39-43 – NCI News

Varmus’s Remarks to the BSA, Nov. 7, 2013 from The Cancer Letter on Vimeo.

Video from NIH Videocast.

As NCI digs out after the two-week shutdown of the federal government, its leadership has to contend with the prospect of another shutdown weeks away, which may kick in after the current continuing resolution expires Jan. 15, 2014.

Meanwhile, the institute’s budget remains unclear. Will funding come through a continuing resolution and remain stagnant throughout the next fiscal year? Can new money materialize? Or will sequestration take another bite?

The institute needs to have clear rules for operating under shutdowns, NCI Director Harold Varmus said at the Nov. 7 meeting of the Board of Scientific Advisors.

A video of Varmus’s opening remarks appears on The Cancer Letter website.

“We need some clearer guidance on what is permitted to be done under the law, without making up all kinds of guidelines that might make the shutdown look terrible, but also makes it actually terrible—and, in my view, ends up costing us money,” said Varmus, a survivor of two government shutdowns.

“We need to protect our trainees, especially those who might be arriving here on Jan. 1, and have not gotten their lives worked out, and we need to deal with a problem that may not concern most of you, but we worry about it, and that is how we deal with the matter of furloughing and paying back contractors who are not directly NIH employees, but nevertheless work side-by-side with those employees and should be treated in a way that is fair, considering the differences in employment status, and other things,” Varmus said.

The lack of clarity about the budget is affecting NCI’s ability to move forward with programs new and old.

At the Nov. 6 meeting of the NCI Clinical Trials and Translational Research Advisory Committee, James Doroshow, director of the NCI Division of Cancer Treatment and Diagnosis, was in no position to offer many details about the status of revamping of the institute’s clinical trials cooperative groups.

“The review of the NCTN occurred in July. The results were presented by Dr. [Meg] Mooney [chief of the Clinical Investigations Branch of the Cancer Therapy Evaluation Program] to the senior leadership committee of the NCI and were accepted.

“All I can tell you for sure is that there will be five groups that will be supported: one pediatric and four adult groups,” Doroshow said. “There will be one Canadian group that will be supported. There will be an organizational infrastructure to support imaging and radiation therapy that will go forward. Exactly how many institutional grants we are able to support as well as the number and size of the translational research grants that we are able to support absolutely depend on what happens over the next couple of months in Congress. So we have a plan, but we can’t execute that plan or anything related to it.

“I hope we will be able to get the money and make the allocations early in 2014, but we will see. “We will announce very shortly after NCI gets a budget. How much is allocated for RFAs and grants and various other pieces so we can put together on the division-by-division level what the support levels would be. After we get a budget, it will be a couple of weeks until we finally get granular enough to know.”

The text of Varmus’s remarks to BSA follows:

Comparative Shutdowns

One of the things the shutdown does is it makes you glad to go to work, when you actually can go to work.

I’m one of the few people who has had the privilege of sitting in two leadership positions at the NIH during two profound shutdowns: one in 1995, which actually lasted longer than the recent one. I was then the NIH director, but the two shutdowns felt very different, with the longer one, in 1995, seeming a whole lot less onerous than the recent one, and it’s worth asking why.

That shutdown occurred on Dec. 15 and ended on Jan. 6. Some of us called that Christmas vacation, and indeed it felt like that. There was a different precipitating issue: at that time the fight was over the budget. That’s what it’s supposed to be about—fighting over an appropriations bill. It made sense. This time, we were fighting about a piece of legislation that was extraneous to the budget battle, and it presented a real threat to the way we conduct our democracy.

Last time, in the 1995 shutdown, the major warring parties, Speaker Gingrich and President Clinton, were actually sitting in a room talking most of the time. This time, there was silence on both sides. It wasn’t clear whether we would ever have an endgame.

There were different sets of guidance issued, this time extremely draconian pieces of advice—like don’t use your government issued email or don’t use your government computer, even to look at a scientific article if you are sitting at home furloughed.

These struck me as complete absurdities.

Last time, the message was quite simple: you may not be officially at work and we can’t guarantee you’ll be paid, but keep the important things, the critical things, that would cost us money going. We can’t spend money, because that would be a violation of the Anti-Deficiency Act, and that all makes sense.

But this time was quite different, and there were consequences that I’ll come back to. Now, given all these differences, I think we have to remember that there was a cosmic significance to the president holding the line here.

