Top 10 HEOR Trends

ISPOR—as the leading professional society in health economics and outcomes research (HEOR)—continues to conduct horizon scanning and monitor the trends that affect healthcare decision making around the globe. This marks the fourth publication of the Society’s Top 10 HEOR Trends report that is now a biennial publication. The “2022-2023 ISPOR Top 10 HEOR Trends” report is based on input from its members and strategic curation from its Health Science Policy Council.

Real-world evidence (RWE) remains the number 1 trend for 2022-2023. The significance of RWE continues to grow, fueled by its importance in addressing the pandemic. Related, health data tie integrally to RWE and joins the trends list at number 9. 

Several new topics have arrived on the 2022-2023 trends list. Health equity comes to the top trends at number 3. While health disparities have always been an issue in healthcare, the pandemic has starkly illuminated these inequities and their devastating impact. Public health has joined the top trends at number 7; also no doubt elevated by the impact of the pandemic. Health technology assessment (HTA) enters the list at number 8, and artificial intelligence joins the top trends at number 10. 

Several themes are woven throughout this report. Healthcare data carry through the trends of RWE (number 1), health data (number 9), and artificial intelligence (number 10). The issue of how we assess and evaluate healthcare interventions can be seen with the trends value assessment (number 2) and HTA and cross-country cooperation (number 8). Patients are a factor in every trend as healthcare ultimately is intended to serve patients’ interests and needs, but directly related trends include patient engagement (number 5) and health equity (number 3), since these disparities have a direct and profound impact on patients. Pricing and financing of healthcare remain prominent themes, as in past trends reports. Healthcare financing (number 4) focuses on how we fund new and innovative therapies and drug and healthcare pricing (number 6) centers on transparency. 

ISPOR’s members will continue their important work on these and other HEOR-related topics toward the Society’s mission to improve healthcare decision making. HEOR provides vital information that helps all healthcare stakeholders—including researchers and academicians, assessors and regulators, payers and policy makers, the life sciences industry, healthcare providers, and patients—make health decisions informed by the best scientific research that is derived from rigorous, proven methodologies.

THE PANDEMIC: ADVANCING HEOR IN THE COVID-19 ERA

The COVID-19 pandemic has been a profound "disrupter" that is still transforming our world by upending healthcare, economies, and the lives of people across the globe. The pandemic has also illuminated and exacerbated many important issues, from health disparities to biopharmaceutical research and development. Importantly, COVID-19 has been a stark reminder of the devastating and expansive impact that pandemics can have on society. It is no surprise that the pandemic also permeates each of this report’s trends and it is for this reason that “The Pandemic” warrants special recognition and placement in this Top 10 HEOR Trends report. 

The Johns Hopkins Coronavirus Resource Center reported in October 2021 that the global death toll from the pandemic has hit the 5 million mark.¹ As an indication of how rapidly the death toll can increase, they note that 4 million deaths were recorded for the pandemic only 4 months prior. A number of organizations have pointed out that most pandemic death rate estimates are vastly undercounted. At about the same time that Johns Hopkins reported the 5 million global deaths number, The Economist reported in November 2021 that the number of COVID-19 deaths is actually closer to 17 million, calling the 5 million tally “a huge undercount.”² As the pandemic persists and as the infection and death rates continue to increase over time, real-time tracking can be found from a number of organizations that track global COVID-19 metrics, including the Johns Hopkins Coronavirus Resources Center and the World Health Organization Coronavirus Dashboard. 

The COVID-19 pandemic has already spurred a number of transformative changes to healthcare. Its disruptive influence will continue to impact not just healthcare, but economies, the workplace, family life, and more. 

Thus far, the pandemic has resulted in the rapid adoption and acceptance of telehealth. McKinsey reports that in April 2020, overall telehealth utilization for office visits and outpatient care in the United States was 78 times higher than in February 2020. As of July 2021, telehealth utilization stabilized to levels 38 times higher than before the pandemic. Since the initial April 2020 telehealth spike, adoption overall has approached up to 17 percent of all outpatient/office visit claims with evaluation and management services.³ 

The pandemic has also illuminated an issue that has long plagued healthcare—health disparities. Health equity is trend number 3 in this report and where this issue is explored in greater detail. 

Collaboration between scientific disciplines is always important—especially during a crisis, such as the global pandemic. Health economics and outcomes research (HEOR) is a vitally important discipline in the research community that has been addressing a spectrum of issues related to COVID-19 and its impact. HEOR professionals are heavily involved in working on pandemic-related healthcare challenges, exploring issues such as disease incidence and health consequences, the economic impacts of the disease, and the value of treatment (vaccines and therapies). Other COVID-19–related topics of cross-disciplinary importance include health system preparedness, the interaction of public health and other sectors of the economy, as well as trust in health science in general and how it is reflected in health behaviors, such as vaccine acceptance. 

The global HEOR community will continue to play an essential role in helping address and move through the pandemic. ISPOR has focused on pandemic-related issues in many of its conference sessions, webinars, and publications. The Society’s COVID-19 Resources web page curates and aggregates internal and external pandemic-related resources for its members and the broader healthcare community.

Real-World Evidence: Using real-world evidence in healthcare decision making

Real-world evidence (RWE) continues to be a significant trend, again topping the list as number 1. RWE holds the promise of timely data at a reasonable cost, can offer large sample sizes that enable analysis of subpopulations and less-common effects, and can provide a representation of real-world practice and behaviors. All of these are difficult to achieve with randomized clinical trials (RCTs).

