Value frameworks offer a structural approach to measure treatment value by quantifying a new health technology’s benefits, risks, and costs. At the same time, it is well known that benefits and risks observed in a clinical trial may not translate into the real world. For instance, real-world medication adherence is often suboptimal, clinical trial populations often differ from those in the real-world, and some trials rely on surrogate outcomes requiring extrapolation to more meaningful real-world outcomes.

More broadly, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) developed a “value flower,” which aims to more comprehensively capture all elements of value relevant for measuring the value of a new health technology. Yet, the COVID-19 pandemic and subsequent roll-out of new treatments and vaccines has highlighted another value element that may need to be added to value discussion: the supply chain.

Overall, there are four high-priority areas where a health technology’s real-world benefits and risk are likely to be impacted by supply chain: (i) vaccines for contagious diseases, (ii) cell and gene therapies, (iii) digital medicines and therapeutics, and (iv) high-risk medications. Below, we review each of these cases in turn and argue that in these four cases, treatment value may be highly impacted by supply chain considerations.

Vaccines

First, the rush to deliver COVID-19 vaccines provides a clear example of how supply chains are vital to delivering real-world benefits for contagious diseases. COVID-19 vaccines—even one dose—greatly reduce transmission risk. Cold-chain storage and transportation capacity is vital for some COVID-19 vaccines. The faster COVID-19 vaccines are manufactured, delivered, and used, the faster we will reach herd immunity.

A recent paper in Science estimated that increasing vaccine capacity from 1 billion to 2 billion would increase the value of global health benefit by $4.5 trillion and would halve the time countries take to reach 70 percent vaccination rate. Aside from COVID-19, having detailed information on influenza vaccine inventory and allocating that to the region or population in need has been shown to reduce infection rates by more than 20 percent. Ebola vaccines supply chains are also vital in order for populations to quickly reach heard immunity.

Cell And Gene Therapies

While COVID-19 vaccines grab the headlines, in the long-run, supply chains may be of even more importance to both cell and gene therapies, as well as digital technologies. One example of cell and gene therapies where supply chains play a vital role is chimeric antigen receptor (CAR T) therapies, used to treat life-threatening cancers such as acute lymphoblastic leukemia (ALL). CAR T therapy requires drawing blood from patients, separating out the T cells and genetically engineering them to produce chimeric antigen receptors (CARs) on the cell surface, expanding the number of antigen-specific CAR T-cells in the laboratory, and then infusing them back on the patient. This process may take up to 4 weeks to complete. Companies that have a robust CAR T supply chains will be able to get treatment to patients faster, more accurately and securely, which likely will result in improved health outcomes.

Digital Medicines And Therapeutics

Digital medicines and therapeutics also require robust supply chains. Consider, for instance, the complexities introduced by the digital medicine Abilify MyCite. Abilify MyCite monitors medication adherence based on whether the patient ingested their pill, but requires the use of not only an antipsychotic medication with an embedded sensor, but also a wearable Bluetooth patch and smartphone app. Not only must all three components be supplied to patients seamlessly, but patients also may require training on how to use the system. While access to real-time patient adherence information would be highly valuable to providers, each of these components must work together seamlessly and be re-supplied on demand for the value to appear in the real world and the supply of tablets and patches must be seamless.

Further, as software evolves, digital systems must be updated to work with the latest mobile or desktop operating systems. As shown by the case of digital glucometers, providers are more likely to adopt digital technologies if they are both integrated into electronic health records and able to communicate relevant information clearly and concisely.

High-Risk Medications

Finally, supply chains are also vital for reducing the adverse impacts of high-risk substances. One obvious example is pain medications that are susceptible to abuse, such as opioids, including fentanyl. The total societal cost of the opioid epidemic was estimated to be $78.5 billion. While opioids may be highly beneficial for some patients (e.g., end-of-life cancer patients), supply chain security is vital to insure that these medications are only given to those in need.

Many states now require prescription drug monitoring programs (PDMPs); their ability to reduce unnecessary opioid use, however, depends on numerous factors such as (i) sending proactive reports to providers to notify them of high-risk patients, (ii) integrating PDMPs into electronic health records, (iii) permitting physicians to delegate PDMP access to other allied health professionals in their office, and (iv) streamlining registration, access and returns.

Incorporating Supply Chains Into Reimbursement: Opportunities And Challenges

For these four treatment areas, supply chain considerations could be integrated into outcomes-based contracts as well. In the case of contagious diseases, purchase agreements could vary reimbursement amounts based on how quickly vaccines and treatments are produced. Similarly, for cell and gene therapies, reimbursement could be higher based on time from blood extraction to re-infusion. In the case of digital medicines and therapeutics, payers might require manufacturers to meet some minimum interoperability level with common operating systems or integration into electronic health record data. For high-risk treatments such as opioids, penalties could also be imposed if high-risk medications reached individuals that clearly did not need them.

Incorporating supply chain considerations into value measurement or pricing decisions, however, does face some challenges. Measuring supply levels and supply times requires extra monitoring on the part of payers, which is not costless. Requiring innovators to ensure digital systems are compatible or even interoperable with other systems would impose extra costs on manufacturers. Further, while preventing misuse of high-risk substances is a laudable goal, identifying “misuse” in practice is often difficult; further additional oversight and restrictions may create access barriers for patients who need treatment. Outside of the four high priority areas, supply chain considerations may be less important, particularly when treatments are not time sensitive or when there are many other treatment alternatives available.

Nevertheless, the COVID-19 pandemic has highlighted the importance of supply chains. For these four treatment areas—contagious diseases, cell and gene therapies, digital health technologies, and high-risk medications—supply chain considerations should be an additional petal to add to the value flower.