natgillin/translations-raw huggingface dataset:
• Hvad angår de to separate studier af lægemiddelanvendelsen til vurdering af effekten af de risikominimerende foranstaltninger, der blev pålagt som følge af indbringelsesproceduren i 2013, konkluderede PRAC, at disse studier, trods begrænsninger som følge af mulig fejlklassificering, er repræsentative for den kliniske anvendelse i EU, og at hovedresultaterne er pålidelige. 
• With regards to the two separate DUSs conducted to assess the effectiveness of the risk minimisation measures imposed as an outcome of the 2013 referral, PRAC concluded that these studies, despite limitations due to possible misclassification, are representative of the clinical usage in the European Union and that key results are reliable.
CMDh noterede sig, at otte EU-medlemsstater deler betænkeligheder vedrørende det medicinske behov, der opstår i tilfælde af suspendering af markedsføringstilladelsen for HES-infusionsvæske, opløsning. 
The CMDh noted that eight EU Member States have shared concerns about a medical need created in case of suspension of the marketing authorisation for HES solutions for infusion.
Den protokol til et studie af lægemiddelanvendelse, der skal forelægges af markedsføringstilladelsesindehaverne, skal indeholde klare målsætninger rettet mod ordinationsbeslutninger, navnlig overholdelse af indikationer og kontraindikationer. 
The DUS protocol to be submitted by the MAHs should include clear objectives, focusing on prescribing decisions, especially adherence to indications and contraindications.
HES-infusionsvæske, opløsning, er godkendt verden over til behandling af hypovolæmi ved diverse sygdomme. 
HES solutions for infusion are authorised worldwide for the treatment of hypovolaemia associated with various conditions.
Mere udtalt hypovolæmi kræver større volumen (dosis) af HES-infusionsvæske, opløsning, og er også forbundet med en større risiko for nyreskade og død. 
A more pronounced hypovolemia requires a greater volume (dose) of HES solutions for infusion and is also associated with a greater risk for renal injury and death.
Otte EU-medlemsstater har angivet, at en suspendering af markedsføringstilladelserne for HES-infusionsvæske, opløsning, ville få betydning for den nationale kliniske praksis, da HES-infusionsvæske, opløsning, på nuværende tidspunkt opfylder et medicinsk behov på deres område. 
Eight EU Member States have mentioned that a suspension of the marketing authorisations for HES solutions for infusion would have an impact in the national clinical practice as HES solutions for infusion fulfils currently a medical need in their territory.
- Indehaveren af markedsføringstilladelsen sikrer, at HES-infusionsvæske, opløsning, kun leveres til akkrediterede hospitaler/centre. 
- The MAH should ensure that HES solutions for infusion are only delivered to accredited hospitals/centres.
CMDh drøftede, om foranstaltninger til afbødning af risiciene forbundet med HES-infusionsvæske, opløsning, herunder især risikoen for øget dødelighed og nyresvigt hos kritisk syge patienter og patienter med sepsis, ville være effektive og gennemførlige i betragtning af nye elementer, der er forelagt af indehaverne af markedsføringstilladelse og medlemsstaterne. 
The CMDh discussed whether measures to mitigate the risks associated with HES solutions for infusion, including in particular the risk of increased mortality and renal failure in critically ill patients and patients with sepsis would be effective and feasible, taking into account new elements provided by the MAHs and Member States.
Disse data er meget bekymrende, da de viser, at HES-infusionsvæske, opløsning, anvendes hos kontraindicerede patientpopulationer som f.eks. kritisk syge patienter og patienter med sepsis3,4,5. 
These data raise serious concerns as they showed use of HES solutions for infusion in patient populations which are contraindicated such as those who are critically ill, or with sepsis3,4,5.
PRAC bekræftede, at de tilgængelige oplysninger, herunder mere nytilkomne kliniske data, ikke ændrer den fastslåede risiko for øget dødelighed og nyresvigt ved brug af HES-opløsninger til infusion hos disse patienter. 
PRAC confirmed that the available information, including more recent submitted clinical data, do not change the established risk of increased mortality and renal failure related to the use of HES solutions for infusion in these patients.
For at optimere materialets anvendelsen hos sundhedspersoner og deres overholdelse af betingelserne for korrekt anvendelse af HES-infusionsvæske, opløsning, bør de videnskabelige samfund inddrages i udarbejdelsen og distributionen af det pågældende oplysningsmateriale. 
In order to optimise the uptake by HCPs and their adherence to the adequate conditions of use of HES solutions for infusion, the learned societies should be involved in the development and distribution of such training materials.