The COVID-19 pandemic has provided examples of how RWE can work well and others where it has not. For example, a retrospective analysis determined that when tocilizumab was administered to patients with a severe course of COVID-19, there were definite improvements in survival, clinical improvement, and the hospital discharge rate.⁴ In contrast, the Surgisphere scandal in 2020, with the discredited papers about hydroxychloroquine use in COVID-19, demonstrated how bad data can undermine confidence in RWE. As The Scientist noted, Surgisphere claimed to have an enormous registry of observational data, but The Lancet study on hydroxychloroquine had impossibly high numbers of cases and other data discrepancies.⁵ Investigation into Surgisphere revealed that its database may never have existed.

In the United States, there have been legitimate uses of RWE by the US Food and Drug Administration (FDA) for drug approvals. One example is Pfizer’s Ibrance (palbociclib) that FDA approved for male breast cancer in 2019. The approval was based on the results of an analysis of real-world data (RWD) from electronic health records (EHRs) as additional supportive data to characterize the use of Ibrance in combination with endocrine therapy in male patients with breast cancer.⁶ Another example is the 2021 approval of a new dosing regimen of Erbitux (cetuximab) that was supported by RWD.⁷ The proposed bipartisan 21st Century CURES ACT renewal announced in June 2021 in the United States calls on FDA to grow its collection and use of RWE. And in May 2021, FDA’s Center for Drug Evaluation and Research (CDER) announced “The FDA Real-World Evidence (RWE) Framework and Considerations for Use in Regulatory Decision-Making.”

In Europe, the Netherlands-based GetReal Institute launched in April 2021.⁸ The Institute aims to be a source of trusted, high-quality RWE education and training. European Medicine Agency’s DARWIN and the RWE Alliance coalition of organizations in the United States are “big data” efforts with a focus on high-quality data for regulatory use.

In the private sector and academia, OPERAND and RCT Duplicate are showing that with the right methods, RWD can achieve similar results as an RCT. The first results of RCT Duplicate were published in the journal, Circulation.⁹ The MRCT Center has collaborated with the Duke-Margolis Center for Health Policy to define a framework to establish best practices for utilizing RWE for regulatory decision-making.¹⁰ The Observational Patient Evidence for Regulatory Approval and uNderstanding Disease (OPERAND) Project was conceptualized by the MRCT Center and OptumLabs and aims to use RWE to emulate Phase III clinical trials. 

ISPOR is vigorously pursuing its work in RWE, and RWE is one of the themes in the ISPOR Science Strategy. The Society’s RWE Transparency Initiative published its recommendations in the September 2020 issue of Value in Health and in 2021 introduced its Real-World Evidence Registry. ISPOR also recently launched a series of introductory “About RWE” content.

Value Assessment: Informing value-driven healthcare decisions

The question that often dominates healthcare discussions is “How much does it cost?” This is why value assessment plays a crucial role in healthcare systems.

But unlike consumer goods, normal supply and demand doesn’t work well for determining healthcare prices because of market distortions caused by health insurance, lack of pricing transparency, patents, imperfect information, and other issues. To inform what reasonable pricing should be for many healthcare products and services, health economic analyses—typically cost-effectiveness analyses—are used. 

Cost-effectiveness analysis provides a standardized approach to value assessment; however, it may not apply well to all situations—acute versus chronic disease treatment, common versus rare diseases, mild versus life-threatening conditions, palliative versus curative therapies, in addition to underserved or disabled populations. Value is also defined differently by each stakeholder—patients, payers, providers, or society at large. 

Defining Value Frameworks 

A number of organizations have issued “value frameworks” in recent years. Many of these existing value assessment frameworks tend to focus on drugs (and to a lesser extent on medical devices). However, most of health spending involves physician and hospital services. An ISPOR Special Task Force on US Value Assessment Frameworks examined a variety of value considerations and assessment methods and issued a set of recommendations (that were outlined in 2 articles published in Value in Health) for conducting value assessment. Two important points in those recommendations were: 

• Value assessment frameworks that focus on health plan coverage and reimbursement decisions should consider cost-effectiveness analyses (CEA), as measured by cost per quality-adjusted life-year (QALY), as a starting point to inform payer and policy-maker deliberations. In many instances, the cost-per-QALY metric can serve well as the core component of these assessments. 
• Elements of costs and benefits not normally included in CEA that affect individual well-being (such as severity of illness, equity, and risk protection) may be relevant for some health plan decisions; however, more research is needed on how best to measure and include them in decision making. 

ISPOR’S “Value Elements” 

For those elements of value not normally included in CEA, the ISPOR value elements provide additional factors to consider. These include “value of insurance,” which is significant because the effective treatment of severe, chronic conditions has inherent value in reducing risk from those conditions, but depends on access to affordable care. The “value of hope” is a value element applicable for treatments that have a chance to be curative or have durable benefit, such as gene and cell therapies in cancer and rare diseases. The rise in demand for diagnostics and genetic testing shows how the value of the “reduction of uncertainty” plays a role in healthcare decision making. And “equity” defines how society sees value in providing treatment to underserved populations. Taken together, these elements can help address the situations where standard CEA may not be adequate by itself. 

ISPOR and its members continue to do much work in this area. Related resources on value assessment are available on the Society’s Value Assessment Frameworks webpage as well as in ISPOR Reports.

Health Equity: Addressing disparities in healthcare

Disparities in healthcare impact many people and can include factors such as race, income level, gender, geography, sexual orientation, and gender identity.

In 2020, the COVID-19 pandemic starkly illuminated economic-based health disparities, as poorer communities and countries saw skyrocketing numbers of cases and deaths. Even as the economy starts to recover, these economic disparities are not going away. 

