科学政策

利用药物经济学和提高市场承诺，以减少医疗保健支出

17.04.23 | 21分钟阅读 | Text by Savva Kerdemelidis + Nicholas C. Fiorenza

概括

By establishing a self-sustaining fund to incentivize pharmaceutical companies to develop new and improved treatment protocols using low-cost, off-patent andunmonopolizable疗法, billions of dollars in cost savings could be realized by US government payers and health insurers in a financially “de-risked” manner while improving quality of care —truly a win/win opportunity.

目前，除非可以使用专利执行垄断价格，否则制药公司不会开发医疗疗法。结果，成千上万的低成本疗法，例如重新使用的仿制药，营养素，植物药物，医疗饮食，生活方式干预和剂量降低方案，缺乏私人经济动机的发展动机。临床上验证这些负担得起的治疗的安全性和功效，将帮助许多患者，同时节省数十亿美元。同时，最大的制药公司正在赚取数万亿美元的收入对于新的专利药物通常会给患者提供有限或没有附加的好处，同时给患者和纳税人造成巨大的经济负担。

我们可以使用新的付款模式（例如介入的药物经济学（IVPE）相关的随机对照试验结果cost savings for healthcare systems, even if RCTs fail, by comparing the efficacy of low-cost therapies to expensive patented drugs. Further, outcomes-based financing mechanisms known as Advance Market Commitments orPay-For-Success (PFS) contracts, can incentivize the successful development of new low-cost therapies, entirely funded by payer costsavings from reduced reliance on monopoly-priced drugs.

我们建议，国家卫生研究院（NIH），国家前进的转化科学中心（NCAT）与付款人（例如Medicare＆Medicaid Services中心（CMS））和美国退伍军人事务部（VA）一起工作，以转让A他们来自IVPE RCT和AMC的成本的一部分，以创建自我维持的“奖品”基金，以开发低成本疗法2010 America COMPETES Reauthorization Act。

借助这些新的支付模式，可以为赞助商创建可扩展且可持续的业务，以开发负担得起的疗法，同时改善患者的结果并节省大量成本。例如，每10,000名根据IVPE RCT + AMC合同进行治疗的患者，将氯胺酮与专利的Esketamine进行比较，这可能是更加有效for treatment-resistant depression, would save payers at least $1.8 billion over 10 years until the expiry of the esketamine patent, part of which can be paid back into the fund. The IVPE + AMC contract can also provide revenues of at least $250 million to a sponsor of the clinical trials for development, FDA-approval, and post-approval (Phase IV) pharmacovigilance studies for ketamine (see Appendix).

挑战和机会

迫切需要更有效的治疗方法，这些治疗易于获得和负担得起。对于许多美国人来说，治疗非常稀缺或昂贵，with an estimated 42% of newly-diagnosed cancer patients losing all of their assets within 2 years。作为national health expenditures continue to rise和drug R&D productivity continues to stagnate，通过实施改进的激励设计系统来支持更好的健康和经济成果，重新思考私人公共的一致性至关重要。

仿制药具有解决医疗保健成本和提高研发生产率的巨大潜力：低成本仿制药节省了美国医疗保健系统过去十年中的1.67万亿美元。Thousands of FDA-approved generic drugs-也50,000+ nutraceuticals, plant medicines, diets, lifestyle interventions, and dose de-escalation regimens (collectively known as unmonopolizable therapies)—could be studied to treat diseases significantly更便宜，更快而不是开发新的专利药物。它花费了估计的$1 billion-plus and takes more than 10–15 years得到一个新的ly patented drug to market, whereas it is significantly cheaper and faster to find new uses for existing drugs and other unmonopolizable therapies that have known safety profiles and mechanisms of action from their use over many years.

