Introduction
Between 2014-2018, 57 cancer medications were launched in the U.S. for 89 indications across 23 different cancer types.1 In 2018 alone, a record 15 new oncology therapeutics for 17 indications were launched with an increasing trend of oral targeted therapy and immuno-oncology approvals.Reference IQIVA Institute2 New cancer treatments generate hope among patients and providers. At the same time, new cancer therapies challenge payers. The rapid increase in anti-cancer medication approvals is due to scientific advances combined with expedited approval processes by the Food and Drug Administration (FDA)Reference Chen, Raghunathan, Prasad, Darrow, Avorn, Kesselheim and Approval3 to provide patients with early access to promising therapies.Reference Gyawali, Hey and Kesselheim4 Expedited approval pathways require less evidence on efficacy and safety for approvalReference Redberg5 and some mandate post-approval confirmatory studies.Reference Pregelj, Hwang, Hine, Siegel, Barnard and Darrow6 However, when evaluated in post-marketing studies, uncertainty about clinical effectiveness often remains;Reference Hwang, Franklin, Che, Lauffenburger, Gyawali and Kesselheim7 some products approved via expedited pathways have not been found to be effective and safety issues have emerged.Reference Naci, Smalley and Kesselheim8 Additionally, these innovations come to market at high and increasing pricesReference Peppercorn9 and pose substantial challenges to societalReference Dusetzina, Conti, Yu and Bach10 and individual affordability of cancer medications.Reference Bestvina, Zullig and Zafar11
Health insurance coverage of expensive cancer therapies is crucial to make new therapies accessible to patients. State laws to ensure cancer therapy coverage, such as off-label use laws, have origins in various federal laws that facilitate such coverage. Some such laws date back to the 1990s when the environment was different: anti-cancer medications consisted of cytotoxic chemotherapy, their effects had been studied more extensively before approval and they were substantially less expensive than today’s new treatments. Moreover, states have enacted additional laws to ensure cancer therapy coverage.12 For example, oral chemotherapy parity laws have been implemented in the past decade to address higher out-of-pocket costs of increasingly prevalent oral therapies as compared to injectables.Reference Kircher, Meeker, Nimeiri, Geynisman, Zafar and Shankaran13 The question arises: to what extent do cancer coverage laws meet the needs of diverse stakeholders given the clinical and regulatory evolution of cancer therapies? Evaluations of coverage policies in cancer care mainly focus on their impacts on the care delivery system,Reference Brooks, Hoverman, Colla, Han, Jemal, Leopold, Park and Nekhlyudov14 healthcare utilization,Reference Alvarez, Keegan, Johnston, Haile, Sanders, Wise, Chino, Suneja, Moss, Zafar, Havrilesky, Chino, Eguia, Cobb, Kothari, Molefe, Afshar, Aranha, Hendryx, Luo, Jemal, Lin, Davidoff and Han15 and affordability by patients.Reference Davidoff, Guy, Hu, Gonzales, Han, Zheng, Dixon, Cole, Dusetzina, Shih, Xu, Liu and Smieliauskas16 To our knowledge no previous research examines the dichotomy between cancer coverage mandates and current realities in oncology care that involve novel therapies, many approved based on limited evidence of benefit or evidence of marginal benefit, at ever-increasing prices. At the same time, leading policy fora are highlighting the important role of the interplay between coverage policies and the legal environment with a call for more research in this area.17
The question arises: to what extent do cancer coverage laws meet the needs of diverse stakeholders given the clinical and regulatory evolution of cancer therapies? Evaluations of coverage policies in cancer care mainly focus on their impacts on the care delivery system, on healthcare utilization, and on affordability by patients. To our knowledge no previous research examines the dichotomy between cancer coverage mandates and current realities in oncology care that involve novel therapies, many approved based on limited evidence of benefit or evidence of marginal benefit, at ever-increasing prices. At the same time, leading policy fora are highlighting the important role of the interplay between coverage policies and the legal environment with a call for more research in this area.
Materials and Methods
Taking Massachusetts (MA) as a case study, we combine legal and qualitative analyses. We first describe cancer coverage laws and then present and discuss the perspectives of expert stakeholders on these laws today. We focus on MA because of its highly specialized cancer care delivery centers and its generous insurance coverage environment.
