Spotlight on Compliance: False advertising laws apply in clinical arena

Advertising, incentives must follow rules

By J. Mark Waxman, JD
General Counsel
CareGroup Healthcare System
Boston

One of the challenges in clinical trial operations is to recruit patients to participate. The Food and Drug Administration (FDA) notes that recruitment "methods and material" also should be reviewed as a part of the IRB oversight function.1

Implementing this guidance will require IRBs to review advertising materials, as well as the payment of recruitment fees whether to the investigator, the patient’s primary care physician, or directly to patients.

The FDA points out that direct-to-participant advertising, such as newspaper, radio, and flyers, is not an objectionable practice. Instead, these efforts are perceived as part of the informed consent process, as well as subject selection. In that context, these advertisements would be subject to IRB review, which, in addition to ensuring factual accuracy and consistency with an approved protocol, would consider whether there is a perception created leading to undue influence. The key elements of concern would be any express or implied representation of a favorable outcome from the trial or the ability to receive some other benefit inconsistent with or beyond what is specifically set forth in an approved protocol. [Where only protocol comparison is necessary, expedited review can be appropriate. See 21 CFR§56.110 (b)(2).] An advertising review also would focus on ensuring that:

  • No express or implied claims that the drug or device being tested is safe or effective for the purposes being tested, or that the item involved is superior (or even equivalent) to any comparable item. In the eyes of the FDA, that representation would be both misleading and most importantly, a violation of regulations which specifically prohibit promotion of investigational drugs;2
  • There is not a representation that the drug or device is not investigational. For example, an advertisement which suggested the trial was or would lead to a new treatment, without making its investigational nature clear, would be misleading;
  • There should not be a promise of "free" drug supplies or devices or "free treatments" if the true facts are simply that there will not be a charge for taking part in the investigation. Indeed, the use of inducements in the form of free treatments or free devices would have to be scrutinized carefully to ensure issues of fraud and abuse do not arise where Medicare or Medicaid patients may be involved. Section 1128A (a)(5) of the Social Security Act addresses a series of circumstances in which such inducements are prohibited.

What can you say?

The FDA suggest the following factually accurate information would be acceptable:

  • the name and address of the investigator, entity, and facility involved;
  • the condition under study and/or the purpose of the research;
  • eligibility criteria;
  • participation benefits;
  • the commitments required of study participants;
  • contact information.

Advertising for subjects is not the same as communications to third parties about trials. For example, an investigators’ brochure is not required to receive IRB approval, although its contents may be useful information for IRB members and staff. Objective and basic information listings of clinical trials being conducted by an institution also would not require IRB approval.

The FDA further has acknowledged that communications not require review. This category includes not only doctor-to-doctor communications, including those soliciting for trial subjects, but also publicity intended for third parties such as investors, which might appear in the trade press or even as advertisements in the financial pages of newspapers.

What can you give?

Payments for participation are recruitment incentives. They may be particularly desirable where benefits are nonexistent (e.g., many trial participants will receive a placebo). The IRB must be informed of such benefits and approve them to ensure they are neither "coercive" or present "undue influence." (21 CFR §50.20.) This means that all information regarding payment should be approved as a part of the approval of the informed consent document. The belief is that material payments may coerce or influence those without means to be to participate in a particular clinical trial. It is generally understood, however, that a payment designed to compensate at a reasonable level for the time commitments required — i.e., as compensation for tests or other participatory activities — can be appropriate. An incentive or bonus for completing the study may also be approved, although the FDA has indicated its view that the entire payment should not be contingent upon completion. This might itself be coercive of an inappropriate continuation in a trial of a participant.

As previously noted, however, where Medicare or Medicaid patients are involved, special concerns exist with respect to participation incentives.

Although the Office of the Inspector General (OIG) has the use of incentives to further clinical trial participation under review, Section 1128A (a)(5) of the Social Security Act ("1128A") pro-hibits the offer or transfer of "remuneration" to a Medicare or Medicaid beneficiary that the person "knows or should know" is likely to influence selection of a provider or supplier of Medicare or Medicaid payable items. A strict interpretation of this provision would mean a cash or noncash gift (in excess of $50 annually per patient) or free goods in connection with a clinical trial where the beneficiary will also receive routine Medicare services may run afoul of the prohibition. And, as the OIG has noted, there is no statutory exception for valuable gifts (e.g., free medications) based upon a beneficiary’s medical condition or its severity.

Recruitment fees to practitioners

Other methods to enhance patient recruitment would be to create financial incentives for the investigators themselves. While varying approaches exist, these incentives could take the form of a per-patient payment or a fixed fee when a minimum or desired enrollment level is met. Either example can create a potential or perceived conflict of interest. As noted by the America Medical Association (AMA), it is unethical to have a conflict of interest arising from payments a researcher might receive which exceed remuneration commensurate with the efforts for the researcher on behalf of the sponsor.3 Therefore, compensation should be at fair-market value and not vary according to the volume of subjects enrolled by the physician receiving the payments. The AMA goes on to note that the nature and source of funding and financial incentives to investigators "must be disclosed . . . as part of the informed consent process."4

The foregoing suggests that an appropriate approach to payments to investigators would be similar to that applied to other areas in which payments are made to physicians for other than direct patient services, most notably the so-called Stark Law and its exceptions. Such approaches focus on documenting both the efforts made and its value. This would include the costs to be incurred for indirect overhead expenses as well as pure time and effort. It also is recommended the amounts involved by established in advance, and records be kept of progress along a budgeted path along the way.

A second variant on payments to obtain trial participants would be a payment to a physician for referring a patient to the trial or the investigator. Payments to another provider to refer study participants are both unethical,5 and likely to violate state (and federal where appropriate) laws prohibiting payments in return for referrals.

References

1. FDA Information Sheets, Guidance for IRBs and Clinical Investigators, 1998 Update. See also IRB requirements with respect to protect participant rights and welfare, 21 CFR§§56.109, 109, 111.

2. 21 CFR§§312.7, 812.7.

3. AMA Opinion E-8.031. Conflicts of Interest: Biomedical Research.

4. AMA Opinion E-8.0315. Managing Conflicts of Interest in the Conduct of Clinical Trials.

5. AMA Opinion E-6.03. Fee Splitting: Referrals to Health Care Facilities.