但是，通常是在经济上不可行为了使制药公司为评估不可过销的疗法的临床试验支付费用，可以在相对较低的成本下开处方标签。通用毒品公司受到保护“瘦标签”立法，这使得为仿制药的新用途执行专利变得困难或不可能。尽管制药公司可以重新制定通用药物并重新质视它们以收取垄断价格，但只有在重新制定比原始仿制药更好的情况下，这可能在商业上可行。在重新制定涉及仿制药的组合的情况下，复合药房可以使用原始的低成本仿制药开出药物。

由于这种市场失败，对于这种低成本疗法，缺乏用于大型且强大的临床试验的资金。原始配方的机会获得了仿制药，获得了FDA批准的新用途接近零when it goes generic. The same problem applies to funding large clinical trials for nutraceuticals, medical diets, lifestyle interventions, and novel dosing regimens, where it is almost impossible to stop doctors and patients accessing these therapies. Patients who desperately need more treatment options are unable to realize the benefits that existing off-patent, unmonopolizable, or low-cost therapies might offer, and由于专利激励措施的差距，可能会对公众造成重大损害。

增加临床试验的直接赠款资金也可以产生次优的结果。在2020年Covid-19的高峰期间，pepcid AC（Famotidine）Covid-19研究raised red flags weeks after a $21 million grant was awarded to study its effects as a potential therapy. Concerns over study integrity, outcome measures, and even administrative protocols were all brought to light. Ironically, such grant funding can lead to even more risk and wasted taxpayer funds, such as$150 million of federal funding on the dietary supplement curcumin studied in more than 120 clinical trials, with no tangible evidence that it is an effective treatment for any medical condition. Further, conservative estimates of publicly funded clinical trials for repurposingphospholipidosis-inducing CADs to treat COVID-19，包括羟氯喹，可能超过60亿美元。除了大而务实的恢复和一起trials initiated by the United Kingdom, which discovered that dexamethasone significantly reduced mortality in COVID patients on respiratory support, funding smaller, low-powered clinical trials did not lead to the development of significantly beneficial COVID therapies for patients. A risk-transferring market mechanism to fund large clinical trials would have been more efficient—or at least not have exposed taxpayers to the risk of failed clinical trials. IVPE RCTs are paid from cost savings, and AMC contracts only pay out when pre-specified requirements are met, so taxpayers and health insurers do not pay for any failures.

To quickly and affordably improve the lives of millions of patients, we propose that Congress should appropriate, and the Biden-Harris Administration should direct, the NIH, CMS, and VA with the support of the NCATSRepurposing Drugs计划，建立利用IVPE RCT和AMC的自我维持基金，用于为节省成本节省成本的负担得起的临床试验（“ IVPE + AMC基金”），并使用其联邦授权在2010年美国建立市场奖励或“奖品”重新授权法。私人保健保险公司的分散性，并有限的激励措施减少4万亿美元的美国医疗保健行业的成本，以证明向其美国客户收取的高保费是合理的，而提供商通过收取更高的费用来赚取更多的收入。但是，从支付费用和PFS合同和基于价值的定价（VBP）方面有些动作。在ERISAlegislation and the2021年合并拨款法，这对自保雇主施加了信托义务，以减少医疗保健支出。由纳税人资助的付款人，例如CMS，VA，美国陆军和大型自给自足的雇主可以使用IVPE RCT和AMC来激励低成本疗法的发展作为受托和财务风险管理机制。他们的净成本节省将远远超过管理IVPE + AMC基金的成本。

特别是，IVPE RCT比较了低成本的仿制药与通常由付款人资助的昂贵的专利药物进行比较。例如，最近有一个提议建立一个自我维持的IVPE基金矩阵行列式值ine the optimal minimum dose for expensive oncology drugs to save costs while reducing side-effects. The price difference between the low-cost and expensive intervention can far exceed the cost of running the RCT, which means it pays for itself in cost savings, even if the RCT fails. And if the RCT shows the low-cost treatment provides at least the same standard of care as the patented drug, this can save payers billions of dollars until the patent expires. If some of these cost savings are transferred back into an IVPE + AMC Fund, this will create a scalable business model for developing new low-cost therapies.

