Clinical trial enrollment continues to present challenges to sponsors seeking to identify, recruit, and enroll patients in their clinical studies. A recent government opinion from the U.S. Department of Health and Human Services Office of Inspector General (OIG) recognizes the importance of eliminating socioeconomic factors that function as a barrier to clinical trial enrollment. This latest opinion continues a current trend of government opinions approving certain programs that subsidize patient cost-sharing obligations in clinical trials, notwithstanding OIG’s long-held concerns with “problematic seeding arrangements.”

Advisory Opinion

OIG published Advisory Opinion 22-05 earlier this month, approving a program through which a medical device manufacturer (Requestor) would subsidize certain cost-sharing obligations for Medicare beneficiaries in the context of a clinical trial involving the Requestor’s investigational devices (the Study). This opinion follows Advisory Opinions 21-13 and 21-17 where OIG approved two similar arrangements, one sponsored by a medical society and one sponsored by another medical device manufacturer.

The Proposed Arrangement

The Requestor sponsors a clinical trial designed to determine the safety and efficacy of an investigational therapy that uses the Requestor’s devices to use the patient’s own cells in the treatment of ischemic systolic heart failure (the Therapy).

The Requestor proposed to pay cost-sharing obligations of Study subjects, including Medicare beneficiaries, directly to the institutions to which the subjects would otherwise owe payment. In the absence of the assistance provided by the Requestor, each Medicare beneficiary enrolled in the Study would incur more than $1,300 in cost-sharing obligations for the treatment and several follow-up appointments.

Under the proposed arrangement, Requestor would pay these cost-sharing obligations for beneficiaries in order to (i) reduce financial barriers to enrollment in the Study and reduce attrition of subjects during the two-year course of the Study, (ii) facilitate socioeconomic diversity of Study subjects, and (iii) preserve blinding of subjects. As a result of the subsidies, Medicare beneficiaries would incur no out-of-pocket expenses relating to their participation in the Study other than meeting any unmet Part B deductible amounts.

The Requestor certified that neither it nor its investigators would advertise the availability of cost-sharing subsidies to prospective subjects. Instead, information about the subsidies would be included in the informed consent documents provided to each subject.

The Agency’s Analysis

According to OIG, the proposed arrangement involved two potential possible sources of remuneration that could implicate the federal Anti-Kickback Statute (AKS) and beneficiary inducement prohibition under the Civil Monetary Penalty Statute — two laws aimed at curtailing fraud and abuse under Medicare, Medicaid, and other federal healthcare programs. First, the subsidies could induce Medicare beneficiaries to participate in the Study, during which they would receive healthcare items and services that would be paid for by Medicare. Second, Requestor would provide remuneration to investigators and sites participating in the Study through guaranteed payments of beneficiary cost-sharing amounts (which would allow the providers to avoid taking on bad debt) and opportunities to bill federal healthcare programs for items and services related to the Study.

Nevertheless, OIG concluded that the program poses minimal risk under the AKS and the beneficiary inducement prohibition based principally on the following key factors.

  • Reasonable Means of Meeting Enrollment Goals. The proposed arrangement is a reasonable means of (i) promoting enrollment, particularly where 40% of participating beneficiaries would not have the potential to receive any therapeutic benefit during the Study; (ii) facilitating socioeconomic diversity of subjects where the out-of-pocket costs to participate would be cost-prohibitive; and (iii) preventing attrition for subjects who might otherwise fail to complete the entire two-year course of the Study.
  • Low Risk of Overutilization or Inappropriate Utilization. The proposed arrangement poses a low risk of overutilization or inappropriate utilization items and services because (i) the availability of cost-sharing subsidies will not be advertised; (ii) beneficiaries must satisfy formal enrollment criteria and execute an informed consent document; (iii) investigators must comply with formal Study protocol and are subject to oversight and monitoring by the Institutional Review Board; and (iv) Study enrollment is capped at 260 subjects. Notably, OIG acknowledges that the proposed arrangement could cause overall utilization of items and services to increase but explains that “there is nothing to suggest that such an increase would be inappropriate.”
  • CMS Approved the Study as a Category B Investigational Device Exception Study. The Centers for Medicare & Medicaid Services (CMS) evaluated the Study and determined that it met the criteria to ensure appropriate patient protections and that the Study design is appropriate to answer questions of importance to the Medicare program and its beneficiaries.
  • Distinguishable From “Problematic Seeding” Arrangements. OIG distinguished the proposed arrangement from problematic “seeding arrangements,” describing such arrangements as “those in which manufacturers initially offer subsidies to lock in future utilization.” OIG noted that the Requestor would provide cost-sharing subsidies for a Therapy that is intended to be a one-time treatment. Further, although beneficiaries may continue to receive Medicare-reimbursable follow-up services related to the Therapy, Requestor would not be in a position to benefit financially from the provision of such items or services.

In light of the industry’s focus on diversity, equity, and inclusion in clinical studies, sponsors and their clinical research and site management organizations should take heed of the latest in OIG guidance pertaining to clinical trial enrollment and the factors OIG evaluates to assess potential seeding risks that may be associated with such arrangements.