According to an August 2015 survey, 72 percent of Americans find drug costs unreasonable, with 83 percent believing that the federal government should be able to negotiate prices for Medicare. Recently, Acting Administrator of the Centers for Medicare and Medicaid Services (CMS) Andy Slavitt commented that spending on medicines increased 13 percent in 2014 while health care spending growth overall was only 5 percent, the highest rate of drug spending growth since 2001.

Some of the most expensive drugs are covered under Medicare’s medical benefit, Part B, because they are administered by a physician. They are often administered in hospital outpatient departments and physician offices, and most commonly used to treat conditions like cancer, rheumatoid arthritis, and macular degeneration. Between 2005 and 2014, spending on Part B drugs has increased annually by 7.7 percent, with the top 20 drugs by total amount of Medicare payments accounting for 57 percent of total Part B drug costs. While overall Part B drug spending is a small portion of Medicare drug spending, the high growth rate is a concern, especially as new expensive breakthrough cancer drugs enter the market and have a negative effect on consumers’ pockets.

Unlike Part D, the prescription drug benefit, there are fewer incentives built in to Part B for providers to consider lower cost treatments for patients even if the lower cost drug may be clinically equivalent to the more expensive drug, because prior to budget sequestration, providers received 6 percent on top of the Average Sales Price (ASP) of the drug. Larger providers and hospitals often receive discounts on these drugs as well, increasing the amount they receive directly on top of the out-of-pocket cost of the drug.

This leads to more out-of-pocket costs for the consumer, as patients usually pay 20 percent of Part B services. The Government Accountability Office (GAO) estimated that in 2013, among new drugs covered under Part B, nearly two-thirds had per beneficiary costs of over $9,000 per year, leading to out-of-pocket costs for consumers of amounts between $1,900 and $107,000 over the year. On top of these high costs, this can lead to problems with medication adherence, even for serious conditions such as cancer.

A New Payment Model

To help change these incentives and control costs, CMS has proposed a new demonstration program, which offers a few different reimbursement methods for Part B drugs. The program includes a geographically stratified design methodology to test and evaluate the different methods. One of the methods garnering a lot of attention is a proposal to lower the administration add-on payment to providers, from current 6 percent of ASP, to 2.5 percent plus a flat fee of $16.80 per administration day.

Policymakers, physician organizations, and patient advocacy organizations have voiced major concerns raising the alarm that this initiative will negatively affect patient access to vital drugs and therefore produce poorer patient outcomes. The sequester will also have a significant impact on the percentage add on, reducing it to closer to an estimated .86 percent plus the flat fee. But we believe the goals of the program and its potential to reduce costs represent an important step in the right direction. We hope the details can be further shaped by the important communities of providers and patients who will deliver and receive medical care.

Geographic Variation

Last year, we wrote a Health Affairs Blog that highlighted some of the uses and limitations of publicly available Part B physician payment data. One major use was to show the geographic variation in practice patterns and drug administration, and we particularly looked at the difference across states in Lucentis v. Avastin usage. As seen in Exhibit 1, variation in administration is wide among states, even though both are drugs used to treat the same condition, age-related macular degeneration, and were proven to have clinically similar outcomes, but the cost of Lucentis was $2,000 per dose, while Avastin was only $50 per dose.

Using the same price estimates from our previous research, which are from 2012, we found that physician reimbursement under the proposed demonstration would potentially change from $120 to $66.80 for Lucentis, and increase from $3 to $18.05 for Avastin. Under the first payment model, providers were receiving 40 times as much to administer Lucentis instead of Avastin, while under the new proposed payment model, they would only receive 3.7 times as much.

While still a formidable gap, this new policy would have decreased financial reimbursement for providers to administer Lucentis, a costly, clinically similar drug to the much cheaper Avastin. As seen in Exhibit 1, a majority of physicians prescribe Avastin, thus this policy will allow for increased reimbursement in those cases, but in states where Lucentis is prescribed in higher proportions, prescribing patterns might start to change as a result of the proposed demonstration.

Source: Author’s estimates using 2012 CMS Cost Data and Sequestration Estimates from DrugAbacus.org

The proposed demonstration program includes much more than the ASP modifications in its second phase, including:

• discounting or eliminating beneficiary copays,
• indication-based pricing that would vary payments based on the clinical effectiveness,
• reference pricing for similar drugs,
• risk-sharing agreements with drug manufacturers based on clinical outcomes of the drug, and
• creating clinical decision tools for providers to help develop best practices.

