Archive for the ‘Biomedical research’ Category

New Webinar: “Mistakes Commonly Made on NIH Grant Applications”

In an effort to provide cost-effective training to the broadest group possible, I am launching a series of webinars in the upcoming months. The first of these will be in early February, and the goal will be to help grantees recognize and correct common submission mistakes.

Unlike many who conduct NIH submission training programs, I myself work on NIH submissions full time. I see clients make the same types of mistakes repeatedly– mistakes that are easily avoided.

Each year I am fortunate to have dozens of clients share their Summary Statements with me. Because I regularly read reviewer comments from a multitude of study sections, I can easily identify trends in pink sheets. I also keep track of evolving trends at NIH based on information I find in FOAs, Notices, and Appropriations Testimony. Study sections change, funding priorities evolve. It is important to understand NIH’s priorities right now.

I have helped clients land over $200 million in federal funds in the past five years. Your NIH submission will entail several hundred hours of work by you and others. Why not learn strategies to optimize your success on this and future submissions?

What: Webinar entitled “Mistakes Commonly Made on NIH Grant Applications

Who: Ideal for faculty preparing to submit a K, R21, R03, or R01 in an upcoming cycle, and the senior faculty and administrators who advise them.

When:Wednesday 4 February 2015, 11am-12:30pm EST or
Thursday 12 February 2015, 11am-12:30pm EST
Cost: $149
Takeaways: At the end of this 90-minute session, participants will be able to:
1) Predict some key criticisms reviewers may make
2) Identify problems in their or their colleague’s draft applications
3) Utilize that information to write stronger drafts

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Ketamine — A New Drug Treatment For Depression?

Koratmember

Credit: Koratmember at FreeDigitalPhotos.net

Remember ketamine, the old veterinary (and sometimes street) drug? Apparently it rapidly and significantly reduces anhedonia in those with treatment-resistant bipolar disorder, according to a new study.

Anhedonia, which is a lack of interest in activities that once gave a person pleasure, is a key feature of treatment-resistant bipolar disorder. According to a recent NIH-funded clinical trial, ketamine restored pleasure-seeking behavior independent of its other antidepressant properties in these patients. What’s more, it did so about 40 minutes after a single infusion, and the effect lasted as long as 14 days.

To me the most interesting part of this study is that ketamine did not act on the midbrain areas typically involved in depressive symptoms. Rather, PET scans on patients in the depressive phase of bipolar disorder showed that after ketamine infusion, there was activity in the dorsal anterior cingulate cortex (dACC). This region lies deep within the brain, resting on the medial surface of the frontal lobes. Its precise role remains somewhat elusive, though it is thought to govern conscious control of goal-directed behavior. The most recent significant study I could find on its function was a 2012 paper in Nature suggesting that the dACC is involved in optimizing behavioral adaptations to continuously evolving demands by predicting the difficulty of a task.

“Our findings help to deconstruct what has traditionally been lumped together as depression,” explained Carlos Zarate, M.D., of NIMH. “We break out a component that responds uniquely to a treatment that works through different brain systems than conventional antidepressants — and link that response to different circuitry than other depression symptoms.”

Imaging studies similar to the one just published are underway in patients with major depression, though results are not yet available. Other studies have suggested that ketamine may be exerting these effects through glutamate and dopamine pathways. Research is underway to explore easier methods of drug delivery, such as nasal spray.

Of late, ketamine has been studied for its rapid antidepressant properties, providing relief within hours rather than the weeks required for traditional medications to work. At present, ketamine is not FDA approved for treatment of depression and it is still used primarily in a veterinary setting.

Ketamine is an NMDA receptor antagonist, though it also inhibits reuptake of dopamine, serotonin, and norepinephrine. It was developed in 1962 and has been used in both humans and animals. It is categorized as a dissociative agent. It has been used for general anesthesia, sedation, and as a pain killer. Side effects include amnesia and agitation, and its street use has led to hallucinations, delirium, and death.

NIH Awards $31M To Increase Diversity in The Biomedical Research Workforce

Credit: Photokanok at FreeDigitalPhoto.net

Credit: Photokanok at FreeDigitalPhoto.net

In late October, NIH issued a news release stating that it will award $31 million to enhance diversity in the biomedical research workforce in FY14. The award will go to over 50 recipients who will be part of the national Diversity Program Consortium, established to engage researchers from underrepresented backgrounds. Award recipients work at geographically diverse institutions across the country that serve underrepresented communities. Members of the consortium will develop, implement, and evaluate methods for encouraging individuals to pursue careers in biomedical research and remain in this field.

