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NIH Extramural Nexus
Updated: 10 hours 48 min ago

4 Questions For Researchers and Institutions Involved In Human Subjects Research

Fri, 08/11/2017 - 13:01

Last September, and in January of this year, we wrote about a suite of initiatives aimed at improving the quality and transparency of the NIH-supported research that most directly engages human participants – clinical trials. These initiatives include dedicated funding opportunity announcements for clinical trials, Good Clinical Practice training, enhanced registration and results reporting on ClinicalTrials.gov, and required use of single IRBs for multi-site studies. We are now entering the final phases of implementation of these initiatives – so, if you are contemplating research involving human subjects, please read on.

We’ve received queries from members of the research community seeking clarity on whether their human subjects research will be affected by these new policies, and if so, how. So, we want to call your attention to four questions researchers involved in human s studies need to ask, and answer. These questions are:

  1. Does the study involve human participants?
  2. Are the participants prospectively assigned to an intervention?
  3. Is the study designed to evaluate the effect of the intervention on the participants?
  4. Is the effect that will be evaluated a health-related biomedical or behavioral outcome?

If the answer to all four questions is yes, then we consider your research a clinical trial.

The NIH definition of a clinical trial is “a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes”. The definition was published in 2014, after extensive public input, and affirmed, after even more public input, in our policy published in September 2016. The clinical trial definition encompasses a wide variety of study types, as shown in figure 1. These range from mechanistic studies to behavioral studies, to pilot/feasibility studies, all the way to large-scale efficacy and effectiveness trials.

Figure 1

The breadth of the NIH definition is intentional, given the nature of the NIH portfolio and imperatives for maximal transparency. Transparency shows respect for the participants who put their trust in us, in the face of unknown outcomes, to help advance science. Our concerns about transparency stem in part from the issues surrounding the reporting of clinical trials data. For both NIH-funded and non-NIH funded trials, unreported data and untimely dissemination of results has been documented over and over again.  Others have expressed concern that the NIH has not collected needed trans-NIH data to enable it to function as proper stewards of clinical trials.

Some have argued that we should not expect trial registration and reporting for small or exploratory trials, for trials that focus on safety, or for trials that fail to meet enrollment targets. As we stated last September, NIH chose to emphasize the value of transparency for these kinds of trials as well, as “the benefits of transparency and the need to fulfill the ethical obligation to participants is as relevant to these types of trials as to any other type.”  We have an ethical obligation to report results, and this is especially true when volunteers contribute their time as study participants in prospective experiments, whether large or small. And, to be effective stewards of precious and constrained taxpayer monies, we need to collect a minimum of standardized data.

This transparency complements existing efforts to promote data sharing, public access to NIH-funded research results, and scientifically rigorous research design, all of which ultimately benefit the research community directly, as well. By developing and sharing robust data, we maximize the value of NIH’s investment in research by allowing scientists to build upon solid results. The definition, and our clinical trial policies, are an integral part of our efforts to enhance scientific stewardship, dissemination of information, transparency, and to excel as a federal science agency that manages for results.

Why is it important to know whether you are proposing to conduct a clinical trial? Correctly identifying whether your study is a clinical trial is crucial to complying with NIH policies, many of which are now in effect,  such as registering and reporting all NIH supported clinical trials in ClinicalTrials.gov and good clinical practice training. Very soon, your answer will be crucial to picking the appropriate NIH funding opportunity for your application, writing your research plan correctly (since some information will be captured in the new human subjects and clinical trials form), and ensuring that your application includes all the information required for peer review.

If you are having difficulty answering the four questions that determine whether a study meets the NIH definition of a clinical trial, we encourage you to consult the case studies and FAQs that are available on our webpage on clinical trial requirements for grants and contracts. We’ll be following up with additional blogs and NIH Extramural Nexus articles that provide more depth on the various initiatives. We strongly encourage you to look at these materials, and share them with your colleagues, to ensure that as an awardee conducting clinical trial research, you are aware of the need to register your trial and report its results.

