Toward an effective translational science engine

Abstract

The journey of innovation and scientific discovery toward widespread clinical implementation is often meandrous, with many roadblocks, changeovers, or transitions. The traditional funded research pathway starts from ideation, request for application, and funding of the basic science or laboratory-based exploration (T0), to early-phase translational investigation in humans (T1), to clinical studies on patients in various practice settings (T2), then exploration of health in different communities (T3), to global approaches in the larger population (T4), and eventually to societal outputs via regulatory changes, policy, or new health systems' creation (T5). Unfortunately, the linear process of translation may encounter strictures at every stage of the way (Figure 1a). This is perhaps not surprising, as the linear nature of a very complex process conforms to the well-known theory of constraints, as articulated by Goldratt.¹ Additionally, the well-known pipeline model of translation (Figure 1a) does not include bidirectional flows of knowledge, for example, transitions from laboratory to clinic, community, or population and sometimes back to the laboratory. One can argue that the cartography of translation is not even a continuous function, as temporal disruptions may lead to dead ends, abandoned paths, wasted opportunities, unsurmountable funding gaps, or overt unrealized discoveries.

In 2011, NIH created the NCATS in order to pursue, encourage, catalyze, and grow funding opportunities for disruptive translational innovation, using both intra- and extramural mechanisms.² In the current NCATS' strategic plan, one aim is to accelerate translation by addressing both scientific and operational barriers, recognizing that innovation, creativity, and technology can aid and accelerate translational science and translational research efforts, including identification of new opportunities to pursue effective and efficient transitions or translations through teamwork and transdisciplinary collaboration.³ Translational science is an eclectic discipline that studies the translational processes and operations in order to establish their scientific governing principles, mechanisms, and inner-workings, moving translation from empiricism to predictivity.⁴ It has been asserted that moving an intervention or innovation in the well-described develop–demonstrate–disseminate cycle all the way to public health requires sometimes no <20 distinct scientific disciplines, each with its own language, heuristics, frameworks, or specific outcomes.^{4, 5}

We contend that the traditional translational pipeline model can be successfully modified (Figure 1b) so that linearity and unidirectionality are corrected by a hybrid serial–parallel system of communicating vessels, with finely tuned firepower (i.e., adequate local resources, differential support gauged specifically and adaptively to overcome local bottlenecks) applied in CTSA hubs, in loco-regional or national consortia, at every phase of the investigation. This approach could allow anterograde and retrograde flows or “spillover” into adjacent loops (Figure 1c), augmenting the final output, and enhancing it by a strong community engagement component.⁶ Further, we propose a modified model of Team Science approach, moving from the traditional tall, narrow, and brittle T (Translation) to a shorter, broader, and more robust T (Figure 2), centered on trans-disciplinarity⁷ and borrowing capabilities from several specialties⁵ that allow creating a powerful translational science engine, while strengthening the community engagement in the design, conduct, and dissemination of research. Understandably, these proposed changes to be implemented in the real world will require both local system redesigns and potentially structural changes in the future funding mechanisms.

Along the translational spectrum, adoption and dissemination of new discoveries have been marred by structural or functional challenges, barriers, system strictures, bottlenecks, chokepoints, funding winters, death valleys, or long, unexplained delays. While progress in both basic and translational research has remained highly intertwined with clinical observations, the explosive successes in fundamental laboratory research seen so far in the 21st century far outpaced clinical and translational investigation outputs.

Translational research is defined by NCATS as the endeavor to traverse a particular step of the translational process for a specific target or disease, which aims to bridge the gap between scientific discoveries and practical, real-world applications in medicine and health care.⁸ It often entails multidisciplinary approaches, which address several transition stages (T0-5, Figure 1) and involve moving research findings across settings, languages, methodologies, and study designs, or from laboratory to clinical practice and eventually into community- and population-level health benefits. Translational research is often used to develop novel medical devices, new therapeutic approaches, strategies, or healthcare interventions based on initial, often laboratory-based scientific discoveries. Translational research involves collaboration among scientists, clinicians, patients, community members, government officials, and other stakeholders (Team Science) to ensure that research findings are effectively translated into practice and public health policy.

In contrast, translational science evolved toward a separate discipline, dealing with the systematic investigation and the practice of operationalizing the translation of innovation from one language, ecosystem, environment, contextual landscape, phase of development, culture, scientific discipline, area, or domain into another. Translational science deals with various methodologies, technologies, and processes geared toward finding best solutions and strategies able to sustainably overcome inherent barriers or roadblocks between different phases of investigation. Translational science also encourages transdisciplinary collaborations across basic science, clinical research, epidemiology and public health, biomedical informatics, data science, and healthcare delivery. Equity-driven patient or community-centered perspectives and approaches are also central to translational science. The focus of translational science is on the efficiency, effectiveness, and informativeness of translations from laboratory (“bench”) into practical applications for patient care (“bedside” or “clinic”), to communities and populations at large, and back (the traditional “pipeline”).

