Patients on active therapy during the coronavirus disease 2019 (COVID-19) pandemic, as well as oncology care providers, have increased levels of perceived and posttraumatic stress, according to preliminary data from the COVIPACT study. These data highlight a gap in psychosocial support resources that help promote emotional resilience and reduce the risk of posttraumatic stress in patients on active therapy.

Baseline results from the prospective trial (NCT04366154) presented at the European Society for Medical Oncology Virtual Annual Congress 2020 showed that “there was a high level of stress among patients,” according to Florence Joly, MD, PhD, who led the data review.

Between April 8 and May 29, 2020, during the French lockdown, investigators collected questionnaire responses on patients’ psychoemotional status. The COVIPACT population included 621 patients with hematological malignancies or solid tumors receiving systemic therapies from the outpatient departments of 2 respective French cancer centers. Assessing the proportion of patients with treatment modifications during the COVID-19 lockdown in France was the primary end point of the study.

Investigators reported that modifications occurred in 27% of patients, including treatment interruptions for 15%, post-ponement for 32%, changes to the administration schedule for 19%, and adapted monitoring for 30%. Treatment modifications were more frequent in patients receiving single-agent immune checkpoint inhibition (49%) and targeted therapy—based combination therapy (47%; Table). Notably, shifts in administration schedule were more common in patients who initiated treatment during the lockdown (33.0% vs 15.6%).

Measuring “the psychological impact of the pandemic-related lockdown” on patients and medical oncologists was the secondary end point of COVIPACT. Patients were asked to fill out self-questionnaires on:

impact of event scale—revised (IES-R), perceived stress (PSS), sleep difficulty severity/insomnia (ISI), quality of life (QOL), and cognitive complaint (FACT-COG).

Completed stress-related questionnaires were available for 93% of patients. Medical oncologists were also asked to complete self-questionnaires on PSS, as well as on professional accomplishment and personal efficiency.

Posttraumatic stress questionnaires—corresponding to stress related to the event&mdash;contained 22 items and used IES-R which categorized results as high, medium, or low stress. Results from this questionnaire showed that patients with cancer who were subject to COVID19—related oncological treatment modifications experienced higher stress; specifically, of the 152 patients who experienced modification, 27% experienced high stress compared with 19% of the 423 patients whose therapeutic course was not altered (P = .049).

Further, low stress levels per IES-R were also slightly elevated among patients who experienced a treatment modification versus those who did not (35% vs 32%). “We assessed the pandemic-induced therapeutic modifications of patients’ cancer treatment and the psychological impact on patients and caregivers,” said Joly, head of medical oncology at François Baclesse Cancer Centre in Caen, France. Findings from the baseline analysis indicate that treatment modifications have a “negative impact on stress” in patients, she added.

In contrast with the high and low findings in the IES-R questionnaire, medium stress levels were more prevalent among patients who did not have a treatment modification versus those who did (49% vs 38%). Overall, 46% of the 575 questionnaire responders said they experienced medium stress. Low stress related to the event accounted for 33% of the questionnaire responses; high, 21%.

The stress patterns in the IES-R analysis were also present in the PSS evaluation. In the 571 completed PSS questionnaires, 48%, 46%, and 6% of the responses indicated low, medium, and high levels of perceived stress, respectively. Just as treatment modifications led to a greater likelihood that patients would report high event-related stress, they also predisposed patients to experience higher perceived stress. Nine percent of patients whose treatment was changed said they had high perceived stress compared with 5% of patients whose treatment was not altered (P = .061).

Low levels of perceived stress remained slightly elevated among patients with modifications (50% vs 47%), whereas medium levels were more common among patients who did not experience a treatment modification compared with those who did (49% vs 41%, respectively).

A total of 570 patients responded to the insomnia questionnaire. Those who did not have a treatment modification were moderately less likely to have no or slight insomnia (77% vs 75%). The opposite was true for moderate or severe insomnia, which affected 25% of patients with a modification and 23% without one, respectively.

Interestingly, despite their effects on patient-reported stress, COVID-19—related treatment modifications did not negatively affect patients’ QOL from a cognitive standpoint, Joly said. In both patients who did and did not experience treatment alterations, the FACT-COG QOL score was the same, 4.6 (P = .5).

