Conference Coverage: AACR, AMCP, ISPOR

June 18, 2020

Coverage from virtual meetings of the American Association of Cancer Research, the Academy of Managed Care Pharmacy, and the International Society for Pharmacoeconomics and Outcomes Research.

AACR: COVID-19 Increases Overall Risk of Death, Complications in Patients With Cancer, Study Shows

Patients with cancer who become infected with coronavirus disease 2019 (COVID-19) are far more likely to die or suffer severe complications than patients with COVID-19 who do not have cancer, according to new findings.

In a study released April 28, a team of researchers from China, Singapore, and the United States showed that patients with cancer who develop COVID-19 were more likely to develop in-hospital infections or chest distress, or spend time in the intensive care unit (ICU). Patients being treated with immunotherapy appear to be at particularly high risk. The results were published online in Cancer Discovery and reported at the virtual meeting of the American Association of Cancer Research.1

With a yearly estimate of 1.8 million new cancer cases for the United States in 2020, the patient population with compromised immune systems who could be affected by COVID-19 will only grow.2 The results were based on data collected through March, when 800,000 people in more than 200 countries had become infected with COVID-19, and there had been more than 40,000 deaths.1

As of April 28, more than 3 million people were infected worldwide, including 1“million in the United States; more than 214,000 have died, including more than 55,000 in the United States.3

The pandemic has left in its wake forced treatment delays, shuttered clinical trials, and decimated pain medication supplies, said Howard A. “Skip” Burris, MD, chief medical officer and executive director of the Sarah Cannon Research Institute and president of the American Society of Clinical Oncology. In a presentation to the virtual meeting of the Community Oncology Alliance, Burris called these challenges “daunting,” because they can be “devastating for patients with fast-moving or hard-to-treat cancers.”4

Fourteen hospitals from Wuhan, China, provided data for the randomized, controlled study of 641 patients enrolled between January 1, 2020, and February 24, 2020. There were 2 patient cohorts: patients without cancer who had COVID-19 (n = 536) and patients hospitalized with cancer and COVID-19 (n = 105). The mean ages were 64.00 and 63.50 years, respectively. They were matched by hospital, length of hospital stay, and age.

Overall, the patients with cancer fared worse compared with the patients without cancer, respectively, in number of in-hospital infections (19.04% vs 1.49%; P <.01) and smoking history (34.28% vs 8.58%; P <.01). In addition, there were more instances of chest distress in patients with both cancer and COVID-19 than among those with COVID-19 only: 14.29% versus 6.16% (P = .02).

Results were divided by clinical outcomes, cancer type, cancer stage, cancer treatment, and timeline of severe events. In these subcategories, patients with both cancer and COVID-19 fared worse across the board.

Clinical outcomes. The overall result in this subcategory was that the condition of patients with cancer and COVID-19 declined more rapidly than those with COVID-19 and no cancer. Specifically, they also had higher rates of the following:

• Death (odds ratio [OR], 2.34; 95% CI, 1.15-4.77; P = .03)

• ICU admission (OR, 2.84; 95% CI, 1.59-5.08; P <.01)

• At least 1 severe complication (OR, 2.79, 95% CI; 1.74-4.41; P <.01)

Cancer type. The most common cancers among patients with COVID-19 and cancer were lung (20.95%), gastrointestinal (12.38%), breast (10.48%), thyroid (10.48%), and hematological (ie, leukemia, lymphoma, myeloma) (8.57%). From this cohort, patients with hematological and lung cancers, respectively, fared the worst, with higher overall rates of death (33.33% and 18.18%), ICU admissions (44.44% and 27.27%), risk of severe/critical symptoms (66.67% and 50.00%), and possible use of invasive mechanical ventilation (22.22% and 18.18%).

Cancer stage. Cases of metastatic cancer (stage IV) in patients with COVID-19, compared with patients with nonmestatic cancer, led to overall higher risks for death (OR, 5.58; 95% CI, 1.71-18.23; P = .01), ICU admission (OR, 6.59; 95% CI, 2.32-18.72; P <.01), severe conditions (OR, 5.97; 95% CI, 2.24-15.91; P€<.01), and use of invasive mechanical ventilation (OR, 55.42; 95% CI, 13.21-232.47; P€<.01).

