FrancophonIA/ELRC3.0 huggingface dataset:
English: When excluding this centre, a statistically significant centre effect was seen and the statistical significance was lost for both co-primary variables, as well as for the physician's global assessment endpoint.
Danish: Da dette center blev udelukket, blev der observeret en statistisk signifikant centereffekt, og den statistiske signifikans gik tabt for begge de coprimære variabler og for endepunktet med lægens samlede vurdering.
English: Finally, the CHMP noted that the total number of reports was low, and as per the Weber effect, a decline in reporting of adverse events is likely over time.
Danish: Endelig bemærkede CHMP, at det samlede antal rapporter var lavt, og i henhold til Weber-effekten er en nedgang i rapporteringen af bivirkninger sandsynlig med tiden.
English: • The CHMP considered the procedure under Article 31 of Directive 2001/83/EC for Symbioflor 2 (Escherichia coli bacteria (cells and autolysate)) and associated names (Symbioflor 2);
Danish: • CHMP behandlede indbringelsen i henhold til artikel 31 i direktiv 2001/83/EF for Symbioflor 2 (Escherichia coli-bakterier (celler og autolysat)) og relaterede navne (Symbioflor 2).
English: Whereas it cannot generally be stated that probiotics are efficacious or not efficacious in the treatment of IBS, it appears that specific probiotic species or strains could potentially be efficacious for specific symptoms of the disease.
Danish: Selv om det generelt ikke kan fastslås, at probiotika er effektive eller ikke effektive til behandling af IBS, lader det til, at specifikke probiotikaarter eller -stammer potentielt kan være effektive mod specifikke sygdomssymptomer.
English: Symbioflor 2 is available in the European Union (EU) in Austria (AT), Germany (DE) and Hungary (HU) as a medicine not subject to prescription or over-the-counter (OTC).
Danish: I Den Europæiske Union (EU) fås Symbioflor 2 i Østrig (AT), Tyskland (DE) og Ungarn (HU) som et lægemiddel, der ikke er receptpligtigt, dvs. som håndkøbsmedicin (OTC).
English: Symbioflor 2 is composed of 10 different isolates of Escherichia coli which are partly autolysed and partly presented as living bacteria.
Danish: Symbioflor 2 består af 10 forskellige isolater af Escherichia coli, som dels er autolyseret og dels er til stede som levende bakterier.
English: The CHMP therefore concluded that the possibility that significant bias had compromised the validity of the results of this study could not be ruled out.
Danish: CHMP konkluderede således, at muligheden for, at signifikant bias havde kompromitteret validiteten af denne undersøgelses resultater, ikke kunne udelukkes.
English: However, indirect risks associated with the intake of a potentially inefficacious medication for IBS with regards to continued impairment of quality of life and potential consequences regarding work- and health-care-seeking -related behaviour need to be considered.
Danish: Det er dog nødvendigt at tage højde for indirekte risici i forbindelse med indtagelsen af et potentielt uvirksomt lægemiddel mod IBS, hvad angår en fortsat forringelse af livskvaliteten og potentielle konsekvenser med hensyn til arbejds- og plejerelateret adfærd.
English: On this basis and considering the absence of new data since the initial marketing authorisation, the CHMP considered changes to the product information to include the information of this review necessary.
Danish: På dette grundlag og i betragtning af manglen på nye data efter den første markedsføringstilladelse var CHMP af den opfattelse, at det var nødvendigt at ændre produktinformationen og medtage informationen fra denne gennemgang.
English: • An observational non-interventional study in 203 children and adolescents conducted between 2007 and 2008 in Germany “Efficacy and tolerability of Symbioflor 2 in children with Irritable Bowel Syndrome”.
Danish: • en ikke-interventionel observationsundersøgelse hos 203 børn og unge med irritabel tyktarmssyndrom foretaget i Tyskland mellem 2007 og 2008, "Efficacy and tolerability of Symbioflor 2 in children with Irritable Bowel Syndrome".
