natgillin/translations-raw huggingface dataset:
In addition, upon request from the PRAC, the MAH provided analyses of the overall results on the observed inhibitor incidence in the light of the study design and patient selection. 
Nadalje, nakon zahtjeva PRAC-a, nositelj odobrenja dostavio je analize ukupnih rezultata o uočenoj incidenciji inhibitora s obzirom na dizajn ispitivanja i odabir bolesnika.
The EUHASS study was established in 2008 as an adverse event reporting system for patients with inherited bleeding disorders, including Haemophilia A, in Europe. 
Ispitivanje EUHASS započeto je 2008. kao sustav za prijavljivanje nuspojava za bolesnike oboljele od nasljednog poremećaja krvarenja, uključujući i hemofiliju A, diljem Europe.
Five out of 37 (14%) PUP and 4 out of 23 (17%) MTP patients treated with Helixate NexGen developed inhibitors within 20 ED (exposure days). 
Pet od 37 (14%) PUP-ova i 4 od 23 (17%) MTP-ova koji su liječeni lijekom Helixate NexGen razvilo je inhibitore unutar 20 DI (dana izlaganja).
Annex IV Scientific conclusions and grounds for variation to the terms of the marketing authorisations 
Znanstveni zaključci i razlozi za izmjenu uvjeta odobrenja za stavljanje lijeka u promet
As a consequence, the marketing authorisation holder (MAH) for Kogenate Bayer and Helixate NexGen supported two EU registries: 
Slijedom toga, nositelji odobrenja za stavljanje u promet lijekova Kogenate Bayer i Helixate NexGen podržali su dva registra na razini EU:
Grounds for the variation to the terms of the marketing authorisations 
Razlozi za izmjenu uvjeta odobrenja za stavljanje lijeka u promet
In 2006, an EMA expert meeting1 on FVIII products and inhibitor development concluded that there was a need to collect comparable clinical data on the immunogenicity of recombinant and plasmaderived FVIII products as a long-term objective. 
Godine 2006. na sastanku stručne skupine pri EMA-i1 o lijekovima koji sadrže FVIII i razvoju inhibitora zaključeno je da postoji potreba za prikupljanjem usporedivih kliničkih podataka o imunogenosti rekombinantnih faktora VIII i onih dobivenih iz plazme, te je to postavljeno kao dugoročan cilj.
Overall summary of the scientific evaluation of Kogenate Bayer and Helixate NexGen 
Cjelokupan sažetak znanstvene ocjene lijekova Kogenate Bayer i Helixate NexGen
Haemophilia centres in Western Europe and major haemophilia centres in North America enrolled a total of 60 PUPs/MTPs without pre-existing inhibitors in two studies (200021EU and 100074US). 
Europi kao i veći centri za liječenje hemofilije u Sjevernoj Americi upisali su ukupno 60 PUP-ova/MTP-ova bez prethodno postojećih inhibitora u dva ispitivanja (200021EU i 100074US).
The efficacy of Kogenate Bayer/Helixate NexGen is recognised and the PRAC reviewed the data related to inhibitor development in PUPs and MTPs. 
Prepoznata je djelotvornost lijekova Kogenate Bayer/Helixate NexGen, a PRAC je pregledao podatke povezane s razvojem inhibitora u PUP-ova i MTP-ova.
The PRAC was of the view that the available data are consistent with the general experience that most inhibitors develop within the first 20 EDs and that the overall data does not provide evidence that factor VIII products differ from each other in terms of inhibitor development in PUPs. 
PRAC je bio mišljenja da su dostupni podaci u skladu s općenitim iskustvom da se većina inhibitora razvija tijekom prvih 20 dana izlaganja te da cjelokupni podaci ne pružaju dovoljno dokaza da se lijekovi koji sadrže faktor VIII razlikuju jedan od drugog u smislu razvoja inhibitora u PUP-ova.
In patients given KOGENATE Bayer/Helixate NexGen, 64 out of 183 developed an inhibitor (37.7%), of which 40 had a high-titre inhibitor (25.2%). 
U bolesnika koji su primili lijekove KOGENATE Bayer/Helixate NexGen, 64 od 183 razvilo je inhibitor (37,7%), od kojih je 40 imalo visoki titar inhibitora (25,2%).