Cancer treatments. There were higher rates of death and chances of critical symptoms if patients with cancer and COVID-19 received immunotherapy: 33.33% and 66.67%, respectively. However, if these patients instead underwent surgery to treat their cancer, they had higher rates of ICU admission (37.50%) and use of invasive mechanical ventilation (25.00%).

Timeline of severe events. The principal measure here was hospital length of stay. The cohort with both cancer and COVID-19 had a 52.2% longer mean (SD)

hospital stay compared with the COVID-19—only group: 27.01 (9.52) days versus 17.75 (8.64) days. “Although COVID-19 is reported to have a relatively low death rate of 2% to 3% in the general population, patients with cancer and COVID-19 not only have a nearly 3-fold increase in the death rate than that of COVID-19 patients

without cancer, but also tend to have much higher severity of their illness.

Patients with cancer also have a 10-fold higher incidence of nosocomial SARS-COV-2 infections than patients without cancer. Altogether, these findings suggest that patients with cancer are a much more vulnerable population in the current COVID-19 outbreak,” the researchers concluded.

They suggested additional studies using a larger patient population, either from China or several countries, because data are still very limited on the patient population that has both cancer and COVID-19 and because the 3 continents with the highest rates of COVID-19 (Asia, Europe, North America) also have the highest incidences of cancer. Therefore, the results may not be generalizable.

References

1. Dai M, Liu D, Liu M, et al. Patients with cancer appear more vulnerable to SARS-COV-2: a multi-center study during the COVID-19 outbreak. Cancer Discov. Published online April 27, 2020. aacr.ent.box.com/s/2mh5713e6irjvcz6hb4c6y72bu1pljxq.

2. Cancer stat facts: common cancer sites. National Cancer Institute / Surveillance, Epidemiology, and End Results Program. Accessed April 29, 2020. seer.cancer.gov/statfacts/html/common.html.

3. Coronavirus Resource Center. Johns Hopkins University & Medicine. Accessed April 28, 2020. coronavirus.jhu.edu/us-map.

AACR: Phase 3 EMBRACA Findings Suggest No Overall Survival Benefit With Talazoparib in Advanced BRCA-Mutated Breast Cancer

4. Shaw M. We must bring clinical trials to our communities, Burris says. The American Journal of Managed Care®. Published April 24, 2020. Accessed April 28, 2020. ajmc.com/conferences/coa2020/we-must-bring-clinical-trialsto-our-communities-burris-says.Data from the phase 3 EMBRACA trial presented April 27 at the American Association for Cancer Research annual meeting indicated that the PARP inhibitor talazoparib exhibited no statistically signifi cant benefi t in the secondary end point of overall survival (OS) in patients with metastatic HER2-negative breast cancer and mutations in the BRCA1/2 genes. However, OS findings may have been understated, as most patients included in the study went on to receive subsequent systemic therapies.1

EMBRACA is the largest trial to date examining PARP monotherapy in patients with germline BRCA-mutated, HER2-negative advanced breast cancer. Previously, the trial’s primary analysis found that patients treated with talazoparib experienced signifi cantly prolonged progression-free survival (PFS) compared with chemotherapy (median PFS, 8.6 months vs 5.6 months), which led to its FDA approval in 2018.

While PFS was substantially benefi ted by talazoparib, OS can prove a challenge for patients with metastatic breast cancer due to the availability of numerous treatment options, said Jennifer Litton, MD, professor of breast medical oncology at MD Anderson Cancer Center, who presented results during AACR.2 The trial randomized 431 patients (2:1) with locally advanced or metastatic HER2-negative breast cancer and hereditary BRCA1/2 gene mutations to receive either talazoparib

(nš=š287) or physician’s choice of treatment of singleagent therapy (n = 144), including capecitabine, eribulin, gemcitabine, or vinorelbine.

In the trial, nearly half of patients in the talazoparib group received a subsequent PARP inhibitor or platinum therapy compared with almost 60% of patients in the chemotherapy group. When stratifi ed for only those receiving PARP inhibitors, approximately one-third of patients in the chemotherapy group received a subsequent PARP inhibitor compared with only 4.5% of those administered talazoparib.

