Clinical trial enrollment continues to present challenges to sponsors seeking to identify, recruit and enroll patients in their clinical studies. A recent government advisory from the Office of Inspector General (OIG) of the U.S. Department of Health and Human Services recognizes the importance of eliminating socioeconomic factors that act as a barrier to clinical trial enrollment. This latest opinion is part of the current trend of government opinions endorsing certain programs that subsidize patient cost-sharing obligations in clinical trials, despite longstanding OIG concerns about “problematic seeding arrangements.” .
The OIG issued Advisory Opinion 22-05 earlier this month, approving a program by which a medical device manufacturer (the plaintiff) would subsidize certain cost-sharing obligations for Medicare beneficiaries under a clinical trial involving applicant’s investigational devices (the study). This notice follows Advisory Notices 21-13 and 21-17 in which the OIG approved two similar arrangements, one sponsored by a medical company and the other sponsored by another medical device manufacturer.
The proposed arrangement
Applicant is sponsoring a clinical trial designed to determine the safety and efficacy of an investigational therapy that utilizes Applicant’s devices to utilize the patient’s own cells in the treatment of ischemic systolic heart failure (the Therapy).
The plaintiff offered to pay the study subjects’ cost-sharing obligations, including Medicare beneficiaries, directly to the institutions to which the subjects would otherwise have to pay. In the absence of plaintiff-provided assistance, each Medicare beneficiary enrolled in the study would incur more than $1,300 in cost-sharing obligations for treatment and multiple follow-up appointments.
Under the proposed arrangement, the applicant would pay for these cost-sharing obligations for recipients to (i) reduce financial barriers to study enrollment and reduce subject attrition over the two years of the study, (ii) facilitate the socio-economic diversity of the study subjects, and (iii) preserve the blinding of the subjects. With the grants, Medicare beneficiaries would incur no out-of-pocket expenses related to their participation in the study other than settling unmet Part B deductible amounts.
The applicant certified that neither he nor his investigators would advertise the availability of cost-sharing grants to potential subjects. Instead, grant information would be included in the informed consent documents provided to each subject.
According to the OIG, the proposed arrangement involved two potential sources of compensation that could involve the Federal Anti-Kickback Act (AKS) and the Beneficiary Inducement Prohibition under the Monetary Civil Penalties Act – both statutes aimed at reduce fraud and abuse under Medicare, Medicaid, and other federal health care programs. First, the grants could incentivize Medicare beneficiaries to participate in the study, during which they would receive health care items and services that would be paid for by Medicare. Second, the claimant would compensate the investigators and sites participating in the study through guaranteed payments of cost-share amounts with recipients (which would allow providers to avoid incurring bad debts) and the ability to bill federal healthcare programs for study-related items and services. Study.
Nonetheless, the OIG has concluded that the program poses minimal risk within the scope of the AKS and prohibition on inducing recipients, primarily based on the following key factors.
- Reasonable Means of Accomplishing Enrollment Goals. The proposed arrangement is a reasonable way to (i) promote enrollment, particularly when 40% of participating beneficiaries would not have the potential to receive therapeutic benefit during the study; (ii) facilitate the socio-economic diversity of subjects where the costs to pay to participate would be prohibitive; and (iii) prevent attrition for subjects who might not otherwise complete the full two-year course of the study.
- Low risk of overuse or misuse. The proposed arrangement presents a low risk of overuse or inappropriate use of items and services because (i) the availability of cost-sharing grants will not be advertised; (ii) beneficiaries must meet formal enrollment criteria and sign an informed consent document; (iii) investigators must comply with the formal study protocol and are subject to the oversight and control of the institutional review board; and (iv) study enrollment is capped at 260 subjects. Notably, the OIG acknowledges that the proposed arrangement could result in an increase in the overall use of items and services, but explains that “nothing suggests 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 criteria to ensure appropriate patient protection and that the study design was appropriate to answer questions important to the Medicare program and its beneficiaries.
- Distinguishable from “problematic seeding” arrangements. The OIG distinguished the proposed arrangement from problematic “priming arrangements,” describing such arrangements as “those in which manufacturers initially offer subsidies to lock in future use.” The OIG noted that the applicant would provide cost-sharing grants for therapy intended to be a one-time treatment. Additionally, while beneficiaries may continue to receive therapy-related Medicare reimbursable follow-up services, the claimant would not be able to benefit financially from the provision of such items or services.
In light of the industry’s emphasis on diversity, equity, and inclusion in clinical studies, sponsors and their clinical research and site management organizations should consider the latest guidelines from the OIG regarding clinical trial enrollment and the factors that the OIG assesses to assess the potential seeding risks that may be associated with such provisions.