English: Supplementary Integrated Clinical Study Report Final PAZ 9527-5-S2”, of the study conducted in 1988 in Germany entitled “Schaffstein, W. and Burkard, I.: Symbioflor 2 - Eine therapeutische Alternative zur Behandlung des irritablen Kolons.
Danish: Supplementary Integrated Clinical Study Report Final PAZ 9527-5S2", og af den undersøgelse om irritabel tyktarm, der blev foretaget i Tyskland i 1988 med titlen "Schaffstein, W. and Burkard, I.: Symbioflor 2 - Eine therapeutische Alternative zur Behandlung des irritablen Kolons.
English: The evaluation of the results was descriptive and thus did not allow establishing whether the differences in efficacy between Symbioflor 2 and placebo were statistically different and clinically meaningful.
Danish: Evalueringen af resultaterne var deskriptiv og gjorde det derfor ikke muligt at fastslå, om virkningsforskellene mellem Symbioflor 2 og placebo var statistisk forskellige og klinisk betydningsfulde.
English: It is therefore unlikely that post-marketing data will provide significant further information on the safety profile of Symbioflor 2 in the treatment of IBS.
Danish: Derfor er det usandsynligt, at data efter markedsføringen vil give signifikante yderligere oplysninger om sikkerhedsprofilen for Symbioflor 2 til behandling af IBS.
English: In the re-evaluation report of Study S2 (2005), the endpoints were redefined, combining parameters of a patient-centred assessment of spontaneous symptoms with endpoints based on physical examination by the physician.
Danish: I reevalueringsrapporten for S2-undersøgelsen (2005) blev endepunkterne ændret med henblik på at kombinere parametre, der omfattede en patientcentreret vurdering af spontane symptomer med endepunkter, der var baseret på en lægeundersøgelse.
English: Symbioflor 2 (Escherichia coli bacteria (cells and autolysate)) and associated names (Symbioflor 2) is a probiotic containing living Escherichia coli bacteria, which exist in normal gut flora in humans.
Danish: Symbioflor 2 (Escherichia coli-bakterier (celler og autolysat)) og relaterede navne (Symbioflor 2) er et probiotikum, der indeholder levende Escherichia coli-bakterier, som findes i den normale tarmflora hos mennesker.
English: The evaluations presented in the Study Report of Study S2 (1989), based on a primary endpoint of “global evaluation” of efficacy by the investigator at the end of the trial, showed that Symbioflor 2 administered over an 8-week period had better outcomes than placebo on most of the evaluated endpoints.
Danish: De evalueringer, der fremlægges i undersøgelsesrapporten for S2-undersøgelsen (1989), er baseret på et primært endepunkt med investigatorens "overordnede evaluering" af virkningen ved undersøgelsens afslutning og viste, at Symbioflor 2 indgivet over en 8-ugers periode gav bedre resultater end placebo for de fleste af de evaluerede endepunkter.
English: Apart from data on IBS, no controlled or uncontrolled clinical study or literature data are available to assess the efficacy and safety of Symbioflor 2 in the treatment of these diseases.
Danish: Bortset fra dataene om IBS er der ingen kontrollerede eller ukontrollerede kliniske undersøgelses- eller litteraturdata tilgængelige til at vurdere virkningen og sikkerheden af Symbioflor 2 til behandling af disse sygdomme.
English: On 30 March 2016 Germany triggered a referral under Article 31 of Directive 2001/83/EC, and requested the CHMP to assess the benefit-risk balance of Symbioflor 2 in the claimed indications ("functional gastrointestinal disorders'', "irritable bowel syndrome") and to issue an opinion on whether the relevant marketing authorisations should be maintained, varied, suspended or revoked.
Danish: Den 30. marts 2016 indledte Tyskland en indbringelse i henhold til artikel 31 i direktiv 2001/83/EF og anmodede CHMP om at vurdere benefit/risk-forholdet for Symbioflor 2 i de påståede indikationer ("funktionelle lidelser i mave-tarm-kanalen" og "irritabel tyktarmssyndrom") og afgive en udtalelse om, hvorvidt de pågældende markedsføringstilladelser burde opretholdes, ændres, suspenderes eller inddrages.
