Drug Costs: What Can Infectious Diseases Physicians Do?

(See the Prespective by Costantini and Walensky, on pages 690–6.)

The cost of health care in the United States is increasing, driven by myriad factors that seem to be out of the individual physician’s control. In this issue of The Journal of Infectious Diseases, Costantini and Walensky issue a call to arms to infectious diseases physicians to address the rising costs of prescription drugs [1]. The authors raise a critical issue at a critical time, as costly new antimicrobials are developed, others go off-patent, the government turns its attention to drug pricing, and policymakers are motivated to curb price increases and contain costs. We physicians have the opportunity to act.

Costantini and Walensky illustrate the pricing issues for both branded and generic prescription drugs [1]. For branded drugs, the need to provide appropriate compensation for innovation competes with the need for affordability and patient access. The example of sofosbuvir (Sovaldi) for hepatitis C is an apt illustration of the tension between the value of a curative treatment and the ability and willingness of payers to cover it. Despite the high initial price of Sovaldi and its successor sofosbuvir/ledipasvir (Harvoni), cost-effectiveness studies supported their value for hepatitis C virus (HCV) treatment [2–4]. However, due to budgetary concerns, payers instituted authorization restrictions that limited access to patients with specific indications [5, 6]. The price of HCV treatment has declined since then, pushed by advocacy and media pressure, but also through emergence of a competitive marketplace. The authors highlight a similar issue for linezolid: cost-effectiveness studies reinforced the value of the drug, but prices only decreased after competition was introduced by approval of generics [7].

However, generic formulations do not guarantee lower prices. For generics, competition directly influences pricing. In a monopoly market, opportunistic business decisions (eg, Turing Pharmaceuticals’ pricing of pyrimethamine) and interruptions in manufacturing and supply (eg, penicillin) increase prices. In a recent study, monopoly markets were associated with price increases of 47% from 2008 to 2013, compared with decreases of 31% for drugs with 4 or more manufacturing competitors [8]. Drugs for which there is no effective substitute may be even more vulnerable to price increases. Prices rise after a manufacturing shortage, and the effect is magnified for drugs with fewer than 4 manufacturers [9]. The Food and Drug Administration has recognized the importance of a healthy generic marketplace and promised to reduce barriers for generic manufacturers [10]. Drug manufacturing is a business, and market factors play a critical role in price setting for both branded and generic drugs.

With the complexity of the prescription drug market, it may not be clear how we as physicians can respond. We underscore 3 of Costantini and Walensky’s recommendations [1] to:

1. improve our understanding of drug value and pricing

2. develop strategies to incorporate value and costs into patient-level decision making

3. incorporate drug value and costs into guidelines.

The authors advocate for increased physician awareness about the value of medical interventions. National initiatives, such as the American College of Physicians’ Choosing Wisely campaign, point out easy targets for practice change [11]. A basic understanding of health care economics can arm the next generation of physicians with skills needed to assess value. Formal “value rounds,” advocated by Costantini and Walensky, can reinforce this information [1]. To improve our understanding, we need to increase transparency about the cost of health care interventions. Ideally, costs to both the patient and the health care system must be considered. The published average wholesale prices used by the authors exclude negotiated rebates and discounts, and do not represent actual prices that purchasers pay. Actual prices are considered trade secrets, opaque to external decision makers and clinicians. The out-of-pocket cost to patients, which varies based on the insurance plan and pharmacy benefit managers, is even more complex. In addition, pharmaceutical companies offer coupons to patients, offsetting cost-sharing policies set by insurers. All of these discounts may create incentives to choose drugs that provide less value for money to society than alternatives [12, 13].

We also need to establish a framework on how to incorporate value and costs into clinical decision making—societal cost-effectiveness thresholds are useful for policymakers and payers, but do not add much insight at the bedside, where trade-offs between quality and cost are individualized. Physicians may not feel comfortable discussing costs with their patients or may not know what to recommend [14]. Patients may have varying preferences as well: a study about out-of-pocket costs for the new heart failure drug sacubitril-valsartan identified 5 different approaches that patients used in deciding whether they would take the new drug at a high price [15]. While it is laudable for physicians to be informed about costs of care, determining how they should respond to that information still needs refinement.