The subsequent treatments provided were highlighted by Litton as she described how they may have potentially infl uenced results. In fact, after carrying out 2 sensitivity analyses to account for subsequent PARP inhibitor and/or platinum therapy, data suggest that the OS analysis underestimated the treatment benefit of talazoparib.

Aligned with findings from the primary analysis, patient-reported quality-of-life measures were improved among those administered talazoparib compared with chemotherapy as shown by a prolonged time to deterioration of overall health (26.3 months in the talazoparib group vs 6.7 months in the chemotherapy group).

“Talazoparib remains an option for patients with advanced breast cancer and a germline BRCA mutation due to its improvements in progression-free survival,” said Litton. “Other advantages include it being an oral once-daily option, as well as [the] improvements in quality of life [it] demonstrated.”

References

1. Litton JK, Hurvitz SA, Mina LA, et al. CT071: talazoparib (TALA) in germline BRCA1/2 (gBRCA1/2)-mutated human epidermal growth factor receptor 2 negative (HER2—) advanced breast cancer (ABC): final overall survival (OS) results from randomized phase 3 EMBRACA trial. Abstract presented at: American Association of Cancer Research Virtual Annual Meeting; April 27-28, 2020. https://www.abstractsonline.com/pp8/#!/9045/presentation/10773

AMCP: COVID-19 Upends Drug Purchasing Patterns, and More Disruption Likely, IQVIA Expert Says

2. Study finds no overall survival benefit, but improved quality of life with talazoparib in advanced BRCA-mutated breast cancer. News release. EurekAlerts. April 27, 2020. Accessed April 29, 2020. eurekalert.org/pub_releases/2020-04/uotm-sfn042420.phpThe global pandemic of coronavirus disease 2019 (COVID-19) has wreaked havoc on every part of the pharmaceutical business, from purchasing patterns to drug launches, and the upheaval will continue when Medicaid enrollment booms, according to an industry expert.

Douglas M. Long, MBA, vice president of industry relations for IQVIA, surveyed the pandemic’s eff ects on April 20, 2020, as he kicked off AMCP eLearning Days, a webinar series held in place of the annual meeting of the Academy of Managed Care Pharmacy (AMCP), which was canceled due to COVID-19.

Telemedicine’s explosion and the increased authority given pharmacists to help patients during the crisis could be positive changes that last beyond the pandemic, Long said. But his review of data shows that lockdowns and social distancing have been mostly disruptive to the health care system, and some players may not survive. Among the trends he sees:

• Medicaid enrollment could rise between 5 million and 10 million people, as record numbers of Americans lose jobs and employer-sponsored health care. Historically, Medicaid patients must wait longer to see a doctor, which could delay new prescriptions or refills.

• Rates of prescription abandonment, which were already rising along with out-of-pocket costs, could increase, and the price at which patients leave drugs at the counter could fall.

• Recently reported data show that 80% of clinicians are under “severe” or “close-to-severe” fi nancial strain, and only 34% have cash on hand to last 4 weeks.

• 5% of clinicians have closed temporarily, and 61% are uncertain if they will be open after 4 weeks.

• While telehealth visits have soared, with claims rising 1581% from prior levels by the week of March 27, the revenue will not off set losses from in-person visits, laboratory tests, and other income streams.

Overall, Long said, COVID-19 could lead to “an overall decline in health,” as patients delay being seen for new conditions, and new treatments are not started.

On the plus side, the number of physicians using telehealth for the first time rose more than 3000%. Like other experts, Long sees the rise of telemedicine as a phenomenon that’s here to stay. “It’s going to be hard to put that back in the bottle,” he said.

In the weeks leading into lockdowns, prescription purchasing patterns shifted to more 90-day fills, as patients stocked up on drugs they would need for the coming weeks. Long spotted spikes in prescriptions for drugs being used in a COVID-fi ghting cocktail—chloroquines and azithromycin (Zithromax)—as well as the HIV antiviral ritonavir—as well as tadalafi l, sold as Cialis.

Thus, Long will be eyeing June prescription figures to see whether patients get refi lls when the 90-day supplies run out, or whether any shortages emerge. Right now, he said, the biggest shortages are in sedatives used by hospitals.

