Accelerating Clinical Research by Streamlining Multi-Site Review of Human Subjects Research

Research involving human participants is key to improving public health and advancing medicine. Oversight of such research by institutional review boards (IRBs) both protects research participants  and promotes ethical science.  IRB review and approval is a critical step in initiating the start of a research project and for multi-site studies, NIH is taking an important step to help streamline the process.

Today, NIH is issuing the NIH Policy on the Use of a Single Institutional Review Board (IRB) for Multi-Site Research (sIRB Policy) in both the Federal Register and the NIH Guide to Grants and Contracts.  The sIRB policy establishes the expectation that a single IRB of record will be used to conduct ethical reviews for domestic sites of multi-site, non-exempt human subjects research protocols that are funded by NIH.   The goal is to promote effective IRB review of multi-site research proposals while eliminating the unnecessary repetition of those reviews across sites.  In developing the policy, NIH considered input from a range of stakeholders who commented on a 2014 draft version. The comments are discussed in the preamble to the final policy, and a compilation of the public comments are available on the NIH Office of Science Policy (OSP) website.

This move to a single IRB model also presents a unique opportunity to harmonize the standards and agreements used in clinical research. The NIH National Center for Advancing Translational Sciences (NCATS), through its Clinical and Translational Science Awards (CTSA) Program, convened experts across the nation to develop a “single IRB reliance model” for multi-site clinical studies. This model, the NCATS “Streamlined, Multisite, Accelerated Resources for Trials” (or “SMART”) IRB Reliance Platform, provides investigators and clinical research review networks with a flexible and user-friendly toolkit.  Several CTSA-supported institutions have already adopted this platform leading the goal to have all CTSA institutions use the SMART IRB Reliance Platform. More information about SMART IRB is available on the NCATS website.

To give the research community ample time to prepare for this change, the NIH is providing a long lead time before the policy takes effect on May 25, 2017.  In addition to the SMART IRB Reliance Platform, guidance on implementation of the sIRB policy is available, such as how costs may be charged to NIH awards. Information and resources, such as FAQs, will be posted to the NIH OSP website, as they are developed. NIH will continue to add information to this page prior to the policy implementation date.

We look forward to working with our stakeholders to facilitate implementation, and welcome input on additional information or clarifications that may be helpful.  We also encourage you to read a statement published today by NIH Director Francis Collins on the importance of this issue.

For further questions or additional information about the policy, we invite you to contact us at [email protected].

Dr. Mike Lauer is the NIH Deputy Director for Extramural Research and blogs about NIH research funding policies and data at his blog, Open Mike.

Posted by Dr. Carrie D. Wolinetz, June 21, 2016

Dr. Mike Lauer
NIH Deputy Director for Extramural Research

Emerging Biotechnologies and the Role of the NIH RAC

Next week, we mark the 40th anniversary of the first publication of the NIH Guidelines governing experiments using recombinant DNA. On June 23rd, 1976, former NIH Director Dr. Donald Frederickson announced that all NIH funded and conducted research involving recombinant DNA would be expected to follow the NIH Guidelines, noting both the great potential benefits that could arise from this new technology and the lack of certainty about the risks.

We have come a long way in 40 years, and the use of recombinant DNA is ubiquitous in research, medicine, and many other aspects of our daily lives. Recently, the NIH announced revisions to the NIH Guidelines that included amending the criteria and process for how human gene transfer protocols would be selected for review by the Recombinant DNA Advisory committee (RAC), limiting in depth review and public discussion only for exceptional cases.

Just such an exceptional case comes before the RAC during their meeting this week. During the June 21-22 meeting, the RAC will review a protocol involving the first-in-human use of gene editing via CRISPR/Cas9 technology.  This T cell immunotherapy protocol involves the use of CRISPR/Cas9 to edit two genes in T cells also modified to express T cell receptors targeting myeloma, melanoma, and sarcoma tumor cells.  Consideration of this study underlines the purpose of changing the RAC process: to better use the collective breadth of experience of the RAC members in reviewing gene transfer trials and novel technologies that pose unknown risks, exactly as described by Dr. Frederickson four decades ago.