På grund af den alvorlige risiko for den offentlige sundhed overvejede Sverige at suspendere markedsføringstilladelserne for ovennævnte lægemidler og anmodede derfor om en hastegennemgang af sagen på europæisk plan og bad PRAC om at vurdere betydningen af ovennævnte problemstilling, hvad angår benefit/risk-forholdet for HES-infusionsvæske, opløsning, og fremsætte en anbefaling om, hvorvidt markedsføringstilladelserne for disse lægemidler bør opretholdes, ændres, suspenderes eller tilbagekaldes. 
Due to the serious public health impact, Sweden was considering suspending the marketing authorisations for the above mentioned medicinal products, and therefore requested an urgent review of the matter at the European level, and asked the PRAC to assess the impact of the above concerns on the benefit-risk balance of HES solutions for infusion and issue a recommendation on whether the marketing authorisations of these products should be maintained, varied, suspended or revoked.
I lyset af andelen af patienter, der eksponeres for disse risici i fravær af effektive risikominimerende foranstaltninger, og da der er tale om alvorlige sikkerhedsmæssige betænkeligheder, der kan have alvorlige konsekvenser for den offentlige sundhed, herunder potentielt øget risiko for død, konkluderede PRAC, at benefit/risk-forholdet for HES-opløsninger til infusion ikke længere er gunstigt, og anbefalede, at markedsføringstilladelserne suspenderes. 
In view of the seriousness of the safety issues and that the proportion of patients who are exposed to these risks in the absence of effective risk minimisation measures could have important public health consequences including a potentially increased mortality, the PRAC concluded that the benefit risk balance of hydroxyethyl starch solutions for infusion is no longer favourable and recommended the suspension of the marketing authorisations.
Som overordnet konklusion vurderede CMDh, at den ovenfor beskrevne risikominimering ville være gennemførlig og effektiv og vil have synergistisk virkning, da den er målrettet mod bestemte sundhedspersoner i alle trin af ordination og administration af HES-infusionsvæske, opløsning. 
As an overall conclusion, the CMDh considered that the risk minimisation described above would be feasible and effective and will have a synergistic effect as they allow targeting specific HCPs at all the steps of the prescription and administration of HES solutions for infusion.
CMDh noterede sig i øvrigt PRAC's betænkelighed ved, at manglende overholdelse ikke alene skyldtes manglende bevidsthed hos de ordinerende om de begrænsninger, der er pålagt HES-infusionsvæske, opløsning. 
Besides, the CMDh acknowledged the PRAC's concern that non-adherence would not only be due to a lack of awareness by prescribers of the restrictions imposed to HES solutions for infusion.
• PRAC anerkendte også, at den aktuelle klinisk erfaring viser, at det er vanskeligt at skelne mellem de patientpopulationer, hvor der i randomiserede kliniske studier er set alvorlig skade, og de populationer, der er omfattet af den godkendte indikation. 
• The PRAC further acknowledged that the current clinical experience suggests that it is difficult to clearly separate patient populations where randomised clinical trials have shown serious harm from populations targeted by the approved indication.
• Dette program for kontrolleret adgang er en nøgleforanstaltning til at sikre, at sundhedspersoner overholder betingelserne i markedsføringstilladelsen, både ved at øge de pågældende sundhedspersoners opmærksomhed om risiciene ved brug af HES-infusionsvæske, opløsning, og ved at sikre, at de har modtaget tilstrækkelig oplæring, før de kan bruge HESinfusionsvæske, opløsning. 
• This controlled access program is a key measure to ensure adherence of HCPs to the terms of the MA by increasing both the awareness of the relevant HCPs to the risks associated to the use of HES solutions for infusions and ensuring that they have received appropriate training before they can use HES solutions for infusion.
Blandt de andre sikkerhedsrelaterede data gennemgik PRAC resultaterne fra to separate studier af lægemiddelanvendelsen til vurdering af effektiviteten af de risikominimerende foranstaltninger, der blev pålagt som følge af indbringelsesproceduren i 2013, og konkluderede, at disse studier, trods en potentiel begrænsning gennem mulig fejlklassificering, er repræsentative for den kliniske anvendelse i EU, og at hovedresultaterne er pålidelige. 
Amongst other data related to safety, the PRAC reviewed the results from two separate DUSs conducted to assess the effectiveness of the risk minimisation measures imposed as an outcome of the 2013 referral, and concluded that these studies despite a potential limitation of possible misclassification, are representative of the clinical usage in the European Union and that key results are reliable.
