Reproducibility Initiative gets $1.3M grant to validate 50 cancer studies

http://blog.scienceexchange.com/2013/10/reproducibility-initiative-receives-1-3m-grant-to-validate-50-landmark-cancer-studies/

by djkn0x • 13 years ago

236 34 13 years ago

blog.scienceexchange.com

dnautics• 13 years ago

this is really phenomenal. Congratulations, SE.

brianbreslin• 13 years ago

awesome congrats guys!

ypandit• 13 years ago

Congratulations SciEx !

irollboozers• 13 years ago

Science Exchange is leading and pushing ahead with this very important work. They are addressing what the public funders and private industry can't and won't do, but at scale this becomes really powerful. Great stuff.

Create• 13 years ago

They did it publicly, ie

Why Most Published Research Findings Are False. PLoS Med 2(8): e124. doi:10.1371/journal.pmed.0020124

and privately: the matter of fact is, pharma companies are unhappy, because according to them, over 70% is irreproducible (euphemism for BS).

This is why ie. BMJ will only accept papers from January on that publish evidence ie. data also. One wonders what happened before...

BMJ 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f5975

gabemart2• 13 years ago

I don't know very much about how reproducibility validation works. Is it the case that, if we assume p= ~0.05 and all 50 original studies are perfect, we would expect the first iteration of reproducibility validation to fail for ~2 of the 50 studies?

mjn• 13 years ago

Not necessarily 5%, no. The p-value is controlling the false-positive rate, i.e. it constrains the likelihood that a seemingly-significant result was really just by chance. Therefore, if we were now given the real ground truth, it's likely that ~5% of the original positive results (if the studies were properly conducted) would turn out to be unsubstantiated after all.

But you seem to be positing the reverse: a hypothetical case where we assume that the results of the original studies were in fact correct (i.e. ground truth), and we want a sort of false-negative rate, the chance that a fact would not be confirmed by a replication study, despite actually being true. That depends on several things about the replication attempt, such as sample size and methodology, summarized into the concept of statistical power: http://en.wikipedia.org/wiki/Statistical_power

The overall failure-to-replicate rate would involve both aspects, with four possible outcomes at varying likelihood: 1) a correct result that was confirmed; 2) a correct result that failed to be confirmed; 3) an incorrect result that was confirmed anyway; and 4) an incorrect result that failed to be confirmed. Obviously it would be ideal if #1 and #4 were much higher than #2 and #3.

gabemart2• 13 years ago

Thanks, very interesting. It was silly of me to assume that the p-value could be used in that way when, as you explain, it's not measuring or indicating that at all.

yummyfajitas• 13 years ago

it's likely that ~5% of the original positive results (if the studies were properly conducted) would turn out to be unsubstantiated after all.

Not quite. Assume P of the tests are truly positive, and N are truly negative.

We expect to see approximately 0.05 x N + A x P positives in the entire sample, where A is the probability of a false negative. So the fraction of true positives not replicated is likely to be 0.05 x N / (0.05 x N + A x P).

gwern2• 13 years ago

That depends on several things about the replication attempt, such as sample size and methodology, summarized into the concept of statistical power: http://en.wikipedia.org/wiki/Statistical_power

It's not just power, you also need prior odds if you want to make an unconditional estimate. This is pretty much the core of Ioannides's famous paper http://www.plosmedicine.org/article/info:doi/10.1371/journal... - even after taking power into account, the replication rate could be anywhere from 0 to say 80% depending on the prior odds.

bmahmood3• 13 years ago

This is Bilal from Science Exchange, and I help with the Reproducibility Intiative as well.

I think that in general you're right, with the assumption that p=0.05. However, each of the studies being replicated is composed of many intricate experiments. We will be reproducing most of those experiments, so while the odds of a single validation experiment failing are certainly not zero, I think the chances of an entire paper's worth of reproduction experiments being false negatives is much less likely. All of the protocols and reagents used, and the data from the replication studies, will be publicly available when they are complete, so that everyone can see what we did and how we did it.

Eliezer• 13 years ago

I think that in general you're right

Oh, dear. This is very much not a good sign, since answer to grandparent's question is "no" as pointed out above and anyone who knows statistics should see that immediately. (Checks Science Exchange site.) Okay, Bilal Mahmood is "customer support and outreach" so this is not necessarily fatal. Still worrisome.

Osmium2• 13 years ago

Honestly, I'm impressed $1.3M is enough for 50 studies! Though, of course, verification should be cheaper than the original research since you know exactly what to look for and how to find it.

mathattack2• 13 years ago

If $1.3M can cover 50, they should fund reproducing 500, or even 5000.

I suspect that many pure science studies are relatively easier to reproduce since it's more about basic properties. If you're getting into medicine, it's more expensive because you may need to reproduce trials. Psychology even more so because the tests are so soft. But of course psych and medical studies are the ones most in need of replication.

Osmium2• 13 years ago

I suspect that many pure science studies are relatively easier to reproduce since it's more about basic properties.

