Clinical Pharmacology & Therapeutics, Nov 19, 2021
We outline our vision that by 2025 the use of real-world evidence will have been enabled and the ... more We outline our vision that by 2025 the use of real-world evidence will have been enabled and the value will have been established across the spectrum of regulatory use cases. We are working to deliver this vision through collaboration where we leverage the best that different stakeholders can bring. This vision will support the development and use of better medicines for patients.
Mittels bildgebender Verfahren wie die Single-Photon-Ernission-Computed-Tomography (SPECT) und di... more Mittels bildgebender Verfahren wie die Single-Photon-Ernission-Computed-Tomography (SPECT) und die Positron-Emission-Tomography (PET) konnten bei psychiatrischen Erkrankungen Perfusionsstorungen verschiedener Hirnareale nachgewiesen werden. Bei Schizophrenien hatte man in den fruheren Studien Veranderungen im Frontallappen (Buchsbaum et al. 1982) gefunden. Diese Befunde konnten in den neueren Arbeiten nicht repliziert werden, hingegen scheint der Temporallappen besonders betroffen zu sein (Buchsbaum et al. 1990, deLisi et al. 1989) Bei affektiven Storungen sind Veranderungen im prefrontalen Cortex (Baxter et al. 1989, Cohen et al. 1989) und im Temporallappen (Post et al. 1987, Amsterdam et al. 1992) festgestellt worden. Bei den meisten der obengenannten Untersuchungen — besonders den PET-Studien — wurde meistens die Psychopathologie zum Zeitpunkt der Untersuchung vernachlassigt. Daher haben wir uns im Rahmen des jetzigen Projektes zum Ziel gesetzt, zu untersuchen, inwiefern eine spezifische bzw. globale Psychopathologie im Zusammenhang mit Durchblutungsverhaltnissen (gemessen mit der HMPAO-SPECT-Technik) steht.
Background: In Germany, physicians who prescribe cannabis-based medicines at the expense of the s... more Background: In Germany, physicians who prescribe cannabis-based medicines at the expense of the statutory health insurance are obliged to take part in an accompanying survey. Pain was the most commonly reported diagnosis, making an interim evaluation for the indication of pain feasible. Methods: Patient-related data was transmitted to the German Federal Institute for Drugs and Medical Devices via an online portal. In addition to demographic data, information on the treated disease or symptoms, the course of therapy, adverse reactions and treatment success were evaluated. Results: A total of 3138 data sets were evaluated for the main diagnosis of pain. Dronabinol was the most frequently (64%) prescribed cannabis-based drug. On average, patients were 57 years old and women and men were equally represented. Patients treated with cannabis flowers were significantly younger (48 years). The proportion of men in this group was 68% and 83% in the group of 18- to 40-year-olds. According to the assessment by treating physicians, pain was significantly improved in 35.5% of the patients. The most frequent side effects (fatigue, dizziness, nausea) corresponded to those already known from the product information of the cannabis-based medicinal products authorized under the pharmaceutical law. Treatment was discontinued in 1179 patients within 1 year. Conclusion: Physicians should comply with their legal obligation to participate in the accompanying survey. Pain is by far the most common diagnosis in cannabis drugs. For about one third of these patients, physicians reported a clear improvement in pain. Due to the amount of data hitherto and the limitations in the accompanying survey, the results should not be overinterpreted in terms of efficacy and should always be related to existing reviews. The lower age and higher proportion of men among patients treated with cannabis flowers were remarkable. At 37.6%, the overall drop-out rate was high. The most frequent side effects related to vigilance and are therefore highly relevant in terms of driving ability, work ability and risk of falling. For a differentiated evaluation of treatment success, more data needs to be available.
Atopic conditions (atopic dermatitis, rhinitis, and asthma) belong to the most common noncommunic... more Atopic conditions (atopic dermatitis, rhinitis, and asthma) belong to the most common noncommunicable diseases and are driven by chronic inflammatory reactions. They have a strong impact on the quality of life and represent a substantial and growing socio-economic burden. Interestingly, there is an increasing interest in the development of new therapeutic options with a number of biologics and small molecules targeting potential key mechanisms in atopic conditions. However, besides the safety issue, most of the new active substances are still evaluated according to the traditional efficacy paradigm focusing on the success in treating exacerbations and flares. Instead, the future approaches in drug development and assessment should rather concentrate on the long-term control of these diseases and consider their potential as disease-modifying strategies in the era of precision medicine. To reach this goal, a number of unsolved issues have to be addressed and consensually accepted by the stakeholders in this field. Thus, a successful and rapid development of new treatments requests a paradigm shift and a new way of thinking in the mind of physicians, pharmaceutical industry, regulators, and HTAs. This seems mandatory in order to optimize drug development and to facilitate the accessibility of new therapies to the growing population of patients suffering from atopic conditions on a global level.