Some people say this whole thing didn’t have to happen—and on the one hand, perhaps it didn’t have to happen because of those who precipitated it—but it did have to happen, and to continue from the administration’s side, because to fold over the issue of whether we are going to allow Congress to hold the country hostage, because they wanted to reverse legislation that had already been voted on over 40 times, reviewed by the Supreme Court, and endorsed by the public, both in polls and in the 2012 election, struck me as completely inconsistent with the better parts of our democracy.

So I applaud the president for the strong stand he took in not negotiating under terms that would have been similar to a hostage situation. During the shutdown, for those of you who were not on campus, I don’t think anyone in this area was happy.

It was hard to be at home and wanting to be at work. It was hard to be on campus without the usual intensity, the usual companionship, and the esprit de corps. For all of us, the lack of communication and uncertainty of when this shutdown was going to end added to the difficulty.

It was only 15-16 days, depending how you count them. It was not a good time. I’m very grateful to my colleagues who are NCI employees for a great deal of flexibility—and special kudos for those of you who did have to come to work and do the things on an empty, inconvenient campus: from providing essential care to our patients at the clinical center, to keeping our animals healthy, to keeping existing research investments going.

Because it may be a violation of the Anti-Deficiency Act to try to buy reagents—it’s also, in my view, a violation of our fiscal responsibility to let experiments die and have to be redone at expense later on.

I think it was important to keep a low level of research going; not everybody agrees with that. I was especially grateful to some of the leaders of the intramural research program who had to thread the needle here, and try to understand that the rules that were coming from high up in the administration, and to reconcile those with what is a sensible thing to do.

Our postdocs, many of whom came from abroad—some of them arriving on Oct. 1—to do government work, were not sure what the hell was going on in this so-called advanced economy. And without a salary and without a place to live, they had quite a lot on their minds—and to have their goals of trying to make progress against cancer on the NIH campus thwarted by political events they couldn’t possibly understand was a little frustrating.

So we are trying to think ahead about that. I’ll come back to the issue of how we make use of lessons learned from this debacle on the one hand, but in a sense a triumph on the other, because it did turn out alright.

On Restarting

The shutdown is one thing; the startup is another. There was a lot of anxiety about the startup. Many of you received a memo from me—not something I was encouraged to do by higher-ups, but I sent you a memo to warn you that, while the extramural community was somewhat spared during the actual shutdown, there would be demands placed on you later.

It was clear already as we got into the second week of the shutdown that we would be canceling site visits and study sections. That was true both in Paulette’s office [Paulette Gray is the director of the Division of Extramural Activities] at NCI and within the larger NIH community, especially through [the NIH] Center for Scientific Review.

There would be a need to reschedule meetings fairly promptly, and we were to ask for a lot of flexibility from you.

In addition, we knew the startup would involve getting payroll systems starting up again. All the managerial things that had been shut down had to get up to speed. And although I know it wasn’t easy, it did seem a little easier than I thought. The payroll system worked—it not only worked, it incorporated pay for the first several days in the previous pay period in the first part of the shutdown, that wasn’t going to be covered by the first payroll period.

So we got all that done, we got all the NIH employees got their fully expected pay. Many other systems got rolling quite quickly, such as our budget system and grant making system, and I’m grateful to John Czajkowski [NCI deputy director for management] and his colleagues who worked hard to make these things happen with systems that seem inherently more robust, compared to other systems that give us trouble.

I am grateful to Paulette and her colleagues, and to many of you in this room and not in this room for helping us to get site visits and study sections rescheduled.

Indeed, everything that was postponed has been rescheduled in a reasonably timely way. There will be no significant delays in getting grants reviewed, processed, discussed, and awarded—as you might have hoped. And I’m grateful for all that.

Threat of Another Shutdown

Now, as you all know, the shutdown ended with a continuing resolution that lasts three months. It ends Jan. 15. I’m not going to review all the political machinations that are currently underway, including the high-level budget discussions to try to reach a consensus on how to move forward in the fiscal year after Jan. 15.

I would have thought there couldn’t be a shutdown. It would be a bad political move. It was called a bad move up to Oct. 1 too, and yet it happened. I’m not going to make predictions this time because the predictions I made last time were all wrong.

But it is possible we’ll have a shutdown, so we are thinking through the lessons learned.

Namely, we need a better means to communicate within the intramural program, and between NIH central and with our tens of thousands of investigators and others.

We need some clearer guidance on what is permitted to be done under the law, without making up all kinds of guidelines that might make the shutdown look terrible, but also makes it actually terrible—and, in my view, ends up costing us money.