Sense of Accomplishment, Stress Both High Among HCPs

Questionnaires from 73 respondents quantified the psychological impact of the COVID-19 quarantine on medical oncologists and oncology day care unit caregivers. The mostly female caregiver population (81%) comprised 35 nurses, 4 nursing assistants, 23 medical oncologists (including 1 hematologist), 5 residents, and 6 contributors in other qualifying but unspecified roles. The median age was 40 years (range, 22-63).

When evaluated in the caregiver cohort, PSS questionnaire results showed that health care providers (HCPs) were experiencing high levels of perceived stress, Joly said. The continuous PSS score was 16.3 (± 7.1). When stratified by high, medium, and low, the PSS scores were 10%, 53%, and 37%, respectively. Most respondents (56%) felt a low level of emotional exhaustion.

Despite observed stress, HCPs reported high levels of professional accomplishment and personal self-efficacy, noted Joly. Specifically, 60% said they felt a high sense of professional accomplishment. Thirtythree percent felt a medium level of personal accomplishment, and only 7% reported a low perception of accomplishment. Data also showed that the personal self-efficacy score was 32.8 (of 40.0; ± 4.5).

Patients and participating HCPs were asked to respond to the questionnaires at not only baseline but also 3- and 6-month follow-ups. Following the presentation of the baseline findings on patient stress and other cognitive and QOL-related factors, the next step in the COVIPACT study is “evaluating the evolution of psychosocial parameters over these 2 periods after the lockdown among patients and caregivers,” Joly said.

These data are expected to shed light on the longer-term magnitude of treatment modifications on patients with cancer, as well as the determinants of posttraumatic stress for both patients and providers. In the meantime, oncology centers should seek to establish psychosocial support resources for patients receiving active therapy in an effort to minimize IES-R, Joly concluded.

Joly F, Leconte A, Grellard JM, et al. LBA69: impact of the COVID-19 pandemic on management of medical cancer treatments and psychological consequence for the patients. Ann Oncol. 2020;31(suppl 4): S1200. doi:10.1016/j.annonc.2020.08.2310

Articles

Patients on active therapy during the coronavirus disease 2019 (COVID-19) pandemic, as well as oncology care providers, have increased levels of perceived and posttraumatic stress, according to preliminary data from the COVIPACT study. These data highlight a gap in psychosocial support resources that help promote emotional resilience and reduce the risk of posttraumatic stress in patients on active therapy.
 

COVID-19 Pandemic Boosts Cancer-Related Stress

Cancer is independently associated with mortality in patients admitted to the hospital due to coronavirus disease 2019 (COVID-19) infection, according to data from The Clinical Characterization Protocol UK (CCP-UK) study, organized by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) and COVID-19 Clinical Information Network (CO-CIN).

Insights from the CCP-UK study (ISRCTN66726260), which comprises Europe’s largest prospective dataset, included 66,594 patients in the United Kingdom (UK) with complete outcomes, 10.5% of whom had cancer, 2.5% of whom were receiving active treatment for their cancer, and 8.0% of whom had a history of cancer upon data extraction on August 17, 2020.Data made available at the virtual 2020 ESMO Congress showed that, at the time of the presentation, 44.3%, 42.3%, and 29.5% of patients with a history of cancer, patients receiving anti-cancer therapy, and patients without cancer or a history of cancer had died, respectively.

In line with these findings, additional results demonstrated a “significantly higher” 30-day mortality rate among patients with cancer compared with patients who did not have cancer, according to Carlo Palmieri, BSc, MB, BS, PhD, FRCP, who presented the findings (40.5% vs 28.5%; unadjusted HR, 1.62; 95% CI, 1.56-1.68; P <.001).

When stratified by age, 30-day mortality was consistently higher in all age-specific subgroups of patients with cancer versus patients without cancer. Among the 4 age-defined subsets studied—less than 50 years; 50 to 69 years; 70 to 79 years; and older than 80 years&mdash;30-day mortality was highest in patients with cancer in this last group (46.8% vs 42.5%, no cancer).

“The hazard ratio was highest in patients [younger] than 50, at 4.09, and lowest in patients [older] than 80, with a hazard ratio of 1.17,” said Palmieri, a professor of Translational Oncology and medical oncologist in the Department of Molecular and Clinical Cancer Medicine at the University of Liverpool’s Institute of Translational Medicine in England (95% CI, 2.99-5.60; P <.001 and 95% CI, 1.11-1.23; P <.001). “Although the older patients have the worst 30-day mortality outcomes, the greatest absolute differences were seen in the younger patients,” he added.

