NPC Comments on CMS' Proposed Changes to Protected Classes

NPC commented on a proposed rule that would revise the prescription drug benefit program (Part D) regulations (as well as other CMS programs and policies) to implement revised statutory requirements.

March 7, 2014

Marilyn B. Tavenner
Centers for Medicare & Medicaid Services
U.S. Department of Health and Human Services
200 Independence Avenue, SW
Washington, DC 20201 

RE: Medicare Program; Contract Year 2015 Policy and Technical Changes to the Medicare Advantage and the Medicare Prescription Drug Benefit Programs. [CMS-4159-P] [RIN 0938-AR37]

Submitted electronically via

Dear Administrator Tavenner:

The National Pharmaceutical Council (NPC) appreciates the opportunity to submit comments regarding the Centers for Medicare and Medicaid Services (CMS) notice of proposed rulemaking, Medicare Program; Contract Year 2015 and Technical Changes to the Medicare Advantage and the Medicare Prescription Drug Benefit programs. The proposed rule would revise the prescription drug benefit program (Part D) regulations (as well as other CMS programs and policies) to implement revised statutory requirements. 

NPC is a health policy research organization dedicated to the advancement of good evidence and science and to fostering an environment in the United States that supports medical innovation. NPC is supported by major U.S. research-based biopharmaceutical companies. NPC focuses on research development, information dissemination, education and communication of the critical issues of evidence, innovation and the value of medicines for patients. Our research helps inform critical healthcare policy debates and supports the achievement of the best patient outcomes in the most efficient way possible. 

Our comments are meant to highlight evidence that should be factored into decision making so that CMS programs and policies can best serve patients. Specifically, our comments are focused on the proposed provision related to drug categories or classes of clinical concern and exceptions, commonly referred to as “protected” classes. 

Drug Categories or Classes of Clinical Concern and Exceptions

Provision 14 of the proposed rulemaking would revise the criteria and existing beneficiary protections for determining whether drug categories or classes of clinical concern require further protection. The revised criteria and protections remove antidepressants and immunosuppressants from protected classification in 2015, and antipsychotics from protected status in 2016. The original protected classes policy was created by CMS in 2005 and codified by Congress in 2008. The existing policy has served patients well. Protected Classes ensure that Medicare beneficiaries have access to substantially all medications within these drug categories because Part D plans cannot prohibit their access through formulary restrictions. 

Heterogeneity of Treatment Effects

Access to high quality and innovative medicines is the cornerstone of patient-centered healthcare, ensuring that individual patients are able to get the best treatment options for them. Under the new proposal, for those drug classes that will lose their protected status, Part D plans would no longer be required to carry “substantially all” of the chemically distinct drugs in these categories, but rather would only be required to carry one brand name drug and one generic drug. This limitation can lead to the unintended consequence of restricting treatment options to what may work best for the “average” patient.  For healthcare to be patient-centered, it is necessary to consider patient heterogeneity of treatment effects (HTE). Different patients can have very different responses when it comes to different treatment options. The treatment that is best for most patients may not be the one that is right for an individual. Healthcare coverage and benefit design that is focused on “average” treatment response can result in restricting a patient from access to the particular treatment option that is most effective for him or her. 

When patients don't receive the medications best matched for them, worsening of symptoms, avoidable hospitalizations, and impaired quality of life would likely result. For some health conditions, policies that delay optimal treatment even for a few months while patients are required to try ineffective treatment options may cause irreversible damage. This is the case for immunosuppressant therapy for patients with autoimmune conditions or organ transplant. In the absence of optimal treatment, these patients can experience substantial tissue degradation. Furthermore, medications are often not interchangeable. A patient who is taking a medication that works well in treating his or her chronic illness could experience vastly different effects and side effects if forced to switch to another treatment that is not suited for his or her individual use. 

Restricted access greatly impacts individual patient health, but also could have a substantial impact on downstream healthcare costs as patients’ conditions progress in the absence of the most effective treatment and/or they suffer from increased adverse events. Policies designed to save upstream costs by restricting access to expensive drugs can actually have a net negative economic impact mainly because of reduced health among patients who do not receive timely effective treatment due to these restrictive policies.  Thus, consideration of HTE can contribute to more individualized and more efficient healthcare.

Educational Materials and Research Examples

The extent to which such HTE exists and to what degree patients are able to benefit from the consideration of HTE varies depending on the healthcare condition. For some health conditions, there may be a low amount of patient HTE, and allowing plans to manage medication formularies might not have a negative impact on patient health and healthcare efficiency. However, when HTE exists, flexible and open policies are needed to ensure appropriate treatment options are available for each patient. The original six protected categories and classes policy recognizes this need for access to the full range of treatment options for patients with conditions related to those protected classes. These classes and categories of drugs were given protected status so that the design of the plan would be non-restrictive.  Expeditious access to drugs in these categories was recognized as “necessary for enrollees as their health condition requires.” The importance of access to the full range of these treatment options has not changed. The protected classes are used to treat conditions for which it is most critical to provide patient-centered care and to consider HTE in treatment decision making.

