natgillin/translations-raw huggingface dataset:
The CHMP conclusions in response to these points raised by the MAH are given below. 
Zaključki odbora CHMP v odziv na te točke, ki jih je izpostavil imetnik dovoljenja za promet z zdravilom, so podane spodaj.
However none of the arguments presented refute the conclusion derived from the results of the intranasal (and oral) studies, which suggests that that there is an increased risk of cancer associated with the use of calcitonin. 
Nobeden od predstavljenih argumentov pa ni zavrnil sklepa, izpeljanega iz rezultatov intranazalnih (in peroralnih) študij, kar nakazuje na obstoj povečanega tveganja raka, povezanega z uporabo kalcitonina.
The CHMP considered that BMD, is still regarded to be an important surrogate marker, which was shown to have a modest but statistically significant increase in comparison with placebo. 
Odbor CHMP je presodil, da se mineralna kostna gostota še vedno upošteva kot pomemben nadomestni označevalec, ki je dokazal zmerno, vendar statistično pomembno povečanje v primerjavi s placebom.
With regards to the use of injectable calcitonin in acute bone loss prevention, the evidence of efficacy is based on published literature. 
Pri uporabi kalcitonina za injiciranje za preprečevanje akutne izgube kostnine dokazi o učinkovitosti temeljijo na objavljeni literaturi.
The CHMP is of the view that it is not possible to reach a conclusion about the association between calcitonin and cancer progression from the results of the published non-clinical in vitro studies. 
Odbor CHMP je mnenja, da ni mogoče doseči zaključka v zvezi s povezavo med kalcitoninom in napredovanjem raka iz rezultatov objavljenih nekliničnih študij in vitro.
Data from the Sanofi-Aventis pharmacovigilance database and the Novartis Global Safety Database were also analysed to identify all cases mapping to the Neoplasms benign, malignant and unspecified system organ class (SOC). 
Prav tako so analizirali podatke iz farmakovigilančne zbirke podatkov družbe Sanofi-Aventis in globalne varnostne zbirke podatkov družbe Novartis, da bi odkrili vse primere skladno z organskim sistemom za benigne, maligne in nerazvrščene neoplazme.
For this purpose the methodology used was judged to be sufficient by the CHMP. 
Zato je odbor CHMP presodil, da je uporabljena metodologija zadostna.
The CHMP noted that the low reporting is not unexpected in this particular situation where the event under scrutiny (i.e malignancies), is not uncommon in the target population that otherwise receive a number of concomitant medications, where the risk increases with time making it very unlikely for physicians to establish a possible relation. 
Odbor CHMP je upošteval, da nizke stopnje poročanja v tej določeni situaciji niso pričakovane, saj dogodek, ki ga pregledujejo (tj. maligne bolezni) ni redek v ciljni populaciji, ki sicer prejema številna sočasna zdravila, pri katerih se tveganje povečuje s časom, zato je zelo malo verjetno, da bi zdravniki vzpostavili možno razmerje.
Based on these data, the CHMP confirmed the benefits of injectable calcitonin in the short term treatment of the Paget's disease. 
Na podlagi teh podatkov je odbor CHMP potrdil koristi kalcitonina za injiciranje pri kratkotrajnem zdravljenju Pagetove bolezni.
In this setting, the statistical significance is superseded by clinical relevance. 
V teh okoliščinah statistično pomembnost nadomesti klinična pomembnost.
• Safety aspects 
• Vidiki varnosti
• The Committee also took in to account that in patients with osteoporosis, intranasal calcitonin treatment is to be administered on a long-term basis. 
• odbor je prav tako upošteval, da je treba pri bolnikih z osteoporozo zdravljenje z intranazalnim kalcitoninom uporabljati dolgotrajno;
The CHMP considers that while this argument might be valid for the metaanalysis conducted on the studies with the oral formulations, it cannot be supported in the analysis with all intranasal trials where no clear heterogeneity is observed. 