Indeed, the 30-day mortality rates and percent differences in patients with cancer compared with patients without cancer in the 2 youngest subsets were 18.7% vs 6.3% in patients less than 50 years, translating to a 12.4% difference; and 31.4% versus 18.4% in patients aged 50 to 69 years, equating to a 13.0% difference (HR, 2.00; 95% CI, 1.82-2.20; P <.001). In patients aged 70 to 79 years, the 30-day mortality was only slightly different, at 40.1% among those with cancer and 34.1% in healthy patients, representing a 6.0% differential (HR, 1.27; 95% CI, 1.18-1.37).

Despite the consistently elevated mortality rate observed in patients with cancer of all ages, “no clinically significant differences in symptoms” at COVID-19 presentation were observed in patients with cancer, Palmieri said. However, “significant differences” were seen with respect to admission to critical care and ventilation patterns between patients with and without cancer, he added.

For example, patients with a history of cancer (7.6%) or those actively receiving anti-cancer therapy (9.5%) were the least likely to be admitted to critical care versus patients without cancer or a history of cancer (14.6%). Interestingly, this trend continued in investigators’ analysis of invasive mechanical ventilation use, where patients without cancer had the highest rate of ventilation (8.9%). The ventilation rates in patients with a history of cancer and patients on active treatment were nearly identical, at 4.1% and 4.0%, respectively.

As in the analysis of 30-day mortality, age remained a key distinguishing factor in a multivariable analysis of HR for mortality adjusted for age, sex, chronic cardiac disease, chronic renal disease, and dementia. Patients younger than 50 years who had a history of cancer had an HR of 3.50 (95% CI, 2.31-5.31; P < .001). “Therefore, patients younger than 50 with a history of cancer are 3.5 times more likely to die from COVID-19,” Palmieri observed. The HRs for patients with a history of cancer in the other 3 age groups were 7.23, 9.73, and 11.17, respectively.

Among patients younger than 50 years receiving active treatment for their cancer, the HR was 4.86 (95% CI, 3.17-7.44; P <.001). In patients 50 to 69 years; 70 to 79 years; and older than 80 years, the HRs for active therapy were 8.54, 9.55, and 11.64, respectively. The “differences in the age groups appeared to decrease with age,” Palmieri said, citing the HRs for patients without cancer (10.07), a history of cancer (11.17), and patients on active treatment (11.64) older than 80 years, as an example.

In the multivariable analysis and in the assessments of critical care admission, ventilation use, death, and 30-day mortality, a lack of information about cancer type, stage, and treatments received represented a limitation, because details on cancer or type of therapy were not collected, Palmieri said.

CCP-UK was activated on January 17, 2020 via the ISARIC and CO-CIN, and as of August 17, 2020, included 258 participating healthcare facilities sharing inpatient data. Through the CCP-UK, the ISARIC and CO-CIN sought to characterize the presentation, critical care admission, use of invasive mechanical ventilation and in-hospital mortality among hospitalized patients with cancer and COVID-19 and compare these outcomes to patients without cancer. CCP-UK is a multidisciplinary project developed to broadly characterize the presentation and course of COVID-19 in patients with cancer to inform and subsequently improve practice.

The August 17, 2020 pool of CCP-UP patient data included those who were hospitalized with a confirmed SARS-CoV-2 infection from January 17, 2020 onwards, and excluded individuals who were registered to CCP-UK fewer than 14 days before data extraction. The inpatient data were collected across sites in the UK using a questionnaire adopted by the WHO. Patients with malignant neoplasm were also withheld from this main dataset following their identification via a case report form (CRF) used to select patients with malignant neoplasm. A history of cancer was considered a comorbidity on this CRF.

In April 2020, the CRF was amended on the subject of “active treatment” to record patients receiving chemotherapy, immunotherapy/an antibody treatment, or targeted therapy; patients who underwent a bone marrow or stem cell transplant in the past 6 months; patients with lung cancer who received radical radiotherapy for lung cancer; and patients with hematological malignancies at any stage of treatment. Although cancer type, stage, and therapies received were not included in this analysis, a companion study will collect additional data, including tumor type, treatment, the timing of treatment to COVID-19 episode, and long-term outcomes in an effort to quantify the impact of cancer and treatment type and the timing of relevant interventions on outcomes and escalation of care.

“In addition, the match cohort of patients without cancer within CCP-UK will enable us to carry out a matched cohort study, controlling variables,” Palmieri said. Controlled variables will include age, sex, ethnicity, and comorbidities. Additionally, biological samples collected as part of CCP-UK will support translational research on COVID-19 and cancer.

