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The Pharmacoeconomics of Oral and Self-Administered Cancer Treatments

December 30, 2021

Oral and patient-administered forms of chemotherapy have come a long way since the 1950s, when mercaptopurine and methotrexate were first approved by the U.S. Food and Drug Administration (FDA). Several oral anticancer medications (OAMs) have since gained regulatory approval and, increasingly, these agents are joining the ranks of standard-of-care for the treatment of hematologic malignancies and other cancers.

OAMs have been embraced because of their convenience, efficacy, and safety but, because insurers cover them differently than intravenous drugs, prescribing OAMs can impose burdensome levels of cost-sharing on patients. And it's easy to see how: with list prices often exceeding $100,000 per year, almost any level of proportional cost-sharing could be prohibitive.1

This disparity in coverage between OAMs and intravenous drugs places hematologists in a medical and ethical predicament, according to Alan Rosmarin, MD, professor of medicine at University of Massachusetts Medical School and chief mission officer of the Samuel Waxman Cancer Research Foundation in New York.

"As hematologists, we want our patients to have the most effective drugs – those that improve their lives," explained Dr. Rosmarin, who also is chair of the American Society of Hematology's (ASH's) Committee on Government Affairs. "We don't care about what form the drug is in, but we don't want to give a second-class treatment because cost is an issue for the patient – especially when costs are due just to idiosyncrasies in insurance-plan design."

"Oral parity" is the proposed legislative solution that could alleviate coverage discrepancies between oral and intravenous anti-cancer medications. Advocates for oral parity laws also want to bring financial relief to patients who are shouldering unmanageable drug costs. Here, ASH Clinical News examines the advantages and disadvantages of OAMs and the efforts underway to address financial issues associated with their use, as well as those of other anti-cancer drugs.

America's Byzantine Insurance Structure

OAMs are used across a large and growing range of cancer types and constitute the first choice of treatment for remission induction and maintenance in certain hematologic malignancies. In chronic myeloid leukemia (CML), for example, firstline treatment involves an oral tyrosine kinase inhibitor.

"To give anything but a tyrosine kinase inhibitor these days if these drugs are available would be malpractice, unless that person was going to get a transplant for some reason," Dr. Rosmarin said. Nevertheless, he and other oncologists regularly encounter patients with limited access to OAMs because of unmanageable out-of-pocket (OOP) costs.

Most insured cancer patients in the U.S. contribute financially to their medications. When the treatment is an infused anti-cancer agent, the payment is usually covered under the health plan's "medical benefit;" patients pay a standard, flat co-payment for an office visit that may include outpatient intravenous medications.

However, patient-administered anti-cancer drugs (mostly oral agents, but self-injected drugs also are included in this classification) generally are covered under the patient's "pharmacy benefit." Oral and self-injected drugs tend to appear on separate specialty tiers, which may have higher co-payments than intravenous drugs. Covered drugs might also have high deductibles and annual benefit caps, all of which result in proportionally higher cost-sharing than what is required for parenteral drugs administered in a clinic or hospital setting – even if the actual costs of the drugs are similar.

And, if patients can't afford their medications, they can't benefit from them. Research has shown that sticker shock impacts treatment adherence. A study of claims data from more than 38,000 people who received a new prescription for one of 38 OAMs from 2014 to 2015 found that, as OOP costs rose, fewer patients filled their prescriptions.2

When the required co-pay was less than $10, only 10 percent of patients failed to pick up their prescriptions. This figure jumped to 32 percent for patients whose OOP costs were between $100 and $500, and to 41 percent when OOP costs were between $500 and $2,000. When the OOP costs exceeded $2,000, nearly half of patients (49%) never filled their prescriptions.

Delayed initiation of treatment was also significantly higher for those with higher cost-sharing burdens.

"Patients in our study were facing a new cancer diagnosis or a change in their disease that required a new treatment. Imagine leaving your doctor's office with a plan, ready to start treatment, only to find you can't afford it," lead author Jalpa A. Doshi, PhD, from the Perelman School of Medicine at the University of Pennsylvania, said in an accompanying press release. Approximately one in eight patients identified in the retrospective study had OOP costs above $2,000 and, even more sobering, many physicians were unaware that their patient opted out of filling a prescription for an OAM because of cost, she added.

"This study provided important data that are missing from most other studies [on] how often people are leaving their drugs behind," commented Stacie B. Dusetzina, PhD, from Vanderbilt University School of Medicine in Nashville. Her own research on the impact of parity legislation on OOP expenses was not able to consider individuals who abandoned their prescriptions due to costs.