Research shows that economic, social, and cultural factors significantly influence the pursuit of science careers. Dr. Hannah Valentine, NIH chief officer for scientific workforce diversity, asserts, “These awards represent a significant step toward ensuring that NIH’s future biomedical research workforce will reflect the unique perspectives found within the diverse composition of our society.”

The Diversity Program Consortium is part of a five-year plan with three major initiatives. The goal of the first initiative, BUILD, is to explore new approaches to attract students from diverse backgrounds to the biomedical science workforce. The goal of the second initiative, the National Research Mentoring Network (NRMN), is to develop best practices for mentoring individuals from underrepresented groups. Finally, work carried out as part of the Coordination and Evaluation Center is designed to assess the effectiveness of the training and mentoring approaches developed by BUILD and NRMN. It will also establish short- and long-term methods for measuring the effectiveness of both training and mentoring programs.

Scientists Explore Shared Biology In Human, Fly, and Worm Genomes

 

ID-100203689

Credit: rajcreationzs at FreeDigitalPhoto.net

Researchers analyzing human, fly, and worm genomes have found that these species have a number of key genomic processes in common, reflecting a shared ancestry. Three papers were published in the Aug. 28, 2014 issue of Nature offering insights into embryonic development, gene regulation, and other biological processes vital to understanding human biology and disease.

These studies utilized data generated by the model organism ENCyclopedia Of DNA Elements (modENCODE) and the ENCyclopedia Of DNA Elements (ENCODE) Project, both supported by NHGRI. Launched in 2007, the goal of modENCODE is to create a comprehensive catalog of functional elements in the fruit fly and roundworm genomes for use by the research community. Initial catalogs were published in 2010. The ENCODE Project is building a comprehensive catalog of functional elements in the human and mouse genome.

More than a dozen modENCODE Consortium papers have been or will be published in the journals Nature, Genome Research, Genome Biology, and the Proceedings of the National Academy of Sciences this year. This collection of papers is the culmination of the modENCODE program, for which funding ended in 2012. More than 100 papers using modENCODE data by groups outside of the program have already been published. It is anticipated that the data and resources produced by modENCODE will continue to be used by the broader research community for years to come.

World RePORT: A Worldwide Health Research Database

Credit: Stuart Miles at FreeDigitalPhoto.net

Credit: Stuart Miles at FreeDigitalPhoto.net

An article recently published in the September 12th issue of  Science discusses the necessity of creating a global map of    health R&D activities. The goal is to improve coordination  of research and create a “global observatory” for health research.

The Science article states, “How to finance research and   development where normal market forces are absent has been the focus of a number of studies organized by the World Health Organization (WHO), culminating in 2012 with a report that assessed the strengths and weaknesses of more than 100 new financing mechanisms (1). One of the issues that became clear in compiling this report was the absence of good data. There is no global health R&D map that provides a comprehensive picture of research funding, ongoing research, and results that could be used to guide the allocation of the limited available funding. Consequently, the member states of WHO have called for the establishment of a global observatory on health R&D to address this lack of information (2).”

While a truly comprehensive global health observatory is still years away, the World Health Organization recently created a database, the World Research -Portfolio Online Reporting Tool (World RePORT), which constitutes an important first step toward this goal. Released last year, the beta version of World RePORT was initially limited to research conducted in sub-Saharan Africa. However since then, a new funding organization has been added (the European & Developing Countries Clinical Trials Partnership; EDCTP) and coverage has been expanded to include NIH projects funded in 2013 and projects emanating from South Asia and East Asia/Pacific regions of the world.

As existing funders update the database with projects funded in 2013 across this expanded set of regions, the hope is that the database will help researchers build more effective networks and allow governments and donors to invest their time and money more strategically. Complete information from all ten current funders, as well as information on new organizations joining the World RePORT, will be available on the site soon.

As to the question of funding, the article explains: “As with many WHO projects of this type, it is a new activity and will require new and additional funding outside of its existing budget. A conservative estimate is that $11.5 million will be needed in the first 5 years to cover project staff and software development and to build capacity in those countries (the majority) that do not report health R&D data.”

Top Ten Things NIH Reviewers Should NOT Say In A Review

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Credit: Ambro at FreeDigitalPhotos.net

The Center for Scientific Review publishes their Peer Review Notes three times a year, and the most recent issue came out yesterday. The news items are always interesting and it is worth subscribing, if you don’t already. This issue contained an item about things NIH reviewers should not say. I repeat the list in its entirety here—I thought it might be fun for my grantees to see reviewers critiqued for a change.