English: This study therefore cannot be considered to contribute to further establishing the safety profile of Symbioflor 2.
Danish: Derfor kan denne undersøgelse ikke anses for at bidrage til en yderligere fastlæggelse af sikkerhedsprofilen for Symbioflor 2.
English: Additional bias might have been introduced by various other deficiencies encountered in the conduct of Study S2, including the fact that the endpoint was solely based on the rating by the investigator on a weekly basis rather than selfassessed by the patient closer to the administration of Symbioflor 2.
Danish: Yderligere bias kan være blevet indført af forskellige andre mangler ved gennemførelsen af S2undersøgelsen, herunder den kendsgerning, at endepunktet udelukkende var baseret på investigators vurdering på ugebasis i stedet for at blive vurderet af patienten selv tættere på indgivelsen af Symbioflor 2.
English: In general, the CHMP was of the opinion that, although the reporting might have been suboptimal and uncertainties remain with regards to the nature and frequency of the adverse events occurring with Symbioflor 2 in order to fully characterize its safety profile and notably its long term safety profile, the analysis of the safety data did not raise particular concerns.
Danish: CHMP var generelt af den opfattelse, at selv om rapporteringen måske har været suboptimal, og der stadig er usikkerhed med hensyn til arten og hyppigheden af de uønskede hændelser, der fandt sted med Symbioflor 2, når det gælder om at opnå et fuldstændigt kendskab til dets sikkerhedsprofil og navnlig dets langsigtede sikkerhedsprofil, gav analysen af sikkerhedsdataene ikke anledning til særlige betænkeligheder.
English: Based on the review of all available data in the framework of this Article 31 procedure, the CHMP concludes that there are no new elements since the granting of the marketing authorisation for Symbioflor 2 (Escherichia coli bacteria (cells and autolysate)) and associated names, and therefore the previous conclusion of the national competent authorities on a positive benefit-risk balance remains unchanged.
Danish: På baggrund af gennemgangen af alle tilgængelige data i forbindelse med denne artikel 31-procedure konkluderer CHMP, at der ikke er fremkommet nogen nye oplysninger siden udstedelsen af markedsføringstilladelse for Symbioflor 2 (Escherichia coli-bakterier (celler og autolysat)) og relaterede navne, og derfor forbliver de nationale kompetente myndigheders tidligere konklusion om et positivt benefit/risk-forhold uændret.
English: Two reports in support of the claimed indication in the treatment of irritable bowel syndrome (IBS) were submitted in the context of this referral procedure:
Danish: Der blev fremsendt to rapporter til støtte for den påståede indikation til behandling af irritabel tyktarmssyndrom (IBS) i forbindelse med denne indbringelsesprocedure:
English: The CHMP concluded that this study cannot be regarded as adequately supporting an indication for Symbioflor 2 in this age group.
Danish: CHMP konkluderede, at denne undersøgelse ikke i tilstrækkelig grad kan anses for at støtte en indikation for Symbioflor 2 i denne aldersgruppe.
English: Proof of the efficacy of Symbioflor 2 in this patient population would have required a prospective, double-blinded, randomized and placebo-controlled trial as per the guideline CPMP/EWP/785/97 in force at the time of the conduct of the study.
Danish: Et bevis for virkningen af Symbioflor 2 i denne patientpopulation ville have krævet en prospektiv, dobbeltblindet, randomiseret og placebokontrolleret undersøgelse efter CPMP's vejledning, CPMP/EWP/785/97, som var gældende på det tidspunkt, hvor undersøgelsen blev udført.
English: • Considering available safety data from the clinical trial and post-marketing experience with Symbioflor 2, the CHMP came to the conclusion that the demonstrated risks were overall low.