Odbor CHMP upošteva, da čeprav je ta argument lahko upravičen za metaanalize, opravljene na študijah s peroralnimi formulacijami, ga ni mogoče podpreti v analizi z intranazalnimi preskušanji, kjer ni jasno ugotovljene heterogenosti.
Importantly, cancer mortality was again considerably higher in calcitonin treated patients in these trials compared to placebo; 7 cases (37.5%) compared to 2 (10.5%). 
Pomembna ugotovitev je bila, da je bila umrljivost zaradi raka v teh preskušanjih ponovno precej večja pri bolnikih, ki so jih zdravili s kalcitoninom, kot pri placebu; 7 primerov (37,5 %) v primerjavi z 2 primeroma (10,5 %).
Efficacy of calcitonin for this indication is supported by established use of calcitonin in clinical practice. 
Učinkovitost kalcitonina pri tej indikaciji je podprta z uveljavljeno uporabo kalcitonina v klinični praksi.
As mentioned before, it is agreed that the PROOF study shows a modest efficacy of calcitonin in the reduction of the risk of vertebral fractures. 
Kot že omenjeno, je sklenjeno, da študija PROOF prikazuje zmerno učinkovitost kalcitonina pri zmanjšanju tveganja za vertebralne zlome.
Possible explanations for these discrepant results include the lower dose in the osteoporosis trial, and the premature discontinuation of male patients and an intensive prostate cancer screening programme in the second osteoarthritis trial, which identified additional cases and may have masked possible imbalances of cancer cases across the different treatment arms in these trials. 
Morebitna razlaga za ta odstopanja pri rezultatih lahko vključuje manjši odmerek v preskušanju osteoporoze in prezgodnjo prekinitev sodelovanja moških ter intenzivni presejalni program za raka prostate v drugem preskušanju osteoartritisa, s katerim so odkrili dodatne primere in kar je lahko prikrilo morebitno neravnovesje pri primerih raka v različnih skupinah v teh preskušanjih.
However despite the likelihood that calcitonin is involved in cancer promotion the exact mechanism that could explain the increased occurrence of malignancies in calcitonin treated patients has not been fully elucidated. 
Kljub verjetnosti, da je kalcitonin vključen v spodbujanje raka, točnega mehanizma, s katerim bi lahko razložili povečano pojavnost malignih obolenj pri bolnikih, ki so se zdravili s kalcitoninom, ni mogoče popolnoma obrazložiti.
The Odds Ratio (OR) for the incidence of cancer in these trials in patients treated with calcitonin was 1.61 (1.11-2.34). 
Razmerje verjetnosti (Odds Ratio, OR) za incidenco raka v teh preskušanjih pri bolnikih, ki so jih zdravili s kalcitoninom, je bilo 1,61 (1,11-2,34).
A possible explanation, for the relatively short time of onset is that calcitonin promotes tumour progression rather than oncogenesis, as has also been suggested in the published literature addressing the role of calcitonin in prostate cancer. 
Morebitna razlaga za relativno kratek čas do pojava je, da kalcitonin spodbuja napredovanje tumorjev in ne onkogeneze, kot je bilo omenjeno tudi v objavljeni literaturi, ki obravnava vlogo kalcitonina pri raku prostate.
It was also agreed that periodic re-treatment may be considered in these patients taking into account the potential benefits and the association of cancer with long term calcitonin use. 
Prav tako se je strinjal, da se lahko pri takih bolnikih razmisli o občasnem ponovnem zdravljenju, pri čemer je treba upoštevati morebitne koristi ter povezavo raka in dolgotrajne uporabe kalcitonina.
In addition, the mortality analysis revealed that only patients treated with calcitonin died from cancer during these trials, which suggests that calcitonin accelerates tumour growth. 
Poleg tega je analiza umrljivosti pokazala, da so med temi preskušanji zaradi raka umrli samo bolniki, ki so se zdravili s kalcitoninom, kar kaže, da kalcitonin pospeši rast tumorjev.
