Healthcare Reform, Comparative Effectiveness Research, and P&T Decisions

It is the goal of publicly sponsored comparative effectiveness research (CER) to “assist patients, clinicians, purchasers, and policymakers in making informed health decisions,” thereby reducing uncertainty, increasing precision, and ultimately improving health outcomes.¹ In pharmaceutical care, there is a long-standing and well-known maxim that the ultimate objective for decision makers is to ensure that the right drug is prescribed to the right patient at the right time. Although this objective is difficult to dispute, it also is difficult to achieve. Despite the best judgment of healthcare policymakers and providers, sometimes precision in healthcare decision making is either not fully realized or realized only after an iterative process that may expose patients to a variety of healthcare interventions that are not well matched to their unique needs and circumstances.

CER in Healthcare Reform

In the recently enacted healthcare reform legislation, the Patient Protection and Affordable Care Act of 2010, CER is positioned to support the development of comparative evidence that will better inform healthcare decision making. However, many questions remain about how the new law will be implemented. The American Recovery and Reinvestment Act of 2009 provided $1.1 billion in new public funds for CER and set in motion a series of activities including the development of federal priorities for CER and efforts to enhance the nation’s research infrastructure to conduct CER in real-world settings. To help manage and augment the new public focus on CER, the 2010 healthcare reform law created the nonprofit Patient-Centered Outcomes Research Institute (the Institute). It is not a government agency, but rather an independent organization with a multistakeholder board of governors and sustained public—private funding for CER that will reach nearly $650 million by 2014.

How will this new Institute and the research that it supports impact the role and responsibilities of pharmacy & therapeutics (P&T) committees, and how will the comparative evidence created help to inform P&T decisions? Like many of the questions surrounding CER, the answers are not entirely clear. However, it may be useful to consider a few of the specifics in the new law, as P&T committees will be critical first-line users of the findings from publicly sponsored CER. Recommendations of P&T committees are, of course, essential in determining how pharmaceuticals are considered in health insurance benefi t designs and drug utilization review programs, which in turn impact the therapeutic options available to providers, who increasingly face a complex mix of clinical considerations and patient preferences as they make prescribing decisions.

Placing Pharmaceuticals in a Broader Context

The CER provisions in the new law build on the definition of CER established by the Federal Coordinating Council on CER, which was created in the American Recovery and Reinvestment Act in 2009 and which has sunset with the enactment of the 2010 healthcare reform law. This definition stipulated that CER should provide real-world evidence regarding the comparative benefits and harms associated with a variety of healthcare interventions. Unlike evidence produced for regulatory approval of new pharmaceuticals, which focuses on safety and effi cacy in controlled clinical trial settings, real-world evidence will provide insight on the use of therapies in the usual clinical practice environment.

In establishing the Institute, the new healthcare reform law enhances this focus on CER in real-world settings and provides for a more comprehensive definition of CER. This definition includes research evaluating and comparing health outcomes and the clinical effectiveness, risks, and benefits of 2 or more medical treatments and/or services. In addition, it includes protocols for treatment, care management processes, delivery system options, procedures, medical devices, diagnostic tools, integrative health practices, and “any other strategies or items being used in the treatment, management, and diagnosis of, or prevention of illness or injury in, individuals.”^1(p609) Successful implementation of the new law could mean that future P&T decisions will have an enriched new evidence basefrom which to address a broad range of therapeutic questions and that CER on therapeutic alternatives will include pharmaceutical therapy in the broader context of available medical services.

Broader Mandate for CER Priority Setting and Richer Set of Decision-Making Tools

The Institute will have an extensive role in establishing priorities for CER, including consideration of chronic conditions that drive major morbidity, a more robust understanding of gaps in current evidence of broadly defined health outcomes, understanding the underlying causes of significant clinical practice variations, and a greater focus on geographic health disparities.

