Tag: Science Policy Coordination

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

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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

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

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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
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A New NIH Resource on the Lasting Legacy of Henrietta Lacks

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The amazing and tragic story of Henrietta Lacks became part of the public’s consciousness in large part thanks to Rebecca Skloot’s 2010 book “The Immortal Life of Henrietta Lacks,” which spent 75 weeks on the New York Times Best Seller’s list.  Prior to her untimely death at the age of 31 from an aggressive form of cervical cancer, Henrietta’s doctors at Johns Hopkins extracted cells from her tumor and were able to keep those cells alive and replicating.  These cells, thereafter known as HeLa cells, have helped enable some of the most important advances in biomedical research over the past 65 years.

In 2013, researchers in Germany published a paper that described the full sequence of the HeLa genome.  This publication immediately raised privacy concerns with respect to the Lacks family because of the potential to identify the family’s potential disease risk.  In response to this, NIH partnered with the Lacks family to provide a mechanism for whole genome sequence data generated from HeLa cells to be used to advance research, while respecting the family’s privacy and wishes.

In subsequent conversations with NIH, members of the Lacks family have emphasized how much they value learning about the nature and progress of HeLa cells in research.  This got us here at NIH thinking “how can we quantify the impact of HeLa cells over the past six decades?”

To answer that question, the NIH Office of Science Policy (OSP), in collaboration with the NIH Library recently put together the first ever systematic and comprehensive literature review on the contributions of HeLa to biomedical science.  We have taken the results of this review and have added several new pages to the OSP website that display the data in a powerful, interactive and interesting way

The new pages feature:

  • A timeline of significant research milestones that were enabled by the use of HeLa cells;
  • An interactive world-map where users can scroll to see the number of publications there have been in each of the 142 countries with a publication since 1953;
  • A relational chord chart that shows the interconnectivity between HeLa cells and many essential areas of biomedical research; and
  • Links and information on the most highly cited papers relating to HeLa cells from 1953-2017.

This resource can be accessed at: https://osp.od.nih.gov/scientific-sharing/hela-cells-landing/. While there, you can take a deep dive into how HeLa cells have contributed to the development of the polio vaccine, the advent of recombinant DNA technology, nanotechnology treatment for cancer, and many other impactful applications over the past 65 years.

I invite everyone to take a look at this new resource so that they can get a sense of how important Henrietta and the Lacks family’s contribution to biomedical research has been.  OSP will continue to update the information on the site as necessary so that the site will remain a living testament to Henrietta.  The generosity of the Lacks family has ensured that Henrietta’s legacy will continue to be one of scientific progress and hope for a healthier world.

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The Protocol Template for Behavioral and Social Sciences Research Involving Humans: A New Community Resource!

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A few months ago, back in August 2018, we authored a blog letting the community know that we were working on a new resource for behavioral and social science researchers to prepare research protocols for human studies measuring a behavioral or social outcome or testing a behavioral or social science based intervention. We are now happy to report back that the template has been finalized and is ready for researchers to utilize.  Even better news is that the template has been fully integrated into the NIH’s Clinical e-Protocol Writing Tool!

As you may recall from our previous post, the Behavioral and Social Clinical Trials Template was derived from the successful NIH-FDA Phase 2/3 IND-IDE Clinical Trial Template but was adapted to include terminology and approaches used by behavioral and social scientists. While use of the template is not required, we would like to share a few of the reasons why we encourage investigators to take advantage of the benefits it affords.

TOP REASONS TO USE THE NEW BEHAVIORAL AND SOCIAL SCIENCES RESEARCH TEMPLATE

  • The template is an effective resource for communicating the science, methods, and operations of a clinical trial thus allowing for standardization of procedures and guiding replication studies.
  • Consistent use of the template will reduce the chance for inaccuracies in study procedures that could potentially result in null or spurious findings.
  • It fosters training and accountability of study staff and allows for efficient review by peers and oversight bodies.
  • It assists investigators who are less familiar with the information and level of detail expected in a clinical protocol and fully adheres to the International Conference on Harmonisation (ICH) E6 Good Clinical Practice guidelines.
  • Utilizing the template through the e-Protocol Writing Tool allows users to seamlessly send and edit protocol information through the e-Protocol Writing Tool allows users to seamlessly send and edit protocol information directly to clinicaltrials.gov.

These are just a few of the reasons that we are excited about this template and why we believe that it is such a valuable resource to the research community.

We also recognize that many researchers involved in clinical behavioral and social sciences research already prepare protocols, whether they be for submission to an IRB or for an operations manual aimed at research staff.  This template can also be an important tool for preparing those documents.

While the template is a suggested format for clinical trials that are testing a behavioral or social intervention or manipulation it can be an effective tool to help anticipate decision-points and potential challenges before a study launches, thus helping avoid delays down the road.

We encourage all of our clinical behavioral and social sciences stakeholders to take a look at both the template document and the associated e-protocol writing tool.  We think once you start using these resources you will see the value they offer.  Also, we would appreciate any feedback users have on their experiences with the template and tool.  These resources are meant to be “living” tools that will evolve based on feedback so that they are of maximum utility to the community.

This blog was co-authored by Dr. William Riley, Director of the NIH Office of Behavioral and Social Sciences Research (OBSSR). More information about OBSSR can be found at https://obssr.od.nih.gov.

William Riley
Director of the NIH Office of Behavioral and Social Sciences Research
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