"When the standard treatments were all intravenously administered, they were covered by insurance, but now we have a group of standard treatments that are not being covered and also present some difficulties in terms of adherence and compliance," said Jonathan W. Friedberg, MD, MMSc, from the University of Rochester Medical Center in New York. Dr. Friedberg recently co-chaired a Lymphoma Research Foundation workshop on the complexities and challenges of adherence to oral therapies in lymphoid malignancies. For more about the epidemiology of nonadherence to OAMs, see SIDEBAR 1.

Oral-Parity Disparity

Forty-three states plus the District of Columbia have passed oral-parity legislation to limit patient OOP costs for OAMs, and a number of other states have similar legislation on the agenda. (See the "Oral Anti- Cancer Therapy Access Legislative Landscape" map.)

State parity laws, however, only apply to certain commercial health insurance plans, including those that are purchased by small groups and individuals. Self-funded patients, patients covered by health plans that fall under the federal ERISA law (usually large, multi-state health plans), or those covered by Medicare and other federally funded insurance plans are not eligible. Estimates vary from state to state, but it's possible that only half of all U.S. patients are protected.3

"The state parity laws are not a silver bullet," warned Marialanna Lee, senior director of state government affairs at the Leukemia & Lymphoma Society (LLS). "There are many different insurance plan designs out there. These laws are tailored to address one feature of benefits design – which we saw was presenting problems years ago."

"The momentum that cancer advocates have built by passing so many successful state laws has made a profound impact on Capitol Hill, and I think oral parity is one of the few health-care issues that has a chance to get across the finish line this Congress," said Brian Connell, senior director of federal affairs at LLS.

In March 2017, Reps. Leonard Lance (R-NJ) and Brian Higgins (D-NY) introduced the Cancer Drug Parity Act (H.R. 1409), which has a bipartisan list of 151 cosponsors – 75 Democrats and 76 Republicans.4 The bill seeks to "amend the Public Health Service Act to require group and individual health insurance coverage and group health plans to provide for cost-sharing for oral anti-cancer drugs on terms no less favorable than the cost-sharing provided for anti-cancer medications administered by a health-care provider."

Companion legislation in the Senate hit a wall when its two sponsors both left their posts. Sen. Mark Kirk (R-IL) lost his seat in the November election and Sen. Al Franken (D-MN) resigned in January 2018.

Mr. Connell told ASH Clinical News that significant progress has been made in advancing federal oral parity in the current Congress. The bill has wide bipartisan support in the House and several members of the Senate have reached out to cancer advocates offering to help lead the oral-parity effort in the coming months.

"This legislation is not trying to solve all our problems in terms of medication pricing and insurance, but oral parity is a patientoriented, short-term fix that is simply asking why we are ‘picking on' oral and self-injected drugs to make them unaffordable," Dr. Rosmarin added.

As a member of the Coalition to Improve Access to Cancer Care (CIACC), ASH is working with organizations such as LLS to actively advocate for the Cancer Drug Parity Act to ensure people with cancer have equality of access (and equality of insurance coverage) for all approved anti-cancer regimens. ASH also has supported legislative efforts at the state level and continues to work with stakeholders and advocacy groups to support ongoing efforts in a number of states that still lack legislation.

For many years, ASH and other organizations have been lobbying on Capitol Hill to encourage the passage of federal oral-parity law. Visit for fact sheets, talking points, tips for contacting elected officials, and more information about the need for oral parity.

Do Parity Laws Work?

Data on the effectiveness of oral-parity laws are limited, but what has been published supports the claim that legislative efforts are, at best, only a partial solution. A study published last November by Dr. Dusetzina and colleagues showed only "modest" improvement in financial protection for patients in states with parity laws on the books.3

"We found really mixed results for the effectiveness of parity legislation," Dr. Dusetzina said. "For most people it decreased OOP spending, but strangely it increased spending for those with the higher cost-sharing levels."

" … Oral parity is a patient-oriented, short-term fix that is simply asking why we are ‘picking on' oral and self-injected drugs to make them unaffordable."

—Alan Rosmarin, MD

In states that implemented oral-parity laws, prescriptions for OAMs with $0 copayments increased from 15 to 53 percent, which was more than double the increase in plans not subject to parity (12.3% to 18.0%; p<0.001). At the same time, though, the proportion of patients with OOP spending higher than $100 per month increased from 8.4 to 11.1 percent, compared with a slight decline in plans not subject to parity (p=0.004). She added that this was the first large study on the topic that included information on plan-funding types, which allowed researchers to differentiate between plans that had to comply with state parity laws and those that didn't.

