FrancophonIA/ELRC3.0 huggingface dataset:
English: 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.
Slovenian: 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.
English: 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.
Slovenian: 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.
English: 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.
Slovenian: 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.
English: 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.
Slovenian: 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.
English: 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.
Slovenian: 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.
English: The increase in absolute risk of cancer for patients treated with calcitonin compared with placebo in the intra-nasal trials was 2.36%.
Slovenian: 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.
English: The consistency of the results in the oral and intranasal trials suggests that the reported events are causally associated with calcitonin.
Slovenian: Skladnost rezultatov v preskušanjih peroralne in intranazalne formulacije kaže, da so poročani dogodki vzročno povezani s kalcitoninom.
English: 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
Slovenian: 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
English: 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.
Slovenian: 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.
English: 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.
Slovenian: Nadaljnji dokazi pozitivne povezanosti kalcitonina in raka izhajajo iz analize nedavno izvedenih preskušanj z novo peroralno formulacijo kalcitonina.
English: 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.
Slovenian: 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).
English: 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.
Slovenian: 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.
English: • 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.
Slovenian: • odbor meni, da podatki iz kliničnih študij omogočajo dokaze za povečano tveganje raka ob dolgotrajni uporabi kalcitonina.
English: 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.
Slovenian: 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.
English: 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.
Slovenian: Glede na značaj indikacije pri napredovalem raku se razmerje med tveganji in koristmi pri tej indikaciji še vedno šteje kot pozitivno.
English: 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.
Slovenian: 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.
English: • 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.
Slovenian: • 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.
English: 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.
Slovenian: 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.
English: The most commonly reported malignancy in this study was prostate cancer.
Slovenian: Maligno obolenje, o katerem so v tej študiji poročali najpogosteje, je bil rak prostate.
English: 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.
Slovenian: 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).
English: • Treatment of hypercalcaemia of malignancy (injectable formulation)
Slovenian: • Zdravljenje hiperkalciemije pri malignem obolenju (formulacija za injiciranje)
English: 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.
Slovenian: Omejene podatke o učinkovitosti pri tej indikaciji je treba pretehtati glede na povečano tveganje raka, kot je pokazala analiza preskušanj kalcitonina.
English: 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)).
Slovenian: 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)).
English: 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.
Slovenian: Ob prepoznavi potencialnih omejitev kliničnih preskušanj, vključenih v analizo, je treba ugotovljeno povečano tveganje raka uravnotežiti glede na zmerno korist kalcitonina.
English: The MAH considers that the exclusion of four studies from the meta-analysis in which no cancer cases were observed, lacks basis.
Slovenian: Imetnik dovoljenja za promet z zdravilom meni, da je izključitev štirih študij iz metaanalize, v kateri niso ugotovili primerov raka, neutemeljena.
English: 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.
Slovenian: 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.
English: Its hypocalcaemic properties are mediated primarily through the inhibition of osteoclast-mediated bone resorption.
Slovenian: Njegove hipokalcemične lastnosti so predvsem posledica zaviranja kostne resorpcije, ki jo povzročajo osteoklasti.
English: 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.
Slovenian: 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.
English: The MAH questions the results of the meta-analysis because of the use of fixed-effects models in the presence of heterogeneity.
Slovenian: Imetnik dovoljenja za promet z zdravilom dvomi v rezultate metaanalize zaradi uporabe modelov s fiksnimi učinki v prisotnosti heterogenosti.
English: As a result, an intensive posthoc prostate cancer screening programme was implemented for all male participants in the two osteoarthritis trials.
Slovenian: Zaradi tega so pri vseh moških udeležencih dveh preskušanj osteoartritisa uvedli intenzivni post-hoc presejalni program za raka prostate.
English: 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)).
Slovenian: 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)).
English: In November 2010, preliminary safety findings relating to prostate cancer were observed during two clinical trials for the new oral formulation of calcitonin.
Slovenian: Novembra 2010 so med dvema kliničnima preskušanjema peroralne formulacije kalcitonina opazili preliminarne varnostne ugotovitve, povezane z rakom prostate.
English: The most commonly reported malignancies in these trials were basal cell carcinoma and breast cancer.
Slovenian: Maligni obolenji, o katerih so najpogosteje poročali v teh preskušanjih, sta bila bazalnocelični karcinom in rak dojke.
English: 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.
Slovenian: • 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.