• Treatment of osteoporosis in order to reduce the risk of vertebral fractures (intranasal formulation) 
• Zdravljenje osteoporoze za zmanjšanje tveganja vertebralnih zlomov (intranazalna formulacija)
The MAH addressed a number of non-clinical, pharmacovigilance, and statistical issues in relation to the CHMP assessment of the risk of cancer with the use of calcitonin-containing medicinal products. 
Imetnik dovoljenja za promet je obravnaval številna neklinična, farmakovigilančna in statistična vprašanja v zvezi z oceno odbora CHMP glede ocene tveganja raka ob uporabi zdravil, ki vsebujejo kalcitonin.
The consistency of the evidence across clinical trial data, provide strong evidence of a causal association. 
Skladnost dokazov pri vseh podatkih kliničnih preskušanj je trden dokaz za vzročno povezavo.
While this argument might be valid for observational studies, the CHMP is of the view that potential bias in randomised clinical trials that could favour one of the treatment arms is unlikely, as the randomisation procedure provides sufficiently well balanced groups. 
Čeprav je ta argument morda upravičen za opazovalne študije, je odbor CHMP mnenja, da bi možna pristranost v randomiziranih kliničnih preskušanjih malo verjetno lahko privilegirala enega od krakov zdravljenja, saj postopek randomizacije omogoča zadovoljivo uravnotežene skupine.
Based on the totality of the data available on the safety and the efficacy of intranasal calcitonincontaining medicinal products and having noted the opinion of the Ad-Hoc Expert meeting, the CHMP confirmed its initial conclusion that the limited efficacy in this indication needs to be balanced against evidence from clinical trials for an increased risk of cancer with long-term use of calcitonin. 
Na podlagi vseh podatkov, ki so na voljo glede varnosti in učinkovitosti intranazalnih zdravil, ki vsebujejo kalcitonin in ob upoštevanju mnenja ad-hoc sestanka strokovnjakov, je odbor CHMP potrdil svoj začetni sklep, da je treba omejeno učinkovitost za to indikacijo uravnovesiti z dokazi kliničnih preskušanj za povečano tveganje raka ob dolgoročni uporabi kalcitonina.
The MAH also raised some points on the methodological flaws of the meta-analysis of the 17 intranasal calcitonin studies and provided a re-analysis of data. 
Imetnik dovoljenja za promet je izpostavil tudi nekatere točke v zvezi z metodološkimi pomanjkljivostmi metaanalize 17 študij intranazalnega kalcitonina in poskrbel za ponovno analizo podatkov.
Although these studies in isolation were considered so far insufficient to establish a causal association due to some important limitations and the lack of any robust evidence of risk in humans, they assume a new significance in light of the more recent data from the calcitonin clinical trials. 
Čeprav menijo, da so te študije kot posamezne študije nezadostne za potrditev vzročne povezave zaradi nekaterih pomembnih omejitev in pomanjkanja trdnih dokazov o tveganju pri človeku, pa predstavljajo novo pomembnost z vidika novejših podatkov iz kliničnih preskušanj kalcitonina.
Even though there is some uncertainty surrounding the true magnitude of this risk which appears to be different across the different trials the relative risk is consistently higher in patients treated with calcitonin compared with placebo. 
Kljub temu obstaja nekaj negotovosti glede resnične razsežnosti tega tveganja, za katero se zdi, da je različno med različnimi preskušanji, saj je relativno tveganje v primerjavi s placebom dosledno večje pri bolnikih, ki se zdravijo s kalcitoninom.
The increase in absolute risk of cancer for patients treated with calcitonin compared with placebo in the intra-nasal trials was 2.36%. 
Povečanje absolutnega tveganja raka pri bolnikih, ki so se zdravili s kalcitoninom, v primerjavi s placebom je bilo v preskušanjih intranazalne formulacije 2,36-odstotno.
The consistency of the results in the oral and intranasal trials suggests that the reported events are causally associated with calcitonin. 
Skladnost rezultatov v preskušanjih peroralne in intranazalne formulacije kaže, da so poročani dogodki vzročno povezani s kalcitoninom.