“We hope these data will inform policy makers, [encourage] better clinical decision making, and more importantly, enable our patients and their families to make proper decisions around treatment and societal interactions,” Palmieri concluded.

1. Palmieri C, Turtle L, Docherty A, et al. Prospective data of first 1,797 hospitalised patients with cancer and COVID-19 derived from the COVID-19 Clinical Information Network and international Severe Acute Respiratory and emerging Infections Consortium, WHO Coronavirus Clinical Characterisation Consortium. Presented at: 2020 ESMO Virtual Congress; September 19-21, 2020; virtual. Abstract 1670O.

This article was originally published on OncLive as, "

Europe’s Largest Prospective Dataset Confirms Cancer’s Correlation With COVID-19 Mortality

Cancer is independently associated with mortality in patients admitted to the hospital due to coronavirus disease 2019 (COVID-19) infection.

Cancer and COVID-19 Death: What's the Correlation?

Treatment with immune checkpoint inhibitors (ICIs) did not increase the risk of mortality in patients with COVID-19 and cancer, according to findings from a multicenter, retrospective analysis presented during the 2020 AACR Virtual Meeting: COVID-19 and Cancer.

Data showed that the mortality rate of patients with COVID-19 and cancer who received immuno-oncology agents was 8%. “This rate is similar to the mortality rate in the general cancer population, which is reported to be in the range of 7.6% to 12%,” lead study author, Aljosja Rogiers, said during the medical meeting.

Nine of the 113 patients included in the study population died, however, none of these deaths were attributed to treatment with checkpoint inhibitors. All patients who died on study had advanced cancer; 7 died due to COVID-19.

The analysis by Rogiers et al analysis included data from 113 patients with laboratory-confirmed COVID-19 from 19 centers across North America, Europe, and Australia who received immunotherapy within 12 months of testing positive for COVID-19. Most patients (82%) received 1 anti—PD-1 or PD-L1 agent; 13%, an anti–PD-1 agent in combination with an anti–CTLA-4 drug; and 5%, another immunologic therapy. None of the patients were treated with chemotherapy. Data points included symptoms, comorbidities, and medications, in addition to investigations and treatments implemented for COVID-19. Investigators assessed the following outcomes: hospital and intensive care unit (ICU) admission and mortality.

The evaluation was conducted to shed light on the clinical implications of immune checkpoint blockade. “To what extent immune checkpoint inhibition [affects] COVID-19 infection in patients with cancer is unclear. Theoretically, inhibition could either mitigate or exacerbate COVID-19 infection. This study was designed to help us answer this question,” said Rogiers, a fellow at the Melanoma Institute Australia, in Sydney.

At the data cutoff of May 15, 2020, the median age was 63 years (range, 27-86) and the majority of patients (65%) were male. Few patients had an ECOG performance status of 2 or greater compared with 0 to 1 (10% vs 90%). Regarding the geographic regions to which patients belonged, most of the patients included in the analysis were from Europe (64%). North America and Australia accounted for 33% and 3% of the patient population, respectively.

Sixty percent of the 113 patients were symptomatic for COVID-19. Having contact with someone who was COVID-19—positive provided the rationale for testing the asymptomatic individuals included in this study, Rogiers said. Among the symptomatic patients, fever (68%) and cough (59%) were the symptoms of COVID-19 witnessed, followed by dyspnea (34%) and myalgia (15%). Beyond diabetes, which affected 15% of patients, the comorbidities that investigators observed were of a cardiovascular (27%), pulmonary (12%), and renal (5%) nature. When investigators examined the use of immunosuppressive agents used in this population, they noted the use of 10 mg or more of prednisone per day in 13% of patients, and use of another immunosuppressive agent in 3%.

Fifty-seven percent of patients had melanoma; 17%, melanoma; 9%, renal cell carcinoma (RCC); and 17%, another type of cancer. Most cases were treated in the advanced/metastatic setting (74%); 26% were addressed with a neoadjuvant treatment intervention. Reponses to therapy were as follows: partial response, complete response, or no evidence of disease, 30%; stable disease, 18%; progressive disease, 15%; not available, 37%.

Hospital, ICU Admissions and Mortality Outcomes

Twenty-nine percent of patients were admitted to the hospital, where antibiotics, oxygen therapy, glucocorticoids, antivirals, intravenous immunoglobulins, and anti—interleukin-6 agents were administered to 25%, 20%, 10%, 6%, 2%, and 2% of patients, respectively. Five percent of patients were admitted to the ICU, where were put on mechanical ventilation and vasopressin (3%; 2%). One percent underwent renal replacement therapy.

