CT directors should take steps to manage risk

Think of subjects' financial risk as well

Clinical trials directors should take reasonable steps to manage their organization's risk in human subjects research. It's not wise to assume that someone else is taking care of this issue, an expert advises.

"Keep in mind that subjects don't understand all this legal stuff, and it's up to us [to handle it] at the site level," says Barbara M. Longmire, MSN, director of the office of clinical trials at the University of North Carolina at Chapel Hill in Chapel Hill, NC. Longmire was a scheduled speaker about managing risk at the 2010 MAGI Clinical Research Conference - East, held May 23-26, in Boston, MA.

"We have a reputation to uphold, and we have moral and ethical obligations, as well," Longmire adds. "So keep this in mind when you're negotiating a contract with a sponsor."

Longmire offers these suggestions for managing a CT site's risk:

• Make certain sponsor is insured sufficiently: CT directors should make certain sponsors have insurance that will cover problems with the drug, biologic, or device, Longmire suggests.

"Be sure the contract shows that they have sufficient insurance to meet their obligations, and that they can provide proof of it," she says.

"We've had contracts with companies that filed [Bankruptcy] Chapter 7 or 11, and were left owing money," Longmire says. "So be sure the company is solvent."

• Understand indemnification: Clinical research contracts include language regarding indemnification.

"Indemnification is a contractual obligation assumed by or legally imposed on one party to protect the other party against losses or damages from specific liabilities," Longmire says.

This basically is the terminology used to explain who is responsible for what when something goes wrong, Longmire says.

"The wording could say, 'We'll indemnify you for our own negligence,'" she adds.

A CT site could indemnify the sponsor for any negligence on its part, such as if the CT site did not follow the protocol properly, and a subject was injured because of that negligence.

There are two main ways for a company to reimburse for a subject's injury: one is to have a completely separate contract provision that is not part of the indemnification clause, and the other is to have them indemnify a site for a subject's injury that is related to a study product or procedures, Longmire says.

"If the sponsor will agree to a separate contract provision for subject injury then they agree to reimburse however it's defined -- upon receipt of documentation or invoice -- and the lawyers can stay out of it," she explains. "We try to get a separate subject injury provision that is not part of indemnification because sometimes going through the indemnification process takes a long time, and the subject's medical bills will build up."

• Check contract language and informed consent document for inconsistencies: "Make sure there is consistency between the contract subject injury section and the injury section in the informed consent document," Longmire advises.

If the contract clearly states that no subject injury costs will be reimbursed, then it would be a mistake to have an informed consent form that says any treatment for injuries suffered because of the research will be covered by the sponsor, she adds.

"Patients have to be able to trust that what is in the informed consent is accurate, and the contract backs that up," Longmire says. "There's a huge gap usually between the research subject's knowledge of this whole process and what is in the contract."

• Keep in mind that PI-initiated trials are handled differently: Trials initiated by principal investigators typically have no subject injury provision by the drug or device sponsor, Longmire says.

"And there's very little indemnification, because it's not the sponsor's protocol," she adds. "So even if the research organization receives $500,000 in funding from the pharmaceutical company, if it's a PI-initiated protocol, then the pharmaceutical company will say it's not the sponsor."

CT sites need to make certain the informed consent conveys this message.

• Think of subjects' financial risk, as well: "Most people think of the risk-benefits section of informed consent as only addressing physical risk or benefits to participating," Longmire says. "But in my opinion, I think there is a financial risk to the subject for participating in the research, and it's seldom disclosed in detail."

For example, the subject may be responsible for insurance co-pays and deductibles resulting from procedures done during the study.

And there is even a bigger financial risk in some device trials.

"I saw a contract one time for a device trial that said the cost of the device will be billed to the subject or to the subject's insurance company," Longmire says. "But what they didn't say was that if the insurance company rejected the claim, then the device would cost the person $28,000."

For most people, the prospect of having to pay $28,000 out-of-pocket is a potential risk, she adds.

• Watch for contract carve-outs: Sometimes contract language will say that the sponsor will pay for treatment injury so long as the injury doesn't fall into one of the common categories, such as an adverse event that is related to a pre-existing disease or condition, Longmire says.

"I've seen contracts that say they won't pay for treatment if the subject fails to follow instructions, and that's open to a lot of different interpretations and meanings," she adds.

For example, a subject could live a couple of hours away from the research site. Then on the day of one scheduled visit, the subject's car breaks down, and the subject misses the appointment, showing up a couple of days later. If the subject later has an adverse event, the sponsor could say that injury treatment is not covered because the subject didn't follow instructions when he failed to make the visit at the appointed time, Longmire says.

"I would negotiate to have this carve-out language taken out of the contract," she says.

Some universities have written policies stating they will not enter into a contract with a sponsor unless the sponsor contractually agrees to cover all the costs related to the adverse event, she adds.

"We at UNC probably spend as much time negotiating the subject injury section of the contract as we do anything else in it," Longmire says. "We feel strongly that if a subject is volunteering in a research study and he's injured, then the cost of treating the injury should be covered by the sponsor, who stands to benefit if the product is approved."

• Consider CR site's own risks: If research organizations are not careful when negotiating the risk part of contracts, then they might find themselves in great risk of harm financially and to their reputation.

"In university hospitals and teaching hospitals, your research subjects come from your clinical population," Longmire says. "So that's an additional reason to pay really close attention to what you do."

Also, sites often say that subjects are not waiving any of their rights when they sign an informed consent form. But sponsors might want the site to include IC language that basically says the sponsor will cover treatment costs for injuries related to the trial, but that they will not cover loss of wages, pain and suffering costs, Longmire says.

This conflict has to be worked out, or it will create some risk for the CR site.

The key is to keep in mind that people involved in clinical research should be treated fairly, particularly when they're at risk of injury.

"Sponsors are looking for ways to limit their potential liability, and I understand why they're doing it, and I don't disagree that they need to limit their costs," Longmire says. "But it shouldn't be at the risk of research subjects."