The National Pharmaceutical Council and other organizations have conducted extensive research examining HTE and the policy implications of a one-size-fits-all approach to clinical and formulary decision making. There are a number of peer-reviewed studies and educational materials that show that it is detrimental to both patients and payers to restrict treatment choices based on the response of the “average population.” These materials can serve as evidence regarding the importance of considering HTE in healthcare decision making, and to promote awareness of the need to consider HTE to all stakeholders:

  • The NPC educational booklet, “The Myth of Average: Why Individual Patients Matter”[1] gives a general overview of HTE and the policy implications of a one-size-fits all approach to medicine. This booklet is written in lay terminology and is meant to promote awareness of the issue to all audiences.
  • NPC sponsored a peer-reviewed economic analysis in the Journal of Health Economics, “The Impact of Comparative Effectiveness Research on Health and Health Care Spending”[2]  which describes the potential consequences of comparative effectiveness research (CER) results that point to a best treatment option based on the average response in the full population. The report focused on the real-world consequences of restricting access to antipsychotics based on average response.  In our analysis of treatment effect heterogeneity, we showed that product specific coverage policies may negatively impact health when they fail to account for patient-specific treatment effects. 

    In a corresponding NPC-sponsored white paper, “Blue Pill or Red Pill: The Limits of Comparative Effectiveness Research”[3], we showed that the “average” response does not reflect all patients. The study estimates that policies that restrict access to second generation antipsychotics would reduce schizophrenia patient health by 13,138 quality-adjusted life years (QALYs) because of reduced health among the patients who were not responsive to first-generation antipsychotics and who, because of the restrictive policy, received no other drug therapy. These drugs are one of the largest classes of medication for Medicaid patients, and are included in the proposed rule to lose protected status in 2016.
  • NPC sponsored a study published in the journal Health Economics, “Heterogeneity in Action: The Role of Passive Personalization in Comparative Effectiveness Research”[4], which describes HTE in schizophrenia patients through patient-centered treatment effects estimation and demonstrates that the average effects from a CER study cannot be replicated in practice because the studies fail to account for the patient-centeredness of care that already exist in practice. Specifically, the study results show that patients receiving a limited choice of generic antipsychotic medications experienced significantly higher numbers of overall and schizophrenia related hospitalizations within one year compared to those who had broad treatment options, including branded antipsychotics. The study also suggests that coverage policies that respond to results focused on average response generate higher spending.
  • The Agency for Healthcare Research and Quality (AHRQ) 2007 Comparative Effectiveness Review report, “Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression,”[5] includes HTE information about antidepressants, another class of drugs set to lose protected status in 2015 under the proposed rule. The AHRQ report shows that heterogeneity of efficacy, effectiveness, or harms were associated with the following subpopulations: elderly or very elderly patients; other demographic groups (defined by age, ethnic or racial groups, and sex); patients with medical comorbidities (e.g., ischemic heart disease, cancer); patients with psychiatric and behavioral comorbidities (e.g., substance abuse disorders); and patients taking other medications. These factors influencing HTE are clearly some of the most relevant factors to Medicare and Medicaid enrollees. The report concludes that although second-generation antidepressants appear similar in average efficacy and effectiveness, they cannot be considered identical drugs. Evidence supports differences among individual drugs with respect to onset of action and some measures that could affect health-related quality of life.

It is important to consider this evidence when making policy decisions that could impact formulary management under Part D. The CMS Part D drug categories or classes of clinical concern and exceptions include protected classes for which HTE is an important factor in treatment decision making.  NPC is concerned that the proposed ruling would adversely impact patient access to needed medications, which can lead to suboptimal outcomes for both patients and payers. 


NPC shares CMS’ goal to provide patients and healthcare providers with safe and effective therapies that will best serve the needs of patients and the healthcare system. Meeting that goal will require strategies that are based on sound evidence and that reflect patient-centered principles. Recognizing the evidence for and importance of HTE and accounting for it by maintaining the existing protected classes will go a long way in supporting patient health.

Thank you for the opportunity to provide these comments.

Respectfully submitted,

Dan Leonard
National Pharmaceutical Council



[1] National Pharmaceutical Council, “The Myth of Average: Why Individual Patient Differences Matter.” [Internet]. Washington (DC); [cited 2014 February 24].

[2] Basu, A., Jena, AB., and Philipson, TJ. “The Impact of Comparative Effectiveness Research on Health and Health Spending.” Journal of Health Economics, 2011; 30 (4): 695-706.

[3] Philipson, TJ., and Sun, E. “Blue Pill or Red Pill: The Limits of Comparative Effectiveness Research.” Manhattan Institute for Policy Research Project FDA Report, June 2011.

[4] Basu, A., Jena, AB., Goldman, DP., Philipson, TJ., and Dubois, R. “Heterogeneity in Action: The Role of Passive Personalization in Comparative Effectiveness Research” Health Economics, 2014, 23 (3), 359–373.

[5] Gartlehner G, Hansen RA, Thieda P, DeVeaugh-Geiss AM, Gaynes BN, Krebs EE, Lux LJ, Morgan LC, Shumate JA, Monroe LG, Lohr KN. “Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Comparative Effectiveness Review No. 7.” Rockville, MD: Agency for Healthcare Research and Quality Report. January 2007.