The MAH will continue to support the RODIN/PedNet registry as well as the EUHASS registry, as per current obligations defined in the RMP, to further investigate individual risk factors for inhibitor development and risk mitigation in PUPs. 
Nositelj odobrenja nastavit će podržavati registar RODIN/PedNet kao i registar EUHASS, u skladu s aktualnim obvezama definiranima u RMP-u, kako bi dalje istražio faktore individualnog rizika za razvoj inhibitora i smanjivanje rizika u PUP-ova.
According to the MAH, since the Marketing Authorisations, 42 changes in the manufacturing process of KOGENATE Bayer have been introduced. 
Sukladno nositelju odobrenja, od trenutka izdavanja odobrenja za stavljanje lijeka u promet, uvedene su 42 izmjene u proizvodni postupak lijeka KOGENATE Bayer.
Post-hoc analysis of the RODIN study showed that PUPs with severe haemophilia A given Kogenate Bayer were more likely to develop inhibitor than those given another recombinant antihaemophilic factor VIII (adjusted hazard ratio, 1.60; 95%-CI: 1.08 -2.37). 
Post-hoc analiza ispitivanja RODIN pokazala je da su PUP-ovi oboljeli od ozbiljne hemofilije A koji su primili lijek Kogenate Bayer bili podložniji razvoju inhibitora od onih koji su primili drugi rekombinantni koagulacijski faktor VIII (prilagođeni omjer opasnosti, 1,60; 95%-CI: 1,08 -2,37).
However, the data presented by the MAH indicate that there are no significant changes in the posttranslational modifications, aggregation profile, specific activity or excipients since MA of Kogenate Bayer that might have increased the risk for inhibitor development over time. 
No, podaci koje je dostavio nositelj odobrenja ukazivali su na to da nije bilo značajnih izmjena u posttranslacijskim modifikacijama, profilu agregacije, specifičnom djelovanju ili pomoćnim tvarima od trenutka izdavanja odobrenja za stavljanje u promet lijeka Kogenate Bayer koji bi mogli povećati rizik od razvoja inhibitora tijekom vremena.
• The PRAC considered the procedure under Article 20 of Regulation (EC) No 726/2004 for Kogenate Bayer and Helixate NexGen. 
• je PRAC razmotrio postupak u skladu s člankom 20. Uredbe (EZ) br. 726/2004 za lijekove Kogenate Bayer i Helixate NexGen,
The MAH also submitted data from four interventional clinical trials and six observational studies, which investigated the safety and efficacy of Kogenate Bayer/Helixate NexGen in haemophilia A patients, including studies 200021EU and 100074US in PUPs and minimally treated patients (MTPs). 
Nositelj odobrenja dostavio je također podatke iz četiri intervencijska klinička ispitivanja i šest opservacijskih ispitivanja, koja su istražila sigurnost i djelotvornost lijekova Kogenate Bayer/Helixate NexGen u bolesnika koji boluju od hemofilije A, uključujući ispitivanja 200021EU i 100074US u PUP
In this context, the PRAC noted that Kogenate Bayer and Helixate Nexgen is potency labelled based on an one-stage clotting assay, in accordance with the approved quality documentation for the product, and not the chromogenic assay as per the European Pharmacopeia. 
U ovom kontekstu, PRAC je uočio da su lijekovi Kogenate Bayer i Helixate Nexgen potencijalno označeni na temelju eseja koagulacije jedne faze, u skladu s odobrenom dokumentacijom o kvaliteti za lijek, a ne u skladu s kromogenskim esejom prema Europskoj farmakopeji.
• The PRAC considered though that the frequency for inhibitor development in PUPs should be amended from “common” to “very common” in the section 4.8 of the SmPC and also recommended that the product information should be updated to reflect the most recent results from the RODIN study. 
• je PRAC zaključio da se učestalost za razvoj inhibitora u PUP-ova treba izmijeniti iz „često” u „vrlo često” u dijelu 4.8 SPC-a te je također preporučio da se informacije o lijeku trebaju ažurirati tako da prikazuju najnovije rezultate ispitivanja RODIN,
In one observational study, the incidence of inhibitor development in previously untreated patients with severe haemophilia A was 64/183 (37.7%) with Helixate NexGen (followed up to 75 exposure days). 