After supratentorial infarction crossed cerebellar diaschisis has been described. This report con... more After supratentorial infarction crossed cerebellar diaschisis has been described. This report concerns the rare phenomenon of crossed cerebral diaschisis in cerebellar infarction. Relative distribution of cerebral and cerebellar blood flow was measured using three-dimensional, qualitative single-photon-emission-computed-tomography (SPECT) with a rotating gamma camera and ~23I-IMP. Regional cerebral blood flow was calculated with the two-dimensional, quantitative ~33Xe-inhalation-technique. Reduced uptake was observed in the left cerebral hemisphere (-13.9%) contralateral to the cerebellar infarction with the most marked reduction in the left premotor region (-21%). This might be explained by the functional depression of cerebello-ponto-thalamo-cerebral pathways.
Verhandlungen der Deutschen Gesellschaft für Neurologie, 1987
Although its first-pass extraction following administration (nearly 100%) and stable distribution... more Although its first-pass extraction following administration (nearly 100%) and stable distribution for a certain period by the slow washout from the brain (3) suggest the desirable nature of123I-N-isopropylamphetamine (IMP) for quantitative evaluation of regional cerebral blood flow (rCBF), uncertainty about high-capacity nonspecific receptor-binding sites for amines in the brain may limit the reliability of the IMP technique for quantitative rCBF evaluations. In this study, we validated semiquantitatively assessed cerebral IMP uptake with a three dimensional single-photon emission computed tomography (SPECT) device without arterial sampling as compared with the two-dimensional 133Xe inhalation method in patients, with reference to findings in normal baboons.
Neue epidemiologische Studien haben die grose soziookonomische Bedeutung der Demenzerkrankungen b... more Neue epidemiologische Studien haben die grose soziookonomische Bedeutung der Demenzerkrankungen bestatigt. Die mit Abstand haufigste Ursache der Demenzerkrankungen stellt mit einem Anteil von ca. 60% die Demenz vom Alzheimer-Typ (DAT) dar. Neben klinischer und neuropsychologischer Untersuchung hat die Entwicklung neuer bildgebender Verfahren in der Differentialdiagnostik dementieller Abbausyndrome grose Bedeutung erlangt. Regionale Veranderungen von Hirnstoffwechsel und Hirndurchblutung wurden v.a. nach Anwendung der Positronen-Emissions-Tomographie bei der DAT beschrieben [3]. Wegen ihres hohen apparativen und personellen Aufwands eignet sich diese Methode jedoch nicht fur Routineuntersuchungen. Insbesondere bei der DAT wurden fokale Veranderungen der zerebralen Durchblutung aber auch mit der 133Xe-Inhalationszerebrographie (rCBF) [6] und der Single-Photon-Emissons-Computertomographie (SPECT) [5] erhoben. Bei 15 Patienten mit der klinischen Diagnose einer DAT wurden daher beide Methoden eingesetzt und die Ergebnisse miteinander verglichen.
& Avid (paid to institution); and has patents as co-inventor, but received no royalties: A patent... more & Avid (paid to institution); and has patents as co-inventor, but received no royalties: A patent in vitro multiparameter determination method for the Diagnosis and early diagnosis of neurodegenerative disorders. Patent number: 8916388 Issued. A patent in vitro procedure for diagnosis and early diagnosis of neurodegenerative diseases.
After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease... more After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single "magic bullet" drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological makeup. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker guided early preclinical disease stage clinical trials.
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in Engli... more Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Fehler im Umgang mit Medizinprodukten stellen ein signifikantes Risiko fur die Patientensicherhei... more Fehler im Umgang mit Medizinprodukten stellen ein signifikantes Risiko fur die Patientensicherheit dar. Im Rahmen der Forschung zur Anwendungssicherheit von Medizinprodukten untersucht das Bundesinstitut fur Arzneimittel und Medizinprodukte daher, inwieweit Merkmale von Medizinprodukt, Anwender und Anwendungskontext (oder deren spezifische Kombination) einem sicheren Umgang des Anwenders mit dem Produkt entgegenstehen. Zwei Themenbereiche werden beispielhaft adressiert: der Umgang der Anwender mit Alarmierungen (als eine weit verbreitete und besonders kritische Geratefunktion) sowie die Bedeutung von Informationen zur Sicherheit fur den Umgang mit Medizinprodukten generell. Beide Themen werden in der Literatur zurzeit als problematisch diskutiert – systematische empirische Untersuchungen fehlen allerdings weitgehend. Die vorliegende Arbeit gibt einen Uberblick uber die (wenigen) jeweils existierenden Befunde und diskutiert offene Fragen, deren sich das BfArM in seiner laufenden Forschung zur Anwendungssicherheit von Medizinprodukten annimmt.