Danish: • I betragtning af de tilgængelige sikkerhedsdata fra den kliniske undersøgelse og erfaringen med Symbioflor 2 efter markedsføringen kom CHMP til den konklusion, at de påviste risici overordnet set var lave.
English: Although Study S2 was conducted before requirements of the current IBS guideline “Guideline on the evaluation of medicinal products for the treatment of irritable bowel syndrome” (CPMP/EWP/785/97) or the previous CHMP point to consider on IBS came into force, the original protocol of Study S2 neither defined a primary endpoint nor planned for a statistical analysis.
Danish: Selv om S2-undersøgelsen blev foretaget, inden kravene i den aktuelle IBS-retningslinje "Guideline on the evaluation of medicinal products for the treatment of irritable bowel syndrome" (CPMP/EWP/785/97) eller det tidligere CHMP-dokument om punkter, der bør tages i betragtning, trådte i kraft, var der i den originale protokol for S2-undersøgelsen hverken fastlagt et primært endepunkt eller planlagt en statistisk analyse.
English: However, the CHMP concluded that there were no new elements to motivate a change in the established benefit risk balance since the initial marketing authorisation for Symbioflor 2 in adult patients for the treatment of IBS;
Danish: CHMP konkluderede dog, at der ikke var nogen nye oplysninger, som begrundede en ændring i det fastlagte benefit/risk-forhold siden den første markedsføringstilladelse for Symbioflor 2 hos voksne patienter til behandling af IBS.
English: Overall, the evaluations presented by the MAH indicated that the decrease in symptom score was more important in the Symbioflor 2 than in the placebo arm.
Danish: Samlet set viste de evalueringer, som indehaveren af markedsføringstilladelsen fremlagde, at nedgangen i symptomscoren var større i Symbioflor 2-armen end i placeboarmen.
English: From post-marketing experience, only 18 adverse reactions have been reported to Eudravigilance for Symbioflor 2, covering both the treatment of IBS and other functional gastrointestinal disorders despite significant exposure over several decades of marketing and the pharmacovigilance system put in place by the MAH since the early 2000.
Danish: Ud fra erfaringerne efter markedsføringen er der kun rapporteret 18 bivirkninger til Eudravigilance for Symbioflor 2, og de dækker både behandlingen af IBS og andre funktionelle lidelser i mave-tarm-kanalen, på trods af den væsentlige eksponering over flere årtier efter markedsføringen og det lægemiddelovervågningssystem, som indehaveren af markedsføringstilladelsen indførte i starten af 2000.
English: The adverse events were generally benign in nature, and mostly restricted to the gastrointestinal tract (such as abdominal pain and nausea) or related to the occurrence of skin efflorescences.
Danish: Bivirkningerne var generelt lette og var for størstedelens vedkommende begrænset til mave-tarm-kanalen (såsom mavesmerter og kvalme) eller relateret til forekomsten af hududslæt.
English: In 2005, rather than conducting a new study in line with the “Note for guidance on statistical principles for clinical trials” (CPMP/ICH/363/96) then in force, the MAH decided to perform a post-hoc reevaluation of Study S2, i.e. establishing the definition of the primary hypothesis, the corresponding evaluation plan and the statistical analysis methods in full knowledge of the results.
Danish: I 2005 besluttede indehaveren af markedsføringstilladelsen - i stedet for at gennemføre en ny undersøgelse i tråd med vejledningsnotatet om statistiske principper for kliniske undersøgelser, "Note for guidance on statistical principles for clinical trials" (CPMP/ICH/363/96), som var gældende på daværende tidspunkt - at foretage en post hoc-reevaluering af S2-undersøgelsen, dvs. at fastlægge definitionen af den primære hypotese, den tilsvarende evalueringsplan og den statistiske analysemetode med fuldt kendskab til resultaterne.
English: The CHMP acknowledged the deletion of the indication “functional gastrointestinal disorders” during this procedure.
Danish: CHMP anerkendte sletningen af indikationen "funktionelle lidelser i mave-tarm-kanalen" under denne procedure.