U jednom opservacijskom ispitivanju, incidencija razvoja inhibitora u prethodno neliječenih bolesnika oboljelih od ozbiljne hemofilije A iznosila je 64/183 (37,7%) s lijekom Helixate NexGen (nakon 75 dana izlaganja).
The CHMP considered the below PRAC recommendation dated 5 December 2013 with regards to the procedure under Article 20 of Regulation (EC) No 726/2004 for Kogenate Bayer and Helixate NexGen. 
CHMP je razmotrio niže navedenu preporuku PRAC-a od 5. prosinca 2013. u vezi s postupkom provedenim u skladu s člankom 20. Uredbe (EZ) br. 726/2004 za lijekove Kogenate Bayer i Helixate NexGen.
Kogenate Bayer and Helixate NexGen are full-length recombinant human antihaemophilic factor VIII (octocog alfa) produced in baby hamster kidney (BHK) cells. 
Kogenate Bayer i Helixate NexGen su rekombinantni ljudski koagulacijski faktor VIII (oktokog alfa) pune dužine proizveden u bubrežnim stanicama mladunčadi hrčka (BHK).
Finally in support of the above mentioned clinical data, the MAH provided quality data with regards to the manufacturing process for Kogenate Bayer and Helixate Nexgen. 
Naposljetku, u prilog prethodno navedenim kliničkim podacima, nositelj odobrenja dostavio je podatke o kvaliteti u vezi s proizvodnim postupkom za lijekove Kogenate Bayer i Helixate Nexgen.
In addition, the PRAC noted an update from the on-going EUHASS data, and results showed an inhibitor incidence for Kogenate Bayer and Helixate Nexgen comparable to other products: whereas no adjustment for known risk factors for inhibitor development could be performed due to the study design, the PRAC noted that the 95 % CIs of the point estimates of PUP inhibitor incidence were overlapping substantially between different products. 
Nadalje, PRAC je skrenuo pozornost na ažuriranje iz kontinuiranih podataka ispitivanja EUHASS, a rezultati su dokazali incidenciju inhibitora za lijekove Kogenate Bayer i Helixate Nexgen koja je usporediva s drugim proizvodima: budući da zbog dizajna ispitivanja nisu bila moguća podešavanja poznatog faktora rizika za razvoj inhibitora, PRAC je uočio da se 95 % CI-ova točke procjene incidencije inhibitora u PUP-ova značajno preklapalo između različitih lijekova.
The amendments to the relevant sections of the Summary of Product Characteristics and package leaflet are set out in Annexes I and III. 
Izmjene relevantnih dijelova sažetka opisa svojstava lijeka i upute o lijeku navedene su u Dodacima I i III.
The objective of the RODIN/Pednet study was to examine the inhibitor development in PUPs with severe haemophilia A given recombinant or plasma-derived FVIII products. 
Cilj ispitivanja RODIN/Pednet bio je ispitati razvoj inhibitora u PUP-ova koji boluju od ozbiljne hemofilije A, a koji primaju rekombinantni faktor VIII ili faktor VIII dobiven iz plazme.
The MAH provided data on the above-mentioned observational studies with regards to the risk of inhibitor development in PUPs receiving FVIII products, including KOGENATE Bayer/Helixate NexGen. 
Nositelj odobrenja dostavio je podatke o prethodno navedenim opservacijskim ispitivanjima u vezi s rizikom razvoja inhibitora u PUP-a koji su primali lijekove koji sadrže FVIII, uključujući KOGENATE Bayer/Helixate NexGen.
Kogenate Bayer/Helixate NexGen are indicated for treatment and prophylaxis of bleeding in patients with hemophilia A (congenital factor VIII deficiency). 
Kogenate Bayer/Helixate NexGen indicirani su za liječenje i profilaksu krvarenja u bolesnika oboljelih od hemofilije A (prirođenog nedostatka faktora VIII).
Following the provisions under Article 20 of Regulation (EC) No 726/2004, the CHMP, having considered the PRAC recommendation dated 5 December 2013, is of the opinion that the marketing authorisations for Kogenate Bayer and Helixate NexGen should be varied as recommended by the PRAC. 