This is all at the same time that a new model in oncology care (OCM) is being launched, which could help to draw attention to total cost of care. It is important that CMS try to address rising drug costs, but also be sure to consider all relevant considerations during the comment period to fine-tune the proposal to avoid negative effects on beneficiaries’ care.

We believe CMS should consider offering a waiver for organizations already participating in Center for Medicare & Medicaid Innovation (CMMI) models like the OCM, because financial benchmarks are based on past performance and any savings recognized in the future could be artificial, attributable to this demonstration rather than to better care coordination and some of the other practice requirements that are part of the proposed OCM. Furthermore, because this demonstration sets a new research precedent and because it is mandatory in the selected study areas rather than voluntary, CMS must try to anticipate and avoid unintended consequences related to geographic stratification.

For example, it is possible to imagine organizations with multiple locations directing patients to optimal sites for their business. Also, without a control group, some findings may be unreliable. The proposed rule currently lacks much detail, and there does not seem to be enough time for organizations to evaluate the impact of the proposed rule on their operations. Having said that, it will be important for stakeholders of all types to submit comments to the proposed rule in an effort to improve the final rule prior to implementation.

The critical question for the policymakers and stakeholders is whether this model can align with the multitude of other payment model reforms — unintended consequences could mitigate all the positive outcomes that a CMMI model offers to beneficiaries. Helping beneficiaries is and should be CMS’ ultimate obligation.

As the biological basis of more diseases are fully revealed, and the drugs targeting medical problems become more focused and effective, more patients are finding themselves on costlier specialty medicines. At the same time, consumers find themselves paying a growing portion of their drug bills out of pocket as the structure of insurance changes. These two developments have combined to result in significant consumer hardship.

In response to these trends, there has been political pressure to enact policies giving federal and state governments authority to set drug prices or limit price increases. However, these policies could have the unintended consequence of reducing the incentive to develop more effective drugs.

In Europe, government price-setting authorities systematically overpay for some older, less innovative drugs while reducing the prices of and access to newer, more significant breakthroughs. Many worry that enacting a similar policy in the United States would reduce the profitability of new, innovative research endeavors.

We believe that certain regulatory reforms can address these concerns and encourage more robust competition within the drug market. These policies would allow prices to more easily adjust to reflect how medicines are prescribed and the outcomes they deliver, and thus would help control rising spending and reduce the burden of drug costs for consumers. One way to make drug pricing more competitive is to implement selling models that tie the price of drugs more closely to the usefulness of the clinical setting in which they are being prescribed. However, existing regulations obstruct this type of market-oriented approach.

Pricing Based On Indication And Outcomes

The Centers for Medicare and Medicaid Services (CMS) recently announced that as early as 2017, it plans to pursue changes in the way Medicare pays for injectable drugs under its Part B program to give drug makers more flexibility to price products based on indications and outcomes. Yet the Medicare program left open how the relative value of different indications would be determined. Would drug makers be free to vary prices based on clinical demand and the benefits being offered in different clinical settings? Or as the rule suggests, will CMS try to influence these conclusions with an assessment of clinical value?

CMS’ proposed rule also does not address several challenges associated with a value-based pricing framework. For example, the proposal did not address the small molecule drugs that are the focus of much of the price scrutiny, only injectable drugs paid for as part of the medical benefit. Moreover, enabling such a framework for value-based pricing would require simultaneous regulatory reforms at the Food and Drug Administration (FDA), as well as the Office of the Inspector General. Because the impediments to this sort of policy effort cut across multiple agencies, it will likely require a legislative remedy to fully enable.

Inside CMS, enabling drug makers to adjust prices based on the purpose for which medicines are being prescribed will require changes to the existing rules that govern drug pricing. For example, federal regulators will need to relax the way that they implement current price-setting constructs like the calculation for Medicaid best price, the ceiling price for the 340B program, and the reporting rules for Medicare’s Part B average sales price. These rules complicate the ability of companies to price the same drug differently, based on how it’s being prescribed, or to enter into “value-based’ contracts that tie drug prices and discounts to measures of how a population of patients benefit from a given treatment.