According to the Bill and Melinda Gates Foundation’s 2021 Goalkeepers Report, economic recovery is uneven between, and even within, countries. “By next year, for example, 90% of advanced economies are expected to regain prepandemic per capita income levels, while only a third of low- and middle-income economies are expected to do the same,” the Foundation says.¹¹ 

According to the American Public Health Association, in its November 2017 article, “Reducing Income Inequality to Advance Health,” income inequality leads to more widespread health problems, citing studies that say it has been demonstrated to correlate with worse outcomes in life expectancy, infant mortality, teenage birth, obesity, mental illness, and drug and alcohol addiction—with more than 884,000 deaths per year in the United States alone attributable to underlying income inequality.¹² Conversely, a study in the April 26, 2016 issue of JAMA, found that higher income was associated with greater longevity.¹³

Economic disparity has also been very apparent in the distribution of COVID-19 vaccines. The Gates Foundation estimates that 80% of all COVID vaccines have been administered in high-income and middle-upper-income countries, with less than 1% administered in low-income countries. “These inequities are a profound moral outrage—and raise the very real risk that high-income countries and communities will begin to treat COVID-19 as another epidemic of poverty,” the Foundation writes.¹¹

In the context of economic disparity in health are racial disparities. Within the United States, Black and Indigenous communities bore the greatest impact from COVID-19, with case and death rates much higher than in White communities. And according to Kaiser Family Foundation, vaccination coverage remains uneven throughout much of the country, with Black and Hispanic people receiving smaller shares of vaccinations compared to their shares of cases in most reporting states.¹⁴ But the data also show that these disparities are narrowing over time, particularly for Hispanic people, which according to the Office of Assistant Secretary for Planning and Evaluation, reflects efforts that are focused on increasing vaccination rates among people of color.¹⁵

Policy makers have tried to address some of these issues in programs to improve certain health measures. However, in the United States, efforts made over the past 25 years have not achieved the promise of improving health equity, according to an analysis in the June 28, 2019 issue of JAMA.¹⁶ “Greater or different efforts than those tried in the past will have to be mustered if health equity is to improve,” the authors say, suggesting that performance tracking of health equity may help to keep policy makers accountable.

Much work is still needed to bring equity to healthcare, and HEOR can contribute toward addressing this important issue. ISPOR has established a Health Equity Research Special Interest Group to advance equity-informative methods and data for health economics and outcomes research that help to reduce unfair differences in health.

Healthcare Financing: Funding innovative health technologies

As biopharmaceutical research continues to make breakthroughs with innovative health technologies, the issue of how to best and most appropriately fund this research remains a high-interest topic, calling for innovative methods to understand how society can fund research and development (R&D) for these therapies.

At the forefront of these expensive, yet novel technologies are therapies for rare disease, which typically have small patient populations and long-term problems related to illness. The most expensive rare disease therapy currently on the market is Zolgensma (onasemnogene abeparvovec-xioi), for the treatment of spinal muscular atrophy (SMA), at $2.125 million.17 Biogen’s Spinraza (nusinersen), also for the treatment of SMA, costs $750,000 for the first year of treatment and then $375,000 per year afterward for the rest of the patient’s life. Zokinvy (lonafamib), for the treatment of Hutchinson-Gilford progeria syndrome and processing-deficient progeroid laminopathies, costs $1.03 million per year.

The seemingly high prices of therapies for rare diseases are at least in part due to the need to amortize the still-substantial development cost for these therapies over a very small number of patients. Along with some other incentives, they have helped provide a steady pipeline of products for patients with rare diseases who may not otherwise have had effective treatment for their diseases.

Therapies for “big” diseases such as Alzheimer’s disease, which impacts many patients, also can have a high total cost for the treatment population. Aduhelm (aducanumab), which costs $56,000 a year, could affect the economics of Medicare in the United States, according to some experts.¹⁸

Discussions of financing high-cost therapies inevitably raise the issue of whether the long-term outcomes are worth the cost. Zolgensma was approved as a “one-and-done” treatment, but at this point it is unknown whether patients will have to be dosed again in their lifetimes. In the United Kingdom, NICE has recommended a managed entry agreement for use of Zolgensma in babies with certain SMA genotypes while more data are collected on their outcomes.

These innovative therapies present challenges for traditional modes of payment and reimbursement, because of either very high prices for small patient populations or large total expenditures for therapies impacting larger populations. In the United States, one well-known solution to pay for hepatitis C therapies—the so-called Netflix model—has been adopted by several states. 

Another approach for controlling costs is negotiating warranty programs with manufacturers. Pfizer was running a pilot warranty program for its lung cancer drug, Xalkori (crizotinib), through 2021, in which the company reimbursed patients’ out-of-pocket costs if they discontinued the drug early.¹⁹ A recent Organisation for Economic Co-operation and Development (OECD) working paper provided a review of managed entry agreements, both financial and performance-based, in OECD countries and EU member states.²⁰

ISPOR offers several ISPOR Reports related to this issue and a number of the Society’s member groups, including the Rare Disease Special Interest Group, focus on these issues.

Patient Engagement: Infusing the "patient voice" in healthcare research

Much of healthcare research—especially drug company research—is often trying to address unmet needs. Usually, however, this pertains to unmet clinical needs, as conveyed by physicians. But to best understand the aspects of a disease that have the most impact on patients, researchers need to listen to the patient voice.