Not necessarily true at all actually. To use an example, the field I work in requires that we grow our own semiconductor crystals. Different growth reactors in different universities producing nominally the exact same substance will result in sometimes vastly different properties of the end result when studied (usually due to minute trace impurities, or marginally different temperatures or flow rates during growth, or a host of other things–all of which need to be analysed and vetted–and this happens even if they're using growth reactors made by the same manufacturer!). It makes replication very difficult and often results in slow progress. And it's expensive too. So it's not just medicine that has that problem.

Edit: I should add that obviously in the end it works out because these materials eventually make it into industry and into millions of devices. So it's ultimately reproducible. But that gap between first discovering a process or a mechanism or just something interesting and making it reproducible consistently enough and at a large enough scale for industry is just huge.

Fomite2• 13 years ago

Beyond it being expensive to replicate once, for observational studies and clinical trials, you need many repetitions because of statistical variability. That gets expensive in a hurry.

bmahmood3• 13 years ago

Hi this is Bilal from Science Exchange, and I help with the Reproducibility Initiative.

You are right that the per study costs are cheaper than normal as the original protocol is already developed, and there is less trial and error involved. In certain cases, we may not need to validate every aspect of a study as well, only those specific experiments that warrant replication. And depending on the study, those experiments may vary in cost (i.e. a mouse model component would be expensive, but RNA extraction and western blot testing relatively inexpensive).

Additionally, we will leverage expert labs on Science Exchange which perform experiments regularly on a contract basis, allowing for bulk savings on reagents and supplies.

loceng• 13 years ago

Bulk Science. I like it.

001sky• 13 years ago

I came here to say the same thing. For important research, it would be interesting to see more cost/benefit analysis being put to bear in this way. The cost of replication should be so much lower than original work, in many cases. And it would be interesting to evaluate the "science" of academic "science", especially given the controversy around peer review quality controls in general on academic publishing.

DaveWalk• 13 years ago

I'd be interested to know which studies they are targeting. Is SciEx testing a key figure from an expansive publication, or the entire methodology from discoveries with few tests? To me, this seems to be a conceptually difficult decision to make...most discoveries do not discuss the number of years (or failed attempts) that goes by before obtaining the quantifiable result.

And where is the peer review in this process? I suppose as soon as something turns up unreproducible we will find out.

napoleoncomplex• 13 years ago

Reproducibility in science is something that badly needs this push. It's an incredibly difficult "sell" to anyone with funds for research, and I'm extremely happy that they've found capital for it.

The foundations of our scientific knowledge need to be solidified, and from all the science news and developments, this one is the one that makes me by far the most excited for the future of science.

Next on the list, open source repositories for protocols of experiments! Maybe someone surprises me with a link to an existing solution :).

Alex39174• 13 years ago

Assuming there are about 3 dozen common scientific mistakes in medical journal articles, each appearing in on average 10-20% of papers with a relatively high degree of independence, there isn't really much foundation for medical science to begin with. (And I think these assumptions are probably fairly accurate.)

tokenadult• 13 years ago

You haven't validated any of those assumptions. Moreover a "common scientific mistake," while regrettable and something to reduce, may not have a lot of impact on actual clinical practice based on what physicians read in published medical journal articles. You'll have to connect a lot more dots to show that there is a high-impact problem here.

Meanwhile, life expectancy at age 40, at age 60, and at even higher ages is still rising throughout the developed countries of the world,[1] so at least the trend lines look good for continued improvements in health as medical research is incrementally improved. Girls born since 2000 in the developed world are more likely than not to reach the age of 100, with boys likely to enjoy lifespans almost as long. The article "The Biodemography of Human Ageing"[2] by James Vaupel, originally published in the journal Nature in 2010, is a good current reference on the subject. Vaupel is one of the leading scholars on the demography of aging and how to adjust for time trends in life expectancy. His striking finding is "Humans are living longer than ever before. In fact, newborn children in high-income countries can expect to live to more than 100 years. Starting in the mid-1800s, human longevity has increased dramatically and life expectancy is increasing by an average of six hours a day."[3] An article in a series on Slate, "Why Are You Not Dead Yet? Life expectancy doubled in past 150 years. Here’s why"[4] makes clear that it's progress here, and progress there, and a lot of little things adding up that have resulted in the dramatic increases in healthy lifespan over the last few generations.

[1] http://www.scientificamerican.com/article.cfm?id=longevity-w...

[2] http://www.demographic-challenge.com/files/downloads/2eb51e2...

[3] http://www.prb.org/Journalists/Webcasts/2010/humanlongevity....

[4] http://www.slate.com/articles/health_and_science/science_of_...

dwaltrip• 13 years ago

The point of your comment isn't clear. Should everyone go home and give up then? This initiative surely alleviates some of your concerns, yes? And while I don't have too much specific knowledge, my general sense is that our medical knowledge has increased enormously in the past 100 years, and that this trend seems primed to continue. But I'm generally pretty optimistic.

doctoboggan• 13 years ago

This is awesome. I met some of the people behind The Center For Open Science at SciPy this year. They seemed very passionate. I hope the idea of reproducing experiments as a matter of course becomes more common. Maybe in the future to be a reputable scientist you will have had to reproduce many of the current experiments of the time.

Reproducibility Initiative gets $1.3M grant to validate 50 cancer studies

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