Annex II Scientific conclusions and grounds for variation to the terms of the marketing authorisations of the injectable formulations of calcitonin and suspension of the marketing authorisations of the intranasal formulations of calcitonin 
Dodatek II Znanstveni zaključki in podlaga za spremembo pogojev dovoljenj za promet s formulacijami kalcitonina za injiciranje in začasni umik dovoljenj za promet z intranazalnimi formulacijami kalcitonina
In addition, the metaanalysis of the trials with the new formulation showed a statistical significant increase in the incidence rate ratio for patients treated with calcitonin, 1.33 (1.035-1.72), similar to the increase observed during the intranasal trials. 
Poleg tega je meta analiza preskušanj z novo formulacijo pokazala statistično pomembno povečanje razmerja incidence pri bolnikih, ki so se zdravili s kalcitoninom, 1,33 (1,035-1,72), kar je bilo podobno povečanju, ki so ga opazili v preskušanjih intranazalne formulacije.
Further evidence of a positive association between calcitonin and cancer was provided from the analysis of recently conducted trials with the new oral calcitonin formulation. 
Nadaljnji dokazi pozitivne povezanosti kalcitonina in raka izhajajo iz analize nedavno izvedenih preskušanj z novo peroralno formulacijo kalcitonina.
The indication of fracture prevention in osteoporosis, is supported by results from a reasonably sized, placebo controlled double blind study known as the PROOF (Prevent Recurrence of Osteoporotic Fractures) study. 
Indikacijo za preprečevanje zlomov pri osteoporozi podpirajo rezultati razumno velike, s placebom nadzorovane, dvojno slepe študije, imenovane PROOF (Prevent Recurrence of Osteoporotic Fractures - Preprečevanje ponovitve osteoporotičnih zlomov).
Further evidence of a possible association between calcitonin and the risk of cancer is provided by a meta-analysis of 17 randomised, controlled, double blind studies with intranasal calcitonin performed by one of the MAHs. 
Nadaljnje dokaze o morebitni povezavi med kalcitoninom in tveganjem raka je predložila meta analiza 17 randomiziranih, nadzorovanih, dvojno slepih študij z intranazalnim kalcitoninom, ki jih je opravil eden od imetnikov dovoljenja za promet z zdravilom.
• The Committee is of the opinion that data from clinical studies provide evidence for an increased risk of cancer with long-term use of calcitonin. 
• odbor meni, da podatki iz kliničnih študij omogočajo dokaze za povečano tveganje raka ob dolgotrajni uporabi kalcitonina.
In order to maintain a positive benefit/risk balance for the indications of injectable formulation of calcitonin-containing products, the CHMP recommended changes to the Product Information, mainly in relation to the risk of cancer. 
Da se vzdržuje pozitivno razmerje med tveganji in koristmi pri indikacijah formulacije za injiciranje pri zdravilih, ki vsebujejo kalcitonin, odbor CHMP priporoča spremembe v informacijah o zdravilu, predvsem v povezavi s tveganjem raka.
Considering the nature of the indication in the setting of advanced cancer, the benefit/risk balance in this indication is considered still to be positive. 
Glede na značaj indikacije pri napredovalem raku se razmerje med tveganji in koristmi pri tej indikaciji še vedno šteje kot pozitivno.
However, the short-term nature of the intended use of calcitonin in these patients is expected to minimise the potential risk of cancer, and therefore the benefit/risk balance is considered to be positive, but the treatment duration should be limited. 
Kljub temu se pričakuje, da bo kratkotrajni značaj predvidene uporabe kalcitonina pri teh bolnikih zmanjšal morebitno tveganje raka, zato je razmerje med tveganji in koristmi pozitivno, vendar se trajanje zdravljenja ne sme preseči.
• The Committee in light of the previous review and in the absence of new efficacy data, considered that the intranasal calcitonin-containing medicines can be effective in the treatment of established postmenopausal osteoporosis in order to reduce the risk of vertebral fractures. 
