Where is RDoC headed? A look at the eating disorders FOA

Thomas Insel, director of NIMH, made a splash recently with the announcement that NIMH funding will be less strictly tied to the DSM. That by itself would be good news, given all the problems with DSM. But the proposed replacement, the Research Domain Criteria (RDoC), has worried some people that NIMH is pursuing biology to the exclusion of other levels of analysis, as opposed to taking a more integrated approach.

We can try to divine NIMH future directions from RDoC description and the director’s blog post, but it’s hard to tell whether mentions of behavior and phenomenology reflect real priorities or just lip service. Likewise for social and cultural factors. They come up in a discussion of “environmental aspects” that might interact with neural circuits, but they do not appear as focal units of analysis in the RDoC matrix, leaving them in a somewhat ambiguous state.

Another approach is to look at revealed preferences. Regardless of what anybody is saying, how is NIMH actually going to spend its money?

As an early indication, the NIMH RDoC overview page links to 2 funding opportunity announcements (FOAs) that are based on RDoC. Presumably these are examples of where RDoC-driven research is headed. One of the FOAs is for eating disorders. Here is the overview:

Eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), and their variants, are a major source of physical and psychological morbidity and constitute the major contribution to excess mortality from psychiatric disorders.  Clinical presentations of eating disorders are highly heterogeneous, involving broad and often overlapping symptomatology, which is often further complicated by metabolic and nutritional challenges that result from restricted food intake, excessive exercise, and repeated binge and/or purge episodes.  The recognition that relatively specific behaviors, cognitive operations, and affective processes are primarily implemented by particular neural circuits suggests that dysregulated functions and associated neural circuits should be a critical focus of study, and, ultimately, the target of assessment and treatment for eating disorders.

Here is a list of words that do not appear anywhere in the eating disorders FOA:

peer (when not followed by “review” referring to the funding processes)
body image
self (when not followed by “-report” in a rote recital of the RDoC units of anlaysis)

And maybe I shouldn’t get too hung up on a choice of a definite vs. indefinite article, but what’s up with stating that neural circuits should be “ultimately, the target of assessment and treatment”?

Eating disorders isn’t my area. So I might have missed something. Perhaps NIMH is planning to issue another RDoC-based eating disorders FOA that invites research on sociocultural factors. Or maybe I’m missing some other important way that they will be incorporated into NIMH’s priorities for studying eating disorders. But if not — if NIMH thinks that basic research on media, on family environments, on peer influence, on self-concept, on cultural norms are not terribly important for understanding and treating eating disorders — well, that’s really hard to defend. And not a good sign of where things are headed more broadly.

Improving the grant system ain’t so easy

Today’s NY Times has an article by Gina Kolata about how the National Cancer Institute plays it safe with grant funding. The main point of the article is that NCI funds too many “safe” studies — studies that promise a high probability of making a modest, incremental discovery. This is done at the expense of more speculative and exploratory studies that take bigger risks but could lead to greater leaps in knowledge.

The article, and by and large the commenters on it, seem to assume that things would be better if the NCI funded more high-risk research. Missing is any analysis of what might be the downsides of adopting such a strategy.

By definition, a high-risk proposal has a lower probabilty of producing usable results. (That’s what people mean by “risk” in this context.) So for every big breakthrough, you’d be funding a larger number of dead ends. That raises three problems: a substantive policy problem, a practical problem, and a political problem.

1. The substantive problem is in knowing what would be the net effect of changing the system. If you change the system so that you invest grant dollars in research that pays off half as often, but when it does the findings are twice as valuable, it’s a wash — you haven’t made things better or worse overall. So it’s a problem of adjusting the system to optimize the risk X reward payoffs. I’m not saying the current situation is optimal; but nobody is presenting any serious analysis of whether an alternative investment strategy would be better.

2. The practical problem is that we would have to find some way to choose among high-risk studies. The problem everybody is pointing to is that in the current system, scientists have to present preliminary studies, stick to incremental variations on well-established paradigms, reassure grant panels that their proposal is going to pay off, etc. Suppose we move away from that… how would you choose amongst all the riskier proposals?

People like to point to historical breakthroughs that never would have been funded by a play-it-safe NCI. But it may be a mistake to believe those studies would have been funded by a take-a-risk NCI, because we have the benefit of hindsight and a great deal of forgetting. Before the research was carried out — i.e., at the time it would have been a grant proposal — every one of those would-be-breakthrough proposals would have looked just as promising as a dozen of their contemporaries that turned out to be dead-ends and are now lost to history. So it’s not at all clear that all of those breakthroughs would have been funded within a system that took bigger risks, because they would have been competing against an even larger pool of equally (un)promising high-risk ideas.

3. The political problem is that even if we could solve #1 and #2, we as a society would have to have the stomach for putting up with a lot of research that produces no meaningful results. The scientific community, politicians, and the general public would have to be willing to constantly remind themselves that scientific dead ends are not a “waste” of research dollars — they are the inevitable consequence of taking risks. There would surely be resistance, especially at the political level.

So what’s the solution? I’m sure there could be some improvements made within the current system, especially in getting review panels and program officers to reorient to higher-risk studies. But I think the bigger issue has to do with the overall amount of money available. As the top-rated commenter on Kolata’s article points out, the FY 2010 defense appropriation is more than 6 times what we have spent at NCI since Nixon declared a “war” on cancer 38 years ago. If you make resources scarce, of course you’re going to make people cautious about how they invest those resources. There’s a reason angel investors are invariably multi-millionnaires. If you want to inspire the scientific equivalent of angel investing, then the people giving out the money are going to have to feel like they’ve got enough money to take risks with.