Overview of the January 2015 National Advisory Neurological Disorders and Stroke Council Reply

Further discussion of a concept for an innovative new funding mechanism (had been discussed at the previous Council), as well as concept approval for clinical studies related to emergency medicine and adolescent brain development, headlined the January 2015 National Advisory Neurological Disorders and Stroke Council (NANDSC), my first as acting Institute Director.

Following my opening remarks about important NINDS-related news, which I address at the end of this message, Director of the NINDS Division of Extramural Research Bob Finkelstein introduced a proposal for a new funding mechanism (the R35) that would give principal investigators (PIs) broad, sustained, and flexible support for their research programs.

The R35, which would fund PIs’ overall research programs, rather than individual projects, is intended to enhance the stability of funding to research labs and to allow scientists greater flexibility in pursuing new research directions. Nearly half of federally-funded PIs need multiple grants to support their labs; according to a 2012 report external link, PIs estimated that an average of 42% of their research time associated with federally-funded projects was spent on meeting requirements rather than conducting active research. By providing more stable funding through an award with a longer duration than an R01, the R35 mechanism could reduce time spent writing multiple grant applications, allowing investigators more freedom to perform research that breaks new ground or extends previous discoveries in new directions.

The review process would assess the merit and impact of the PI’s previous accomplishments, focus on the potential significance of the proposed research program, and consider the potential for the investigator’s productivity and impact to continue at a high level. To ensure enough time for applicants to establish appropriate track records, they must have had at least four years of R01 (or R01-equivalent) support at the time of R35 application.  Council was enthusiastic about NINDS moving forward with this new mechanism, and a funding opportunity announcement could be released this summer.

Council also approved the idea of NINDS joining seven other NIH ICs in participating in the ABCD (Adolescent Brain Cognitive Development) Initiative, a longitudinal study assessing the cognitive development of about 10,000 nine- to ten-year-old children. Assessments will be made of physical health, development, psychosocial factors, cognition, and academic achievement. Neuroimaging and biomarker data will also be collected. NINDS will co-fund a Phase 1 U01 for approximately $500,000 and later will fund a Phase 2 mission-specific RFA. NINDS is especially interested in the effects of concussion on adolescent development.

Dr. Ray Dorsey, Professor of Neurology at the University of Rochester Medical Center, discussed a recently completed evaluation of the NETT (Neurological Emergencies Treatment Trials) external link program. NETT, an emergency neurology clinical trial network of 17 hubs jointly coordinated by the University of Michigan and the Medical University of South Carolina, has to-date conducted six large-scale clinical trials that have had a profound impact on neurology emergency research. The conclusion of the evaluation is that NETT has conducted its trials with greater efficiency than similar trials outside the network. Recommendations include increasing NETT’s impact by conducting more trials, improving its contracting processes, and engaging key groups including minorities and junior investigators.

Building off the successes of NETT and planning for a future emergency research network, Dr. Patricia Walicke, Medical Officer in the Office of Translational Research, presented the SIREN (Strategies to Innovate EmeRgENcy Care) clinical trials concept, which was approved by council. Half of the top ten complaints driving the approximately 136 million U.S. emergency department visits annually involve issues related to the brain, heart, or lungs. The SIREN program seeks to bring together investigators and NIH scientists from diverse disciplines to efficiently conduct at least four randomized, clinical endpoint trials related to emergency medicine over a five-year period at 10-15 pre-hospital and emergency department hubs with additional scalable spokes. The SIREN program will be a partnership between NINDS, NHLBI—whose council approved SIREN in October 2014—NCATS, and the US Army Medical Research and Material Command—whose command is especially interested in trauma research. RFAs for network infrastructure are expected to be published by NINDS in November 2015, with funds to be released in October 2016.

Dr. Marie Gill, Health Program Specialist in the NINDS Office of Clinical Research, and Dr. Elizabeth McNeil, Acting Director of the NINDS Office of Clinical Research, gave an overview of the biennial report “Inclusion of Women and Minorities as Subjects in Clinical Research.” Congress mandates that women and minorities must be included in all NIH-funded clinical research in appropriate numbers based on the scientific question being studied. To address this mandate, NINDS has included language on the NIH inclusion policy in our Phase 3 clinical trial FOAs. Going forward, performance on inclusion will be considered during the discussions of overall study performance/milestone setting for funded Phase 3 clinical trials.