The Institute will create and carry out a research agenda to address the priorities established for CER, including the impact of treatment alternatives on patient health and well-being, the overall quality of care, and patient preferences. The research agenda also will focus on the need to consider CER in the context of relevant subpopulations by “taking into account the potential for differences in the effectiveness of healthcare treatments, services, and items as used with various subpopulations, such as racial and ethnic minorities, women, different age groups, and groups of individuals with different comorbidities, genetic and molecular subtypes, or quality-of-life preferences.”^1(p612)

Setting Quality Standards for CER Methods

The Institute will have a new and intense focus on appropriate methods and standards for the conduct of CER. The impact and success of the Institute ultimately will depend on the quality and timeliness of the research it sponsors and the value of the CER findings for decision makers. To help ensure that scientifically rigorous methods are used in Institute-sponsored CER, the new law establishes a methodology committee that will define methodologic standards to guide the conduct of CER. These methods may include randomized controlled trials, practical clinical trials, observational studies, systematic reviews of existing research, secondary database analyses, and other study designs that are aligned with and appropriate for the research questions posed in the prioritization scheme defined by the Institute. The focus on appropriate methods and standards is a particularly important component of the new law, because without consistent understanding of and agreement on methodologic standards, interpretation of the fi ndings of CER might vary widely and unpredictably. P&T committees will always be concerned with developing recommendations that are appropriate for their covered population. Recognized and agreed-on quality standards for the conduct and interpretation of CER will help to ensure a high-quality decision-making process on behalf of covered beneficiaries. The volume of research evidence already feels overwhelming, with more than 18,000 randomized controlled trials being published each year.² With the number of observational studies, meta-analyses, and systematic reviews conducted annually, the weight of evidence to inform healthcare decisions is daunting, and the task of judging its quality is extremely challenging for decision makers. Although the standards for CER to be developed by this new methodology committee may not be available for up to 2 years as envisioned by the new law, this work may be an important contribution to the available tools for P&T decision makers.

Assessing CER Findings

Assessing CER findings may require a new focus on appropriate interpretation for decision makers. The new law requires the Institute to convey the findings of research it supports in a manner that is comprehensible and useful to patients and providers making healthcare decisions. The findings must include discussion of issues related to specific subpopulations, risk factors, and comorbidities, and also must include limitations of the research. The Office of Communication and Knowledge Transfer at the Agency for Healthcare Research and Quality is charged with focusing on how best to communicate and disseminate the results of CER. It will be responsible for creating “informational tools that organize and disseminate research findings for physicians, healthcare providers, patients, payers, and policymakers” and will also “develop a publicly available resource database that collects and contains governmentfunded evidence and research from public, private, notfor- profit, and academic sources.”^1(p621)

The need for, and barriers to, appropriate dissemination and application of research findings is a well-recognized issue in the medical literature.³ Addressing this problem begins with appropriate interpretation of CER findings. This challenge is illustrated in a new study, titled Demystifying Comparative Effectiveness Research: A Case Study Learning Guide,⁴ which reviews several major CER studies and provides an easy-to-use guide to key study characteristics that should be considered in judging the strengths, limitations, and potential for generalizability of CER results.

Using case examples, the report, written by researchers at Cerner LifeSciences and sponsored by the National Pharmaceutical Council, illustrates the most importantqualities to assess in 3 major types of CER studies—randomized controlled trials, observational studies, and meta-analyses. Although the framework and questions are not sufficiently technical to guide the detailed assessment of CER by a P&T committee, they can serve as a useful reminder for those aspects of study design that are likely to be critical for appropriate interpretation and decision making. A simple framework is proposed in considering the results of CER: (1) For whom are the findings applicable? (2) Is it likely that any aspects of the study design might affect the results? (3) Are study conclusions likely to change with new research?

There are additional questions and issues to be considered within each of these 3 broad areas. For example, do the results from a randomized controlled trial meet your real-world needs? For meta-analysis, pay close attention to the studies excluded as well as included; ignoring negative studies, for example, could bias the meta-analysis. Observational studies look at the real world, but for the study to be applicable, make sure the population looks like yours. The case studies described provide examples of how specific research has addressed these key issues.

Building Confidence

Although CER has recently received new public policy focus, CER itself is not new. Numerous privateand public-sector organizations have been engaged in evaluating comparative evidence for alternative healthcare interventions. These efforts, however, do not reflect a recognized set of national priorities, and often they do not address the critical questions that payers, providers, and patients have when assessing available healthcare interventions for a given condition. Moreover, CER conducted in nonexperimental settings lacks a recognized set of standards that could provide greater confidence in the evidence base created by this research. The result is inconsistent, unpredictable interpretation and application of the available evidence for healthcare decisions. If the increased public and private investment in CER that is mandated under the Institute is to provide the highest return, it will be critical to address these issues effectively in the early efforts to implement the new Institute.

Comparative effectiveness research can play an important role in fulfilling the right-drug, right-patient, right-time maxim, but only if the conduct and interpretation of CER builds confidence that the research will help to enable improved access to healthcare interventions that are appropriately matched to specific patient needs.