Navigating the entire development pathway from benchtop to bedside requires a vast array of knowledge and skill sets. Most biotechnology and biopharmaceutical companies rely heavily on their partnerships with contract research organizations (CROs) for added expertise and support to reduce expenditures, reduce time to market, and deal with the growing complexity of many new therapeutic approaches including cell and gene therapies.
Not surprisingly, the COVID-19 pandemic has had an effect on CROs, but in this instance, the effect could be characterized as positive. Innovations that had started to win approval prior to 2020 are being utilized more widely, facilitating processes such as decentralized clinical trials, where new technologies are meeting the growing need for flexibility in clinical research and enabling virtual and hybrid trials.
IQVIA, a provider of advanced analytics, technology solutions, and clinical research services to the life sciences industry, recently announced that more than 60 trials spanning over 40 countries utilize the company’s decentralized clinical trial solutions. Many of these trials, launched in 2020 as virtual and patient-centric solutions, are providing business continuity measures to sponsors during the global pandemic.
“Obviously, our infectious disease portfolio has seen a big ramp-up due to COVID-19-related trials, but we also see opportunities in other indications,” says Costa Panagos, president, R&D Operations, IQVIA. “In addition to the standard approach, we are managing a mix of fully virtual and hybrid trials globally.”
IQVIA is focusing on several areas of investigational clinical research. Besides COVID-19, these areas include other infectious diseases as well as immunological, central nervous system, cardiovascular, oncological, and dermatological disorders.
The virtual model offers the adaptability necessary to meet operational requirements and is supported by a range of capabilities including artificial intelligence– and machine learning–powered direct-to-patient engagement, telehealth technologies, virtual site management, and home health nursing.
Patient centricity is at the core of decentralized and hybrid trial design. “We used to bring the patient to the trial, but now we bring the trial to the patient,” Panagos asserts. The idea is to design trials that seamlessly mesh with patients’ day-to-day activities and that capture important trial information while reducing the burden on both patients and investigators.
By greatly reducing barriers for participation and digitally matching the right patients to the right trials at the right time, decentralized options open up clinical trials to more geographically, socioeconomically, racially, and ethnically diverse patient populations.
COVID-19 has been an industry accelerator facilitating change. The transformation was underway, but according to Panagos, the adoption of digital patient engagement, remote monitoring, and virtual trials has certainly quickened.
“We believe a trend toward integrating clinical research within the patient point of health care or ‘Clinical Research as a Care Option’ can yield improved patient outcomes, reduce the cost of care, and advance beneficial research,” Panagos declares.
The use and application of real-world data and advanced analytics is also increasingly important to inform clinical trial work. Enhanced analytical models allow better informed, faster decisions around trial execution, saving time and money. IQVIA continues to develop sophisticated artificial intelligence and machine learning algorithms to further enable decision automation and improve overall trial management quality and efficiency.
According to Jim Anthony, senior vice president, global head, Parexel Biotech, new proposals and project awards cover a diverse and evolving landscape of therapeutic indications and patient populations. Nearly 50% of all new trial starts are in hematology and oncology, reflecting the growing number of cancer patients worldwide. And as the number of new cell and gene therapy treatments drive innovation forward, Parexel Biotech is expanding and recruiting across an array of potential applications.
Full-service projects continue to lead the way with customers seeking globally integrated solutions for both large and small trials. “We are continually bundling our regulatory, clinical, and safety services,” Anthony says, “[and our vendor deployments] further support trial designs to drive faster enrollment.”
Parexel’s projects today are dramatically different from its projects in the pre-COVID-19 environment. “Biopharma sponsors are actively looking to be more inclusive in their target patient populations to enhance enrollment from minority and classically underserved populations,” Anthony emphasizes. “The pandemic was a catalyst for renewed focus on diversity, as COVID-19 has disproportionately affected African-Americans and Hispanics, evidencing greater frequency and severity.”
Improving inclusivity in clinical trials is the only way to ensure that potential therapies can effectively treat all patients. This includes culturally diverse populations as well as individuals who are uninsured, underinsured, marginalized, or socioeconomically disadvantaged. Health is determined in part by access to social and economic opportunities: income, education, community safety and support, nutrition, and other social determinants of health.
The example set by Operation Warp Speed for COVID-19 vaccines and treatment reviews is helping set the stage for greater innovation across the industry. “Biopharma sponsors are more open to applying new approaches to trials, for example, using adaptive trial designs and synthetic control arms that drive more efficient, informative, and flexible trials,” Anthony observes. “Greater than 80% of Phase II/III trial proposals and 100% of real-world evidence (RWE) study proposals include decentralized approaches.”
Major trends already impacting the industry will continue to develop over the next few years including decentralized clinical trials for sites, patients, and monitoring staff; diversity and inclusion efforts to serve underreported populations; adaptive study designs; and risk-based quality management (RBQM).
The path forward
CROs help their customers understand regulatory requirements, develop safety assessment strategies, and conduct studies. “Some companies with limited or no previous vaccine or antiviral therapy development experience are shifting into developing vaccines, inhaled therapies, and drug-device combination products for COVID-19 therapy,” says Samuel Chuang, PhD, director, Scientific Advisory Services, Charles River Laboratories. “COVID-19 reminded us of the benefit of platform approaches and novel ways of collaborating in order to be able to respond in the necessary time frames.”
The heightened awareness of the potential for future pandemics is likely to ensure that interest in vaccine development remains increased above pre-pandemic levels for some time. Important lessons are being learned from the current pandemic which will be leveraged in addressing future health crises.
“On another front,” Chuang notes, “many families and foundations seeking novel genetic therapies are directly engaging in drug development for ultrarare diseases and for individual patients.”
Projects require the full breadth of in vitro and in vivo services and capabilities in drug discovery and safety testing for novel therapy development. Gene therapy programs also require the development of molecular biology and bioanalytical assays encompassing the areas of immunology, biodistribution, and pharmacodynamic and/or safety biomarkers, all in support of investigational new drug applications.
Typically, programs to develop therapies for rare and genetic diseases face resource constraints and critically short timelines due to patients’ health status. This has challenged sponsors, CROs, and regulatory agencies to identify the most efficient and lean paths forward to patient treatment without compromising safety. Streamlining the process will influence renovation of past review practices at the U.S. Food and Drug Administration and other regulatory authorities both for rare diseases and drug development as a whole.
Both the advent of novel therapies, such as advanced cell and gene therapies, and the rise of global threats, such as viral pandemics, have tested the conventional strategies and review processes for drug and vaccine development. Development programs require the creation of novel complex analytical assays and innovative approaches.
“Accelerated drug development programs can be difficult for all stakeholders and often require an approach to drug development that varies from the traditional model of CROs simply following service requests,” explains Chuang. “They require that the industry’s members, including CROs and regulatory authorities, work closely and collaboratively with each other to meet the incredible demand for new medicines.”