VDP-91: CrowdFundedCures.org & VitaDAO Partnership - Interventional Pharmacoeconomic + Pay-For-Success Feasibility Study to Fund Off-Patent Interventions to Improve Healthy Lifespan

Summary

  • In January 2022, Crowd Funded Cures (CFC) was allocated $40,000 under VDP-17 partnership proposal to commission a feasibility study by Guidehouse or another leading consulting firm to support establishment of Pay-For-Success (PFS) contracts as a new model of research funding for unmonopolizable therapies (including repurposing of generic drugs and nutraceuticals), which could also improve healthy lifespan. The goal of the feasibility study is to obtain payer backing and create a business model for funding off-patent longevity-related therapies that VitaDAO could support in the future, including through the use of Open Source IP-NFTs.
  • Due to the amount allocated being insufficient for large consulting firms, CFC wishes to use this funding to conduct the feasibility study internally (with support from contractors) and to help obtain backing of a pilot interventional pharmacoeconomic randomised controlled trial (IVPE RCT) from a payer, a form of de-risked PFS contract using payer cost saving to fund low-cost / off-patent therapies, before the end of 2023.

Key Deliverables

  • Main deliverable would be conducting a feasibility study for a pilot interventional pharmacoeconomic randomised controlled trial (IVPE RCT), which has a negative cost for payers, which creates a scalable business model for funding low-cost unmonopolizable therapies using cost savings from comparing them with expensive patented drugs. The goal is to obtain backing for a pilot IVPE RCT from a payer (e.g. health insurer, government, or philanthropy). This will help drive funding into the DeSci ecosystem generally, while specifically creating a business model for VitaDAO members to invest into unmonopolizable longevity-related therapies using Open Source IP-NFTs.
  • The feasibility study will include funding of literature reviews, clinical studies, outreach to obtain market validation from payers and other stakeholders which are concerned with cost-containment (e.g. self-insured employers, government) regarding the IVPE RCT model. It will also include pharmacoeconomic modeling to show payer / social cost savings under the IVPE RCT / PFS model.
  • Goal is to obtain the backing of a pilot IVPE RCT / PFS contract with a payer and/or external funder.

Background

The first longevity-related interventions might be already among us and some of the most promising interventions include generic drugs such as rapamycin, metformin, NMN, resveratrol, vitamin D, caloric restriction, bisphosphonates, ketamine and other psychedelics for mental health, and other therapies which are off-patent, accessible and affordable. Dietary interventions also have longevity and healthspan implications such as keto which can treat a multitude of serious diseases, including Glioblastoma, Parkinson’s and Alzheimer’s Disease, and the use of micronutrients to reduce the risk of pre-term births which increases adult risk of early mortality. These “unmonopolizable therapies” have well-established safety profiles, are generally cheap to produce and easy to acquire, ultimately resulting in faster and more cost-effective clinical trials, with a potentially massive global impact. However due to being off-patent and unmonopolizable because they are available at low cost from multiple sources, there are no private incentives to fund large-scale clinical trials. The IVPE RCT / PFS contract model can address this market failure by using these low-cost therapies to exploit the arbitrage opportunity provided by analysing their equivalence to expensive patented drugs, in order to fund the clinical trials from cost savings.

We therefore request to allocate $40k from VDP-17 to conduct a feasibility study to support a pilot IVPE RCT / PFS contract to establish the efficacy of a low cost unmonopolizable therapy to improve healthspan and/or lifespan (e.g. ketogenic diet to treat cancer), mental health (e.g. repurposing generic ketamine), or another healthy longevity-related indication. The IVPE model can provide the clinical data needed for FDA-approval of a low cost generic paid from immediate cost savings. This can create billions of dollars in future cost savings for payors under a Pay-For-Success contract or Advance Market Commitment, as well as improving global health, as anticipated in the go-to-market strategy of CFC’s GR15 Gitcoin Grant.

The VitaDAO community’s Return on Investment for a feasibility study to support an IVPE RCT pilot will be that it creates an business model for VitaDAO to invest in an Open Source IP-NFTs and generic drug repurposing such as a method of use patent for covering a treatment protocol or dosing regime to improve healthy longevity. This would be a world first - showcasing and cementing VitaDAO’s role in truly democratizing R&D.

In the following sections, we break down the Team involved, the Implementation Timeline and Milestones, as well as our Budget Ask

Core Team

Feasibility Study Implementation: Timelines & Milestones

  • February-March 2023

  • Outreach campaign to payers to obtain market validation for leveraging the IVPE RCT model to repurpose a low cost generic drug or unmonopolizable therapy (e.g. ketamine vs esketamine for treatment resistant depression, ketogenic diet to treat cancer) to improve healthspan, including development of collateral for the feasibility study and engaging with payers.

