Three years in: what has the $42M Atopic Dermatitis Research Network produced?

In July it will be three years since the NIH awarded National Jewish Health in Denver, CO $31 million to create and administer the Atopic Dermatitis Research Network, a consortium of five academic sites across the US. A contractor, Rho Federal Systems of Chapel Hill, NC, won an $11 million contract to operate a center to coordinate statistics and clinical trials for the project.

That makes $42 million—spread over five years—which puts the project on the large end of NIH funding for individual biomedical efforts. The typical NIH research grant ranges from $100 thousand to $2 million, and anything bigger is fodder for university news releases. Which raises the question: what have US taxpayers gotten in return?

I ask this as a patient who is grateful that these scientists are working to understand a disease that affects me, my family, and millions in the US and worldwide.

The answer is not obvious, since the publications page on the ADRN website hasn’t been updated since July 2011.

According to the website:

The Atopic Dermatitis Research Network (ADRN) is a consortium of academic medical centers that will conduct clinical research studies in an attempt to learn more about skin infections associated with atopic dermatitis (AD). The studies will focus on antibiotic-resistant Staphylococcus aureus infections and widespread viral infections of the skin, both of which are more prevalent among AD patients. The ADRN will build on the work of the Atopic Dermatitis and Vaccinia Network (ADVN) which conducted clinical studies focused on making smallpox vaccinations safer for people with AD. 

This research will lead to a greater understanding of the immune system in AD patients and may lead to novel therapeutic strategies to manage or prevent infectious complications associated with this disease. 

The ADRN will conduct a number of clinical studies over the next five years and will be enrolling large numbers of people with AD.

A search on clinicaltrials.gov returns two entries for the ADRN: one (open) to create a database of patients for the study of genetic markers connected to susceptibility to infections, and one (completed) to look into how AD patients respond to a new flu vaccine.

The ADRN’s NIH contract number is HHSN272201000020C. A search in the NIH’s PubMed database returns 12 papers that acknowledge funding by that contract number. Three of those are review papers (which did not involve new research).

So that makes  two clinical trials and nine research papers, three years into a five-year $42 million project.

Should US taxpayers expect more; be satisfied; or be impressed?

The answer is probably that we will have to wait to find out.

In each year, a typical top university research lab operates on about $2-3M a year and publishes somewhere around ten papers. That’s roughly $200k a paper.

Three of the five years in the ADRN contract are up; three-fifths of $42M is around $24M. We might therefore naively estimate that we should have seen upwards of 100 papers produced so far.

Most likely the reasons there are only 12 at the moment are that you don't start publishing papers right at the outset of a project. The research must be done first and then written up; and the process of getting accepted to a journal takes months. And the ADRN appears largely to rely on clinical trials--which take time to set up.

So why do we only see two trials listed on clinicaltrials.gov?

I've never had anything to do with a clinical trial, but when I was a researcher, I conducted animal experiments, and there were formidable administrative hurdles to get over before I could start work. I imagine that trials with human subjects are heavily regulated by the government, and for good reason. So the apparently small output of the ADRN to date is, I'm guessing, because it takes a long time to plan trials, get approval, and conduct them, before you can begin analyzing data and reporting it.

Still, let's keep in mind that the ADRN is an extension of the ADVN. It’s not like the ADRN began from scratch—the scientists had the momentum of existing expertise and administration and research aims.

Looking at the titles of the published papers, I can't immediately judge which are the most important. So I emailed Donald Leung, the principal investigator for the ADRN (he's a professor and head of the Division of Pediatric Allergy and Immunology at National Jewish Health), and asked him whether he could summarize the consortium’s findings so far and highlight key points. I hope to hear back from him soon and perhaps to interview him on the phone.

I’d like to know what ADRN scientists have found that surprises them. What have they learned that is truly new?

And what is going to be truly useful to patients in the end? Publishing papers should not be the be-all and end-all of scientific research. What about patents? I’d like to know whether anyone in the ADRN has thought about controlling intellectual property and commercialization. While it’s true that clinical studies may highlight the ideal dosing amount or schedule for existing therapies, and this does not involve creating a new commercial enterprise, most medical technology must pass through the marketplace before it can benefit the consumer/patient.

Someone has to do the dirty work of developing scientific discovery into therapy, and it’s not academic scientists.

More to come.

NEA eczema research grants too small. Philanthropist needs to step up

Julie Block at the National Eczema Association recently announced that the NEA offers research grants of $10-25k/year. I am all for supporting eczema research, both basic investigations into the causes of eczema and applied projects to help treat it. That’s why, as a patient and parent, although I applaud the NEA’s program--who else is doing this for us?--but I think it’s way too small. Someone needs to give it a boost.

