SPONSORED ARTICLE REGULATORY
ation of the entity. Of further concern to the industry are statements, such as by the head of PCORI, that while PCORI will not focus on cost effectiveness, “cost analysis” is undefined in PPACA, and patients will decide whether PCORI will fund research regarding costs and healthcare outcomes.4 Indeed, PCORI has undertaken a plan to fund CER in certain specific areas, such as the treatment of uterine fibroids, in addition to its general methodological research, furthering concerns that the entity will develop into a cost reduction mechanism through its sponsored research.5 PCORI recently announced its first head-to-head comparative effectiveness drug trial, involving inflammatory bowel drugs.6 Notwithstanding the stated limitations on government use of CER set out in PPACA, the statute does allow the Centers for Medicare and Medicaid Services (CMS) to use CER results to make a determination concerning Medicare coverage if (1) such use is through an iterative and transparent process and (2) a determination to deny Medicare coverage for a product or service is not based solely on CER. These aspects of the statute raise industry concerns that CER could be used by CMS if the agency is careful to incorporate its use within these parameters. This potential for expanded governmental use of CER has been exacerbated by suggestions by other agencies about promoting use of CER, such as the Agency for Healthcare Research and Quality’s proposal to encourage use of “academic detailing” to disseminate CER to healthcare providers,7 assertedly to counter biopharma industry promotional activities. As a consequence, the American Medical Association (AMA) remains concerned that PCORI will apply CER using cost analysis, and has opposed any such activities in its comments to PCORI on the definition of “outcomes research”.8 By contrast, the American Hospital Association has proposed using CER, including cost analysis, to improve healthcare quality and efficiency.9
Potential Limitations on Use of CER
CER clearly has great promise for use by government and private payers in establishing price and payment restrictions. However, there are significant practical limitations on the use of CER in pricing and reimbursement decisions. These include the absence of accepted research protocols for
CER, the absence of a critical mass of historical CER studies for comparison purposes that have been conducted in accordance with acceptable and defensible research protocols, and significant controversy within the scientific community regarding the proper interpretation of CER results. With respect to biopharma products, for example, CER data was available for only about half of the new drugs approved by the Food and Drug Administration (FDA) over the past decade.10 Such limitations raise significant concerns regarding the practicality and propriety of government or private payers using CER for pricing/reimbursement decisions absent greater definition of “appropriate and acceptable research” and an enhanced database of CER. Further, as with any efforts to limit access to healthcare products or services, the application of CER to do so can be expected to generate substantial opposition in many circumstances. The potential for controversy is illustrated by the substantial public opposition to the 2009 recommendations by the US Preventive Services Task Force to end routine mammograms for women in their 40s, on the asserted basis of a failure to establish that such tests were necessary, which resulted in reversal of the recommendation. In addition to these potential limitations, FDA’s traditional hostility to use and dissemination of CER also may provide restrictions on practical use of results, particularly for CER generated and disseminated by biopharma industry companies. FDA traditionally has required two comparative clinical studies for cost or comparative effectiveness claims. Notwithstanding the direction under Section 114 of the FDA Modernization Act of 1997, amending the Food, Drug, and Cosmetic Act, for FDA to provide guidance regarding the proper scope of communication of healthcare economic information to formulary committees, the Agency has not do so, providing no guidance either on what constitutes “substantial clinical experience” as a potential basis for promotion of products or on what constitutes proper “scientific exchange.”11 FDA’s senior drug review official has repeatedly expressed skepticism of CER in recent years, and the need to adhere to FDA’s traditional requirement of comparative clinical studies as the basis for any marketing claims.12 FDA thus has required a very high level
of evidence—comparative clinical trial—to support claims based on CER. For insurers’ formulary committees and other healthcare technology assessment entities, however, there is a perceived utility of and acceptability of CER based on other elements, such as accepted methods of pharmacoeconomics such as econometric analysis and nonclinical trials-based outcomes research. This demand for CER from biopharma products manufacturers, coupled with the desire to expand use of CER by those government agencies responsible for product reimbursement, may influence FDA to adapt its historic approach and allow use of non-clinical trials-based CER in marketing and promotion. Some potential for evolution of FDA’s traditional approach was suggested by recent public statements by a reviewer in the FDA’s Center for Drug Evaluation and Research that social media can be used to help validate the content of patient-reported outcomes to support labeling claims.13 The potential for development of parallel reviews by FDA and CMS that may include consideration of CER also should be monitored, although there has been little progress in this direction. The agencies proposed a pilot Parallel Review program to conduct overlapping FDA premarket reviews and CMS national coverage determinations for certain innovative products, when sponsors agree.14 The agencies suggested, in their Notice, that the proposed Parallel Review process “could also create incentives for venture capitalists and companies to increase their investment in innovative products by reducing the time to return on investment for those products eligible for parallel review.”15 Similarly, the potential uses of CER in determinations by other governmental/scientific entities affecting product use should also be monitored. For example, a decision by the Centers for Disease Control’s Advisory Committee on Immunization Practices to limit the recommendation for vaccinating adults against hepatitis B to those under age 60 was assertedly based on cost effectiveness considerations.16
Use of CER to A ffect Biopharma Pricing and Reimbursement
Notwithstanding FDA reluctance to support expanded use of CER, and the slow development of CER through PCORI, private payers in the US are aggressively mov-
LMG LIFE SCIENCES 2013
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