U.S. Clinical Trials: Federal Government Considers Safe Harbors to Encourage Enrollment and Retention

The U.S. Department of Health and Human Services Office of Inspector General (OIG) recently issued a Request for Information (RFI) seeking public comment on whether modifications to the federal Anti-Kickback Statute (AKS) safe harbor regulations and / or beneficiary inducement prohibition under the federal Civil Monetary Penalty Statute (Beneficiary Inducements CMP) exceptions are needed to protect remuneration provided to individuals participating in U.S. clinical trials.

In addition to soliciting input on potential regulatory changes, OIG is also seeking stakeholder input on whether additional guidance — such as a Special Advisory Bulletin or frequently asked questions (FAQ) document — would “foster arrangements that facilitate clinical trial participation, while also protecting against harms caused by fraud and abuse.” Comments are due to the agency by August 24 at 5 pm ET.

The RFI follows a series of favorable Advisory Opinions issued by OIG over the past several years involving proposed arrangements under which clinical trial sponsors would subsidize certain cost-sharing obligations for Medicare beneficiaries participating in their trials to promote and facilitate trial recruitment, enrollment, and study subject retention.¹

The RFI also comes amid broader efforts by the Administration to reduce barriers to conducting clinical trials in the U.S. In recent years, sponsors have increasingly conducted clinical trials in countries that offer lower costs and fewer operational burdens. The RFI suggests that the Administration is evaluating whether existing fraud and abuse laws unnecessarily impede clinical trial recruitment and participation in the U.S. and whether modifications to the AKS safe harbor regulations or Beneficiary Inducements CMP exceptions could complement broader efforts to encourage domestic clinical research while preserving appropriate safeguards against fraud and abuse.

OIG seeks comments on the following topics, among others:

• Legal Barriers and Considerations
  • Whether the AKS or the Beneficiary Inducements CMP operate as barriers to offering and providing appropriate remuneration to clinical trial participants and, if so, why;
  • Whether additional or modified safe harbors to the AKS or exceptions to the definition of “remuneration” under the Beneficiary Inducements CMP are necessary to protect remuneration to clinical trial participants and any arrangements necessary to offer and provide such remuneration, including any key provisions that should be included in any additional or modified safe harbor or exception;
  • Potential broader impacts or implications that may result from the provision of remuneration to clinical trial participants, additional or modified safe harbors to the AKS, or exceptions to the definition of “remuneration” under the Beneficiary Inducements CMP; and
  • Whether there are opportunities where OIG could clarify its position through guidance (e.g., a Special Advisory Bulletin or FAQ response) as opposed to regulation.
• Categories and Timing of Incentives
  • Which categories of remuneration (including, e.g., reimbursement for such actual incurred expenses such as travel, lodging, parking, childcare, and meals; stipends; compensation for a participant’s time; incentives to encourage enrolling in and completing the trial) and at what levels those categories of remuneration are useful to facilitate participation in clinical trials and why
  • Whether remuneration to clinical trial participants is provided during all stages of product development (e.g., phase 1-4 clinical trials) and whether different amounts or types of remuneration are necessary to promote participation in early-stage versus late-stage development
  • Whether there are specific types or categories of clinical trials that should or should not pay remuneration to clinical trial participants
• Protections for Clinical Trial Participants
  • Any safeguards that should be in place to ensure clinical trial participants who receive remuneration to participate in a clinical trial are not inappropriately steered to items or services offered by the individual or entity offering the remuneration outside the clinical trial
  • Whether there should be advertising limitations relating to remuneration to clinical trial participants to protect the integrity of the clinical trial and guard against the harms resulting from fraud and abuse

Clinical trial sponsors and other interested stakeholders should consider submitting comments to help inform any proposed rulemaking or future guidance.