Uredbe (EZ) br. 726/2004, nakon što je razmotrio preporuku PRAC-a od 5. prosinca 2013., mišljenje je CHMP-a da se odobrenja za stavljanje u promet lijekova Kogenate Bayer i Helixate NexGen trebaju izmijeniti sukladno preporuci PRAC-a.
The PRAC considered results from the publication of the RODIN/PedNet study, the preliminary findings from the European Haemophilia Safety Surveillance System (EUHASS) registry and all available data submitted from clinical trials, observational studies, published literature as well as quality data for Kogenate Bayer and Helixate NexGen with regards to its potential risk of inhibitor development in previously untreated patients (PUPs) and minimally treated patients (MTPs). 
PRAC je razmotrio rezultate dostupne iz publikacija ispitivanja RODIN/PedNet, preliminarnih nalaza iz registra Europskog sustava za sigurnosni nadzor hemofilije (EUHASS), kao i sve dostupne podatke dostavljene iz kliničkih ispitivanja, opservacijskih ispitivanja, objavljene literature te podatke o kvaliteti za lijekove Kogenate Bayer i Helixate NexGen u vezi s njihovim potencijalnim rizikom od razvoja inhibitora u prethodno neliječenih bolesnika (PUP-ova) i minimalno liječenih bolesnika (MTP-ova).
• The PRAC considered the publication of the results of the RODIN/PedNet study, the preliminary findings from the European Haemophilia Safety Surveillance System (EUHASS) registry and all available data submitted from clinical trials, observational studies, published literature and quality data for Kogenate Bayer and Helixate NexGen with regards to its potential risk of inhibitor development in previously untreated patients (PUPs). 
• je PRAC razmotrio rezultate dostupne iz publikacija ispitivanja RODIN/PedNet, preliminarnih nalaza iz registra Europskog sustava za sigurnosni nadzor hemofilije (EUHASS), kao i sve dostupne podatke dostavljene iz kliničkih ispitivanja, opservacijskih ispitivanja, objavljene literature te podatke o kvaliteti za lijekove Kogenate Bayer i Helixate NexGen u vezi s njihovim potencijalnim rizikom od razvoja inhibitora u prethodno neliječenih bolesnika (PUP-ova),
• The PRAC noted that the efficacy of Kogenate Bayer/Helixate NexGen is not questioned and, on the basis of the available data, concluded that the current results do not confirm an increased risk of developing antibodies against Kogenate Bayer and Helixate NexGen when compared with other factor VIII products in PUPs with the bleeding disorder haemophilia A. 
NexGen nije upitna, te da je na temelju dostupnih podataka zaključio da aktualni rezultati ne potvrđuju povećani rizik od razvoja protutijela protiv lijeka Kogenate Bayer i Helixate NexGen u usporedbi s lijekovima faktora VIII u PUP-ova s poremećajem krvarenja hemofilije A,
Development of inhibitors against FVIII is the most significant complication of replacement therapy for haemophilia A. These antibodies inactivate the pro-coagulant activity of FVIII and inhibit patients' response to FVIII replacement therapy which may result in life-threatening bleedings and sequelae. 
Ova protutijela inaktiviraju prokoagulacijsko djelovanje faktora VIII i inhibiraju odgovor bolesnika na zamjensku terapiju faktorom VIII što može rezultirati krvarenjima i posljedicama opasnima po život.
Having noted the above, the PRAC concluded that the benefit-risk balance of Kogenate Bayer and Helixate NexGen indicated as for the treatment and prophylaxis of bleeding in patients with hemophilia A (congenital factor VIII deficiency) remains favourable subject to the changes to the product information agreed. 
Nakon što je istaknuo prethodno navedeno, PRAC je zaključio da omjer koristi i rizika lijekova Kogenate Bayer i Helixate NexGen indiciran za liječenje i profilaksu krvarenja u bolesnika oboljelih od hemofilije A (prirođenog nedostatka faktora VIII) ostaje povoljan i podliježe usuglašenim izmjenama informacija o lijeku.
The PRAC therefore concluded that the benefit-risk balance of Kogenate Bayer and Helixate NexGen indicated as for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency) remains favourable subject to the changes to the product information agreed. 
stoga je PRAC zaključio da omjer koristi i rizika lijekova Kogenate Bayer i Helixate NexGen indiciran za liječenje i profilaksu krvarenja u bolesnika oboljelih od hemofilije A (prirođenog nedostatka faktora VIII) ostaje povoljan i podliježe usuglašenim izmjenama informacija o lijeku.