Results from the outcome concerning hospital and ICU admission showed that 61% of patients were discharged, 12% remained in the hospital, and 27% of those admitted (9 patients) had died by the data cutoff. Data from the mortality outcome assessment demonstrated that 92% of the 113 patients were alive and 8% (9 patients) died.

“Median age of the patients who died was slightly higher [than in the general population,” Rogiers said, citing the median as 72 years (range, 49-81). Among the patients who died, 2 had melanoma; 2, NSCLC; 2, RCC; and 3, another type of cancer. “Although the numbers are small, they may indicate that COVID-19 has a slightly higher mortality rate in patients with non—small cell lung cancer than melanoma, given that 57% of patients had melanoma and 17% of patients had non–small cell lung cancer,” he added.

Seven of the patients who died were treated with an anti—PD-1 agent. The other 2 patients received a combination anti–PD-1 and anti–CTLA-4 regimen.

1. Rogiers A, Tondini C, Grimes JM, et al. Clinical characteristics and outcomes of coronavirus 2019 disease (COVID-19) in cancer patients treated with immune checkpoint inhibitors (ICI). Presented at: 2020 AACR Virtual Meeting: COVID-19 and Cancer; July 20-23; Virtual.

Immunotherapy Use Does Not Correlate With Increased Mortality in Patients with COVID-19, Cancer

Treatment with immune checkpoint inhibitors did not increase the risk of mortality in patients with COVID-19 and cancer.

Immunotherapy Does Not Increase Death Risk in Patients With COVID-19

The ongoing coronavirus disease 2019 (COVID-19) pandemic has magnified the value of real-world data (RWD) in oncology. The FDA is presently spearheading several initiatives aimed at refining the role of RWD in cancer care to guide clinical trial development, procure answers to pressing clinical questions, and support regulatory decisions for in vitro diagnostics, according to presentations shared during a major symposium at the AACR Virtual Annual Meeting II.

“We now find ourselves in a grand experiment,” said Paul G. Kluetz, MD, deputy director of the Oncology Center of Excellence at the FDA. “By necessity, COVID-19 has pushed the cancer clinical trial community out of its comfort zone to rapidly deploy remote assessments and digital health technology, [prompting] unprecedented collaboration to explore the use of real-world data. We cannot lose this opportunity to learn and advance our knowledge of the strengths and limitations of decentralized trials and real-world data to move our cancer research enterprise to a more efficient and more patient-friendly model.”

Long before COVID-19, calls to learn from RWD and “decentralize” standard components of cancer clinical trials for favor of more “patient-friendly” alternatives such as digital health technology to facilitate remote assessments were heard in oncology, Kluetz explained. However, only now has the oncology field so broadly begun to adopt different operational tactics and draw upon RWD to inform management approaches for both COVID-19 and cancer. “We’ve witnessed a great interest in taking advantage of real-world data to rapidly expand our knowledge of the natural history of disease and treatment,” Kluetz said.

With widespread interest in RWD in place, many clinical questions now require answers, including several that are particularly germane: for example, can we leverage data collected from cancer trials conducted during COVID-19 to understand the effects of remote assessments and decentralized trial procedures on safety and efficacy outcomes?; and how can we use RWD to characterize the natural history of COVID-19 and its effects on patients with cancer?

The FDA is currently working with data holders, data analysts, and research institutions around the world to develop initiatives that not only address these inquiries but also probe beyond them, to clarify when and how specifically RWD can be most optimally used to improve current methodologies in oncology and inform new ones in the age of COVID-19

The COVID-19 Evidence Accelerator, a collaborative, RWD-driven cooperative, unites partners at the FDA with fellow federal health organizations such as the National Institutes of Health and Patient-Centered Outcomes Research Institute, with the accelerator’s managers, the Reagan-Udell Foundation for the FDA/Friends of Cancer Research.

Participants in the COVID-19 Evidence Accelerator developed a common set of core data elements and an initial set of priority questions regarding the therapeutic interventions, treatment settings, and associated outcomes that would guide early COVID-19 focused data aggregation efforts. The general epidemiology of COVID-19, the predictors of patients who would be at risk of developing severe COVID-19, and the patterns of general outcomes for people with COVID-19, including death and time to disease resolution, represent just 3 of the urgent clinical inquiries that multiple organizations and teams can simultaneously address. The questions have been crowdsourced, curated, and prioritized, so teams across the country can identify the highest priority items, according to Amy P. Abernethy, MD, PhD, principal deputy commissioner and acting chief information officer of the FDA.

