David Tuller: Trial By Error: “Talk is Cheap,” Patients Tell NIH

[Andy]

Earlier this month, NIH director Francis Collins and other agency officials held a meeting with five representatives from #MEAction. According to the group’s post about the meeting, the goal was “to discuss accelerating research in order to more rapidly provide diagnostics and treatments to people with ME.” Specifically, #MEAction urged the agency to develop “bold leadership for ME,” “disease-specific, multi-year Request for Application (RFAs) and investigator-initiated funding opportunities,” and “a strategic plan: comprehensive, fully-funded, cross-Institute and outcome-driven.”

From #MEAction’s perspective, the outcome of the meeting left much to be desired. According to the group’s account, “NIH leadership is not yet ready to significantly accelerate NIH’s approach and commitment to ME because they feel the science is not ready, and that the field lacks the needed researchers and high-quality grant applications.”

http://www.virology.ws/2018/12/26/trial-by-error-talk-is-cheap-patients-tell-nih/

 

[Andy]

Not too enthused by the publicity for the "ICC is the one true definition of ME" crowd, and the less said about Erik Johnson the better, all in my own opinion of course. #MEAction may have their flaws, as all of us do, but at least, as far as I can see, they are trying to be as inclusive and as representative, as is possible, rather than exclusive based on personal opinion.

 

[Alvin]

This reads like the NIH version of ‘thoughts & prayers.

Thats clever

As i posted in the MEAction thread

So in other words they are creating a fake Mexican standoff by saying there is no one good enough to do research hence we won't fund new research and everyone and anyone you present is not good enough (and probably never will be, this part is silent).
No other disease funding works like this so they are acting in bad faith even if they choose to believe they are not.

There is no chicken or the egg problem here, there is a we are not interested but won't admit this even to ourselves problem.

It seems their real goal is to divide and conquer, by pretending they are on our side they can keep us off track and just keep denying resources to ME research. By attempting to gaslight us they can keep us off track, assuage their own cognitive dissonance and hopefully keep us busy trying to meet their goalposts which will keep moving because the real goal is to not fund research (that part is also silent).

How many Nobel prize winners will it take, do we need to bring a few hundred back to life before one gets funding? How many other diseases need more then we have before they start funding research above a pittance?

If anyone wants to calculate such a ratio i'm sure the results will be illuminating. Or if someone with Twitter wants to point out we have several but they won't fund any that would be great. Since a Nobel prize can't get funding from the NIH what will? I'd like to see the answer to that question.

 

[Sean]

I understand the NIH not wanting to commit serious money on unproductive wild goose chases. There is something in the argument that it is possible to go too hard too early, before we have a good sense of which directions to move.

On the other hand, if there is no real money, and no career path potential, then why would researchers make the effort and take the risk, and how else do we find out which are the best directions to move?

Hitting some initial dead ends, especially in a grossly under-researched disease like ME, is a normal part of the scientific process. It is no reason to not cough up some decent money at the start.

We need a starting point of at least 50-100 million per year, even if for no other reason then it would show researchers that the NIH is seriously committed.

As I suggested previously, they could make it up by simply saying to all other research areas in the NIH that they have to find 0.1% (or whatever it takes) off their budget to go to ME research.

If those other areas don't like it, they can sod off. We are asking for nothing more than parity, nothing more than our very very long overdue fair share.

 

[Hoopoe]

I agree we're stuck in a situation where the funding is withheld because our knowledge is limited, yet funding is the only way to advance knowledge.

The plan by the NIH seems to be to wait for an indefinite number of years until they feel that the risk of research waste is low enough to commit to substantially higher funding.

 

[Jonathan Edwards]

“NIH leadership is not yet ready to significantly accelerate NIH’s approach and commitment to ME because they feel the science is not ready, and that the field lacks the needed researchers and high-quality grant applications.”

I can imagine that his may well be the situation and I think the NIH may be right. I am not hearing of lots of projects not being funded by NIH that look worthy of big funding.

NIH is giving out funding. The money is available. Parity with other conditions means the same height of bar for research quality. There are serious issues about quality evaluation but it makes no sense to dish out money unless there is a reasonable chance of success.

I can imagine that it does not help persuade the NIH to have some of the comments that follow. They illustrate why there has to be quality control. Looking for moulds is not going to help anyone and nor, I think, is a focus on ICC. The Incline Outbreak is history and probably of no real interest now.