Patients can help answer questions such as how a disease actually affects their lives, what outcomes they think will best serve them or improve their lives, how a given treatment will intersect with their needs, and how researchers can most effectively communicate the overall outcomes and finer points of a new treatment. Health economics and outcomes research (HEOR) also needs to incorporate learnings from patients about their clinical journey so that policy makers can do a better job of understanding all the costs and benefits that are relevant to an economic evaluation. With this understanding, any policies or rulings created can better represent the patient perspective. 

Patient engagement poses several challenges to HEOR researchers. Some experts believe that patients cannot interact with researchers in such a way that they can provide information that will have meaning under the protocols of the research. One way of addressing this concern is by increasing patient engagement in core outcomes set development. According to researchers in the July 2021 journal, Patient, including core outcomes sets (COS) in clinical development programs and HEOR can produce relevant, consistent outcomes for healthcare decision making, resulting in faster patient access to new therapies. By developing patient-centered COS, HEOR studies and decisions made using these sets would be relevant to patients.²¹

The case studies included in the Patient article demonstrated efforts to enhance dialogue between patients and researchers, by educating patients so that they can meaningfully interact with researchers. Researchers partnered with patient organizations, conducted orientation and training, and used the consensus process. The development of core outcomes sets and other methods demonstrates how HEOR has made a science of methods to measure outcomes from the patient’s point of view. These techniques help clinical researchers understand how to collect meaningful and reliable data about patient outcomes. 

ISPOR continues to focus on patient engagement efforts, and patient-centered research is one of the Society’s Science Strategy themes. ISPOR’s Patient Engagement in HEOR initiatives include many conference sessions, posters, trainings, and publications on this topic. ISPOR has several Good Practices and other ISPOR Reports focused on Patient-Centered Research, such as “Defining Patient Engagement in Research: Results of a Systematic Review and Analysis.” ISPOR member groups engaged in patient-centered research issues include the Patient Council; Patient Representatives Roundtables in Asia Pacific, Europe, Latin America, and North America; the Patient-Centered Special Interest Group; and the Using Patient Preferences to Inform Decision Making Task Force.

Drug and Healthcare Pricing: Improving price transparency 

Just as with society at large, pricing for drugs and healthcare overall remains a top 10 trend for 2022-2023, as determined by ISPOR members. 

In the previous 2020 Top 10 report, drug pricing was the number 2 trend and price transparency was number 7. These 2 concerns have coalesced into one for this report. 

Pricing issues continue to drive many policy conversations in the United States, which is unique among industrialized countries as it does not have universal healthcare coverage, but rather operates under a highly fragmented system with multiple payers that include private insurance and government programs such as Medicaid and Medicare. While drug pricing was a big part of President Joe Biden’s 2020 campaign, it is uncertain if or what type of legislation might pass as priorities in his domestic spending package are debated. 

In the United States, pharmacy benefit managers’ (PBMs) contracts and pharmaceutical company rebates drive much of the pricing conversation. The drug rebates the industry negotiates with PBMs in contracts are common and typically confidential. These rebates effectively reduce the net drug price the PBM pays, but there are concerns that these price reductions are not transmitted to the ultimate payer or to the patient. While the need for confidential private contracts is recognized in the United States, the effects on patient out-of-pocket costs has been seen as problematic. Also complicating matters are Medicaid “best pricing” rules and discounts offered under the 340B program, which requires drug makers to offer discounts on all outpatient drugs to hospitals and clinics that serve low-income populations. 

Some progress has been made in making nondrug pricing more transparent in the United States, such as measures for hospital pricing, where the Center for Medicare and Medicaid Services implemented the Hospital Price Transparency Final Rule beginning in 2021.²² Among other things, it requires “display of shoppable services in a consumer-friendly format.” In July 2021, the Biden administration issued an interim final rule to implement parts of the No Surprises Act, meant to protect patients from “surprise” medical bills resulting from unexpected balance billing, especially from out-of-network providers. The No Surprises Act also places limits on patient cost-sharing, where patients pay a portion of healthcare costs that are not covered by insurance.^23,24 

Drug pricing concerns are a global issue. Similar issues occur across other countries as they negotiate confidential drug price discounts or rebates relative to the posted price. The confidentiality of these agreements is not necessarily seen as good practice by all concerned and has been a subject of debate. As of April 2021, Europe has been trying to bring more transparency into the process. At the center of the debate are managed entry agreements.²⁵ A survey done by EURIPID suggests that the current possibility to improve price transparency across countries is limited and the issue probably requires international institutional engagement, at least to coordinate initiatives toward a greater collaboration among member states.²⁶ 

ISPOR members have been working on the challenges posed by pricing through conference sessions and other means. The Society’s journal, Value in Health, has tackled pricing as the subject of a number of articles curated in its Value and Pricing Virtual Collection.

Public Health: Focusing on key priorities

While a number of ISPOR members work in the public health sector, this marks the first appearance of public health as a topic in the Top 10 HEOR Trends. Driving its inclusion is the COVID-19 pandemic, which has highlighted and exacerbated the importance of public health priorities while balancing them with economic priorities. For example, lockdowns, wearing masks, and vaccinations have been essential in slowing down the number of deaths from SARS-CoV-2.