Beyond this general list of COVID-19 specific inquiries, questions regarding the management of COVID-19 in patients with cancer have also been crowdsourced, in an effort to define how RWD efforts can help inform the Oncology Center of Excellence’s COVID-19 related research endeavors. Questions included the safety and efficacy of immunotherapy in patients with COVID-19 and lung, melanoma, bladder, and other malignancies, as well as the rates and severity of COVID-19 mortality in patients with cancer.

“Key to the accelerator is [our] focus on data holders, [such as] technology companies where large datasets are already well-curated and analytic teams are ready to analyze datasets,” Abernethy said. “We ask them to now start working on this prioritized list of questions in order to have pragmatic, real-time work directed at the COVID-19 pandemic.”

To structure researchers’ investigative efforts, the Reagan-Udell Foundation for the FDA/Friends of Cancer Research has defined common data elements and translation tables between data models that researchers are encouraged to use. Common protocols for repeated analyses of priority research questions; meetings and forums for rapid cycle feedback and learning from the insights of participating data partners; and individual accelerator subcommunities dedicated to specific topics, such as therapeutics, diagnostics, and vaccines, have also been established.

Data holders and aggregators participate in 1 or more focused work streams, which currently include Therapeutics, Diagnostics, and Vaccines. Individual research questions are generated and investigated within each work stream. Evidence Accelerator collaborators meet weekly to discuss findings from their respective weekly parallel analyses. In contrast with the Therapeutics, Diagnostics, and Vaccines work streams, the oncology work group, established in June 2020, does not limit or divide its investigative focus to just 1 of these areas, but rather evaluates each of them.

Following the COVID-19 Evidence Accelerator’s launch with its first lab meeting on April 16, 2020, the pool of data holders and number of weekly lab meetings has increased, with a Diagnostics Evidence Accelerator established on May 28, 2020. The overlapping efforts of both Evidence Accelerators and the oncology workgroup within the COVID-19 Evidence Accelerator reflect the FDA’s commitment to “creating opportunity out of crisis,” according to Kluetz. Additionally, the efforts support the widely recognized importance of moving expeditiously to find answers to pressing clinical questions during this unprecedented time in medicine, Abernethy said. “The work of the Evidence Accelerator sits in this larger global data community, where partners across the community understand 1 critical thing: we need to address the questions of COVID-19 with urgency, and we need to understand the natural history of disease and the effectiveness of potential treatments, and use the information to plan clinical trials,” Abernethy concluded.

In addition to shaping future oncology clinical trials, RWD generated and collected during the COVID-19 pandemic and thereafter can also be used to evaluate investigational medical devices and extend marketing approvals where necessary. However, as with all clinical efforts that involve RWD, the data that supports these decisions must be fit for purpose, meaning that the data are “complete, consistent, accurate, and contain all critical data elements needed to evaluate a medical device and its claims,” said Wendy Rubenstein, MD, PhD.

“A key problem in leveraging real-world diagnostics is the lack of information on the specific test used and the manufacturer,” added Rubenstein, director of Personalized Medicine at the FDA. The Systemic Harmonization and Interoperability Enhancement for Lab Data (SHIELD) project is the FDA’s response to this widespread problem.

“SHIELD is a cross-center and multi stakeholder initiative that supports efforts to harness nontraditional in vitro diagnostic data sources while reducing burdens to the health care ecosystem,” Rubenstein explained. At present, the SHIELD network encompasses the FDA, Centers for Disease Control and Prevention, National Institutes of Health, Office of the National Coordinator of Health Information Technology, Centers for Medicare and Medicaid Services, US Department of Veterans Affairs, in vitro diagnostic manufacturers, electronic health record (EHR) vendors, laboratories, College of American Pathologists, standards developers, Pew Charitable Trusts, National Evaluation System for health care Technology, and academia.