NINDS Program Director Dr. Shai Silberberg provided an overview of the important issue of maintaining a high level of scientific rigor in order to increase the reproducibility of research findings. While a number of factors contribute to irreproducibility, Dr. Silberberg pointed to bias and poor scientific rigor as the primary culprits. In 2012, NINDS leadership organized a workshop at NIH that explored ways to increase scientific rigor that are now being implemented. In general, the recommendations external link focused on proper randomization, blinding, sample-size estimation, and data handling. More recently, a meeting convened by NIH, Nature, and Science in June 2014 brought together editors from more than 30 journals with representatives of funding agencies to strengthen reporting standards. This meeting led to the creation of a list of “Principles and Guidelines for Reporting Preclinical Research.” In addition, NINDS has signed onto an NIGMS RFA to provide R25 grants that will support the creation of training modules about conducting reproducible research aimed at graduate students, postdoctoral researchers, and junior investigators. NINDS has also signed onto an NIGMS RFA to provide R01 awards that will support empirical research on research integrity. Other planned trans-NIH actions include reviewer checklists for reporting standards and scientific rigor, a biosketch with a focus on accomplishments rather than just publications, longer-term awards to reduce “perverse incentives” to publish too quickly, and supporting replication studies.

Finally, I discussed the recent activities of two NIH-wide working groups focused on different aspects of our biomedical workforce, as well as a handful of Institute highlights that have transpired since the last advisory council.

  1. The NIH Physician Scientist Workforce (PSW) Working Group recently announced several recommendations, including increased training support for MD/PhDs, supporting more physician scientists through individual fellowships rather than institutional training grants, establishing a new granting mechanism to facilitate physician scientists’ transition to independence, expanding the loan repayment program, and enhancing physician scientist diversity.
  2. The NIH Common Fund has recently established the “Enhancing the Diversity of the NIH-Funded Workforce” program. The goal of the program is to figure out ways to merge social science with biomedical research training to develop and test new approaches to training and mentoring on a large scale. Action areas include: recruitment and retention; leadership and professional development for postdocs and early tenure track PIs; enhancing the NIH climate of inclusion and belonging; building partnerships with diverse institutions; and leveraging new disciplines as opportunities to attract next generation researchers.

Other NINDS Highlights:

  • NINDS and NIMH each received increases of $12.3 M for the NIH BRAIN Initiative.
  • The NIH Scientific Management Review Board is looking for ways to further optimize the process of reviewing, awarding, and managing grants in a way that maximizes the time researchers can devote to research. An internal analysis indicated that NINDS grants management is exceptionally efficient, and is a leader among NIH ICs for quickest median time-to-award (from study section release to awarding of funds) during each of the January, May, and October 2013 council rounds.
  • NINDS released the “Promoting Research in Basic Neuroscience” funding opportunity to stimulate increased research applications addressing fundamental questions in basic neuroscience.
  • The Office of Translational Research migrated the entire suite of translational funding mechanisms to the CREATE, BPN 2.0, and IGNITE programs. OTR funding also led to several successful efforts.
  • NINDS co-sponsored the Seizure Prediction Challenge external link to improve the prediction of epliptic seizures. More than 500 teams entered the crowd-sourced contest. The winning team, comprising a neuroscientist, a mathematician, and three engineers, developed an algorithm that predicted seizures with greater than 80% accuracy. Stronger seizure prediction can provide individuals with epilepsy enough warning to avoid potentially dangerous activities like swimming and driving. Also, being able to predict when seizures are likely to occur can help individuals decide the best times for taking medication and can help reduce the overall need for medication.
  • A second Epilepsy Center without Walls (CWOW) was established to tackle sudden unexpected death in epilepsy (SUDEP), the leading cause of premature death in human epilepsy.
  • NINDS co-hosted a small blood vessels workshop that focused on the need for integration of research findings across model systems, organ systems, and technologies.

A link to the video cast of the council is available. The next council will take place on May 28-29, 2015.

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