First, we performed a content analysis of relevant legislation in MA. We searched Lexis Nexis and other sources for legislation relevant to clinical trials, off-label medication use, and coverage of chemotherapy (Table 1). Our search for legislative documents included state-level laws enacted and possibly amended since 1990 and still in-effect as of January 2018. We then collected key information on each law, including: 1) type of law/benefit, 2) law provision and title, 3) date of authorizing legislation, 4) effective date, 5) types of insurance policies affected, 6) types of insurance policies exempted, 7) coverage requirements, 8) coverage exemptions, 9) cost-sharing or other insurer managed care approaches allowed, and 10) law citation and Uniform Resource Locator (URL). To put the MA laws into context, we include an overview table of similar laws in Connecticut (CT), Maine (ME), and New Hampshire (NH) (Annex 1).
Table 1 Search criteria and sources for legislative documents
Next, we conducted semi-structured interviews to elicit perspectives of experts about the MA cancer coverage laws to understand how well (or not) existing cancer coverage laws meet the current cancer care needs. The research team leveraged connections with relevant organizations in MA to identify experts for interviews. Different from quantitative studies where the ideal sampling standard is random sampling,Reference Ritchie, Lu, Williams, Day and Patton18 we purposefully invited seven experts from regulatory agencies, public and private payers and provider organizations to cover a range of views and experiences of key stakeholder groups in cancer drug coverage. These represent information-rich key informants to illuminate the question of interest, which is the overall purpose of qualitative research. Sample size is justified on the basis of information power.Reference Malterud, Siersma and Guassora19 We summarized the identified key laws in MA in a table, which we shared with interview partners prior to the interviews. We developed a semi-structured interview guide that included 11 open-ended questions, categorized into three sections: 1) regulating cancer medication coverage — mapping the legal basis, 2) regulating cancer medication coverage — understanding the process of coverage, and 3) regulating cancer medication coverage — broader considerations. We had separate questionnaires for representatives of provider organizations, state regulators, and insurers. The questionnaires were tested among colleagues at the Department of Population Medicines at Harvard Medical School and Harvard Pilgrim Healthcare Institute (a questionnaire is available in Annex 1).
Interviews were conducted by phone between January and March 2018, lasted one hour each, and were audio-taped. Participation in the interview was voluntary and consent was explicitly given by all participants. CL, RLH, and AKW jointly conducted all interviews; recordings were transcribed. Using qualitative content analysis methods, we systematically extracted themes that emerged across interviews and categorized them into overarching areas.Reference Cho, Lee and Mayring20 After several rounds of review, no further new themes emerged and the investigators created a consensus summary of all themes and selected representative quotes to illustrate the key points made by interviewees. The research protocol and interview guides were approved by the Harvard Pilgrim Health Care Institutional Review Board.
Results
We first describe and summarize in Table 2 the most relevant laws and regulations concerning insurance coverage of cancer treatments in MA. In addition, we include an overview table of similar laws in CT, ME, and NH in online Annex 1. National laws were not included in this overview unless they directly influenced state legislation.
MA Cancer Treatment Coverage Mandates
We identified five laws as most relevant for the coverage of cancer treatments. These included the MA offlabel drug use law, the MA clinical trial law, the MA oral chemotherapy parity law, MA health reform legislation, and the federal Patient Protection and Affordable Care Act (ACA) — including the Essential Health Benefits defined at the state level. During the interviews, “White-Brown Bagging” emerged as another relevant policy to consider.21 The off-label drug use law dates back to the 1990s; the other laws were implemented between 2003 and 2013.
