natgillin/translations-raw huggingface dataset:
Another factor that could explain low reporting rate is the fact that calcitonin have been authorised for nearly 40 years.
Drug dejavnik, ki bi lahko razložil nizko stopnjo poročanja, pa je dejstvo, da je kalcitonin odobren že skoraj 40 let.
Parenteral formulations of calcitonin were first licensed in Europe in 1973.
Parenteralne formulacije kalcitonina so bile v Evropi prvič odobrene leta 1973.
One IU corresponds to approximately 0.2μg of synthetic salmon calcitonin.
Ena i.e. ustreza približno 0,2 μg sintetičnega lososovega kalcitonina.
The CHMP also consulted a group of experts on 6 November 2012 to gain their view on a number issues.
Odbor CHMP se je 6. novembra 2012 posvetoval tudi s skupino strokovnjakov, da je pridobil njihov pogled na izpostavljena vprašanja.
Overall summary of the scientific evaluation of calcitonin-containing medicinal products (see Annex I)
Splošni povzetek znanstvenega vrednotenja zdravil, ki vsebujejo kalcitonin (glejte Prilogo I)
Moreover, beyond any discussion of whether the statistical significance is achieved in some cases or not, there is an evident, consistent and clear trend of an increased risk of cancer.
Poleg tega mimo vseh razprav o tem, ali je v nekaterih primerih dosežena statistična pomembnost ali ne, obstaja očiten, konsistenten in jasen trend povečanega tveganja raka.
As expected, the risk of cancer increases when excluding the four studies with no events.
Po pričakovanjih se tveganje raka poveča, če izključimo štiri študije brez dogodkov.
The issue was however kept under close monitoring.
Skrbno spremljanje te težave se je zato nadaljevalo.
The product can be administered intramuscularly, subcutaneously or intravenously.
Zdravilo se lahko uporablja intramuskularno, subkutano ali intravensko.
The intranasal formulation is available at 100 or 200 International Units (IU)/ml.
Intranazalna formulacija je na voljo v odmerku 100 ali 200 mednarodnih enot (i.e.)/ml.
A reduction in hip fractures has not been demonstrated.
Zmanjšanja kolčnih zlomov niso pokazali.
In view of the safety concerns the CHMP was of the view that it was necessary to restrict the target population for this indication.
Glede varnostnih težav je odbor CHMP menil, da je nujno omejiti ciljno populacijo za to indikacijo.
For Paget's disease, the evidence of efficacy is based on published literature of a number of small studies, where the treatment duration was in most cases between 3-18 months.
Pri Pagetovi bolezni dokazi o učinkovitosti temeljijo na objavljeni literaturi iz številnih majhnih študij, v katerih je zdravljenje večinoma trajalo od 3 do 18 mesecev.
Concerns on the efficacy of certain indications were previously raised, which resulted in a referral under Article 12 of Directive 75/319/EC (corresponding to Article 31 of Directive 2001/83/EC) in 2000.
Pred tem so se pojavili pomisleki glede učinkovitosti nekaterih indikacij, zaradi česar je bil leta 2000 sprožen napotitveni postopek v skladu z 12. členom Direktive 75/319/ES (kar ustreza 31. členu Direktive 2001/83/ES).
Non-clinical aspects
Neklinična vprašanja
However, review of available data at the time by National Competent Authorities did not indicate a causal relationship.
Vendar pa takratni pregled razpoložljivih podatkov, ki so ga opravili nacionalni pristojni organi, ni pokazal vzročne povezave.
Since 1987 calcitonin has also been available as an intranasal formulation.
Od leta 1987 je kalcitonin na voljo v obliki intranazalne formulacije.
The MAH also discusses the lack of causality based on the Bradford-Hill criteria, which have been taken into account and assessed.
Imetnik dovoljenja za promet z zdravilom razpravlja tudi o pomanjkanju vzročnosti na podlagi kriterijev Bradford-Hill, ki so bili upoštevani in ocenjeni.
