5th February 2024See What we can do
The pharmaceutical industry grapples with a significant challenge in the form of diminishing efficiency in research and development (R&D). A startling revelation from the Tufts Center for Drug Development indicates a staggering 145 percent surge in the total sponsor cost per new drug approved in the US over a mere 15 years, reaching a staggering $2.5 billion in 2014. Alarmingly, only seven percent of first-in-human drugs successfully secured FDA approval during this period. This inefficiency primarily stems from an antiquated clinical trial model, where nearly $1.5 billion per approved new drug is allocated to clinical development, primarily for clinical studies. Biopharmaceutical (biopharma) Research and Development (R&D) find itself at a pivotal juncture, where the primary impediment to innovation is no longer rooted in scientific advancements or funding availability. Instead, the critical bottleneck lies in the speed at which clinical trials can be concluded, a challenge stemming from a scarcity of willing study participants and a shortage of essential clinical site professionals, such as principal investigators (PIs), site coordinators, and nurses. In this dynamic landscape, the trailblazing entities in clinical trial sponsorship, namely biopharma manufacturers responsible for initiating, managing, and financing trials, will be those that successfully transform their clinical trial delivery models, creating a compelling value proposition for both study participants and the sites involved. This article delves into the obstacles hindering R&D productivity, encompassing protracted clinical trial timelines and recruitment difficulties, and explores strategic actions sponsors can undertake to augment trial participation rates and enhance the overall experience for clinical trial sites.
INSIGHTS: The current development model, structured around three fixed trial phases and designed to meet regulatory requirements for therapies targeting large patient populations, is woefully inadequate in addressing the contemporary demands of the industry. These include managing pipelines for intricate new therapies targeting smaller and more diverse patient populations, adhering to heightened evidence standards from payers embracing value-based reimbursement models, and accommodating the growing influence of patients in care decisions. As development cycles lengthen, trial complexity increases, and scrutiny of the economic value of new treatments intensifies, pharmaceutical R&D business models face significant pressure to enhance efficiency. It is imperative for the industry to embrace an entirely new framework for development infrastructure and processes, transcending mere cost containment and focusing on fundamental reforms that expedite the market entry of treatments. A survey conducted in the pharmaceutical industry sheds light on the challenges faced by executives and professionals regarding Pharma R&D Efficiency. Key operational issues cited include patient enrollment (56%), site start-up (43%), and regulatory approval delays and changes (43%). These challenges underscore the difficulty of designing studies that cater to critical patient and investigator needs while adapting to evolving regulations. While there is a realization within the industry about the need for a holistic effort to transform trials, the survey reveals that only one in five respondents claim their organization currently employs a holistic/integrated approach for clinical trials transformation. Many organizations still maintain siloed efforts to drive operational efficiencies, potentially hindering their full potential in delivering process efficiencies and economic value. Integration of efforts is crucial for their effectiveness.
Efforts to elevate efficiency and enhance trial savings center around patient identification and recruitment, as well as risk-based approaches to study monitoring. According to industry experts, the top five areas with the most potential for generating savings and improving trial efficiency include improving protocol development (38% of respondents), study start-up activities (37%), patient recruitment and retention (37%), vendor selection and management (32%), and study monitoring (25%). The decline in pharmaceutical R&D efficiency and the subsequent erosion of return on investment can be attributed to prolonged development cycles characterized by escalating trial complexity and regulatory approval delays. These challenges underscore the need for a paradigm shift in clinical trials to address the deep structural changes in therapeutic markets that traditional models are ill-equipped to handle.
PRESENT MEASURES: Presently, the biopharmaceutical industry is witnessing the fruition of decades of pioneering research, boasting its most extensive and varied clinical pipeline in history. The number of distinct drugs in development has surged from 3,200 in 2012 to an impressive 6,100 in 2022. Notably, this pipeline exhibits a growing diversity, with 14 percent of assets utilizing modalities validated within the past five years, prominently featuring various forms of cell and gene therapy.
The realization of such an expansive pipeline has been made possible through a combination of government investments and private sector contributions. Government support, exemplified by an estimated $18 billion allocated for Operation Warp Speed, and a substantial annual investment of $48 billion by the National Institutes of Health alone, has played a pivotal role. Concurrently, private markets have demonstrated their commitment, with an approximate infusion of $146 billion in life sciences venture capital funding over the past three years. This collaborative financial backing has become the bedrock for advancing groundbreaking research and propelling the biopharma industry into an era of unparalleled innovation.