J. Med. 368, 231 (2013)) were made available and seemed to suggest that Kogenate Bayer/Helixate NexGen were associated with an increased risk of inhibitor development in previously untreated patients (PUPs) when compared to another recombinant antihaemophilic factor VIII, after adjustment for confounding factors. 
NexGen povezani s povećanim rizikom od razvoja inhibitora u prethodno neliječenim bolesnicima (PUP-ima) prilikom usporedbe s drugim rekombinantnim koagulacijskim faktorom VIII, nakon podešavanja usporednih faktora.
In view of the above, the PRAC agreed that the current evidence does not confirm an increased risk of developing antibodies against Kogenate Bayer and Helixate NexGen when compared with other factor VIII products in PUPs with the bleeding disorder haemophilia A. However the PRAC considered that the frequency for inhibitor development in PUPs should be amended from “common” to “very common” in the section 4.8 of the SmPC and also recommended that the product information should be updated with results from the RODIN study as part of the routine risk minimisation activities. 
No, PRAC je zaključio da se učestalost za razvoj inhibitora u PUP-ova mora izmijeniti iz „često” u „vrlo često” u dijelu 4.8 SPC-a, te je preporučio da se informacije o lijeku ažuriraju rezultatima ispitivanja RODIN kao sastavni dio rutinskih aktivnosti za smanjivanje rizika.
In support of the above mentioned clinical data, the MAH provided information with regards to the manufacturing process (i.e. growth condition, purification) of Kogenate Bayer /Helixate Nexgen and discussed any change which took place since the studies 200021EU and 100074US. 
/Helixate Nexgen, te je raspravio sve izmjene koje su primijenjene nakon ispitivanja 200021EU i 100074US.
Further information on Cyramza can be found on the Agency's website: ema.europa.eu/medicines/human/EPAR/cyramza. 
Više informacija o lijeku Cyramza dostupno je na internetskim stranicama Agencije: ema.europa.eu/medicines/human/EPAR/cyramza.
Although the effects were modest, the size of the benefit was considered clinically relevant given the normally poor prognosis in these patients. 
Premda su učinci bili skromnih razmjera, opseg koristi od lijeka smatrao se klinički značajnim s obzirom na uobičajeno loše prognoze za te bolesnike.
Cyramza received a marketing authorisation valid throughout the EU on 19 December 2014. 
Lijek Cyramza dobio je odobrenje za stavljanje u promet koje je na snazi u EU-u od 19. prosinca 2014.
What measures are being taken to ensure the safe and effective use of Cyramza? 
Koje se mjere poduzimaju kako bi se osigurala sigurna i učinkovita primjena lijeka Cyramza?
What is Cyramza and what is it used for? 
Što je Cyramza i za što se koristi?
• hepatocellular carcinoma (a type of liver cancer) that is advanced or cannot be removed with surgery. 
• hepatocelularnog karcinoma (vrste raka jetre) koji je uznapredovao ili se ne može ukloniti kirurškim zahvatom.
• metastatic colorectal cancer (cancer of the large bowel that has spread to other parts of the body). 
• metastatskog kolorektalnog raka (raka debelog crijeva koji se proširio na ostale dijelove tijela).
Other information about Cyramza 
Ostale informacije o lijeku Cyramza
Cyramza is a cancer medicine used to treat adult patients with: 
Cyramza je lijek protiv raka koji se primjenjuje za liječenje odraslih osoba oboljelih od:
The European Medicines Agency decided that Cyramza's benefits are greater than its risks and it can be authorised for use in the EU. 
Europska agencija za lijekove zaključila je da koristi od lijeka Cyramza nadmašuju s njim povezane rizike te da lijek može biti odobren za primjenu u EU-u.
Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Cyramza have been included in the summary of product characteristics and the package leaflet. 
Preporuke i mjere opreza kojih se zdravstveni radnici i bolesnici trebaju pridržavati u cilju sigurne i učinkovite primjene lijeka Cyramza nalaze se u sažetku opisa svojstava i u uputi o lijeku.
