DCT Methods Helped Lung Cancer Trial Enrollment as COVID Surged, New Study Shows
Remote and flexible trial approaches have been a hallmark of clinical trials during the pandemic and are widely believed to have been the primary factor in keeping trials open and operating. Now, there is evidence showing that such measures as telehealth visits, off-site diagnostic/monitoring procedures and remote consenting were at least partially responsible for the ability of lung cancer trials to weather the storm.
A new study conducted by the International Association for the Study of Lung Cancer (IASLC) found that although enrollment in lung cancer trials dropped by 13 percent in the U.S. and 14 percent globally from 2019 to 2020, newly adopted decentralized trial measures helped these trials keep enrolling participants and moving forward. With this proof of concept, the study’s authors say, the trials industry can be confident in applying such measures to strengthen trials even after the pandemic ends.
“The COVID-19 pandemic created many challenges causing reductions in lung cancer clinical trial enrollment. Mitigation strategies were employed and, even though the pandemic worsened, trial enrollment began to improve. A more flexible approach — removing unnecessary barriers — may improve enrollment and access to clinical trials, even beyond the pandemic,” says Matthew Smeltzer, lead author of the study and associate professor of epidemiology and biostatistics at the University of Memphis.
Assessing monthly enrollment data from 294 lung cancer trials in 2020 and comparing them to the previous year, the researchers found that single-site trial enrollment was significantly impacted by the pandemic between April and June 2020. In the first three months of 2020, multisite trial enrollment took a notable hit as well.
Overall, the greatest decrease in lung cancer trial enrollment was seen from April through August 2020, according to Smeltzer. Sites responding to an IASLC survey said the months in which they first experienced the pandemic’s impact were March, April and May.
These enrollment woes improved by the fourth quarter of 2020, however. Neither single-site trials nor multisite trials saw a meaningful difference in enrollment from October to December 2020 compared to 2019, the researchers found. This rebound of trial enrollment figures despite consistently increasing numbers of COVID cases suggests the approaches sites used in response to pandemic restrictions and patient fears were effective in lung cancer trials and could be helpful for enrollment efforts going forward, says Smeltzer.
The hurdles raised by the pandemic were significant; more than half of sites saw moderate or greater impacts on their phase 1 to 3 lung cancer trials, the survey shows. Challenges were seen most in chemotherapy (52 percent of sites), immunotherapy (51 percent) and targeted therapy trials (38 percent); as expected, trials of infusion drugs appeared to be hit harder by the pandemic than those for targeted therapies. Sites were permitted to select all responses that applied in the survey.
Sites named telehealth visits, remote patient-reported symptom collection, off-site diagnostic/monitoring procedures (all 85 percent) and remote consenting (89 percent) as the most effective mitigation strategies they used, but not all sites questioned used these approaches.
The most frequent strategies implemented by sites to keep patients enrolling were modified monitoring requirements (47 percent of respondents), telehealth visits (45 percent), phone visits (42 percent) and mail-order drugs (25 percent), according to the IASLC survey. In addition, some sites allowed patients to do laboratory (27 percent) and radiology (21 percent) tests at off-site facilities, and a lesser portion moved to alter their consent processes (10 percent) or use eConsent (11 percent).
IASLC’s site survey also shed light on the biggest pandemic challenges faced in lung cancer trials. The most frequent issue identified as moderate or greater was a lower number of eligible patients (63 percent), followed by protocol compliance (56 percent) and trial suspensions (54 percent).
Unsurprisingly, sites named fear of COVID infection (89 percent) as the top patient challenge during the crisis. Other deterrents included willingness to visit the site (59 percent), ability to travel (54 percent) and site access (49 percent), as well as securing transportation (38 percent) and lab/radiology access (16 percent).
Patients with lung cancer have more comorbidities and are often quite ill, making enrollment a difficult task in general when traveling is required to participate, says Vamsidhar Velcheti, a medical oncology specialist and director of thoracic medical oncology at NYU Langone’s Perlmutter Cancer Center.
“Patients who have lung cancer have a higher risk for having adverse outcomes if they have COVID-19 infection. That in itself made a lot of our thoracic oncologists be very cautious about how we can protect our patients and restrict the number of unnecessary visits to hospitals and healthcare facilities to minimize the risk for infection,” he says. “I think that definitely impacted trial accrual, because trials require very frequent visits and [patients] have to come into the city to participate. In the middle of the pandemic, our accrual definitely took a dip because of that.”
Study author Upal Roy, assistant professor at the University of Texas Rio Grande Valley and executive director of LUNGEVITY Research, offered specific recommendations for sites and sponsors to make lung cancer trials more patient-centric, many of which were used during the pandemic.
When possible, he advises that they conduct remote clinical, laboratory and radiological assessments (as applicable to the trial phase), use mail-order delivery of the trial drug and allow for remote infusions when they’re considered low risk. Roy notes that distribution, storage and recording use of the study drug can be done at local infusion centers and adverse event monitoring done in real-time.
Electronic patient-reported outcomes that remotely monitor symptoms and telehealth visits that employ video or telephone conferencing based on patient preference are also effective ways of making lung cancer trials more appealing, Roy says.
The pandemic forcing researchers to quickly adapt their trials has created some momentum to apply lessons learned and make trials more flexible across cancer types, Smeltzer told CenterWatch Weekly. This momentum could and should be leveraged to significantly improve enrollment in oncology trials and make participation easier for cancer patients.
“I am hopeful some of these strategies will be adopted beyond the pandemic,” Smeltzer says. “The proportion of adults diagnosed with cancer who participate in clinical trials is quite low. If additional flexibility made participation feasible for just one out of 10 persons who would not have otherwise enrolled, we would see large increases in overall enrollment.”
In addition, “the use of electronic binders or electronic source data for sponsor/CRO remote data monitoring reduces burden on sites and improves productivity for sponsors/CROs as now on-site visits are eliminated or greatly reduced,” says Sandra Smith, WCG’s senior VP of clinical solutions and strategic partnering.
Velcheti, who believes the pandemic has illuminated the large number of unnecessary procedures and visits in clinical trials that may not be needed to properly conduct them, feels that the changes put in place during the pandemic may be here to stay and will improve clinical trial accrual if they do become standard.