Investigators: Equity, Fees, Patents and Their Own Patients

Part of Conflict of Interest in Clinical Research: Conflicts by Role at the Site.

About 5 minutes. Free, in your language, no account needed.

Expert review pending. CRLN wrote this lesson against the primary sources listed under References. A subject-matter expert has not yet reviewed it. Where your institution's policy or your sponsor's instructions are stricter, follow them.

Why this matters

Principal investigators and sub-investigators make the judgments that most affect participants and data: eligibility, causality of adverse events, efficacy ratings and the decision to stop a participant's treatment. They are also the people sponsors most want as consultants, speakers and inventors. That combination makes investigators the focus of the federal rules, and it is why their interests need the most careful handling.

Equity in the sponsor

Owning part of the company whose product you test gives you a direct stake in a favorable result. Under FDA's rule, any equity in a sponsor that is not publicly traded is disclosable, and equity in a publicly traded sponsor is disclosable once it exceeds $50,000, during the study and for 1 year after (21 CFR 54.2(b)). The Public Health Service rule for federally funded research uses a lower bar: equity plus remuneration from a public company above $5,000, or any equity in a private one (42 CFR 50.603).

Remember that both rules count the holdings of your spouse and dependent children (21 CFR 54.2(d); 42 CFR 50.603). Stock options count as equity.

Consulting, advisory boards and speaker fees

Paid consulting, advisory board seats and speaking engagements for the sponsor are common and are not forbidden. They are disclosable. Under FDA's rule they can be "significant payments of other sorts" once payments from the sponsor that support the investigator's activities exceed $25,000 during the study or the following year, not counting the costs of conducting clinical studies. The rule's own examples include retainers for ongoing consultation and honoraria (21 CFR 54.2(f)).

The amount is only part of it. A sponsor's paid speaker who also assesses the primary endpoint in that sponsor's trial may face a management plan even when the money is below a federal threshold.

Patents, royalties and licenses

A patent, trademark, copyright or licensing agreement in the tested product is a proprietary interest, disclosable at any value (21 CFR 54.2(c)). Compensation that could be higher for a favorable outcome, such as a royalty tied to sales, is disclosable as compensation affected by the outcome (54.2(a)).

Inventors are often the people best placed to run early studies of their own invention, so the rules do not simply exclude them. Instead, institutions manage these conflicts, for example by having someone else serve as principal investigator, by using an independent monitor, or by changing who assesses outcomes (42 CFR 50.605(a)(1) lists examples of this kind).

Enrolling your own patients

Many investigators are also treating physicians, and their patients are a natural source of participants. Nothing in the general rules forbids it, but it creates a dual role. The patient trusts the doctor's advice about care; the investigator also needs enrollment. The patient may feel unable to refuse their own doctor, or may assume the doctor would never suggest something that is not in their best interest.

ICH E6(R3) says neither the investigator nor site staff should coerce or unduly influence a participant to take part or continue (Annex 1 §2.8.3). Common ways sites reduce the pressure, subject to the protocol and IRB approval, include:

Therapeutic misconception

Therapeutic misconception is a participant's belief that every part of a study is designed for their personal benefit, as ordinary treatment would be. It is especially likely when the person explaining the study is the participant's own doctor.

The consent discussion must cover that the trial involves research, the probability of random assignment, the reasonably expected benefits (including when there is no intended clinical benefit), and the alternatives (ICH E6(R3) Annex 1 §2.8.10). An investigator with a financial or professional stake has an extra duty to be precise about these points rather than reassuring. Phrases like "this is the new treatment I recommend" blur research and care.

Delegation does not remove the conflict

The investigator keeps ultimate responsibility for delegated work (Annex 1 §2.3.1). Handing a task to a sub-investigator is a management step only if the sub-investigator is independent of the interest. If the sub-investigator also consults for the sponsor, the handoff changes nothing.

In practice

A principal investigator co-invented the device under study and receives royalties through his university. The university's management plan names a colleague as principal investigator for the trial, keeps him off consent discussions and outcome assessments, requires the royalty to be disclosed in the consent form, and appoints an independent monitor who reports to the conflict committee. He remains a sub-investigator for device training only.

Key takeaways

References