• glede na prejšnji pregled in odsotnost novih podatkov o učinkovitosti odbor meni, da so lahko intranazalna zdravila, ki vsebujejo kalcitonin, učinkovita za zdravljenje potrjene postmenopavzalne osteoporoze zaradi zmanjševanja tveganja vertebralnih zlomov.
In addition to the published literature in relation to the use of injectable calcitonin for hypercalcaemia in malignancy, this indication is further supported by its established use in clinical practice. 
Poleg objavljene literature, povezane z uporabo kalcitonina za injiciranje pri zdravljenju hiperkalciemije pri malignih boleznih, to indikacijo nadalje podpira uveljavljena uporaba kalcitonina v klinični praksi.
The most commonly reported malignancy in this study was prostate cancer. 
Maligno obolenje, o katerem so v tej študiji poročali najpogosteje, je bil rak prostate.
The increased risk of cancer with calcitonin in the other two trials with the new oral formulation, was not statistically significant incidence rate ratio of 1.61 (0.81-3.16) and 1.10 (0.821.48) for studies C2302 and A2303 respectively. 
Povečano tveganje raka pri uporabi kalcitonina v drugih dveh preskušanjih nove peroralne formulacije ni bilo statistično pomembno; razmerje incidence v študiji C2302 je bilo 1,61 (0,81-3,16) in v študiji A2303 1,10 (0,82-1,48).
• Treatment of hypercalcaemia of malignancy (injectable formulation) 
• Zdravljenje hiperkalciemije pri malignem obolenju (formulacija za injiciranje)
The limited efficacy data in this indication need to be balanced against an increased risk of cancer as demonstrated in the analysis of calcitonin trials. 
Omejene podatke o učinkovitosti pri tej indikaciji je treba pretehtati glede na povečano tveganje raka, kot je pokazala analiza preskušanj kalcitonina.
The results of the biggest of the trials conducted with intra-nasal calcitonin , study CT320 (also known as the PROOF study), provides some evidence of an increased risk of cancer in the calcitonin arm compared with placebo even though the reported results fail to reach statistical significance (relative risk, 95%CI: 1.47 (0.91-2.36)). 
Rezultati največjega preskušanja z intranazalnim kalcitoninom, študije CT320 (imenovane tudi študija PROOF), so dali nekaj dokazov o povečanem tveganju raka v skupini s kalcitoninom v primerjavi s placebom, čeprav poročani rezultati niso dosegli statistične pomembnosti (relativno tveganje, 95-odstotni IZ: 1,47 (0,91-2,36)).
Recognising the potential limitations of the clinical trials included in the analysis, the observed increased risk of cancer needs to be balanced against the modest benefit of calcitonin. 
Ob prepoznavi potencialnih omejitev kliničnih preskušanj, vključenih v analizo, je treba ugotovljeno povečano tveganje raka uravnotežiti glede na zmerno korist kalcitonina.
The MAH considers that the exclusion of four studies from the meta-analysis in which no cancer cases were observed, lacks basis. 
Imetnik dovoljenja za promet z zdravilom meni, da je izključitev štirih študij iz metaanalize, v kateri niso ugotovili primerov raka, neutemeljena.
However the PSA analysis alone is of limited value as it is known that factors other than prostate cancer can influence PSA values and cannot explain the higher incidence of prostate cancer in patients treated with calcitonin. 
Vendar ima sama analiza PSA omejeno vrednost, saj je znano, da lahko na ravni PSA vplivajo tudi drugi dejavniki, ne samo rak prostate, in da z njo ni mogoče razložiti večje incidence raka prostate pri bolnikih, ki so se zdravili s kalcitoninom.
Its hypocalcaemic properties are mediated primarily through the inhibition of osteoclast-mediated bone resorption. 
Njegove hipokalcemične lastnosti so predvsem posledica zaviranja kostne resorpcije, ki jo povzročajo osteoklasti.
Considering the availability of alternative treatments in this indication, the CHMP agreed that the use of calcitonin in Paget's disease should be limited to 3 months, and only in patients who do not respond to alternative treatments or for whom such treatments are not suitable, for example those with severe renal impairment. 