Categories: NIH-Funding

Perspectives on Evidence-based Funding

Fri, 06/23/2017 - 16:17

At the NIH Regional Seminar this past May, I had the pleasure of giving the keynote talk and presenting different perspectives on how NIH can further the impact of our research funding. Some of the topics I presented in this talk will be familiar to frequent Open Mike blog readers – our concerns about the hypercompetitive nature of applying for NIH support, for example. Others we haven’t discussed in depth here yet – such as how we might measure the contributions of NIH-supported research to treating diseases. My staff recorded this talk and has made it available to you on the NIH Grants YouTube channel. If you’re interested in the topics covered here on the blog (which I hope you are, since you are reading this now!) then you may be interested in this talk.

 

Categories: NIH-Funding

NIH’s Next Generation Researchers Initiative

Fri, 06/16/2017 - 12:22

At the Advisory Committee to the Director meeting last week, NIH Principal Deputy Director Dr. Larry Tabak presented a new NIH initiative to strengthen the biomedical workforce. This presentation followed extensive discussions with stakeholders both here through this blog, at stakeholder meetings, and at NIH advisory council meetings over the last month. We heard unequivocal endorsements for supporting early-career and mid-career researchers given the hypercompetitive funding environment — a challenge we have addressed many times in our blog posts. However, many voiced concerns about our taking a formulaic approach to capping grant funding and called on us to be more direct in enabling greater support for the next generation of biomedical researchers.

For this reason, we have shifted our approach to a focused initiative to support early- and mid-career investigators. As described in a June 8 NIH Director’s statement, and in recognition of the call for such action in the 21st Century Cures Act, we are naming this effort the Next Generation Researchers Initiative. We will take a multi-pronged approach to increase the number of NIH-funded early-stage and mid-career investigators and stabilize the career trajectory of scientists. We describe these approaches on a new web page that we will continue to update. Our activities address both research workforce stability, and evaluation of our investments in research. In brief, NIH will:

  • commit substantial funds from NIH’s base budget, beginning this year with about $210 million, and ramping to approximately $1.1 billion per year after five years (pending availability of funds) to support additional meritorious early-stage investigators and mid-career investigators
  • create a central inventory and track the impact of NIH institute and center funding decisions for early- and mid-career investigators with fundable scores to ensure this new strategy is effectively implemented in all areas of research
  • place greater emphasis on current NIH funding mechanisms aimed at early- and mid-career investigators
  • aim to fund most early-career investigators with R01 equivalent applications that score in the top 25th percentile
  • encourage multiple approaches to develop and test metrics that can be used to evaluate the effectiveness of our research portfolio, and assess the impact of NIH grant support on scientific progress, to ensure the best return on investment

Applicants do not need to do anything special to be eligible for this funding consideration. Beginning this fiscal year, the NIH institute or center (IC) who would fund the grant will give your application special consideration for support if you are:

  • an early-stage investigator (within 10 years of completing your terminal research degree or medical residency and have not previously received a substantial independent NIH research award) and receive a score in the top 25th percentile (or an impact score of 35 if the application is not percentiled)
  • a mid-career investigator (within 10 years of receiving your first NIH R01 equivalent award) who scores in the 25th percentile, and either:
    • are at risk of losing all support, or,
    • are a particularly promising investigator currently supported by a single ongoing award (i.e, NIH will prioritize funding an additional concurrent research project grant award)

NIH ICs make funding decisions to support their mission, and this plan provides flexibility in how ICs will meet the NIH-wide goal of supporting highly scoring early-stage and mid-career researchers. Each IC will make its decisions about how it will prioritize funding to support this initiative.

As further details are announced, we will be updating the Next Generation Researchers Initiative web page with this information. In the meantime, we encourage you to read the NIH Director’s statement, and look at the Advisory Committee to the Director presentation and webcast recording.

We appreciate your feedback in addressing the very important issue of stabilizing the biomedical research workforce. Your comments to this blog (or via email, if preferred) are welcome. With the continued input from individuals at every career stage, as well as research institutions and other stakeholders, we can work together to make changes that ensure the long-term stability and strength of the U.S. biomedical research enterprise, and that advance science to improve health for all.