  • Conducting literature review and clinical study for longevity-related intervention that can be used in an IVPE RCT (optimal dosing regime for ketamine for TRD or impact of ketogenic diet on glioblastoma).

  • Conducting pharmacoeconomic analysis of cost impact and financial model for IVPE RCT.

  • Finalization of feasibility study to support negotiation of pilot IVPE / Pay-For-Success contract with payor for unmonopolizable therapy.

  • April - July 2023.

    • MoU signed with contract research organization (CRO) partner to support IVPE RCT. Subject to securing external funding, the goal will be to integrate with our blockchain-secured data capture partners, e.g. Rymedi, and ensure integration with Molecule’s IP-NFTs platform.

    • Leverage Feasibility Study to obtain MoU / LoI from a payer to support pilot IVPE RCT for repurposed generic drug, nutraceutical or other unmonopolizable therapy.

  • August - December 2023

    • IVPE RCT pilot initiated (e.g. Phase 2 RCT of 150 patients, comparing ketamine to esketamine).
    • Minting of OS IP-NFT to support development of optimal treatment protocol for repurposed generic drug, nutraceutical or other unmonopolizable therapy, which can be commercialised under IVPE model.

Budget Ask:

  • $40k for research study and feasibility study (allocated, need confirmation to repurpose for reasons listed above).

Accountability Metrics

By the end of the months of April, July, and December 2023, CFC will provide updates on the status of budget spent from VDP-17, including deliverables.

As per Tim Peterson’s post below, can folks that voted no please provide reasons. The community has already voted to allocate funds for a PFS feasibility study and the purpose of this vote is to confirm scope. A no vote means we would need to post another proposal for scope and would be in the same position until this can be clarified.

  • Agree
  • Revisions Requested (Details in Comments)
  • Disagree

0 voters

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What can the money be used for? If VitaDAO disagree the funds will use for longevity directly or growing community?

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To clarify, the community voted to allocate the funds under the VDP-17 partnership proposal for the purpose of a feasibility study, and this vote is to ratify what kind of feasibility study it would be, rather than voting for it to be used in some other way. There has already been significant work performed by CFC this year trying to engage with various external management consulting firms (e.g. Guidehouse, with internal pitch competition, BCG, PwC, Ernst & Young, Grant Thornton, Oxford University etc). We would like to clarify the scope of the feasibility study and push forward with a IVPE pilot.

Absent of some evidence of misallocation or inability to execute on the feasibility study, in light of efforts already made by unpaid volunteers within Crowd Funded Cures (a NZ charity), it I think it would be not be commercially reasonable if the community votes that the funds should be used for some other entirely different purpose. If someone in the community would like that, they should file a separate proposal for funding. The purpose of this vote should be to confirm the scope of the feasibility study.

Thanks for the write up Savva. If I understand correctly, this proposal isn’t asking for more funds from VitaDAO but it’s only to specify the plans regarding the feasibility study for which funds were already allocated in VDP-17. Am I understanding this right?

If this is the case, wouldn’t the VDP nomenclature be unnecessary given that the project wouldn’t need to go to phase 3? Cc. @consigli3re

I agree with @0xdad, since you’re making a poll, it would be important to know what are the implications of voting no.

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Thanks @Savva always supportive of the PFS concept and admire the passion for it. It seems to me like this an authorization for the money to be spent by CFC rather than Guidehouse? If so, probably needs another on-chain vote.

I would feel better if the $40K would go towards planning a specific already identified project. It’s not dissimilar to what we demand of our research projects that there is already a PoC in hand.

Bottom line is PFS needs a payer. Do you have a soft commit from any? That to me would influence voters.

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Thanks for the write up Savva. If I understand correctly, this proposal isn’t asking for more funds from VitaDAO but it’s only to specify the plans regarding the feasibility study for which funds were already allocated in VDP-17 . Am I understanding this right?

No worries. Yes, it’s approval that we can conduct the study + clinical research and payer outreach to obtain backing by a payer / philanthropy.

If this is the case, wouldn’t the VDP nomenclature be unnecessary given that the project wouldn’t need to go to phase 3? Cc. @consigli3re

It’s a relatively minor change from the original scope - the issue was that the amount was not enough for a large management consulting firm (we thought we might be able to get a low-bono price as one of our advisors was an internal champion at Guidehouse). However, ultimately, we could not get any traction with them and other firms we engaged with. We received quotes of around 10x the budget. So plan B is to conduct the study internally and using contractors.