What I think is needed is some objective clinical documentation of the illness in day to day circumstances that leads to intelligent research questions about its origin. I think a lot of research groups are starting at the wrong end.

 

[WillowJ]

Nobody is asking for money given out randomly.

NIH needs to make a plan for how to get from here to there.

M.E. got left behind decades ago when research standards were different. It's not clear how you get from knowing not much to doing high-quality research, in any kind of reasonable time frame.

However it's unconscionable to leave patients to rot, and continue to be stigmatized, because you don't like the odds of finding something by casting a wide net.

NIH needs to fix this, and they need to fix it considering time to be of the essence. There's no other decent option.

 

[ME/CFS Skeptic]

There are serious issues about quality evaluation but it makes no sense to dish out money unless there is a reasonable chance of success.

Not sure about that. Maybe success should not solely be defined as a good study or paper but as getting the research field going and attracting new researchers. It seems like we're in a vicious cycle of inertia: there aren't any good researchers because there is no secure funding, and there is no funding because there are no good researchers. The NIH could break that cycle by RFA's and it's quite possible that they only have to do it once.

I also see no reasons why they don't set up another high quality study themselves, for example following up on persons who get EBV (there has to be something that changes biologically that explains why a small fraction never recovers from such infections).

 

[Hoopoe]

What I think is needed is some objective clinical documentation of the illness in day to day circumstances that leads to intelligent research questions about its origin.

Tht sounds like exploratory research without a hypothesis. The NIH doesn't fund this kind of research.

The way the NIH is doing things works for illnesses that are well enough understood but it doesn't work for ME/CFS.

 

[Trish]

NIH is giving out funding. The money is available. Parity with other conditions means the same height of bar for research quality. There are serious issues about quality evaluation but it makes no sense to dish out money unless there is a reasonable chance of success.

I agree funding should only be given to high quality science. So far we are pretty much stuck at the stage in the UK where ME charities fund small projects, hope these will produce sufficiently interesting results that will then enable application for funding for much larger projects, as Karl Morton is currently preparing to apply to the MRC in the UK. I'm sure the UK ME Biobank could easily use more funding.

And yet the MRC and the NHS research funding body have given out and continue to give out millions to really crap CBT/GET/IAPT variations. Why is the bar so much lower for this extremely poor quality research, yet they make it so hard for biomedical scientists to get funding.

 

[wdb]

How does the funding work, if say they budget $100M are they committed to spending it all or could it just be earmarked as available should sufficiently high quality research proposals be received ? As it is nobody is going to propose a high quality $20M research study if there is no indication that it could ever be funded.

 

[Jonathan Edwards]

Tht sounds like exploratory research without a hypothesis. The NIH doesn't fund this kind of research.

The way the NIH is doing works for illnesses that are well enough understood but it doesn't work for ME/CFS.

It isn't really without a hypothesis. The hypothesis is that there are one or more objectively documentable abnormal clinical patterns in ME. I am thinking in terms of using accelerometers to document changes in activity patterns. The hypothesis is almost certain to be right but more importantly it is highly likely that with intelligent analysis the patterns can be documented specifically. So it is a solid bet for NIH.

Moreover, NIH do fund work of this sort. They are funding work at the UK ME Biobank which is pretty similar in terms of trying to document objective abnormalities - whatever they might be.

 

[Jonathan Edwards]

NIH needs to make a plan for how to get from here to there.

We all want a plan to get from here to there but plans in scientific research are not there ready to take off the shelf. The whole point about scientific research is that it involves thinking of a solution to a question that nobody has so far thought of. You have to have an application from a scientist who has hit on the right idea about how to get an answer. You cannot put that out to tender like buying a telephone service!

I realise that I sound negative but I am currently acting as independent advisor for exactly the same process in the UK through the equivalent government body. And although there are some sensible ways forward being proposed that will have applications made on it is very far from clear that any of us can see an obvious way to go. UK scientists have got together to pool resources and try to think of a really promising way to test an idea and it is far from easy. You have to have the right idea and also someone with the right expertise in a position to test the idea.

I am all for emphasising the urgency of the problem but I think it is all too easy to put the science community off by making criticisms of NIH that may not be that reasonable.

 

[Jonathan Edwards]

Why is the bar so much lower for this extremely poor quality research, yet they make it so hard for biomedical scientists to get funding.

Because of a specific political problem that needs addressing.

