What do we mean by subject injury? It is an umbrella term for any adverse event/reaction, illness, or injury experienced by a person due to their participation in a clinical trial. Subject injury language can be found in two places: the informed consent form (ICF) and the clinical trial agreement (CTA). This blog will cover subject injury compensation in the CTA, address common language and concerns, and examine sponsor responsibilities. You’ll gain real-world insights and discover practical-application solutions. Working together with sponsors, we as stakeholders want to do the best job possible – protecting patients while advancing science.
Subject Injury Compensation
Factors leading to subject injury may include the actual drug, device, or biologic being studied – or the implementation thereof. Examples are the surgery required to implement the device, the injection of the drug, or anything caused by protocol-mandated activities. Remember, we are not just concerned about the drug but anything that the protocol instructs the principal investigator (PI) to do. All these concepts fall under the umbrella of subject injury.
The CTA subject injury provision is a specific paragraph or section addressing subject injury and the associated costs. It sets a foundation with the sponsor, as well. How will the costs of subject injuries be handled? Who will pay for them?
Addressing subject injury and compensation in the CTA helps allocate risk and avoid confusion between the sponsor and the site. The exception: You may be silent on the topic for a study that has nothing to do with patient care (e.g., a chart review study or a registry study).
Studies involving patient care or interventional care should address sponsor responsibility for subject injury and the associated expenses, including:
- Other costs
Exceptions are expenses resulting from the site’s failure to comply with the protocol or from site negligence – unless expenses result from the normal or expected progression of the participant’s underlying condition.
Why should sponsors pay for subject injuries? Because the drug or device is the sponsor’s product, they are responsible for its design and manufacture, along with the study protocol, and so they are responsible for the implementation. For the sponsor’s product to be submitted to the FDA and made commercially available, they need the study data. Therefore, they rely on volunteers to sign up for their study. Ideally, they will commercialize this product, so they are well suited to take on the financial risk.
Common Language & Concerns
Perhaps a sponsor states that a subject injury means an unanticipated immediate physical injury suffered by a study participant as a direct result of the study drug, as determined by a sponsor.
What concerns should this language raise? First, unanticipated can mean that subject injuries are only things we aren’t expecting to happen. Therefore, anything addressed in the ICF as a potential risk doesn’t count – only the unanticipated effects. This approach is unacceptable; subject injury should mean anything that happens to a patient, including adverse events/reactions – whether or not the sponsor expects them.
Let’s consider the language of immediate injury. Does that mean the moment a study participant has a drug injected? Within 15 minutes? An hour? A day? The meaning is unclear because you don’t know who gets to determine what is immediate. Worst case scenario: The sponsor says, “This case does not count because it was a latent effect; it happened three years down the road.” The sponsor’s responsibility should remain true, whether the injury happens right away or down the road.
Next, consider the meaning of physical injury. The sponsor may want it to be anything that’s obviously affecting the subject’s physicality. This language could exclude any change to mental health due to their study drug. You have likely seen ads for drugs that talk about “increased symptoms of depression” or “increased thoughts of suicide.” The physical injury notion would exclude any of these adverse reactions, which should raise a flag.
Specifying the direct result of the study drug may be acceptable in the context of a vaccine, where the vaccine site shows a reaction or a minor infection requiring an antibiotic. That reaction is a clear, direct result of the vaccine. However, if the study drug or device has a more systemic effect on the participant, you do not know the limitations associated with “direct results.” Because the limitation favors the sponsor and not the patient, that language should be avoided.
Terms around a subject injury need to encompass any part of the study, not just of the study drug. Factors could include the study drug, protocol-mandated activities, or protocol-directed instructions. Watch for these potential limitations in your CTA.
Last, let’s consider the term as determined by the sponsor. The PI has the closest relationship with the study participant – enrolling them, accessing their medical records, communicating with them, and providing their care. They also have the relevant medical expertise. If the sponsor determines whether the sponsor must pay for a subject injury, there is a conflict of interest. The sponsor should not be in the sole decision-making position for these subject injuries, so avoid this language.
How do we address these common language issues? See the graphic for a suggested fix. You may have to adjust some language during negotiations, but you want to be as broad as possible to protect the institution and, more importantly, the patients.
Next, let’s address the subject injury provision and sponsor responsibilities. See the common language in our graphic.
What are the concerns? Expenses incurred at site connotes that the sponsor will pay for reasonable and necessary expenses incurred at the site. However, we do not know where the subject might be treated. For example, if a subject faints at the grocery store, EMTs will transport them to the nearest facility, excluding their treatment from coverage. You have no control, and so this language is unacceptable.
Next, consider the term emergency care. The sponsor is qualifying what type of care they will cover. You cannot control the injury and where it occurs; perhaps the subject has a reaction during a physical, and their doctor provides a prescription to address it. Because this was not emergency care, is the treatment not covered? Unacceptable.
If you’ve handled contract negotiations, you’ve likely seen the language “which are not covered by a study participant’s insurance.” Essentially, it means that the sponsor will pay for expenses but bill the patient’s insurance first; whatever insurance doesn’t cover, the sponsor will pay. Why is that a problem? First, it violates the Medicare secondary payer rule: If you have a Medicare patient on your study, you cannot bill Medicare before the sponsor in this circumstance. The Medicare secondary payer rule says that if there is more than one payer or insurer on any medical bill, Medicare will not be the primary payer; they will be the secondary payer (also true for Medicaid beneficiaries).
How do we fix these issues? See our graphic for a modified version of the original language. We removed the notion that expenses must be incurred at the site. Also, we addressed the idea that it must be emergency care; the sponsor doesn’t make that call. We added payment for diagnostic costs. Finally, we addressed any treatment related to the subject’s injury, removing any notion of the cost not covered by a study participants’ insurance.
What about exceptions? See our graphic for common exception language provided by sponsors.
What are the issues? Subsection ii references the site’s failure to comply with the sponsor’s recommendations or suggestions. If the site must follow a directive and there is a chain reaction from them not doing so, the instructions need to be crystal clear. Suppose the sponsor changes a study directive, and the subject’s compensation for resulting injuries is affected. The instructions need to be absolutely clear – including protocol amendments instead of loose recommendations.
Regarding exceptions around the preexisting conditions or underlying diseases, we recommend building in language that exacerbations related to the study will still be covered by the sponsor. For example, the sponsor might not have to pay for an effect that is a normal progression of the underlying disease. However, if the study drug exacerbated the process, the sponsor cannot avoid their obligations.
You may have seen references to study participant’s early withdrawal. The sponsor cannot tie their willingness to pay for subject injuries to the patient’s rights established in the ICF; the patient has the right to withdraw at any time. The sponsor cannot coerce their continued enrollment in the study by saying that injuries would only be covered if the subject continues the study.
We sometimes see this last issue – study participant’s failure to comply – involving vulnerable populations, such as Alzheimer’s studies. The study participant likely doesn’t have a copy of the protocol. The sponsor cannot say that the participant did not follow directions, so their injuries will not be covered.
What is the solution? See our modifications in the graphic. You will note that we eliminated vague recommendations, suggestions, and other non-specific language.
Be cautious about conditional language, expiration of sponsor’s obligations, and silence. See several real-world insights in our graphic.
To summarize, take your time when considering subject injury language in your CTA, and think of how the terms might apply. Do not hesitate to ask the sponsor, “What does this language mean?” They may ask you to suggest better language and offer to compromise. Working together as stakeholders, we can protect our valuable clinical trial participants while advancing science.
Interested in learning more about how WCG can help your site navigate the contract negotiation process? Contact us today to chat with our experts.