Wednesday, 5 August 2015

What ticks your box.

You said

"Team G seems to have a high opinion of themselves and they can easily point faults at others"......but "Team G are several rungs down the ladder than those who they criticize".

This is a opinion and we have given you a gun and you take pot-shots (is it wise to shoot you arms supplier :-)) but why do you look up to any lab and put it on a pedestal
Is it the number of Nature/Science/Cell papers? (The person above has a point). Their altmetrics and media attention. The influence/reproducibility of their work

Is it the ability to deliver/deliver ideas that become MS treatments? (The person above doesn't have a leg to stand on I'm afraid).

Is it their budget? 

(One lab MS spent more on peptides for one experiment than my total years budget) 

I guess personal experience is key....if you have a good experience/outcome, you are going to think the person treating you is ace. Cast that aside we know that...

So what makes a lab worth putting on a pedestal? (You can put concepts rather than specifics)

P.S. It is usually possible to find fault with any piece of work 
If we said everything was great we would be the same as many other MS blog sites.....No one is above critisism including ourselves, but it helps if it is constructive rather than some mindless rant that gets you in spam. It helps if it is based on correct information.

Should we burst any bubbles?

37 comments:

  1. I'm not sure why you are bothering. Really some people will never change their mind once they have a fixed idea that suits their psychological make up. I think the majority of people on this forum have more flexibility and would have ignored the debate you are alluding too. The personal insults that were thrown about, say to me insecurity and using this debate to feel better about him/herself by attacking others.

    ReplyDelete
  2. i'd appreciate it if you were more critical about your own studies e.g. charcot trial.....that would endear you more to people. it would be fine to say charcot trial/siblings study etc won't give any definitive answer to anything, but we did the best we could with the money we had etc

    ReplyDelete
  3. I'ld appreciate it is you were more critical about your own studies....eh?

    We post on our published work, indeed it is a forum for our published work just like we post on other peoples work. Which paper do you want us to critique more? Should we point out where the holes of our studies are?. Surely there are enough people out their that will do this for you.

    I could say "Charcot project won't give any definitive answer to anything, but we did the best we could with the money we had etc" There you go. Only problem is this, is the results has not been published yet and therefore why would anyone be discussing the study yet. I could say the Charcot project will give us the answer too.. However, how can I do this because I have not seen the final data.

    We are not going to give the results of the trial on the blog first, simple as that, but to be critical because we are not open enough about what we do.......OK our experiment yesterday didn't work.....Does this make you happier?

    I know it would make people and ProfG happier if I did not rise to the bait....but as you know I am not a saint:-)

    ReplyDelete
    Replies
    1. You'd make me happier too;) but you've opened the floodgates now. Just remember Marcus Aurelius and his version of sticks and stones.

      Delete
    2. Lots a versions of it, the best I've found over the years is in his book Meditations (translated by Gregory Hays) which I don't have to hand at the moment so here is one version, with a little explanation of it and stoicism -well, sort of). Aurelius was far from the picture portrayed in Gladiator but without writing an essay it is difficult to sucintly describe. www.wildmind.org/blogs/quote-of-the-month/marcus-aurelius-pain

      Delete
    3. I'd like to point out we did rip apart the lamotrigine trial! The second version is the phenytoin trial in ON which is a significant improvement...

      Delete
    4. p.s. Today my experimemt worked a treat....corkingly good result.

      Delete
    5. And believe me folks, it's rare that MD gets excited ;-)

      Delete
  4. Mouse,

    This is an excellent blog and your hard work is appreciated.

    I think a trick was missed with the Charcot trial. It created a real buzz on this site (own comments page) and was the hot topic at the research days. Unfortunately, academic research protocols got in the way and it seems like the project got bogged down. This project could have used a different approach - realtime reporting of progress. It was a very small trial c20 people taking some tablets. How it took so long is beyond me. Unfortunately it shows how the bureacracy of research can slow good ideas down to a snails pace.

    ReplyDelete
    Replies
    1. You cant do anything in a double blind trial until it is all done....the problem was the data lock. It took too long ensuring the data was correct before it is locked and then unblinded.