Take, for example, the Medicaid Best Price rules. Best price is the lowest manufacturer price paid for a drug by any purchaser. It’s defined by the Medicaid statute as “any wholesaler, retailer, provider, health maintenance organization, or nonprofit or government entity” with some exceptions (Note 1). In short, it’s the cheapest price at which a drug is sold. A drug’s reported best price is required to reflect all discounts, rebates, and other pricing adjustments. It’s the benchmark that the government uses to make sure that state Medicaid programs are receiving the lowest price for which a drug is being offered to any purchaser.

Under these rules, if a drug maker enters into a contract with a private health plan to discount a drug based on how it’s being used (or the clinical results that it achieves) then the discount that’s offered when the drug is used in settings that are judged to yield less value would become the new benchmark for calculating the Medicaid best price. The rebates offered to a private insurer under the terms of just one value-based contract would establish the new price offered to all Medicaid programs, regardless of whether or not the Medicaid plans were also entering into similar contracting arrangements. So Medicaid plans that did not contract to pay higher prices when drugs were used in certain higher value settings, and lower prices when they were prescribed for lower value indications, would nonetheless pay a price for all of their prescriptions that reflected the lowest price offered under a value-based arrangement. This new Medicaid price could, in turn, influence other price schedules.

Consider a drug maker that offered a 90 percent discount on a drug when it didn’t produce any of its expected benefit. Under current rules, that deeply discounted price would become the new Medicaid best price, but not necessarily the blended price that reflects the average price being paid under a contract where the price fluctuated based on how a drug was being prescribed. This could create a significant disincentive for manufacturers to offering indication and outcome-based prices. For these reasons, enabling drug makers to adjust prices based on these parameters will require changes to rules on how drug makers must track and report prices to the government under Medicaid and to the 340B drug program.

Similar challenges to value-based pricing are posed by Medicare’s calculation of average sales price (ASP) as part of its framework for reimbursing injectable drugs paid under Part B. The ASP is defined as a manufacturer’s sales of a drug to all U.S. purchasers in a calendar quarter divided by the total number of units of the drug sold by the manufacturer in that same quarter (Note 2). The ASP is net of any price concessions, such as volume discounts, prompt pay discounts, cash discounts, free goods contingent on purchase requirements, chargebacks, and rebates other than those obtained through the Medicaid drug rebate program.

Manufacturers that offer discounts under commercial, value-based contracts would probably face reductions in their calculated ASP as a result of the concessions. In turn, they would see their reimbursement under Medicare Part B also decline, regardless of whether Medicare entered into the same outcome or indication-based contracts. Since the private market pegs its own pricing off of the ASP, a single value-based contract that served to lower the ASP could have the effect of reducing a drug maker’s reimbursement across every other contract. For drug manufacturers, this is another disincentive to entering into these arrangements.

Moreover, without significant regulatory changes, it is unlikely that Medicare would participate in a value-based system due to both legal and practical limitations. In the past, CMS has avoided these contracting arrangements when sponsors have approached the agency with such proposals. Even if CMS asserts the legal authority to enter into such arrangements, it is unclear whether the agency has the informational capacity to implement them. Managing a value-based system would require careful tracking of how and when drugs are prescribed, and collecting information to measure outcomes. Currently, CMS probably lacks the capacity to carry out this level of measurement and analysis. So for now, it will mostly be left to private payers to pursue value-based arrangements.

Reducing Regulatory Barriers

To reduce obstacles to value-based pricing, new regulations would need to be issued to clarify how drug makers, insurance plans, and health systems can rationalize value-based and indication-based contracts with their price reporting calculations. Medicare probably has the requisite authority to do so under constructs created by the Affordable Care Act. Additionally, Congress could provide clear authority and direction through legislation addressing these policy opportunities.

The Medicare and Medicaid programs could exempt value-based contracts that meet certain criteria from the requirement that the resulting prices, and the discounts, be used toward calculating Medicaid best price. CMS recently signaled that it had the existing authority to address some of these issues through a pilot program designed under the Center for Medicare and Medicaid Innovation (CMMI). Such a program could enable commercial health plans to adapt their reporting obligations to test how value-based and indication-based contracts would impact overall spending and outcomes. While the proposed regulation lays out Medicare’s general intent to pursue these strategies, it does not outline the parameters needed in order to go forward.

Some of the regulatory discretion that is required to change drug-pricing systems may be outside of the Medicare agency’s direct control. For example, the Office of the Inspector General (OIG) would have to change its interpretation of anti-kickback rules to enable drug makers to provide discounts based on the clinical indications for which drugs are prescribed, as well as the outcomes they deliver. Otherwise, under the OIG’s existing interpretation of its authority, these arrangements could be perceived as inducements to prescribing.