We need to protect our trainees, especially those who might be arriving here on Jan. 1, and have not gotten their lives worked out, and we need to deal with a problem that may not concern most of you, but we worry about it, and that is how we deal with the matter of furloughing and paying back contractors who are not directly NIH employees, but nevertheless work side-by-side with those employees and should be treated in a way that is fair, considering the differences in employment status, and other things.

I think at this point, there were not a lot of casualties from the shutdown.

The extra work of rescheduling site visits and study sections I’ve mentioned already. We had a very important roundtable to discuss the future work of the Center for Cancer Genomics. You heard Lou Staudt [head, molecular biology of Lymphoid Malignancies Section and Deputy Branch Chief at the Center for Cancer Research] at the last meeting discussing that ambitious program. A roundtable that had been scheduled for early October has now been, I believe, rescheduled for Dec. 3. That was a delay that I wasn’t happy about.

We discussed in June and received an enthusiastic endorsement for our plans to go forward with an outstanding investigator award. There’s been no progress with those awards because of all these interfering activities.

Let me say a few things about what has come out of the resolution, and what Congress is doing. As you know, the continuing resolution we are working on until Jan. 15 is at fiscal year 2013 levels.

So it’s the same amount of money as projected in that period, but the allocation to us was larger than first continuing resolution we received last year.

Last year, we got about 28 percent of what we expected to get for the year for the first six months, based on previous spending patterns. This time, we have 29 percent of the year’s allocation for the next three months. That means that we can be a little more liberal in the way we give out money for non-competing and even our competing applicants until Jan. 15.

What will happen then? Well, setting aside the stalemate issue, assuming something happens, I think there are at least three general propositions, and many in between. We could end up with a year-long continuing resolution at FY13 levels.

We could see an additional decline in our budget, because the original rules of the sequestration process would have dictated another 2 percent be reduced, and that of course would create problems. We’re trying to think through what we would do if that happened.

And then there’s also the possibility that we’ll end up with the withdrawal of the sequestration directive, or the award of some flexibility to the appropriators—so they can favor favored agencies in giving out money, and not do an across-the-board, mindless reduction. If that happened, that could lead to increases.

Whether we’ll actually get the level that the president recommended for the NIH for this year—which would be about 1.5 percent above FY12 levels—that would be a great moment, because it would feel like a great increase. But if it’s possible to end up with something above last year’s level, we’ll have to see.

Meeting Approval

In the interim, there is some good administrative news—not a whole lot, but some—and these were issues that you cared about last time.

One is that there’s been some relaxation from OMB about the approval of meetings. So now meetings like this, FACA advisory committee meetings, don’t need to be approved each time we want to have them. That seems like a very small thing in the history of mankind, but it’s some relief, and we don’t need that kind of approval for study sections.

Again: an absurdity, when relieved, makes us feel good—but it’s absurd to begin with.

We also have learned that we’ve been given back the ability to make some bonuses. These are relatively small amounts of money, but being able to serve an appropriate function as a manager by being able to award extra work and good work is very important to us. Having that ability back is certainly a good thing. There are said to be some other good things coming, so we’re holding our breath, but we’re happy about that.

We are, of course, in the process of awarding grants now.

As is common in situations like this, we’re paying our non-competing awards, Type 5s, at the 90 percent level.

We expect to restore some of the additional money, but when it will get to the 100 percent of the money is not clear. That will depend on the final determination of the FY14 budget, but, at least for the moment, we’re giving out the expected full-year award for type 5s and we’re making our other awards as we did in the first part of FY13.

It’s now possible to say a few things about what happened in FY13: when, as you recall, we had roughly a 6 percent decline in our budget, when you add together the roughly 5.1 percent reduction from sequestration, plus some taps from the department that were essential to help fund the insurance exchanges.

I want to give you a little synopsis.

There’s a chart, and we’ll get all this data up on our website where we show the retrospective look at prior years, but first the highlight:

You’ll recall that we planned our budget for FY13 once we knew what it was with the proviso or the goal of making more or less the same number of competing awards as we made the previous year in FY12.

We’ve almost exactly achieved that. There are some who think it serves a political purpose to be able to say 200 people who would have gotten their grant didn’t get their grant, and that sequestration is monstrous.

I chose, and I think most people around our table agree with this, to make cuts in other parts of the portfolio, to be sure that we were maintaining the grant award numbers, because people’s careers end when they don’t get grants.

I think this was the wise thing to do. But it shouldn’t be understood that there’s no pain when you do that. We are shrinking everything. It’s a little bit like climate change. Things change all around you; it’s not all that perceptible. A percent here, a percent there, and pretty soon it is real money.