What do you think of this list? Have you seen one or two of these on your Summary Statements? Me personally? I have seen variations on # 2, 4, and 10 in Summary Statements, and have strongly suspected reviewers of #1 and 5. I almost fell out of my chair laughing when I read # 7, sometimes I think CSR is a little out of touch with what actually happens on Study Sections:

  1. “I didn’t read the application, but I scanned it and saw the applicant said XXX. He doesn’t know what he’s doing.” Damning statements like this can skew a review discussion over something that might be insignificant in the context of the overall application. It’s better for you to ask other reviewers who have read the application carefully what they think about XXX.
  2. “This New Investigator does not appear to be fully independent since he continues to co-publish with his fellowship mentor/department chair, or does not have designated lab space, or has not been promoted in the past several years.”  Academic research organizations have widely diverse policies for faculty advancements and lab space, and many PIs maintain productive and healthy collaborations with mentors for many years after establishing themselves as bona fide investigators. You should focus more on the investigator accomplishments, such as being the first or senior author on a significant publication or giving presentations at major scientific meetings.
  3. “This application is not in my area of expertise . . . “  If you’re assigned an application you feel uncomfortable reviewing, you should tell your Scientific Review Officer as soon as possible before the meeting.
  4. “I don’t see this basic science research affecting my clinical practice any time soon.” An application does not necessarily have to show the potential for clinical or timely impact—if the applicant doesn’t make such claims. Basic research often takes time to pay off, and you’re charged to assess the “likelihood for the project to exert a sustained, powerful influence on the research field(s) involved.” Absence of an effect on public health does not necessarily constitute a weakness in basic science.
  5. “I like this project but I’m giving it a poorer score because the applicant has too much money.” Other funding is not a scoreable matter. You should focus on the application’s scientific and technical merit. However, you can note an excessive budget request in the budget section for NIH to consider.
  6. “This application has 2 great aims and 1 bad one. I would recommend deleting Aim 3, and I can give it a 1 or 2.” You cannot trade aims with scores. The application needs to be evaluated as a whole.
  7. “This R21 application does not have pilot data, which should be provided to ensure the success of the project.” R21s are exploratory projects to collect pilot data. Preliminary data are not required, although they can be evaluated if provided.
  8. “The human subject protection section does not spell out the specifics, but they already got the IRB approval, and therefore, it is ok.” IRB approval is not required at this stage, and it should not be considered to replace evaluation of the protection plans.
  9. “This application was scored a 25 and 14th percentile last time it was reviewed . . . .” You should not mention the previous score an application got, because this could skew the review discussion. Focus on the strengths and weaknesses of the current application as well as the responses to previous critiques.
  10. “This is a fishing expedition.” It would be better if you said the research plan is exploratory in nature, which may be a great thing to do if there are compelling reasons to explore a specific area. Well-designed exploratory or discovery research can provide a wealth of knowledge.

NIH Funding to Study Sex as a Fundamental Variable in Clinical Research

Credit: Photokanok at FreeDigitalPhotos.net

Credit: Photokanok at FreeDigitalPhotos.net

I am popping up from my mountain of R01 drafts to bring attention to an important NIH news release. Yesterday, NIH announced it has devoted over $10 million in supplemental funding for 82 grantees to explore sex differences in their clinical and pre-clinical research.

The news release states, “These awards are the latest round of funding in a program described in a May 2014 Nature commentary by [Janine Austin Clayton, M.D., NIH associate director for women’s health research] and NIH Director Francis S. Collins, M.D., Ph.D. This commentary informed NIH grantees and other stakeholders of the agency’s intent to develop policies that will require applicants to address the influence of sex in the design and analysis of biomedical research with animals and cells.”

The news release states that the goal of the supplements is to serve as “…a catalyst for considering sex as a fundamental variable in research.”

NIH began this program in FY13, initially funding 50 supplements ($4.6 million total.) The initiative has been led by the Office of Research on Women’s Health. Most of the NIH ICs have funded supplements since the inception of the program.

Historically, medical research has been conducted predominantly on white male subjects. NIH has made efforts to expand the scope of clinical research to include both sexes and to represent multiple races and ethnicities. Grantees who want to succeed in the NIH arena would be wise to incorporate such variables into current and future studies.

 

 

Update on the New NIH Biosketch Format

Credit: adamr at  FreeDigitalPhotos.net

Credit: adamr at FreeDigitalPhotos.net

There are changes pending for the NIH biosketch format, and I think it is good news for NIH grantees. The new NIH biosketch format will allow up to five pages for the entire biosketch, as opposed to the current four-page limit. Even better, rather than simply listing publications, the new format will give researchers the opportunity to highlight the magnitude and significance of the scientific advances associated with their discoveries and the specific role they played in those findings.

