NIH Funding - Present and Future - Lisa Halvorson, MD, FACOG

NIH Funding - Present and Future -  Lisa Halvorson, MD, FACOG

Endofound Medical Conference 2017
"Breast, Ovary and Endometriosis"
October 28, 2017 - Lotte New York Palace Hotel


NIH Funding - Present and Future

Lisa Halvorson, MD, FACOG

Chief, Gynecologic Health and Disease Branch
National Institute of Health/NICHD/HHS

Now for something totally different, let's talk about money, or in some cases lack thereof. I know some of you in the audience are actually experts on how the NIH works. For the rest of you, I'll at least try to give you a broad overview in very quick succession. Now, is this going forward? No. Backwards.

The green one. Yup.

Oh, that way. Would have thought that was reverse.

Okay, so, this is just a brief outline. I'll tell you a little bit about how NIH is organized, funding trends, speak more specifically about the institute that I'm part of and the branch within that institute, mention a few other NIH funding opportunities that may be relevant in the clinical space we're talking about today, briefly mention some non-NIH funding opportunities, again, very non-specifically, I'd be glad to talk to any of you in more detail after this presentation later today, and then a few suggestions for the future.

Okay, so, National Institutes of Health, I would hope everybody in this room has heard of the NIH. It actually is comprised of 27 institutes and centers. 24 of these are institutes, they're listed here. Oh, there we go again ... that are listed, that are shown here in the boxes. Up in the right hand, I've put one of the three centers that's quite relevant to this group, which is the Office of Research and Women's Health. You can see that I've highlighted a couple of the institutes, and probably for various reasons we could highlight even more of them. Obviously, NICHD is the primary source of funding for endometriosis, and my home base is very important to me. We're obviously talking quite a bit about cancer also, so I've highlighted here the National Cancer Institute. But there are other groups that clearly are interested in some other research done here. The research Dr. Berger talked to you about has been supported by the NIA off and on. I've also had some conversations with people over at the National Institute of Environmental Health Sciences, NIEHS, and again, today we've heard some discussion about the impact of lifestyle choices and exposures to environmental toxins, as they can affect endometriosis and breast and ovarian cancer. And then we've heard a lot about genomics, so certainly the National Human Genome Research Institute is another place that has a lot of relevance for today's topics.

Okay, so, let's talk about what's been happening with funding at the NIH over the last 20 years or so. We don't have fully compiled data after 2015. What you can see is that there's been about a doubling in the number, maybe even a little more, in the number of grants that have been submitted. About the same amount of money, maybe a little bit more money over this 20 year period, but the grants themselves have also gotten more expensive as personnel and supply costs go up. And basic arithmetic tells you that what happens then is that the success rates go down. So what was about a 30% success rate is now below 20%. Some people in the audience would say, "I wish it was anywhere near 20%." It depends how you calculate what is a repetitive grant, what year did it come in, etc., because if you look at the data a different way, shown here, this is the so-called pay lines for what are considered the bread and butter NIH grants, the so-called RO1 grants. This is for the year 2015.

So this is 2015 data. This is the abbreviations, the alphabet soup that we love at NIH. Here we have the National Institute of Aging, National Cancer Institute, Child Health and Human Development, Environmental Health Sciences, and you can see that there really are not great differences in the funding rate. Some do a little bit better. NICHD has a reputation for funding horribly, but in fact we're in good company if you want to try to consider the glass half full.

Now, this is, I think, relatively sad news. This is NIH expenditures by what is termed at NIH the RCDC codes: Research, Condition, and Disease Categories. So FY13, 14, 15, and 16. Numbers have not changed significantly. You can see the blue is in millions, the amount of grant money spent on endometriosis. Large bar here, breast cancer; ovarian cancer, and endometrial cancer. So you can see that in terms of the incidence of these conditions, not talking ultimately about mortality, but in terms of incidence, there's clearly a huge mismatch, in terms of the amount of money spent on these disorders and how frequently they occur in the population. I think we've heard a lot today about breast cancer, a lot of the outreach that they've done, I think absolute power to them. We do all know those pink ribbons. I give any advocacy group that can get a bunch of football players to wear bright pink gloves and bright pink sneakers, they're doing something right. But I think it really is a call to the arms for the endometriosis community that we need to do a better job and perhaps learn from some of our predecessors who have been so successful in convincing Congress that we need more money for breast cancer, that that needs to be applied to other women's health disorders.