Dr. Dusetzina, who was at the University of North Carolina at Chapel Hill when she published this research, suggested higher deductible spending could explain this unexpected finding. "We think that the proportion of people on private insurance plans that have large deductibles has gone up," she said.

Along with parity laws, the authors argued that U.S. insurers need more direct controls on cost-sharing. "It's not just making prescription-drug benefits equal to medical benefits, but also thinking about putting some more formal limits on OOP spending, like a cap per pill, that really limit the total amount of financial exposure a person would have when they fill their prescription," she suggested.

"Dr. Dusetzina's data raise questions about the other methods that insurers can use to shift costs onto patients. For example, high-deductible health plans are preventing patients from fully benefitting from parity laws," Ms. Lee commented.

"The state legislations can only extend so far, and then we look to the federal government to pick up the mantle and carry it further," she added. (See SIDEBAR 2 for another side effect of patient-administered therapies: waste.)

"It's the Prices, Stupid"

Oral parity does have its limitations. For one, the legislation would only make OAMs as expensive as intravenous chemotherapies.

"If you peel the issue back to its base, we have absurd drug prices in the United States," Dr. Rosmarin said, "and the prices for oral anti-cancer drugs are nothing compared to the next generation of drugs that are coming our way, like chimeric antigen receptor T cells and other immune-based therapies."

In his well-known paper explaining why health-care costs are so high in the U.S. compared with other developed countries, the late Princeton health economist Uwe Reinhardt, PhD, and authors bluntly suggested, "It's the prices, stupid." Indeed, some researchers and clinicians suggest that the real answer to oral parity lies in lower oncology drug prices overall. Any other efforts are just serving to shift the burden of costs to insurers, who will ultimately pass along those costs to policyholders in the form of increased premiums.6

America's Health Insurance Plans (AHIP), a political advocacy and trade association with about 1,300 member companies that sell health insurance to more than 200 million Americans, is in full agreement with this theory. "We need to find ways to bring the ever-increasing prices of prescriptions under control," said Cathryn Donaldson, AHIP's director of communications. "Health plans are committed to ensuring that patients have access to medications that are safe, effective, and affordable. However, oral-parity legislation would place an arbitrary limit on cost-sharing between medical and pharmacy benefits, forcing premiums to increase for all consumers as a result – not just those who would use oral chemotherapy."

This position, at least so far, seems to have little support. Ms. Lee noted that in the states that passed oral-parity legislation, there is no evidence that premiums have risen. Also, in Dr. Dusetzina's study, overall costs (insurance payments for OAMs plus OOP costs) did not increase for patients covered under state parity laws.

"We also didn't observe any huge shift in use of drug, suggesting that there was no pent-up demand that wasn't being met before parity was available," said Dr. Dusetzina. "There might have been a small subset of patients who were able to afford their treatment post-parity, but what other [studies] have shown is that people will generally do what they need to do to get access to their cancer therapies."

For Dr. Rosmarin, all roads lead to the same place: "We just want to be able to deliver to our patients the care that they ought to be getting, and it breaks your heart to see financial or social barriers that might get in the way of best possible care."—By Debra L. Beck


  1. Dusetzina SB. Drug pricing trends for orally administered anticancer medications reimbursed by commercial health plans, 2000-2014. JAMA Oncol. 2016;2:960-1.

  2. Doshi JA, Li P, Huo H, Pettit AR, Armstrong KA. Association of patient out-of-pocket costs with prescription abandonment and delay in fills of novel oral anticancer agents. J Clin Oncol. 2018;36:476-82.

  3. Dusetzina SB, Huskamp HA, Winn AN, et al. Out-of-pocket and health care spending changes for patients using orally administered anticancer therapy after adoption of state parity laws. JAMA Oncol. 2017 November 9. [Epub ahead of print]

  4., "H.R.1409 – Cancer Drug Parity Act of 2017." Accessed May 2, 2018, from

  5. Anderson GF, Reinhardt UE, Hussey PS, Petrosyan V. It's the prices, stupid: Why the United States is so different from other countries. Health Aff (Millwood). 2003;22:89-105.

  6. Wang B, Joffe S, Kesselheim AS. Chemotherapy parity laws. A remedy for high drug costs? JAMA Int Med. 2014;174:1721-2.