English: The MAH discussed the low number of post-marketing spontaneous cases of cancer reported with calcitonin.
Slovenian: 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.
English: 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.
Slovenian: Podatki metaanalize študij intranazalnega kalcitonina kažejo na povečano tveganje raka pri bolnikih, zdravljenih z intranazalnim kalcitoninom, v primerjavi s placebom.
English: 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.
Slovenian: 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.
English: • Efficacy aspects
Slovenian: • Vidiki učinkovitosti
English: • The Committee considered that in order to maintain a positive benefit-risk for the above indications additional changes to the product information (section 4.2 Posology and method of administration, section 4.4 Special warnings and precautions for use and section 4.8 Undesirable effects) in relation to the risk of cancer should be included.
Slovenian: • odbor meni, da je treba za vzdrževanje pozitivnega razmerja med tveganji in koristmi za zgoraj navedene indikacije dodati spremembe v informacije o zdravilu (v poglavje 4.2 Odmerjanje in način uporabe, poglavje 4.4 Posebna opozorila in previdnostni ukrepi za uporabo in poglavje 4.8 Neželeni učinki), povezane s tveganjem raka; zato je odbor priporočil spremembo dovoljenja za promet z zdravili, ki vsebujejo kalcitonin (formulacijami za injiciranje), skladno s spremembami informacij o zdravilu, kot je določeno v Prilogi III mnenja odbora CHMP.
English: The MAH argued that the improvement in bone mineral density (BMD) underestimates fracture efficacy.
Slovenian: Imetnik dovoljenja za promet z zdravilom je trdil, da izboljšanje mineralne kostne gostote podcenjuje učinkovitost glede zlomov.
English: • In view of the new safety concerns in relation to the risk of cancer in long-term use and the limited efficacy of calcitonin in the treatment of osteoporosis, the Committee is of the opinion that pursuant to Article 116 of Directive 2001/83/EC the benefit-risk balance of the intranasal formulations of calcitonin-containing medicinal products is not positive under normal conditions of use.
Slovenian: • odbor glede na nove varnostne težave, povezane s tveganjem raka pri dolgotrajni uporabi, in omejeno učinkovitost kalcitonina pri zdravljenju osteoporoze skladno s 116. členom Direktive 2001/83/ES meni, da razmerje med tveganji in koristmi pri intranazalnih formulacijah zdravil, ki vsebujejo kalcitonin, v normalnih pogojih uporabe ni pozitivno; je odbor priporočil začasen umik dovoljenj za promet z intranazalno formulacijo kalcitonina.
English: Overall there appears to be sufficient and consistent evidence from the intranasal and oral calcitonin trials, that calcitonin is associated with an increased risk of cancer.
Slovenian: Na splošno se zdi, da so dokazi iz preskušanj intranazalnega in peroralnega kalcitonina, da je kalcitonin povezan s povečanim tveganjem raka, zadostni in skladni.
English: The re-examination of the CHMP opinion was related to the benefit-risk balance of the intranasal formulation of calcitonin in the indication “treatment of osteoporosis in order to reduce the risk of vertebral fractures”.
Slovenian: Ponovna presoja mnenja odbora CHMP je bila povezana z razmerjem med tveganji in koristmi intranazalne formulacije kalcitonina v indikaciji „zdravljenje osteoporoze za zmanjšanje tveganja vertebralnih zlomov“.
English: It is also pointed out by the MAH that the point estimate OR is used, which is more likely to provide a significant result than the corresponding RR.
Slovenian: Prav tako je imetnik dovoljenja za promet z zdravilom opozoril, da je uporabljena točkovna ocena razmerja verjetnosti, ki bolj verjetno poda pomemben rezultat od ustrezne RR.
English: Concerns of a possible association between calcitonin and prostate cancer have been raised and considered at different times.
Slovenian: V različnih obdobjih so bili izpostavljeni in obravnavani pomisleki glede povezave med kalcitoninom in rakom prostate.
English: For the lifting of the suspension the MAH(s) should provide new randomised controlled data that will be able to robustly demonstrate that the benefits of calcitonin-containing medicines outweigh their risks in patients with osteoporosis and taking into account the increased risk of cancer and cancer mortality associated with long term use of calcitonin.
