Race to Develop COVID-19 Vaccines/Treatments Could Transform the R&D Process in Biopharma | Deloitte US has been saved
By Sonal Shah, senior manager, Deloitte Center for Health Solutions, Deloitte Services, LP
Over the past several years, I have been researching ways the biopharma industry could improve the historically long and expensive research and development (R&D) process. It has been amazing to see how quickly the industry has shifted into high-gear to develop treatments and vaccines for COVID-19. Many biopharma companies are taking advantage of existing technologies and novel clinical trial paradigms to research, develop, test, and get drugs to market as quickly as possible.
Some companies are expecting to have vaccines available for emergency use by the early part of 2021. Clinical-cycle times for infectious disease treatments typically average five or six years, according to our research. If COVID-19 vaccines become available in early to mid- 2021—one year after the pandemic struck—it would be a monumental achievement for the industry. This accelerated R&D process, if adopted systematically, could lead to dramatic improvements in productivity long after this crisis passes—not just for infectious disease, but across all therapy areas.
Collaboration for new clinical trial approaches
“It takes a village” to bring new treatments to market: biopharma companies have a long history at being the center of the R&D ecosystem, which includes health systems, academic labs, public agencies, patients, regulators, and others. Over the past two months, we have seen unprecedented levels of collaboration, not just among these stakeholders but within the industry. R&D executives from several biopharma companies have been meeting regularly to determine how to effectively combine and leverage their resources to respond to the pandemic.1 Even competing companies have joined forces to leverage their relative strengths to develop vaccines.2
Public health agencies—using master protocols—are also bringing stakeholders together to evaluate the clinical potential of treatments and vaccines for COVID-19. Master protocols are adaptive, collaborative clinical studies that allow for the simultaneous evaluation of multiple treatments and multiple questions for individuals who have specific diseases or disease subtypes within the same trial structure. Historically, these trials have predominantly been established in oncology and neurology where the complexity of the disease and need to identify specific patient subpopulations warrants bringing stakeholders together.
In March, the World Health Organization stood up the global mega-trial SOLIDARITY to evaluate four treatment options for severely ill patients in more than 100 impacted countries. France established a European add-on called Discovery, and the United Kingdom established its RECOVERY trial. In mid-April, the National Institutes of Health and the Foundation for the National Institutes of Health (FNIH) announced the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership. This public-private partnership, which includes other health agencies and 16 biopharma companies, is developing a collaborative framework for prioritizing and testing the vaccine and drug candidates.3 The partnership includes a master protocol. Most recently, a pre-competitive consortium has come together to apply the learnings and infrastructure of the I-SPY master protocol platform (with over 10 years of experience in breast cancer) to evolve our understanding of what works for acute respiratory distress syndrome caused by COVID-19.
Our research evaluating prior examples of master protocols, including I-SPY, shows that there can be several benefits to both industry and patients:
- Patient centric: Patients enroll in one trial, are screened once, and are automatically matched to the trial arm that is most likely to be most beneficial for them. There is also a joint control arm, which reduces the number of patients who are put on a placebo.
- Top expertise: These collaboratives bring together the leading research and clinical experts to establish protocols and share learnings.
- Reduced cost and cycle time: Shared infrastructure and resources can reduce the cost and time to establish study sites, enroll patients, monitor trials, and verify data. This can represent a 13-18 percent improvement in cycle time, and cost savings of 12-15 percent over standard, single-company sponsored trials.
- Drug combinations: The protocol design enables easy comparisons of multiple drug combinations.
- Rolling and unbiased data analysis: Data is analyzed by an independent statistical working group that can share results for any arm as soon as they become statically significant.
Each of these variables is extremely important in addressing an urgent global pandemic.
Elevated importance of real-world-data and evidence
Real-world evidence (RWE), or evidence generated from data collected from sources outside of randomized controlled trials (RCTs), could also play a role in evaluating existing and repurposed drugs that could be effective against COVID-19. For example, the Patient-Centered Outcomes Research Institute partnered with an academic clinical research organization to establish a patient registry as part of their Healthcare Worker Exposure Response and Outcomes (HERO) study, collecting clinical data on health care workers on the front lines and offering them an opportunity to enroll in clinical research.
Synthetic control arms—constructed from health data about routine care for patients who have a certain condition (for example electronic medical-record data for patients receiving the standard of care)—could be valuable in the evaluation of treatments for patients with severe COVID-19 symptoms. This approach could reduce the number of patients required to enroll in individual controlled trials. It also helps to eliminate ethical questions of putting severely ill patients on placebo.
Synthetic control arms were ranked as one of the most impactful future applications of RWE, according to our survey of RWE capabilities among top biopharma companies. However, 70 percent of companies in our most recent RWE survey said the lack of research-grade data is hindering their efforts to leverage RWE in R&D, including establishing synthetic control arms. This calls for greater partnerships with health systems and other stakeholders to curate purpose-built data sets to better understand the course of disease in COVID-19 patients. To this end, the Institute for Systems Biology has established a consortium of companies, health systems, and researchers to investigate the molecular mechanisms for COVID-19. Researchers plan to amass genomic, proteomic, and metabolomic data on patients to understand how the disease progresses over time and impacts organs.4
Real-world data is also helping biopharma companies plan and recruit patients for COVID-19 trials. Applying artificial intelligence (AI) to clinical data can identify patients who are at high risk of developing disease and predict where the next hot spot is likely to emerge. Real-time information about which clinics are actively treating COVID-19 patients can help identify sites that can enroll patients in a study.
RWE could also play an important role in helping to evolve our understanding of new treatments after they are marketed. New treatments are being evaluated by expedited trials and are likely to be approved under accelerated pathways like emergency use. RWE could enable a deeper understanding of how these drugs impact different patient subpopulations, or patients treated in different settings, once they are available and being used in the real world.
Will these approaches become commonplace post-COVID?
In a recent blog, my colleague Dawn Anderson pointed out that the virtualization of health care amidst COVID-19 is jumpstarting a digital revolution in clinical trials. After years of experimentation, companies are finally implementing digital tools to collect data remotely in order to maintain ongoing clinical trials. This will have the benefit of not only preparing our clinical trials infrastructure for continuity in the face COVID, but also drastically improving patient experience and driving efficiencies in clinical trials moving forward.
As a researcher, I look forward to evaluating the effectiveness of these approaches to accelerate treatments and vaccines that address the pandemic. I wonder, will investments in partnerships and consortiums for COVID-19 translate to other therapy areas? Will the adoption of master protocols, adaptive trials, and RWE accelerate R&D productivity and reverse the decline in returns on pharmaceutical innovation more broadly?
Endnotes
1. Pharmas on one page with action plan to solve COVID-19 together, BIOCENTURY, March 25, 2020
2. GlaxoSmithKline CEO calls coronavirus vaccine partnership with Sanofi an ‘unprecedented collaboration’, CNBC, April 15, 2020
3. NIH partners with 16 drug companies in hopes of accelerating Covid-19 treatments and vaccines, STAT, April 17, 2020
4. Merck joins Seattle consortium to uncover COVID-19's molecular workings, FierceBiotech, April 27, 2020
