Pay to Participate in Research: Regulations and WCG’s Position

In most research studies, the costs of the research intervention are covered by the sponsor or a grant from a federal or other organization. When research activities are not funded by grants or industry, researchers may consider other models, such as having the participants of a research study pay for the study product or parts of their participation. However, there are serious issues with requiring participants to pay for research participation, even if a research study could be part of people’s medical care, is very similar to what they would receive for medical care or provides a benefit not otherwise available. WCG’s general position is that research participants should not have to pay for costs of the research, including participant direct costs in different types of studies, from clinical trials of high-risk FDA-regulated products to unregulated novel concepts. There are several different layers of issues to address when discussing studies that require participants to pay to participate.

Regulatory Restrictions on Charging for Investigational Products

FDA: Charging for an Investigational Drug

For a clinical investigation of a drug under an IND, the FDA released updated guidance in February 2024.^[i] The guidance details questions and answers about the regulatory requirements. For an investigational drug in a clinical trial, including an investigational use of an approved drug, a sponsor must do all of the following to obtain authorization from FDA to charge for the drug:^[ii]

• Provide evidence that the drug has a potential clinical benefit that would provide a significant advantage over available products.
• Demonstrate that the data to be obtained from the clinical trial would be essential to establishing the drug is effective or safe or would support a significant change in the labeling of an approved drug.
• Demonstrate that the clinical trial could not be conducted without charging because the cost of the drug is extraordinary to the sponsor.^[iii]
• Provide documentation to support its calculation for cost recovery accompanied by a statement from an independent certified public accountant.

The FDA decides if a sponsor may charge but does not decide who receives the bill — a third-party payor or the trial participant — or if a third-party payor should pay the bill. The guidance recommends consulting with the third-party payor. FDA’s guidance does advise sponsors to ensure that charging for investigational drugs does not create barriers to a ccess that may exacerbate disparities in clinical trial participants or expanded access patients.

In contrast to non-expanded access, for individual patient expanded access, the sponsor may only charge for direct costs associated with acquiring an investigational drug, such as shipping and handling fees.^[iv] The requirement for FDA authorization to charge does not extend to administrative costs in a clinical trial, such as pharmacy, nursing, or equipment costs.

FDA: Charging for an Investigational Device

Similar to the drug regulations, the Investigational Device Exemption (IDE) regulations allow FDA to authorize sponsors of a clinical investigation under an IDE to charge for the investigational device. To do so, the sponsor must provide in the IDE application:^[v]

• The amount to be charged.
• A justification for the proposed charges as not more than necessary to cover the costs of manufacture, research, development, and handling of the investigational device.
• An explanation for why the charge does not constitute commercialization.

For devices, there is a clear pathway for that cost to potentially be covered at least in part by Medicare insurance. FDA has a Memorandum of Understanding with the Centers for Medicare and Medicaid Services (CMS). With an approved IDE comes a risk-based FDA assignment to one of two categories: Experimental/Investigational (Category A) or Non-experimental/Investigational (Category B).

A Category A device is one for which “absolute risk” of the device type has not been established. That is, initial questions of safety and effectiveness have not been resolved, and the FDA is unsure whether the device type can be safe and effective. CMS will provide no coverage for a Category A device but may approve coverage of routine care and services in the study. If FDA determines the device is a Category B device, Medicare may provide coverage for the device. Category B devices are those where the underlying questions of safety and effectiveness of that device type have been resolved, or it is known that the device type can be safe and effective because, for example, other manufacturers have obtained FDA approval for that device type.^{[vi] [vii]} For Category A devices and all uncovered costs for Category B devices, the cost is passed directly on to participants.^[viii]

These regulations provide, for studies under an IND or IDE, a way to have participants pay for participation. While allowed by regulation, the underlying message is that even then, pay-to-participate trials should require clear and substantive justification.^[ix]

WCG’s Policies and Guidance on Participants Paying for Research

Many studies are not under an IND or IDE, so they have no requirement to have FDA review for a clear and substantive justification. Even if FDA has reviewed and authorized charging, the practice still has ethical and separate IRB issues to address. For those reasons, WCG has an expanded and more protective policy.