The last two decades have witnessed remarkable advancements in patient outcomes thanks to groundbreaking innovations in biopharmaceuticals. Cure rates for hepatitis C now stand at an impressive 95 percent, cancer mortality rates have seen a notable reduction of 27 percent, and COVID-19 vaccines have proven highly effective, achieving up to 95 percent efficacy in preventing symptomatic infections. Despite these notable achievements, the same period has seen clinical development success rates, speed, and productivity persistently plateau, even in the face of a substantial surge in global research and development (R&D) investments. In the United States, R&D spending has doubled from $40 billion to $80 billion between 2001 and 2019, underscoring the need for a critical examination of the factors influencing the translation of increased investment into improved clinical development outcomes.
Advancing Equity in Clinical Trials through Hybrid Approaches: Navigating Logistical Challenges for Inclusivity
Enhancing access to trials and technology is a critical goal, and the adoption of hybrid trials emerges as a strategic approach. While decentralized trials and remote monitoring contribute to addressing issues of convenience and engaging diverse populations in geographically distant areas, challenges persist for underserved and minority communities. Disparities may arise, notably concerning access to broadband, availability of caregivers, and home healthcare.
Recognizing that not all trials can be entirely decentralized, the concept of hybrid trials, which involve community outreach to connect with patients in their local environments, is gaining prominence. However, it is essential for researchers to acknowledge the logistical challenges associated with certain in-person provider interactions and laboratory tests that are integral to the trial process. Participants may encounter difficulties related to travel constraints, including issues of access and cost, reluctance from employers to approve job absences for study activities, and mobility challenges stemming from underlying medical comorbidities. Addressing these concerns is paramount to ensuring equitable participation and representation in clinical trials.
Case: CVS Health Pioneers Accessible Clinical Trials through Retail Innovations
CVS Health's Clinical Trial Services, originally established in response to the pandemic, is expanding its reach to provide broader access to clinical trials within local communities. In collaboration with the pharmaceutical industry, CVS Health played a pivotal role in facilitating clinical trials for investigational COVID-19 vaccines and treatments. Leveraging a specially crafted digital model and screening protocols, the company successfully engaged over 300,000 volunteers for consideration in COVID-19 vaccine trials, connecting them to studies in close proximity to their residences.
The focus on creating a more streamlined and convenient experience aims to enhance participant retention and improve overall research effectiveness. CVS Health envisions that its innovative clinical trial approach will not only benefit participants but also extend advantages to healthcare providers, clinical research organizations, and study sponsors. The company's initial efforts concentrate on amplifying three core capabilities: precision patient recruitment, efficient clinical trial delivery, and the generation of real-world evidence and studies. This expansion signifies CVS Health's commitment to advancing clinical research accessibility through novel retail-based initiatives.
The landscape of clinical trials is evolving, with emerging evidence highlighting the productivity of novel approaches. Notably, decentralized trials (DCTs) relying on remote strategies are proving to be not just a temporary solution but a lasting paradigm shift. Research indicates that these trials are delivering a substantial return on investment, establishing their significance in the future of clinical research.
A pivotal aspect of this transformation is digitization, which plays a crucial role in alleviating patient burden and mitigating reporting subjectivity, all while enhancing the accuracy of outcomes.
Case: Tufts Study Reveals Remarkable Financial Returns: Decentralized Trials Shine in Efficiency and Cost
A recent in-depth study conducted by the Tufts Center for the Study of Drug Development has unveiled compelling insights into the financial landscape of decentralized clinical trials (DCTs). The study, comparing established benchmarks on trial cycle times and costs with data sourced from over 150 decentralized trials orchestrated by software firm Medable, brings to light the substantial advantages associated with embracing decentralized approaches. On average, the study demonstrates that DCTs exhibit notable reductions in clinical trial timelines, along with enhanced recruitment and higher retention rates. For instance, phase 2 studies conducted in a decentralized manner were completed 1 to 3 months more swiftly than their traditional counterparts, resulting in a financial return on investment up to five times greater than the initial upfront costs. The impact was even more pronounced in phase 3 trials, where the return on investment soared to an impressive 14 times greater than the upfront investment required. This groundbreaking research underscores the substantial financial benefits of incorporating decentralized trials, positioning them as a highly efficient and cost-effective strategy in the realm of clinical research.