Crucial to SHIELD is the development of code mapping manuals to allow for the consistent mapping of the Logical Observations Identifiers Names and Codes (LOINC) that correspond with a given in vitro diagnostic. LOINC is the most widely used coding system for clinical laboratories and EHRs. For in vitro diagnostics, LOINC codes are used to identify the type of diagnostic used to test a clinical measure.2 Although the code mapping process was instituted to streamline electronic searches for in vitro diagnostics and corresponding test results, across institutions, codes are often “inconsistently applied and this ambiguity erodes the usability of the data,” Rubenstein said. Non-uniform entry of the codes is not limited to institutions: in vitro diagnostic manufacturers and laboratories also frequently assign different and inaccurate codes for a given device.2 SHIELD will “provide a process for consistent definition and use of codes,” thereby supporting interoperability, Rubenstein added.

Leveraging RWD for public health initiatives involving both COVID-19 and cancer is an overarching goal of SHIELD, which aims to establish interoperability to standardize data sharing among in vitro diagnostic data sources and support regulatory decisions involving diagnostics. Despite the widely recognized reality that interoperability is necessary to facilitate fluid and complete data sharing among and between these data sources to enable the use RWD in this manner, full-scale interoperability has not been achieved, and has consequently impeded this specific application of RWD.

However, the clinical shifts catalyzed by the COVID-19 pandemic have further illuminated the value of RWD in the oncology space and in medicine at large, and are providing the impetus for change, vis-á-vis SHIELD: “The urgency of the COVID-19 pandemic is supplying the activation energy we need, and the societal reaction is collaboration across all sectors to build the infrastructure to finally harness RWD. Once interoperability and data exchange are accomplished for COVID-19, success will be within reach to leverage RWD for public health more widely,” Rubenstein said.

1. COVID-19 and cancer: guidance for clinical trial conduct and considerations for RWE. Presented at: American Association for Cancer Research Virtual Annual Meeting II. June 22-24, 2020. Major symposium SYPOL07. https://www.abstractsonline.com/pp8/#!/9045/session/161

2. SHIELD- standardization of lab data to enhance patient-centered outcomes research and value-based care. Office of the Assistant Secretary for Planning and Evaluation. Accessed June 22, 2020. https://aspe.hhs.gov/shield-standardization-lab-data-enhance-patient-centered-outcomes-research-and-value-based-care

COVID-19 Pandemic Accelerates RWD-Based Initiatives in Oncology.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has magnified the value of real-world data (RWD) in oncology. The FDA is presently spearheading several initiatives aimed at refining the role of RWD in cancer care to guide clinical trial development, procure answers to pressing clinical questions, and support regulatory decisions for in vitro diagnostics.

COVID-19 Pandemic Highlights the Importance of Real World Data in Oncology

From implementing telemedical approaches to resequencing treatments, cancer centers across the nation have nimbly adapted to face the clinical challenges posed by the novel coronavirus 2019 disease (COVID-19). These adjustments in standard operating procedures mitigate the risk for virus spread among clinicians and patients alike.

Although the pandemic-specific protocols upheld by respective oncology institutions vary, clinicians agree that telemedicine has quickly become an invaluable component of cancer care amid the COVID-19 pandemic.

“We’ve had the ability to use telemedicine in oncology but have not rolled it out until now, in response to COVID-19,” said Abraham Chachoua, MD, in an interview with OncLive®.“We’re anticipating that it’s going to grow and interestingly, I think that’s one of the things that will stay with us after COVID-19 is under control, because once people find out what a useful [tool] it is, I don’t think you can say we’re just not going to do it anymore.” Chachoua is the associate director of Cancer Services at New York University’s Perlmutter Cancer Center in New York, New York.

The “added innovation” that the widespread adoption of telemedical methods has brought to the field of oncology constitutes a “silver lining” of the COVID-19 crisis, added Chachoua, who also serves as section chief of Medical Oncology at Perlmutter.

Many oncology centers are relying on telemedicine to facilitate consultations and other patient interactions, such as follow-up appointments, to reduce the number of patients who visit the clinic each day, as a preventive measure to stymie disease spread.

Chachoua recounted a virtual consultation with a patient with a thyroid node. “I know what my treatment plan is going to be, and it will eventually include a biopsy. This person doesn’t necessarily have to come in to see me for me to say that to her,” Chachoua said.

He added that collecting information on the patient’s demographic and family history of cancer and subsequently performing and reviewing scans are preliminary steps that he can take before he brings this patient in to the clinic for a biopsy. “Instead of doing something in 2 visits, you can do it in 1,” Chalchoua explained.