Fostering outcomes-based and indication-based pricing will also require FDA to adapt some of its existing rules and practices. Currently, drug makers are largely prevented from offering price concessions based on how a drug is used unless all of the prescribing options are listed precisely and completely on the drug’s label. When a drug maker secures approval for a new medicine, what appears on its drug label forms the basis for any outcomes-based contracts with health plans or Pharmacy Benefit Managers (PBMs), even if it would make more sense to contract for drugs based on measuring outcomes for which the drug is not explicitly approved. So far, FDA’s sometimes-purposeful ambiguity over the scope of its authority in these areas of commercial speech creates enough legal risk to discourage these sorts of business interactions.

In order to enable these arrangements, FDA would have to concede that commercial, contract-related communications constitute protected speech under the First Amendment and thus are not subject to the agency’s active regulation. At the least, FDA could stipulate that it does not forfeit its authority to regulate these and similar forms of commercial communication, but as a matter of policy will exercise enforcement discretion when it comes to value-based contracts and their negotiation. Better still, Congress can more firmly establish the same safe harbors in legislation, rather than leaving it up to FDA to stipulate these important legal principles in non-binding guidance or regulation.

Another impediment to contracting based on outcomes measurement is uncertainty over the FDA’s regulation of pre-approval communication. FDA prohibits pre-approval communication, but has not specified whether these restrictions extend to discussions between drug makers and drug purchasers that are conducted as part of contracting discussions prior to a drug’s launch. Pre-market commercial discussions are an important part of the ability to negotiate these complex, value-based contracts, as the contracts would need to be put into place at the time of approval. Because targeted pre-approval conversations between manufacturers and health plans are not inherently promotional, FDA as a matter of policy should not seek to regulate them.

Absent these collective regulatory impediments, drug makers and those who pay for medicines could have more ability and incentive to engage in price negotiations based on the indication for which a medicine is being prescribed by providers and the variable outcomes that it delivers to patients. In the absence of reforms to make drug pricing more competitive, the political alternative may well be regulated pricing. This approach would end up skewing investment because it would inevitably allocate capital based on political priorities rather than scientific priorities and clinical goals.

The discussion over drug prices is driven by a fair degree of politics, but the debate arose because of secular changes in the political economy of health care, and increasing costs to consumers. These challenges need to be addressed with constructive measures that foster access to and competitive pricing of medicines, while preserving market-based rewards for innovation, and the efficient allocation of capital to these efforts.

Note 1: Exceptions to the best price include prices that are charged to certain federal purchasers (sales made through federal supply schedule, single award contract prices of any federal agency, federal depot prices, and prices charged to the Department of Defense, Department of Veterans Affairs, Indian Health Service, and the Public Health Service), eligible state pharmaceutical assistance programs, and state-run nursing homes.

Note 2: Section 1847A(c) of the Social Security Act (the Act), as added by the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA), P.L. No. 108-173, defines an ASP as a manufacturer’s sales of a drug to all purchasers in the United States in a calendar quarter divided by the total number of units of the drug sold by the manufacturer in that same quarter.

Editor's Note: Both authors consult with and invest in life science and healthcare services companies.

Editor's note: This piece originally appeared in Health Affairs Blog.

Event Information

As the prevalence of drug-resistant bacteria continues to rise, there is a pressing need for new drugs to combat infections by these organisms. However, research and development in this area has slowed, creating a public health concern that we lack the drugs necessary to treat multi-drug resistant infections. Challenges to promoting antibacterial drug development may be scientific, methodological, regulatory, or economic in nature.

On Wednesday, May 9, 2012, the Engelberg Center for Health Care Reform convened an expert workshop, "Facilitating Antibacterial Drug Development,” that explored solutions to methodological and regulatory challenges that could make the development process more efficient. This meeting brought together diverse multi-stakeholder experts—including medical product developers, health care professionals, researchers, patient advocates, representatives of the U.S. Food and Drug Administration, and other groups—to explore the following issues:

• Existing paradigms for antibacterial drug development;
• Novel approaches to further antibacterial drug development, including use of pharmacokinetics and pharmacodynamics, Bayesian methods, innovative clinical trial designs, new data sources, alternate clinical endpoints, and new regulatory tools; and
• Short- and long-term opportunities to advance the antibacterial drug development enterprise through collaboration among stakeholders, improved regulatory science, and other means.