I agree with @0xdad, since you’re making a poll, it would be important to know what are the implications of voting no.

Voting no would mean that we would need to go with the original plan to get a large management consulting firm to do a feasibility study with low-bono / in kind support or we submit another proposal (although am not sure what this would be).

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Thanks @Savva always supportive of the PFS concept and admire the passion for it. It seems to me like this an authorization for the money to be spent by CFC rather than Guidehouse? If so, probably needs another on-chain vote.

Thanks @Tim - Yes, that’s correct and we felt it was appropriate to get VitaDAO community support to proceed with doing the feasibility study internally and getting feedback from payers. We have been working on engaging with payers now for over 12 months, including CMS and VA in the US, NICE in the UK, and Pharmac in NZ, using our own funds as a charity.

I would feel better if the $40K would go towards planning a specific already identified project. It’s not dissimilar to what we demand of our research projects that there is already a PoC in hand.

We would not want to pre-empt a specific unmonopolisable therapy use case as this is ultimately up to the payer. However, we are leaning towards ketamine vs esketamine due to it being a great example of a low cost intervention that could be more effective than the patented intervention, and also has implications for mental health / longevity. We are also interested in ketogenic diet to treat glioblastoma, which currently has one of the worst prognoses for cancer. As noted in the proposal and you are aware, we are also open to specific longevity interventions (e.g. rapamycin, zoledronate), although more difficult to get payer support due to longevity not being recognised by FDA as a disease.

Bottom line is PFS needs a payer. Do you have a soft commit from any? That to me would influence

We have had several calls now with VA regarding a ketamine vs esketamine IVPE RCT who have committed to providing free emergency care for suicidal veterans, which means they should be interested in ways to lower their costs. There are a lot of political barriers, but we are working with key stakeholders (e.g. Ketamine Task Force) and just had a call with Partners in Health who have been supportive to explore a pilot. We are also in the process of applying to the EHIR Academy which will allow us to pitch and get feedback from large self-insured employers (who are incentivised to lower costs as this improves their profitability). The IVPE model makes financial sense - I believe it a matter of time before we get a pilot. The sooner it happens, the better for DeSci and also the more patients will benefit.

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seems promising. I think if that can be firmed up that would be a big help. i sadly still worry about whether that trial would be mission aligned enough. We had this issue with several other projects recently, e.g., zbiotics.

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@Tim - regarding the connection to longevity, Garri Zmudze from Longevity Science Foundation recently spoke about the role of mental health for healthy longevity at Wonderland Psychedelics Conference which I also attended and spoke about VitaDAO and IP-NFTs creating a business model for generic drug repurposing. Crypto, longevity and psychedelics seem to have quite a lot of cultural alignment - although not all longevity researchers will agree :wink:

However, per Garri’s statement, researchers have also shown ketamine can help regrow neural connections, a potentially groundbreaking finding in developing future treatments for aging-related neurodegenerative diseases.

Regarding getting payer support first before funding the feasibility study, there is a chicken and egg problem i.e. the point of the feasibility study is to help convince payers and/or philanthropic orgs to back an IVPE RCT pilot.

But I think ultimately, if we can validate the IVPE + PFS model, this will help DeSci and longevity generally. As you might be aware, we are working on a pilot Generic Drug Repurposing LongevityPrize.com with Hypercerts.xyz. Challengeworks.org have also just greenlit helping us design and get backing for a Treatment-Resistant Depression Prize, which is exciting because they are other than XPrize, the leading organisations for incentive prizes (e.g. having established the £10m Longitude Prize on antibiotic resistance).

To those who downvoted please explain. The $40k would be in limbo if the vote doesn’t pass, and people generally agree on the promise on PFS so let’s talk about what the problems are here so we can move forward.

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If I understand this correctly, you found a way to conduct the study in a more relevant way for less money than going with some big consulting firm and would like to pursue it?

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If I understand this correctly, you found a way to conduct the study in a more relevant way for less money than going with some big consulting firm and would like to pursue it?

Yes, basically, the goal of using a management consulting firm is they would do the work of engaging with payers to get feedback and help “sell” the idea of using IVPE + PFS contractual innovation to pay for clinical trials for low-cost therapies out of cost savings. This way we use the funds ourselves to conduct the feasibility study in a more targeted and scaled down way (e.g. get access to medical records and conduct a retroactive case study to support an RCT, reach out to payers for feedback via EHIR Academy, research payer requirements including regulatory requirements / pre-IND FDA meetings etc).