Before the federal ACA, MA provided health insurance coverage to its uninsured and low-income residents and offered affordable health insurance coverage options to all its residents since 2006 (Table 2). MA residents are required to obtain, and most employers must offer, health insurance or face financial penalties. As of 2017, MA plans offered on the ACA exchanges were obligated to cover chemotherapy, radiation, and specialty generic and brand-name drugs, all without limitations on quantity (Table 2). In addition to these general insurance coverage requirements, some longstanding laws targeting commercial plan coverage of cancer care also exist in MA. Individual and group insurance policies that provide prescription coverage must generally cover anti-cancer medications, including for indications that have not been FDA-approved (i.e., the “off-label drug use law”, Table 2). Also, these plans must cover general patient services furnished to cancer patients enrolled in qualified clinical trials (i.e., the “clinical trial law,” Table 2). Finally, since 2013, any plan offered in MA that covers cancer chemotherapy must cover orally administered chemotherapy medications as generously as its covers injectables (i.e., the “oral chemotherapy parity law,” Table 2). Taken together, these laws are intended to benefit patients by mandating that commercial insurers cover cancer care and treatments along the pathway from clinical research to on- and off-label use of marketed products.
Table 2 Summary of key legislation on cancer care coverage in Massachusetts
Abbreviations: DOD = Department of Defense, FDA = Food and Drug Administration, IRB = Institutional Review Board, MA = Massachusetts, NIH = National Institutes for Health, VA = Veteran Affairs
While such laws also exist in similar form in CT, ME, and NH, their effective dates and scopes differ somewhat from those in MA. For example, the requirements for off-label drug coverage vary between the states: CT law mandates coverage of off-label use if the cancer treatment is mentioned in standard reference compendia; ME and NH laws require evidence from standard reference compendia or the medical literature (ME law specifies two publications from high impact journals); the MA law specifies that off-label evidence could also come from a panel of 6 medical experts and then recognized by the MA insurance commissioner. The oral chemotherapy parity laws are similar in substance (except that MA explicitly forbids meeting this coverage requirement by increasing cost sharing for injectable anticancer medications), but effective dates vary across states: CT implemented it’s law in 1991, MA in 2003, ME in 2009, and NH in 2017.
Seven experts from regulatory agencies, public and private payers and provider organizations participated in the interviews. To describe the relevance of these laws and how they impact cancer drug coverage in the real world, we present in the following paragraphs the main themes and statements that emerged from key informant interviews. Under each theme, key messages from the interviews are summarized and relevant quotes are included in Table 3 to exemplify the main points of the interviews.
Table 3 Themes and representative quotes by key subject areas
Abbreviations: ASCO = American Society of Cancer Oncology, FDA = Food and Drug Administration, MA = Massachusetts, NCCN = National Comprehensive Cancer Network
1 “White-bagging” refers to the distribution of patient-specific medication from a pharmacy, typically a specialty pharmacy, to the physician’s office, hospital, or clinic for administration. It is often used in oncology practices to obtain costly injectable or infusible medications that are distributed by specialty pharmacies and may not be available in all non-specialty pharmacies. “Brown-bagging” refers to the dispensing of a medication from a pharmacy (typically a specialty pharmacy) directly to a patient, who then transports the medication(s) to the physician’s office for administration.40
Coverage of Cancer Treatments Faces Unique Challenges
Interviewees emphasized that oncology is a particularly “difficult” area when it comes to insurance coverage decisions. Reasons for this include: 1) a fastchanging treatment environment in which we observe a switch from organ-based to tumor-based treatments independent of a specific organ, 2) a treatment setting with very expensive medications that are often approved based on insufficient data of clinical benefits, and finally 3) the fact that cancer therapy coverage is a sensitive topic given unmet need, hope, and hype in public media.
MA May be Exceptional in Terms of Both Cancer Treatment and Legislation of Cancer care
Interviewees emphasized that MA might be more generous when it comes to covering cancer treatments than other states. Several reasons were offered to support these claims: 1) in contrast to other states, health plans in MA do not seek to maximize profits and may have more generous coverage policies; 2) MA is a hub of highly specialized cancer centers with highlytrained, highly-specialized oncologists who conduct trials of cutting-edge therapies; and 3) in MA, oncologists and legislators know each other and can easily communicate about policies.
Differential Applicability of Laws in the Private versus the Public Sector
The state cancer coverage laws are largely only relevant for commercial insurers, meaning that private health plans regulated by the Division of Insurance at the Department of Health must comply with the regulations; public plans, including Medicaid, were not directly affected by the state cancer coverage laws we identified. Medicaid’s coverage determination process is agnostic about the therapeutic category and includes a literature review for all FDA-approved medications. Medicaid employs a set process for making all coverage determinations but does engage an oncologist on the Medicaid Drug Use Review Board. Nevertheless, cancer treatments are not assessed or viewed differently from any other therapeutic class. Respondents from private health plans pointed out that they conduct faster coverage assessment and review processes for oncology products.