For more information on FDA’s Antibacterial Drug Development Task Force, click here.

Event Materials

• May 9 Event Summary
• Antibacterial Drug Development Participant List
• Facilitating Antibacterial Drug Development Agenda
• Facilitating Antibacterial Drug Development Discussion Guide
• Panel 1 Brad Spellberg Presentation
• Panel 1 George Talbot Presentation
• Panel 1 John Powers Presentation
• Panel 1 Thomas Fleming Presentation
• Panel 2 George Drusano Presentation
• Panel 2 Scott Emerson Presentation
• Panel 3 Daniel Benjamin Presentation
• Panel 3 Edward Cox Presentation
• Panel 3 John Rex examples
• Panel 3 John Rex Presentation
• Panel 4 Helen Boucher Presentation

Event Information

As part of ongoing cooperative work with the U.S. Food and Drug Administration, the Engelberg Center for Health Care Reform has formed a council to bring together expert perspectives on the challenges facing antibacterial drug development. Designed to include representatives from academia, patient advocacy groups, industry, providers, and government agencies, the Brookings Council on Antibacterial Drug Development (BCADD), will convene twice a year to discuss pressing issues in the treatment of infectious diseases and potential steps to address them.  

The first BCADD meeting, held on August 30, 2012, brought stakeholders together to discuss the following:

• Ongoing antibacterial initiatives at FDA and the Clinical Trials Transformation Initiative
• Statistical and methodological approaches that could be harnessed to improve the efficiency of antibacterial drug development
• Balancing benefit-risk and uncertainty considerations with public health needs
• Next steps for council action

For more information on FDA’s Antibacterial Drug Development Task Force, click here.

Event Materials

• 30 antibacterial drug development summary
• Presentation Slides
• FINAL BCADD Discussion Guide 20120828
• FINAL May 9 Summary 20120828
• Participant List_Final

Event Information

As part of an ongoing cooperative agreement with the U.S. Food and Drug Administration (FDA), the Engelberg Center for Health Care Reform at Brookings has formed the Brookings Council on Antibacterial Drug Development (BCADD) to identify steps to address the major technical, regulatory, and financial barriers impeding antibacterial drug development. At the first meeting of the BCADD, stakeholders emphasized the importance of concentrating on discrete policy and program areas to revitalize the antibacterial drug development enterprise.

BCADD convened a diverse group of stakeholders, including FDA officials, industry and biotech representatives, payers, providers, clinicians, and academic researchers Wednesday, February 27, 2013, to discuss two of the economic challenges facing antibacterial drug development:

• Better understanding the potential role of incentives in drug discovery and development; and
• Identifying potential reimbursement models that can support both stewardship and expanded investment for antibacterial drug products.

Event Materials

• meeting summary 20130925 FINAL
• Discussion Guide
• Participant List
• Presentation

Event Information

Antibacterial drug resistance is a global public health threat poised to worsen due to the combination of the inappropriate use of existing drugs and a marked decline in innovative antibacterial drug development. In order to tackle this problem, stakeholders must consider comprehensive strategies that address both drug development and stewardship.

On February 7, the Engelberg Center for Health Care Reform convened an expert workshop, “Modernizing Antibacterial Drug Development and Promoting Stewardship” to explore a two-pronged approach to combating antibacterial drug resistance that includes: 1) the development of pathogen-focused antibacterial drugs that target the most serious public health threats; and 2) stewardship efforts for all antibacterial products in order to preserve their utility. Participating stakeholders included experts from the drug development and health care industries, the clinical community, government, and academia. These stakeholders shared their insights on potential frameworks and evidentiary considerations for pathogen-focused drug development, and efforts underway to promote the appropriate use of commonly used antibacterial drugs in the ambulatory care setting.