The early assessment of benefits of newly approved drugs with novel active substances or new appl... more The early assessment of benefits of newly approved drugs with novel active substances or new applications, which came into force on 1 January 2011 still represents a challenge to all parties involved. This article highlights the definitions, regulatory requirements and interaction between drug marketing approval and early assessment of benefits in Germany. The constellation of an extensively harmonized European and even international drug authorization process with a predominantly national regulation of drug reimbursement situation inevitably causes friction, which could be markedly reduced through early joint advisory discussions during the planning phase for pivotal clinical trials. During the year 2015 the Federal Institute for Drugs and Medical Devices (BfArM) carried out 300 scientific advice procedures of which 34 were concerned with applications in the field of indications for the central nervous system (CNS). In comparison 98 advisory meetings were held by the Federal Joint Committee (G-BA) of which the BfArM provided advice in 12 instances and in 2 cases on CNS indications. Study design, endpoints and appropriate comparative therapies are the key issues in exchanges and discussions between the BfArM, the G‑BA and applicants. Under these aspects the BfArM and G‑BA promote an early and consistent involvement in early advice procedures regarding the prerequisites for drug approval and assessment of additional benefits.
Die Migräne ist eine chronische Erkrankung, bei der es aufgrund einer vermutlich genetischen Vera... more Die Migräne ist eine chronische Erkrankung, bei der es aufgrund einer vermutlich genetischen Veranlagung zu rezidivierenden Schmerzattacken kommt. Diese Schmerzattacken gehen obligat mit vegetativen und fakultativ mit vorübergehenden, fokal-neurologischen Symptomen (Aura) einher. Man unterscheidet 2 Hauptformen der Migräne: Migräne ohne Aura und Migräne mit Aura. Mit etwa 80-85 % ist die Migräne ohne Aura die häufigste Form. Die Klassifikation der Migräne und migräneartiger Erkrankungen erfolgt gemäß der Richtlinien der "International Headache Society" (IHS) [1]. Der typische Kopfschmerz bei einer Migräneattacke erfüllt mindestens 2 der folgenden 4 Kriterien: Er ist halbseitig, hat eine mäßig starke bis starke Intensität, einen pulsierenden Charakter und verstärkt sich bei körperlicher Anstrengung. Begleitend treten Übelkeit und Erbrechen sowie eine Licht-und Geräuschempfindlichkeit auf. Migräneanfälle mit einer Aura sind häufig von optischen oder sensorischen Wahrnehmungsstörungen geprägt. Dabei treten Gesichtsfeldausfälle, Sehstörungen, Gefühlstörungen (z. B. Kribbeln) in den Armen oder andere neurologische Ausfälle vor den Kopfschmerzen auf. Eine chronische Migräne liegt vor, wenn ein Patient an mehr als 15 Tagen im Monat über mehrere Monate (≥ 3) hinweg unter einer Migräne leidet. Davon abzugrenzen ist der chronische Kopfschmerz bei Medikamenteneinnahme, der insbesondere durch einen Übergebrauch von Analgetika induziert wird. Zur Behandlung der akuten Kopfschmerzphase eines Migräneanfalls und zur Migräneprophylaxe steht heute eine Vielzahl unterschiedlicher pharmakologischer Behandlungsansätze zur Verfügung. Die Deutsche Gesellschaft für Neurologie (DGN) und die Deutsche Migräne-und Kopfschmerzgesellschaft (DMKG) haben diese Behandlungsansätze analysiert und Therapieempfehlungen mit dem Ziel einer Optimierung der Migränebehandlung zusammengefasst [2]. Während sich diese Therapieempfehlungen an verfügbaren klinischen Studien, medizinischen Veröffentlichungen und Expertenerfahrungen orientieren, sollen nachfolgend in erster Linie die für die Migränetherapie zugelassenen Arzneimittel vorgestellt und aktuelle Erkenntnisse diskutiert werden.