Differential Relevance of These Laws for Coverage
We learned from the interviewees that each of the highlighted laws has differential relevance in real-world coverage decisions. While the oral chemotherapy parity law is financially impactful for private health plans — as it requires insurers to charge members no more for oral chemotherapies than for medications administered in a clinical setting (i.e., no higher cost sharing for oral chemotherapies) — it is less impactful for patients in Medicaid plans under which out-of-pocket payments are negligible.
With respect to the clinical trial law respondents from private health plans voiced their concerns for the ability to manage patients in clinical trials because for insurers, it is unclear when a patient is part of a clinical trial and which services then must be covered. Again, this seemed to be less of a concern for public payers.
All respondents agreed that the off-label drug use law is less relevant to the reimbursement environment at this time because 1) insurers acknowledge that new drugs are being used off-label; 2) they trust the clinicians in MA in their prescribing, and 3) outside of prior authorization requirements, insurers don’t typically check drug use against diagnoses.
Stakeholders’ Concerns with Respect to the Legal Environment
When asked about specific concerns regarding MA regulation relevant to cancer treatments, respondents mentioned the “White-Brown Bagging” policy,22 which requires that medications for specific patients are filled in specialty pharmacies and then either delivered directly to administering clinicians in hospitals (“white-bagging”) or picked up by patients from pharmacies and brought to clinicians for administration (“brown-bagging”). In both cases, prescriptions are filled for a specific patient and if medications are not picked up, they cannot be returned to the pharmacy stock and used for other patients.23 Respondents were concerned that white-bagging could lead to wasting expensive products if patients do not receive the ordered medication; and that brown-bagging could lead to unsafe handling of medications outside of health care settings.
Policy Options Toward Sustainable Coverage of Cancer Care
Respondents pointed out that the coverage environment is changing, and alternative policies relevant for all therapeutic classes are being tested and implemented. Some of these approaches are already in use or are being developed by public and private insurers. Approaches include the implementation of a closed formulary, in which not all medications are automatically covered after approval by the FDA; formal comparative- effectiveness assessments as part of coverage decision-making; and value-based reimbursement.
Discussion
This study combined legal and qualitative analyses. We identified relevant legislation in MA and, to add context, provided parallel information on similar laws in CT, ME, and NH. We presented the legal analysis to and elicited perspectives from experts about the MA cancer coverage laws to understand how existing cancer coverage laws meet the current cancer care needs. In the discussion, we reflect on the insights from the interviews and the juxtaposition of the laws with the state of cancer therapies today.
Although our interview partners represented different stakeholders, similar themes emerged from their perspectives on legislation of coverage of cancer care in MA. Interviewees emphasized that cancer therapy coverage is uniquely challenging and has for decades had special insurance coverage legislation. Among the five relevant state laws and policies, the oral chemotherapy parity law was identified as the most impactful in terms of costs in the private insurance sector. Respondents’ suggested implementation of closed formularies (e.g., potential exclusion of medications from coverage), comparative cost-effectiveness studies and value-based reimbursement approaches to address the high cost burden of cancer therapies.