However, while lockdowns hit many in-person businesses (such as leisure and hospitality) hard, in some parts of the world, organizations are now struggling to hire employees. In the United States, this is being attributed to the effect known as “The Great Resignation,” as millions of workers who are rethinking their priorities during the pandemic are deciding that they want to spend their lives differently.²⁷

Public health policies are often well intended, but the effects of these policies need to be tracked to ensure that the intended results are being achieved—and not at the expense of unintended consequences. While vaccine mandates are expected to cut COVID-19 hospitalizations and deaths, they are also causing political fallout, as some workers—particularly in healthcare—are quitting their jobs rather than getting vaccinated. There are fears that these mandates could cause labor shortages at US hospitals, but many officials say these mandates are working, ensuring worker and patient safety.²⁸ A number of European countries have also enacted mandates that have been deemed politically risky and are resulting in a shortage of healthcare workers.²⁹ 

In addition to the severe challenges that public health systems are facing during the pandemic, measures employed to help prevent the spread of COVID-19 have resulted in some unintended consequences for other health issues. Mental health is a public health concern that has been exacerbated by social distancing and isolation.

Drug overdoses have also increased during the pandemic, presumably due to economic hardships and isolation. Additionally, preventable infectious diseases have spiked because many countries have paused their immunization programs due to lockdowns and travel restrictions.³⁰ 

Unfortunately, COVID-19 has also severely strained public health systems globally. A review of hundreds of health departments in the United States indicates that local public health across the country is less equipped to confront a pandemic now than it was at the beginning of 2020. To remake public health, some experts predict that changes will happen over the next 5 years and in 3 phases that include reactive crisis management, efforts to maintain initial gains, and efforts to sustain and enhance progress.³¹

ISPOR continues to take note of public health issues as well as the future of public health and HEOR. The Virtual ISPOR 2021 plenary, “Public Health…Economics?“ featured a renowned panel of experts discussing how public health officials made tradeoffs between health and economic concerns during the pandemic. There are also almost 3000 posters and sessions from around the world with public health content in the ISPOR Presentations Database and more than 8000 in the epidemiology and public health taxonomy category. ISPOR Good Practices Reports and other ISPOR Reports on Health Policy and Regulatory also cover public health issues, and ISPOR’s journal, Value in Health, has featured a Health Policy Virtual Collection.

Health Technology Assessment: Supporting cross-country HTA cooperation

For the first time, health technology assessment (HTA) comes to the Top 10 list for 2022-2023 with a focus on cross-country cooperation. While HTA is also a key theme in the ISPOR Science Strategy, the emphasis in the Top 10 is on how HTA programs can develop compatible cross-country standards.

In the European Union (EU), European Network for Health Technology Assessment (EUnetHTA) brought together 80 European HTA agencies in 2005 to come up with common methodologies, dossier formats, and other standards to allow for greater efficiency and consistency for both sponsors and HTA bodies. One of the goals of EUnetHTA has been to develop a sustainable system of HTA knowledge sharing. The activities of EUnetHTA have been supported through the establishment of the EUnetHTA Collaboration 2009, the EUnetHTA Joint Action 2010-2012, EUnetHTA Joint Action 2 2012-2015, and most recently, EUnetHTA Joint Action 3 2016-2020. The latter is now developing the final phase of establishing a permanent HTA working structure for Europe.³²

Although EUnetHTA funding has been extended for another 2 years, the project is reaching the end of its mandate. While the European Union has been exploring more permanent practices to either institutionalize or encourage collaboration across European HTA bodies, there are some hurdles toward this goal. One in particular has been limited agreement that relative effectiveness evaluations should be done on a European-wide basis—and there are a few notable country holdouts. However, in October 2021, the European HTA agencies launched a Heads of Agencies Group, chaired by Professor Santos Ivo, Vice President of INFARMED, the Portuguese National Authority of Medicines and Health Products. Then in November 2021, the European Council gave its final go-ahead for the adoption of the legislation, “Regulation of the European Parliament and of the Council on Health Technology Assessment and Amending Directive,” to bring HTA procedures in alignment. 

Outside of Europe, there is the International Network of Agencies for Health Technology Assessment (INAHTA), a collaboration of HTA agencies across the world; HTAsiaLink in the Asia-Pacific Region; and RedETSA in the Latin America Region. At present, there is a great need to build capacity and improve HTA capabilities in low- and middle-income countries and to understand how well HTA evaluations can be adapted across countries. Generally speaking, HTA organizations across the globe are looking to strengthen regional cooperation, leverage their capabilities, and improve their methodologies to support better decision-making processes.

In the United States, with its highly fragmented healthcare system, there is neither a formal nationwide HTA process nor an HTA body that conducts health technology assessments. While several organizations have emerged to assess medical technologies and provide recommendations, there is no consistent practice of HTA across the country.

ISPOR’s work in HTA includes HTA Central, a comprehensive repository of resources and tools to support HTA. ISPOR has also generated a number of Good Practices and other ISPOR Reports on HTA, such as “Identifying the Need for Good Practices in Health Technology Assessment.” The Society’s Joint HTAi-ISPOR Deliberative Processes for HTA Task Force was formed to develop a consensus definition for a deliberative process from an HTA perspective.

Health Data: Addressing infrastructure and interoperability

The volume of health data has exploded. According to RBC Capital Markets, about 30% of the world’s data is being generated by the healthcare industry. These experts say that by 2025, the compound annual growth rate of data for healthcare will reach 36%—which is 6% faster than manufacturing, 10% faster than financial services, and 11% faster than media and entertainment.³³

Forbes quotes estimates that each single patient generates nearly 80 megabytes each year in imaging and electronic medical record (EMR) data.³⁴ 

Health data siloed away in individual systems are of limited use. Interoperability is key. The Healthcare Information and Management Systems Society (HIMSS) defines interoperability as “the ability of different information systems, devices, and applications (systems) to access, exchange, integrate, and cooperatively use data in a coordinated manner, within and across organizational, regional, and national boundaries, to provide timely and seamless portability of information and optimize the health of individuals and populations globally.” Health information exchange (HIE) is also necessary to move information electronically among different healthcare systems without the meaning of that information being garbled or lost.³⁵ 

The goal of interoperability is to have commonly available data sets with common record formats that can be used by researchers, policy makers, and regulators. Data sets with common record formats are more amenable to being merged to allow for more generalizable analysis and to bring complementary types of data into play. 

