Will we fund "Project Helio"?
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resolved Oct 7
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YES

Will the project "Project Helio" receive receive any funding from the Clearer Thinking Regranting program run by ClearerThinking.org?

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Below, you can find some selected quotes from the public copy of the application. The text beneath each heading was written by the applicant. Alternatively, you can click here to see the entire public portion of their application.

Activities involved in project

Building a paper-based [point of care] biosensor for population assessment of vitamin B-12 deficiency in [low income countries]

Populations that would benefit

Nigeria, whereby populations at risk (children + women) have not had vitamin B-12 data collected on them within the last 20 years even though 31% of the population is estimated to be severely deficient. They should be evaluated every 5 years, however, this has not been made possible due to the high costs of data collection ($10M). As a result, there are no current reports of large-scale intervention programs. We have chosen Nigeria as a suitable country, but eventually it will benefit populations in all LMICs.

Project Pitch

How much funding they are requesting

$30,000 USD


What they would do with the amount specified

Purchase wet-lab prototyping materials: lateral flow test kits, glucometers, glucose strips, antibodies, gold nanoparticles, buffer solution, magnetic beads, holoTC (we are still trying to find pure form), human serum, and the Axis-Shield assay.

Spreadsheet of all the materials we are planning to purchase, including their costs and quantities.

Here you can review the entire public portion of the application (which contains a lot more information about the applicant and their project):

https://docs.google.com/document/d/1eIgnvLBi_7OFoh4mLWtZh0WoBXWMobpGpRIRPD9gM6Q/edit

Sep 20, 3:30pm:

Sep 20, 3:50pm:

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predictedYES

Can I ask how many of these grants will actually get funded given the developments with FTX?

predictedNO

For the same reason that WHO recommends large-scale deworming, it does not seem worth identifying who is B12 deficient if, as stated in the application, "in most LMICs, ⅓ of the population is estimated to be severely B-12 deficient". It looks like 50 people could be supplemented with B12 for 1 year for the cost of 5 $ of the proposed test:

  • B12 requirement (mg/person/year): 50 * 365.25 * 10^-3 = 18.3.

  • Population of Nigeria: 218 M.

  • Nigeria B12 requirement (kg/year): 218 M * 18.3 * 10^-6 = 3.99 k.

  • B12 bulk price ($/kg): 2585.50 / 0.5 = 5.17 k.

  • Cost to supplement all the population of Nigeria with B12 ($/year): 3.99 k * 5.17 k = 20.6 M.

  • Cost of proposed test ($/person): 5.

  • Cost of testing all the population of Nigeria for B12 ($): 218 M * 5 = 1.09 G.

  • Ratio between the cost of annual B12 supplementation and the proposed test: 20.6 M / (1.09 G) = 1.89 %.

  • People whose annual B12 requirement could be satisfied for the cost of the proposed test: 1 / (1.89 %) = 52.9.

In addition, I do not think there is any problem with supplementing the 2/3 of people who are presumably not defficient. Since B12 is water-soluble, "your body absorbs only as much as it needs, and any excess passes through your urine" (from here).

@VascoAmaralGrilo hey vasco, a couple of things to note:
- we talked to people from the WHO (as well as organizations like the Food Fortification Initiative and the CDC) about this, and actually governments do not permit intervention unless you can provide concrete evidence (in the form of results from blood tests) that there is a micronutrient deficiency. it's a "country pride thing" where "every country thinks they have the best diet." BTW I am directly quoting them. it is not just the WHO who would go in with the intervention but typically it is in partnership with the country's ministry of health or other government body. so these surveys are necessary and things get problematic if a nonprofits like the WHO just tries to go in with an intervention.
- we do not need to take 218 M samples (the entire population). it does not work like that. at most for a population the size of nigeria, 50,000 samples would have to be taken (which is 0.02% of the population). currently it costs $10 million with the status quo method of shipping samples overseas and testing this many samples. but our method could reduce the cost to $240k. so no it does not cost over a billion as you calculated
- we're using nigeria as only one potential area for implementation. but there are 51 LMICs that are estimated to have micronutrient deficiencies. we just don't know which ones. and there is no way it would be ideal for the WHO to go in and implement B-12 programs for every one of these countries for every person. they would if they could - I asked. in looking at the broader scheme, this sensor would help nonprofits + govs narrow down which countries to tackle, and within each country what region.

hopefully this makes sense!

predictedNO

@AshleyMo That does make some sense, thanks for the feedback!

In your application, you mention that:

  • "Currently, to assess the status of Nigeria, it costs $10 million USD which allows for surveys to be conducted every 20 years".

  • "Nigeria, whereby populations at risk (children + women) have not had vitamin B-12 data collected on them within the last 20 years even though 31% of the population is estimated to be severely deficient".

Some questions:

  • If B12 data have not been collected within the last 20 years, and they tend to be collected every 20 years, is B12 data about to be collected?

  • Why does the government not act on the estimate that 31 % of the population has a severe B12 deficiency? Could you link to source that estimated this number?

@VascoAmaralGrilo hey vasco!

