In March 2020, The World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak a global pandemic. No more than 8 months later, Moderna and Pfizer reported over 90% efficacy in trials of their respective COVID-19 vaccines, with a target launch of a safe and effective vaccine in January 2021. In short, if all goes according to plan, it would have taken approximately 1 year total for the discovery, development, testing, and launch of a pharmaceutical entity — an unprecedented timeline.
Can you imagine if the same can be said for cancer drugs?
It typically takes over 10 years for a drug to go from lab to patient. That is one sentiment rarely contested: despite technological advances left and right, it still takes too long to develop new, life-saving medicines, and we need to do better for the patients fighting every day.
In 2020, traditional clinical research is unsustainable
Focusing on oncology, the US has experienced an explosion in the number of cancer clinical trials over the past 20 years, from 388 trials initiated in 2005 to 813 trials initiated in 2019 (clinicaltrials.gov). While this may suggest a rich pipeline of drugs for cancer patients, deeper problems exist that prohibit the full opportunity for patients.
- Patient enrollment is one issue. As stated in a recent publication: “It is estimated that only 3% of cancer patients participate in clinical trials”. This deficit has led to a recruitment struggle for the biopharma industry which, unsurprisingly, has become a leading cause of delays in clinical trials. Furthermore, since research is still generally limited to the same go-to populations at academic medical centers, we don’t see trials tapping into similar populations treated at smaller institutions.
- Trial design also presents a barrier. Originally, studies focused on large disease cohorts and asked broad questions such as, “Did a non-specific chemotherapy stop the growth of cancer cells?”. In recent years, targeted therapies have become the focus of anticancer drug development and are perceived to be the cornerstone of precision medicine. Targeted therapies interfere with specific molecules that are involved in the growth, progression, and spread of cancer, which allows for potentially better outcomes and fewer safety issues (i.e., side effects) than traditional chemotherapy. However, targeted therapies, as its name suggests, are increasingly focused on niche cohorts, which are often defined by a specific genomic marker that may only exist in 5% of a particular cancer population. As such, today’s trials often face a scarcity of eligible patients due to more stringent enrollment criteria.
- Diversity is compromised. The lack of diversity (race, ethnicity, sex, age, amongst others) is no stranger to the research world. Black and Hispanic patients are consistently underrepresented in trials, and cultural stigmas against experimentation still exist as barriers to participation. When trial participants are homogenous, findings inevitably result in clinical knowledge that is not generalizable to all groups. In 2020, trial diversity is further threatened by COVID-19 and its disproportionate impact on communities of color, and it is no better served by the aforementioned struggles with recruitment and trial design.
And the above issues are not invisible to the pharmaceutical industry. Across all clinical trials, less than 20% of studies are completed on-time. COVID-19 has also exacerbated these issues, with nearly 100 companies reporting clinical trial disruptions as a result of the pandemic through the first half of 2020. Through our inability to adapt and avoid these compounding delays, COVID-19 has forced us to not only recognize the need for change, but also demand immediate action.
How do we increase the efficiency of clinical trials, maintain patient safety, and accelerate access to novel therapies?
The Promise of Real World Evidence
In recent years, the concept of Real World Data (RWD) has been gaining traction in the drug development space.
In traditional randomized controlled trials (RCTs), a group of patients is randomized into experimental and control arms, the latter of which typically account for 33–50% of study participants. While patients in the control arm are put through the same demanding requirements as the experimental arm — frequent hospital visits, blood draws, and other potentially invasive diagnostics to monitor the cancer — they neither receive the new therapy nor are made aware of this fact. In other words, if you were a clinical trial participant, you do not know if you are going through all this to receive a promising new treatment or just the standard of care (or worse, a placebo, i.e., “sugar pill”).
Rather, imagine if you can be certain you will receive the drug being studied — a world in which the control group is composed instead of data curated from electronic health records (EHR) from the real world, creating a digital cohort of patients.
The collection of this “Real World Data” (RWD) can be used to replace or replicate patient-powered control groups with synthetic, EHR-powered control groups, allowing us to:
- Shorten drug development time, particularly in niche and rare populations, by reducing time-to-recruit
- Allow all patients to receive promising new agents rather than placebos or existing, standard of care treatment
- Create digital cohorts of truly diverse populations without expending additional recruitment resources
Although its benefits are undeniable and the FDA has demonstrated a willingness to consider this trial design, this external comparator arm (ECA) design is still complex; it is not a silver bullet for all studies and many discussions are still needed to shape and refine this approach. The ECA will never be as perfect as the control arm of an RCT, but in many cases it can be good enough — good enough to show drug safety and good enough to show if a drug offers meaningful prognostic improvement. Currently, not all biopharma companies explore the feasibility of using RWD, but they owe it to all cancer patients to at least try.
Drug development needs to do better
Sometimes, progress and innovation are simply about being creative, thoughtful, and persistent in how we use existing techniques. Fighting cancer is a team sport and we all need to do our part to give patients their best chance of recovery, remission, and survival.
Note: this piece was co-authored by Zoe Li, Scott Phillips, and Emma Mei
