Watch Out for ‘Toxic’ Studies When Adding New Hospital to HRPP
Research conduct not in compliance
When WellSpan Health in York, PA, was merging with a community hospital, an unexpected problem came to the attention of the human research protection program (HRPP). It had to do with 17 open studies at the hospital joining the WellSpan Health system.
A study coordinator who worked in a physician’s office connected to the hospital approached Tara Moore, quality assurance specialist at WellSpan, to ask how research would be handled going forward.
“The ink wasn’t even dry on the merger yet,” Moore recalls. “We hadn’t even discussed a plan. We weren’t even aware there was research going on, but because this coordinator brought it to our attention, we started thinking about what we needed to do.”
Further investigation revealed the open studies had been reviewed by seven external IRBs. There were only three principal investigators involved, including one who had 13 of the open studies.
That should have been a red flag, but Moore and colleagues believed the IRBs involved had provided enough checks and balances.
“We were familiar with all of them, and we assumed that everything would be fine,” she says. “The study coordinator was very knowledgeable, and we relied on her to keep us informed of what was going on with the research, and we still hadn’t come up with a plan.”
Since WellSpan has an electronic IRB submission system, Moore asked the study coordinator to upload the most recent protocols and informed consent forms into the system. Just loading the informed consents took several months.
“At that time, I was also the IRB coordinator, and I didn’t have the time to educate and monitor [the situation],” Moore says.
Then the study coordinator quit only six months after the merger.
“Then, my director said, ‘Tara, why don’t you go out and check on their paperwork to see what’s going on,’” Moore says.
She did, and the hornet’s nest burst open.
The following is what the quality assurance (QA) staff learned about the studies WellSpan had acquired with the hospital:
• Enrollment was counterintuitively high. Moore and a colleague reviewed one study’s regulatory binders, patient binders, and study documentation. They selected a study with 15 participants, which was a large number for a study in a small, rural hospital to have recruited.
The original study coordinator emphasized the high enrollment and how much money it brought into the hospital.
“She put an emphasis on that, and it was uncomfortable,” Moore says.
• There were consenting and other errors. “When we started looking at the registry, the documentation was atrocious,” Moore says. “Documentation was not anything like we expected.”
The documents contained consenting errors and inclusion criteria mistakes. Subjects who should have been excluded were enrolled. “We were overwhelmed by the number of errors,” she notes.
There was an unlocked drug closet. An expired study drug was sitting on the floor. Informed consent forms had words crossed out and patient signatures in the wrong places. The study coordinator and research nurse signed and dated in the wrong places. However, none of the findings indicated any patient harm.
“We found that monitoring visits occurred and discrepancies were noticed by the monitor, but there was never a follow-up and no documentation of the site correcting its errors,” she explains. “There was no documentation that the monitor reminded them.”
Moore found it difficult to understand why sponsors and IRBs allowed the study to continue despite the site’s flaws. She learned that the principal investigator was responsible for the conduct of the study.
• An independent audit was needed. “We wrote a report and sent it to my supervisor, who escalated it to hospital leadership,” Moore says. “They put enrollment on hold on all open studies and said, ‘We’re going to figure this out.’”
Moore had too many responsibilities to take on the work of auditing the studies, so the organization contracted with an outside expert.
Two auditors were onsite for 4.5 days, interviewing staff, reviewing policies and procedures, and reviewing 11 research projects and study financials. They wrote a summary and recommendations.
• WellSpan notified stakeholders. “We were responsible for the conduct of research, so my director sent a notification letter to the seven external IRBs and study sponsors and said, ‘FYI, the studies are on hold while WellSpan completes an audit of each of the studies,’” Moore says.
Being on hold meant the studies were suspended to new enrollment. Updated information could be added to the studies, but everything else was on hold, and study participants were notified.
The study departments/sites had to write corrective action plans for the problems discovered by the internal audit.
“For instance, the patient/subject signs a consent and signs in the consenter’s spot,” Moore says. “When we found things like that, we wrote a note to the file and attached it to the file, saying it was noticed on this day that the subject signed this line. Consent occurred and the subject agreed to be in the study, but it was verified that the subject signed it on an incorrect line.”
The study staff needed education on WellSpan’s research policies and procedures and human research protection regulations.
Also, the IRB and Moore spoke with department leadership about the physical needs of studies, including the need for drug closets to be double-locked, and separate copier/scanner equipment.
“We provided a lot of information to them over a six-month period to get their studies up and running again, and we closed out the studies we could,” Moore says.
For instance, some studies were in long-term follow-up or data analysis, and these could be closed.
“Everyone was overwhelmed,” Moore recalls. “At the same time this was going on, the principal investigator who had the most open studies left the system, as well.”
The department hired a new doctor who was interested in becoming a principal investigator. The remaining ongoing studies, which were still on hold, were transferred to the new physician.
“The department leadership opened up one study at a time,” Moore says. “We went in, educated, cleaned up everything, and did one study at a time.”
• The FDA got involved. “They announced a full FDA audit in December 2015,” Moore says. “A research nurse spent a lot of time with her.”
Ultimately, the FDA audit held the principal investigator, who had left, responsible for the problems, Moore says.
“The auditor said there was clear evidence that once WellSpan came in, there were improvements, and WellSpan did the right things and took the right action,” Moore says.
The experience with the hospital’s problematic studies was an eye-opening experience for Moore and others at WellSpan.
“Moving forward, we’re very proactive,” she says. “We had another hospital join our system within three months of the merger, and they had only one study that was open.”
Moore visited the hospital’s study staff, made introductions, and made sure documentation was correct.
“I talked to the principal investigator and made sure everything was being followed as far as rules and regulations,” she notes.
The standard practice now is to meet and greet research staff at newly merged hospitals and provide them with a minimal education. The staff is given time to adjust to new requirements and changes, and the IRB monitors the progress.
“We look at things, and it’s very informal and casual, and what we hear is positive feedback,” Moore says. “They appreciate this, and they’ve embraced the research efforts.”
Among the lessons learned is that a research institution cannot assume everything is perfectly fine with a study just because the study was reviewed by an external IRB. Every study and research team’s work should be monitored continually to prevent the problems WellSpan found with the newly merged hospital’s open studies.
“It was a very, very interesting experience — and one I hope never to have to repeat,” Moore says
When WellSpan Health merged with a community hospital, an unexpected problem came to the attention of the human research protection program -- having to do with 17 open studies at the hospital joining the WellSpan Health system.
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