We have to remember that, while our grant numbers overall look pretty good, that everybody is getting less for everything. We already know that over the past decade, NIH budgets have not kept up with either the computed inflation rate. Even the Biomedical Research and Development Price Index is below the estimates, most of us who run labs know, to be the increasing cost of research.

The kits, machines, high-throughput stuff, and more animal models have driven the cost of research up in a way that can’t be captured by simple inflationary indices. We know that we are starving everybody, in requiring co-funding by institutions and advocacy groups and lots of other folks, and eventually the belt-tightening all around us doesn’t work. Then Florida is drowned and more glaciers melt, and we have got to keep an eye on that.

But minimizing the pain in the short run to me seems to be the reasonable thing, while, at the same time, I think we should all be thinking about what is actually happening with the non-sustainable industry that we are a part of.

This enterprise is built on some assumptions that worked well in the early days, and don’t work so well anymore. I think all of us should be paying some attention to what these changes mean.

Let me just say a couple of things in greater detail about last year’s grant numbers. There were some small declines in the numbers of R01s issued, both Type 1 and Type 2. And that, in part, reflects some declines in the number of applications. The success rates didn’t really change, but we are particularly concerned by a very modest, but it seems to be persistent, decline of early-stage investigators and new investigators applying for R01s. So we need to keep an eye on that.

There was a moderate increase in the number of R21s, exploratory two-year grants, including increases in the applications. The success rates remain lower, especially for new investigators. They are R21s but they are an appealing way to apply for funding—whether the perception is that it’s easier to get a smaller grant; that’s wrong. The success rate is lower. How good those applications are is another issue. It’s a little harder to evaluate.

There were a few more P01s with better success rates, whether that reflects that this round we had a lot of really good P01 groups coming in for review, or whether it reflects the perception that is generally shared around our leadership table: that in bang-for-the-buck, P01s are really pretty good.

Anyway, we’ll get those numbers up on the website and let you all know so you can look at them in more detail.

Changing the Biosketch

We talked last time about the biosketch changes that the NCI is endorsing, and I feel very strongly about getting a biosketch that depends on an account by the applicant of that person’s five most contributions to science—as opposed to placing a lot of weight on a bibliography that’s read by looking at the positions of the author in a pile of authors and seeing where the paper was published.

And I think most people agree with this. Nevertheless, this seems to be a process-oriented government department, and we’re going through a pilot phase. Paulette has used the new biosketch for a couple of RFAs and we’re going to be asking some informal questions of the reviewers who have used the system, and hopefully we can get some answers.

What I’d like to do is see the whole NIH adopt this biosketch proposal, which is very similar to some of our institutions on the outside and is used by the Howard Hughes Medical Institute.

There continues to be a lot of interest in the problem of replicating data from work supported by the NIH, and we discussed this in some detail last time.

If you haven’t seen it already, I urge you to have a look at an article that appeared in The Economist recently with an editorial. There’s not a lot new there, but it’s got a pretty good summary of what’s going on. An elite population of readers is looking at this issue, and we’ve already received questions from Sen. [Richard] Shelby (R-Ala.) at the hearings.

Having this idea more generally known in the politically astute community is going to result in you all encountering questions about what the hell is going out there, and what is going on at the NIH, and why do you guys want more money.

Some of you may be aware that there is a group that has positioned itself to attempt to reproduce work done by NIH scientists, and they have chosen 50 papers published in the last three years that have had many citations—and many of these to try to undergo replication of the work.

I see at least one, two—quite a few people around this table, and some who should be around this table, like Dr. Andrea Califano [professor of systems biology, chief of the Division of Biomedical Informatics, and associate director of bioinformatics at Columbia University Herbert Irving Comprehensive Cancer Center]—who have such papers, and have been approached by the replicators.

They have proposed, how, I don’t know, to replicate work that took several years and cost literally hundreds of thousands of dollars over a short term with relatively small amounts of money, and without the necessary skills.

So, NIH is not intending to issue an RFA for replicating work. We would like to improve the way work is done in the first place, and there is a lot of discussion about how that could be done—both by trying to examine the underlying conditions that impel people to publish prematurely and without adequate attention to detail.

A lot of that has to do with the culture of science. We’re very proud that, here at the NCI, the work that [NCI Biostatistician] Lisa McShane and her colleagues have done to establish checklists. Just a few weeks ago, that group published a paper—actually in two places, in Nature and the BMC [Medicine] journal—that provided guidelines to carrying out so-called omics studies.

You’ll recall that, just after I arrived here, we had an unfortunate episode. At one of our leading universities, studies that led to the design of clinical trials were based on work in the omics domain that were not sound.