English: • The CHMP considered that “functional gastrointestinal disorders” is a heterogeneous group of individual diseases with a wide range of different underlying pathophysiologies and symptoms that require different treatment modalities.
Danish: • CHMP var af den opfattelse, at "funktionelle lidelser i mave-tarm-kanalen" er en heterogen gruppe af individuelle sygdomme med en lang række forskellige underliggende patofysiologier og symptomer, der kræver forskellige behandlingsmåder.
English: Although the results of Study S2 point at a possible efficacy of Symbioflor 2 in the treatment of IBS, a large unexplained heterogeneity was observed among centres in terms of treatment effect and response rate.
Danish: Selv om resultaterne af S2-undersøgelsen peger i retning af en mulig virkning af Symbioflor 2 til behandling af IBS, blev der observeret en omfattende uforklarlig heterogenitet blandt centrene, når det gjaldt behandlingseffekt og responsrate.
English: Indication in the treatment of irritable bowel syndrome
Danish: Indikation til behandling af irritabel tyktarmssyndrom
English: In addition, the CHMP was of the opinion that the adequacy of a global evaluation criterion defined by the MAH for the assessment of the efficacy of Symbioflor 2 in the treatment of IBS was questionable in comparison to the specific, better measurable and less subjective evaluation of changes in stool related abnormalities and pain.
Danish: Desuden var CHMP af den opfattelse, at egnetheden af et globalt evalueringskriterium, som indehaveren af markedsføringstilladelsen havde opstillet for vurderingen af Symbioflor 2's virkning til behandling af IBS, var tvivlsom sammenlignet med den specifikke, bedre målbare og mindre subjektive evaluering af ændringerne i afføringsrelaterede uregelmæssigheder og smerter.
English: The value of an observational study for substantiating the efficacy of the product in this patient population is limited and therefore the CHMP concluded that this study could not be regarded as adequately supporting the efficacy of Symbioflor 2 in this age group.
Danish: Værdien af en observationsundersøgelse for at fastslå lægemidlets virkning hos denne patientpopulation er begrænset, og derfor konkluderede CHMP, at denne undersøgelse ikke i tilstrækkelig grad støttede virkningen af Symbioflor 2 hos denne aldersgruppe.
English: No study was submitted to support the indication in the treatment of functional gastrointestinal disorders.
Danish: Der blev ikke fremsendt nogen undersøgelse til støtte for indikationen til behandling af funktionelle lidelser i mave-tarm-kanalen.
English: • A 2005 re-analysis of a 1988 study “Efficacy and tolerability of Symbioflor2: A randomised, multicentre, double-blind, placebo-controlled trial in 298 patients with irritable bowel syndrome treated continuously for 8 weeks with Symbioflor 2 (clinical phase IV).
Danish: • en reanalyse fra 2005 af en undersøgelse fra 1988 om sikkerheden og virkningen af Symbioflor 2 med titlen "Efficacy and tolerability of Symbioflor2: A randomised, multicentre, double-blind, placebocontrolled trial in 298 patients with irritable bowel syndrome treated continuously for 8 weeks with Symbioflor 2 (clinical phase IV).
English: Given the heterogeneity of the disease and the absence of data, the CHMP asked the MAH to submit evidence to support this indication.
Danish: I betragtning af sygdommenes heterogenitet og de manglende data bad CHMP indehaveren af markedsføringstilladelsen om at fremsende evidens til støtte for denne indikation.
English: The CHMP recommends amendments to the product information and in view of the limitations of the currently available efficacy data for Symbioflor2 in the treatment of irritable bowel syndrome (IBS), the CHMP is of the view that a post-authorisation efficacy study should be conducted.
Danish: CHMP anbefaler en ændring af produktinformationen, og i betragtning af begrænsningerne ved de aktuelt tilgængelige virkningsdata for Symbioflor 2 til behandling af irritabel tyktarmssyndrom (IBS) er CHMP af den opfattelse, at der bør foretages en virkningsundersøgelse efter markedsføringstilladelsen.