Herunder tog CMDh i betragtning de supplerende detaljer fra indehaverne af markedsføringstilladelse om det foreslåede program til kontrolleret adgang. 
In particular, the CMDh took into consideration the additional details from the MAHs on the proposed controlled access program.
CMDh er derudover af den opfattelse, at indehaverne af markedsføringstilladelse bør udføre et studie af lægemiddelanvendelse for at vurdere effektiviteten af de nye foranstaltninger, der anbefales. 
In addition, the CMDh is of the view that the MAHs shall perform a Drug Utilisation Study, in order to assess the effectiveness of the new measures recommended.
Formidlingstiltag 
Communication measures
Intensive Care Medicine (SSAI) og fem skandinaviske videnskabelige samfund suspenderingen af markedsføringstilladelserne for HES-opløsninger til infusion. 
On the contrary, the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) and five Scandinavian learned societies supported the suspension of the marketing authorisations for HES solutions for infusion.
Advarslen og dens visuelle udformning bør underkastes en brugertest, der er i overensstemmelse med "Guideline on the Readability of the labelling and package leaflet on medicinal products for human use" (Retningslinjer for læsbarheden af mærkning og indlægssedler for humanmedicinske lægemidler) og forelægges inden 1 måned efter Kommissionens afgørelse. 
"Guideline on the Readability of the labelling and package leaflet on medicinal products for human use", to be submitted within 1 month from the Commission Decision.
Formålet med et sådant program er at sikre, at HES-infusionsvæske, opløsning, kun leveres til hospitaler/centre, hvor sundhedspersoner, der forventes at ordinere eller administrere (i det følgende benævnt "relevante sundhedspersoner"), er blevet tilstrækkeligt uddannet til korrekt anvendelse af HES-infusionsvæske, opløsning, uanset hvilke(n) afdeling(er) de arbejder i. 
Controlled access program The objective of such program is to ensure the delivery of HES solutions for infusion to only hospitals/centres where HCPs expected to prescribe or administer (hereinafter ‘relevant HCPs') have been trained adequately on the appropriate use of HES solutions for infusion, irrespective of the department(s) where they operate,.
Studie af lægemiddelanvendelse 
Drug Utilisation Study (DUS)
CMDh er af den opfattelse, at de foreslåede supplerende foranstaltninger, der beskrives nedenfor, vil være gennemførlige og effektive til at minimere risiciene tilstrækkeligt ved at øge bevidstheden hos sundhedspersoner og sikre, at adgangen til HES-infusionsvæske, opløsning, forbeholdes sundhedspersoner, som har fået tilstrækkelig oplæring. 
The CMDh is of the position that the proposed additional measures described below would be feasible and effective to sufficiently minimise the risks by increasing awareness of HCPs, as well as ensuring that access to HES solutions for infusion is reserved to HCPs that have received adequate training.
Det bemærkes også, at skønt der er påvist en fordel i form af en volumenbesparende effekt, og selvom der er nogen støtte for kortvarige hæmodynamiske virkninger, er det usikkert, i hvilket omfang dette er ensbetydende med mere patientrelevante resultater. 
Is it also noted that although the benefit has been demonstrated in terms of a volume-sparing effect, and there is some support for short-term hemodynamic effects, it remains uncertain to what extent this translates into more patient-relevant outcomes.
PRAC undersøgte nøje alle de oplysninger, der var givet vedrørende et potentielt udækket medicinsk behov på nationalt plan, hvis markedsføringstilladelserne for HES-infusionsvæske, opløsning, skulle blive suspenderet. 
The PRAC carefully considered all the information provided in relation to a potential unmet medical need at national level should the marketing authorisations for HES solutions for infusion be suspended.
CMDh vedtog desuden en plan for formidlingen af dette direkte brev til sundhedspersoner. 
The CMDh also agreed on a communication plan for the dissemination of this DHPC.
Der kan således forventes en direkte korrelation mellem indikationen for behandling med HES-infusionsvæske, opløsning, den nødvendige dosis heraf, og risikoen for nyreskade og død. 
Consequently, a direct correlation is to be expected between the indication for treatment with HES solutions for infusion, the dose of HES solutions for infusion required and with the risk for renal injury and death.
Under hensyn til meningsforskellene blandt eksperterne om visse vigtige spørgsmål, PRACmedlemmernes synspunkter på den nationale situation, hvad angår den kliniske anvendelse af disse lægemidler, og interessenternes svar, mener PRAC ikke, at lægemidlernes kliniske nytte opvejer risikoen for død og nyresvigt hos den andel af patienterne, der har kritisk sygdom eller sepsis, som fortsat vil blive eksponeret for HES-opløsninger til infusion. 
