Meeting minutes and supplementary materials are available that summarize discussions related to the ethics and regulatory issues associated with each of the new UG3 Demonstration Projects. These discussions, which took place by teleconference, included representation from study principal investigators and study teams, members of the NIH Collaboratory Regulatory/Ethics Core, NIH staff, and NIH Collaboratory Coordinating Center personnel as well as some IRBs responsible for oversight of the projects.
On January 17, 2018, the Department of Health and Human Services and 15 other federal departments and agencies announced a delay to both the effective and compliance dates for the revisions to the “Federal Policy for the Protection of Human Subjects” (also known as the Common Rule). Most provisions in the revised Common Rule were scheduled to go into effect on January 19, 2018. The Interim Final Rule announced a delay until July 19, 2018, with the option for further delay, to give institutions additional time to prepare to implement the revisions. Before July 19, 2018, institutions may only begin implementing provisions of the revised Common Rule that do not conflict with the pre-2018 Common Rule.
A notice of proposed rulemaking (NPRM) is also in development to seek public comment on a proposal for further delay in the required implementation of the revised Common Rule (for example, until January 21, 2019). A decision will be made after considering public comments.
We recently asked Drs. Jeremy Sugarman and Kevin Weinfurt, Co-chairs of the Regulatory/Ethics Core, to reflect on the first 5 years of the Core as well as on the challenges ahead. The regulatory and ethical landscape for pragmatic clinical trials was not well defined when the Core began 5 years ago, and the Core helped to map and navigate the emerging landscape to enable the implementation of Demonstration Projects in ways that satisfied ethical and regulatory criteria.
“The Core’s work has led to the creation of a substantial body of scholarship contributing to the ongoing policy and ethics debates about pragmatic clinical trials.” – Drs. Sugarman and Weinfurt
As part of their ongoing effort to improve the speed and efficiency of conducting clinical trials, the NIH-FDA Joint Leadership Council has created a draft clinical trial protocol template. The template contains instructional and sample text intended to assist NIH-funded investigators in writing protocols for phase 2 or 3 clinical trials that require Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications. Feedback is sought from investigators, investigator-sponsors, institutional review board members, and other stakeholders involved in protocol development and review.
Our goal is to provide an organized way for creative investigators to describe their plans so that others can understand them. – Dr. Pamela McInnes, NIH
Details on the rationale and development of the protocol template are on these blog posts:
Notice Number: NOT-OD-16-043. Responses accepted through April 17, 2016. You can access the template document as well as a template shell, comment form, and other resources at NIH’s Clinical Research Policy website.
Petra Kaufmann, MD, MSc
Director, Office of Rare Diseases Research and Division of Clinical Innovation
National Center for Advancing Translational Sciences
National Institutes of Health
Rachael Fleurence, PhD
Program Director, CER Methods and Infrastructure Program
Patient-Centered Outcomes Research Institute
Sabune J. Winkler, JD
Director, Regulatory Affairs Operations
Webinar details: March 2, 2016 3pm - 4pm ET To join the WebEx, click here: http://bit.ly/1TGRTFS Call-in number: 1-855-244-8681 Access code: 737 807 582
The NIH Collaboratory’s Health Care Systems Interactions Core has published a document entitled Lessons Learned from the NIH Health Care Systems Research Collaboratory Demonstration Projects. The Principal Investigators of each of the Demonstration Projects shared their trial-specific experience with the Core to develop the document, which presents problems and solutions for initiation and implementation of pragmatic clinical trials (PCTs). Lessons learned are divided into the following categories: build partnerships, define clinically important questions, assess feasibility, involve stakeholders in study design, consider institutional review board and regulatory issues, and assess potential issues with biostatistics and the analytic plan.
Other tools available from the Health Care Systems Interactions Core include a guidance document entitled Considerations for Training Front-Line Staff and Clinicians on Pragmatic Clinical Trial Procedures and an introduction to PCTs slide set.
The Office for Human Research Protections (OHRP) has posted a series of six webinars explaining the recent Notice of Proposed Rulemaking (NPRM) regarding revisions to the Common Rule (the federal policy for human subjects protection). The presentations by policy experts can be viewed anytime; they cover the following topics:
- Overview of the NPRM
- Exclusions and exemptions
- Informed consent
- IRB review and operations
- Research with biospecimens
- Secondary research use of data
For more information on the NPRM, visit the OHRP website. The deadline for comments on the proposed revision has been extended to January 6, 2016.
A new series of 12 articles published in a special issue of the journal Clinical Trials addresses ethical and regulatory challenges particular to pragmatic clinical research. Pragmatic clinical trials are designed to efficiently provide answers to important clinical questions, yet they present special challenges in conforming to the ethical and regulatory guidelines that were developed for more traditional clinical research. The special issue describes these challenges and begins to outline possible solutions that will protect the rights and welfare of research participants while allowing pragmatic clinical trials to gather much-needed evidence for informing healthcare decisions. An introductory article is followed by 11 articles addressing individual topics, such as alteration of informed consent, privacy, gatekeepers, and defining minimal risk research. The effort was funded by the NIH Health Care Systems Research Collaboratory, with additional support from the Patient-Centered Outcomes Research Institute (PCORI), and involved diverse groups of stakeholders, including researchers, patient advocates, bioethicists, and regulatory experts. Robert M. Califf, MD, and Jeremy Sugarman, MD, MPH, were editors of the special issue.
For more information:
- Press release
- Articles on the Clinical Trials website are freely available for a limited time until November 15 , 2015
- Descriptions and links to each article on the Living Textbook
- A special series of Grand Rounds presentations will feature topics from the special issue presented by the authors on the third Friday of each month
The Clinical Trials Transformation Initiative (CTTI) has released new recommendations encouraging adoption of a central institutional review board (IRB) model for multicenter clinical trials. The recommendations are based on results from its Central IRB Advancement Project. Along with the recommendations, CTTI offers tools, including evaluation checklists and an IRB authorization agreement template, to help organizations implement a central IRB model.
Read the complete announcement on the CTTI blog.
On December 3, 2014, the National Institutes of Health (NIH) issued a draft policy promoting the use of a single institutional review board (IRB) for multisite studies. IRBs play a critical role in assuring the ethical conduct of research, and studies must be reviewed and approved by an IRB before they can begin. Yet over time, the clinical research landscape has become increasingly complex, expanding from studies formerly conducted at single institutions to large, diverse studies across networks and multiple sites. This situation challenges the practicality of using local IRBs to conduct initial and ongoing reviews for such studies.
The goal of permitting use of a single IRB—also called a central IRB or IRB of record—is to enhance and streamline the process of IRB review for multisite studies so that research can proceed efficiently without compromising ethical principles and protections. While both the FDA and Office for Human Research Protections support the use of a single IRB, too few institutions involved in multisite studies are taking advantage of the option.
Read the NIH draft policy here.
“By using single IRBs in multi-site studies, we reduce duplication of effort, speed the initiation of important research, and save time and taxpayer funds.”
Francis S. Collins, MD, PhD, NIH Director
Among the current NIH programs incorporating the use of a single IRB are:
- National Cancer Institute’s Central Institutional Review Board (CIRB)
- National Institute of Neurological Disorders and Stroke’s Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT)
- Network for Stroke Research (NIH StrokeNet)
Dr. Sally Rockney, NIH deputy director for extramural research, explains the NIH perspective in her blog. Public comment on the draft policy extends for 60 days, through January 29, 2015. When finalized, the policy will apply to all NIH-funded multisite studies carried out in the United States, whether supported through grants, contracts, or the NIH intramural program.