Clinical Pharmacology & Therapeutics, Nov 19, 2021
We outline our vision that by 2025 the use of real-world evidence will have been enabled and the ... more We outline our vision that by 2025 the use of real-world evidence will have been enabled and the value will have been established across the spectrum of regulatory use cases. We are working to deliver this vision through collaboration where we leverage the best that different stakeholders can bring. This vision will support the development and use of better medicines for patients.
Mittels bildgebender Verfahren wie die Single-Photon-Ernission-Computed-Tomography (SPECT) und di... more Mittels bildgebender Verfahren wie die Single-Photon-Ernission-Computed-Tomography (SPECT) und die Positron-Emission-Tomography (PET) konnten bei psychiatrischen Erkrankungen Perfusionsstorungen verschiedener Hirnareale nachgewiesen werden. Bei Schizophrenien hatte man in den fruheren Studien Veranderungen im Frontallappen (Buchsbaum et al. 1982) gefunden. Diese Befunde konnten in den neueren Arbeiten nicht repliziert werden, hingegen scheint der Temporallappen besonders betroffen zu sein (Buchsbaum et al. 1990, deLisi et al. 1989) Bei affektiven Storungen sind Veranderungen im prefrontalen Cortex (Baxter et al. 1989, Cohen et al. 1989) und im Temporallappen (Post et al. 1987, Amsterdam et al. 1992) festgestellt worden. Bei den meisten der obengenannten Untersuchungen — besonders den PET-Studien — wurde meistens die Psychopathologie zum Zeitpunkt der Untersuchung vernachlassigt. Daher haben wir uns im Rahmen des jetzigen Projektes zum Ziel gesetzt, zu untersuchen, inwiefern eine spezifische bzw. globale Psychopathologie im Zusammenhang mit Durchblutungsverhaltnissen (gemessen mit der HMPAO-SPECT-Technik) steht.
Background: In Germany, physicians who prescribe cannabis-based medicines at the expense of the s... more Background: In Germany, physicians who prescribe cannabis-based medicines at the expense of the statutory health insurance are obliged to take part in an accompanying survey. Pain was the most commonly reported diagnosis, making an interim evaluation for the indication of pain feasible. Methods: Patient-related data was transmitted to the German Federal Institute for Drugs and Medical Devices via an online portal. In addition to demographic data, information on the treated disease or symptoms, the course of therapy, adverse reactions and treatment success were evaluated. Results: A total of 3138 data sets were evaluated for the main diagnosis of pain. Dronabinol was the most frequently (64%) prescribed cannabis-based drug. On average, patients were 57 years old and women and men were equally represented. Patients treated with cannabis flowers were significantly younger (48 years). The proportion of men in this group was 68% and 83% in the group of 18- to 40-year-olds. According to the assessment by treating physicians, pain was significantly improved in 35.5% of the patients. The most frequent side effects (fatigue, dizziness, nausea) corresponded to those already known from the product information of the cannabis-based medicinal products authorized under the pharmaceutical law. Treatment was discontinued in 1179 patients within 1 year. Conclusion: Physicians should comply with their legal obligation to participate in the accompanying survey. Pain is by far the most common diagnosis in cannabis drugs. For about one third of these patients, physicians reported a clear improvement in pain. Due to the amount of data hitherto and the limitations in the accompanying survey, the results should not be overinterpreted in terms of efficacy and should always be related to existing reviews. The lower age and higher proportion of men among patients treated with cannabis flowers were remarkable. At 37.6%, the overall drop-out rate was high. The most frequent side effects related to vigilance and are therefore highly relevant in terms of driving ability, work ability and risk of falling. For a differentiated evaluation of treatment success, more data needs to be available.
Atopic conditions (atopic dermatitis, rhinitis, and asthma) belong to the most common noncommunic... more Atopic conditions (atopic dermatitis, rhinitis, and asthma) belong to the most common noncommunicable diseases and are driven by chronic inflammatory reactions. They have a strong impact on the quality of life and represent a substantial and growing socio-economic burden. Interestingly, there is an increasing interest in the development of new therapeutic options with a number of biologics and small molecules targeting potential key mechanisms in atopic conditions. However, besides the safety issue, most of the new active substances are still evaluated according to the traditional efficacy paradigm focusing on the success in treating exacerbations and flares. Instead, the future approaches in drug development and assessment should rather concentrate on the long-term control of these diseases and consider their potential as disease-modifying strategies in the era of precision medicine. To reach this goal, a number of unsolved issues have to be addressed and consensually accepted by the stakeholders in this field. Thus, a successful and rapid development of new treatments requests a paradigm shift and a new way of thinking in the mind of physicians, pharmaceutical industry, regulators, and HTAs. This seems mandatory in order to optimize drug development and to facilitate the accessibility of new therapies to the growing population of patients suffering from atopic conditions on a global level.