That's this one, okay. So, again, NICHD is my home. I'm not gonna read all this to you, but there was a so-called scientific visioning process. Results were published in 2012. One of the outcomes of that process was a recognition that while there was some research being done in endometriosis and other benign conditions that we've heard about today, fibroids, adenomyosis, etc., that really there was not a specific branch within NICHD that was focused on these benign conditions. So pretty much the studies were aimed at the impact of these conditions on fertility and infertility, which is not unimportant, but obviously they impact women at many other times in their lives, as again we've heard in detail today.

So at that point, what they decided to do was to reorganize the way that NICHD was set up, and instead of having a few centers, they broke us down into branches, and they actually generated a whole new branch focused purely on gynecologic health and disease, so benign gynecologic disorders, which is how I came into the picture three years ago. Again, as you can see here, basically the idea was that we need to develop novel approaches to prevent, diagnose, and manage these benign conditions. Of course, to improve quality of life across the lifespan. May not kill you, doesn't mean it can't make your life miserable, and I think it's a little shocking to me that it took til 2012 to recognize that about these disorders, at least to have it formalized in terms of a branch. But there's the history, and let's call it the good news. We're off and running now.

So, NICHD is broken up into 12 branches. Again, I'm just showing you my branch here. There's also a lot of work done on endometriosis within the Fertility and Infertility branch. Of course, the Contraception Research branch is doing a lot of work on steroidal and non-steroidal manipulation of fertility, whether that be changes in endometrial function or preventing ovulation, which again is a topic we've heard about during various talks today.

Just to briefly, since you gave me a moment, tell you about the GHDB a bit more, these are some of the specific areas that we're interested in. Endometriosis, adenomyosis, uterine fibroids, as they're related to abnormal menstrual bleeding as well as other causes of abnormal menstrual bleeding. OF course, endometriosis is a major cause of pelvic pain, but there are other gynecologic pain symptoms. We're also interested in pelvic floor disorders, ovarian cysts, polycystic ovarian syndrome, etc. So you can see that today's talks really resonate with me, because they're touching on many of the diseases that we're really very interested in pursuing and supporting research in these areas.

About a year ago, all of the branches at NICHD were asked to identify what they consider to be their cross-cutting research priorities. In other words, this was a way for us to speak to the community out there, tell you what kind of work are we interested in. And we could have just listed the disorders that I showed you on the previous slide, but we decided we wanted to talk in more of a cross-cutting way about the type of research, the type of approaches, the type of concepts that we thought would be important. And again, I think all of the talks today really touched on many of the things that we have here, which is very satisfying to me. Not to belabor it too much, but obviously we've talked a lot today about the role of progenitor cells in benign and cancer disorders. As you saw in that earlier side, there are 27 institutes and centers at NIH, and we do work in silos. We heard earlier it'd be better if we didn't have silos in our clinical treatment. Well, it would certainly be better if we didn't have silos in our research support. Some of that is the nature of the beast, you have to have some artificial divides. But I do think that this is an opportunity to think about ways of crossing those divides, not just scientifically but also in terms of funding.

Anyway, so my branch is benign disorders, but I think that's clearly on a continuum of benign to less benign, whether it be hypercellularity, increased mitotic index, deep infiltrating endometriosis, etc., all the way up through pre-cancerous and outright cancerous conditions. Anyways, going back to these research priorities. Certainly interested in the role of stem and progenitor cells in gynecologic disorder. The role of the various omics: you've heard a lot today about genomics, this is just a catchall phrase for broad expression of genetic changes, epigenetic changes, protein expression, etc. You've heard a lot today about hormones, particularly estrogen and progesterone, as they impact both normal and abnormal physiology, as well as the use of some of these various hormone preparations for the treatment of these benign GYN disorders. So we have a big interest in promoting non-hormonal treatments as an alternative approach, so perhaps you can leave a woman's estrogen level intact, as it's ... Thumbs up from Dr. Berger. So we can perhaps leave the estrogen levels helping her to mentate, while at the same time targeting the endometriotic growth that she's experiencing dueing to those estrogens, as one example.