Once the data sets can be brought together, there must be an infrastructure to generate tools to aid researchers in analyzing data. There are several programs that are creating these tools. The United States Food & Drug Administration (FDA) has the Sentinel Initiative, which supports the Sentinel System and FDA-Catalyst. The Sentinel System helps answer the FDA’s questions by creating computer programs that analyze electronic healthcare data. FDA-Catalyst supplements the Sentinel System with data from interactions with patients and/or providers.³⁶ 

Another initiative, OHDSI (Observational Health Data Sciences and Informatics; pronounced “Odyssey”), is a multistakeholder, interdisciplinary collaborative designed to bring out the value of health data through large-scale analytics. 

The European Commission is currently working on the European Health Data Space to provide a framework for the primary and secondary use of health data in the EU Member States. To make health data findable, the Commission is supporting mapping of existing health data registries and other data sources to establish common data sets for exchanges for health research and policy-making purposes. 

ISPOR supports its members with the tools, education, and training they need to work with health data. Among ISPOR’s Good Practices Reports on Real-World Data is “Reporting to Improve Reproducibility and Facilitate Validity Assessment for Healthcare Database Studies V1.0.“ The Society’s member groups include the Digital Health Special Interest Group, Real-World Evidence Special Interest Group, and Machine Learning in HEOR Task Force.

Artificial Intelligence: Leveraging AI and advanced analytics

The Healthcare Information and Management Systems Society (HIMSS) defines artificial intelligence (AI) as “computer systems able to perform tasks that usually require human intelligence.” They note that AI is significantly changing healthcare by analyzing large amounts of data using algorithms to learn how to do tasks without being explicitly programmed.³⁷ 

The richness and variety of real-world evidence (RWE) that is available—from physician reports, postmarketing studies, patient registries, and other sources—presents challenges to traditional analytic methods. Machine learning techniques and AI in general often provide more flexible ways to analyze data and obtain insights about real-world healthcare practices and behaviors. They can be used especially for prediction of likely outcomes for situations that have been commonly observed in the past. 

As noted in trend number 1 on real-world evidence, there are currently 2 initiatives using databases and machine learning platforms to analyze RWE: Observational Patient Evidence for Regulatory Approval and uNderstanding Disease (OPERAND) and the RCT-DUPLICATE initiative (Randomized, Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology).^38,39 

The objective of OPERAND is to understand how real-world evidence can be used effectively in a regulatory environment. The initiative beings together diverse experts from industry, academia, government, and others to advise, oversee, and replicate clinical trials using de-identified clinical and administrative claims data from the OptumLabs Data Warehouse. This is a rich, linked data set that can be used to conduct broad or narrow investigations on populations and unique subsets within them.

RCT-Duplicate uses a structured process to design RWE studies emulating randomized, controlled trials (RCTs) and compare results. The initiative published the results of a project in Circulation, reporting the findings from 10 RWE studies designed to emulate RCTs for cardiovascular outcomes of antidiabetic or antiplatelet medications.³⁹ To create the cohort and study variables, researchers used the Aetion Evidence Platform, which is software that uses proprietary rapid-cycle analytics to turn real-world data into transparent, reliable, and replicable RWE. Rapid cycle analysis is a technique that quickly assesses the effectiveness of program components by testing different treatment conditions, while facilitating ongoing feedback to staff to support program improvement. 

Another AI-supported technique is the “target trial approach” where the data are analyzed with some restrictions that mirror what would have happened if an observed patient was participating in an RCT. Target trials are specifically algorithmic emulations of randomized studies.⁴⁰ 

ISPOR has held a number of conference sessions, trainings, and webinars on AI in HEOR, including a plenary at Virtual ISPOR 2020, and continues to feature related content in its journals. The Society’s member groups include the Digital Health Special Interest Group and a Machine Learning Methods in HEOR Task Force.

ISPOR—the professional society for health economics and outcomes research (HEOR)—is an international, multistakeholder, scientific and educational nonprofit organization that is recognized globally as the authority in HEOR and its use in decision making to improve health. ISPOR is the primary source for scientific conferences, peer-reviewed and MEDLINE^®-indexed publications, good practices guidance, education, collaboration, and tools/resources in the field. ISPOR’s Health Science Policy Council and Chief Science Officer Richard J. Willke, PhD, have led efforts in developing this list of the “2022-2023 Top 10 HEOR Trends.”

ISPOR’s Health Science Policy Council
The ISPOR Health Science Policy Council serves as an advisory council to the Board of Directors to ensure that the Society addresses key research issues in outcomes research. The Health Science Policy Council was established in 2004 and is composed of invited members, including ISPOR past presidents, Avedis Donabedian Lifetime Achievement Award honorees, and other key thought leaders from the ISPOR membership base. In addition to its involvement in the HEOR trends initiative, the Health Science Policy Council also serves as an advisory body for the Society through horizon-scanning efforts and critical review and oversight of proposals for ISPOR’s Good Practices Reports.

The Health Science Policy Council includes 3 key committees—the Policy Outlook Committee, the Science Research Committee, and the Task Force Review Committee. These committees are co-chaired by Health Sciences Policy Council members and include representatives from other ISPOR groups, including the Institutional Council, Faculty Advisor Council, Health Technology Assessment Council, Patient Council, Education Council, Latin America Consortium, Asia Consortium, Central and Eastern Europe Consortium, Africa Network, Arabic Network, the Editors in Chief of Value in Health, and ISPOR’s Chief Science Officer.