After supratentorial infarction crossed cerebellar diaschisis has been described. This report con... more After supratentorial infarction crossed cerebellar diaschisis has been described. This report concerns the rare phenomenon of crossed cerebral diaschisis in cerebellar infarction. Relative distribution of cerebral and cerebellar blood flow was measured using three-dimensional, qualitative single-photon-emission-computed-tomography (SPECT) with a rotating gamma camera and ~23I-IMP. Regional cerebral blood flow was calculated with the two-dimensional, quantitative ~33Xe-inhalation-technique. Reduced uptake was observed in the left cerebral hemisphere (-13.9%) contralateral to the cerebellar infarction with the most marked reduction in the left premotor region (-21%). This might be explained by the functional depression of cerebello-ponto-thalamo-cerebral pathways.
Verhandlungen der Deutschen Gesellschaft für Neurologie, 1987
Although its first-pass extraction following administration (nearly 100%) and stable distribution... more Although its first-pass extraction following administration (nearly 100%) and stable distribution for a certain period by the slow washout from the brain (3) suggest the desirable nature of123I-N-isopropylamphetamine (IMP) for quantitative evaluation of regional cerebral blood flow (rCBF), uncertainty about high-capacity nonspecific receptor-binding sites for amines in the brain may limit the reliability of the IMP technique for quantitative rCBF evaluations. In this study, we validated semiquantitatively assessed cerebral IMP uptake with a three dimensional single-photon emission computed tomography (SPECT) device without arterial sampling as compared with the two-dimensional 133Xe inhalation method in patients, with reference to findings in normal baboons.
Neue epidemiologische Studien haben die grose soziookonomische Bedeutung der Demenzerkrankungen b... more Neue epidemiologische Studien haben die grose soziookonomische Bedeutung der Demenzerkrankungen bestatigt. Die mit Abstand haufigste Ursache der Demenzerkrankungen stellt mit einem Anteil von ca. 60% die Demenz vom Alzheimer-Typ (DAT) dar. Neben klinischer und neuropsychologischer Untersuchung hat die Entwicklung neuer bildgebender Verfahren in der Differentialdiagnostik dementieller Abbausyndrome grose Bedeutung erlangt. Regionale Veranderungen von Hirnstoffwechsel und Hirndurchblutung wurden v.a. nach Anwendung der Positronen-Emissions-Tomographie bei der DAT beschrieben [3]. Wegen ihres hohen apparativen und personellen Aufwands eignet sich diese Methode jedoch nicht fur Routineuntersuchungen. Insbesondere bei der DAT wurden fokale Veranderungen der zerebralen Durchblutung aber auch mit der 133Xe-Inhalationszerebrographie (rCBF) [6] und der Single-Photon-Emissons-Computertomographie (SPECT) [5] erhoben. Bei 15 Patienten mit der klinischen Diagnose einer DAT wurden daher beide Methoden eingesetzt und die Ergebnisse miteinander verglichen.
& Avid (paid to institution); and has patents as co-inventor, but received no royalties: A patent... more & Avid (paid to institution); and has patents as co-inventor, but received no royalties: A patent in vitro multiparameter determination method for the Diagnosis and early diagnosis of neurodegenerative disorders. Patent number: 8916388 Issued. A patent in vitro procedure for diagnosis and early diagnosis of neurodegenerative diseases.
After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease... more After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single "magic bullet" drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological makeup. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker guided early preclinical disease stage clinical trials.
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in Engli... more Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Fehler im Umgang mit Medizinprodukten stellen ein signifikantes Risiko fur die Patientensicherhei... more Fehler im Umgang mit Medizinprodukten stellen ein signifikantes Risiko fur die Patientensicherheit dar. Im Rahmen der Forschung zur Anwendungssicherheit von Medizinprodukten untersucht das Bundesinstitut fur Arzneimittel und Medizinprodukte daher, inwieweit Merkmale von Medizinprodukt, Anwender und Anwendungskontext (oder deren spezifische Kombination) einem sicheren Umgang des Anwenders mit dem Produkt entgegenstehen. Zwei Themenbereiche werden beispielhaft adressiert: der Umgang der Anwender mit Alarmierungen (als eine weit verbreitete und besonders kritische Geratefunktion) sowie die Bedeutung von Informationen zur Sicherheit fur den Umgang mit Medizinprodukten generell. Beide Themen werden in der Literatur zurzeit als problematisch diskutiert – systematische empirische Untersuchungen fehlen allerdings weitgehend. Die vorliegende Arbeit gibt einen Uberblick uber die (wenigen) jeweils existierenden Befunde und diskutiert offene Fragen, deren sich das BfArM in seiner laufenden Forschung zur Anwendungssicherheit von Medizinprodukten annimmt.