A paradigm shift is underway in clinical trial strategy as sponsors increasingly adopt a data-and-analytics approach to site selection and management. Leveraging rich datasets encompassing claims, electronic health records, and information from consortia, sponsors are augmenting their historical data with sophisticated, AI-driven models. These models, capable of predicting the underlying drivers of enrollment for specific indications or therapeutic areas, surpass the predictive power of models solely based on historical data.
This analysis underscores the transformative impact of these models, revealing their ability to identify opportunities for accelerating recruitment by an impressive 15 to 20 percent. This is achieved by predicting sites that demonstrate the fastest recruitment potential while concurrently reducing reliance on sites that are less likely to meet enrollment targets. AI-driven models excel in accounting for variables such as site congestion, expanding the pool of viable sites beyond traditional sponsor affiliations. Moreover, these models create a dynamic feedback loop, providing sponsors with insights into how enrollment drivers influence timelines, including the potential impact of introducing additional target endpoints.
As trials progress, real-time performance tracking becomes instrumental in identifying dormant sites, while analytics algorithms predict the likely conclusion of enrollment based on current trajectories and the anticipated impact of remedial actions. This data-centric approach not only enhances the efficiency of site selection but also empowers sponsors with proactive insights for effective trial management throughout its lifecycle.
In the pursuit of consistent, regulatory-quality clinical trial data to substantiate the efficacy of treatments, life sciences companies are navigating a landscape where researchers are tasked with gathering, analyzing, and curating diverse streams of structured and unstructured data. The advent of digital health technologies, including telemedicine, mobile devices, wearables, and sensor-based technologies, is significantly amplifying the volume of data collected, primarily fueled by the rise of decentralized trials and remote monitoring. Beyond clinical data, the integration of genomic information and advancements in technology, such as Artificial Intelligence (AI) and quantum computing, is reshaping the approach of life science organizations towards drug discovery and development. Real-world data (RWD) and real-world evidence (RWE) collected in contemporary settings hold the potential to revolutionize clinical trial design and execution, offering insights previously considered unattainable. Deloitte's annual survey of C-suite biopharma leaders reflects the strategic importance of RWE, with 100% of respondents acknowledging its significance.
In a pivotal move, the US Food and Drug Administration (US FDA) issued draft guidance at the close of 2021, outlining the use of digital health technologies for remote data acquisition from participants in clinical trials. This guidance extends an opportunity not only to sponsors and investigators but also to developers and manufacturers, offering a framework to derive substantial benefits from the evolving landscape of digital health technologies in the realm of clinical research.
In the era of digital transformation within clinical investigations, sponsors face the crucial task of selecting digital and virtual tools that are not only technologically sound but also tailor-made for their intended purpose. The emphasis lies on ensuring these tools are "fit-for-purpose," possessing the capacity to adequately support their use and provide interpretable data for the study. Establishing secure data transmission mechanisms with manufacturers and drafting user-friendly end-user licensing agreements are imperative elements in this process.
1. Validation for Virtual Platforms: Rigorous validation of tools for virtual platforms is essential. The collection of sufficient data during the validation process allows a comprehensive understanding of each tool's functionality, and it is crucial to identify tools that seamlessly transition to virtual settings.
2. User-Friendly Interfaces: Digital tools must feature user-friendly interfaces catering to both supervisors and patients. This ensures efficient utilization and engagement throughout the trial.
3. Wearables and Data Accuracy: While wearables contribute to reducing subjectivity in data, their accuracy may vary. A critical approach to data interpretation is necessary, questioning the reliability of data and its relevance to the study.
4. Relevance of Data Collected: Verify that digital tools align with the study's objectives by measuring clinically relevant data that holds significance for patients.
5. Clinical Expert Involvement: The design teams for trials should incorporate clinical experts alongside statisticians. These experts bring invaluable clinical analysis a priori, examining outliers for clinical relevance. The anticipated value lies in the synergy of human-enabled AI—where expert clinical knowledge combines with AI and machine learning (ML) analysis to yield comprehensive insights.
In navigating the digital frontier, the strategic selection of tools aligns not only with technological capabilities but also with a meticulous understanding of clinical objectives, ensuring a harmonious integration of digital advancements into the fabric of clinical trials.
Case: Integrating Pandemic-Era Innovations: Biopharma's Blueprint for Enhanced Clinical Studies in 2022
As the biopharma landscape navigates 2022, valuable insights garnered from the COVID-19 experience are shaping the industry's approach to planning, designing, and executing studies with heightened efficiency. Drawing from successful measures implemented during the pandemic, companies are adopting several strategies:
At-Risk Development: Facilitating at-risk development for high-priority programs, allowing for strategic bypassing of specific stage-gates to expedite crucial initiatives.