Overall, taking into account the divergences amongst the experts on some important issues, the position from the PRAC members on the national situation regarding the clinical use of these products and the stakeholders submissions, PRAC did not consider the clinical utility of these products to outweigh the risk of mortality and renal failure to the proportion of patients with critical illness or sepsis that continue to be exposed to HES solutions for infusion.
PRAC har taget hensyn til alle elementer, der er udtrykt vedrørende den virkning, som en suspendering af markedsføringstilladelsen for HES-infusionsvæske, opløsning, vil have på et potentielt udækket medicinsk behov på nationalt plan, herunder de skriftlige og mundtlige bemærkninger fra indehaverne af markedsføringstilladelse, svarene fra medlemsstaterne samt andre interessenters synspunkter. 
The PRAC has considered all elements expressed in relation to the impact of a suspension of the marketing authorisation for HES solutions for infusion on a potential unmet medical need at national level, including comments submitted by the MAHs in writing and at oral explanations, responses from Member States and other stakeholders' views.
HES-infusionsvæske, opløsning, fandtes desuden at blive anvendt til behandling af livstruende medicinske tilstande. 
It was also considered that HES solutions for infusion are used for the treatment of life-threatening medical conditions.
• Udvalget for Risikovurdering inden for Lægemiddelovervågning (PRAC) har behandlet sagen vedrørende hydroxyethylstivelse (HES), infusionsvæske, opløsning (jf. bilag I) i henhold til proceduren i artikel 107i i direktiv 2001/83/EF. 
• The Pharmacovigilance Risk Assessment Committee (PRAC) considered the procedure under Article 107i of Directive 2001/83/EC, for hydroxyethyl starch (HES) solution for infusion (see Annex I).
PRAC anbefalede desuden, at der blev foretaget et studie af lægemiddelanvendelse for at vurdere disse risikominimeringsforanstaltningers effektivitet. 
PRAC also recommended a drug utilisation study to evaluate the effectiveness of these risk minimisation measures.
CMDh vedgik, at de ordinerende ikke ofte ville komme til at administrere opløsningen og derfor ikke ville se denne advarselsetiket. 
See all contraindications in the SmPC.” The CMDh acknowledged that the prescribers would not often administer the solution and therefore could not see this warning label.
PRAC bemærkede, at de kliniske studier (TETHYS og PHOENICS), der blev pålagt efter de tidligere indbringelsesprocedurer med henblik på at beskrive HES-lægemidlers effekt og sikkerhed ved traumer og elektiv kirurgi, dvs. lægemidlernes målpopulation, stadig er i gang. 
The PRAC noted that the clinical studies imposed following previous referrals procedures (TETHYS and PHOENICS) to characterise the efficacy and safety in trauma and elective surgery, which is currently the target population for which the product is indicated are ongoing.
PRAC har desuden yderligere overvejet risikominimeringsforanstaltningernes gennemførlighed og forventede effektivitet. 
The PRAC have also further considered for the feasibility and likely effectiveness of risk minimisation measures.
Protokollen til studiet af lægemiddelanvendelse skal forelægges PRAC til vurdering senest 3 måneder efter Kommissionens afgørelse. 
The DUS protocol should be submitted for assessment to the PRAC within 3 months of the Commission Decision.
I sin vurdering gennemgik PRAC den samlede evidens, herunder alle nytilkomne data siden de forrige indbringelsesprocedurer, herunder resultater fra studier af lægemiddelanvendelsen, kliniske studier, metaanalyser af kliniske studier, erfaring efter markedsføring, EudraVigilance-databasen, litteraturgennemgang, skriftlige og mundtlige svar fra indehaverne af markedsføringstilladelse samt interessentsvar og ekspertudtalelser fra et ad hoc-ekspertmøde, idet der også er taget hensyn til beskrivelsen af fordele og risici i de forrige indbringelsesprocedurer. 
In its assessment, the PRAC considered the totality of evidence which includes all newly available data since the previous referral procedures, including results from DUSs, clinical studies, meta-analyses of clinical studies, post-marketing experience, Eudravigilance data, literature review, responses submitted by the marketing authorisation holders (MAHs) in writing and at oral explanations as well as stakeholders' submissions and views expressed by experts during an ad-hoc experts meeting, taking into account also the characterisation of benefits and risks concluded in the previous referral procedures.