The self-sustaining nature of the IVPE + AMC Fund could be demonstrated, for example, by providing market rewards up to $100 million (which can be pooled between federal agencies) to reimburse a sponsor recruiting patients into IVPE trials comparing low-cost and expensive therapies. The reimbursement amount should ideally be less than the cost of the expensive therapy and the resulting guaranteed payer cost savings from the low-cost therapy substituting the expensive therapy could be paid back to increase the size of the fund. The IVPE clinical trial would require ethics approval and provide valuable data to “de-risk” whether the low-cost therapy works, without requiring additional taxpayer support. AMCs then would act as a “pull” mechanism to reward sponsors of large Phase III Randomized Controlled Trials (RCTs) that result in FDA approval with higher reimbursement price for an otherwise low-cost therapy that would substitute the expensive therapy. For example, a sponsor can partner with a generic drug manufacturer to guarantee supply of a repurposed generic in return for sharing revenue under an AMC. The sponsor can then submit bioequivalence and efficacy RCT data under the 505(b)(2) pathway to obtain a new “label” for the new use, which also provides a 3-year period of data exclusivity. Alternatively, a sponsor can leverage the revenue from the AMC to develop a nominal reformulation (e.g. new mechanism of administration or dose) to disincentivize generic substitution and obtain a 5-year period of data exclusivity under the 505(b)(1) New Drug Application pathway. The sponsor can earn additional revenue from the sale of the repurposed generic or RCT data to other healthcare systems, with the payers backing the IVPE + AMC Fund receiving a lower price or royalties. Payer cost savings from substituting an expensive therapy with the lower-cost therapy can be paid back into the IVPE + AMC Fund to ensure long-term sustainability.

AMC contracts are already implemented in various other contexts to address market failures. For example, so-calledSocial Impact Bonds（SIBS）是一种AMC合同，已被用来帮助预防无家可归和囚犯累犯的项目，并过度$700 million in SIBsraised to date.Operation Warp Speed使用AMC通过FDA批准和实验室到患者的阶段来激励疫苗开发。与IVPE RCT类似的方法也已被用来证明低剂量的贝伐单抗（avastin）可以治疗与年龄相关的黄斑变性，而不是获得专利的ranibizumab（lucentis），据估计该变性为save Medicare Part B $18 billion over 10 years。

因此，IVPE + AMC基金可以通过开发新的低成本疗法来减少对昂贵疗法的依赖，从而可以从付款人那里获得数十亿美元的收入。它还可以通过鼓励制药公司（1）来解决专利系统下的未对准激励措施“脱离链接”利润（2）确保获得专利的药物有价值而不是追求“常绿”strategies such as patenting slight modifications of generic drugs to extend the period of monopoly pricing, and (3) pursue the most effective therapiesrather than the most patentable。如果没有昂贵的比较器治疗或其他情况，IVPE方法论可以比较常规的护理，AMC也可以用于激励低成本疗法的开发以满足未满足的医疗需求。

A Market Failure Caused by a Tragedy of the Commons

成千上万的潜在安全有效的非成本和低成本疗法是currently ignored due to misaligned incentives under the patent system。这场悲剧的核心是，验证治疗方案的安全性和有效性的临床试验数据对医疗保健付款人和患者而言是有价值的，而不是该药物的活性成分是否是新的。从本质上，涉及非专利和不可单位疗法的新用途的治疗方案是非矛盾和“高度不可判断”的公共物品。The co-author Savva Kerdemelidis’s2014年硕士论文结论是，由于专利制度为制药行业提供了开发这种“不可分割的疗法”的激励措施不足，因此需要替代的“奖品样”激励措施。这使付款人可以将临床试验数据定价验证，以验证这些新的，更负担得起的治疗方案的功效。

通过IVPE RCT和AMCS缩放低成本疗法的发展

IVPE RCTs and AMCs (see definition in FAQ section) recognize that the value of a therapeutic intervention is not the cost of an active ingredient but the clinical trial data showing it is safe and effective in a particular patient population. To accelerate the development of unmonopolizable therapies through the clinical and regulatory pipeline, we propose that payers—specifically government agencies such as CMS and VA as well as health insurers responsible for pharmaceutical reimbursement (ideally a consortium of payers)—support IVPE RCT pilots to de-risk early-stage clinical research and the use of AMC contracts through the IVPE + AMC Fund. The AMC will incentivize a sponsor fund the Phase III studies need to obtain FDA approval and conduct post-approval (Phase IV) pharmacovigilance studies. It will be self-sustaining if a percentage of savings from the availability of low-cost therapies is paid back into the IVPE + AMC Fund.