- I talked to someone from UNICEF Nigeria, and the 20 years is a very rough number. sometimes it's longer than that. they told me they are running a micronutrient panel right now but B-12 isn't on it this time (because funds don't permit and B-12 is always "underrated" anyways). but even if it were to be collected this time, they should be collecting it every 5 years. so we're trying to make that happen by reducing cost.
- that 31% is also a rough number (I would actually just generalize it to slightly less than a third). precise data is very tricky to get, and I got this stat from someone at UNICEF Nigeria since I couldn't find any data online. but even they weren't too sure (but it's the best I can get). typically this number is estimated by looking at different factors like the national food supply for a certain year, the average income, the average diet, stunting in children, etc. it's an "estimated risk of B-12 deficiency," but apparently it's not "solid enough evidence" for a country to be convinced that they may have a B-12 problem and for an intervention to be established. just to give a random example, spinach is considered to be a high b-12 food. the food supply and diets may be showing that the citizens are eating lots of spinach, but depending on where it was grown we actually don't know how much B-12 it has. spinach grown on one side of the world may have different b-12 levels than spinach grown on the other side. and for symptoms like stunting, it could be because of other micronutrient deficiencies and we wouldn't be able to confirm which ones. the only solid evidence is the direct measurement of B-12 concentrations in the blood.

everything is pretty complicated to explain, but hopefully this makes sense again!

predictedNO

@AshleyMo I see, thanks for clarifying. Regardless of the outcome of this particular grant, good luck!

seems like a high chance of failure but for the cost and expected value seems well worth it.

This is the shortest application I've read and yet one of the most clear. Bonus points for working out of a public Notion doc just like us.

Not saying a $5 biosensor with ~5% error isn’t possible, but this seems Theranos-tier to think they’ll blow past state of the art (and somehow make it work in Nigeria, vs a lab)

@Gigacasting It is worth $30K to find out.

predictedNO

seems earnest and only asking for materials,

But “The test itself would later also have to undergo FDA approval, as well as IRB or ASIA PAC approval depending on if we deploy the assay in Africa or Asia.”

Getting FDA approval and blowing past state of the art (strips instead of giant machines) is a bit naive and/or dreamy.

Hope it succeeds, but wouldn’t bet on it

@Gigacasting Hmm dont think we should care about fda approval. If we find something that works we'll just deploy it.

There was biosensor microfluidic funding vacuum after theranos making it neglected despite many promising avenues. Haven't looked much at details yet but 30k was low ask

(obviously top quartile regardless of feasibility - zero-grift asks should be almost an auto-fund before any of the “my salary” ones)

predictedYES

@GeorgeVii @Gigacasting They shouldn't have included speculation about regulatory approval, that is not relevant at all. Focusing on designing a solid trial across multiple populations comes after the engineering, which is the focus of the applicants. Purdue biomedical engineers are best of the best too. This one is a no-brainer - FUND IT!!

@Gigacasting the pitch video say a "~$5 error rate," but we filmed that back in may. apologies for not making this clear but we are aiming for a <20% rate now. ideally <10% in the span of a year. and that is just for vitamin B-12.

@GeorgeVii i've gotten comments too often saying this project is "theranos 2.0" but theranos strived to measure a practically unattainable number of biomarkers from glucose, to opiates, and all sorts of antibodies in one drop of blood. we're just measuring one biomarker (holoTC) and we will start off with a couple of drops (apologies if "one drop" was said in the older video, but all the updated information is in the document). it should also be noted that our prototype will not be looked as a diagnostic tool yet - just screening so there is more room for error. theranos was labelled as a diagnostic tool.

predictedYES

@AshleyMo Theranos was also valued at 300,000x your proposal.

Don't sweat it, you're doing just fine (participating in prediction markets is probably a much better way of learning to “keep your feet on the ground” than listening to naysayers who heard about your project for 5-mins, also seems like you have a good collection of profs and others you can trust for technical and general judgement, most other stuff is just noise ;)

Hmm it seems OWIDs vitamin A data is from 2005 mostly https://ourworldindata.org/micronutrient-deficiency, you indicate there might be more up-to-date data on vit-a? If so could you link it that I may update them.


How much are ELISA tests when adding the shipping, cold storage, analysis etc?

Where does the 40x come from?



Wondering why ELISA's require cold storage yet strips don't?



I am slightly surprised to hear EV hasn’t funded you (or at least gotten back to you quickly). When did you apply?
 Have you applied for funding elsewhere since?




“The lack of funding is the only barrier at the moment towards making progress”. Counter-factual impact is good if this is true.

@GeorgeVii What is the general sensitivity/specificity of screening vs diagnostic tool? What is usually considered the lower bound whereby sensitivty is considered too low for a screening tool?

@GeorgeVii hey george!

could you give more clarification into your vitamin A question? apologies, i am just confused.

ELISA tests for B-12 are $15-60 USD each. And it's not the ELISAs themselves that need the cold storage. The ELISAs are in first world countries like Germany (there's a lab there called VitMin - may have spelled this wrong), and so samples have to be shipped overseas. but blood is tricky to handle, and you need to have a cold supply chain. From what I've heard the cold supply chain + shipping costs for the size of Nigeria (50k samples) can cost upwards of $8 million. BTW it is difficult to include sources since I asked for this information directly from people at the WHO/CDC/UNICEF in Zoom meetings. Data is really tricky to get sometimes.

The whole purpose of our strips is so then you don't need to ship samples overseas to access the ELISAs. you can just do the test in homes/in tents on site. Strips don't have to be refrigerated, but we will need to find an ideal way to store them (probably with desiccant or some sort of chemical but not a cold supply chain).

Regarding the minimum threshold for sensitivity (for screening tools), it is 80%. We will try to aim for this, but sometimes 75% is acceptable too (for some covid-19 rapid tests it is around this).

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