Slowdown Anticipated for Clinical Trials, New Agent Adoption

Clinical trials for biosimilars and other agents are likely to slow down, if not stall, as coronavirus disease 2019 (COVID-19) wends its course, said Jim M. Koeller, MS, a professor of pharmacotherapy with the Graduate School of Biomedical Studies at UT Health in Austin, Texas.

“The clinical trials will be the easiest thing to put on hold. I don’t see a new trial starting until some of this stuff levels out,” he said in an interview with The Center for Biosimilars^® . “We’re still talking about supplies of masks and gowns.”

Similarly, new agents that become available for use following FDA approval will likely not find their way into circulation within medical institutions because the resources needed to conduct the extensive internal reviews by pharmacy and therapeutics committees simply are not available at this time, he said.

What’s more likely is that hospitals and clinics will devote their energies to attending to the patients expected to become sickened by COVID-19. In addition, clinical trial activity will be downsized for weeks, possibly months, until conditions normalize, he said.

“I think people who are under treatment currently will continue to get treatment. It’s unlikely that new patients will go on trial protocols before we figure out what’s going on,” Koeller said.

The University of Texas MD Anderson Cancer Center, which encompasses UT Health, is the largest cancer treatment center in the United States and has an extensive body of ongoing clinical trial activity.

Although some major drugmakers such as Eli Lilly and Co and Bristol Myers Squibb (BMS) recently hit the pause button on starting new clinical trials, there has been a scarcity of guidance filtering down to investigators from trial sponsors about how they wish ongoing trials to proceed, Koeller said. “The emails have gone silent.”

Eli Lilly, which has been developing an insulin biosimilar, has delayed most new clinical studies and halted enrollment in most ongoing studies. Treatment, however, will continue for patients already enrolled.

“The severe burden on healthcare systems caused by this pandemic has also impaired the ability of many research sites to start new studies or enroll new patients,” the company said in a statement Monday, March 23. “At the same time, Lilly recognizes that for patients already enrolled in clinical trials, discontinuation would disrupt their treatment and potentially diminish the societal value of the research information to which they are contributing. Therefore, we will maintain ongoing studies, but with study-by-study consideration."

For its part, BMS has decided to allow new patient enrollment if sites can demonstrate the ability to recruit and manage patients effectivity and in compliance with protocol. However, BMS is not activating new study sites.

The company asked investigators to suspend or not initiate treatment for patients with signs of COVID-19 until the symptoms resolve.

A Sandoz spokesperson said the company is monitoring its clinical trials programs closely, aided by a real-time system established in 2018 that culls information at the individual-patient level and enables the company to rapidly implement contingency changes. “As of now, we have kept the majority of our trials operating amid the COVID-19 situation,” said Allison Schneider, director of communications.

Not just patients but also clinicians and investigators are preoccupied daily with figuring out how to work under such conditions as COVID-19 has created, obtain food, and look after family members, Koeller said. As hospitals start to see a deluge of patients affected by COVID-19, resources available for normal activities will become scarce.

Many decisions have yet to be made about how ongoing clinical trials can be conducted in these conditions, such as whether family members may accompany patients on trials for onsite care. “There are a lot of things changing by the minute,” he said.

Late last week, the FDA issued clinical trial guidance indicating that modifications to clinical trials may be acceptable if they are well reasoned and well documented. The unusual conditions brought about by COVID-19 allow for such departures from previously approved protocol, the FDA said, although at the end of the process, investigators will need to produce reliable evidence. Koeller notes that some patients may simply lose their eligibility to participate in trials, given infection with the new coronavirus.

The National Cancer Institute (NCI), which conducts a multitude of clinical studies, also has issued advice to allow flexibility needed to continue clinical trials. “We continue to closely monitor NCI-supported clinical trials to help address the needs of investigators to implement accommodations to maintain continuity of care for their patients who are being treated on trials as much as possible,” the NCI said.

Accommodations such as allowing patients to receive treatments from local providers who are able to maintain trial protocols, such as examinations and tests, are allowable, the NCI said.

“The activities provided by the local healthcare provider must be conducted under the oversight of the responsible investigator in accordance with the protocol and with assurances that processes are in place to report all required information to the responsible investigator who is responsible for ensuring that the data are entered into the data management system for the trial,” the NCI wrote.