Oral anti-cancer medications (OAMs) present some distinct challenges to hematologist-oncologists accustomed to prescribing infused anti-cancer drugs. First, unlike most other specialists, they're not used to patients skipping their meds.

"With chemotherapy, we are actively administering the drugs in clinic for a defined period of time, so we know exactly what patients are getting," Jonathan Friedberg, MD, MMSc, told ASH Clinical News.

"With infused drugs, patients generally are assessed before each treatment, so we understand much more what is happening with them and we can assess whether they are fit for treatment," Dr. Friedberg explained. "But with the oral drugs, we send patients home with a prescription and we don't know exactly what the patients are taking, if they're taking them in the way prescribed, or even if they are taking them at all."

In October 2017, Dr. Friedberg and Michael E. Williams, MD, ScM, from the University of Virginia Cancer Center, cochaired the Lymphoma Research Foundation's "Adherence and Oral Therapies in Lymphoma and CLL Workshop," which brought together scientists, clinicians, policy makers, regulators, drug developers, and patients to discuss the unique challenges of adherence with OAMs.

In March 2018, the foundation released a white paper covering the key discussion points that emerged from that meeting, including the ways in which nonadherence may contribute to poor treatment outcomes and lead to increased use of health-care resources.1

"To me, the most concerning issue in the lymphoma space is what drives adherence and compliance, which includes the issue of the financial burden to patients," Dr. Friedberg noted. "What is less understood in lymphoid disorders than in other diseases are the implications of ‘drug holidays,' or breaks in therapy, on the ultimate outcome of that disease."

One challenge identified by workshop participants is identifying the optimal methods for monitoring patients, which the workshop participants acknowledged often requires a change in infrastructure. "At our institution, we now have a pharmacist in the clinic who helps to ensure compliance. It's another layer that we didn't have before, just to make sure that patients are as compliant as possible."

In many cases, OAMs are administered as maintenance treatment for blood cancers, and yet there is little information available on the effects of daily compliance. The National Cancer Institute (NCI) has put out a request for applications and earmarked funds to support research in this area.2

In addition to prescription abandonment from financial toxicity, the side effects of OAMs are usually less severe than with infused agents, but perhaps more difficult to manage, noted Dr. Friedberg.

"Infused chemotherapy is usually administered over four to six months and, even if the toxicity is severe, it's generally acute and for a defined period of time," he said. "With oral chemotherapy, the patients might experience chronic, low-grade suffering that goes on for months and months. A mild rash is okay for a little while, but it can really disrupt patients' lives if it persists for a long period of time."

That said, for patients who cannot tolerate the acute toxicities of intravenous chemotherapy, the oral agents can be "transformational," he added.


  1. Lymphoma Research Foundation. "Adherence and oral therapies in lymphoma and CLL: a lymphoma research foundation white paper." Accessed May 2, 2018, from
  2. National Institutes of Health. "Funding opportunity: oral anticancer agents: utilization, adherence, and health care delivery (R21)." Accessed May 2, 2018, from

Waste is a concern across all areas of medicine, but with oral anti-cancer medications, the dollar amounts are truly staggering, according to a study of the financial impact of this type of medical waste.

Varun Monga, MD, from the division of hematology-oncology and bone marrow transplantation at the University of Iowa Carver College of Medicine, and colleagues looked at 83 patients who were prescribed OAMs at their cancer center during a three-year period.1 The cost of wasted tablets/capsules was calculated from dispensing data and average wholesale prices. The investigators found that waste occurred with 41 percent of patients, mostly for reasons of cancer progression, but also due to death, toxicity, and dosing changes. All told, 1,179 tablets or capsules were wasted from all causes, priced at a total of $248,595.69.

"This problem is not unique to oral drugs," Dr. Monga told ASH Clinical News. But, because OAMs make up the single largest category of specialty-drug spending and their use is rapidly evolving, the financial burden to society from wastage of these medications is substantial.

"Discoordination of prescription fills and disease-assessment clinic visits accounted for the majority of waste," the authors reported. "Every effort should be made between patient and oncologist to coordinate the two." They also suggested that "mandated manufacturer preparation of high-cost medications in unit-dose packaging would increase the number of medications eligible to be reused, decreasing society- and patient-related cost." Iowa is one of 20 states with active laws governing repository programs that allow medications to be reused at no cost to patients.


  1. Monga V, Meyer C, Vakiner B, Clamon G. Financial impact of oral chemotherapy wastage on society and the patient. J Oncol Pharm Pract. 2018 January 1. [Epub ahead of print]


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