Categories: NIH-Funding

Getting to Know Federal Funders and their Research Interests

Tue, 06/06/2017 - 15:29

Working with NIH applicants and awardees as an extramural program division director, I often shared the NIH RePORTER resource as a tool for exploring the research topics NIH supports.  Learning what projects we support, using a robust database of historical and newly-funded projects (updated weekly), provides researchers valuable insight as they consider developing their own research programs and applications for funding.

Another valuable tool which you might be familiar with is Federal RePORTER, which expands the RePORTER concept to support searching over 800,000 projects across 17 Federal research agencies, with trans-agency data updated annually. As Federal RePORTER recently received an update to introduce some new functions and additional agency data we’d like to highlight some of the ways it helps both the public and scientific researchers alike understand the government’s research portfolio and trace its impact through published articles and patents.

Figure 1

Search or browse data across agencies: Federal RePORTER is designed for ease-of-use. The homepage offers quick search tools for the most commonly used fields, or you can skip the search and use the interactive bar charts and maps on the home page to quickly drill down to projects funded by a certain agency or projects occurring in a particular state. We’ve also added easy-to-follow walkthroughs as “Guided Tour” links on the home page, advanced search page, and results page to learn more. From your search results, you can refine results through links on the sidebar, or read more about individual projects (including a description, and details on the investigator, research organization, and funder.)

Figure 2

Figure 3

Figure 4

Explore search results even further:  As with NIH RePORTER, you can export the results for further exploration and analysis, or use the built -in “Charts”, “Map”, or “Topics” tools from the sidebar to learn more about the projects, as in the examples shown below. For example, you can summarize the projects by agency, state, or fiscal year (Figure 2), or map where the research is taking place (Figure 3). You can also explore groups of scientific topics within your search results (for example, a search for “lead” and “drinking water” returns groups of projects covering “ground water”, “ early life”, “arsenic exposure”, and more.) From there, you can drill down into subgroups, to generate lists of projects in that group (Figure 4).

Identify research outcomes: Federal RePORTER aims to link Federal funding to the outcomes of research including publications and patents. Using agency-supplied information, the public can trace the impact of the funding by seeing what academic publications and patents cited the project funding.

With growing resources for identifying agency-supported publications, future plans include expanded coverage of these two important measures of research impact.

These are just a few of the excellent Federal RePORTER features that can help you find collaborators, get to know the research interests of federal science-funding agencies, understand your institution’s sources of support, and prepare your applications and research plan equipped with additional knowledge. We are grateful to all of the federal agencies and offices that provide data and support to Federal RePORTER and make this resource possible.  These new functions, additional agency data, and modernized user interface make it easier for you – and all stakeholders in the U.S. scientific enterprise – to learn about the Federal science and engineering portfolio.

Categories: NIH-Funding

Following Up on Your Feedback on How to Strengthen the Biomedical Research Workforce

Mon, 06/05/2017 - 13:07

We appreciate the many thoughtful comments posted to the blog about working together to improve NIH funding support for early- and mid-career investigators to stabilize the biomedical workforce and research enterprise using a measure called the Grant Support Index (GSI). Some clear themes have emerged, including:

  • Possible unintentional adverse consequences
  • Possible deleterious effects on collaborative research
  • If/how institutional training grants should factor into the GSI
  • Other ways to support a larger number of scientists
  • Other approaches to measure PI effort
  • Discussion of the GSI values (point scale)
  • Having us look internally at NIH’s intramural program

Based on community feedback from the blog, council meetings, and other discussions with stakeholders, we have made changes to the planned policy to include additional measures beyond GSI to strengthen NIH funding support for early-and mid-career investigators. We will also provide greater flexibility in the use of GSI as a measure for guiding NIH funding decisions, and will make other changes to be sure that this approach does not discourage collaboration and training. These updates will be presented at the June meeting of the NIH Advisory Committee to the Director. We encourage you to tune in via NIH videocast to the presentation on Thursday, June 8.

To provide us with additional feedback, please post comments to this blog or send an email to PublicInput@od.nih.gov.