Grantees will be permitted to describe up to five of their most significant contributions to science, the influence of their contributions on their scientific field, and any subsequent effects of these contributions on the fields of medicine or technology. This will help reviewers better focus on the applicant’s most important contributions to science. Researchers also will be able to include a link to their complete list of publications in SciENcv or My Bibliography.

NIH recently launched a new round of pilot tests (here and here) to make sure the new format will work well for both applicants and reviewers. The pilot will involve surveys of both reviewers and applicants to help NIH fine tune the application instructions and guidance to reviewers. NIH plans to roll out the modified biosketch for all grant applications received for FY 2016 funding and beyond (which generally refers to applications submitted in early 2015).

To learn more about the NIH’s new Biosketch format click *here*

 

NIH Commits to 12-Year Plan for BRAIN Initiative

Credit: Koratmember at FreDigitalPhotos.net

Credit: Koratmember at FreDigitalPhotos.net

Last month a federal report was released calling for $4.5 billion in funding for brain research over the next 12 years. On June 5th, 2014 the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative was presented to NIH Director Francis Collins by his Advisory Committee to the Director (ACD). The report, drafted by the ACD BRAIN Working Group, maps out a sustained commitment of $4.5 billion in new federal funding over 10 years, beginning in fiscal year 2016, to achieve seven primary goals (see bullets below).

NIH has already announced an investment of $40 million in fiscal year 2014 and President Obama has made a request for $100 million for NIH’s component of the initiative in his fiscal year 2015 budget. The working group emphasized in its report that its cost estimates assume that the budget for the BRAIN Initiative will supplement — not supplant — NIH’s existing investment in the broader spectrum of basic, translational, and clinical neuroscience research.

The NIH efforts on the BRAIN Initiative will focus on mapping the circuits of the brain, measuring the fluctuating patterns of electrical and chemical activity flowing within those circuits, and understanding how their interplay creates our unique cognitive and behavioral capabilities.

The following seven scientific goals were identified as high priorities for achieving this vision:

  • Identify and provide experimental access to the different brain cell types to determine their roles in health and disease.
  • Generate circuit diagrams that vary in resolution from synapses to the whole brain.
  • Produce a dynamic picture of the functioning brain by developing and applying improved methods for large-scale monitoring of neural activity.
  • Link brain activity to behavior with precise interventional tools that change neural circuit dynamics.
  • Produce conceptual foundations for understanding the biological basis of mental processes through development of new theoretical and data analysis tools.
  • Develop innovative technologies to understand the human brain and treat its disorders; create and support integrated brain research networks.
  • Integrate new technological and conceptual approaches produced in the other goals to discover how dynamic patterns of neural activity are transformed into cognition, emotion, perception, and action in health and disease.

The BRAIN Initiative is jointly led by NIH, Defense Advanced Research Projects Agency (DARPA) of the U.S. Department of Defense, National Science Foundation, and Food and Drug Administration. Private organizations are also committed to ensuring success through investment in the initiative.

About the ACD:

The ACD advises the NIH Director on policy matters important to the NIH mission of conducting and supporting biomedical and behavioral research, research training, and translating research results for the public. For more information on the ACD and the full agenda of this meeting, visit: http://acd.od.nih.gov/index.htm

 

 

NIH Common Fund Celebrates 10th Anniversary

Credit: Stuart Miles at FreeDigitalPhotos.net

Credit: Stuart Miles at FreeDigitalPhotos.net

This month the NIH celebrates the 10th anniversary of the NIH Common Fund, a funding mechanism created to support cross-cutting, trans-NIH programs that require participation by at least two NIH Institutes or Centers (ICs). These large collaborative, multi-disciplinary research projects often have the potential to encourage the development of innovative technologies and research tools that, until the development of the Common Fund, would have had difficulty meshing with the plans of any single one of the existing 27 NIH Institutes or Centers.

Over the last decade, the Common Fund has supported significant and transformative research, including the Human Microbiome Project, Big Data to Knowledge (BD2K), Extracellular RNA, Nanomedicine, Epigenomics, Undiagnosed Diseases Program, as well as the High-Risk, High-Reward Research Program that funds individual scientists with particularly innovative ideas or transformative technologies that may lack the preliminary data typically used to evaluate NIH grant applications.

To celebrate this significant milestone in the program’s history, on July 19th the NIH hosted the Common Fund Symposium featuring talks by Dr. Zerhouni, former director of the NIH (2002-2008), as well as many of the remarkable scientists who have led research projects supported by the NIH Common Fund. For those unable to attend the symposium, an archived version of the webcast is accessible to the public here. In addition, over the course of the Symposium, the winners of the first-ever Common Fund video competition were unveiled. This competition encouraged researchers to describe their work to the public utilizing wonderfully creative and often humorous methods, and are well worth a look!

 

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