Slovenian: Za preklic začasnega umika mora(jo) imetnik(i) predložiti nove randomizirane nadzorovane podatke, ki bodo stabilno pokazali, da so koristi zdravil, ki vsebujejo kalcitonin, večje od tveganj pri bolnikih z osteoporozo, pri čemer mora(jo) upoštevati povečano tveganje raka in umrljivost zaradi raka, povezana z dolgotrajno uporabo kalcitonina.
English: • Prevention of acute bone loss due to sudden immobilisation such as in patients with recent osteoporotic fractures (injectable formulation)
Slovenian: • Preprečevanje akutne izgube kostnine zaradi nenadne imobilizacije, kot denimo pri bolnikih z nedavnimi osteoporotičnimi zlomi (formulacija za injiciranje) Za to indikacijo so na voljo samo omejeni dokazi o učinkovitosti.
English: However, in all trials there was a higher incidence of malignancies reported in calcitonin treated patients compared to placebo.
Slovenian: Vendar pa je bila incidenca malignih obolenj v vseh preskušanjih večja pri bolnikih, ki so se zdravili s kalcitoninom, kot pri placebu.
English: in patients with impending pathologic fracture, the CHMP agreed that the treatment duration may be extended up to a recommended maximum of 6 months.
Slovenian: Odbor CHMP se je strinjal, da se lahko v izjemnih okoliščinah, na primer pri bolnikih z neizogibnim patološkim zlomom, trajanje zdravljenja podaljša na priporočenih največ 6 mesecev.
English: Considering the limited evidence of efficacy, the risk of cancer associated with the use of calcitonin, and the long term duration of treatment required for this indication, the benefit risk balance for the intranasal formulation of calcitonin for the treatment of osteoporosis in order to reduce the risk of vertebral fractures, which is the only indication for this pharmaceutical form, is considered to be negative.
Slovenian: Glede na omejene dokaze o učinkovitosti, tveganje raka, povezano z uporabo kalcitonina, in dolgotrajno trajanje zdravljenja, potrebno za to indikacijo, je razmerje med tveganji in koristmi za intranazalno formulacijo kalcitonina za zdravljenje osteoporoze za zmanjšanje tveganja vertebralnih zlomov, ki je edina indikacija za to farmacevtsko obliko, negativno.
English: Considering the limited evidence of efficacy, the risk of cancer with the use of calcitonin, and the long term duration of treatment required for this indication, the benefit risk balance for the intranasal formulation of calcitonin for the treatment of osteoporosis in order to reduce the risk of vertebral fractures, which is the only indication for this pharmaceutical form, is considered to be negative.
Slovenian: Ob upoštevanju omejenih dokazov o učinkovitosti, tveganja raka ob uporabi kalcitonina in dolgoročnosti zdravljenja, ki je potrebno za to indikacijo, je razmerje med tveganji in koristmi za intranazalno formulacijo kalcitonina za zdravljenje osteoporoze za zmanjšanje tveganja vertebralnih zlomov, ki je edina indikacija za to farmacevtsko obliko, upoštevano kot negativno.
English: The Committee also concluded that the benefit-risk balance of calcitonin-containing intranasal formulation indicated for the treatment of osteoporosis is no longer positive under normal conditions of use and recommends the suspension of the corresponding marketing authorisations.
Slovenian: Odbor je prav tako sklenil, da razmerje med tveganji in koristmi pri intranazalni formulaciji, ki vsebuje kalcitonin, indicirani za zdravljenje osteoporoze, ni več pozitivno pri normalnih pogojih uporabe ter priporoča začasen umik zadevnih dovoljenj za promet z zdravilom.
English: Grounds for the suspension of the marketing authorisation for the intranasal calcitonincontaining medicinal products Whereas
Slovenian: Podlaga za začasen umik dovoljenja za promet z intranazalnimi zdravili, ki vsebujejo kalcitonin Ob upoštevanju naslednjega:
English: Calcitonin is a hypocalcaemic compound secreted from the thyroid.
Slovenian: Kalcitonin je hipokalcemična snov, ki jo izloča ščitnica.
English: Overall conclusion of the re-examination procedure The scope of the re-examination was the benefit/risk of intranasal formulation of calcitonin-containing medicinal products in the indication of “treatment of osteoporosis in order to reduce the risk of vertebral fractures”.
Slovenian: Obseg ponovne presoje je bilo razmerje med tveganji in koristmi intranazalne formulacije zdravil, ki vsebujejo kalcitonin v indikaciji „zdravljenje osteoporoze za zmanjšanje tveganja vertebralnih zlomov“.