Author: admin

‘Twas the Night Before……

Posted on

‘Twas the night before Christmas, And nobody’s here.

All of us Feds are on break, But please don’t you fear…

The policy gurus, soon will return,

NIH’s midnight oil will not cease to burn.

The NExTRAC working groups are now on their way,

Emerging biotech we need to think on today.

And the Draft Data Policy is finally out,

Waiting for comments, the cheers and the shouts.

The BESH researchers are nestled, snug in their delay,

As we work with them on ensuring results see light of day.

Rumors are flying on the public access front,

We have no comment, if I may be so blunt.

The Common Rule at long last will go into effect,

Genomic Summary Results, you can now freely detect.

Return of results, we’re still thinking deep thoughts,

How to respect research participants, who we care about lots.

We’re thinking about ethics for humans, monkeys, and BRAIN,

That doesn’t mean new policy, is our constant refrain!

And I, in my role as NIH Chief of Staff,

“What work-life balance?”, I’ve been known to laugh.

On sexual harassment, let me be very clear,

Unacceptable, immoral, and not welcome here.

The culture that allows bad behavior to occur,

Is something everyone of us is responsible for.

Science needs to change, NIH needs to drive it,

We must unite with those who have somehow survived it.

“So, on civility, on respect, on diversity and inclusion!

On safe research spaces, down with biased exclusion!

On polices that promote only science that is best,

Rigorous and translatable, when put to the test!”

And when the NSABB convenes in the first quarter of ’20,

Biosecurity and transparency, we’ll talk about plenty!

The NIH Guidelines need a refresh,

And improving clinical trials goes well beyond BESH.

Heritable gene editing is still all the rage,

Will the world’s governance bodies get on the same page?

Policy opportunities abound in the coming New Year!

From all of our stakeholders, we’re dying to hear…

But for now let’s pause, as we rarely do,

To say from NIH OSP, happy holidays to you!

Blog Roll

A Quick Word About Human Embryo Model Systems

Posted on

Rapidly emerging areas of science can pose interesting challenges for policy frameworks intended to provide oversight of biomedical research or statutory limitations on NIH funding. A recent example, as described in this story on NPR, is an area of research in which scientists are hoping to gain insight on human development by creating structures that model certain aspects of embryonic development. The methods used to create these various model systems generally use human pluripotent stem cells, which are then differentiated into cell types with characteristics and/or organization similar to those seen in human embryos.

NIH has had a long-standing statutory limitation on funding research involving human embryos. The limitation, sometimes called the ‘Dickey-Wicker” amendment, is included annually in HHS appropriations language and has been incorporated into the NIH Grants Policy Statement (GPS). The GPS specifies that “NIH funds may not be used for (1) the creation of a human embryo or embryos for research purposes…”

You can probably anticipate the question I usually have to address. Can research involving various models of aspects of human embryo development be supported by NIH? The answer is “it depends.”

As a steward of taxpayer funds, NIH considers, on a case-by-case basis, whether we can support specific research proposals given the limitations set by the NIH GPS. NIH applies the same considerations to both research proposing the use of human embryos and research that aims to create or use experimental systems with human cells that model human embryos. We examine all experimental details specific to that experiment in order to make an informed decision about whether the research could be supported.

It is also important to note that even if NIH were to determine that proposed research is supportable under the limitation–NIH Institutes and Centers consider scientific merit, program priorities, their portfolio balance, and the availability of funds in making final funding decisions.

To help identify and better understand some of the unknowns associated with this nascent field of research, the National Academies of Science, Engineering, and Medicine will be holding a state of the science workshop on mammalian embryo model systems on Friday, January 17, 2020. I am looking forward to hearing more from the experts in the field about the opportunities and challenges that face this type of research.

Related Blog Post: Sharing Our Current Thinking: Models Containing Aspects of Human Embryos

Posted by Dr. Carrie D. Wolinetz, October 10, 2019

Blog Roll

Update on the “NIH Workshop on Optimizing Reproducibility in Nonhuman Primate Research Studies by Enhancing Rigor and Transparency”

Posted on

I’ve received a lot of emails from folks asking why NIH announced and then subsequently postponed the “NIH Workshop on Optimizing Reproducibility in Nonhuman Primate Research Studies by Enhancing Rigor and Transparency.”  With everything going on in this space, NIH decided to pump the brakes on our NHP workshop to make sure we were putting together an agenda that moves the conversation forward and takes advantage of the expertise and groundwork already laid.

Over the past few years, NIH has been bolstering activities and policies focused on enhancing the rigor and reproducibility of the science it funds.  A notable example of this would be the work we have been doing to improve the quality and transparency of clinical trials. As discussed at the June meeting of the Advisory Committee to the NIH Director (ACD), the agency is now turning its attention to identifying gaps and opportunities to improve the rigor, reproducibility, translational validity, and transparency of studies involving animal models.

At that same meeting, NIH Director Francis Collins made it clear that nonhuman primate (NHP) research is essential to the NIH portfolio given the fundamental role it plays in both basic and translational research. In fact, the NIH Office of Research Infrastructure Programs (ORIP) recently released a two-part report on assessing nonhuman primate needs and resources for biomedical research, which projected an increased and unique need for NHP models, particularly in the areas of neuroscience and infectious disease.

While the NIH effort is focused rightfully on all species used in biomedical research, NHP research presents some unique opportunities and challenges. This has long been recognized in the animal welfare arena (for example, the Office of Laboratory Animal Welfare has six species-specific publications on enrichment for NHP) and has been well documented in considerations of scientific justification and oversight.  Moreover, the very qualities that make NHPs the best – and sometimes only – models for the study of human disease and translation of medical advancements also make them the subject of great public interest of which we, as a publicly funded research agency, are cognizant.