Methodology
The methodology for development of the “2022-2023 Top 10 HEOR Trends” included:

Topic Exploration
Comprehensive exploration to generate a “long list” of potential topics was conducted by examining HEOR-related topics at a variety of industry conferences (including ISPOR conferences and other industry events), articles in scientific journals, research/industry blogs, and articles in trade publications.

Review and Vetting
ISPOR’s Health Science Policy Council (including its committees) reviewed and vetted the “long list” to generate a “short list” of more than 40 potential HEOR trends for consideration.

Thought Leader Survey
A survey of ISPOR members was conducted to rate the topics curated by the Health Science Policy Council.

Finalization
The Health Science Policy Council and its committees reviewed and finalized selections for the Top 10 list based on the survey results.

1. Voice of America. Johns Hopkins: World COVID-19 Death Toll Nears 6 Million. VOA News. Published October 31, 2021. Accessed November 20, 2021. https://www.voanews.com/a/johns-hopkins-world-covid-19-tally-nears-5-million/6292641.html

2. The Economist. The number of people who have died from Covid-19 is likely to be close to 17m. Economist. Published November 2021. Accessed November 20, 2021. https://www.economist.com/graphic-detail/2021/11/02/the-number-of-people-who-have-died-from-covid-19-is-likely-to-be-close-to-17m

3. Bestsennyy O, Gilbert G, Harris A, Rost J. Telehealth: a quarter-trillion-dollar post-Covid-19 reality? McKinsey.com. Published July 9, 2021. Accessed November 20, 2021. https://www.mckinsey.com/industries/healthcare-systems-and-services/our-insights/telehealth-a-quarter-trillion-dollar-post-covid-19-reality

4. Zarebska-Michaluk D, Jaroszewicz J, Rogalska M, et al. Effectiveness of tocilizumab with and without dexamethasone in patients with severe COVID-19: a retrospective study. J Inflamm Res. 2021;14:3359-3366. https://doi.org/10.2147/JIR.S322645

5. Offord C. The surgisphere scandal: what went wrong? Scientist. Published October 2020. Accessed November 20, 2021. https://www.the-scientist.com/features/the-surgisphere-scandal-what-went-wrong—67955

6. How real world evidence was used to support approval of Ibrance for male breast cancer. The Cancer Letter. 2019;45:7-10. Accessed November 20, 2021. https://cancerletter.com/the-cancer-letter/20190419_2/

7. Flatiron Health. New York NY. July 20, 2021. Flatiron Health real-world data support FDA approval of new dosing regimen for ERBITUX® (cetuximab). Press release. Accessed November 20, 2021. https://flatiron.com/press/press-release/flatiron-health-real-world-data-support-fda-approval-of-new-dosing-regimen-for-erbitux-cetuximab/

8. About the GetReal Institute. RWE for better health-care decision-making. GetReal Institute. Accessed November 20, 2021. https://www.getreal-institute.org/about-us/

9. Franklin JM, Patorno E, Desai RJ, et al. Emulating randomized clinical trials with nonrandomized real-world evidence studies: first results from the RCT DUPLICATE initiative. Circulation. 2021;143(10):1002-1013. doi: 10.1161/CIRCULATIONAHA.120.051718

10. Berger M, Daniel G, Frank K, et al. A framework for regulatory use of real-world evidence. White paper. Robert J. Margolis, MD, Center for Health Policy at Duke University. Published September 13, 2017. Accessed November 21, 2021. https://healthpolicy.duke.edu/sites/default/files/2020-08/rwe_white_paper_2017.09.06.pdf

11. Gates B, Gates MF. Innovation & Equality. 2021 GoalKeepers Report. Bill and Melinda Gates Foundation. Accessed November 21, 2021. https://www.gatesfoundation.org/goalkeepers/downloads/2021-report/2021-goalkeepers-report_en.pdf

12. American Public Health Association. Reducing income equality to advance health. Policy number 20179. APHA.org. Published November 7, 2017. Accessed November 21, 2021. https://www.apha.org/policies-and-advocacy/public-health-policy-statements/policy-database/2018/01/18/reducing-income-inequality-to-advance-health

13. Chetty R, Stepner M, Abraham BA, et al. The association between income and life expectancy in the United States, 2001-2014. JAMA. 2016;315(16):1750-1766. doi:10.1001/jama.2016.4226

14. Ndugga N, Hill L, Artiga S, Haldar S. Latest data on COVID-19 vaccinations by race/ethnicity. Kaiser Family Foundation. Published November 17, 2021. Accessed November 21, 2021. https://www.kff.org/coronavirus-covid-19/issue-brief/latest-data-on-covid-19-vaccinations-by-race-ethnicity/

15. Gonzales A, Lee EC, Grigorescu V, Smith SR, De Lew N, Sommers BD. Overview of barriers and facilitators in COVID-19 vaccine outreach. ASPE.hhs.gov. Published September 13, 2021. Accessed November 21, 2021. https://aspe.hhs.gov/reports/covid-19-vaccine-outreach

16. Zimmerman FJ, Anderson NW. Trends in health equity in the United States by race/ethnicity, sex, and income. JAMA Network Open. 2019;2(6):E196386. Accessed November 21, 2021.  doi:10.1001/jamanetworkopen.2019.6386