Therefore, the scarce number of cases of cancer in patients who are or have been treated with calcitonin that are found in global safety databases cannot lead to any conclusions, mainly when balanced against data coming from clinical trials.
Zato skromno število primerov raka pri bolnikih, ki so ali ki so bili zdravljeni s kalcitoninom, ki jih je najti v svetovnih bazah podatkov o varnosti, ne more voditi v zaključke, še posebej kadar so uravnoteženi s podatki iz kliničnih preizkušanj.
The majority of the cancer cases reported in the calcitonin trials occurred after 12 months of treatment.
Večina primerov raka, o katerih so poročali v preskušanjih kalcitonina, se je pojavila po 12 mesecih zdravljenja.
• Overall benefit-risk assessment
• Splošna ocena tveganj in koristi
The inconsistency in the summary statistics given is recognised by the CHMP but the impact on the overall interpretation must be regarded as marginal or non-existing.
Odbor CHMP priznava neskladnost podanih statistik povzetka, vendar pa je treba vpliv na splošno interpretacijo upoštevati kot marginalen ali neobstoječ.
However, as previously concluded by CHMP there are concerns in relation to the lack of a dose response in this study as well as in relation to other methodological limitations.
Kot pa je že prej zaključil odbor CHMP, obstajajo zadržki v zvezi s pomanjkanjem učinkovanja odmerka v tej študiji kot tudi v zvezi z drugimi metodološkimi omejitvami.
In addition to the lack of a dose response, the results of this study are further limited by important methodological limitations (lack of adjustment for multiple testing and very high percentage of patients discontinuing the study).
Poleg odsotnosti odziva na odmerek so bili rezultati te študije nadalje omejeni zaradi pomembnih metodoloških omejitev (pomanjkanje prilagajanja pri več preiskavah in zelo velik delež bolnikov, ki so prekinili sodelovanje v študiji).
The third one was study A2303, a phase III study with the new oral calcitonin formulation, conducted in postmenopausal women with osteoporosis.
Tretja je bila študija A2303 III. faze z novo peroralno formulacijo kalcitonina, ki je bila opravljena pri postmenopavzalnih ženskah z osteoporozo.
• The Committee considered the referral made under Article 31 of Directive 2001/83/EC for calcitonin-containing medicines;
• odbor je pregledal napotitveni postopek, opravljen v skladu z 31. členom Direktive 2001/83/ES, za zdravila, ki vsebujejo kalcitonin;
The CHMP also considered information provided by third parties during the referral procedure.
Odbor CHMP je upošteval tudi podatke, ki so jih med napotitvenim postopkom predložile tretje strani.
On the basis of this new safety information the UK requested the opinion of the Committee for Medicinal Products for Human Use (CHMP), under Article 31 of Directive 2001/83/EC whether the marketing authorisations for medicinal products containing calcitonin should be maintained, varied, suspended or withdrawn.
Na podlagi teh novih varnostnih informacij je Združeno kraljestvo zaprosilo za mnenje odbora za zdravila za uporabo v humani medicini (CHMP) v skladu z 31. členom Direktive 2001/83/ES o tem, ali naj se dovoljenje za promet z zdravili, ki vsebujejo kalcitonin, ohrani, spremeni, začasno umakne ali ukine.
Two of these were osteoarthritis studies (C2301 and C2302), where patients received 0.8mg twice daily.
Dve od teh sta bili študiji osteoartritisa (C2301 in C2302), v katerih so bolniki prejemali 0,8 mg dvakrat na dan.
The indications currently authorised as per the outcome of the previous referral procedure that was concluded in 2003, were reviewed in the current procedure.
V trenutnem postopku so pregledali indikacije, trenutno odobrene glede na izid prejšnjega napotitvenega postopka, ki je bil opravljen leta 2003.
The CHMP also endorsed a communication i.e. Dear Healthcare Professional Communication (DHPC), to communicate the outcome of the present review.