 WCG requires sponsors and investigators to notify the IRB if participants will be required to pay to participate in a study. The IRB will then review the research and the information provided about the context of the participant payment. Assuming there are no questions regarding the scientific basis of the risks and benefits or the research design, during review, the following factors are considered:

• Charging for approved products being used for their approved indications is generally acceptable. In as much as possible, those costs should be sent to third party payors including in advance of study enrollment (prior authorization).
• Charging for approved products being used as part of participant care as research procedures may be acceptable. Factors that are considered include:
  • Are the costs substantial? For example, the implantation of a device requires surgery and long-term follow up compared to a short-term use of a low-risk product.
  • If the costs are likely to be or are covered by third party payors.
  • The proximity of the research procedures to an accepted standard care. For example, a commonly used treatment, but in the context of research, it is an investigational use.
• Charging for the administration of the study product when the investigational product is provided at no cost may be acceptable. For example, site costs for administration of the investigational product when it is used as standard care for the participant’s treatment. Charging for administration or other ancillary costs of investigational products when the investigational product is not provided as part of a standard treatment is almost never acceptable.
• Charging for investigational products where the cost is solely borne by the participants is almost always unacceptable.

Despite FDA’s authority to allow charging for investigational products as noted above, FDA also advises sponsors to ensure that charging for drugs in clinical trials or expanded access use does not create barriers to access that may exacerbate disparities in clinical trial participants or expanded access patients. Considering the financial situation of many potential clinical trial participants, and the IRB’s requirement to ensure equitable selection, the requirement to pay for investigational products would almost invariably restrict those with limited financial means from participating. This could further exacerbate disparities, including those for which economic status are proxy. Any significant, uncovered charges could exacerbate disparities and result in a failure of equitable selection for that study. Third-party payor coverage of an investigational device may mitigate this impact and be acceptable, for example, if the sponsor has obtained CMS coverage assurance in a study under an IDE.

Some may incorrectly argue that equitable selection is achieved overall when charging for participation as those with more money will bear the burdens of research and once the intervention is proven, the benefits accrue to those who were not able to participate as they could not pay. However, the data collected from studies with limited diversity of participants are not necessarily relevant to the wider population. In fact, another study with those populations who were not included due to their inability to pay could be needed to prove the benefit of the intervention. Similarly, the argument that the direct benefit from participation is sufficient to balance the burdens of costs also fails. Research studies are done prior to establishing benefit, and participation in a trial is a burden unto itself with the additional burden of risk. Because the risks of research must be reasonable in anticipation of the benefits, overcoming the weight of risk and participation burdens leaves little room for the weight of potential benefit to also outweigh the burden of costs.

WCG’s Process for Review of Participant Payment

If either WCG as a company or the IRB determine that the study is not acceptable as proposed, we will work with sponsors to try to reach a mutually acceptable outcome.

In all cases, all costs to participants — both investigational product and the administration procedures — are required to be disclosed in the consent form. This includes providing clear information regarding costs that may be considered by participants to be part of their care that third party payors may not cover. The consent form has a related requirement which includes clearly describing which procedures are research procedures as compared to which would occur regardless of the research. The clarity of this requirement directly relates to the need for clarity in the costs of the research to participants.

As noted above, FDA regulations allow for certain studies with clear and substantive justification to have the sponsor be authorized to bill for costs of the investigational product. Even in that case, and for all other studies that include participants paying for research participation, WCG will carefully review the research and proposed charges to participants to assure their rights and welfare are protected.

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References

[i] Charging for Investigational Drugs Under an IND Questions and Answers Guidance for Industry. February 2024.

[ii] 21 CFR 812.8(b) & (d).

[iii] The costs that are extraordinary are relative to the sponsor. A cost that is considered extraordinary to a small start-up company may not be considered extraordinary to a large, established company.

[iv] 21 CFR 312.8(d)(1)(ii).

[v] 21 CFR 812.7(b).

[vi] https://www.cms.gov/medicare/coverage/investigational-device-exemption-ide-studies Accessed March 5, 2024.

[vii] FDA Categorization of Investigational Device Exemption (IDE) Devices to Assist the Centers for Medicare and Medicaid Services (CMS) with Coverage Decisions. December 2017.

[viii] https://www.fda.gov/regulatory-information/search-fda-guidance-documents/charging-investigational-products Accessed March 6, 2024.

[ix] DHHS, Secretary’s Advisory Committee for Human Research Protections. Charging Subjects for Clinical Trial Participation. Attachment A to Letter to the HHS Secretary, November 20, 2019. https://www.hhs.gov/ohrp/sachrp-committee/recommendations/november-20-2019-attachment-a/index.html. Accessed March 6, 2024.

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