Very interested in non-invasive diagnostic and assessment tools. Why is this? Again, you've heard the gold standard method, really the only method for formally diagnosing endometriosis is biopsy obtained at the time of surgery. It would certainly be nice if we could make that diagnosis without needing to go to surgery, if in fact the patient was a candidate for non-surgical treatment of her disorder. It might also be a nice way to follow the course of her endometriosis, if there was some quantitative association between the degree of the disease and the level of whatever we chose to measure. Also would like these tools to be used to distinguish benign from true metastatic disease. Big push is in transdisciplinary research. Again, we've heard a lot about that today, about pathologists working with gynecologists, working with medical oncologists, etc., and I think that that's gonna be very important at the research level, not just the clinical level. We need some long-term longitudinal GYN studies, again, to fully understand the course of these diseases, so that we can diagnose them early, treat them early, and prevent progression, or even better, prevent them from ever developing. And then we have a lot of interest in various gynecologic pain syndromes.

Okay, so I just thought I'd briefly mention a couple of requests for applications that should be coming out this fall. The hope would be for receipt dates some time next spring, and funding by fall of 2018. Now, that's a long time away, so there's another one of the points I want to make is funding through the NIH takes a long time, so you have to plan well ahead of time if you're gonna put in a grant. And if you have an idea for a direction that we should be going, in terms of what kind of funding we should be doing, we have to think about that way ahead of time and make a lot of plans. It's just not a fast-moving ship. So the things that we're interested in, again, you can see directly how these directly relate to my high-program priority areas.

We're interested in non-invasive diagnostics to improve GYN health. This is through what's called the Small Business Innovation Research grants. So it's [inaudible 00:17:02] partnering with small businesses to put in proposals. And one of our emphasis points is to accurately distinguish between benign and malignant GYN disorders, so I've been speaking to people over at NCI to see whether I could get some co-funding, and hopefully be able to support more applications under this RFA. The other one is the role of stem cells in the pathogenesis or treatment of GYN disorders. You can see which disorders are included here. Again, hoping that NCI will be interested because of this concept of continuum from benign to malignant disorders. And I'm talking to the NIEHS also about some potential co-funding, because of the role of environmental factors for these benign disorders. Again, as we've heard today, we'll see if the money comes through. Everybody's tight.

Last, but not least, there is a large program project grant mechanism, the P50 that has historically required a focus on fertility or infertility, and the next competition, which again should be next spring, will allow sites that are purely focused on benign gynecologic conditions. So hopefully we'll get some good response there. I think all of these are areas in which it would be possible to put in proposals that were linking many of the concepts that we've talked about today. They need to focus, if I'm gonna be funding them, on the benign aspects of the disorders, but it doesn't mean that they can't be learning from what has been discovered in the oncology field, and we've heard about some of that today, identification of oncogenes in benign disorders. Conversely, I would think that some of what might be discovered in terms of breaks for the GYN disorders may be of interest to the oncologists. They may want to know why those breaks aren't working in the case of cancers or ways in which to turn on those breaks for treatments.

The NCI is a morass, even to those of us who are at NIH. Huge, huge. They have ... Oops, sorry. They have 30 divisions of their own, as well as multiple offices and centers. These are the four that I thought seemed most relevant for the group today. There's a Division of Cancer Biology that funds primarily basic research; Division of Cancer prevention that focuses on, as its name suggests, prevention or relief of symptoms from cancer or its treatments; Division of Cancer Diagnosis focused on clinical applications; and a Division of Cancer Control and Population Sciences, which is sort of the epidemiology and behavioral arm. What there does not seem to be is ... They have not divided up the NCI, with a few exceptions, for example, Barrett's esophagus, they've not divided it up by specific cancer type. But I would like to speak to some of the experts in here who may be getting funding from the NCI about who they would suggest would be the best contacts. So even being inside the game does not always help with this.

