Clinical trial legal experts discuss lessons learned from mock trials

Be diligent with informed consent process

Clinical trial sites and research professionals should be cautious and learn from their peers' mistakes to prevent clinical research (CR) litigation, experts say.

Although CR litigation remains fairly infrequent, there have been high-profile problems in the past decade that raise questions of whether trial sites are doing all they can to improve informed consent and reduce risks.

This is part of the reason many research professionals have attended a clinical research mock trial over the past decade. The mock trial is held at the Horsham, PA-based Drug Information Association's (DIA's) annual meeting.

"We put on a fictional trial at DIA where we demonstrate some of the issues presented or alleged by plaintiffs," says Mark C. Hegarty, JD, a partner and attorney with Shook, Hardy & Bacon of Kansas City, MO. Hegarty was the chairperson of the most recent DIA mock trial. His practice focuses on defending companies in pharmaceutical and medical device product liability cases.

"The audience can then see how a plaintiff's lawyer might interpret what went on at a clinical trial to their advantage," Hegarty says.

Some of the mock trials have been based on real cases, and many include lessons such as how anyone involved in research can be dragged into litigation.

"A plaintiff's lawyer names everyone in the process before determining if there's liability or not," says John Isidor, JD, chief executive officer of Schulman Associates IRB in Cincinnati, OH, and editorial advisory board member of Clinical Trials Administrator. Isidor has also participated in the DIA mock trials, portraying a judge. Isidor and Hegarty plan to continue their roles in a mock trial planned for the 44th DIA Annual Meeting, June 22-26, 2008, in Boston, MA. Before heading an independent IRB, Isidor was a trial lawyer for 14 years.

Also, CR litigation might occur even when those involved in the research are convinced that nothing they did in the study resulted in a subject's injury or death.

"When we're dealing with research, occasionally people are going to get sick and have serious adverse events in clinical trials," Isidor says. "That's part of the research process — not everyone is going to have a good result in a trial."

In some cases, litigation has proceeded even when the FDA conducted an investigation determining that the clinical trial had nothing to do with the subject's death, Isidor notes.

With the help of the Internet, it's become a little easier for CR participants to find lawyers who specialize in suing CR sponsors, investigators, and research teams, Hegarty notes.

"You can do a search on Google and type in 'clinical trial lawsuit,' and there will be lawyer advertisements coming up," Hegarty says. "The Internet is certainly a source of information for people looking to inquire about these sorts of things."

Failure to warn and standard of care

Some industry experts say there has been a rise in CR litigation, but it's probably most accurate to say that researchers and sponsors are being sued and will continue to be sued in the future, he says.

"For the most part the lawsuits are brought against sponsors, investigators, and even IRBs," Hegarty says.

"The claims against sponsors have been primarily claims about failure to warn," he adds. "The claims against investigators and IRBs have included primarily failure to provide adequate informed consent."

Physician investigators might also have a claim about failure to meet the standard of medical care.

Medical malpractice cases often are grouped together with research litigation, but they can be brought separately, Hegarty says.

"A common allegation is that the investigator failed to provide proper care to the patient," he adds. "The particular focus is often on whether the investigator strictly followed the protocol and/or if the risks associated with participating in the study were adequately conveyed to the patient."

Cases often hinge on a determination of the duties owed to the patient, which is the care owed to the patient and the party responsible for providing the care, Hegarty says.

On a positive note, there hasn't been a rash of lawsuits involving research sites because the informed consent process and patient care are typically adequate, Hegarty notes.

"But there are certainly people out there who would contend otherwise," he adds.

SOPs, documentation, and follow-up

Although bad luck can play a role in determining which investigators end up in court and which don't, there also are some simple policies and procedures that CR sites can follow to reduce their legal risk.

"Sites need to be very careful in conducting the informed consent process," Isidor says. "Research personnel need to make sure the subject has consented and that he understood the document."

Likewise, CR sites should be diligent when screening and enrolling subjects by making certain that subjects are screened carefully in accordance with the protocol inclusion and exclusion criteria, Isidor says.

"I've seen a couple of cases where a plaintiff might not have had a good case, but people were in such a hurry or were sloppy when determining whether a subject was qualified for the trial that they enrolled someone who was not eligible," Isidor explains.

Sponsors should follow-up on the adverse event profile as trials proceed, he suggests.

"They should look for any trends that may require either modification of a consent document or possibly re-looking at the value of a trial," Isidor says. "Sponsors need to effectively monitor the site to make sure the proper people are being enrolled in the trial and that the trial is being properly conducted by the investigator and the investigator's support personnel."

Since even IRBs can be sued, IRB members and staff also need to be careful.

"IRBs need to make sure they have the proper expertise on their boards and make sure the proper initial review and continuing reviews are done," Isidor says. "They should have solid standard operating procedures [SOPs] and make sure their decisions and the way they document those decisions are in compliance with their SOPs."

Schulman Associates IRB has internal checks and balances, including self-audits, he adds.

Research sites also should have internal audits.

Recruitment and appropriate incentives

Although this isn't a common area of CR litigation, research sites need to make certain that all recruitment incentives are documented and disclosed.

"One thing I would be concerned about is if there were undisclosed monetary incentives to physicians regarding recruitment and enrollment of subjects for clinical trials," Isidor says. "If there's a dispute about the consent process or whether someone is properly enrolled in a trial, then it could get complicated if there are monetary incentives to investigators which are not disclosed to subjects through the informed consent form."

Problems might occur if sponsors offer investigators significant enrollment incentives that are beyond what is listed in the clinical trial agreement and which are above what both parties had agreed was fair compensation for conducting the trial, he explains.

If enrollment is slow and sponsors and clinical research organizations (CROs) decide to provide additional incentives, then they should arrive at a fair market value that is documented in the revised clinical trial agreement, Isidor says.

Research professionals should keep in mind that all of their activities must be both legal and pass the smell test, he notes.

"If you had an injured subject, and there was a significant undisclosed incentive payment by the CRO and/or sponsor to the investigator to target that person for participation in the trial, then it would be difficult to show that the informed consent process was unbiased and appropriate," Isidor says. "It doesn't pass the smell test, and the smell test in litigation can be quite important at times."

A plaintiff's attorney would be quick to argue in court that the undisclosed incentives would significantly compromise the neutrality of the investigator and therefore would invalidate the subject's informed consent, he says.

"Most potential subjects will ask the study coordinator and/or investigator if the study is a good idea for them," Isidor explains. "They're greatly influenced by the coordinator's response because people invest a lot of trust in their health care professionals."

Oversight of informed consent and documentation also is important.

"Make sure all protocol-required testing procedures and questionnaires and documentation are done to properly assess the potential subjects' qualifications," he says. "And sites should maintain a proper level of oversight throughout the trial."

Attendees to the mock trials also have learned, often to their surprise, how research staff's e-mails, notes, patient charts, and other notes can be used by a plaintiff's attorney to reinforce a case, Isidor says.

"If an investigator sends a poorly thought-out e-mail in a flippant manner and you have an injured party in the clinical trial, then that thing that was flippantly said never goes away," Isidor says. "It can come back to haunt you."

It's a lesson research professionals should take home: "You need to be diligent in the research process by recording information in a thoughtful, accurate, and clear manner," Isidor says.