COVID-19’s long-term fallout won’t be fully felt for months or years, as clinical trials stall and companies opt to delay drug launches. In response to a question, Long said it wouldn’t be a surprise if the FDA is forced to delay some approval dates under the Prescription Drug User Fee Act.

Specialty drug administration is down 64.8% from pre-COVID levels, but the rate varies by disease area: Treatments for multiple sclerosis and diabetic retinopathy declined far less than vaccines and cosmetic procedures.

In-office contraception treatments are down 55%, and new fertility treatments have plummeted 70%, while those who have cycles to use are moving to complete them.

“Oncology is holding up much better than expected,” Long said, adding that he would not be surprised to see a shift to oral oncolytics.

COVID-19 has increased attention on social determinants of health, Long noted, as issues such as poor housing, low incomes, and lack of education factor heavily in medication adherence rates. The worst state for adherence is Mississippi, followed by Texas; neither state has expanded Medicaid.

Generics and Biosimilars

These drugs were making an impact in the marketplace prior to COVID-19, and Long says they are much needed. Overall drug spending was up 4% in 2019, but the annual spike was 11% in specialty pharmacy and just 1% in traditional drugs. Specialty sales had just about approached 50% of the market when the virus hit. Most of the late-stage pipeline growth is fueled by specialty and what Long called “niche” therapies.

In the past decade, generics and biosimilars have saved $96 billion; last year saw a record number of biosimilar approvals, but many of these products do not ultimately launch. “We are going to need specialty generics and biosimilars if we are to hold down spending going forward,” Long said.

Use of biosimilars in oncology “is starting to hit a critical mass,” Long said. However, the focus on drug prices—or at least what people pay at the counter—has eased in the wake of COVID-19, and many reforms to help biosimilars reach the market were connected to that movement.

The unknowns in managed care pharmacy abound. When will people go back to work? How quickly will we recover? Both are diffi cult to answer, especially

with IQVIA’s own projections of a nationwide peak in the virus ranging from April 30 to May 11.

AMCP: More Biosimilar Launches in 2020, Presenters Say

And then, the biggest unknown of all, said Long: “Will there be a second round of this in the fall?”The year 2020 has seen 4 biosimilar launches in the United States through mid-April, and those could be augmented by several more, although the coronavirus disease 2019 (COVID-19) pandemic has introduced a wild card to the mix, said presenters at the American Academy of Managed Care Pharmacy (AMCP) eLearning Days virtual meeting.

But the pipeline from 2021 to 2025 is stocked with at least 5 approved biosimilars to adalimumab, and potentially 4 others, all of which could conceivably launch in

2023, and 14 other potential biosimilar products, which could make the next several years a very active growth time for the US biosimilar space, the presenters said.

The pace of clinical trials has also been aff ected, but with regard to approvals, the FDA’s most recent notice has been that there will be no “near-term” eff ect on these, said Leslie Fish, RPh, PharmD, who co-presented with Jeffrey Casberg, MS, RPh, in the April 21 session, “Drug Pipeline: Traditional Pharmaceuticals and Biosimilars.” Fish and Casberg, both experts on the pharmaceutical pipeline, are with IPD Analytics.

One possibility is that any delays caused by COVID-19 in 2020 could lead to a slew of backlogged approvals or launches in 2021, Fish said.

Some companies have stated that they will slow their existing studies or hold up new studies of various agents, because they’re now working on COVID-19

therapies or vaccines, she added.

The Biosimilar Launch Pad for 2020

Multiple biosimilar agents could be reaching the market in the oncology space for the remainder of 2020, Fish and Casberg said. One such agent is HSP-130,

a pegfi lgrastim biosimilar that Hospira and Pfi zer intend to launch against Amgen’s Neulasta originator drug. However, HSP-130, expected to launch this June, would join other pegfi lgrastim biosimilars already on the market, including Ziextenzo, Udenyca, and Fulphila.

An additional drug in this class is Rolontis (efl apegrastim). The FDA accepted the application for this investigational granulocyte-colony stimulating factor

analogue in December 2019. Rolontis, under development by Hanmi Pharma and Spectrum, is targeted for an October 2020 launch. Another biosimilar that could debut this year is a bevacizumab copy (SB8) that Samsung Bioepis and Merck hope to bring to the US market in September, according to Casberg and Fish. Two bevacizumab biosimilars, Mvasi and Zirabev, introduced last year, are on the market currently. The reference product is Avastin.