Regulatory Collaboration: Expanding collaborative dialogues with regulators, utilizing data-sharing infrastructure, and harmonizing approaches across geographies to streamline processes.
Endpoint Rationalization: Limiting the number of relevant endpoints to enhance the efficiency of trial protocol design.
Master Protocols and Adaptive Designs: Embracing rapid assessment and development through the implementation of master protocols and adaptive trial designs.
Digital Technologies Acceleration: Expediting the use of digital technologies to conduct decentralized and hybrid studies, optimize site selection, recruit diverse study populations, and remotely collect data and monitor patients.
In the pursuit of becoming the "sponsor of choice," biopharma sponsors are recognizing the pivotal role of optimizing the site experience. Insights from the existing surveys emphasize a positive correlation between trial enrollment, patient retention, and a high-quality investigator experience. To bolster this connection, sponsors can implement several strategies:
A. Streamlined Interactions: Simplify interactions with sponsors by designating dedicated points of contact. This approach ensures a cohesive and integrated experience for sites, providing bespoke support tailored to individual needs. Support may include staff augmentation, assistance with physician referrals, or collaboration in trial marketing activities.
B. Digital Tools for Accessibility: Employ digital tools to grant sites easy and immediate access to trial information, training materials, and real-time data on site performance. This not only enhances communication but also facilitates efficient collaboration.
C. Process Reevaluation: Reconsider key site-facing processes, such as contracting, budgeting, and site initiation, to minimize friction. This could involve broader use of master service agreements, elimination of confidential disclosure agreements, simplification of budgeting processes, expedited decisions on site selection, and an increased reliance on virtual formats for site training.
As the biopharma industry collectively strives to accelerate clinical trial timelines, reduce costs, and maintain the highest-quality trials, an enhanced PI and patient experience emerges as a strategic imperative. While scientific advancements and superior clinical assets remain foundational to R&D productivity, increased focus on patient enrollment and site engagement is deemed critical to realizing these ambitions. Recognizing that no single change can address all challenges, a series of collaborative actions, in partnership with global sites, has the potential to significantly alleviate the international burden of clinical trials on both the industry and patients.
In summary, the discussions in this chat have covered various aspects of clinical trials, ranging from the challenges faced by the pharmaceutical industry to innovative approaches and recommendations for improvement. Here are key recommendations derived from the insights shared:
Embrace Decentralized Trials, the adoption of decentralized trials has proven to be a transformative strategy, not only enhancing efficiency but also offering a more patient-centric approach. This includes leveraging digital technologies, ensuring user-friendly interfaces, and critically validating instruments for virtual platforms. Strategic Data and Analytics, incorporating a data-and-analytics approach to site selection and management is paramount. Rich datasets, AI-driven models, and predictive analytics can significantly streamline processes, leading to improved recruitment rates and more effective clinical trial outcomes. Revolutionize Site Selection, strategic selection of digital tools for clinical trials is crucial. Tools must be "fit-for-purpose," ensuring interpretability and secure data transmission. Wearables and other technologies should be critically evaluated for accuracy, and tools should measure clinically relevant data. Learn from COVID-19 Experience, lessons from the COVID-19 era suggest adopting successful measures such as at-risk development, collaborative dialogue with regulators, and the use of master protocols and adaptive trial designs. Additionally, accelerating the use of digital technologies for decentralized and hybrid studies remains a key recommendation. Enhance Site Experience, improving the site experience is essential for sponsors aiming to position themselves as a "sponsor of choice." This involves simplifying interactions with sponsors, designating points of contact, utilizing digital tools for easy access to trial information, and reevaluating key site-facing processes to minimize friction. Accelerate Process Simplification, to expedite clinical trial timelines and reduce costs, sponsors should consider simplifying key site-facing processes, such as contracting, budgeting, and site initiation. This may involve broader use of master service agreements, elimination of confidential disclosure agreements, faster decisions on site selection, and increased use of virtual formats for site training. In the pursuit of these recommendations, a holistic and collaborative approach is essential. By combining innovative technologies, streamlined processes, and a patient-centric focus, the biopharma industry can usher in a new era of clinical trials marked by efficiency, inclusivity, and improved outcomes for both sponsors and patients.