The early assessment of benefits of newly approved drugs with novel active substances or new appl... more The early assessment of benefits of newly approved drugs with novel active substances or new applications, which came into force on 1 January 2011 still represents a challenge to all parties involved. This article highlights the definitions, regulatory requirements and interaction between drug marketing approval and early assessment of benefits in Germany. The constellation of an extensively harmonized European and even international drug authorization process with a predominantly national regulation of drug reimbursement situation inevitably causes friction, which could be markedly reduced through early joint advisory discussions during the planning phase for pivotal clinical trials. During the year 2015 the Federal Institute for Drugs and Medical Devices (BfArM) carried out 300 scientific advice procedures of which 34 were concerned with applications in the field of indications for the central nervous system (CNS). In comparison 98 advisory meetings were held by the Federal Joint Committee (G-BA) of which the BfArM provided advice in 12 instances and in 2 cases on CNS indications. Study design, endpoints and appropriate comparative therapies are the key issues in exchanges and discussions between the BfArM, the G‑BA and applicants. Under these aspects the BfArM and G‑BA promote an early and consistent involvement in early advice procedures regarding the prerequisites for drug approval and assessment of additional benefits.
Die Migräne ist eine chronische Erkrankung, bei der es aufgrund einer vermutlich genetischen Vera... more Die Migräne ist eine chronische Erkrankung, bei der es aufgrund einer vermutlich genetischen Veranlagung zu rezidivierenden Schmerzattacken kommt. Diese Schmerzattacken gehen obligat mit vegetativen und fakultativ mit vorübergehenden, fokal-neurologischen Symptomen (Aura) einher. Man unterscheidet 2 Hauptformen der Migräne: Migräne ohne Aura und Migräne mit Aura. Mit etwa 80-85 % ist die Migräne ohne Aura die häufigste Form. Die Klassifikation der Migräne und migräneartiger Erkrankungen erfolgt gemäß der Richtlinien der "International Headache Society" (IHS) [1]. Der typische Kopfschmerz bei einer Migräneattacke erfüllt mindestens 2 der folgenden 4 Kriterien: Er ist halbseitig, hat eine mäßig starke bis starke Intensität, einen pulsierenden Charakter und verstärkt sich bei körperlicher Anstrengung. Begleitend treten Übelkeit und Erbrechen sowie eine Licht-und Geräuschempfindlichkeit auf. Migräneanfälle mit einer Aura sind häufig von optischen oder sensorischen Wahrnehmungsstörungen geprägt. Dabei treten Gesichtsfeldausfälle, Sehstörungen, Gefühlstörungen (z. B. Kribbeln) in den Armen oder andere neurologische Ausfälle vor den Kopfschmerzen auf. Eine chronische Migräne liegt vor, wenn ein Patient an mehr als 15 Tagen im Monat über mehrere Monate (≥ 3) hinweg unter einer Migräne leidet. Davon abzugrenzen ist der chronische Kopfschmerz bei Medikamenteneinnahme, der insbesondere durch einen Übergebrauch von Analgetika induziert wird. Zur Behandlung der akuten Kopfschmerzphase eines Migräneanfalls und zur Migräneprophylaxe steht heute eine Vielzahl unterschiedlicher pharmakologischer Behandlungsansätze zur Verfügung. Die Deutsche Gesellschaft für Neurologie (DGN) und die Deutsche Migräne-und Kopfschmerzgesellschaft (DMKG) haben diese Behandlungsansätze analysiert und Therapieempfehlungen mit dem Ziel einer Optimierung der Migränebehandlung zusammengefasst [2]. Während sich diese Therapieempfehlungen an verfügbaren klinischen Studien, medizinischen Veröffentlichungen und Expertenerfahrungen orientieren, sollen nachfolgend in erster Linie die für die Migränetherapie zugelassenen Arzneimittel vorgestellt und aktuelle Erkenntnisse diskutiert werden.
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