Categories: NIH-Funding

Implementing Limits on Grant Support to Strengthen the Biomedical Research Workforce

Tue, 05/02/2017 - 15:15

NIH realizes that, as stewards of the American investment in biomedical sciences, we must do all we can to protect the future of the biomedical research enterprise, taking additional measures regardless of our budget situation. In the opening pages of this blog, we noted that our increasingly hypercompetitive system is threatening the future of biomedical research and of the hundreds of thousands of scientists who we look to for discovering tomorrow’s cures. This is a strange irony, given that the last 25-50 years have been times of extraordinary discovery and progress in basic, translational, and applied science. Death rates from cardiovascular disease have plummeted, and death rates from cancer are falling steadily. Scientists have a much deeper understanding of human biology to the point where this knowledge can drive the design of drugs and biologics. Big data and high-throughput technologies now enable rapid development and testing of hypotheses that previously would have taken years. The successes are myriad. But so are the problems, problems so real that some have gone so far as to write, “It is time to confront the dangers at hand and rethink some fundamental features of the US biomedical research system.”

In these pages and elsewhere we have seen:

  • Concerns that the core problems besetting biomedical research are “too many researchers vying for too few dollars, [and] too many postdocs competing for too few faculty positions”
  • Data showing that since the NIH doubling ended, the number of scientists seeking NIH funding has increased at a much higher rate than the number of scientists NIH funds
  • Concerns that we are not paying enough attention to the number of investigators we support, as, given the unpredictable nature of science, we are more likely to generate transformational discoveries by funding more laboratories and research groups
  • Data showing that the supply of scientists continues to outstrip demand
  • Data showing that a relatively small proportion of scientists are receiving a large proportion of available funds; other data showing that there may be an increasing concentration of funds going to relatively few institutions
  • Data and models showing that the scientific workforce is aging at a much more rapid rate than the general workforce, leading to concerns that promising younger and mid-career investigators risk being crowded out
  • Data suggesting that scientific productivity tracks only weakly with funding; larger scientific groups or greater degrees of funding may not generate as much additional scientific output as expected due to the impact of diminishing returns
  • Data and concerns suggesting that the group of scientists who are most seriously affected by all these trends are young faculty, who see the need for funding as the biggest threat to their long-term success

These many concerns have drawn much attention – and perhaps of greatest concern is the wellbeing of the next generation of scientists. The US Congress, in the 21st Century Cures Act, has called on NIH to develop and promote policies that will attract and sustain support for diverse groups of outstanding young and new investigators.

What can be done to relieve the pressures of hypercompetition, to offer a brighter future for today’s early and mid-career investigators, and to minimize the impact of diminishing returns? How can we increase the number of independent early career scientists and stabilize the career trajectories of those who do high quality work? While we have seen some success with the implementation of our Early Stage Investigator policy, the concerns persist.

Going back to the opening pages of this blog, we noted a few of the recommendations that others have put forth: these included capping support for individual laboratories, capping salary support, supporting programs as opposed to projects, supporting more staff scientists, raising post-doc salaries, training scientists for non-academic careers, and assuring more efficient funding of expensive core facilities.

Shortly after we released that post, FASEB, which represents 30 scientific societies that count over 125,000 members, released a detailed report with extensive recommendations on how to sustain discovery in a strained biomedical research system. These recommendations included a call on research sponsors to “monitor the amount of funding going to a single individual or research group to ensure a broader distribution of research funding.” The report goes on to say, “Limiting the amount of funding awarded to any individual scientist or laboratory would enable more people to be actively engaged in research. With more ‘hands at the bench,’ the number of ideas would increase, and this could expedite progress in many areas of science.” A possible cap could be $1 million of RPG funding – such a cap could potentially free up enough NIH money to fund an additional 2,000 scientists. Kimble et al wrote, though, that any “redistribution” of funds from well-funded to unfunded (or nearly unfunded) investigators “will be painful, especially for established senior investigators, but necessary to support the next generation and cutting edge research.”

We and others have noted, however, that focusing on money alone as a measure of support may be problematic, as different areas of research entail different levels of expense: it is inherently more expensive to run clinical trial networks and large-animal research facilities. Therefore, we developed and described a different measure of grant support, which we called the “Research Commitment Index,” and will now refer to as the “Grant Support Index.” This is effectively a modified grant count, one that allows for different cost scales across diverse types of research, while at the same time accounting for the differing levels of intellectual and leadership commitment entailed by various NIH grant mechanisms. Consistent with what others have found with money or with personnel, we find that increasing levels of the Grant Support Index are associated with diminishing incremental returns.