One other bevacizumab biosimilar candidate, Bmab-100, is under development by Biocon. This also has the potential to augment the number of biosimilar

bevacizumabs available to providers, Fish said.

Last in the oncology class of emerging biosimilars is a rituximab biosimilar, ABP 798, the product of an Amgen/Allergan partnership, with a debut scheduled for the fourth quarter of 2020. It would compete with 2 biosimilars already launched: Truxima by Celltrion and Ruxience by Pfizer. The reference product is Rituxan by Biogen and Genentech.

“With this many biosimilars on the market, and available, there will be a decrease in costs. This decrease in cost will be seen in increasing rebates and better contracting in both the branded and biosimilar space,” Fish said.

Loose Ends in Patent Litigation

Casberg said that eyes have been following the attempts by Sandoz to bring an etanercept biosimilar (Erelzi) to market. That issue was held up in court over patent litigation with originator manufacturer Amgen. “We’d been waiting for an Amgen versus Sandoz decision for quite a while. Turns out, Amgen prevailed, and we likely will not see an Enbrel biosimilar until 2029,” Casberg said. “There is still 1 pending court case that could change that, but odds are in favor of Amgen keeping protection for Enbrel through 2028/2029.”

Two infl iximab biosimilars, Infl ectra and Renfl exis, are on the market currently, and a third, Avsola (Amgen) will likely launch this year, Casberg said. Avsola was approved in December 2019. “A couple of other infliximab biosimilars are coming down the road,” he said. “Those won’t be available for another year or more.”

Hopes for an adalimumab biosimilar to AbbVie’s blockbuster Humira product had been on hold owing to patent litigation. Much of that legal activity has subsided, Casberg said, resulting in individual patent settlements with 9 potential competitors, each with an agreement to launch at some point in 2023. “So, 2023 will be a big year for biosimilar Humira,” he said. Of the 9 products for which settlements have been hammered out, 5 are approved by the FDA. Looking down the road a few years, “quite a few bigger products [are] in the works,” Casberg said. From 2021 to 2025, up to 14 additional biosimilars could be launched. These include biosimilars for ranibizumab, afl ibercept, eculizumab, ustekinumab, cetuximab, omalizumab, botulinum toxin, natalizumab, abatacept, certolizumab pegol, darbepoetin alfa, golimumab, palivizumab, and ado-trastuzumab emtansine.

Novel drug approvals by the FDA have recently been on the uptick, Casberg noted, with 48 last year and a record 59 in 2018. “This year, we’ll have to see if

COVID-19 has an impact on approvals,” he added.

AMCP: WellDyne Executive Says Formulary Exclusions Are on the Rise

As for launches so far in 2020, 3 trastuzumab biosimilars have reached the market: Ontruzant, Herzuma, and Trazimera. Also, Pfizer launched its rituximab biosimilar, Ruxience, in January. Overall, the FDA has approved 26 biosimilars, and of those, 17 have been launched.EXCLUSIONARY STRATEGIES, the practice of leaving drugs off formulary to save money and direct patients to more clinically eff ective therapies, are on the rise, and biosimilars can be structured into these strategies to make them effective, said Jeenal Patel, PharmD, BCGP, a formulary manager for WellDyne, who spoke April 22, 2020, at the AMCP eLearning Days virtual meeting, which replaced the annual meeting of the Academy of Managed Care Pharmacy (AMCP).

Higher utilization and higher unit costs of specialty drugs continue to drive overall spending upward in the US market, and these rising costs “put pressure

on patients, employers, and providers,” Patel said. WellDyne is a pharmacy benefi t manager (PBM) based in Lakeland, Florida.

Small Volume Increase, High-Cost Result

The year 2018 saw 5.8 billion 30-day equivalent specialty medication prescriptions dispensed, representing a 2.7% increase from 2017, Patel said. “This was primarily driven by new therapies and expanded indications for existing products,” she pointed out.

Specialty medications represent 2.2% of total drug prescription volume, Patel said. Use of this class of drugs has increased at twice the rate of other drugs. “This percentage may seem small, but specialty drugs contribute to a large, large portion of drug spend,” she said.

