Product Development

Reversing the impact of COVID-19 on oncology clinical trials: Guest Commentary

Wide-scale adoption of decentralized clinical trials would have benefits  far beyond insulation from COVID-19 

Wide-scale adoptiom of decentralized clinical trials would have benefits for cancer patients that go far beyond insulation from COVID-19.

The COVID-19 pandemic has harmed thousands of cancer patients by delaying or postponing clinical trials for new anticancer agents in various indications. These patients, whose lives depend on finding new treatment options, now face devastating consequences.

“Ignoring life-threatening non-COVID-19 conditions, such as cancer, for too long may turn one public health crisis into many others,” National Cancer Institute Director Norman Sharpless has warned.

Even as some institutions resume clinical research activities for essential trials, the pandemic’s first wave has led to a lasting slowdown in clinical development progress. As oncology trials make up the bulk of trial growth in the U.S., the impact is disproportionately large for cancer patients.

The 2020 trial delays could have a significant downstream effect on the treatment of cancer for years to come — even a 20% slowdown in enrollment across trials could lead to two or three new oncology drug approvals permanently halted. 

What can be done to reverse the long-term effects of COVID-19 on oncology trials and their patients, and prevent another pandemic or unforeseen disaster from disrupting future research?

The solution lies in new technologies and data that enable a “virtual” or decentralized clinical trial (DCT) model. This alternative model is the key for research continuity no matter what the future brings, and could revolutionize clinical operations in a way that finally puts the patient at the center of research.

The time to embrace clinical trial innovation has come

The pharmaceutical industry has been evolving to accommodate a more remote model of drug development, and the COVID-19 pandemic has heightened the urgency to embrace clinical innovations that have been emerging for almost a decade.

These include electronic tools for enrolling patients in trials, confirming their consent, and collecting patient-reported (PROs) and clinician-reported outcomes (COAs). Along with drug formulation technologies that enable self-administration, which have been available for years, these tools minimize travel, physical interactions and routine paperwork.

Telemedicine has seen an unprecedented uptick since the start of the pandemic. U.S. telehealth claim lines increased 4,347% among privately insured individuals from March 2019 to March 2020. These platforms allow clinicians to virtually monitor adverse events and advise patients, and the frequency and efficiency of video visits keep patients engaged, which means fewer drop out of trials and studies complete earlier.

The massive surge in telemedicine usage is a test case that we believe will prove the utility and efficiency of telehealth are too high to return to business as usual after the pandemic.

Synthetic trial control arms are a more recent development that can also benefit from a decentralized trial model, and are poised to become equally important to more established tools. These arms harness real-world data (RWD) — from electronic health records (EHR) from routine care, medical and pharmacy claims, lab results and other sources — to supplement or replace the data collected through traditional trials. Comparing the treatment decisions and outcomes with RWD can often replace a study control arm.

In short, the innovative technologies needed to decentralize clinical trials exist but aren’t being adopted quickly enough or at scale.

Adopting DCTs at scale will bring many patients into the clinical trial enterprise who have historically been left out, including minority groups and those who don’t live near a major medical center.

“Patients with limited access to trials have been asking for decentralization for decades,” notes cancer survivor and patient advocate Joan Venticinque. “With virtual visits, eConsent, wearable technology, direct shipping of orally administered drugs along with routine monitoring, patients can have access like never before. The decentralized model is long overdue."

Overcoming hurdles 

In today’s age of digital connectivity and mobile devices, virtual trials might seem like they should be easy. On the surface, that is a fair assumption since virtual methods can improve data quality and reduce the cost and time to bring drugs to market. However, clinical trials are extremely complex, with long-established workflows and tools that are entrenched into standard operating procedures.

Successfully implementing new technology requires interoperability of multiple platforms and devices that can be integrated into existing workflows, in accordance with standards — and it isn’t easy.

Fortunately, there is traction across technology players who are building tools to make the clinical trial process digital and virtual. Some are working to develop end-to-end virtual solutions, including telehealth and remote patient monitoring, eConsent/ePRO/eCOA, global device provisioning and trial analytics. As more contract research organizations, such as Covance, and sponsors start to work with advanced decentralized clinical trial platforms, it will speed the rate of innovation and improve the patient experience.

The digitization of clinical trial data and processes should make it easier, in theory, to use data generated from routine care as part of drug development. RWD can be used to inform trial design and eligibility, as well as construct synthetic trials. And it can provide deeper insight into the patient journey before, during or after the trial.

The challenge has been the fragmented nature of the data sources, as well as the difficulty of ensuring patient consent and protecting patient privacy as the data are aggregated.

The good news is that RWD exists in large quantities, and the Food and Drug Administration (FDA) has new supportive efforts designed to evaluate the use of these data as real-world evidence (RWE).

Moreover, researchers have already proven that RWD can be used to test new treatments. In 2017, Bavencio avelumab from Merck & Co. Inc. (NYSE:MRK) and Pfizer Inc. (NYSE:PFE) received accelerated approval from the FDA for two indications, metastatic Merkel cell carcinoma and urothelial carcinoma, based on a Phase II study using historical data. The data were sourced from electronic healthcare records and a German patient registry.

The 21st Century Cures Act encourages the use of RWD to generate RWE for regulatory decision-making. As the FDA has repeatedly emphasized, the key is to ensure that researchers have access to data that is fit-for-purpose.

Applying pandemic urgency and collaboration to cancer

The pandemic has shown that swift industry collaboration can be powerful in improving patient outcomes.

The American COVID-19 Collaborative Enabling Seamless Science (ACCESS), for instance, formed to quickly deploy virtual trial technology for monitoring, testing and developing diagnostics and treatments. The ACCESS vision aims to provide data for mitigation efforts, as well as RWD to accelerate evidence generation on new treatments and vaccines. It also aims to enable immediate screening and enrollment of participants for clinical trials, and to create a dynamic system with modern technology to protect Americans’ health and national security.

Collaborative approaches, such as ACCESS and the COVID-19 Research Database (a pro-bono consortium to make RWD available for COVID-19-related public health research), provide the infrastructure for more accessible clinical trials and accelerate the use of RWD for research and drug development. These types of novel approaches are critical to shortening timelines without adding clinical burden.

The technology to go virtual and the RWD needed to develop standard-of-care cohorts for cancer research are available today. If the industry moves with urgency, researchers can leverage virtual technology and RWD for synthetic trial arms at scale.

The pharmaceutical, healthcare technology and advocacy communities will need to rally to make that happen for patients who desperately need it. If all stakeholders across the industry commit to these efforts, it’s possible to change the future of clinical development and re-write how the story for cancer patients will inevitably play out.

Vera Mucaj is the Head of Clinical Trials Solutions at Datavant, and Ingrid Oakley-Girvan is SVP of Research and Strategy at Medable.

Signed commentaries do not necessarily reflect the views of BioCentury.