The recently passed healthcare reform legislation implemented various provisions related to comparative effectiveness research (CER), including a section that created an independent, nonprofit organization, the Patient-Centered Outcomes Research Institute. This institute will be charged with conducting research that informs the public and healthcare providers about the comparative risks and benefits of marketed drugs, devices, and medical products.

According to the legislation, the Patient-Centered Outcomes Research Institute will “assist patients, clinicians, purchasers, and policymakers in making informed health decisions by advancing the quality and relevance of evidence concerning the manner in which diseases, disorders, and other health conditions can effectively and appropriately be prevented, diagnosed, treated, monitored, and managed through research and evidence synthesis that considers variations in patient subpopulations and the dissemination of research findings with respect to the relative health outcomes, clinical effectiveness, and appropriateness of medical treatments, services, and items.”

The legislation also instructs for the establishment of an independent 15-member research methods committee that will be responsible for “developing and improving the science and methods of comparative clinical effectiveness research.” The committee members will be experts from various fields, including genomics, biostatistics, and molecular diagnostics.

But industry analysts believe given that IVDs play a pivotal role in the vast majority of medical decisions and are expected to play an even larger role in the development of effective and cost-efficient personalized medicine strategies, there are many unanswered questions regarding how CER will be applied to IVDs.

“The IVD industry has a great opportunity to work with agencies performing CER to further define the following: appropriate study designs and methods for assessing the value of IVDs; how and when cost-per-test data should or can be appropriately used; the timing of CER assessments relative to market entry; and opportunities for IVD manufacturers to work with users of CER data for funding studies,” says Michele Schoonmaker, PhD, executive director, government affairs at Cepheid (Sunnyvale, CA).

Best practices. What are the best practices for methods of evaluating IVDs in the context of CER? Most IVDs do not undergo randomized clinical trials, so CER will need to recognize other study designs as appropriate for evaluating IVDs.

Use of cost data. Should cost-per-test data be used to measure the value of medical technologies as done in most international technology assessments? If so, how should it be calculated, and how should the cost related to not ordering the test be determined? In other words, would more restricted use of IVDs result in reduced expenditures in the short term, followed by an eventual increase in overall costs as expensive therapeutics are indiscriminately applied to patient care? What costs should be measured and to whom (e.g., patients, healthcare facilities, insurers)? Health insurers should consider working with professionals in health outcomes research (such as the International Society for Pharmacoeconomics and Outcomes Research) to promulgate guidelines for assessing the value of IVDs.

Timing of CER assessments. At which point in the life cycle of an IVD should CER be applied, given the shorter life cycle of IVDs versus therapeutic products? Certainly, FDA and payers (e.g., CMS, private companies) have an interest in CER findings. However, because CER focuses on patient outcomes, such studies may present too high of a hurdle in the premarket phase of IVDs. Rather, innovative post-market activities, with collaboration between IVD manufacturers, the academic medical community, and payers, should be considered. If CER is applied prior to marketing, an IVD may never get to market. Reimbursement conditions may be negotiated to incentivize data collection and/or participation in registries in the post-market setting.

Funding of studies and reimbursement. CER represents large, multicenter trials and registries, and a significant expense to small IVD companies, many of which will not be able to support the effort. In addition to collaborative efforts between IVD manufacturers, medical centers/providers, and payers, payers should consider rewarding manufacturers that meet a threshold of evidence (i.e., being open to value-based reimbursement arrangements rather than resource-based pricing such as current fee schedules).

Other analysts believe that CER should be viewed as an opportunity for data and methods standardization in the IVD industry.

“Molecular sub-stratification of human disease as it relates to clinical management will only be successful in CER if and when IVD manufacturers effectively engage in evidence generation and clinical study protocols that produce sufficient data to warrant systematic review,” says Sharon Terry, president and chief executive officer at Genetic Alliance.

According to Terry, the narrow scope and definition of CER in the healthcare reform legislation “is the conduct and synthesis of systematic research comparing different interventions and strategies to prevent, diagnose, treat, and monitor health conditions.” The immediate limitation of CER is that the entire enterprise will be arranged to look backward at already published data and completed studies that were conducted many years ago. As a result, very few opportunities exist for evidence to emerge supporting quality decision making around IVD testing and its value to an accountable healthcare delivery system. In the absence of such data, there will be no comparators for CER to assess quality and informed decision making in many clinical circumstances.