Clinical Researcher—October 2022 (Volume 36, Issue 5)
OPINION
Musaddiq Khan, MBA
The pace of development for new medicines has traditionally been slow and burdened with lengthy enrollment, conduct, and analysis timelines. However, COVID-19 was a catalyst to adopt novel approaches to drug development that have harnessed technology to create new, accelerated processes for conducting clinical trials. Technology-enabled hybrid and decentralized clinical trials (DCTs) are now moving from the periphery into starring roles across many areas of research—with a notable exception. Though vaccine developers rapidly adopted DCTs during the pandemic, today there is a surprisingly slow uptake of novel technologies across vaccine studies compared to other therapy areas.
Background
Only 17% of vaccine trials today use some form of decentralization,{1} even as nearly nine in 10 sponsors use decentralized technology to support at least one of their clinical trials, according to the 2022 State of Clinical Trial Operations Report.{2} This is ironic, given the importance of speed to vaccine development, which is often initiated to urgently prevent a pandemic or stop the spread of a highly infectious disease variant.
At the same time, vaccine clinical trials are being re-prioritized by manufacturers, who are historically less incentivized to develop vaccines for diseases that eventually vanish. From an economics perspective, preventative vaccines are durable goods with long-term effects in contrast to therapeutics, which are ongoing treatments purchased repeatedly. As The Economist summarizes, “profits in vaccine making are low.”{3} This may be one reason that between 2014 and 2018, the U.S. Food and Drug Administration (FDA) approved only nine vaccines, compared to 213 therapeutic drugs.{4}
Public policymakers have a different perspective, however, as they say vaccines ultimately save money. According to research from the Decade of Vaccine Economics (DoVE) Project, every U.S. $1 invested in vaccine programs returned an estimated $20 in saved healthcare costs, lost wages, and lost productivity.{5} “It costs less to prevent disease than it does to continuously treat disease,” said Marty Anderson, chief strategy officer at Meridian Clinical Research, which specializes in vaccine trials. “The economics of missing work, childcare, [and] hospitalization far outweighs the development costs.”
Bottom line, vaccines are vital to humankind’s survival. Between 2020 and 2030, vaccination programs against 10 pathogens in 98 countries are projected to save 32 million lives—the vast majority will be children under age five.{5} Aggressive vaccination campaigns inspired by the pandemic and fears of future COVID-style lockdowns have prompted greater investment in vaccine development across both public and private sectors. GlaxoSmithKline (GSK) now has more than 30 potential new vaccines and medicines (including preclinical assets) in 13 high-burden infectious diseases{6}; Merck & Co. makes vaccines for 11 of the 17 diseases on the Center for Disease Control’s recommended immunization schedules{7}; and Pfizer is investing $470 million into its vaccine research facilities at its location in Pearl River, N.Y. to develop a new portfolio of mRNA vaccines.{8}
Fear of Change vs. Grounded Logic
Logic points to a convergence of vaccine trials and a DCT model today, but logic isn’t sticking while fear of change is.
“Vaccines are a niche business,” said Steve Clemons, senior vice president of client delivery for Velocity Clinical Research. “Organizations that have professionalized vaccine trials believe they already know best practices and don’t want anything slowing them down in running these high-volume trials. They don’t want to add steps to the trial, fearing any additional layers of complexity could delay enrollment. For instance, DCTs are perceived to bring integration challenges, device provisioning concerns, and regulatory considerations, so sponsors and sites stick to what they know—even if that [means] aging, paper-based processes.”
In reality, hybrid and decentralized trials can help to speed trials. The DCT model has proven to reduce timelines over traditional trial processes through faster patient recruitment and enrollment and other efficiencies. In fact, a new study from the Tufts Center for the Study of Drug Development shows that DCTs reduce development cycle times, lower clinical trial screen failure rates, and have fewer protocol amendments. These benefits yield net financial benefits ranging from five to 13 times for Phase II and Phase III trials, equating to roughly $10 million and $39 million in return on investment, respectively.{9}
Vaccines are the cornerstone of the management of emerging and re-emerging infectious disease outbreaks and are the surest means to defuse pandemic risk. The faster a vaccine is deployed, the faster an outbreak can be controlled. Following a traditional research and development pipeline, it takes between five and 10 years to develop a vaccine for an infectious agent. The standard vaccine development cycle is not suited to the needs of explosive pandemics. DCTs, however, can shorten that cycle and make it possible for multiple vaccines to be more rapidly developed, tested, and produced.
Real-World Benefits and Public Perception
Consider the speed of COVID-19 vaccine trials, many of which leveraged digital technologies. These vaccines were available for public use in seven months from the start of clinical trials in a record-breaking, cross-stakeholder response to rapidly spreading, unchecked viral infections. Rather than go backwards, the industry needs to continue to build on the progress gained in the early days of the pandemic and make hybrid trials instrumental in vaccine development.
“At the same time, we must balance speed with public perception—or misperception—that speed equals cutting corners,” added Anderson. “We should embrace faster, decentralized approaches in vaccine development while working in parallel to build public confidence.”