Just briefly about the NIEHS, they have a number of interests that overlap, again, with today's discussion. They are certainly interested in the environmental influence on molecular events underlying cell reprogramming. We've heard a lot today about cell reprogramming, as it moves from, say, normal endometrial tissue to endometriosis, and from endometriosis to ovarian cancers. They are interested in looking at the toxic and nontoxic mechanisms of agents in altering stem cell differentiation ... again, something we've talked about a lot today ... as well as determining the effects of common environmental exposures, particularly endocrine disruptors on timing and severity of these windows of disease, of these diseases, particularly this focus on windows of susceptibility. And we heard a little bit really about the long window of susceptibility for breast cancer, due to the slow development of the breast, so probably each of these disorders has different times at which exposure to these environmental factors is most likely to negatively impact future physiology.

Not gonna read through these for you. I'm not sure if the slides will be sent around, but you can talk to me if you want them. Basically, these are ... Oops, sorry. So these are a few grants, again, that are funded by NCI and/or NCI and NIEHS, or this case, National Institute of Aging, that I think if you think outside the box, this might not be the usual place where you would go for your funding, but you probably can fine ways in which those of you doing oncology can think of ways to link it to benign disorders and vice versa, while we don't at the moment have good co-funding opportunities that link the two.

Briefly wanted to mention the Office of Research on Women's Health, which is one of the so-called centers. What that means is that they do have an NIH budget, but they do not have direct grant-making, grant-funding abilities. So they come up with initiatives that then get managed often through either the director's office, so Francis Collins's office, or one of the other institutes. They are responsible for the so-called trans-NIH strategic plan for women's health, and have asked for input on the cross-cutting themes that they have suggested should be important for the next three to five years of emphasis by the ORWH. So please look at these, please look up this notice, which you can do here. Just google that number. Forget NIH links; I google everything, it's quicker. 300 words or less, you can tell them what you like or do not like about these cross-cutting themes. You can tell them where you think that they should be more focused, and the fact is that it will translate into what areas they consider for funding in the next few years. So it could definitely be worth your time.

Not gonna read this laundry list, it's just to remind me to remind you that there are many other institutions, other agencies that do support research. Remarkably, people are always surprised about the VA, but of course there have always been family members of veterans, as well as some female veterans, and now quite a few female veterans. So there is actually large growth in the women's health arena through the VA, including even in IVF these days. So it's definitely ... Think outside the box, there are some other funding mechanisms.

There are of course non-federal sources of funding, and I think maybe Endofound has some grants that we were gonna hear about. So it should've been on my list. See what I learned today by finally looking at the agenda. Again, these professional organizations went through very hard times. A lot of them, I think, closed down some of their funding. But that seems to be expanding again, at least with the groups that I work with. So there are definitely more and more pilot grants, bridge grants that are available. I think some of these organizations are, again, becoming a little less siloed and speaking to each other. So for example, what is it, is there an SSR presentation at ASRM? And so I think that for those of you who are in the professional societies, there are some great opportunities for some of these cross-cutting topics we've talked about today, to speak to your societies and say, "We would like," say, "as the American Cancer Society, we would like to have a little mini-symposium where we talk about the basic science of cancer research as it may impact fertility, benign gynecologic conditions, etc." Just as a way to try to get some of that cross-fertilization going. Obviously, never forget about institutional and industry funding, though industry funding I think is getting quite a bit tighter these days, more focused on product, not fundamental science.

So how do we build interest? This is my future slide. I'm afraid it's not particularly detailed. Certainly, we start with meetings like this, where we have a very broad audience, with different backgrounds, different interests. Again, developing symposia at professional meetings. Get people talking to each other at the clinical and research levels. We need communication between advocacy organizations. Again, get the Endometriosis Foundation to learn from the breast cancer organizations, and maybe vice versa, so we can look for commonalities. Talk to your program officer at NIH, that's for the investigators in the room, some of whom don't call us as often as we'd like to hear from them. Yeah, we get a lot of phone calls, but the fact is that we'd love to tell you about what kind of research we're hoping will begin, will come in, in order to meet some of what we see as the most important directives. And then sometimes we hear from our scientific community that we're totally off the wall, missed a paper that just came out, etc., and need to redirect. And that's fine, too. Okay, again, big emphasis on developing transdisciplinary collaborations. And don't forget industry.

So with that, I will go ahead and stop. Oh, no I won't, because I don't know which way to hit these buttons. Oh, there it is. I guess we're not doing questions, til later. Thank you.