Practice (GCP) Guidelines [2], CIOMS guidelines [3] and UNESCO’s Universal Declaration on Bioethics and Human Rights [4].

Responsible conduct of trials also requires compliance with relevant laws and regulations in countries where trials are conducted, and requires competent and continuing oversight by ethics review bodies [ERC/IRBs] at national, local and institutional levels.

Finally, transparency about clinical trial details, progress and results is critical, primarily via registries such as the U.S. National Library of Medicine’s ClinicalTrials.gov and registries aggregated in WHO’s International Clinical Trials Registry Platform.

A key milestone around trials transparency and informed consent was achieved as the revised Common Rule and the associated regulation at 45 CFR 46.116(h) came into force in 2019 [excerpts below]. The regulation requires that for any clinical trial conducted by, or supported by, a Common Rule department or agency [a U.S. government department/agency], a consent form used in enrolling trial participants be posted on either clinicaltrials.gov or regulations.gov within a specific time frame.

The purpose and anticipated benefits of this requirement are discussed in 82 FR 7228 

“The primary purpose of this provision is to improve the quality of consent forms in federally funded research by assuring that—contrary to current practices, under which it is often very difficult to ever obtain a copy of these documents—they eventually would become subject to public scrutiny and that they will provide useful models for others. The consent form plays a key role in making sure that someone asked to enter a clinical trial receives the information they need to be making an informed decision about whether to enroll in that trial. Accordingly, it also plays a key role in supporting and justifying the public’s trust in the integrity of our clinical trial enterprise. 

“Fundamentally, this proposal is about increasing the transparency of one of the most important aspects of our human subjects protection system. Increased transparency is in general a good thing, and in this instance, as in many others, it offers multiple benefits—including increased trust—at very low cost. This provision is not a form of shaming, but rather an effort to ask people to work together to create a system that will improve the quality of informed consent….

“Having a repository of such forms freely available for analysis and public discussion will create multiple opportunities for improving these forms. In an era in which we have previously unheard of capabilities for analyzing textual material and processing large amounts of data, the fact that there will be a high volume of consent forms posted should be a minor impediment, if any, to the ability to learn from the content of this database…”

Of course, the arguments and anticipated benefits supporting this regulation apply, in principle, beyond “federally-funded research”. Indeed, improving the quality of informed consent is a goal which should be a continuous imperative across all clinical trial activity.

While it is still relatively early to measure compliance with this ICF posting requirement, clinicaltrials.gov has added functionality to enable easy posting of ICF documentation, and advanced search functionality allowing for quick searching of all trials where ICF documents have been posted.

Statement

We the undersigned are aligned in efforts to strengthen informed consent practice in genomic medicine, specifically around IC transparency in clinical trials involving gene editing/gene therapy development.

We assert that a broad normative standard around ICF transparency has been established via the ICF posting requirements for trials involving U.S. federal agencies or funding [revised Common Rule and 45 CFR 46.116(h)].

We note that “…public posting of consent forms is intended to increase transparency, enhance confidence in the research enterprise, increase accountability, and inform the development of future consent forms…” 82 FR 7229  and that these outcomes will benefit both current and future clinical trial participants/patients and their families, and the genomic medicine field overall.

We argue that this normative standard should become an imperative across all clinical trial activity, regardless of trial sponsor, funding source, or research focus.

We note that one of the most historically-significant, innovative, and potentially beneficial areas of current biomedical research is genomic medicine. Development of therapies and interventions involving gene editing and similar emerging technologies is now addressing a range of unmet medical needs, including many rare and ultra-rare diseases. 

We further note several important dimensions of gene editing/gene therapy clinical trials including [1] the basic nature and irreversibility of the interventions involved, [2] the long-term follow-up periods involved for trial participants which can span a decade or more, and [3] the age and limited assent/consent capacity of children and adolescents often involved in such trial contexts.

