REGULATORY SPONSORED ARTICLE
ing to utilize CER in their decisions regarding pricing and reimbursement. For example, a large healthcare insurer, WellPoint, has released its own standardized CER guidelines for use in its evaluations of drug coverage.17 Another large insurer, United Healthcare, has suggested that CER will foster the broader use of copay structures that discourage patients from seeking higher cost treatments that offer no real benefit over use of lower-cost drugs.18 Similar to Wellpoint, the United BioSource unit of a large pharmacy benefits manager, Medco, has developed 13 principles for conducting comparative effectiveness research.19 From the medical device context, Medtronic has entered into an agreement with another large healthcare insurer, Aetna, to provide economic data in support of purchase of its products.20 All of these initiatives illustrate the increasing focus by US private payers on the potential use and increasing importance of CER in assisting with their payment and reimbursement decisions.21 Further, a recent study concluded that CER would be very useful in assessing patient outcomes through “understanding the clinical value of existing treatments of known efficacy.”22 Use of CER has been incorporated earlier and more broadly in coverage and payment decisions internationally. In the United Kingdom, the National Institute for Health and Care Excellence (NICE) has made numerous decisions denying coverage using CER, including: • a decision not to recommend use of Takeda’s bone cancer drug Mepact, based on its cost-effectiveness criteria, even though it stated that the drug “might represent a potentially valuable new therapy;”23 • rejection of Bristol-Myers Squibb’s Yervoy on cost-effectiveness grounds;24 • rejection of GlaxoSmithKline’s Benlysta on cost-effectiveness grounds;25 • proposed rejection of Sanofi’s new bowel cancer drug Zaltrop as not cost effective, while acknowledging clinical effectiveness;26 and • rejection of Savient’s gout treatment Krystexxa on the basis of its “very high cost compared with the known benefit.27 NICE has rejected more than 60% of new cancer drug applications since the beginning of 2011.28 Other European Union healthcare technology assessment (HTA) organizations also have become increasingly active in uti20
lizing CER, for example, through the creation of a new cost and comparative effectiveness—based system for review of healthcare products in Germany (conducted by the Institute for Quality and Efficiency in Healthcare),29 and the establishment in France of a subgroup (CEESP) similar to NICE in its reimbursement authority over healthcare products. Other nations, including Canada, Australia, and recently Taiwan,30 also have established entities similar in purpose and operation to NICE. A recent study suggests that the consequence of such HTAs using CER has been price reductions compared to US levels.31
Implications of Incorporation of CER in Lifecycle Management
The increasing utilization of CER by government and private payers presents several important implications for product lifecycle management for biopharma companies: 1. It is highly advisable to incorporate outcomes research into clinical trials to provide a strong basis for obtaining formulary acceptance and to enable marketing and promotion of the product to government and managed care payers.32 2. It is advisable for biopharma product developers to have discussions with payers at the clinical development stage concerning what CER might be necessary and appropriate to develop to support a positive coverage and reimbursement decision. 3. The potential for a reduction in the expected rate of return on product investment by reason of the increased use of CER should be incorporated into product candidate investment and R&D decisions, which assessment should include the increased costs by reason of CER evidence development. 4. The utility and desirability of developing nonclinical trials-based CER to support payment and reimbursement should be evaluated, for example, by pharmacoeconomics studies of value. 5. Consideration of forming partnerships with insurers and other payers to enhance development of appropriate data to support positive coverage/payment decisions, as Pfizer has done with Medco and AstraZeneca has entered into with WellPoint.33 6. Development of integrated market access cross-functional operations to effectively generate, manage, and apply CER from
the drug and biologic development stage, through reimbursement and market access negotiations, to marketing and promotion, as well as across national boundaries. 7. Consideration of the potential of personalized medicines to enhance the likelihood of payer acceptance.34 8. Evaluation of the potential use of CER in later stages of the product lifecycle to support new indications and to support the product in competition with other products or therapies. 9. Consideration of company strategy with respect to potential negotiations with or demands by government or private payers regarding refunds or other pay-forperformance approaches to obtain formulary approval.
Novel Private Litigation Challenges to Biopharma Marketing and Promotion with CER
As discussed above, there is an increasing and unavoidable demand by government and private payers for CER data to support coverage and reimbursement determinations. The need by biopharma companies to develop and disseminate such CER data as part of drug and biologic marketing and promotion presents difficult issues regarding FDA’s traditional enforcement approach. In addition to the risk of FDA enforcement, it is important for biopharma companies to be aware of recent novel private litigation challenges to the W6R?b4U"???&?WF??r?B&???F????6???2?fR&VV?'&?Vv?B'?vw&?WfVB6??WF?F?'2??f&??W2&6W2???6?VF??rf?6RGfW'F?6??rV?FW"F?R????7B?7FFRV?f?"6??WF?F????BFV6WF?fR&7F?6W27FGWFW2?FVf?F???????W&??W2f?6V???B??BF?'F??W2??FW&fW&V?6R?F?W6R7F???2??6VV?F?f??BF?&V7B6???V?vW2&6VB??f???F???2?bF?Rf??B?G'Vr??B6?6?WF?27B?"dD ( ?2&VwV?F???2?6??6RF?W&R?2??&?fFR&?v?B?b7F???V?FW"F?R7B?F?R6???V?vW2?fR&VV?&6VB???&?WF??r?B&???F???7F?f?F?W2??v?FR&?vR?b6??FW?G2???6?VF??rV&?6F????b4U"??VW"?&Wf?WvVB66?V?F?f?2??W&??2?&W6V?FF???2?b4U"B66?V?F?f?2?VWF??w2?&W72&V?V6W2?7V&?76???2F??W'2??B&W6V?FF???2'?6?W2f?&6W2?F?&VR?Wr???fV??F?vF???6???V?vW2?fR&VV?f??VB'?6??WF?F?'2F?F?RW6R?BF?76V??F????b4U#?????r?dR44?T?4U2#0??