We asked the Institute of Medicine to do a report on high-throughput studies that have clinical relevance. That report was influential, and for the work that Lisa and her colleagues have done, I congratulate them for pushing forward here and getting a lot of attention focused on building checklists that can be used to improve the likelihood of replicatibility.

We’ve been discussing for the past few meetings our response to the so-called Recalcitrant Cancer Act. A brief update, since Jim Doroshow has had to sit in for me at the institute directors’ meeting, which occurs Thursday mornings.

He normally reports on this, but the report on pancreatic ductal adenocarcinoma research is nearly done. A workshop was held earlier this summer on small-cell lung cancer. There were some interesting conclusions from that meeting, and a report is in progress.

I’ve mentioned in the past the interest in several members of the NIH leadership have in working more closely with the Centers for Medicare and Medicaid Services. Those discussions have been reactivated and allowed me to go back to a point that I tried to make two or three years ago: that CMS needs to pay close attention to helical CT scanning for lung cancer.

Of course, now with the U.S. Preventive Services Task Force draft report, it’s now clear that there will be a need for reimbursement policy to provide the rules for coverage by Medicare and Medicaid of this test, and the insurance companies will be following along with their deliberations.

There is now an active group of staff from NCI and leading staff from CMS talking about some of the issues that were raised there. It’s not just a matter of saying we’re going to follow the National Lung Screening Trial and the results of that trial. It’s a matter of saying what coverage is appropriate for the follow-up tests. There is a very high percentage of false positives in these tests, even in the trial, which used only healthy smokers. There were a lot, 25 percent, of people had to have something else done besides than the low-density helical CT scan. And when you put in the smokers who were not well—you’re going to have a lot more bronchitis and false positives.

How do you incentivize the improvements in the methodology, what do you do about the coverage of other aspects, and what do you do about the people who don’t quite fit the criteria? There are going to be a lot of significant issues.

There’s also some developing interest in the issue of developing diagnostics that depend on genomics and other molecular technologies in diagnosis of cancer, which, of course, leads frequently to hopefully a more correct, precise choice of therapies. And we’re finally going to have some discussion with CMS about that as well.

Just a few things about meetings and events, for those of you who want to be oriented to these things. You heard last time about the President’s Cancer Panel’s report on human papilloma virus vaccinations. We hope that report will be done sometime within the next few weeks and presented publically.

Bill Gates is another victim of the shutdown, because his Barmes [Global Health] lecture had been scheduled for early October and has now been rescheduled for Dec. 2, when he and some of his colleagues will be on campus to interact with the institute directors.

A few of us happened to have an off-site discussion with him in early October, and one of the things that he expressed an interest in developing was a wider range of interactions with the NIH, with an increased level of interest in the things that the NCI does.

So we are looking forward to some more substantial interactions with the Gates Foundation, especially on matters of common interest, like infectious cancers, cancers that affect young people and disrupt maternal-infant relationships, and so forth.

There was a very good International Cancer Genome Consortium meeting in Toronto on Oct. 1. Some of us, happily, were there, and there was much discussion about something I mentioned last time—this plan for a global alliance to try and get information about the genetic basis of cancer and the way it’s treated into a digestible, interoperable form.

The alliance is now issuing a monthly newsletter, and the last newsletter said there would be a meeting of planned members of the alliance that intend to join the alliance in March. Hopefully we’ll have more information on what the alliance will actually be able to do.

I’ve talked here in the past about this consortium of leaders of international funding agencies for cancer that Harpal Kumar [chief executive of Cancer Research UK] and I have been organizing for the past couple of years, and I think I’ve distributed a report that we published in Science Translational Medicine last year about the goals of this international group.

We are going to be meeting again—this time happily organized by others; by Fabien Calvo [Deputy General Director of the National Cancer Institute, France], in particular—in Paris Jan. 13-14.

Also, at the risk of apparent immodesty, I’d ask that a recent profile of me and our objectives at the NCI be distributed. I don’t see it on the tabletop. I asked that it be put at everybody’s place; we’ll get it for you during the day. Some of you have seen this.

Frankly, it was a piece that pleased me. But I think it does highlight many of the things that many of us here at the NCI are aspiring to do even in these difficult times. I think it’s probably useful for all of you to see it, if you haven’t.

I think it does portray the message I’m trying to make: that we’re unhappy about limited budgets—that there’s a lot to do, but we’ve got a fair amount of resources to do it with, and we can’t spend all our time whining. We’ve got to be doing some things that are important for world health.