To help think through these unique issues, we will be convening a workshop of experts in the field of NHP models to discuss best practices for how these variables are assessed and taken into consideration. This includes thinking through how welfare considerations (such as housing enrichment, long-term care needs, social engagement, etc.) might clarify – or confound – research findings, as well as discussing whether the intersection of cutting-edge science, like neuroscience or gene editing, might present unique ethical considerations for NHP research.

An important thing to keep in mind is that NIH is not alone in thinking about these issues.  The National Academies recently hosted two workshops on the use of NHPs.  The first workshop focused on opportunities afforded by new NHPs models while the second focused on the care, use, and welfare of marmosets involved in gene-editing research. This mirrors the discussions arising in the scientific and bioethics communities about the intersection of NHP research, emerging technologies, and ethical issues.[1] [2] [3] Additionally, recognizing the value of NHP data and the need to share data efficiently, researchers are beginning to self-assemble to promote collaboration and open science. For instance, the PRIMatE Data Exchange is hosting a meeting in the fall at the Wellcome Trust to bring leading investigators from around the world to develop action plans related to activities in the field of NHP imaging. At the end of the day, all of these efforts have a common goal: assuring the best quality science adheres to commonsense ethical standards in order to improve human health.

We look forward to engaging with stakeholders to share best practices, consider new challenges, and offer pathways for improvement if needed. Stay tuned for further information…

[1] Sadato et al. (2019) Neuroethical issues of the Brain/MINDS project of Japan. Neuron, 101:385-389. https://doi.org/10.1016/j.neuron.2019.01.006

[2] Greely et al. (2016) Neuroethics in the age of brain projects. Neuron, 92(3): 637-641. https://doi.org/10.1016/j.neuron.2016.10.048

[3] Johnson, L.S. (2019) Neuroethics of the nonhuman. AJOB Neuroscience, 10(3):111-136. https://www.tandfonline.com/doi/full/10.1080/21507740.2019.1632973?af=R&

Posted by Dr. Carrie D. Wolinetz, September 16, 2019

Blog Roll

Continuing to Work with the Community on Registration and Results Reporting for Basic Experimental Studies Involving Humans

Posted on

The research that NIH funds doesn’t always fall neatly into a single category.  Basic research involving humans that seeks to understand the fundamental aspects of phenomena also may meet the NIH-definition of a clinical trial.   We refer to these studies as BESH – Basic Experimental Studies involving Humans (see our previous blog). Since this type of research meets the NIH definition of a clinical trial, these trials must register and report summary results information for transparency and other purposes outlined in the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information. However, some researchers have faced challenges in fitting these studies into the data fields for submission in ClinicalTrials.gov.

In response to concerns from the basic science communities, the NIH issued a Request for Information (RFI; NOT-OD-18-217) seeking additional input from stakeholders on how best to implement the NIH clinical trials policies.  NIH asked for examples of BESH that pose challenges for registration and results reporting on ClinicalTrials.gov, asked for potential modifications to ClinicalTrials.gov that would better meet the needs of BESH, and asked about the strengths and weaknesses of potential alternative platforms.

Thanks to the outreach efforts of the basic science communities and organizations, we received a robust response to the RFI.  A predominant theme of these responses was agreement on the importance of registration and results reporting for research transparency and on ensuring that the contributions of human research participants advance science and public health. Examples of challenges included registering and reporting both cognitive and brain function studies, and studies involving a series of trials in which the design of subsequent trials are contingent on the findings of prior trials.

To further understand the challenges of registering and reporting results for BESH on ClinicalTrials.gov, staff at the National Library of Medicine performed an in-depth analysis of several recently published articles selected from respondents to the RFI. Four primary challenges to registering and reporting results of BESH in ClinicalTrials.gov were identified from this analysis:

  1. reporting for multiple, interrelated small studies,
  2. apparent absence of prespecified primary outcome measures in the published articles,
  3. results reported for a few individual participants in a non-aggregated manner, and
  4. iterative preliminary studies to develop or optimize procedures.

These characteristics are difficult to address in a system designed to represent one study per record with at least one pre-specified primary outcome measure and with aggregated summary results information provided in tabular format.

Although most BESH are not expected to have these specific challenges, for those that do, the requirement of registering and results reporting on ClinicalTrials.gov might not communicate what the studies planned to do, or was done, in a scientifically meaningful and useful manner.  The NIH has determined that more time is needed to address these challenges. Today, NIH published a Guide Notice (NOT-OD-19-126) announcing the extension of delayed enforcement of registering and results reporting of BESH on ClinicalTrials.gov through September 24, 2021.  Investigators conducting BESH are still expected to register and report results on alternative, publicly available platforms during this interim period, but are not required to do so on ClinicalTrials.gov at this time.

During this interim period, we will continue to work together with the basic science community to understand more fully the challenges of disseminating information about BESH and explore solutions that are meaningful and useful to other researchers and members of the public. In the coming months, NIH will be reaching out to the basic science community and asking for assistance in helping us reach this goal. Working together, we believe that we can create a system that can facilitate the registration and results reporting for all clinical trials, while maintaining the NIH commitment to stewardship and transparency of the research we support.

This blog was co-authored by Dr. William Riley, Director of the NIH Office of Behavioral and Social Sciences Research (OBSSR) and Dr. Mike Lauer, the NIH Deputy Director for Extramural Research (OER).

More information about OBSSR can be found at https://obssr.od.nih.gov/. Information about OER can be found at: https://grants.nih.gov/grants/oer.htm.

Dr. Mike Lauer
NIH Deputy Director for Extramural Research
William Riley
Director of the NIH Office of Behavioral and Social Sciences Research
Blog Roll