off-label uses of cancer drugs under Part B. One concern is that questions have been raised about the independence of compendia compilers, the degree to which they cite current evidence (or any evidence), the quality of their methods and their assessments of evidence, and the potential for official acceptance of such compendia to discourage research aimed at FDA approval of off-label uses (Tillman and Gardner, 2004; Abernethy et al., 2009; Butcher, 2009; Mitka, 2009; Sox, 2009; see also ASHP, 1992; Gillick, 2009).
To inform future off-label coverage determinations, CMS commissioned a technology assessment from the Agency for Healthcare Research and Quality (AHRQ) to summarize the process by which anticancer drugs are added to various compendia and to identify methods used to collect evidence for listed drugs and biologics and their indicated uses (Abernethy et al., 2009). The assessment covered six compendia and a sample of 14 anticancer combinations that were selected to include newer and older agents, common and rare cancers, and biologics and drugs. Among the findings was that there was little agreement in the evidence regarding efficacy cited by the compendia and that the compendia were discordant on whether they discussed adverse effects among patients with specific cancers. Moreover, when compendia did not include off-label indications, the analysts could not determine whether a particular omission reflected a conscious editorial decision following the evaluation of available evidence or whether the available evidence was not identified and evaluated. The authors observed that although they could not generalize to other disease areas, the compendia’s performance might be expected to be highest in oncology, given their importance for reimbursement. The authors also pointed out the major challenges of managing a near-continuous systematic review of large numbers of drug uses not approved by FDA. They also noted that FDA itself was not authorized or prepared to undertake such a review.
For rare diseases, the volume of drugs and uses is obviously much smaller but so is the research to support evaluations of off-label use. The growing databases from Part D claims could, when linked to Medicare hospital and physician claims data, be a resource for studying the nature and outcomes of some off-label use of orphan and other drugs for patients with rare conditions.
Congress has not provided CMS itself with the authority to negotiate prices with pharmaceutical manufacturers. However, as noted above, to the extent that private health plans, including Part D plans, are able to “move market share” across drugs in a class using such financial incentives, then plans have the potential to negotiate sizable rebates or discounts from