Multiple sessions at the American Association for Cancer Research Virtual Annual Meeting II covered how COVID-19 is affecting cancer patients, from how clinical trials needed to be modified during the pandemic to how real-world evidence can play a role now and in the future.
Francis Collins, director of the NIH, noted that we'll be living with the effects of the pandemic for some time since it has caused a steep drop in cancer diagnoses as people stopped going in for screening and diagnoses. "These are not deaths that are going to be counted as directly due to the virus, but in a certain way, they are. And we have to do everything we possibly can, now that things are starting to open up, to catch up and make sure that those folk who have waited don't keep on waiting any longer," Collins told the conference attendees.
As the pandemic came to fruition, the FDA issued guidance on the conduct of clinical trials for various medical products during the COVID-19 public health emergency. "The overarching message of this guidance is that ensuring the safety of trial participants is paramount during this time," Nicole Gormley, acting director of the FDA's division of hematologic malignancies 2, told the audience.
The guidance suggested sponsors consider alternative methods for safety assessments, for example phone contact or virtual visits, and the agency allowed protocol changes for safety to be made immediately with subsequent review by institutional review boards and notification of the FDA.
"Most guidances take months to years to release whereas these guidances have been released within weeks," Paul Kluetz, deputy director of the FDA's oncology center of excellence, said in another session, noting that the guidances didn't go through public comment, which helped expedite getting the information to companies and clinical trial sites.
As helpful as the guidance can be, Kluetz pointed out that the needs of clinical trials can vary widely and "questions that are specific to an individual trial, things like unique drug factors or trial endpoints, they still may require companies or investigators contact the FDA review divisions for more formal and specific advice."
The FDA used the guidances to signal that the agency expects that trial modifications would need to occur. "It's expected, at this time, that there will be some missing data or inability to capture some data," Gormley said.
While missing or substituted data is to be expected, Kluetz stressed that "it's important that investigators and sponsors carefully document COVID-19 contingency methods so that these can be taken into account when we do analyze the data at trial completion."
On the front lines
Being in New York, the Icahn School of Medicine at Mt. Sinai had to shut down its clinical trials during the pandemic, Miriam Merad, director of Mt. Sinai's precision immunology institute and its human immune monitoring core, told BioWorld.
The clinical trials are back up and running, but the hospital still isn't running at 100% staffing. "We cannot accrue as efficiently as we could before the pandemic," Merad noted. "It's very unfortunate."
While the oncology doctors have been slow to restart their clinical trials, they've been pitching in helping their colleagues design clinical trials to test treatments for COVID-19 patients. "Cancer doctors are much more used to writing trials than any other type of doctor, so they were extremely mobilized to help the infectious disease team," Merad said.
Immuno-oncologists also have an enormous understanding of the immune system, making them a vital asset to the viral immunologists studying T-cell exhaustion in COVID-19 patients. "We have put enormous effort into understanding T-cell dysfunction in the context of tumor antigen expression," Merad said of immuno-oncologists.
Finally, because COVID-19 can cause immune overreactions similar to immuno-oncology treatments, such as CAR T therapies, oncology doctors have been called in to help identify cytokine release syndrome and help treat COVID-19 patients the same way they would their cancer patients.
While the pandemic has created many issues with clinical trials, the FDA’s Gormley said she sees the experience that sponsors are having with the use of local services and remote monitoring as potentially having a positive impact on clinical trials in the future since decentralized trials can increase the ease of trial participation. "I'm hopeful these sorts of trends will continue, but there is a learning curve associated with that," she said.
Kluetz had a similar thought, "By necessity, COVID has pushed the cancer clinical trial community out of its comfort zone, rapidly deploying remote assessments and digital health technology and stimulating unprecedented collaboration to explore the use of real-world data."
While he's hopeful that the experience will change the way clinical trials are conducted in the future, Kluetz said he sees a need to analyze the results before moving forward. "I think the most important thing that we need to do is make sure that we understand very well the impact on certain types of remote assessments on trial integrity. And I think we're going to have the opportunity to do that with the clinical trial data that we're going to be receiving over the next months to years," Kluetz said, noting that the clinical trials happening during the pandemic offer an opportunity to compare standard protocols and remote monitoring within a single trial.
The pandemic also offers the opportunity to explore the use of real-world data in the context of clinical treatment to answer questions without requiring clinical trials. "I've been pretty proactive in reaching out to some institutions who are considering doing this to try and consider the patient-reported outcome systems that have been rigorously developed," Kluetz said. "There's certainly opportunities to deploy rigorous assessments in the clinical care community."
C.K. Wang, chief medical officer of Cota Inc., agreed that the data streams from real-world data need to be validated and tested. "The way we think about data is the more the better," Wang told the audience. "The challenge is not in the collection of the data, but how we use the data."
Jonathan Hirsch, founder and president of Syapse Inc., used electronic health records to look at the effect on how racial and socioeconomic data affected treatments and outcomes of COVID-19 patients. Using existing data streams, Syapse was able to do the analysis in just five days, and while the data are under review and couldn't be presented, Hirsh noted that the company "found a number of interesting things" in the study, which will be presented in the coming months.