In considering such a framework, we need to be aware of the tension between our primary duty to the patient and our responsibility to promote just allocation of health care resources. In many cases, these interests will align and reduce health care costs by discouraging lower-value interventions. However, we should be cautious of supporting initiatives that impair patient access to effective high-value health care, or those that put undue financial burden on our patients, especially patients with lower incomes. Out-of-pocket drug costs may force patients to forego needed treatment [16, 17]. Cost-related nonadherence is well documented in chronic diseases and, for example, may become a factor with human immunodeficiency virus (HIV) infection as cost-sharing programs for antiretrovirals are proposed by Medicare and by private payers [18–20]. Other means of cost containment may also come with negative consequences. Costantini and Walensky highlight a recent UnitedHealthcare initiative called MyScriptsRewards, which offers patients financial incentives to switch from coformulated antiretroviral regimens to multipill regimens containing tenofovir disoproxil fumarate, an older formulation associated with increased rates of bone and kidney toxicities [1]. Critics of this program raised the potential for the program to be coercive, as patients may choose to accept higher drug toxicity for cost savings. Prior authorization restrictions also hinder treatment access, such as in the case of hepatitis C, where there are disparities in medication denials based on insurance type [21, 22]. Of course, prior authorization also places an uncompensated administrative burden on providers and pharmacies.

We agree with Costantini and Walensky that physicians must play an informed role in the debate, but there are complicating factors to consider [1]. Physicians have financial relationships with hospitals and health care practices, payers, and pharmaceutical companies. These relationships need to be recognized and acknowledged, even as we maintain our primary professional duties to our patients and society. We also need to be aware that even as we engage in the effort to contain health care costs, these savings may be diverted. In the private sector, cost containment may increase insurance company profits, rather than fund other aspects of health care. In the public sector, reallocation to health care is not guaranteed either, as evidenced by the recent diversion of $5.7 million from the Ryan White HIV/AIDS Program to offset the costs associated with detainment of individuals at the US border [23].

Costantini and Walensky call on guidelines committees to incorporate cost and value into their recommendations [1]. We agree that professional societies should be leading the conversation about value in health care. Many Infectious Diseases Society of America (IDSA) guidelines incorporate cost effectiveness, but not in a routine way, while some guidelines for HCV and HIV include dedicated sections on cost and cost effectiveness [24–26]. Other societies have taken stronger steps: the American College of Cardiology/ American Heart Association and the American Society of Clinical Oncologists have each released statements on how guideline panels should incorporate value into clinical guidelines [27, 28]. Though the methodologies differ between the 2 approaches, the IDSA can follow suit, adopting a framework that guidelines committees can follow to ensure that assessments of value are done in a uniform and consistent way. Other frameworks, such as those used by the Institute for Cost-Effectiveness Research, also can inform panels in assessing value [29]. Now is an ideal time for IDSA to act—as new costly antimicrobial agents are developed and as HCV and HIV have entered an era where multiple effective therapies are available. IDSA guidelines panels’ opinions on how to prioritize the value of treatments can help providers, payers, and policymakers make informed decisions.

With the complexity of drug pricing, and competing interests of the stakeholders involved, our voice is critical to ensure the best health care for our patients with the resources that we spend. We must use our role as trusted professionals and caregivers to shape these decisions and fulfill our priorities for patient care and public health. We support Costantini and Walensky [1] in their call to arms to infectious diseases physicians and guidelines panels to be informed and active members of the drug pricing debate.

Notes

Disclaimer. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the views of the funding agency.

Financial support. This work was supported by the National Institute of Mental Health (grant number T32 MH073553 to S. N. K.).

Potential conflicts of interest.  S. N.K. is a coinvestigator on research grants paid to Weill Cornell from Gilead Sciences Inc. for the study of hepatitis C treatment and receives no salary support from this source. R. M. G. reports no potential conflicts. The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.