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    Review of 'Using Interventional Pharmacoeconomic Clinical Trials and Outcomes-Based Contracts to Repurpose Generic Drugs with Cost-Savings'

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    Using Interventional Pharmacoeconomic Clinical Trials and Outcomes-Based Contracts to Repurpose Generic Drugs with Cost-SavingsCrossref
    The article presents a possibility for payers to engage in clinical trials for cost savings.
    Average rating:
        Rated 2.5 of 5.
    Level of importance:
        Rated 3 of 5.
    Level of validity:
        Rated 3 of 5.
    Level of completeness:
        Rated 2 of 5.
    Level of comprehensibility:
        Rated 2 of 5.
    Competing interests:
    I represent not for profit, solidarity based health insurers and therefore have reviewed the abstract from this angle.

    Reviewed article

    • Record: found
    • Abstract: found
    • Article: found
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    Using Interventional Pharmacoeconomic Clinical Trials and Outcomes-Based Contracts to Repurpose Generic Drugs with Cost-Savings

    One of the greatest barriers to the repurposing of generic drugs is the lack of a financial model to recover the costs of clinical trials. Academics have acknowledged this “problem of new uses” for many years.[1] And so despite their great medical and cost-saving potential, repurposed generic drugs are referred to as “financial orphans” [2], “highly non-excludable therapies” [3], or “unmonopolisable therapies” [4], that are extremely unlikely to receive the funding needed for regulatory approval. One proposed solution to the problem of new uses is to restrict off-label use and allow reimbursement of the repurposed generic at a higher price for the new indication.[5] Another option is the increased public funding of clinical trials. However, this has been politically, legally and practically difficult to achieve. A financially-innovative solution to the problem of new uses is to leverage the immediate and future cost savings of health insurers. In particular, the novel discipline of interventional pharmacoeconomics (IVPE) allows for self-funding clinical trials by comparing a low-cost intervention (such as a repurposed generic) to expensive standard of care.[6] The cost savings from patients taking the low-cost intervention in one arm can exceed the cost of the trial itself, even if it fails, which means there is no financial risk. However, an IVPE trial requires the substitution of the low-cost intervention for expensive standard of care, and may not be appropriate for all repurposing opportunities, especially where no expensive comparator intervention is available. For this latter situation, it is possible to use outcomes-based incentives similar to prizes called Pay-For-Success (PFS) contracts, Advance Market Commitments (AMC) [7], or Social Impact Bonds (SIBs).[8] Such “prize-like” incentives have been used to accelerate the development of Covid vaccines [9] and antibiotics [10], but not yet for repurposing generic drugs. The IVPE concept has been called a ‘revolving research fund’ in Europe, where the cost-savings of clinical trials are used to fund additional research.[11] Similar cost-saving trials are also being funded by a consortium of health insurers in the Netherlands on a case-by-case basis.[12] It is hereby proposed that establishment of an IVPE + AMC fund by private or public health insurers can develop repurposed generic drugs, which can address the “financial toxicity” of new patented drugs while improving patient outcomes.[13] There are many known IVPE opportunities, for example, comparing repurposed generic IV ketamine to patented esketamine for treatment resistant depression [14] or off-label bevacizumab (Avastin) to ranibizumab (Lucentis) for macular degeneration.[15] There is an opportunity to discover and medically de-risk additional IVPE repurposing candidates for self-funding trials by conducting retrospective studies and meta-analyses of medical records and clinical data.
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      Review information

      10.14293/S2199-1006.1.SOR-LAW.ADS2EC.v1.RDSPIV
      This work has been published open access under Creative Commons Attribution License CC BY 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com.

      Medicine,Intellectual property law,Commercial law & legal protection,Biotechnology,Complementary & Alternative medicine,Public health,Life sciences
      Financial Innovation,Self-Sustaining Fund,Outcomes-Based Contracts,Social Impact Bonds,Generic Drug Repurposing,Interventional Pharmacoeconomics,Advance Market Commitments,Financial Toxicity ,Pay-For-Success Contracts,Generic Drug Repositioning

      Review text

      The article describes a business model that would presents to public health insurance funds the possibility to make savings on costs of drugs when engaging in clinical trials for repurposing of drugs. The abstract that describes models  already applied in the US as well as in the Netherlands, does not further investigate the important legal hurdles as well as ethical concerns for solidarity based, not for profit health insurers to engage in such clinical trials let alone to recrute their insured to participate in them.

      The abstract does refer to legal requirements and the public tasks of health insurers. The European health insurance funds are non commercial, financed either by contributions from employers/employees or from taxes or a mixture of both. Drug reimbursement is usually being organised by or in cooperation with state agencies. The case mentioned from the Netherlands represents not only health insurers, but is a cooperation of teaching hospitals, treating physicians, (hospital) pharmacists and government. They are supported in this process by a Scientific Advisory Board, Intervention Board and Financial Board. (see: https://treatmeds.nl/wat-we-doen/). Such a partnership including the cooperation with state agencies and a sound supervision on both the financial, as well as the ethical, pharmaceutical and impact on patients would be necessary in any other European country, if the legal framework regulating health insurance funds in the different European countries. 

      The abstract describes that there are no financial risks, however, the upfront costs would have to be paid by the health insurers without a security of the success of the clinical trial. The financial risk can only be judged after a successful trial.

      The abstract should include reference to the need of a sound legal analysis to detect all legal, political as well as ethical hurdles as well as safeguards for the insured that such a model could represent in Europe. 

      Comments

      Dear Sybille,

      Thank you for your review and suggestions. 

      I agree that for IVPE trials to be ethical, ideally the low-cost intervention (e.g. repurposed generic) would not just address financial toxicity, but also have a chance of superiority to the expensive comparator (e.g. generic IV ketamine is 100% bioavailable and likely more effective than patented intranasal esketamine which is 50% bioavailable, according to a systematic review - see https://pubmed.ncbi.nlm.nih.gov/33022440/). It is possible to use retrospective studies of RWD to predict which repurposed generics are most likely to be superior. 

      Regarding the lack of financial risk, the cost-savings of the insurer occur whether or not the trial is successful. In particular, these cost-savings are the result of patients being randomised to receive a low-cost intervention during the IVPE trial rather than the expensive intervention i.e. patients taking generic IV ketamine at <$1k p/a rather than esketamine at >$30k p/a represents a >$29k p/a cost saving for the health insurer, irrespective of whether the primary outcome of the trial is met. This means that insurer funds are not "at risk" : the main risk is the medical risk of clinical trial failure, but this is a risk that can be managed by ensuring ethics approval and informed consent. 

      Thanks again for your comments and will ensure these are taken on board. 

      Regards,

      Savva Kerdemelidis 

       

      2024-05-07 06:18 UTC
      +1

      Thanks, Savva.

      2024-05-07 07:40 UTC

      I thank you for your time and very much agree with your points or concerns and will address them in an editorial recommendation. 

      2024-05-01 17:22 UTC
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