优化早期临床试验，以实现快速、循证决策

Optimizing Early-Phase ClinicalTrials for Rapid, Evidence- Leveraging the rapidly evolving design and delivery strategies to ELIZABETH ALLEN, PhD, Vice-President, Early Phase Development Centre of Excellence, Scientific StrategyRAYMOND COOK, MD, Vice President, Medical Strategy for Early Phase DevelopmentJOANNE EMANUEL, Senior Director, Clinical Project Management, Early Phase Table of contents The rising challenges — and opportunities — in early phase clinical researchMeeting the challenge: the emergence of integrated adaptive designsKey foundational elements required for today’s early phase clinical trialsI. Specialized expertise, experience and capabilities in early-phase design and deliveryII. Enhancement and customization of adaptive-design conceptsIII. Global, therapeutically aligned site access and recruitment infrastructureIV. Integrated delivery model to seamlessly streamline early-to-late-stage transitionLooking ahead: innovating solutions for tomorrow’s early phase trials The rising challenges — andopportunities — in early phase more quickly to patients in need through seamless phaseI/II and model-informed drug development. At its simplest level, this evolving delivery modelconsolidates the early phases of clinical research thatwould ordinarily be staggered. And by combining healthy The landscape of early phase clinical trials continuesto evolve, introducing new challenges over the nextseveral years. Like the world around us, this changingenvironment brings uncertainties, which in turn couldcompel investors to be increasingly cautious. At the same time, drug development costs will face greater scrutiny dueto a range of factors — including revived Most-Favored-Nation policies, Inflation Reduction Act provisions, and the While this may seem simple, designing and executing thesetrials is inherently complex — requiring multidisciplinaryexpertise across pharmacology, quantitative sciences,regulatory strategy, therapeutic specialties and Understanding the complexity of recruitment for bothsubjects and investigators is another key consideration(addressed later in this paper), as poor recruitment of Despite these challenges, substantial opportunities exist.Advances in innovative trial methodologies — includingadaptive and hybrid designs, model-informed drug To be successful, therefore, sponsors and their CROpartners must have — at a minimum — several core, Meeting the challenge: theemergence of integrated “The use of hybrid adaptive trialdesigns provide sponsors and their CROpartners unprecedented opportunities The use of customized, adaptive-design concepts areimportant tools, which — when expertly and carefullyimplemented — provides sponsors and their CRO Key foundational elementsrequired for today’s early requirements around specific biomarkers or raremutations (which can slow recruitment and increase • Global site access and recruitment infrastructure encompassing a range of diverse, therapeuticallyaligned and experienced sites (through networkpartnerships, proprietary clinics, and/or 3rd partysites) that are operationally- and medically-qualified Over the past decade, we at IQVIA have established bestpractices for successfully crafting and navigating thesecomplex early phase clinical studies — which we continue todevelop and enhance — and have identified four key pillars • Specialized expertise, experience and capabilitiesinearly-phase clinical trials and proof-of-concept design • Enhancement and customization of adaptive-design conceptsfor more complex trials and specific • An integrated delivery modelthat seamlesslystreamlines the early-to-late-stage transition should I. Specializedexpertise, experience and is no one-size-fits-all solution; each protocol must betailored appropriately according to the characteristicsof the specific molecule, the goals of the research, andthe target population (and/or caregivers in certain To capably design and implement these addedcomplexities — such as accelerated titration,minimizing patient dosing exposure with optimal predictive, interdisciplinary experts and technologyworking seamlessly in tandem, which ensures additional Sponsors therefore must choose a CRO partnerthat can provide foresight and targeted protocolrecommendations, significant therapeutic and regulatory These core areas fall into three categories:ExpertAdvisory and Specialty Teams(including clinicalpharmacologists, early phase regulatory experts,and Therapeutic Centers of Excellence);Quantitativeand Analytical Sciences(including biometrics, PK/PD “While traditional, straightforwardadministration and blood samplingin healthy volunteers focuseson basic PK/safety data, today’s Quantitative/analytical sciences ïBiostatistics and data management(biometrics)to inform trial design, collect,analyze, and interpret dataïPK/PD mathematical modelingto forecastoutcomes, guide dose selection, etc Expert advisory and specialty teams ïSpecialized clinical pharmacologiststotrans