Katie Moureau is a patient advocate with five boys, ranging in age from 13 years to 22 months, including a son who has respiratory vulnerabilities. “Decentralized vaccine studies are beneficial not only for my 7-year-old, but all those who have immunocompromised systems. More efficient vaccine trials can influence whether participants continue or drop out of a trial, preventing unnecessary delays while protecting those who are vulnerable.”
Templatize to Speed Vaccine DCTs
Vaccine trial protocols are relatively homogenous from trial to trial, taking place over a relatively short period of time and involving a high volume of participants. For all their similarities, vaccine trials are ripe to be templatized to speed set up and analysis.
“A typical Phase III efficacy trial can include upwards of 40,000 participants, so the logistics of managing that many individuals and tracking their post-vaccination status, including diary entries, is one of our biggest challenges,” explained Anderson. “Vaccine trial protocols are somewhat predictable—administer the vaccine, monitor the participants, record typical reactions or events, and potentially monitor the participants over the course of ‘a season.’ DCT technology could help monitor such a high volume of patient-reported outcomes and even automate alerts or reminders for better data collection. So while the trial set up is fairly simple, it is crucial that no events are missed because, especially with efficacy trials, every incidence of infection can be important to trial outcomes.”
Clemons added, “Delays are always a concern with vaccine trials, which typically need 30,000 patients versus 3,000 in a therapeutic trial, and regulators want proof of population representation. Ensuring a diverse participant pool is very time-consuming, but DCT technologies can really speed the process of patient recruitment and consent while expanding geographic access to more demographics.”
DCT solutions that templatize best practices common across most vaccine trials not only speed the process, they also allow for higher quality data to be collected from patients without the burdens of travel and reviewed in real time by investigators. For the same reason, DCTs also expand access to vaccines to more regions—particularly important to vaccine-naïve parts of the world.
Early data show a pre-packaged vaccine DCT-in-a-box reduces study startup time by at least 50%–from 12 weeks to five weeks or less. Speed, access, and data quality are all critical for vaccine trials. By codifying the most common elements across vaccine trials, compliant DCT platforms can minimize the need to do a ground-up build for every new vaccine study.
“As we know, one of the pain points for study participation continues to be hesitancy based on perceived disruptions to our daily lives,” said Allison Kalloo, MPH, a minority patient recruitment specialist and founder of Clinical Ambassador. Kalloo, who is also a vaccine trial participant and member of Medable’s Patient Advisory Council, adds, “Vaccine trials can benefit from a prepackaged solution that can ease access and compliance while communicating transparently and better managing expectations—especially for underrepresented communities of color.”
Leave Room for Flexibility
While pre-packaged DCT solutions enable fast study startup and scalability by standardizing core capabilities required in a vaccine trial, it’s still important to allow for flexibility to accommodate different trial designs. For instance, different vaccine trials may need additional visits or unique physical assessments. The good news is that one of the decentralized model’s trademark benefits is its built-in optionality for all stakeholders, including participants, sites, and sponsors/contract research organizations, while ensuring that the goals of participant safety and collection of robust, reliable data are not compromised.
“A standardized DCT platform that facilitates efficient, one-on-one communication between participants and site staff would be particularly beneficial in vaccine trials, especially considering the sheer volume of participants,” concluded Anderson. “Participants put their trust in the site staff and if you take that away, that hurts everyone. But if you provide a technology that not only offers greater efficiency but also enables better communication, it’s a win-win.”
Conclusion
It’s time that we address and acknowledge the unique challenges and significant responsibility that this new era of vaccine research brings to fighting infectious disease. By applying a modern, technology-driven approach to such vital research, the industry can move faster and may even be able to get a jump on the next pandemic.
References
- Internal Medable customer data (as of September 15, 2022).
- Florence. 2022 State of Clinical Operations Technology Report. See resource here.
- The Economist. 2020. Can the World Find a Good COVID-19 Vaccine Quickly Enough? See resource here.
- See “Biological Approvals by Year” from the U.S. Food and Drug Administration (https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/biological-approvals-year) and Mullard A. 2019. 2018 FDA Drug Approvals. Nature (https://www.nature.com/articles/d41573-019-00014-x).
- Value of Immunization Compendium of Evidence (VoICE), a project of the Johns Hopkins Bloomberg School of Public Health. The Value of Vaccines: Investments in Immunization Yield High Returns. See resource here.
- GlaxoSmithKline. 2022. GSK Announces $1 Billion in R&D Investment Over 10 Years to Get Ahead of Infectious Diseases. See resource here.
- Merck.com
- Griffin R. 2022. Pfizer Invests $470 Million to Develop Tech Behind Covid Shot. See resource here.
- DiMasi J, Getz K, Tenarts P, et al. 2022. eNPV of Decentralized Clinical Trials. Therapeutic Innovation & Regulatory Science. See resource here.
Musaddiq “Muz” Khan, MBA, (musaddiq.khan@medable.com) is Vice President and Head of Therapeutic Area Solutions for Medable and has been involved in clinical research for more than 15 years. He previously has held a variety of leadership roles, primarily in early-phase clinical development programs, at Parexel, Roche, AstraZeneca, and Eli Lilly.