Since the earliest cancer coverage mandate in 1993, additional cancer coverage laws have accompanied the scientific evolution that gives rise to new molecules. The off-label laws were meant to ensure covered access to cytotoxic chemotherapies which kill any fast-growing cell, regardless of the cancer type for which the agent was approved as long as patients tolerate the medications. With increasing cancer research producing scientific advances,24 the clinical trials law in 2003 ensured that cancer patients enrolling in trials have covered access to needed care that is not paid for by the trial. Insurance coverage expansion in 2006 and beyond (including the Federal Medicare Part D drug benefit) also provided incentives for the development of oral cancer treatments. The oral parity law of 2013 ensured that patients’ cost sharing for new oral therapies, usually under an insurer’s pharmacy benefit, were not higher than the usually limited cost-sharing for injectable therapies administered in provider offices and usually paid under an insurer’s medical benefit and with minimal utilization management. While these cancer coverage laws are meant to provide patients with covered access to all available treatments, they limit insurers’ ability to manage the use of the products and negotiate prices. That is challenging given that many oncology medications are now approved based on lowered efficacy and safety standards through expedited review programs,Reference Darrow25 based on surrogate outcomes that do not correlate well with overall survival26 or quality of life,Reference Naci, Davis, Savovi, Higgins, Sterne, Gyawali, Davis, Naci, Gurpinar, Hwang, Gyawali, Kovic, Jin and Kennedy27 and that almost half of the randomized trials that form the basis of approvals are subject to bias that may exaggerate the outcome findings.Reference Lombardi, Marandino and Luca28 Thus, health plans are required to cover new cancer therapies despite increased uncertainty about efficacy, safety, and longterm effectiveness.
Steep increases in costs of cancer care over the last decadesReference Bennette, Richards, Sullivan, Ramsey, Conti, Fein, Bhatta, Shih, Smieliauskas, Geynisman, Kelly and Smith29 have raised concerns of affordability for the overall healthcare system as well as for individual patients. Cancer patients’ struggles to cover their outof- pocket expenses are widely known;Reference Smith, Nicolla, Zafar, Chino, Peppercorn, Rushing, Kamal, Altomare, Samsa, Lathan, Cronin, Tucker-Seeley, Zafar, Ayanian, Schrag and Emanuel30 at the same time, private payers are speaking up about the fact that an increasingly larger share of total health care spending is taken up by higher-priced pharmaceuticals including cancer medications,31 with limited policy tools to manage those costs.Reference Runyan, Banks and Bruni32 Our interview partners shared these concerns. By definition, cancer treatment coverage mandates do not consider overall affordability of the healthcare system or the payer, nor target medication pricing,Reference Smith, Nicolla, Zafar, Chino, Peppercorn, Rushing, Kamal, Altomare, Samsa, Lathan, Cronin, Tucker-Seeley, Zafar, Ayanian, Schrag and Emanuel30 which is often cited to be at the root of the tremendous cost burden.Reference Sarpatwari and Kesselheim34 In fact, state and federal coverage mandates are thought to contribute to high cancer drug prices.Reference Ramsey35
The experts suggested several policy options such as comparative cost-effectiveness studies, the implementation of value-based reimbursement and pharmaceutical company patient access schemes to address the oncology access-evidence-spending conundrums. While some of these approaches are in use (e.g. costeffectiveness studies and patient access schemes), others such as value-based reimbursement are still mainly theoretical.Reference Leopold, Peppercorn, Zafar and Wagner36 Most recently, states are considering the establishment of state-governed “prescription drug affordability review boards” charged with reviewing expensive medications and, if deemed too expensive, setting a new, lower maximum price that insurance plans would pay.37 Maryland was the first state to implement such a review board in July 2019.38 At the same time, it is not clear whether these approaches offer long-term solutions to the affordability of cancer medications in the US.39 These suggested approaches — eliminating parity requirements, having closed formularies or the introduction of cost-effectiveness based reimbursement — need to be implemented in ways that balance affordability and access so that patients who can benefit from treatments have access to the therapies.
This study has limitations. We focused on assessing the legal policy environment in MA, which was the first state to mandate insurance enrollment and which offers historically generous health insurance coverage. Our findings might therefore not be generalizable to other states in the US. The results of our qualitative assessment represent subjective experiences of experts, which may reflect a socially desirable response bias. Notwithstanding these limitations, our focus on MA given its unique environment offers indepth insights into contemporary challenges of cancer therapeutics in health systems. Our findings suggest that in combination with FDA regulations for faster approvals based on more limited evidence and the lack of federal price controls, states like MA may be due for a review of current coverage mandates to assess whether they facilitate covered access to important cancer medicines for patients who can benefit from them while also keeping insurance coverage sustainable and affordable for people in the state.
Conclusions
Given the rapid evolution of science and cancer medication approvals, a review and, if needed, updates of the cancer coverage mandates seem worthwhile to ensure sustainable access to both high quality cancer care and health insurance that is affordable to individuals, health plans, and society.