Revideret begrundelse for PRAC's anbefaling 
Revised grounds for PRAC recommendation
I protokollen bør indehaveren af markedsføringstilladelse tage hensyn til erfaringerne fra det tidligere udførte studie af lægemiddelanvendelse. 
For this protocol, the MAH should take into account the experience gathered from the previously conducted DUS.
Ved elektiv kirurgi og traumepatienter er der godtgjort et positivt benefit/risk-forhold. 
A positive benefit-risk balance has been established in elective surgery and trauma patients.
Udførelse af dette studie vil være en betingelse for markedsføringstilladelserne for HESinfusionsvæske, opløsning. 
The conduct of this study will be a condition to the marketing authorisations for HES solutions for infusion.
PRAC konkluderede, at den påståede kliniske nytteværdi af disse produkter ikke opvejer risikoen for dødelighed og nyresvigt for den del af patienterne, der har kritisk sygdom eller sepsis og fortsat udsættes for HES-infusionsvæske, opløsning. 
The PRAC concluded that the claimed clinical utility for these products does not outweigh the risk of mortality and renal failure to the proportion of patients with critical illness or sepsis that continues to be exposed to HES solutions for infusion.
PRAC konkluderede, at der ikke kan identificeres yderligere risikominimerende foranstaltninger eller kombinationer heraf til opnåelse af en tilstrækkelig sikker og effektiv anvendelse af HESopløsninger til infusion. 
The PRAC concluded that no additional risk minimisation measure or combination of risk minimisation measures, to sufficiently ensure safe and effective use of HES solutions for infusion could be identified.
• Betydningen for klinisk praksis af en eventuel suspendering af markedsføringstilladelserne for HES-infusionsvæske, opløsning 
• Impact on the clinical practice of potential suspension of MA for HES solutions for infusion
- Indehaveren af markedsføringstilladelsen forvalter akkrediteringen af hospitaler/centre og sikrer, at alle relevante sundhedspersoner, der er bestemt til at ordinere/administrere HESinfusionsvæske, opløsning, er tilstrækkelig oplært. 
- The MAH should manage the accreditation of the hospitals / centres, ensuring that all relevant HCPs intended to prescribe/ administer HES solutions for infusion have been adequately trained.
PRAC overvejede yderligere risikominimeringsforanstaltninger, som potentielt kunne minimere denne eksponering tilstrækkeligt, herunder begrænsning af adgangen/distributionen til hospitaler og læger, ændringer i produktinformationen, et direkte brev til sundhedspersoner, oplysningsmateriale, der distribueres i samarbejde med visse videnskabelige samfund, en advarsel på produktets primære emballage, en medicinformular og et opfølgende spørgeskema. 
The PRAC considered further risk minimisation measures which could potentially sufficiently minimise this exposure, including restricted access / distribution to hospitals and physicians, changes to the product information, direct health care professional communication, educational materials to be distributed in cooperation with some learned societies, warning on the primary container of the products, medication form and follow-up questionnaire.
• PRAC gennemgik alle nytilkomne data, herunder resultater fra studier af lægemiddelanvendelsen, kliniske studier, metaanalyser af kliniske studier, erfaring efter markedsføring, data fra EudraVigilance, litteraturgennemgang, skriftlige og mundtlige svar fra indehaverne af markedsføringstilladelse, interessentsvar samt ekspertudtalelser fra et ad hocekspertmøde. 
• The PRAC reviewed all newly available data, including results from Drug Utilisation Studies (DUS), clinical studies, meta-analyses of clinical studies, post-marketing experience, Eudravigilance data, literature review, responses submitted by the marketing authorisation holders (MAHs) in writing and at oral explanations, stakeholders' submissions and views expressed by experts during an ad-hoc experts meeting.
CMDh vedtog derfor, at sundhedspersoner i et direkte brev skulle informeres om resultaterne af studierne af lægemiddelanvendelse, betingelserne i markedsføringstilladelserne og risikoen ved brug af HES-infusionsvæske, opløsning, uden for disse vilkår, samt de nye supplerende risikominimeringsforanstaltninger. 
Therefore, the CMDh adopted a DHPC to inform HCPs of the results from the DUSs, the terms of the MA and the risks related to the use of HES solutions for infusion outside these terms, as well as the new additional risk minimisation measures.
Detaljeret videnskabelig begrundelse for afvigelserne fra PRAC's anbefaling 
Detailed explanation of the scientific grounds for the differences from the PRAC recommendation