I agree things are out of kilter but the inappropriate funding of bad studies is a different issue from failure to fund good studies. Things are not right but my main point is that the message from the NIH does not sound so unreasonable.

 

[Trish]

Re-reading David Tuller's article the thing that strikes me is that the reaction from the patient community that is quoted is not particularly representative of the wider patient community, but focuses on a few individuals active on Twitter, Facebook and in responses to David's blogs that are pushing minority views and experiences.

Not being in the USA it is hard for me to tell how representative of the community there these views are. Is there actually a groundswell of opinion that looking into mold at Lake Tahoe is essential in uncovering what ME is about for the majority of pwME, and is there a general view that the ICC definition is the only true definition of ME and research based on any other definition is wrong?

I am also not particularly comfortable with the #MEAction approach of bombarding funding bodies such as NIH and guideline bodies such as NICE with letters, tweets, e-mails etc from individuals making demands. I wonder whether such things can actually be counterproductive. Looking from the perspective of a busy civil servant, which these people effectively are, with many demands on time to get the job done, having to deal with a snowstorm of individuals demanding action seems to me to be more likely to get in the way useful action, and to cause more annoyance than productive changing of direction.

 

[Jonathan Edwards]

How does the funding work, if say they budget $100M are they committed to spending it all or could it just be earmarked as available should sufficiently high quality research proposals be received ? As it is nobody is going to propose a high quality $20M research study if there is no indication that it could ever be funded.

If a study that deserves $20M is proposed then I see no reason why it should not get funded by NIH or MRC (other than the fact that the peer review system is a lottery across the board). But as we are at the moment I cannot think of anything that would justify $20M. There are leads that could well be followed with $2-5M projects maybe.

The basic problem is persuading people in the funding bodies that projects are good enough to fund. Once you have done that the funds will be routed as needed. Ring fencing might seem to help. But ring fencing for AIDS and Alzheimer's was done at a time when it was obvious to funding bodies that the questions to ask were well enough understand for there to be large numbers of scientists out there who could think of sensible ways of getting answers. NIH is saying we are not there yet for ME and I tend to agree.

 

[obeat]

Has anyone tried to track metabolomics/ immune profiles for 7 to 10 days after a challenge that causes PEM to figure out how it resolves?

 

[ME/CFS Skeptic]

Do not know the details but didn’t the great success stories in medicine like polio or AIDS turn into a success because of political action and campaigning instead of waiting for good research proposals to arise?

To me it seems like NIH is mostly willing to fund what researchers find interesting instead of what is relevant for society. In the case of AIDS, activism was needed to reorient research funding into this disease and stop it from killing more people. Researchers and government agencies did not have the incentives to do that in an apt pace. ME rarely kills but given the numbers of patients and disability it causes, I think we could make a similar argument.

Medical research isn’t merely about doing geeky science stuff IMHO. There isn’t anything admirable in choosing to fund only well designed studies if these miss the topics that are most pressing to society. Bureaucratic procedures can sometimes obscure how irrational it is that we are funding so little research in a disease that torments so many of us.

 

[Andy]

I am also not particularly comfortable with the #MEAction approach of bombarding funding bodies such as NIH and guideline bodies such as NICE with letters, tweets, e-mails etc from individuals making demands. I wonder whether such things can actually be counterproductive. Looking from the perspective of a busy civil servant, which these people effectively are, with many demands on time to get the job done, having to deal with a snowstorm of individuals demanding action seems to me to be more likely to get in the way useful action, and to cause more annoyance than productive changing of direction.

I think the argument would be that the majority of patients have politely, some might say meekly, waited for adequate research/funding for many decades and therefore, arguably, a change in tactic has been required for a long time. Whether or not it is an explicit tactic, but my interpretation would be that it's along the lines of "The squeaky wheel gets the grease". And if it's a counterproductive tactic, then it probably doesn't put us in any worse situation than we are at the moment.

 

[Jonathan Edwards]

Medical research isn’t merely about doing geeky science stuff IMHO. There isn’t anything admirable in choosing to fund only well designed studies if these miss the topics that are most pressing to society.

I don't think anyone is suggesting doing geeky stuff. Far from it. When I say a good study I mean one that has a chance of solving a problem pressing to society.

I am sceptical about the idea that political pressure had much to do with medical breakthroughs. I think AIDS got funding when it was realised (a) that is was an epidemic that potentially could kill everyone and (b) enough was known about a likely virus for lab groups to switch on to it with a high chance of success.