By attaching to VEGFR, ramucirumab blocks this action, reducing the blood supply to the tumour and so slowing the growth of the cancer. 
Vezivanjem na VEGFR, ramucirumab blokira taj razvoj i time smanjuje dotok krvi u tumor, čime se usporava rast raka.
Side effects reported with Cyramza are carefully evaluated and any necessary action taken to protect patients. 
Nuspojave prijavljene za lijek Cyramza pažljivo se procjenjuju i poduzimaju se potrebne mjere za zaštitu bolesnika.
The safety profile of Cyramza is in line with that expected for other medicines blocking VEGFR activity and is considered manageable. 
Sigurnosni profil lijeka Cyramza u skladu je s očekivanim za druge lijekove koji blokiraju djelovanje VEGFR-a i moguće ga je kontrolirati.
As for all medicines, data on the use of Cyramza is continuously monitored. 
Kao i za sve lijekove, podatci o primjeni lijeka Cyramza kontinuirano se prate.
Why is Cyramza authorised in the EU? 
Zašto je lijek Cyramza odobren u EU-u?
An overview of Cyramza and why it is authorised in the EU 
Pregled informacija o lijeku Cyramza i zašto je odobren u EU-u
Cyramza contains the active substance ramucirumab. 
Cyramza sadrži djelatnu tvar ramucirumab.
VEGFRhelps in the development of new blood vessels that supply the tumours. 
Protein VEGFR pomaže u razvoju novih krvnih žila koje opskrbljuju tumore.
What are the risks associated with Cyramza? 
Koji su rizici povezani s lijekom Cyramza?
It can only be obtained with a prescription and treatment should be started and supervised by a specialist who has experience in the treatment of cancer. 
Lijek Cyramza izdaje se samo na recept, a liječenje mora započeti i nadzirati liječnik s iskustvom u liječenju raka.
When used for lung cancer, Cyramza must not be used when there is a cavity in the cancer or if the cancer is close to a major blood vessel. 
Kada se koristi za liječenje raka pluća, lijek Cyramza ne smije se primjenjivati ako rak u sebi ima šupljinu ili ako se nalazi blizu velike krvne žile.
• advanced gastric cancer (cancer of the stomach) or cancer of the area where the gullet (oesophagus) enters the stomach (known as gastro-oesophageal junction adenocarcinoma). 
• uznapredovalog raka želudca (gastričnog raka) ili raka dijela tijela u kojem jednjak (ezofagus) ulazi u želudac (poznat kao adenokarcinom gastroezofagealnog spoja).
• non-small cell lung cancer that is advanced or has spread to other parts of the body. 
• raka pluća nemalih stanica koji je uznapredovao ili se proširio na ostale dijelove tijela.
The most common side effects with Cyramza (which may affect more than 1 in 10 people) include tiredness or weakness, leucopenia (low white blood cell counts), neutropenia (low counts of a particular type of white blood cell), diarrhoea, nosebleeds and stomatitis (inflammation of the lining of the mouth). 
Najčešće nuspojave lijeka Cyramza (koje se mogu javiti u više od 1 na 10 osoba) jesu umor ili slabost, leukopenija (nizak broj bijelih krvnih stanica), neutropenija (nizak broj određene vrste bijelih krvnih stanica), proljev, krvarenja iz nosa i stomatitis (upala sluznice usne šupljine).
The benefit was smaller when Cyramza was given on its own, but this could still be an option when treatment with paclitaxel is not considered appropriate. 
Koristi od lijeka bile su manje ako se lijek Cyramza davao kao monoterapija, ali to može ostati kao mogućnost ako se davanje paklitaksela ne smatra primjerenim.
The dose of Cyramza and how often it is given depends on the patient's weight and the condition being treated. 
Doza i učestalost primjene lijeka Cyramza ovise o tjelesnoj težini bolesnika i stanju koje se liječi.
The active substance in Cyramza, ramucirumab, is a monoclonal antibody (a type of protein) designed to attach to vascular endothelial growth factor receptor (VEGFR), a protein present at high levels in tumours. 
Djelatna tvar u lijeku Cyramza, ramucirumab, monoklonsko je protutijelo (vrsta proteina) namijenjeno vezivanju na vaskularni endotelni faktor rasta (VEGFR), protein koji je prisutan u velikim količinama u tumorima.