可以根据IVPE + AMC基金从IVPE + AMC基金提取的AMC下的总成果支付总量，可以参考产生的临床影响水平或质量调整后的终身寿命（QALYS），降低，降低，残疾调整的终身年度（DALYS）甚至从允许低成本疗法代替昂贵的疗法或降低住院费用而节省的成本也可以节省。例如，可以预先计算出批准的不可单位疗法的QALY数量United Kingdom National Health System’s Subscription-Style-Payment（SSP）激励新抗生素开发的模型。Under an SSP, a fixed amount is paid annually according to the total QALY value of the new therapy, as assessed by an elected, independent Medical Evaluation Committee.同样，路易斯安那州的CMS实施了“Netflix-subscription” model通过同意预先同意固定的年度付款来保证供应低成本仿制药以治疗丙型肝炎。绩效付费和基于价值付款（VBP）合同are similar to AMC contracts and often negotiated with payers to provide more cost-effective delivery of healthcare services, where rewards are based on certain conditions being met. Accordingly, using AMC contracts to reward successful RCTs is not a novel mechanism that will require a significant administrative burden for federal agencies to implement. It may only require changing a few sentences in an existing VBP contract to refer to a repurposed generic drug or low-cost therapy.

以下示例描述了IVPE + AMC模型的工作方式：

1. 付款人（例如CMS）同意IVPE RCT与赞助商进行比较，将重新塑造的通用药物或低成本治疗与专利药物（或昂贵的护理标准）的等效性或优势进行比较。付款人可以以较高的价格或每个患者价格来偿还低成本治疗，足以支付IVPE RCT的成本。如果较高的报销价格低于专利药物或昂贵的治疗，即使RCT失败，它也可以保证付款人节省成本。如果IVPE RCT成功，则付款人同意AMC的价值，例如，至少1亿美元购买了最少数量的重新申请通用药物，或者以较高的价格向赞助商偿还，但要获得获得FDA批准和FDA批准的赞助商负责批准后的药物警戒。值得注意的是，由于IVPE RCT是由于低成本疗法和获得专利药物之间的价格差异而从立即节省的基金中资助的，因此双方在财务上均处于危险中。（有关IVPE + AMC模型的示例，请参见附录1，使用通用氯胺酮与获得专利的Esketamine的示例来治疗抑郁症。）
2. 这家赞助制药公司根据IVPE RCT和1亿美元的AMC的协议，筹集了5000万美元，以进行FDA批准所需的临床试验，但要获得FDA批准和批准后（IV阶段）Pharmacovigialance的批准（IV阶段）。研究表明持续的安全性和功效。
3. If the IVPE RCT is successful and the generic drug or low-cost therapy is shown to be equivalent to or better than the expensive patented drug, the AMC is triggered: sponsors are guaranteed minimum sales of $100M and also have a “branded” generic or low-cost therapy with new label and data exclusivity for three years by filing an缩写新药申请(ANDA) with the FDA. A新药应用排他性(NDA)五年的数据是可能的ble if the generic or low-cost therapy contains a new active ingredient. They can also obtain a method of use patent on the optimal treatment protocol, which provides some commercial benefit and leverage to negotiate AMCs with other payers. A payer’s cost savings from updating their reimbursement guidelines to substitute a low-cost generic drug for the expensive patented drug will exceed the $100 million outcome payments under the AMC, which can be used to top-up the IVPE + AMC Fund to make it self-sustaining. In the case that clinical trials fail, the sponsor loses their investment, unless payers agree to transfer part of their cost savings for the duration of the IVPE RCTs to reimburse the sponsor. This is truly a win-win arrangement to fund new RCTs with very limited commercial risks compared to traditional drug development. The main task is finding repurposed generic drugs or low-cost interventions that could reduce reliance on expensive patented drugs by having at least the same safety and efficacy. There are many low-hanging fruits that are already medically “de-risked” (see generic drug repurposing use cases section below).