Reflecting the normative standard now in place, the benefits to trial participants/patients, the potential to strengthen public trust, and the dimensions of gene editing/gene therapy trials noted above, we argue that there is a critical opportunity  ̶  indeed an imperative  ̶   for the cell-gene field to align around voluntary posting of ICF materials for gene therapy trials on any registry utilized by the trial sponsor, globally.

We therefore urge all those who fund, sponsor or conduct trials involving gene editing and gene therapy development to commit to posting comprehensive ICF content as expeditiously as practical on relevant clinical trial registries. We argue that such ICF posting should meet, at a minimum, the relevant terms of 45 CFR 46.116(h).

More broadly, we call on gene therapy trial sponsors and the genomic medicine development community overall to actively engage with all stakeholders in designing, strengthening and assessing informed consent  ̶  including leveraging the ICF content posted by the leading organizations that respond to this statement.

Finally, we urge directors/trustees/leaders of gene editing/gene therapy development organizations [commercial/governmental/academic/independent], investors and donors, academic medical centers and trial sites, patient organizations and citizens generally to endorse this statement, and to urge those they influence, or have governance responsibility for, to respond to its call to action.

Clinical Trial Informed Consent Form Posting (45 CFR 46.116(h))

The revised Common Rule requires that for any clinical trial conducted or supported by a Common Rule department or agency, one consent form be posted on a publicly available federal website within a specific time frame. The consent form must have been used in enrolling participants in order to satisfy this new provision. You can read more information about the revised Common Rule on the OHRP website (https://www.hhs.gov/ohrp/education-and-outreach/revised-common-rule/index.html).

At this time, two publicly available federal websites that will satisfy the consent form posting requirement, as required by the revised Common Rule, have been identified: ClinicalTrials.gov and a docket folder on Regulations.gov (Docket ID: HHS-OPHS-2018-0021).  HHS and other Common Rule

departments and agencies are developing instructions and other materials providing more information to the regulated community about this posting requirement

…(h) Posting of clinical trial consent form.

(1) For each clinical trial conducted or supported by a Federal department or agency, one IRB-approved informed consent form used to enroll subjects must be posted by the awardee or the Federal department or agency component conducting the trial on a publicly available Federal Web site that will be established as a repository for such informed consent forms.

(2) If the Federal department or agency supporting or conducting the clinical trial determines that certain information should not be made publicly available on a Federal Web site (e.g. confidential commercial information), such Federal department or agency may permit or require redactions to the information posted.

(3) The informed consent form must be posted on the Federal Web site after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject, as required by the protocol.

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[1]  Declaration of Helsinki (World Medical Association) (2013) and the United States (US) Belmont Report (1979)

[2] International Council for Harmonisation (ICH) E6: Guideline for Good Clinical Practice (GCP) (1996)

[3] International Ethical Guidelines for Biomedical Research Involving Human Subjects issued by the Council for
International Organizations of Medical Sciences (CIOMS 2016)

[4]The Universal Declaration on Bioethics and Human Rights adopted by the United Nations Educational,
Scientific, and Cultural Organisation (UNESCO) (2005)

SIGNATORIES [INVITATION TO JOIN AS A SIGNATORY]

If you or your organization/institution would like to become a signatory to this statement, please confirm via the Google Form at this link [also available at the bottom of this page]. If you prefer to confirm via email, or have any other questions, please contact david.r.curry@ge2p2global.org

INDIVIDUALS - Initial signatories at 08 March 2022

David R Curry, MS President & CEO, GE2P2 Global Foundation, Philadelphia, USA

Thalia Arawi, BA, MA, PHD Salim El-Hoss Bioethics & Professionalism Program (SHBPP) American University of Beirut Beirut, Lebanon

Barbara Redman, PhD, MBE Director, Center for Informed Consent Integrity Senior Fellow, GE2P2 Global Foundation Washington, DC, USA

Arthur Caplan, PhD Mitty Professor of Bioethics NYU Grossman School of Medicine, New York, USA

Professor David McQuoid-Mason Centre for Socio-Legal Studies Howard College University of KwaZulu-Natal, South Africa

Robert I. Field, JD, MPH, PhD Professor of Law and Professor of Health Management and Policy Drexel University Kline School of Law and Dornsife School of Public Health Philadelphia, USA

Prof. Dr. Dirk Lanzerath Institut für Philosophie / Department of Philosophy Universität Bonn / University of Bonn, Germany

Christine Gispen-de Wied, MD Gispen4RegulatoryScience, Netherlands

Steven Martin, MPhil Associate Fellow GE2P2 Global Foundation, U.K.

