Though clinical research, in general, has been challenged during the COVID-19 pandemic, oncology trials “have several unique considerations due to disease severity, regimen complexity, and acute care requirements” that have caused even greater challenges, US FDA officials wrote in a new viewpoint published in JAMA Oncology.
Data integrity issues and “pandemic-induced protocol deviations” are a concern for sponsors and FDA alike, and the agency has been attempting to be as flexible as is possible while safeguarding patient wellbeing and clinical trial integrity, according to Anand Shah, FDA deputy commissioner for medical and scientific affairs, Richard Pazdur, director of the FDA Oncology Center of Excellence (OCE), and Kushal Kadaka, health scientist in the office of the commissioner. Telehealth for patient monitoring has burgeoned during the pandemic, for example, an approach that minimizes disease exposure for vulnerable trial participants while allowing data collection to continue.
Still, “not all endpoints may be conducive to virtual assessment,” acknowledged the FDA officials, advising sponsors to seek advice from FDA on how best to proceed when medical imaging and bloodwork are required in a geographic area with high coronavirus activity.
Looking specifically at oncology trials, the authors pointed out that some patients with advanced disease “may rely on trial enrollment to access investigational drugs to treat their condition.”
FDA has been keeping up with its oncology approvals workload during the pandemic: between March and May 2020, OCE has approved eight new molecular entities and 23 new oncology indications, the authors wrote.
Looking forward, there may be lessons for innovation in oncology research. “The FDA intends to review all the temporary policies issued during the pandemic to identify which regulatory flexibilities, if appropriate, should be permanently incorporated into agency practice,” the authors said, adding that this flexibility is in many ways a “natural extension” of efforts already underway.
In an interview, a regulatory affairs professional concurs. “In general, any opportunity to accelerate cancer drug development without negatively impacting clinical trial integrity or data quality would be beneficial to all stakeholders, especially patients,” said Daniel Mannix, FRAPS, vice president of regulatory affairs at MacroGenics.
Mannix pointed to the ongoing use of real-world evidence (RWE) as an example of the flexibility and innovation that the FDA is already employing.
“FDA has been a participant in the RWE pilot sponsored by Friends of Cancer Research to assess several frontline treatment regimens in real-world patients with advanced non-small cell lung cancer,”
Mannix said. Pfizer’s Ibrance approval in 2019 for male breast cancer was also supported by RWE, he noted. “RWE was a component of [Prescription Drug User Fee Amendments (PDUFA)] VI and FDA is looking to build upon this further in PDUFA VII.”
The pandemic is already generating data on how oncology drugs are used outside of the traditional clinical trial setting, and the emergency has forced a reappraisal of how endpoints are being assessed — speeding the adoption of patient-centered outcomes, the authors wrote.
“The shifting of certain aspects of clinical trial operations to community settings to reduce patient burden also could support this acceleration,” Mannix said. “In the past, oncology clinical trials have utilized satellite centers affiliated with a primary clinical trial site, but there have concerns over certain GCP [good clinical practice] elements. Recent FDA guidance documents issued during the COVID-19 pandemic have now addressed how sponsors should deal with these potential GCP issues to help ensure clinical trial integrity.”
Finally, the FDA and sponsors have seen digital platforms used for patient enrollment as well as data collection. Using digital enrollment platforms as part of a community outreach strategy could be a powerful tool to help increase diversity of patient populations in clinical trials, said the authors. Retaining this strategy, along with other innovations, would represent “at least one positive outcome of this challenging time for public health,” the authors said.