17. Keown A. Top 10 Most Expensive Drugs on the Market. Biospace.com. Published March 9, 2021. Accessed November 21, 2021. https://www.biospace.com/article/gene-therapy-zolgensma-tops-goodrx-list-of-10-most-expensive-drugs/

18. Luhby T. How everyone on Medicare could end up paying for the pricey new Alzheimer’s drug. CNN.com. Published July 10, 2021.  Accessed November 21, 2021. https://www.cnn.com/2021/07/10/politics/aduhelm-alzheimers-drug-medicare/index.html

19. Pfizer. A warranty program for patients starting XALKORI. Xalkori.com. Accessed November 21, 2021. https://www.xalkori.com/financial-assistance

20. Wenzi M, Chapman S. Performance-based managed entry agreements for new medicines in OECD countries and EU member states. Organisation for Economic Co-operation and Development. Accessed November 21, 2021. https://www.oecd.org/health/health-systems/HWP-115-MEAs.pdf

21. Clearfield E, Tambor E, Janssen EM, Messner DA. Increasing the patient-centeredness of health economics and outcomes research through patient engagement in core outcome set development. Patient. 2021;14(4):413-420. doi:10.1007/s40271-020-00424-9

22. Centers for Medicare& Medicaid Services. Hospital Price Transparency. CMS.gov. Updated January 1, 2021. Accessed November 21, 2021. https://www.cms.gov/hospital-price-transparency

23. Gottlieb S. Medical bills account for 40% of bankruptcies. BMJ. 2000;320(7245):1295.

24. Center on Health Insurance Reforms. Protecting Patients From Surprise Medical Bills. Georgetown University Health Policy Institute. Accessed November 21, 2021. https://surprisemedicalbills.chir.georgetown.edu/resources/

25. Pluss JD. Europe tries to lower drug prices with small doses of transparency. Stat News. April 13, 2021. Accessed November 21, 2021. https://www.statnews.com/2021/04/13/europe-tries-to-lower-drug-prices-with-small-doses-of-transparency/

26. Russo P, Carletto A, Nemeth G, Habl C. Medicine price transparency and confidential managed-entry agreements in Europe: finding from the EURIPID survey. Health Policy. 2021;125(9):1140-1145.

27. Hsu A. As the pandemic recedes, millions of workers are saying, ‘I quit’. NPR news report. NPR.org. June 24, 2021. Accessed November 21, 2021. https://www.npr.org/2021/06/24/1007914455/as-the-pandemic-recedes-millions-of-workers-are-saying-i-quit

28. Kornfield M, Timsit A. Vaccine mandates stoked fears of labor shortages. But hospitals say they’re working. The Washington Post. October 16, 2021. Accessed November 21, 2021.  https://www.washingtonpost.com/health/2021/10/16/hospital-covid-vaccine-mandate/

29. Walt V, Warner B. No jab, no job: Europe’s workers face tough measures as politicians lay down the law. Fortune. Published October 14, 2021. Accessed November 21, 2021. https://fortune.com/2021/10/14/covid-vaccine-fired-europe-workers-france-italy-draghi-macron-green-pass/

30. Bean M. 5 Public health issues flaring up amid the pandemic. Becker’s Hospital Review. Published August 14, 2021. Accessed November 22, 2021. https://www.beckershospitalreview.com/public-health/5-public-health-issues-flaring-up-amid-the-pandemic.html

31. Brownson RC, Burke TA, Colditz GA, Samet JM. Reimagining public health in the aftermath of a pandemic. AJPH. Published October 7, 2021. Accessed November 21, 2021. https://ajph.aphapublications.org/doi/10.2105/AJPH.2020.305861

32. History of EUnetHTA. European Network for Health Technology Assessment. Accessed November 21, 2021. https://www.eunethta.eu/about-eunethta/history-of-eunethta/

33. RBC Capital Markets. The convergence of healthcare and technology. RBCCM.com. Accessed November 22, 2021. https://www.rbccm.com/en/gib/healthcare/episode/the_healthcare_data_explosion

34. Culbertson N. The skyrocketing volume of healthcare data makes privacy imperative. Forbes. Published August 6, 2021. Accessed November 22, 2021. https://www.forbes.com/sites/forbestechcouncil/2021/08/06/the-skyrocketing-volume-of-healthcare-data-makes-privacy-imperative/?sh=35d2dd976555

35. Interoperability in Healthcare. Healthcare Information and Management Systems Society, Inc. Accessed November 22, 2021. https://www.himss.org/resources/interoperability-healthcare

36. About the Food and Drug Administration (FDA) Sentinel Initiative. Sentineliniative.org. Accessed November 22, 2021. https://www.sentinelinitiative.org/about_us

37. AI in Healthcare: How It’s Changing the Industry. Healthcare Information and Management Systems Society, Inc. Accessed November 22, 2021. https://www.himss.org/resources/ai-healthcare-how-its-changing-industry

38. OPTUM Labs. Using RWD in regulatory decision-making. www.optumlabs.com. Accessed November 22, 2021. https://www.optumlabs.com/work/data-regulatory-decision.html

39. Franklin JM, Patorno E, Desai RJ, et al. Emulating randomized clinical trials with nonrandomized real-world evidence studies. Circulation. 2021;143:1002-1013. doi: 10.1161/CIRCULATIONAHA.120.051718

40. Prosperi M, Guo Y, Sperrin M, et al. Causal inference and counterfactual prediction in machine learning for actionable healthcare. Nat Mach Intell. 2020;2:369-375.

The Society would like to thank all of the members of the Health Science Policy Council and its committees for their thought leadership and advisory role in guiding the development of the “2022-2023 Top 10 HEOR Trends” report.