English: In addition, the CHMP noted that data generated in study S2 have not established the long term efficacy of Symbioflor 2 beyond 8 weeks of treatment.
Danish: CHMP bemærkede endvidere, at de data, som S2-undersøgelsen frembragte, ikke har påvist langtidsvirkningen af Symbioflor 2 ved behandling i længere tid end 8 uger.
English: • The CHMP was of the opinion that, although the results of Study S2 seemed to suggest possible efficacy of Symbioflor 2 in IBS in adult patients, the possibility that significant bias had been introduced compromising the validity of the results could not be ruled out.
Danish: • CHMP var af den opfattelse, at selv om resultaterne af S2-undersøgelsen tilsyneladende tydede på en mulig virkning af Symbioflor 2 ved IBS hos voksne patienter, kunne man ikke udelukke muligheden for, at der var indført signifikant bias, som kompromitterede resultaternes validitet.
English: • To regulate the immune system (immune-regulation): functional disturbances of the gastrointestinal system (HU).
Danish: • Regulering af immunsystemet (immunregulering): funktionelle lidelser i mave-tarm-kanalen (HU).
English: • The CHMP reviewed all available data from clinical studies, published literature, post-marketing experience, including responses and communications submitted by the MAH in writing, on the efficacy and safety of Symbioflor 2 in their proposed indications and sought as well views of the ad hoc expert group on Symbioflor 2;
Danish: • CHMP gennemgik alle tilgængelige data fra kliniske undersøgelser, offentliggjort litteratur og erfaring efter markedsføringen, herunder svar og meddelelser, som indehaveren af markedsføringstilladelsen havde fremsendt skriftligt, om virkningen og sikkerheden af Symbioflor 2 i de foreslåede indikationer, og CHMP anmodede ligeledes ad hoc-ekspertgruppen om Symbioflor 2 om dens synspunkter.
English: Data were not controlled and did thus not account for the contribution of spontaneous fluctuations of IBS symptoms or for a placebo response in the assessment of the benefit-risk of Symbioflor 2.
Danish: Dataene var ikke kontrolleret og kunne derfor ikke bidrage til de spontane udsving i IBS-symptomerne eller til en placeborespons ved vurderingen af benefit/risk-forholdet for Symbioflor 2.
English: In the clinical development program, there were respectively 50 adverse drug reactions reported in the Symbioflor 2 group, and 44 in the placebo group for Study S2 in 79 patients.
Danish: I det kliniske udviklingsprogram blev der i S2-undersøgelsen hos 79 patienter rapporteret henholdsvis 50 bivirkninger i Symbioflor 2-gruppen og 44 i placebogruppen.
English: The CHMP agreed with the MAH's proposal to amend the product information to include the information of this review and concluded that, considering its long presence on the market with limited adverse drug reactions reporting, the safety profile of Symbioflor 2 is generally expected to be benign.
Danish: CHMP var enigt i indehaveren af markedsføringstilladelsens forslag om at ændre produktinformationen og medtage informationen i denne gennemgang, og CHMP konkluderede, at i betragtning af den langvarige tilstedeværelse på markedet og den begrænsede rapportering af bivirkninger forventes sikkerhedsprofilen for Symbioflor 2 generelt at være positiv.
English: In 2005, based on the evaluation of the available evidence at that time in the claimed indications ("functional gastrointestinal disorders'', "irritable bowel syndrome"), the application was refused by the German National Competent Authority on the ground that a positive benefit-risk had not been adequately established.
Danish: På baggrund af evalueringen af den tilgængelige evidens på dette tidspunkt for de påståede indikationer ("funktionelle lidelser i mave-tarm-kanalen" og "irritabel tyktarmssyndrom") gav Tysklands nationale kompetente myndighed i 2005 afslag på ansøgningen med den begrundelse, at der ikke var tilstrækkelig dokumentation for et positivt benefit/risk-forhold.