Event Materials

• Antibiotic Development Slides
• 07 antibacterial expert workshop discussion guide
• 07 antibacterial expert workshop public agenda
• 07 antibacterial expert workshop meeting summary

Event Information

Antibacterial drugs are a critical component of the nation’s public health armamentarium, and have saved millions of lives by preventing and treating a range of bacterial infections. However, antibacterial drug development has been hampered by challenges unique to the antibacterial drug market, which have stifled innovation and left patients and providers with fewer options to treat increasingly resistant infections. One consequence of the dwindling antibacterial drug pipeline has been a reduction in effective oral antibacterial drug treatment options, which are particularly important in the ambulatory and transitional care contexts. Recent proposals to re-invigorate the antibacterial pipeline are geared towards serious infections treated in the inpatient setting, which may lead to a greater focus on intravenous therapies. However, addressing both current and future needs in the infectious diseases space will require a balanced mix of both oral and parenteral antibacterial drugs.

In cooperation with the U.S. Food and Drug Administration (FDA), the Engelberg Center for Health Care Reform at Brookings held an expert workshop on November 20, 2014, to identify the most promising strategies to support oral antibacterial drug development. Participating stakeholders included experts from the drug development and health care industries, the clinical community, government, and academia. These stakeholders shared their insights on potential regulatory, scientific, and economic strategies to reinvigorate the oral antibacterial drug pipeline. 

Event Materials

• Reinvigorating the Oral Antibacterial Drug Development Pipeline Agenda
• Reinvigorating the Oral Antibacterial Drug Development Pipeline Discussion Guide
• Biographies 20141118
• Reinvigorating the Oral Antibacterial Drug Development Pipeline Slide Deck

Legislative proposals to accelerate and improve the development of innovative drugs and medical devices generally focus on reforming the clinical development and regulatory review processes that occur before a product gets to market. Many of these proposals – such as boosting federal funding for basic science, streamlining the clinical trials process, improving incentives for development in areas of unmet medical need, or creating expedited FDA review pathways for promising treatments – are worthy pursuits and justifiably part of ongoing efforts to strengthen biomedical innovation in the United States, such as the 21^st Century Cures initiative in the House and a parallel effort taking shape in the Senate.

What has largely been missing from these recent policy discussions, however, is an equal and concerted focus on the role that postmarket evidence can play in creating a more robust and efficient innovation process. Data on medical product safety, efficacy, and associated patient outcomes accrued through routine medical practice and through practical research involving a broad range of medical practices could not only bolster our understanding of how well novel treatments are achieving their intended effects, but reinforce many of the premarket reforms currently under consideration. Below and in a new paper, we highlight the importance of postmarket evidence development and present a number of immediately achievable proposals that could help lay the foundation for future cures.

Why is postmarket evidence development important?

There are a number of reasons why evidence developed after a medical product’s approval should be considered an integral part of legislative efforts to improve biomedical innovation. First and foremost, learning from clinical experiences with medical products in large patient populations can allow providers to better target and treat individuals, matching the right drug or device to the right patient based on real-world evidence. Such knowledge can in turn support changes in care that lead to better outcomes and thus higher value realized by any given medical product.

Similarly, data developed on outcomes, disease progression, and associated genetic and other characteristics that suggest differences in disease course or response to treatment can form the foundation of future breakthrough medical products. As we continue to move toward an era of increasingly-targeted treatments, this important of this type of real-world data cannot be discounted.

Finally, organized efforts to improve postmarket evidence development can further establish infrastructure and robust data sources for ensuring the safety and effectiveness of FDA-approved products, protecting patient lives. This is especially important as Congress, the Administration, and others continue to seek novel policies for further expediting the pre-market regulatory review process for high-priority treatments. Without a reliable postmarket evidence development infrastructure in place, attempts to further shorten the time it takes to move a product from clinical development to FDA approval may run up against the barrier of limited capabilities to gather the postmarket data needed to refine a product’s safety and effectiveness profile. While this is particularly important for medical devices – the “life cycle” of a medical device often involves many important revisions in the device itself and in how and by whom it is used after approval – it is also important for breakthrough drugs, which may increasingly be approved based on biomarkers that predict clinical response and in particular subpopulations of patients.

What can be done now?

The last decade has seen progress in the availability of postmarket data and the production of postmarket evidence. Biomedical researchers, product developers, health care plans, and providers are doing more to collect and analyze clinical and outcomes data. Multiple independent efforts – including the U.S. Food and Drug Administration’s Sentinel Initiative for active postmarket drug safety surveillance, the Patient-Centered Outcomes Research Institute’s PCORnet for clinical effectiveness studies, the Medical Device Epidemiology Network (MDEpiNet) for developing better methods and medical device registries for medical device surveillance and a number of dedicated, product-specific outcomes registries – have demonstrated the powerful effects that rigorous, systematic postmarket data collection can have on our understanding of how medical products perform in the real-world and of the course of underlying diseases that they are designed to treat.

