Artikeln beskriver begränsningarna med dagens CE-märkning där vi med tydlighet vill föra fram att ett sådant godkännande inte alltid är liktydigt med bra kvalitet hos respektive CGMN utrustning.
I artikeln belyses också att det behövs ett bättre mått än bristfälliga kvalitetsmåttet MARD (totalt), vilket inte säger något om noggtrannheten inom olika glukosnivåer.
I artikeln visar vi i vilken mån respektive produkt analyserats i en typ 1 diabetes population, vilka åldrar samt om alla dagarna av sensorns varaktighet analyserats.
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CGM accuracy: Contrasting CE marking with the governmental controls of the USA (FDA) and Australia (TGA): A narrative review
John S Pemberton BSc, Emma G Wilmot PhD, Katharine Barnard-Kelly PhD, Lalantha Leelarathna PhD, Nick Oliver FRCP, Tabitha Randell MD, Craig E Taplin FRACP, Pratik Choudhary FRCP, Peter Adolfsson PhD
First published: 30 December 2022
The work did not receive any specific funds.
The National Institute for Clinical Excellence updated guidance for continuous glucose monitoring (CGM) in 2022, recommending that CGM be available to all people living with type 1 diabetes. Manufacturers can trade in the UK with Conformité Européenne (CE) marking without an initial national assessment. The regulatory process for CGM CE marking, in contrast to the Food and Drug Administration (FDA) and Australian Therapeutic Goods Administration (TGA) process, is described.
Manufacturers operating in the UK provided clinical accuracy studies submitted for CE marking. Critical appraisal of the studies shows several CGM devices have CE marking for wide-ranging indications beyond available data, unlike FDA and TGA approval.
The FDA and TGA use tighter controls, requiring comprehensive product-specific clinical data evaluation. In 2018, the FDA published the integrated CGM (iCGM) criteria permitting interoperability. Applying the iCGM criteria to clinical data provided by manufacturers trading in the UK identified several study protocols that minimized glucose variability, thereby improving CGM accuracy on all metrics. These results do not translate into real-life performance.
Furthermore, for many CGM devices available in the UK, accuracy reported in the hypoglycaemic range is below iCGM standards, or measurement is absent.
We offer a framework to evaluate CGM accuracy studies critically. The review concludes that FDA- and TGA-approved indications match the available clinical data, whereas CE marking indications can have discrepancies. The UK can bolster regulation with UK Conformity Assessed marking from January 2025. However, balanced regulation is needed to ensure innovation and timely technological access are not hindered.
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From the article
16|BALANCING REGULATION WITHINNOVATION AND ACCESS TOTECHNOLOGY
If the UKCA marking system tightens regulation, there are grounds tosuggest more stringent standards will hinder innovation and slowaccess to the latest technologies. In the United States and Australia,where regulation is more robust than CE marking, the time requiredto gain approval is estimated to be double that of CE marking.85-87For example, the well-evidenced MiniMed 780G68,69is not availablein the United States, and the Dexcom G7™15,16is not available inAustralia, yet, they are both available in Europe. In addition, if UKCAmarking becomes more robust than CE marking, manufacturers maydelay applying for UKCA marking, opting to prioritize the larger andeasier-to-access markets of Europe. For example, the Omnipod®5, Freestyle Libre®3 and Dexcom G7™are not available in Australia,and every CGM and AID device has been available in Europe longbefore Australia. The CE marking system supports commercializationof markets that can drive down price and increase optionality forusers and health care professionals. Users have direct influence byreporting safety concerns using post-market tools such as the MHRAyellow card system. However, there is a need to balance the speed ofaccess to technology with end-user safety. For example, the CE mark-ing of the Medtrum Nano®System for paediatrics and adults despiteno published CGM accuracy or AID system outcome data is concern-ing, particularly, considering people with type 1 diabetes used theMedtrum Nano®System during the UK's national hybrid closed looptrial. The trial team removed the Medtrum Nano®System because ofreported safety issues, and publication of the results will elaborate onthe seriousness of the safety concerns. In addition, the CE markingprocess aims to increase users’options; however, local funding bodiesin the UK have created policies following the NICE guidanceupdates1,2with GlucoRx Aidex™as first choice for adults and adolescents with type 1 diabetes based on cost. Consequently, geo-graphical pockets in the UK offer minimal choice, and the recom-mended choice is a CGM device that has accuracy and safety data ononly 14 adults with type 1 diabetes that is not reported indepen-dently.25Finally, a regulatory system granting indications for useextending beyond the clinical data has implications for the validity ofthe results from pharmaceutical and medical device trials, followingthe international consensus statement on CGM metrics for clinical tri-als.88The statement recommends, The selected CGM device shouldbe used in accordance with the manufacturer product information andregulatory indications for which it is approved. The recommendationraises the possibility of using the GlucoRx Aidex™for CGM outcomedata for a trial investigating people with type 1 diabetes, and theMedtrum TouchCare®Nano or Glucomen Day®for paediatrics withtype 1 diabetes, despite the CGM systems having minimal or no pub-lished accuracy data on those populations. A solution could be for theUKCA marking system and CE marking system to implement studydesign criteria that apply to all CGM devices, with varying accuracyperformance standards for different CGM device categories based onuser safety risk. The IFCC Working Group on CGM is positioned tosupport such a solution.3
Taken at face value, USA FDA and Australian TGA approval arevalid proxies of CGM device accuracy for the indicated populationsbecause of using the highest risk classification with specific assess-ment criteria that requires comprehensive product-specific clinicaldata.
The CDRH of the FDA and Advisory Committee of the TGAcomplete conformity assessments against regulatory requirementsas governmental entities, ensuring consistency without conflicts ofinterest. However, the lack of published standards for study designcriteria introduces ambiguity. In addition, the time taken to receiveFDA and TGA approval risks hindering innovation. In contrast, CEmarking does not appear to be a valid proxy for the accuracy andperformance of CGM devices. Multiple Notified Bodies performconformity assessments against EU regulations without standardizedcriteria risking inconsistency of assessment, and their employmentby the manufacturer introduces a potential conflict of interest. Pub-lication and transparency in the clinical data that justified the CEmarking would be welcome. CE marking for AID requires an urgentappraisal. The CGM-specific study design and accuracy criteria foriCGM approval offer a starting point for the standardization ofCGM Accuracy. However, there is a need to develop clear designverification standards and performance metrics dependent on theCGM device category, for which the IFCC working group on CGMmay provide. In the absence of standardized assessment criteria, weoffer an overview of considerations for the critical appraisal of studydesign, point accuracy reporting and point accuracy performance ofa CGM accuracy study to support stakeholders involved in thedecision-making process. If unable to complete a full criticalappraisal, when presented with a MARD of10%, one enquire,‘Did the study include participants in sufficient numberswith demographics like those I look after. Furthermore, did the pro-tocol induce glycaemic variability on test days, and what is the per-centage of readings within 15/15 agreement rates in the differentglucose ranges?