Odbor CHMP prav tako spodbuja komunikacijo, tj. komunikacijo z zdravstvenimi delavci (Dear Healthcare Professional Communication, DHPC), da se sporočajo izidi predhodnega pregleda.
• Efficacy
• Učinkovitost
The conditions for the lifting of the suspension of the Marketing Authorisations are set out in Annex IV of the Opinion.
Pogoji za preklic začasnega umika dovoljenj za promet z zdravilom so navedeni v Prilogi IV mnenja.
Following the adoption of the CHMP opinion and recommendations during the July 2012 CHMP meeting, a re-examination request was received on 8 August 2012 from one of the MAHs Therapicon, who was involved in the referral procedure.
Po sprejemu mnenja in priporočil odbora CHMP na seji odbora CHMP julija 2012, je bila 8. avgusta 2012 sprejeta prošnja za ponovno presojo, ki jo je poslal eden izmed imetnikov dovoljenja za promet z zdravilom, Therapicon, ki je bil vključen v napotitveni postopek.
Data suggest that there is some relation for prostate cancer but it is not possible to generalise these results.
Podatki nakazujejo, da obstaja povezava z rakom prostate, vendar rezultatov ni mogoče posplošiti.
Bearing in mind that the majority of the cases are very sparsely documented, establishing causality for an adverse event such as cancer based solely on spontaneous reports is not feasible.
Ker je večina primerov dokumentirana zelo razpršeno, ugotavljanje vzročnosti za neželeni dogodek, kot je rak, samo na podlagi spontanih poročil ni mogoče.
The CHMP agrees that the PROOF study provides support for the efficacy with regard to vertebral fracture rates in the 200 IU dose group corresponding to a p-value of 0.032 and with no statistically significant changes in the lower (100 IU) and higher (400 IU) dose groups.
Odbor CHMP soglaša, da študija PROOF predstavlja podporo učinkovitosti glede stopenj vertebralnih zlomov v skupini z odmerkom 200 i.e, kar ustreza vrednosti p = 0,032 in brez statistično pomembnih sprememb v skupinah z nižjim (100 i.e.) in višjim (400 i.e.) odmerkom.
However the CHMP was of the view that regardless of whether OR or RR are used, the signal is apparent, which can even be partly assessed by even looking at crude rates.
Kljub temu je bil odbor CHMP mnenja, da je, ne glede na to, ali je uporabljeno OR ali RR, signal očiten, kar je mogoče celo delno oceniti s pregledom splošnih stopenj.
• Safety
• Varnost
However the evidence of efficacy of intranasal calcitonin-containing medicines in this indication remains limited.
Vendar dokazi o učinkovitosti intranazalnih zdravil, ki vsebujejo kalcitonin pri tej indikaciji ostajajo omejeni;
Injectable calcitonin is available as a solution for injection or infusion at 50, 100 or 200 International Units (IU)/ml.
Kalcitonin za injiciranje je na voljo kot raztopina za injiciranje ali infundiranje v odmerkih 50, 100 ali 200 mednarodnih enot (i.e.)/ml.
However, the new evidence related to the risk of cancer impacts the safety profile of calcitonin-containing medicines.
Vendar pa novi dokazi, povezani s tveganjem raka, vplivajo na varnostni profil zdravil, ki vsebujejo kalcitonin.
When including trials in which no cases of malignancy had been reported the estimated OR is 2.12.
Če se vključijo preskušanja, v katerih niso poročali o nobenih primerih malignih obolenj, je ocenjeno razmerje vrednosti 2,12.
Even so, the CHMP concluded that there is evidence of an increased risk of cancer among the exposed, with some degree of consistency - especially among the larger studies.
Ob tem je odbor CHMP zaključil, da dokaz za povečano tveganje raka med izpostavljenimi osebami obstaja z določeno mero doslednosti - še posebej med večjimi študijami.
