Pandemic Could Help Modernize the Clinical Trial Industry, Oncology Experts Say
The outbreak of COVID-19 had an immediate negative impact on cancer research, causing confusion, trial closings and a need for hasty adaptation to protect its vulnerable patient population, but it’s also ushered in important changes in oncology trials that could have long-term positive effects.
Jounce Therapeutics, a Massachusetts-based developer of novel cancer immunotherapies and predictive biomarkers, opted to keep its ongoing trials open to enrollment and adapt to the many hindrances posed by the pandemic. Manny Lazaro, Jounce’s head of clinical operations and data management, detailed the company’s response during a recent WCG Clinical webinar. The company’s strategy incorporated three phases: an “acute response” phase, an “adaptive implementation” phase and a recovery phase for future planning and preparedness.
Jounce’s initial acute response phase, initiated in March during the declaration of a national state of emergency and Massachusetts’ stay-at-home-order, lasted about two weeks and was its first step toward rejiggering trials in reaction to the pandemic, Lazaro explained.
“Our team rapidly developed mitigation strategies to keep the operation moving,” he said. “One size doesn’t fit all. We knew we couldn’t develop a strategy that would be effective across the board.”
The response phase involved, at its core, a principle of staying flexible and adaptive to local coronavirus situations as sites and service providers reported information, Lazaro said. That required staying in close contact and communication with clinical sites so that studies could adapt according to site situations and local guidelines. In that effort, Jounce implemented routine calls with study coordinators to obtain feedback and information about the challenges they faced and was helped by having already employed medical science liaisons last year to help with study engagement and site management.
The company’s second phase of response, the adaptive implementation phase, began putting those mitigation strategies in place at the start of April. Jounce also deprioritized the resolution of data discrepancies in certain situations, putting some data queries on hold to let the site staff focus on more important trial activities when time was limited or staff resources were reduced.
Like so many others, Jounce incorporated remote monitoring into its studies. Some sites allowed remote access to their electronic medical record systems, but when that wasn’t possible, the company asked them to send redacted health records to a secure portal or in a password-protected email. If neither of those methods was feasible, the clinical research associate would hold a teleconference with investigators or coordinators and go down a checklist of questions focused on patient safety, he said.
It also implemented a strategy for training staff remotely, which had previously been conducted exclusively onsite. In the remote setting, Jounce provided a training video to sites, and sites recorded their technique via video for assessment. The sites found the training video useful and requested other remote trainings be given in the same format, he said.
In a few instances where a site was short on staff, Jounce tapped into a patient recruitment company to provide support for study coordinators. The temporary support was used to help with data entry, patient recruitment and other study coordinator duties, and had been on call before the pandemic, allowing it to be used quickly, he said.
Jounce’s recovery phase, which it is moving into, was designed knowing that there will be a backlog of activity for research staff. In this phase — dubbed the “road to the new norm” — the company will support staff with the backlog of data entry and regulatory files, scheduling patients, detecting protocol violations onsite, managing samples and shipping drug product, and onsite verification of drug accountability.
In its recovery period, Lazaro said the company plans to double the number of CRAs onsite when necessary to help sites catch up after facing numerous delays caused by the outbreak. It is currently evaluating which sites may require their help. In addition, the company is working with its biostatistical team to assess how data integrity may have been impacted both in terms of quality and completeness, and in an overall sense.
Lastly, Lazaro said the company wants to ensure that, at the end of the trial, its trial master file recreates an accurate account of the study and includes the actions taken in response to the pandemic.
“We are still far from a widespread adoption of new, innovative approaches. However, as a community, we have an opportunity to modify the traditional, resource-heavy ways of conducting our business,” he said. “We’re proving it today that we can do it.”
Omer Siddiqui, vice president of development operations at Alector, an immunoneurology firm, said that there were several main issues created by the pandemic in their neurodegenerative trials. Patient screening and enrollment saw the biggest impact, he said, because Alector’s research was mostly conducted in hospitals, where staff were pulled toward pandemic response and weren’t allowed to conduct nonessential research.
Continuous monitoring for patients, however, is tricky to do remotely, given the neurodegenerative conditions of their trial participants, he said.
“In some situations, you can’t [do it remotely]. A lot of these patients have cognitive faculties that are not at the levels that you would think,” such as behavioral symptoms and language issues, he said. “In a lot of the cases, you have to have the patient and caregiver in actually with an investigator, with a trained reader, to conduct these.”
While the pandemic continues, he advised regulatory agencies to keep up with the ever-changing situation and researchers to take a hybrid approach to protocol assessments to see what can be done remotely, in order to reduce site and patient burden.
The pandemic has had a dramatic effect on cancer research, George Demetri, the Dane-Farber Cancer Institute’s senior vice president for experimental therapeutics, said.
The pandemic’s immediate effects led to near-term advancements for cancer research, he said, the first being the FDA’s March guidelines for clinical research trials during a pandemic, which gave the trial industry reassurance that it would accept trial deviations done to protect participants, such as delayed or missed dosing, or minor changes for visits.
Demetri said that the guidance felt, in some ways, like it freed cancer researchers from unnecessary regulatory burdens. Thanks to the agency’s encouragement, oncology study sponsors eventually began accepting the use of virtual visits to obtain data on patient status, the use of local labs for patients that couldn’t make it to study sites and the shipping of oral study drugs to patients’ homes, he said. In addition, the Centers for Medicare and Medicaid (CMS) and states have begun making payors cover services rendered via telemedicine, a development he believes will last long-term.
The fact that many COVID-19 clinical trials have been fast-tracked in their development, review and implementation is promising, he said, because it shows the system is capable of approving things faster than the current three- to six-month timeframe. He warned, however, that some of the trials have been of low quality. There has been “complete and utter confusion” that remains about poorly designed and uncontrolled COVID-19 studies, and that has led to a lack of public trust in clinical research, he said.
The adoption of telemedicine has been one of the most important changes in oncology trials the pandemic has produced, Demetri said. Cancer researchers have begun communicating with patients at a distance, choosing to only have visits that are absolutely necessary, such as for scans and key symptoms, and they’ve started shipping IND oral drugs directly to patients’ homes.
“The only thing we can’t deliver digitally is IV infusions,” he said. “We love the idea that if it was an oral drug, we could deliver it by mail or courier. What a breakthrough for our patients.”
The pandemic has also led researchers to pay more attention to patient preferences and values, and attempt to adhere to them in the way they run their trials, he said. He reminded cancer researchers not to become dependent on industry funding and said that public funding for oncology research needs to continue.
But overall, he predicted that scientists will overcome the pandemic, with the science of oncology “informing some of the most innovative aspects of COVID-19 research.”