Once the repurposed generic or low-cost therapy receives FDA approval and market authorization, the insurer can then market the approved therapy to prescribing medical doctors. Doctors in turn can prescribe the treatment protocol to their patients, who benefit from improved health. Moreover, this payment model that generates revenue from RCT data resulting in costsavings helps redress the conflict of interest and information asymmetry between government and healthcare payers and pharmaceutical companies, who are now incentivized to develop the most effective therapies for the lowest cost.

Financial and Health Impact of the IVPE + AMC Fund

根据管理和预算办公室以及科学技术政策办公室，奖杯使联邦政府受益通过允许联邦机构：

1. 仅支付成功
2. Establish ambitious goals and shift technological and other risks to prize participants
3. Increase the number and diversity of individuals, organizations, and teams tackling a problem, including those who have not previously received federal funding
4. 提高成本效益，刺激私营部门的投资，并最大化纳税人的收益
5. 激励和激发公众解决科学，技术和社会问题

There are additional reasons why implementing a self-sustaining IVPE + AMC Fund as a prize-like “pull” incentive to reward development of low-cost therapies is more efficient and scalable than providing grant funding or “push” incentives (although the approaches can be complementary and push incentives can be superior when likely outcomes are known to the grantor). First, IVPE RCTs de-risk sponsors if the payer cost savings are shared by ensuring payer reimbursement of the low-cost therapy is sufficient to cover the costs of the RCT. Under an AMC contract, there is a transfer of risk from payers to the market: payers are not willing to take on the risk and expense of large RCTs, the responsibility of marketing to patients and doctors, and managing adverse events or product recalls. In turn, the market is comfortable taking on this risk and expense, as long as investors can obtain a standard rate of return (e.g., 10-20% p/a). Second, payers and government agencies are often not as well-qualified or equipped as the pharmaceutical industry, which has access to the most experienced staff and latest technological advances, including artificial intelligence. Third, grant programshave high administration costs, both for grantors and grantees, while the latter are not incentivized to deliver successful outcomes. By comparison, the markets are incentivized to fail fast and efficiently allocate capital to those best able to deliver results for the lowest cost. Lastly, repurposed off-patent and unmonopolizable therapies could outcompete patented drugs by providing improved health outcomes for a lower cost to payers. Pharmaceutical companies may also benefit from IVPE RCTs and AMC contracts versus developing novel molecules, due to decreased risk, costs, and time to market.

IVPE + AMC基金创建了一个临床试验数据市场，该市场激励大规模临床试验的资金，例如低成本的仿制药，可能导致的低成本通用药物在数十亿美元（即使不是万亿美元）中在为健康保险公司和政府节省医疗保健方面，此外，还为患者提供了更好的治疗选择和结果。然后可以将节省这些成本的节省重新投资于额外的IVPE + AMC资金，以激发治疗方案的进一步制定。因此，IVPE + AMC模型不仅激发了对不可单位疗法的投资，还可以用于生成可持续且可扩展的业务模型，以对低成本疗法进行额外投资，从而有助于改善全球南部的医疗保健。