Telemedicine has also supplemented the oncology workflow at the Moffitt Cancer Center & Research Institute in Tampa, Florida, according to John A. Kolosky, CPA, MBA, chief operating officer and president of Moffitt Hospital. He said that the institution is presently using video as a medium to orchestrate what, under other circumstances, would have been in-person visits for patients and care providers. Although Moffitt Cancer Center had marginally incorporated telemedicine into their care algorithm prior to the COVID-19 pandemic, Kolosky said that the national health crisis “definitely accelerated the utilization of telemedicine” at the site.

“Patients are willing not to travel and are much more interested in getting their service via telemedicine if they can,” Kolosky said. In the time since Moffitt’s initial integration of telemedicine into its standard

operating pathway, the cancer center has tasked its telemedicine staff with training and educating clinicians on the technology, to simplify the transition from an in-person to digital format.

Importantly, the widespread adoption of telemedicine in oncology at this time can be attributed not only to increased efforts to avoid unnecessary contact but also in part to a “loosening of regulations,” said Robert J. Keenan, MD, MMM, vice president of Quality and chief medical officer at Moffitt. Keenan cited the Centers for Medicare & Medicaid Services’ (CMS) temporary expansion of Medicare telehealth services, which affords beneficiaries coverage for a broader selection of virtual health offerings for the duration of the COVID-19 public health emergency.1

Under the 1135 waiver and the Coronavirus Preparedness and Response Supplemental Appropriations Act, CMS ruled that care providers could furnish office, hospital, and other visits that would generally occur in person via telemedicine beginning March 6, 2020. The new policy mandates clinicians to use an interactive audio and video telecommunications system that can support real-time communication, and allows patients to receive this virtual care from home. Prior to this adjustment, coverage for telemedicine only applied when the patient resided in a designated rural area or when they left their home to visit a clinic, hospital, or other approved medical facility to receive the telehealth service.1

CMS’ expanded coverage of telemedicine has made the modality not only more financially feasible for some patients with cancer but also more easily accessible, and commercial payers are now following suit, according to Kolosky.

This is also the case at the Carbone Cancer Center, LoConte said, where, beyond surgical procedures, clinicians continue to actively identify the patients who might be able to “limit their touches with the healthcare system” by delaying chemotherapy. However, “some patients need to stay on chemotherapy and cannot take a break,” LoConte said.

It is not currently clear how long of a chemotherapeutic gap care providers could viably extend: “I’m hearing all sorts of things, from 2 weeks all the way through 5 months, and it’s very hard to make medical decisions about whether or not it’s okay to wait that long,” LoConte said.

In a recent address of members’ most frequently asked questions relative to COVID-19, the American Society of Clinical Oncology (ASCO) indicated that clinicians can consider withholding chemotherapy among patients who are in deep remission and are receiving maintenance therapy.

At Perlmutter Cancer Center, providers have sought to delay chemotherapy for some patients on maintenance regimens, to avoid bringing these patients in to the clinic. “We’re not at the point of stopping treatment altogether [and] we’re not going to do that, but there’s no reason that someone who is on maintenance chemotherapy who would be stable for a year has to come in every 3 weeks,” Chachoua said. “We could delay that treatment, so we’ve tried to do that.”

Ultimately, choices to modify or halt chemotherapy “should include consideration of the indication for chemotherapy and the goals of care,” according to ASCO. Oral therapies, for instance, could be an appropriate substitution for intravenous chemotherapy for some patients, and notably would reduce the number of clinic visits required throughout the course of treatment.3

The applicability of alterations such as these to a patient’s therapeutic course is not one size fits all, Chachoua said. “It’s a patient by patient decision and we’re trying to manipulate our treatments to keep our patients as safe as possible.”

1. Medicare telemedicine health care provider fact sheet. Centers for Medicare & Medicaid Services website. www.cms.gov/newsroom/fact-sheets/medicare-telemedicine-health-care-provider-fact-sheet. Published March 17, 2020. Accessed March 27, 2020          

2. Notification of enforcement discretion for telehealth remote communications during the COVID-19 nationwide public health emergency. Department of Health and Human Services website. www.hhs.gov/hipaa/for-professionals/special-topics/emergency-preparedness/notification-enforcement-discretion-telehealth/index.html. Updated March 27, 2020. Accessed March 27, 2020.

3. The American Society of Clinical Oncology. COVID-19 Clinical oncology frequently asked questions (FAQs). Updated March 12, 2020. www.asco.org/sites/new-www.asco.org/files/content-files/blog-release/pdf/COVID-19-Clinical%20Oncology-FAQs-3-12-2020.pdf. Accessed March 27, 2020.

Cancer Centers Go On the Offensive to Reduce COVID-19 Risk