These and other postmarket data systems now hold the potential to contribute to data analysis and improved population-based evidence development on a wider scale. Federal support for strengthening the processes and tools through which data on important health outcomes can be leveraged to improve evidence on the safety, effectiveness, and value of care; for creating transparent and timely access to such data; and for building on current evidence development activities will help to make the use of postmarket data more robust, routine, and reliable.

Toward that end, we put forward a number of targeted proposals that current legislative efforts should consider as the 2015 policy agenda continues to take shape:

Evaluate the potential use of postmarket evidence in regulatory decision-making. The initial Cures discussion draft mandated FDA to establish a process by which pharmaceutical manufacturers could submit real-world evidence to support Agency regulatory decisions. While this is an important part of further establishing methods and mechanisms for harnessing data developed in the postmarket space, the proposed timelines (roughly 12 months to first Guidance for Industry) and wide scope of the program do not allow for a thoughtfully-, collaboratively-considered approach to utilizing real-world evidence. Future proposals should allow FDA to take a longer, multi-stakeholder approach to identify the current sources of real-world data, gaps in such collection activities, standards and methodologies for collection, and priority areas where more work is needed to understand how real-world data could be used.

Expand the Sentinel System’s data collection activities to include data on effectiveness. Established by Congress in 2007, Sentinel is a robust surveillance system geared toward monitoring the safety of drugs and biologics. In parallel to the program for evaluating the use of RWE outlined above, FDA could work with stakeholders to identify and pursue targeted extensions of the Sentinel system that begin to pilot collection of such data. Demonstration projects could enable faster and more effective RWE development to characterize treatment utilization patterns, further refine a product’s efficacy profile, or address pressing public health concerns – all by testing strategic linkages to data elements outside of Sentinel’s safety focus.

Establish an active postmarket safety surveillance system for medical devices. Congress has already acted once to establish device surveillance, mandating in 2012 that Sentinel be expanded to include safety data on medical devices. To date, however, there has been no additional support for such surveillance or even the capability of individually tracking medical devices in-use. With the recently finalized Unique Device Identifier rule going effect and the ability to perform such tracking on the horizon, the time is now to adopt recent proposals from FDA’s National Medical Device Postmarket Surveillance System Planning Board. With Congressional authorization for FDA to establish an implementation plan and adequate appropriations, the true foundation for such a system could finally be put into place.

Event Information

The Risk Evaluation and Mitigation Strategies (REMS) program has become an important tool of the U.S. Food and Drug Administration (FDA) in ensuring that the benefits of a given medical product outweigh the associated risks, and has enabled FDA to approve a number of products that might not otherwise have been made available for patient use. Since the implementation of the REMS program, however, concerns have been raised regarding its impact on patient access to products and the associated burden on providers and health care systems. In an effort to address these concerns—and as part of its commitments under the Prescription Drug User Fee Act reauthorization of 2012—FDA has undertaken efforts to standardize and improve the effectiveness of REMS, and to better integrate REMS programs into the health system. As part of this broader initiative, the Agency is currently assessing the feasibility of integrating accredited continuing education (CE) programs and activities into REMS programs that have been developed for a single drug.

Under a cooperative agreement with the FDA, the Center for Health Policy held an expert workshop on May 18, titled “Incorporating Continuing Education into Single-Drug REMS: Exploring the Challenges and Opportunities”. This workshop provided an opportunity for pharmaceutical manufacturers, regulators, CE providers, accreditors, and other stakeholders to explore the ways that CE can be a valuable addition to the REMS toolkit, discuss potential barriers to the development and implementation of REMS-related CE for single products, and identify strategies for addressing those barriers.

Event Materials

• Bio sheet
• REMS CE Meeting Agenda
• REMS_CE_Meeting_Discussion_Guide_Final
• REMS CE Meeting Summary

For the last several years, the US government has been negotiating a free-trade agreement known as the Trans-Pacific Partnership (TPP) with 11 other countries across the Asia-Pacific and Latin American regions, which could have major impact on the pharmaceutical market.  When finalized it will be the largest free-trade agreement in history, impacting up to one-third of world trade and roughly 40 percent of the global gross domestic product. The deal has attracted a fair share of criticism from a wide range of groups, including concerns over proposed regulations for biologic drugs in participating countries. Specifically, critics are concerned about the length of data exclusivity granted to the companies that hold the patents on these drugs. Below is a primer on biologics and how they are being addressed in the TPP.