存在许多通用药物再利用或低成本治疗候选者

Use Case 1: Metastatic Cancer

Hundreds of non-cancer generic drugs在临床前和临床研究中，研究人员和医师已经对癌症进行了测试，其中一些是II期试验，并表现出了希望。例如，重新利用非专利NSAID Ketorolac作为预防治疗，导致乳腺癌降低10％recurrence would cost $5 million annually (100,000 cases at $50 per case for ketorolac and its administration). The savings could be over $1 billion annually (10,000 patients at approximately $100,000 per patient for the treatment of metastatic disease). These savings would be dwarfed by the cost savings available under anIVPE基金comparing low doses of expensive patented cancer drugs with their standard dose, which can result in fewer side-effects for patients, includingNivolumab, abiraterone, trastuzumab, ibrutinib, paclitaxel, and pembrolizumab. The latter (Keytruda) is the top-selling blockbuster drug, with annual salesin excess of $15B; dosing Keytruda by weightcould reduce use by 25% in approved indications such as lung cancers。

用例2：重度抑郁症和防治抑郁症

Depression is the残疾的主要原因在美国，年龄在15至44岁之间890万成年人和280万had treatment-resistant depression (TRD). A growing body of evidence has shown that infusions ofgeneric ketaminecan be a viable and affordable therapy for both forms of depression, which cost the United States over$320 billion in 2018。自越南战争以来，通用氯胺酮已被用作全身麻醉，成本低于$ 2per dose。However generic ketamine is not authorized to treat any form of depression. The patented and FDA-approved s-ketamine or esketamine,价格为850美元每剂量，用于具有自杀意念的TRD和MDD。

迄今为止，许多临床试验表明generic ketamine is more effective。Moreover, a 2020 study indicated thatEsketamine不太可能具有成本效益除非其价格下跌超过40％，否则在美国的耐药抑郁症的管理。最近，英国付款人不错拒绝偿还埃斯酮胺。大约有900万美国成年人患有耐药性抑郁症，使用自我维持的IVPE + AMC基金成功地重新利用通用氯胺酮可以通过改善的访问和护理标准来挽救许多生命，并节省医疗保健付款人hundreds of millions of dollarsin monopoly prices.

行动计划

The IVPE + AMC Fund can be established through the America COMPETES Reauthorization Act of 2010 (P.L. 111-358），通过授权任何联邦机构的负责人进行一项有可能刺激创新并推进机构使命的竞赛的竞赛，从而鼓励奖金。2016年，《 21世纪治疗法》（P.L. 114-255) directed the director of the NIH to support prize competitions that would realize significant advancements in biomedical science or improve health outcomes, especially as they relate to human diseases or conditions. IVPE + AMC contracts can act like a “prize-like” incentive that is designed to address market failures but also lower healthcare treatment costs for federal agencies (e.g., CMS or VA) by incentivizing the discovery and validation of evidence that low-cost interventions such as repurposed generic drugs may be equivalent to or more effective than expensive interventions such as patented drugs.

简而言之，我们建议建立IVPE + AMC基金并运行如下：

The IVPE + AMC Fund is established through the美国竞争2010年的重新授权法(P.L. 111-358) to support backing of IVPE RCTs by payers as a self-funding mechanism and authorize outcome payments of up to $100 million under an AMC for successful clinical trials of a repurposed generic drug, nutraceutical, and/or other low-cost unmonopolizable therapy to treat a specific indication of high unmet medical need and cost burden (e.g. cancer, treatment resistant depression, glioblastoma, Crohn’s Disease, Alzheimer’s).

IVPE + AMC基金还得到了《 21世纪治疗法》（P.L. 114-255的A司）2002年的支持，该法案要求NIH的董事，该法律规定在美国法典第15届当局。§3719，支持以下一个或两个目标的奖品比赛：

1. 确定和资助生物医学科学领域，可以通过奖项竞争实现重大进步；和
2. 改善健康状况，特别是在严重的人类疾病和疾病方面，代表了美国的重大疾病负担。奖项竞争还可以针对人类疾病和条件，与联邦政府的预防和治疗活动支出以及那些通过减少联邦支出的疾病回报率相对于联邦政府的预防和治疗活动的支出以及那些疾病和条件的可能性不成比例。

The director of the NIH elects a Medical Evaluation Board, which oversees and manages the prize purpose held by the IVPE + AMC Fund as follows:

1. Determining the minimum reimbursement price to sponsors for patients receiving a low-cost therapy under an IVPE RCT which is less than the price of an expensive patented drug or intervention that it substitutes. Then determine the minimum purchase order or outcome payments under an AMC contract relative to total QALY / DALY improvement or cost savings, subject to large Phase 3 RCTs resulting in FDA-approval of the low-cost therapy, and further subject to ongoing safety and efficacy shown in Phase 4 pharmacovigilance studies.
2. The Medical Evaluation Board will be required to collect information on the effect of the IVPE + AMC Fund on advancing biomedical science or improving health outcomes and the effect of the innovations on federal expenditures.

