Sponsors are overwhelming sites with a growing volume of safety reports, and sites are fighting back. The magnitude of the problem of unnecessary and overly burdensome safety reporting is getting worse; in the past three years, some sponsors of oncology drugs have unleashed a five-fold increase in safety reports.

Safety reporting procedures have always been a time-consuming challenge for sites, but sponsor and CRO safety reports that duplicate information or are not needed increase the workload for staff who need to process the reports. The rising complexity of trials and the growing number of oncology trials is amplifying the problem.

“Sites are really starting to take a stand,” said Steven Beales, senior vice president for WCG’s scientific and regulatory division. “Some of the biggest [academic] sites are coming back to sponsors and saying enough is enough. We’re going to see more and more of this pushback from nonacademic sites if sponsors don’t do something,” Beales said.

Part of the problem is that some sponsors and CROs do not differentiate between adverse events caused by the investigational product and those related to factors outside the trial, classifying everything as requiring documentation in a suspected unexpected serious adverse reaction (SUSAR) report. “Sponsors think they’re following the letter of the law by over-distributing and reporting every event,” Beales told attendees of a WCG webinar last week. “That’s not what the FDA wants, and that noise buries true [safety] signals.”

Sites increasingly are articulating what they will and won’t do as far as safety reporting is concerned, passing back to sponsors the responsibility for evaluating whether adverse events are caused by the investigational product (IP) and determining which require reporting to regulators and IRBs. Sponsors should notify sites of IP-related events that are classified as SUSARs, but too often are flooding sites with multiple reports that sites need to process before determining what does and doesn’t qualify as a SUSAR.

Beales said that especially in oncology studies, it is difficult to tease out whether an event was caused by the IP or the underlying disease. The agency doesn’t want sponsors to overreact by sending sites multiple follow-up reports for the same issue. Doing so could lead to complacency and a feeling at sites that the reports represent something of a nuisance, rather than anything actionable.

Elena Jouravleva, director of regulatory affairs for the U.S. Oncology Network, a site network of about 160 integrated, community-based oncology practices, said her team works with more than 100 sponsors that collectively support more than 300 clinical trials, and team members log into about 40 different portals on a daily basis to pull safety reports. She said her team was trying to process between 1,500 and 2,500 safety reports a month during the pandemic, but the number has since declined to a range of between 1,500 and 1,600 safety reports.

After the FDA updated its guidance on safety reporting requirements for investigational new drug applications in April 2020, Jouravleva said her team performed an assessment of the safety reports they had been processing and determined that half of them were not true SUSARs. Consequently, Jouravleva said her team reached out to sponsors individually and said they would only process, acknowledge, review and archive true SUSARs, following the definition outlined in FDA regulations; other reports would not be processed. She also said sponsors were reminded that they — not sites — are ultimately responsible for the grading of safety reports.

“Some [sponsors] are very good at communicating and distributing truly relevant information for FDA regulations,” she said. “And some of them are just blasting us with everything under the sun — even today. The problem is that more is not better. We keep forgetting we distribute this information because a physician’s time is valuable. They need to be able to [quickly] determine if there is something applicable to their patient’s care or not.”

Beales said it takes at least 20 minutes for a site to process one safety report, and Jouravleva said sites are not reimbursed for that extra work. “Maybe that’s something that needs to be considered at some point. You just have to do it because they’re regulations. And when that’s impacting the budget, then maybe the stringency of the review is a little bit higher.”

While Jouravleva said there weren’t any sponsors her network refuses to work with, she advises other sites and site networks to evaluate whether they want to engage in a clinical trial, knowing upfront what the administrative or monitoring burdens are going to be. She says her network tells potential sponsor partners that “these are our policies, this is what we are required to process, this is what we will do, this is what we will not do — because we’re not required to accept anything not clearly indicated as a SUSAR. That’s how we are approaching it, and I highly advise it.”

Sponsors like to communicate with sites using portals because they save sponsors time and money, Beales said. Portals also gives sponsors access to various security and control measures. But he said sites dislike portals for several reasons, particularly that a portal is another proprietary system that a site will need to learn how to use. It also perpetuates the issue of having a different computer system for every trial. Beales said sites also don’t like portals because they feel they take time away from patient enrollment and care, and don’t necessarily see the direct value in such systems.

Beales co-chairs the Safety Reporting Harmonization Working Group, an independent group that is voluntarily trying to address the safety reporting issue on a global scale. He said the group — which includes Genentech, Roche, Janssen, Amgen, Covance and WCG — started by making a portal of global laws to ensure sites get what they need from sponsors. “We’re not forcing the sites to do anything that is not in accordance with those laws. It’s all driven by the key spirit of patient safety and protecting the patient. We want to minimize the time that investigators and other people have to spend away from a patient while making sure all of those valuable safety signals get through.”

Sponsors have several options at their disposal to help ease the burden felt by sites, according to Beales. They could send batch notifications of safety reports, either on a daily or weekly basis, and can have a site’s principal investigator (PI) delegate safety reporting tasks to another member of site staff or a site management organization. Sponsors could also submit a single SUSAR about a specific IP to each study involved instead of blanketing all of the studies’ sites with reports of the same event.

Beales said the working group believes the optimum workflow for sites is a simple email with any appropriate links inside. “There is no need for PIs to be signing individual SUSARs. The FDA does not want that, and the PIs don’t want that.”