Researchers in the field of gene transfer are excited by the potential of utilizing CRISPR/Cas9 to repair or delete mutations that are involved in numerous human diseases in less time and at a lower cost than earlier gene editing systems.  While the application of new gene editing technologies in this field has great potential to improve human health, it is not without concerns.  In a previous statement, NIH Director, Dr. Francis Collins, reiterated NIH’s commitment to support innovations in biomedical research in a fashion that reflects well-established scientific and ethical principles.  Having a body such as the RAC available to publicly discuss the scientific, safety, and ethical implications of such cutting-edge experiments helps to ensure we are living up to that commitment.

As the application of biotechnology innovations moves closer to the clinical realm, we are confident that the changes we have made to the NIH Guidelines will enable the RAC to devote its full resources to where they are most needed. And as science continues to evolve, we will strive for parallel evolution in our policies to make oversight of research commensurate with the risks involved.

I encourage you to either attend the upcoming RAC meeting in person, or through the NIH Videocast to learn more about the exciting advances being made in the field of gene transfer.  Information about the RAC meeting, including an agenda and the meeting location can be found on the OSP website.

Posted by Dr. Carrie D. Wolinetz, June 16, 2016

Capturing Impact: A Method for Measuring Progress

NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.

Let me pose a simple question – how do we know if NIH is achieving its mission?  It’s tricky enough to assess how effective we are at generating fundamental scientific knowledge, though we have decent grasp on that side of the equation.  We can link tens of thousands of biomedical research articles published each year to the NIH grants that supported them.  But can we take it a few sizeable steps further and systematically connect our research efforts to advances in human health?  And how can we use what we learn to design policies and strategies to speed innovation and biomedical progress?

The pathways from research to practice to changes in public health are typically non-linear and unpredictable.  For a scientific discovery to make that journey may take decades or more and involves a complex ecosystem – academic scientists, research funders, policymakers, health product developers, regulators, clinicians, and a receptive public, just to name a few. To better understand these intricate pathways, we conducted a handful of case studies that help illuminate the types of evidence and data that NIH can draw from in order to measure our progress towards our ultimate goal – improving human health.

Today we are publishing three case studies in a new section on the “Impact of NIH Research” website, titled “Our Stories.”  These studies, developed with our partners in the Institutes and Centers, trace the chain of evidence between scientific discoveries to longer-term health impact, reaching back into basic research findings that set the stage for progress and noting NIH’s role as well as that of others along the way.  Study topics range from a childhood vaccine that dramatically reduced the incidence of a deadly infection, to a paradigm-shifting approach for treating cancer, to a suite of neurotechnologies for profound impairments like deafness, paralysis, and Parkinson’s disease.  Focusing on these topics gave us a chance to examine the factors that led to their success and broadly map the data sources and strategies we should cultivate in order to improve our capacity for assessing impact (positive, negative, and null) across NIH’s portfolio.  In an era of big data, when the ability to link and analyze multiple streams of information has never been better, this seemed an opportune time to go on a data hunt.

The data we drew from were wide-ranging, including grants, research publications, press releases, patents, FDA approvals, clinical guidelines, policy and regulatory decisions, industry reports, economic analyses, medical expenditures, and public health statistics.  In piecing these disparate sources together, some clear needs emerged – it would be fantastic to link NIH’s grants data to structured data from other Federal sources, like FDA, CDC, AHRQ, USPTO, and CMS.  Citations in patents, FDA approval packages, clinical trials and guidelines, and regulations could help link such outputs to federal funding.  One of the biggest challenges is the need for strategies to connect research advances to long-term changes in health practice and outcomes, for example data on healthcare utilization, disease statistics, and quality of life measures.  We at NIH, and particularly our colleagues in the Office of Extramural Research and the Office of Portfolio Analysis, are pushing to develop and bring just these kinds of data into our own administrative data systems. We’re hopeful that emerging data tools may one day keep track of our impacts, and our influence on the health of the Nation, almost as thoroughly as we track our grants.

The studies we post today are just a few examples of the continuing work of NIH to measure our progress in improving the health of all Americans and those across the globe.  I invite you to take a look, not just at the story itself, but also the backbone of evidence behind it.  Hopefully, you’ll get a sense of the vibrant and diverse ways that NIH turns discovery into health, and how we’re grappling with making that process even better.

Posted by Dr. Carrie D. Wolinetz, June 1, 2016