Glede razpoložljivosti drugih oblik zdravljenja pri tej indikaciji se je odbor CHMP strinjal, da je treba uporabo kalcitonina pri Pagetovi bolezni omejiti na 3 mesece, in to samo pri bolnikih, ki se ne odzivajo na druge oblike zdravljenja ali pri katerih take oblike zdravljenja niso primerne, na primer pri bolnikih z ledvično okvaro.
The MAH questions the results of the meta-analysis because of the use of fixed-effects models in the presence of heterogeneity. 
Imetnik dovoljenja za promet z zdravilom dvomi v rezultate metaanalize zaradi uporabe modelov s fiksnimi učinki v prisotnosti heterogenosti.
As a result, an intensive posthoc prostate cancer screening programme was implemented for all male participants in the two osteoarthritis trials. 
Zaradi tega so pri vseh moških udeležencih dveh preskušanj osteoartritisa uvedli intenzivni post-hoc presejalni program za raka prostate.
In the first of these trials (study C2301), a statistical significant increased risk of cancer was reported in patients treated with calcitonin compared with placebo (incidence rate ratio 4.13 (1.67-10.19)). 
V prvem od teh preskušanj (študiji C2301) so pri bolnikih, ki so se zdravili s kalcitoninom, v primerjavi s placebom poročali o statistično pomembno povečanem tveganju raka (razmerje incidence 4,13 (1,67-10,19)).
In November 2010, preliminary safety findings relating to prostate cancer were observed during two clinical trials for the new oral formulation of calcitonin. 
Novembra 2010 so med dvema kliničnima preskušanjema peroralne formulacije kalcitonina opazili preliminarne varnostne ugotovitve, povezane z rakom prostate.
The most commonly reported malignancies in these trials were basal cell carcinoma and breast cancer. 
Maligni obolenji, o katerih so najpogosteje poročali v teh preskušanjih, sta bila bazalnocelični karcinom in rak dojke.
As discussed previously the efficacy of calcitonin in the treatment of Paget's disease is limited and is partially validated by its well known use and its pharmacological plausibility. 
• Zdravljenje Pagetove bolezni (formulacija za injiciranje) Kot že omenjeno, je učinkovitost kalcitonina pri zdravljenju Pagetove bolezni omejena ter je delno validirana z njegovo dobro znano uporabo in farmakološko verodostojnostjo.
The MAH discussed the low number of post-marketing spontaneous cases of cancer reported with calcitonin. 
Imetnik dovoljenja za promet z zdravilom je razpravljal o nizkem številu spontanih primerov raka o katerih so poročali v zvezi s kalcitoninom po dajanju zdravila na trg.
From the meta-analysis of the intranasal calcitonin studies, the data point towards an increase in the risk of cancer in patients treated with intranasal calcitonin compared to placebo. 
Podatki metaanalize študij intranazalnega kalcitonina kažejo na povečano tveganje raka pri bolnikih, zdravljenih z intranazalnim kalcitoninom, v primerjavi s placebom.
The Committee concluded that the benefit-risk balance of calcitonin-containing injectable formulations indicated in the treatment of Paget's disease, hypercalcaemia of malignancy and for the prevention of acute bone loss due to sudden immobilisation, remains positive under normal conditions of use, subject to the restrictions in indication (for Paget's disease), limitation of treatment duration and warnings to be introduced in the product information. 
Odbor je sklenil, da razmerje med tveganji in koristmi pri formulacijah za injiciranje, ki vsebujejo kalcitonin, indiciranih za zdravljenje Pagetove bolezni, hiperkalciemije pri malignih obolenjih in za preprečevanje akutne kostne izgube zaradi nenadne imobilizacije, ostaja pozitivno pri normalnih pogojih uporabe ter če se upoštevajo omejitve pri indikaciji (pri Pagetovi bolezni), omejitev trajanja zdravljenja in opozorila, ki bodo dodana informacijam o zdravilu.
• Efficacy aspects 
• Vidiki učinkovitosti