This pivotal study showed that only one of the investigated doses - 200IU calcitonin/day was associated with a statistical significant effect, although for this dose, statistical significance was not achieved when analysing patients with at least 2 new vertebral fractures.
Ta ključna študija je pokazala, da je bil samo eden od proučevanih odmerkov (200 i.e. kalcitonina/dan) povezan s statistično pomembnim učinkom, čeprav pri tem odmerku statistična pomembnost, po analiziranju bolnikov z vsaj dvema novima vertebralnima zlomoma, ni bila dosežena.
More recently a new oral formulation for calcitonin has been developed which consists of the peptide hormone and 5-CNAC (8-(N-2-hydroxy-5-chloro-benzoyl)-amino-carpylic acid), a newly developed enhancer of gastrointestinal peptide absorption.
Pozneje so razvili novo peroralno formulacijo kalcitonina, ki vsebuje peptidni hormon in 5-CNAC (8-(N-2-hidroksi-5-kloro-benzoil)-amino-kaprilna kislina), ki je na novo razviti ojačevalec gastrointestinalne absorpcije peptidov.
The CHMP noted that any meta-analysis driven by a safety signal will always be, per definition, conducted post-hoc, the objective of such an analysis being to quantitatively rule out a potential harm to patients.
Odbor CHMP je navedel, da bodo vse metaanalize, ki jih sproži varnostni signal vedno po definiciji opravljene post-hoc, pri čemer je cilj takšne analize kvantitativna izločitev morebitne škode za bolnike.
The CHMP accepted that some evidence of efficacy in this indication has been provided, mainly by the study by Tsakalakos et al.
Odbor CHMP je sprejel nekatere dokaze o učinkovitosti pri tej indikaciji, ki izhajajo predvsem iz študije, ki so jo opravili Tsakalakos in sodelavci.
The most relevant non-clinical studies are the chronic carcinogenicity assays in rats and mice and they are not conclusive with regard to the carcinogenic potential of calcitonin.
Najpomembnejše neklinične študije so ocene kronične karcinogenosti pri podganah in miših, ki pa niso dokončne kar zadeva karcinogeni potencial kalcitonina.
With regards to prostate cancer, information provided on prostate specific antigen (PSA) levels from all male patients in the first two osteoarthritis studies C2301 and C2302 showed that calcitonin does not have an effect on PSA levels.
Glede raka prostate so podatki o ravneh za prostato specifičnega antigena (PSA) pri vseh moških bolnikih v prvih dveh študijah osteoartritisa C2301 in C2302 pokazali, da kalcitonin ne vpliva na ravni PSA.
These data are also supported by the meta-analysis of the 3 studies (C2301, C2302 and A2303) performed with the oral formulations.
Te podatke podpira tudi metaanaliza 3 študij (C2301, C2302 in A2303), ki so bile opravljene s peroralnimi formulacijami.
The differences are not considered to be sufficiently convincing to alter the previous CHMP conclusion regarding an increased risk of cancer with calcitonin-containing medicinal products.
Razlike se ne upoštevajo kot dovolj prepričljive, da bi spremenile predhodni sklep odbora CHMP glede povečanega tveganja raka ob jemanju zdravil, ki vsebujejo kalcitonin.
A number of published studies using prostate cancer cell lines and animal models have also suggested a role for calcitonin in prostate cancer progression.
Številne objavljene študije, ki so uporabile rakave celične linije in živalske modele, so prav tako omenile vlogo kalcitonina pri napredovanju raka prostate.
• The Committee considered all the available data on the efficacy and safety of calcitonin-containing medicines in particular new data in relation to the risk of cancer.
• odbor je pregledal vse razpoložljive podatke o učinkovitosti in varnosti zdravil, ki vsebujejo kalcitonin, predvsem nove podatke, povezane s tveganjem raka;
Even when overlooking these limitations, the overall clinical benefit of calcitonin in osteoporosis appears to be very modest, with an absolute reduction of approximately 6% and 1.7% in the patients with ≥1 and ≥2 new vertebral fracture respectively compared to patients treated with placebo.