Technically this project falls under “Longevity Dealflow” so it will need to go to phase 3. It is also a unique situation because VDP-17 passed, but not on-chain because we weren’t using Snapshot then.

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Thanks for the answer! Although the proposal did pass an on-chain vote with the staking system we used before snapshot.

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Used ChatGPT to help summarise the proposal to help ease the community’s understanding of it:

This governance proposal is seeking $40,000 from VitaDAO to conduct a feasibility study for a Pay-For-Success (PFS) contract model as a new way to fund unmonopolizable therapies that improve healthy lifespan, using Open Source IP-NFTs.

The goal of the feasibility study is to obtain payer support and create a business model for funding off-patent longevity-related therapies, including the repurposing of generic drugs and nutraceuticals. The main deliverable is to conduct a feasibility study for a pilot interventional pharmacoeconomic randomized controlled trial (IVPE RCT), which is a de-risked PFS contract using payer cost savings to fund low-cost/off-patent therapies. The study will include funding for literature reviews, clinical studies, outreach to obtain market validation, and pharmacoeconomic modeling to show payer/social cost savings.

The goal is to obtain the backing of a pilot IVPE RCT/PFS contract with a payer or external funder and create a business model for VitaDAO members to invest in unmonopolizable longevity-related therapies. The implementation timeline is from February to December 2023.

LFG ChatGPT!!

The only part to fix is that technically, implementation would from February to December 2023.

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Maybe I’m far off, but I would guess some of the negative downvotes are from individuals who voted “yes” to VDP-17 based on the VDP-17 conversation: “…perhaps better to clarify that it would be Guidehouse or some other leading consulting firm with a ‘name’ performing the feasibility study, not CFC…”

Since working with leading consulting firms is not an option, curious if the amount of $$ allocated can be changed alongside the other ammendments to VDP-17?

2 Likes

Thanks for your feedback and would be good if others that downvoted could clarify their concerns or propose amendments so we are not speculating.

To clarify, the purpose of this feasibility study has not changed - the idea is to get payer / philanthropic backing for a pay-for-success contract (although have also introduced the pharmacoeconomic idea of IVPE RCTs). The scope has expanded to include “funding for literature reviews, clinical studies, outreach to obtain market validation”. It is expected that CFC will be using an external CMO and CRO for literature reviews and clinical studies, and a pharmacoeconomist expert for modelling aspect. We have contractors lined up and anticipate the amounts needed will be within the original budget (particularly if we are including outreach). We could re-scope a feasibility study for less, but this would not recognise the significant efforts engaging with various external management consulting firms (e.g. Guidehouse, with internal pitch competition, BCG, PwC, Ernst & Young, Grant Thornton, Oxford University etc), as well as payer outreach over the last 12 months, including CMS and VA in the US, NICE in the UK, and Pharmac in NZ, using our own funds as a charity.

The other option would be to go back and ask for more funding under VDP-17 to get an external consulting firm, but in this proposal, we have found a way to make the budget allocated help achieve the original goal. If the amount budgeted or our progress so far and/or competence to conduct the feasibility study is an issue, I would be happy to discuss and try to address these concerns.

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am a bit confused what you are trying to achieve here? can you clarify what success looks like here in concise terms, and how this feasibility study will help

which payer / foundation wants this feasibility study by cfc itself to back it? isnt it more important to scope out the details of the RCT for a retroactive longevity prize, and maybe use parts of the funds to incentivize the prize vs wasting it

Hi Vincent - the community already agreed to approve a feasibility study for VDP-17 . If you want to propose using VitaDAO funds for the Longevity Prize, this is great and you should consider a separate proposal. But I think it is not wasting money on a feasibility study showing the actual cost savings to backers so we can convince folks to support a much larger prize e.g. spending $40k to raise $1M+ or back an IVPE study that can create billions of dollars in cost savings (e.g. proving that ketamine at $2 a dose is equivalent or superior to esketamine at $850 a dose).

It’s very usual for large (institutional) funders to insist on such feasibility studies, especially if we are talking about a relatively novel and scalable mechanism of funding open source medicine. Doing a 180 now when CFC has been working on getting all the relevant stakeholders together and lined up contractors to conduct a feasibility study is not commercially appropriate and would mean other partners are much less likely to work with VitaDAO (i.e. if they are likely to flip at the last minute).

We can also use part of the funds to conduct a literature review and retrospective ketamine vs esketamine case study looking at existing data to predict the IVPE RCT outcome - this is funding actual clinical research and would support the feasibility study and getting backing for the IVPE RCT.

1 Like