More specialty medications can be expected to debut, as “manufacturer pipelines remain robust,” which suggests that costs will push higher, she said. These trends are pushing payers toward strategies such as formulary exclusion to control costs, Patel said.

Some of the main tactics employed include prior authorization, quantity limits, multi-tier plan design, and step therapy. They help payers to mitigate waste and focus on effi cacious, safe, and cost-saving alternatives, she said.

Exclusions Are a Stronger “Deterrent”

But formulary exclusions are gaining popularity as a means of managing the type and cost of medications used. “Many times when you have an excluded or not-covered product, it’s perceived to be a stronger deterrent to usage, versus to having the product placed on a higher tier, or controlled by prior authorization or step therapy,” Patel said.

Cosmetic and fertility drugs are examples of drugs that are often placed on exclusion lists, she said. About three-fourths of 273 employers surveyed in a report used formulary exclusions, compound exclusions (nonallowed drug ingredients), or prescription exclusions, Patel said. “So, very much, it’s a common practice in formulary management today.

“Even in the specialty arena, we’re starting to see limited drugs available on formulary for narrow therapeutic areas and unique oncology indications, for example. We’re seeing decreased redundancy across the board in broader categories, such as psoriasis and arthritis,” Patel said.

The risk of exclusion can have downward effect on pricing, as it encourages drug discounting for better formulary placement. “It can also encourage manufacturers to demonstrate the value of their products, while payers are focused on trying to balance costs,” she said.

Patel said signs point to rapid growth of the use of exclusions in the future, although she cautioned that these should be utilized to promote use of the most effective drugs while saving money and reducing waste. She also said that exclusions should not be allowed to disrupt ongoing patient therapy.

PBMs are finding exclusions to be “one of the more attractive ways to lower costs” and develop a more competitive pricing landscape, she said. Exclusions may apply to drugs with “hyperinfl ationary” tendencies, or what Patel termed “egregious year-over-year price increases.” Other agents that find themselves on the outside of formulary lists and looking in are “me-too” drugs that have different ingredients but no added clinical value; high-cost brands for which there are generic alternatives; high-cost generics; and “nonessential drugs,” which have not been approved by the FDA.

“Granular Management” of Costs

“A lot of opportunities are out there when it comes to more granular management of these drugs,” Patel said, noting that huge cost savings are possible by looking for alternatives to high-priced, low-value products.

One tactic is to delay formulary placement for new drugs to market. This allows time to review the clinical evidence for or against a particular product. It also provides some buff er against aggressive launch promotion by manufacturers.

And it enables the creation of benefit design programs that incorporate product rebates, for example, thereby allowing for better cost strategies, Patel said. These product placement delays typically do not include drugs for rare or orphan diseases.

To reverse the increasing costs of drugs, Patel suggested a 3-part strategy: Identify the high-cost drugs that can be replaced with lower-cost alternatives; eliminate excessive utilization by employing formulary exclusion, prior authorization, and step therapy; and substitute higher-value agents via a patient engagement program.

“We have to get better,” she said. “We have to identify and substitute with clinically appropriate, lower-cost alternatives that drive the same therapeutic outcomes, and that’s going to be a combination of monitoring the robust pipeline for new generic launches, or looking to see if there are biosimilars to help promote lower cost.”

That’s not to say that exclusionary strategies don’t sometimes lead to higher-cost medications. Patel cited evidence that relatively ineffective diabetes medications on formulary led to an increase in overall costs partly because providers and patients were shifting to higher-cost medications.

Challenges of implementing exclusion practices include patient dissatisfaction with therapy changes and disruption to clinical progress, such as loss of disease control, impact on adherence, or inappropriate changes that increase total costs of care. Providers may complain and there may be a rise in appeals of prior authorization denials, Patel said.

ISPOR: Panelists Weigh the Success of APMs

Alternative payment models (APMS) have long been an experiment in the health care community for incentivizing high-quality, cost-effective care that maintains or improves outcomes, but are they working? This question was addressed by panelists on May 19 during the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) annual meeting, Virtual ISPOR 2020, held May 18-20.