最初，我们建议国会应向NIH提供200万美元的资金，以与NIH收购管理和计划和NCAT的NIH办公室合作建立IVPE + AMC基金计划。其中的重点是创建一个“脱离风险”的低成本疗法菜单，适合于IVPE + AMC基金下的报销，以及可行性研究，以显示为CMS和VA等付款人提供预计的成本节省，以及基于患者的访问福利。在现有的NCAT转化工作中，包括仿制药或剂量降低干预措施，通过将其与IVPE模型下的昂贵专利干预进行比较。例如，为了治疗与年龄相关的黄斑变性可以在10年内节省Medicare部分180亿新元compared with ranibizumab (Lucentis). Or compare the cost of prescribing the generic氟氟voxamine以每QALY $ 6000的价格与Molnupiravir $ 6000治疗Covid，每QALY $ 55,000, substituting sirolimus for nab-sirolumus to treat locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumors (PEComa), or substituting sirolimus for everolimus in various cancers. Significant cost savings from IVPE RCT de-escalation studies comparing a lower dose of an expensive cancer drug to the standard treatment can fund the development of new unmonopolizable therapies. For example, this includes savings fromlow-dose nivolumab对于头颈癌，低剂量的阿比罗酮和曲妥珠单抗，ibrutinib，紫杉醇和pembrolizumab用于其他各种癌症，如上所述。该试点的关键将是一个足够的基于证据的评估过程，以生成低成本IVPE用例菜单。理想情况下，在规模上，IVPE + AMC基金将涵盖广泛的市场失败，但我们建议对专业肿瘤学药物的重新使用仿制药和剂量降低研究的低调果实，然后再扩展到包括其他类型的不可垄断疗法，包括其他类型的疗法医疗饮食，例如ketogenic diet, non-pharmaceutical, and lifestyle interventions that can reduce reliance on expensive therapies.

结论

An IVPE + AMC Fund established under the America COMPETES Act can provide a more flexible, self-sustaining and cost-effective payment model for developing affordable and effective medical therapies, as opposed to the pharmaceutical industry’s traditional model of charging a monopoly price for new patented drugs. Establishing IVPE RCTs that compare low-cost treatments with expensive treatments generates immediate cost savings for payers from reduced reliance on monopoly-priced drugs as well as future cost savings if clinical guidelines are updated to recommend the low-cost treatment. AMC contracts incentivize FDA-approval and help correct misaligned incentives under the patent system by ensuring rewards are脱钩通过最大化一种垄断价格的药物的销售。

If our proposed self-sustaining IVPE + AMC Fund can be implemented, this will create new incentives to leverage the biotech innovations of the last 40 years and optimize the efficient delivery of healthcare, including genetic engineering, personalized medicine (informed by blood tests and low-cost DNA sequencing), artificial intelligence, decentralized clinical trials, and telemedicine. The pharmaceutical industry is not to blame if they can only rely on the patent system to obtain a return on investment for funding medical innovation. New outcomes-based payment models are needed to develop more affordable and effective treatments that can pull the practice of medicine into the 21st century and address significant health inequities.

附录

IVPE RCT + AMC Financial Model Example

这种IVPE RCT + AMC财务模型使用通用的氯胺酮和专利的埃斯酮胺作为如何通过将低成本干预与昂贵的干预措施进行比较来利用即时和未来的成本节省的一个例子，以激励RCT为不可单位的疗法提供RCT的资金。