The well-engrained “pipeline” concept proved to be not only a major over-simplification but, over the years and in the eyes of the public and the regulators alike, also a significant contributor to confusion, lack of understanding and inability to effectively accelerate the drug and innovation development processes. These limitations had wide implications and occasional led to counterproductive measures or approaches for science, public policy, and research funding. Recognizing the distance between simple, linear processes and very complex and meandrous paths that translational science may take, others tried to resolve the complexity of the journey of innovation by conceptualizing a drug discovery, development, and development map (4DM), which organized standard domains into networks of neighborhood activities, which can be arranged both in series and in parallel.⁹

We contend here that a successful translational science machinery at a CTSA hub should move from multidisciplinary or interdisciplinary to transdisciplinary approaches,⁷ and to include additional functional capabilities, smartly borrowing from other fields such as implementation science, quality improvement and management, communication sciences, marketing, system engineering, organizational psychology, human factor engineering, intervention science, data science, decision science, public health, project management, operations, change management and leadership, and working together in mixed, highly functional Team Science groups.⁵ Development and functional use of such capabilities and competencies may serve the field of translational research well, allowing Team Science approaches to be undertaken with wider and faster adoption, more successfully and to more people.¹⁰ At the institutional level, a CTSA hub can serve as designer, owner, and operator of the translational channel of communication, assuring adequate firepower and being the best catalyst for enlarging the pool of stakeholders communicating and contributing by different sets of abilities, capabilities and methodologies, in that specific channel and over specific time periods. Furthermore, in this alternative translational research model (Figure 1b), the phases of investigation can be arranged in a hybrid serial–parallel system. In contrast to the 4DM concept,⁹ we propose here “folding” the complex neighborhood activities into locally conceived and resourced microsystems designed not only for accelerated experimentation, nimble coordination, forward and backward translation, but also for flexibility, process adaptability, and generalizability. The system resources in our own model, represented by water flow (research inputs and outputs) in the T0–T5 phases, are often not adequate for forward flow of the discovery from one communicating vessel to the next, due to the linearity of the constraints and possibly inadequate local firepower for the respective phases of investigation or loops. Figure 1c illustrates that coordinated and finely tuned firepower locally in different phases of translation through various, tactically timed and resourced requests for applications, pilot awards, specific Team Science projects (such as the ones deployed in the last year at the CTSA of Southeast Wisconsin for translational science research) may improve the bidirectional flows of knowledge, faster and more efficient adoption of new evidence and innovations.

In our traditional funding model, financial and logistic support for research generally goes to small groups of scientists or innovators, often “siloed” in specific academic units or development incubators. This may ultimately lead to profound and meaningful dives, deep hard rock drilling, or wide zooming in into the problem at hand, but often with limited breadth of expertise. This endeavor may also unveil an inherent vulnerability to breakage or fragility (tall–narrow–brittle T, Figure 2, left), due to scope, scale, technological or methodological limitations, difficulties in further testing and lack of generalizability of the findings in other contexts or phases of the translational spectrum.

In Figure 2, the tall, narrow (limited width or breadth), and brittle T represents the traditional, narrow-focus approach to research, driven by the aspiration of deep drilling or investigation (aim: depth), and narrowly fueled by specific grant mechanisms, to individual investigators or small groups. Significant roadblocks or barriers may prevent successful investigation, navigation, drilling, or dive for breakthrough discoveries. Figure 2 (middle) illustrates a short, broad (large width or breadth) and robust T, which has a better chance of success by drilling deeper, being enriched by multidisciplinary Team Science approaches. Figure 2 (right) illustrates the proposed novel model of transdisciplinary translational research (community-enhanced short–wide–robust T), constituting a powerful “press” or “engine” (aim: multipronged piercing strength), by using a broader range of capabilities, borrowing and mixing competencies and skill sets from other disciplines and fields of study, and by being community-centric. Involving patients, families, and local communities in translational research Team Science “ensembles” is crucial for ensuring meaningful outcomes, relevant impact, ethical research conduct, and effective dissemination of innovations. In our CTSA hub, we have engaged our local population members, many of them being underrepresented urban and suburban minorities, through a robust, constructive, trust-based, faith-structured community, deeply engaged in Team Science “ensembles,” in community research forums and science café sessions, leveraging the multidisciplinary skill sets and capabilities grown over the years as part of our translational science engine. We have also enriched the expertise available for the Team Science “ensembles” and pilot award investigator teams by gathering resources and faculty with various skill sets, toolboxes, frameworks, specific knowledge bases, and approaches from the contiguous specialties and disciplines. For example, we have started a transdisciplinary monthly conference on translational science and contiguous areas of study such as implementation science, system and human factors engineering, quality improvement, and design thinking, called Implementation Science for Innovation and Discovery. Operationally, we have constituted a CTSA hub Dissemination and Implementation Core (a multifaceted group with enriched knowledge bases, working in transdisciplinary approaches), which will critically appraise new and existing projects—impact and outcomes at individual, service, and implementation levels. The deliberate, declared intent in the Team Science “ensemble” approach was to activate the translational science engine in the early-forming phase and in specific translational science pilot studies, with project-based expertise customization, dedicated project management, specialized and individualized consultation for various grants or scholarly projects, and improvement projects, and by having the community members take a central role in the design and operations of these endeavors.

Translational science principles are not limited to medicine or health care and can be used in other fields, such as environmental science, engineering, and technology. Their central tenet is to ensure that scientific advancements do not remain confined to the laboratory or at the “point-of-innovation,” but are translated into practical solutions and real-life benefits that can improve people's lives. We believe that building a community-enhanced, short, wide, and robust T (translational science engine) is essential to the success of translating research findings and innovations into practice, to communities and populations at large, and it may require equipping CTSA hubs with specific capabilities via borrowing, developing, and/or consulting with specialists from very different and sometimes overlapping domains, fields, or disciplines, and to center the investigative efforts on a robust community engagement component. Successful transformation in the CTSA hubs does not require following predefined, unique recipes, but will necessitate significant redesign, to include system human interfaces with additional transdisciplinary, broader capabilities, robust community stakeholder involvement and active participation, and also diversification of the local support structures and pilot awards geared toward translational science projects, together with national, broader funding mechanisms that could strengthen these new systems and functional capabilities.

NCATS—CTSA: FP00015891; PI: Reza Shaker.

The authors declared no competing interests for this work.