APMs have notched some successes, said Elizabeth Oyekan, PharmD, a senior executive at Precision Value & Health in Centennial, Colorado. There have been cost

savings and improvements in care, but APMs also are connected with higher spending and have been strongly resisted, “especially when it comes to arrangements that require [providers] to assume fi nancial risk,” Oyekan said. Even so, it is clear that APMs have outperformed strict fee-for-service (FFS) payment systems on many performance and quality measures over time, including in diabetes care, preventive services, and hospital admissions, said Oyekan. Accountable care organizations

(ACOs), groups of medical providers that may operate under an APM model, have achieved similar results.

Patient Enrollment Is Up

“APMs and ACOs have benefi ted fi nancially from these improved quality measures,” Oyekan said. “And what we’ve seen is increased [patient] enrollment in addition to the fi nancial benefi t.” Those ACOs with 4 or more stars in the Medicare Advantage Star Rating System have seen a 13.1% increase in enrollment, she noted. “For those that have the coveted 5-stars rating, we have seen that they now have year-round enrollment, which is of extreme benefit to many organizations.”

An additional benefi t is that the administrative burden has been lessened through fewer quality measure requirements. The patient “experience” with health care systems has not deteriorated during the switch from FFS to APMs or ACOs, Oyekan said. “There was fear of some potential major impact, and that has not happened at this point.”

Some CEOs have been able to reduce costs of care by trimming overutilization of lower-value services or therapies and focusing on higher-value therapies, noted Oyekan. “And also, the bonus payments [available to APMs and ACOs] have become a new source of revenue for these entities.”

However, in many cases, APMs and ACOs create incentives to reduce spending without building in appropriate quality protections, and for many APMs in the commercial sector, only minor care quality improvements have been achieved. The Medicare Shared Savings Program, which governs 517 ACOs, has seen increased Medicare spending, causing concern for CMS, Oyekan said.

APMs Are a Major Undertaking

“We’ve heard from many providers, and for many the question is, considering the signifi cant behavioral and practice changes that have to occur and the investments it takes to become an APM, is it really worth it? And for many, with regard to the payments they have seen and the bonuses, they’re not quite sure that the change is worth what is being incentivized at this time,” said Oyekan.

The bottom line is that although the APM may not be the “fi nal answer” for achieving value-based care, it has provided a good initial framework for grappling with improvements in value of care, Oyekan pointed out.

The panel included Anupam B. Jena, MD, PhD, the Ruth L. Newhouse Associate Professor of Health Care Policy at Harvard Medical School in Boston. With respect to the scale of APM involvement in health care, more than $3 of every $5 of health care spending is linked to APMs, Jena said.

Some APMs may include elements of FFS spending and bundled care, in which a single payment is received for a suite of services associated with a single clinical episode.

Have APMs Reduced Admissions?

The FFS APM has been a focus of concern “in terms of whether or not it’s actually reduced readmissions or whether it’s an unintended byproduct of increasing mortality. There are selection concerns as well, in terms of the types of patients who get hospitalized as a result of the program and the incentives that it places. Nonetheless, I think that this program has been very impactful,” Jena said.

A key attribute of these models, Jena said, is that the quality of data and the ability to measure results are much greater now than 20 or 25 years ago.

Further, patient satisfaction is now a metric with many APMs. Patient satisfaction drives patients to a particular health care center, Jena noted. “The interplay between

treatment eff ectiveness and patient satisfaction is going to be quite relevant—more relevant, I think, with APMs.”

Ultimately, for APMs to succeed, there has to be accountability, said Michael Barr, MD, MBA, executive vice president of the National Committee for Quality Assurance in Washington, DC. However, it’s important to clearly defi ne the patient population for which the health care entity will be held accountable. Then, performance data must be supplied regularly to guide care decisions, and these data should be acted upon.

Data for the Sake of Data?

Too much data, or data for the sake of data, can make ineffi cient workflows more inefficient, Barr said. “Let’s work on making data effi cient and not expect

or require any diversion to check a box if any question is not directly related to the delivery of care,” he suggested.

Similarly, outcome measures should be chosen with care. “No APM will work unless the measures matter,” noted Barr. “The best way to undermine an accountability model is to select and highlight measures that are not perceived by clinicians in their teams—or patients, to some degree—to be relevant.” Measures should be logical, feasible, usable, manageable, timely, and actionable, he said.

