应对监管审查：欧盟联合临床试验中的信息请求分析

REGULATORY RAPPORTEURFebruary 2026Volume 23 | No. 2 Amber McNair,Associate Clinical Trial Regulatory Director;Vladimir Vujovic,Director, Clinical TrialRegulatory, both of IQVIA With thanks toChristopher Bamford(IQVIA),Elizabeth Moir(IQVIA) andSarah Johns(MCRA, an IQVIA business) Abstract The In Vitro Diagnostic Regulation 2017/746 (IVDR) reshaped theregulatory landscape for in vitro diagnostic manufacturers and clinicaltrial sponsors conducting clinical trials across the European Union. Byintroducing stricter requirements for clinical evidence, performanceevaluation and risk classification, the Regulation raised the bar forproduct safety and scientific rigour. Sponsors face increasing regulatorycomplexity, particularly when performance studies are conductedalongside clinical trials of investigational medicinal products under EUClinical Trial Regulation 536/2014 (CTR). This article examines common regulatory feedback and documentationrequests arising from clinical performance study submissions,drawing on recent requests for information (RFIs) from both competentauthorities and ethics committees. The authors, subject matter expertsin the EU CTR/EU IVDR interface from IQVIA’s Clinical Trials RegulatoryManagement (CTRM) group, draw on internal regulatory intelligence toanalyse recurring themes, such as risk analysis, document consistency,scientific validity and language clarity, and offer practical guidance tohelp sponsors and regulatory professionals navigate dual submissionsunder IVDR and CTR. Actionable recommendations and summaries areprovided for each key document type to support compliance, reducedelays and improve submission quality. submission processes, each with its own objectives, timelinesand regulatory expectations, often placing strain on resourcesand study approval planning. A crucial aspect of the regulatoryprocess for combined studies requiring dual submissions is themanagement of requests for information (RFIs). Introduction The introduction of Regulation (EU) 2017/746 for in vitrodiagnostic (IVD) medical devices has significantly transformedthe regulatory environment for IVD manufacturers and clinicaltrial sponsors throughout the EU. With a focus on strong clinicalevidence, risk-based classification and thorough performanceevaluation, IVDR aims to enhance patient safety and publichealth protections. Based on an extensive review of combined clinical trialsubmissions managed by IQVIA, and analysis of RFIs receivedfrom multiple EU Member States, this article explores RFIsissued by national competent authorities (NCAs) and ethicscommittees (ECs) during the review of performance studiesunder IVDR when in combination with a clinical trial submittedunder CTR, and identifies recurring themes, regulatorychallenges and areas of ambiguity. Drawing on real-world dataand stakeholder experiences, it offers practical insights andstrategies for proactive regulatory oversight. The analysis isgrounded in an anonymised, categorised internal repository ofRFIs and correspondence compiled by IQVIA’s CTRM group duringvalidation and assessment phases of combined EU CTR/IVDRsubmissions. Findings are reported at aggregate level and areintended to highlight common issues encountered in combinedstudy applications from the perspective of performance studieswithout reference to identifiable sponsors or trials. However, transitioning to this new framework has posedsubstantial regulatory challenges, especially concerning clinicalperformance studies (CPS) in an investigational medicinalproduct (IMP) clinical trial (known as ‘combined clinical trials’).Evolving guidance from the EU’s Medical Device CoordinationGroup (MDCG) and varying expectations across Member Stateshave created a fragmented and unpredictable environment forsponsors conducting combined clinical trials. In response, theEuropean Commission initiated the COMBINE Project,1an effortto harmonise regulatory processes for trials involving bothIMPs and IVDs. By integrating the CTR and IVDR submissionpathways within the Clinical Trials Information System (CTIS),the project aims to minimise duplication, streamline workflowsand provide clearer guidance for sponsors navigating thesecomplex studies. This article aims to help regulatory professionals navigatethe complexities of IVDR implementation in clinical trials andcontribute to broader efforts to harmonise and streamlinecombined clinical trial processes across the EU. Until the COMBINE Project’s pilot phase outcomes are fullyevaluated, sponsors must continue to manage two separate between sponsors, regulators and ethics committees. As theEU continues to refine its regulatory infrastructure,6,7thereis an opportunity to address these challenges and movetowards a more integrated and predictable review process forcombined studies. Discussion: Navigating the regulatorycomplexity of combined studies The examination of RFIs issued during the evaluation ofcombined clinical trials and performance studies underCT