Biologic drugs include any therapy derived from a biological source; a group which includes vaccines, anti-toxins, proteins, and monoclonal antibodies. Because they are typically much larger and more structurally complex than traditional ‘small-molecule’ drugs, they are also more difficult—and much more costly—to develop and manufacture. Biologics are also among the most expensive drugs on the market, costing an average of 22 times more than nonbiologic drugs. Avastin, a cancer drug, can cost more than $50,000 a year, while the rheumatoid arthritis drug Remicade can cost up to $2,500 per injection.

Given these high costs, there is substantial interest in encouraging the development of biosimilars, a term used to describe follow-on versions of an original biologic. Estimates of the potential cost savings vary substantially, but some have predicted that competition from biosimilars could reduce US spending on biologics by $44 to $66 billion over the next ten years.  In the European Union, biosimilars have been on the market since 2006, and a 2013 analysis found that, for the 14 biosimilars on the market, the average price discount was about 25 percent. By 2020, the overall cost savings are projected to total $16-$43 billion.

After the Affordable Care Act (ACA) was passed in 2010, the US Food and Drug Administration (FDA) developed an accelerated approval pathway for biosimilars, modeled after the pathway used for the approval of small-molecule generics. In order to meet the criteria for biosimilarity, the drug must share the same mechanism of action for the approved condition of use, and there must be no clinically significant differences between the two drugs in terms of purity, safety, or potency. FDA recently approved its first biosimilar, Zarxio, which is a copy of the oncology drug Neupogen.

Under current FDA regulations, biologic drugs are granted 12 years of data exclusivity following approval. During this period of exclusivity, the FDA may not approve a biosimilar application that relies on the data submitted as part of the original biologic application. This form of temporary monopoly is distinct from patent protection, which is granted well before approval and is not related to clinical data.  Data exclusivity does not prevent another company from generating the data independently, but drug companies are unlikely to go to the considerable (and costly) effort of replicating a full course of clinical trials for a drug that is already on the market. (Though biosimilars may need to undergo some additional clinical testing under current FDA regulations, the amount of data required to support approval would certainly be less than what is required for an original biologic approval.)

The 12-year exclusivity period for biologics was established in the ACA following intense debate, and has continued to attract criticism. (By contrast, the period of data exclusivity is just five years for small-molecule drugs.) Supporters argue that given the greater cost and difficulty of bringing a biologic to market a longer period of exclusivity is necessary to incentivize innovation. Others argue that the resulting restrictions on competition keep drug prices unnecessarily high, inevitably putting a strain on the health system and keeping potentially life-saving drugs out of reach for many patients.

For the 11 countries besides the U.S. that are involved in the TPP, current data exclusivity protections range from zero (Brunei) to eight years (Japan). Under the Obama Administration’s current proposal, participating countries would increase those periods to match the US standard of 12 years. Curiously, this proposal directly contradicts the administration’s ongoing domestic efforts to lower the period of data exclusivity. Since the ACA passed, the Obama administration has repeatedly proposed reducing it to seven, arguing that this would save Medicare $4.4 billion over the next decade. Some have noted that, once the 12-year period is enshrined in the TPP, it will become significantly more difficult to change it through the US legislative process. Furthermore, imposing US standards on the 11 member countries would inevitably restrict competition at the global level, and many patient advocacy and international humanitarian organizations have argued that doing so would undermine the efforts of US global health initiatives like the Vaccine Alliance and the Global Fund to Fight AIDS, Tuberculosis and Malaria, which rely on price competition to manage program costs.

It is unclear whether the US will be successful in its efforts. There have been reports that the issue of data exclusivity has become a significant point of contention, and the US delegation may seek to compromise on its demands. It may, for example, negotiate exceptions for the poorer countries involved in the negotiation, as the Washington Post notes. However, the details of the negotiations are largely confidential, which makes it challenging to assess the possibilities, their relative advantages, or how the US Trade Representative (which is leading the US negotiations) is balancing the need to ensure adequate incentives for innovation with the need to control drug costs and facilitate patient access to potentially life-saving therapies.

Editor's note: Elizabeth Richardson, a research associate in the Center for Health Policy, contributed to the research and writing of this post.