Tudi če se te omejitve spregledajo, se zdi, da je splošna klinična korist kalcitonina pri osteoporozi zelo skromna, saj je bilo absolutno zmanjšanje približno 6-odstotno pri bolnikih z ≥ 1 novim vertebralnim zlomom in 1,7-odstotno pri bolnikih z ≥ 2 novima vertebralnima zlomoma v primerjavi z bolniki, ki so prejemali placebo.
The scientific points of disagreement presented in the MAHs detailed grounds included efficacy aspects, safety aspects in relation to the risk of cancer (non-clinical, pharmacovigilance, and statistical issues) and overall benefit-risk assessment.
Točke znanstvenega nestrinjanja, ki so bile predstavljene v podrobnih razlogih imetnika dovoljenja za promet, so vključevale vidike učinkovitosti, vidike varnosti glede tveganja raka (neklinična vprašanja, farmakovigilančna vprašanja, statistična vprašanja) in celotno oceno koristi in tveganj.
While it is recognised by the CHMP that the inclusion or exclusion of single trials will adjust the overall odds ratio (OR) in different directions, it is acknowledged that it is reasonable to conduct a list of sensitivity analyses to assess the robustness of the results.
Medtem ko odbor CHMP priznava, da vključitev ali izključitev posameznih preskušanj prilagodi splošno razmerje verjetnosti (OR) v različni smeri, je sprejeto, da je smotrno opraviti seznam analiz občutljivosti za ocenitev stabilnosti rezultatov.
The MAH also questions the validity of the evidence of the available clinical trials that substantiated the efficacy of the product, arguing that the evidence is not valid for safety because of confounding factors.
Imetnik dovoljenja za promet dvomi tudi v veljavnost dokazov razpoložljivih kliničnih preskušanj, ki so podkrepili učinkovitost izdelka, pri čemer oporeka, da dokazi niso veljavni za varnost zaradi motečih dejavnikov.
This is most likely due to tumour growth acceleration, which has also been suggested in the published literature.
To je verjetno zaradi pospeševanja rasti tumorjev, kar omenja tudi objavljena literatura.
The MAH argues that the studies included in the meta-analysis lacked a defined PICO (population, intervention, comparison and outcome) statement.
Imetnik dovoljenja za promet z zdravilom trdi, da študije, ki so bile vključene v metaanalizo, niso imele opredeljene izjave PICO (populacija, intervencija, primerjava in izid).
The CHMP reviewed the currently available short and long-term evidence of efficacy of calcitonin in the authorised indications (as per Commission Decision of 12 June 2003), and the information about the risk of cancer with calcitonin from pre-clinical studies, clinical trials, post-marketing spontaneous reports, pharmacoepidemiological studies and published literature.
Odbor CHMP je pregledal trenutno razpoložljive kratko- in dolgoročne dokaze o učinkovitosti kalcitonina pri odobrenih indikacijah (skladno z odločbo Komisije z dne 12. junija 2003) ter podatke o tveganju za razvoj raka ob uporabi kalcitonina iz predkliničnih študij, kliničnih preskušanj, spontanih poročil iz obdobja trženja, farmakoepidemioloških študij in objavljene literature.
The diminishing use of calcitonin over the last years suggest that there is limited scope to further investigate the association by means of epidemiological studies, which in any case would be difficult to conduct and adequately control for all possible confounders for cancer.
Vedno manjša uporaba kalcitonina v zadnjih letih kaže, da obstaja omejen obseg za nadaljnje proučevanje povezave z uporabo epidemioloških študij, ki bi jih bilo v kakršnem koli primeru težko izvajati in zadostno nadzorovati za vse morebitne spremljajoče dejavnike za raka.
During this procedure the CHMP reviewed the available evidence on the risk of cancer with the use of calcitonin.
Med tem postopkom je odbor CHMP pregledal razpoložljive dokaze o tveganju raka ob uporabi kalcitonina.
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.