Now, I know that the NEA’s primary purpose is patient support, and I know that sometimes these tiny grants can be used as leverage on bigger grant applications. Martin Steinhoff, I think, told me that NIH “study groups” that decide who gets federal money give great weight to grants from patient advocacy groups like NEA. They're a seal of approval.

Nevertheless, let me give a bit of perspective. Modern biology is expensive. The salary alone of a single graduate student is $50k/yr (counting overhead). The last time I looked at NIH research grants, the median grant was $250k. And, from what I’ve seen, the budget for a single lab at the University of California is at least $1M/year. Bigger labs, $2.5M/yr, a hundred times as much as an NEA grant.

Plus, here’s another issue: I don’t think leading scientists are going to bother applying for $10-25k grants. They’re not worth the time of a Kevan Shokat or a Carolyn Bertozzi: an innovator who could make radical discoveries that would transform a research field.

So we need to think bigger. How can the NEA get more money for its grant programs? We can’t rely on the NIH alone to fund eczema research. They don’t even include eczema as a condition worth listing in their public accounts.

The NEA is not going to get money from the government. And at their current annual subscription fee, they’re not going to get it from you or me. They might get it from one or more wealthy philanthropists who either themselves suffer from eczema or who have close family members who do.

And these philanthropists are going to want to know that they are not throwing their money away, giving it to scientists to buy expensive toys. They are going to want to know there is good management in place, with a plan that includes milestones. Would we be ready to convince such a philanthropist that we merit their money?

Or, possibly, someone would be interested in offering a prize, like an X Prize (an Ecz Prize?) of a million dollars or more for the first research group to, say, provide an effective pH-balanced filaggrin-based scalp moisturizer. Big prizes, so the scuttlebutt goes, offer a factor of ten leverage. You pay a prize of $1 million, but you get $10 million worth of research done by competing groups. Plus, a prize draws attention to a challenge.

The question is: what goal would a prize be offered for? Eczema is such a complex problem, and we’re far from a complete understanding of it. So what realistic, inspirational goals could a prize committee set? I’d be happy to learn of parallels where this approach has worked for other conditions.

Dr. Jazz and a truly massive eczema research grant

Today's a special day for me: yes, I'm officially one year older. At this stage of life, I'm satisfied with "Happy birthday, daddy" from the kid who can talk, a slobbery mauling from the one who can't, and a rendition of "Happy Birthday" from Hidden B, who doesn't sing out of tune so much as she sings each line in a different key.

My birthday present to myself? Either I am going to crack open that bottle of Aussie white wine and enjoy a few glasses, or I'm NOT going to open it, and spare myself the consequent itching. Ah, it's no contest: I'm going to open the bottle. You only live once.

I made my first inquiries today, to a doctor I work with professionally, about how to start a foundation. I'll call him Dr. Jazz, since he likes to play jazz on his stereo when he's in the office, so when you're in the conference room you feel like all you need is a highball and a cigarette. Dr. Jazz is deeply involved in translational research (that is, turning bench science into cures). His specialty is prostate cancer. He didn't have a ready answer for me-- he said that if someone suddenly handed me $100k I could, for starters, open a bank account in the name of the foundation. But to create a real foundation you need a lawyer. There has to be a lawyer out there willing to bill this pro bono. Dr. Jazz happens to know a wealthy donor who is on the boards of several patient advocacy foundations, and he's going to put me in touch with him, so I can get some advice and maybe an introduction.

Everyone knows that in the U.S., the National Institutes of Health are by far the most important source of funding for biomedical research. The NIH makes its funding numbers public, and you can look them up. Go to projectreporter.nih.gov and use the search engine. Type in "eczema" and see what comes up.

So I made an interesting discovery. About 45 grants were given in fiscal year 2010. Since some grants are portioned out over several years, and some major grants may have been given in 2008 or 2009 or whatever and still be active, this is just a snapshot, but it's very useful. Most of the grants are for amounts in the range $300k to $500k, with a handful at $2M. So $1M is clearly enough to fund two significant projects, but not a remarkable amount-- I am not out of line to plan on raising $1M.

Here's the humdinger. One of the grants is for $32M. It is by far the largest, two orders of magnitude greater than the median. Donald Leung (in the NIH database, he's listed as "David," but that's not his name) at the National Jewish Health Center in Denver, Colorado, is the principal investigator for an absolutely massive project called the Atopic Dermatitis Research Network. The ADRN brings together scientists from ten campuses for a five-year effort to understand and contain staph-related infections in people with eczema.

I'm going to find out more about the ADRN. From my perspective as a patient with eczema, and the father of one (and cousin, and brother, and grandson) staph infections are a truly nasty aspect of the condition. I've had two severe whole-body outbreaks in my life and I continually experience minor infections that I'm aware could always bust out into something that could put me in hospital. The possibility that the ADRN could produce valuable knowledge and real therapeutics is exciting.