      But here is a problem you are open about what you do and it creates too much expectation success and your slowness gets forgotten eventually, but fail and you can feel like an idiot and then have to defend yourself. Keep quite and non one knows the failure....this is an approach I have favoured.

      Delete
  5. "Pointing out faults" is part of academic criticism! Whoever is making those comments doesn't understand how you all work on a daily basis. I'm sure you're just as rigorous on a daily basis with each other in the lab. And anyone who has ever had to defend a paper or submitted anything for peer review will know that you're only doing what every academic faces from their colleagues. It's all good!

    ReplyDelete
  6. Right after reading your blog I read this! Perhaps it also helps to explain why people don't understand you being "critical".
    http://www.vox.com/2015/3/23/8264355/research-study-hype

    ReplyDelete
    Replies
    1. Thanks for the link to the article. Very good, same ethos we have on the blog. Gives CCSVI a kicking too, what's not to like ;-)

      Delete
    2. Very good article - and also highlights the problem with modern high-profile research publications. To publish anything in a high-profile journal, the work should be viewed as high impact. in the past, this judgement was made by the reviewers and the editor. Now, the authors must demonstrate high impact themselves - and this obviously leads to ever-so-slightly overhyped introductions and conclusions. And then the journalists see how "promising" the published study is, by the authors' own admission, and much greater hype, without real understanding of the content, makes it into press.
      I think many scientists (including MD?) started to develop an allergy to the highest-profile journals. Perhaps over time this will help to break the cycle.

      Delete
    3. We all want to publish in the highest profile journals and so do our bosses,but the bar is being set so high that the studies take years and cost a small fortune, the reviewers ask for blood and all t's an i's to be crossed and people give it to them to get the publication. They publish some amazing big science that change the field but also have a habit of publishing pop science, based on a pack of cards, which will fail the test of time. Therefore there is a far amount of unreproducible guff and some of can be spotted. The truth comes out in the end,

      Delete
    4. I would like someone to do a meta-analysis on publications within high impact journals over the last ten years based on the group, I would not be surprised if it isn't biased towards the ivy leagues and the golden triangle universities...

      Delete
    5. Would they argue that they do the best work?

      Delete
    6. They would but close analysis often reveals that argument to be erroneous.

      Delete
  7. Mouse, the discussion in comments to one of the recent posts seem to indicate that a tutorial on statistics would be very useful to MS researchers and perhaps also MSers. Would you consider such tutorials as a part of your planned continuing education part of the blog?

    ReplyDelete
    Replies
    1. Well here's an introduction.
      http://multiple-sclerosis-research.blogspot.com/2015/04/research-day-drarie-blows-lid-on.html

      Delete
    2. Thank you - great intro indeed. More to follow?

      Delete
    3. Yes this is something that we've continued to talk about but not got round to doing. If there is anything specific you would like explained then let us know and we can start with that!

      Alison

      Delete
    4. How to determine which studies were sufficiently powered
      How to use survival analysis, and how it compares to other methods which are supposed to tell us what trial outcomes are statistically significant
      How to deal with heterogeneous data (e.g. patient groups which include responders and non-responders)

      Well, I guess it's more than enough for now, thanks for considering this

      Delete
    5. I think this is an excellent idea. It can be a difficult one to explain even my learned colleagues do not seem to get it. why do I say that...60% of EAE studies use in my opinion an invalid test to analyse their data.

      Delete
    6. How do you know if a trial is sufficiently powered. They are all powered and generally in the paper they will say how they determine the number of people in the trial so it it is not too few to see and effect and not too big such that you are exposing some people to unnecessary risk as the efect of the rug is an unknown an carries risk...

      Read the sponsor of the trial if it is pharma sponsored it has a reasonable sample size. If it sponsored by an academic/charity it is probably underpowered and too small.

      In the UK an academic trial of over £2-3 million is unlikely to be funded. Pharma could only dream of doing a trial that cheap.so people manipulate the statistical anlaysis to arrive at this amount.