Annex 1— Interview guide professional organization
Semi-structured Interview guide — professional organization
Introduction
Thank you for participating in this interview on cancer therapy coverage laws and mandates. Our interest is to understand the current landscape of cancer therapy coverage legislation and the involvement of different stakeholders in the development and enforcement of coverage mandates. We are particularly interested to learn from you, as a member of a professional organization, about your experiences in advocating for cancer therapy coverage legislation.
My name is Anita Wagner, I am an Associate Professor at the Harvard Medical School Department of Population Medicine (DPM) and I lead this study. With me are Dr. Haffajee, Assistant Professor at University of Michigan and a health policy and health law expert, and Dr. Leopold, Senior Research Fellow at the DPM and a health policy expert.
Your participation in this study is voluntary and you may choose to skip questions or end the interview at any time. We do not expect any risks associated with your participation in our study. What you tell us will be kept confidential.
We have sent you an abbreviated text of cancer coverage legislation and a list of questions we are interested in. It would be helpful if you have those handy but it is not necessary to proceed. There will not be right or wrong answers to these questions. Rather, we wish to get your expert opinion.
Informed Verbal Consent
The interview should take about 30-minutes. Before we go on, please allow me to ask: do you understand the basic picture of this telephone interview study, and the potential risks and benefits to you as a participant? Do you have any questions about the study? Is it OK for me to go ahead and start the interview?
Great, thank you.
[If participant declines, thank him/her for his/her time and end the conversation. If participant consents, proceed.]
If you agree, we would like to record the interview so that we capture what you say without errors. The recordings will be destroyed once we have analyzed all interviews. No information will be attributable to you personally. Is that okay with you?
[If participant declines, remind him/her that you will be taking notes about the discussion. If participant agrees, TURN ON RECORDER]
Great. I’m starting the recording now.
Let’s get started with the interview. First, we would like to ask a few questions on the current legal landscape of cancer drug coverage.
Regulating cancer drug coverage — mapping the legal basis
We identified the following laws and regulations as relevant for cancer drug coverage by public and private insurers (please see the sheet we sent, if you have it handy):
a. Off-label drug use law (Mass. Ann. Laws ch. 175, § 47K-L: Off-Label drug use: cancer treatment & review panel, date of authorizing legislation: 1992)
b. Clinical trial law (Mass. Ann. Laws ch. 175, § 110L: Clinical trials: definitions: coverage, date of authorization legislation: 2002)
c. Oral chemotherapy parity law (Mass. Ann. Laws ch. 175, § 47DD: Coverage for orally administered anticancer medications, date of authorization of legislation: 2012)
d. ACA/Essential Health Benefits (yearly adjusted and define coverage of chemotherapy drugs)
e. MA comprehensive cancer prevention and control plan 2012-2016 1
Which laws / regulations does your organization consider as most relevant for regulating coverage of cancer medicines? Are there new laws/regulations you are proposing or would like to see?
What is your organization’s role in advocating for and/or drafting these proposed laws?
Are you aware of problems the laws and regulations create for regulators, for payers, for patients? Could you give examples of those problems. In particular, has the off-label coverage law provided benefits or posed challenges or both?
How is your organization responding to benefits or challenges that may have come up?
Regulating cancer drug coverage — understanding the process of coverage
5. Does your organization play a role when public or private insurers draft coverage policies for cancer medicines? If yes, in which way?
6. In which way can your organization influence public or private insurers’ coverage decisions?
7. (For NCCN) We understand that you create national cancer treatment guidelines to inform payer coverage decisions. Which stakeholders are consulted when drafting national guidelines?
8. Does your organization receive funding from pharmaceutical industry? If yes, what mechanisms are in place to safeguard against potential conflict of interest?
Regulating cancer drug coverage — broader considerations
9. How does your organization consider affordability for patients in advocacy for coverage policies?
10. How does your organization consider affordability for payers in advocacy for coverage policies?
11. What does your organization currently consider as the biggest challenge in coverage of cancer care?
Close:
Thank you so much for your time. Your insights will be very helpful to us. I am stopping the recording now.