Again — What can be done to relieve the pressures of hypercompetition, to offer a brighter future for today’s younger and mid-career investigators, and to minimize the impact of diminishing returns? How can we increase the number of early career funded scientists and stabilize the career trajectories for those who do high quality work?

NIH Director Francis Collins has announced that NIH is proposing several steps to set us on a stronger, more stable path, and to assure that NIH is maximizing the impact of the public dollars we spend. We will continue our work in monitoring, on a trans-agency level, the number and characteristics of the researchers we support with the idea that by doing so we can broaden and diversify the enterprise. We will take additional efforts to identify funding for even more early stage investigators who submit meritorious applications. When necessary, we will encourage use of bridge funding to offer additional stability and chances for obtaining an award.

To improve opportunities for early established mid-career investigators, we will take special steps to identify meritorious applicants who are only one grant away from losing all funding. Prioritizing these applicants for funding consideration may alleviate the squeeze being felt by mid-career investigators.

And we will monitor, on a trans-agency basis, investigators’ Grant Support Index, with the idea that over time and in close consultation with the extramural research community, we will phase in a resetting of expectation for total support provided to any one investigator. We plan to implement a Grant Support Index cap of 21 points, essentially the equivalent of 3 single-PI R01 grants. Over the next few weeks to months, we will meet with NIH Advisory Councils and other stakeholder groups to explore how best to phase in and implement this cap – so that formal assessment of grant support can be used to best inform, on a trans-NIH basis, our funding decisions.

In our conversations over the next weeks and months, we will need to consider carefully a number of issues and details. How should the Grant Support Index be calibrated? Should we assign more or fewer points to certain grant mechanisms? What headline metrics should we follow? How will we know whether we achieving desired effects of funding more early career investigators and stabilizing their trajectories? How do we assure that we don’t inflict unintended harms on scientific progress, on the productivity of highly productive consortia, or on the stability of the research ecosystem? When would it be appropriate to allow exceptions to caps on individual researchers? How will decisions on exceptions be made? And what analogous steps should be taken with NIH’s Intramural Research Program?

We recognize the serious challenges and dangers that we face given increasing degrees of hypercompetition and scientific complexity. Yet, NIH is committed to assuring the robustness and stability of the next generation of investigators. We have a responsibility to the public to assure that we are optimizing the use of our limited resources to obtain the maximum impact possible. We look forward to working with you to figure how best we can use the tools available to us to “bend the curves,” including resetting expectation on support provided to any one research group. Finally, we will monitor and track data to assess progress, make corrections as needed, and mitigate unintended consequences.

Categories: NIH-Funding

Certificates of Confidentiality for NIH Grants

Fri, 04/28/2017 - 08:29

Earlier this year I wrote a post about the 21st Century Cures Act and its changes that directly affect the NIH. One part of this new legislation contains provisions to improve clinical research and privacy through certificates of confidentiality.

Currently, certificates of confidentiality (or “CoCs”) are provided upon request to researchers collecting sensitive information about research participants. Soon, CoCs will be automatically provided for NIH-supported research, as set forth in the 21st Century Cures Act.

CoCs are an important to both the researchers conducting the study, and to the patient volunteers who make the research possible through their participation. CoCs protect researchers and institutions from being compelled to disclose information that would identify their research participants. They also provide research participants with strong protections against involuntary disclosure of their sensitive health information.

NIH-funded research has evolved since CoCs were first introduced in the 1970s. It is now more common to have projects that involve large-scale data sets and genomic information, and likewise, many thoughts leaders have sought to have the CoC process provide privacy protections more broadly.

We will soon be publishing an NIH Guide notice announcing how and when NIH will begin including certificates of confidentiality in the terms and conditions of award. By automatically providing CoCs as part of the NIH award process, we can provide an additional measure of protection to research participants, through a streamlined process that does not add additional burden to researchers. Stay tuned to the NIH Guide for Grants and Contracts for more detailed information.

Categories: NIH-Funding