      Now to clarify. I would think that all clinical studies are adequately powered in that a statistician has worked out to the probabilitly (P=0.05 is a one in twenty chance, P=0.001 =one in thousand chance) of seeing an effect size of x (how much the drug works) with x amount of power to see an effect.

      However what happens in academic studies is that there are compromises made, so say the drug is powered to show an 50% reduction in neurodegeneration and gives a sample sign of x hundred. However the likely effect is probably a 15-20% reduction but that would mean x times more people in the study and this means the cost is too much for the study to do. So the academic trails often select perhaps unrealistic drug effect sizes to allow them to do the study.

      In phase II trials they may select 80% power to see the effect i.e. in 8 out of ten studies they would see the effect. In phase III pharma may go for 90% power to see an effect. This means hundreds/thousands of people in the trial.

      Delete
    7. I was looking at free online courses and just found this one about understanding health research - doesn't appear to be so much about statistics etc, but looks like it could contain some interesting material
      https://www.coursera.org/course/researchforhealth

      Delete
    8. And here's another one on Design and Interpretation of Clinical Trials:
      https://www.coursera.org/course/clintrials

      Delete
    9. Yes, the main problem is people think they know statistics but have no idea what they are talking about. Time to failure as an endpoint is entirely different than the number of failures. You cannot make an analigy of time to failure with that if a coin flip. Unfortunately to make some people understand is going to require a brain transplant.

      Delete
    10. Thank you, MD and Anonymous 8:20, 8:58.
      I will take a look at coursera courses, and the MIT statistics site suggested earlier seems to be excellent. If only I had time to work through it seriously... (I am an MSer with a full-time job, and it's getting busy here, with the usual MS fatigue on top).

      Delete
    11. My guess is MS research statistics is particularly difficult, due to rather weak signal (20% effect is not huge, is it?) compounded by high level of "noise" (natural history of relapses/remissions). I am not sure there are good formal ways to address the noise issue; waiting for a relapse to happen or not happen takes huge amount of time (or study subjects) to analyze properly.

      Delete
    12. If you want to know how to interpret survival analysis data, you may want to read this paper:

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932959/

      And the example:

      http://i1140.photobucket.com/albums/n563/CvFactor/Mobile%20Uploads/Albuterol%20addon%20relapse%20rate_zpsremfet6e.png

      Delete
  8. There is a nobel price in the game, for the one to solve the MS riddle! If I had achieved a tenured professorship, I would solve the riddle. Why not doing real science? I am not talking about epidemiology and clinical studies with random drugs. You guys should do the real science, go back to the bench, and since you're MDs, you should really look more carefully at patients. You are not bad, I am not saying this, at least you have heard of vit-d levels and granulocytes. But seriously, you guys should again look at the body and where things really happen. It can't be the brain, because a full-blown immune attack against brain tissue would not leave anything left behind. The attacks are rather subtle, so it could be a gut thing. Have you thought about this? Of course you have, but have you checked it by yourself, something like a local inflammation around the gut on your patients?. The other possibility is really looking at proper tissue, I know its hard, but you guys are based in London, it should somehow be possible to get that material? To me it looks a bit like you are loosing yourself in the mass of data and complexity.

    ReplyDelete
    Replies
    1. Tenure seldom happens these days you have a rolling contract so if you do not come up with the goods beware.

      A full blown attack of the brain would not leave anything behind....is clearly not necessarily correct EAE tells us very distinctly otherwise.

      It could be a gut thing and it could not be a gut thing. There are a number of groups looking at the gut and the microbiota. I personally have not wanted to follow this I have my own interests, just as you have yours. Do I think this is the real answer I doubt it.

      You can not do every thing. We dropped focus on the autoimmune response to look at neuroprotection and progression many years ago because other people do the immune stuff and we do not have the resource to compete.

      As a MD mouse doctor I do not have easy access to people with MS and any neuro wanting to study this would need ethical approval.

      We are focused on what we do.

      If you want to fund someone to look at guts we could discuss of find someone with the interest in this area

      Delete
  9. To me, a good lab is looking for neuroprotectives and cares about finding answers for people with progressive MS. So, as a person with PPMS, you tick my box.

    ReplyDelete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.