Getnet Yimer Ali, MD, MSc, PhD Strategic Country Director Ohio State Global One Health LLC Addis Ababa, Ethiopia

Sheila Varadan, PhD, LLM Child Rights Researcher, Bangkok, Thailand

Paige Fitzsimmons, MA Associate Director Center for Informed Consent Integrity GE2P2 Global Foundation U.K.

Dr. Beate Aurich, MRCPCH Fellow, GE2P2 Global Foundation, Paris, France

Jane Kang, MD, MS Fellow, GE2P2 Global Foundation, New York City, USA

Michael Young, MD Fellow, GE2P2 Global Foundation, Boston, USA

Richard Klein Fellow, GE2P2 Global Foundation, Harrisburg, USA

Mary Catherine Collet ALS Advocate, USA

Stephen R. Latham, JD, PhD Director, Interdisciplinary Center for Bioethics Yale University

Benjamin Wilfond, MD Treuman Katz Center for Pediatric Bioethics Seattle Childrens Research Institute and Department of Pediatrics University of Washington School of Medicine, USA

Jestina Doe-Anderson, PhD Senior Fellow/Director, GE2P2 Global Foundation, Atlanta, USA

Hannah Dashefsky, RN, BSN Associate Fellow, GE2P2 Global Foundation, Philadelphia, USA

Eline Bunnik, PhD Associate Professor at the Department of Medical Ethics, Philosophy and History of Medicine at Erasmus MC, Rotterdam, The Netherlands

Daima Bukini, BSc, MBE, MPH, PhD Fellow- Bioethics Muhimbili University of Health and Allied Sciences (MUHAS). Tanzania

Joseph G. Trainor, CPA Senior Fellow, Board Officer, GE2P2 Global Foundation, Philadelphia, USA

Kristen Feemster. MD, MPH, MSHP Senior Fellow, Board Officer, GE2P2 Global Foundation, Philadelphia, USA

Tamra Lysaght PhD Centre for Biomedical Ethics, National University of Singapore

G. Owen Schaefer, DPhil Assistant Professor, Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore

Sarah Blin, MA, MSc GE2P2 Global Foundation [Nepal]

Françoise Baylis, PhD University Research Professor, Dalhousie University, Nova Scoita, Canada

Lisa Eckstein, SJD Senior Lecturer in Law and Medicine/Health Law, University of Tasmania, Australia

Rebekah McWhirter, PhD School of Medicine, Faculty of Health, Deakin University, Victoria, Australia

Susana Pinto Leite Vasconcelos Teixeira Magalhães Integrity Officer, Institute for Research and Innovation in Health (i3S), Portugal

Dr. Mariam Hassan. Pakistan

Fernando Lolas, MD, IDFAPA, Director Interdisciplinary Center for Studies in Bioethics, University of Chile

Maria José Santos, MD, PhD - Rheumatologist, Hospital Garcia de Orta, Almada, Portugal

Maria Alexandra Ribeiro, PhD Professor na Faculty of Medical Sciences, New University of Lisbon, Portugal

INSTITUTIONS - Initial Signatories at 08 March 2022

GE2P2 Global Foundation, USA

Forum for Ethics Review Committees in India, India

Parent Project Muscular Dystrophy [PPMD], USA

I AM ALS, USA

Comité National d'Ethique de Recherche Luxembourg [National Research Ethics Committee of Luxembourg]