Quality measures have evolved, Barr explained. Paperbased measures included claims information, chart extractions, and patient surveys. The next wave was electronic. Electronic health records provided a better way of organizing data. From there, digital quality measures (DQMs) emerged.

“This could be our future if we start working together,” Barr said of DQMs. Patient data could be aggregated from multiple providers and organized by compatible systems linked to decision support. Treatment planning could be updated when guidelines change or new therapeutics are introduced, much the same way smartphone applications are updated. “This is the future, now,” exclaimed Barr.

ISPOR: Panelists Advocate for Global Collaboration in RWE Effort

Global collaboration plays an important role in generating real-world evidence (RWE), and these consultations must involve countries in the developing world as well as corporate stakeholders to actively aid in health care decision making, said panelists during the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) annual meeting, Virtual ISPOR 2020.

RWE has “appeared to promise solutions that would completely revolutionize the way we generate evidence for new drugs and, at the same time, offer both a faster and better evidence basis to the key institutional decision makers,” said Pall Jónsson, PhD, MRes, associate director of research and development at the National Institute for Health and Care Excellence, in Manchester, United Kingdom.

“At the same time, those who are more skeptical emphasize the potential pitfalls of using nonrandomized data and have highlighted issues such as the difficulties of establishing causal inferences, for instance, through such issues as data quality and the potential bias and confounding that you might find in such datasets,” Jónsson said.

Challenges Overcome

Advances in generating and synthesizing data into evidence have overcome some of those challenges, Jónsson said. And many organizations have moved forward with eff orts to obtain value from RWE. This includes the GetReal Initiative, a European Union partnership with the pharmaceutical industry with a mission to facilitate the adoption and implementation of RWE in drug development and health care decision making.

The ISPOR panel represented members from the GetReal Initiative Think Tank, a multistakeholder group of European and US RWE experts from government, industry, and the health care community. “The think tank with this multisector background will help us work out how we can develop consensus and guidance on both key policy and technical challenges facing RWE generation and views,” Jónsson said.

For global collaboration to be successful, panelists said, ideas from lower- and middle-income countries must be incorporated as well as those from higher-income countries. In fact, the coronavirus disease 2019 pandemic has demonstrated that wealthier countries may be at a loss for dealing with this health care crisis, said panelist Bart Barefoot, JD, director, Value Evidence & Outcomes and Real World Evidence Policy and Advocacy, at GlaxoSmithKline in London, United Kingdom.

“I think that really illustrates how countries and regions that are maybe objectively considered higher-income or better-resourced don’t necessarily have better approaches or better answers than countries or regions that are considered lower- or middle-income. So, I think we all have a lot to learn from one another,” Barefoot said.

Although product sponsors make decisions on how data are collected, outside stakeholders—including payers, health technology assessment organizations, regulators, patients, academics, and developers of health care interventions—can all infl uence those decisions, said Barefoot.

“Consortia approaches allow us to learn from each other. Most importantly, from the industry perspective, to achieve buy-in from decision makers, they must be on the journey with us. Or, to put it another way, we must be on the journey with them and working collaboratively,” noted Barefoot.

Monetary and Time Constraints of Data

Additionally, global collaboration shouldn’t be competitive data sharing should be welcomed, despite the fact that today, data are considered commercial, said panelist Alison Bourke, BSc, MSc, scientific director for IQVIA in London.

“We tend to sell data and expertise and consultancy,” Bourke said of IQVIA. “And because we sell it, it seems a bit strange going along to a collaboration and sharing that data. [But]…what you’re looking for is trying to get views aligned, or at least overlapped, to advance that RWE acceptance. What’s really important is a trusting environment that is noncompetitive.”

Bourke and Barefoot both mentioned that these initiatives can be time-consuming, especially if many people with varying objectives are involved. Large variations in geography, health care delivery systems, law, and culture can all prolong the process as well.

“These meetings are meant to be a safe space, and no comments are attributed to a [particular] person. In fact, we encourage debate, because for those particularly challenging areas, we really want to dig into what is the crux of the problem and how can we build consensus,” said panelist Nirosha Mahendraratnam©Lederer, PhD, MSPH, who manages the Real-World Evidence Collaborative at the Duke—Margolis Center for Health Policy, in Washington, DC.