Zusammenarbeit mit klinischen Auftragsforschungsinstituten : Vorstellung eines Fragebogens für klinische Studienzentren

Klinische Studien mit Arzneimitteln oder Medizinprodukten stellen zunehmend komplexe Anforderungen an Sponsoren und beteiligte Zentren. In den letzten 2 Jahrzehnten delegieren Sponsoren regulatorische sowie organisatorische Studienaufgaben zunehmend an medizinische Auftragsinstitute (engl. Clinical Research Organisation [CRO]). In der Regel sind diese Unternehmen die Hauptschnittstelle für die Zusammenarbeit mit den beteiligten Studienzentren. Hauptzweck der Mitwirkung ist die Unterstützung der Studienzentren zur Erzielung einer maximalen Studienqualität. Die in der Arbeitsgemeinschaft DOG Klinische Studienzentren verbundenen Studienzentren beobachten unterschiedliche Erfahrungen in der Zusammenarbeit mit CROs. Solche Erfahrungen sollen künftig systematisch an den beteiligten Zentren erfasst und vom Leiter der klinischen Studie ausgewertet werden. Die Spiegelung dieser Erfahrungen an die jeweiligen Auftragsinstitute und die sie beauftragenden Sponsoren kann in der Zukunft zur Qualität der Unterstützung durch CROs und damit zur Studienqualität beitragen. Die vorliegende Arbeit stellt vor, welche Bereiche der Zusammenarbeit im Fragebogen erfasst und analysiert werden.Clinical trials with pharmaceuticals or medical devices make complex demands on sponsors and participating centers. During the past two decades, sponsors have increasingly delegated regulatory and organizational tasks to clinical research organizations (CRO). As a rule, these companies are the main interface for the collaboration with the participating study centers. The main purpose of the participation is the support of the study centers for achieving an optimal study quality. The study centers involved in the DOG working group on clinical study centers perceived varying experiences in the collaboration with CROs. In the future these experiences will be systematically assessed at the participating study centers and analyzed by the coordinating investigator. Reflecting these experiences to the respective CROs and the delegating sponsors will contribute to the quality of support by CROs and herewith to the quality of clinical trials. This paper presents which areas of collaboration will be assessed and analyzed

Collaboration with clinical research organizations

Zusammenfassung Klinische Studien mit Arzneimitteln oder Medizinprodukten stellen zunehmend komplexe Anforderungen an Sponsoren und beteiligte Zentren. In den letzten 2 Jahrzehnten delegieren Sponsoren regulatorische sowie organisatorische Studienaufgaben zunehmend an medizinische Auftragsinstitute (engl. Clinical Research Organisation [CRO]). In der Regel sind diese Unternehmen die Hauptschnittstelle für die Zusammenarbeit mit den beteiligten Studienzentren. Hauptzweck der Mitwirkung ist die Unterstützung der Studienzentren zur Erzielung einer maximalen Studienqualität. Die in der Arbeitsgemeinschaft DOG Klinische Studienzentren verbundenen Studienzentren beobachten unterschiedliche Erfahrungen in der Zusammenarbeit mit CROs. Solche Erfahrungen sollen künftig systematisch an den beteiligten Zentren erfasst und vom Leiter der klinischen Studie ausgewertet werden. Die Spiegelung dieser Erfahrungen an die jeweiligen Auftragsinstitute und die sie beauftragenden Sponsoren kann in der Zukunft zur Qualität der Unterstützung durch CROs und damit zur Studienqualität beitragen. Die vorliegende Arbeit stellt vor, welche Bereiche der Zusammenarbeit im Fragebogen erfasst und analysiert werden.Abstract Clinical trials with pharmaceuticals or medical devices make complex demands on sponsors and participating centers. During the past two decades, sponsors have increasingly delegated regulatory and organizational tasks to clinical research organizations (CRO). As a rule, these companies are the main interface for the collaboration with the participating study centers. The main purpose of the participation is the support of the study centers for achieving an optimal study quality. The study centers involved in the DOG working group on clinical study centers perceived varying experiences in the collaboration with CROs. In the future these experiences will be systematically assessed at the participating study centers and analyzed by the coordinating investigator. Reflecting these experiences to the respective CROs and the delegating sponsors will contribute to the quality of support by CROs and herewith to the quality of clinical trials. This paper presents which areas of collaboration will be assessed and analyzed.Zusammenfassung Klinische Studien mit Arzneimitteln oder Medizinprodukten stellen zunehmend komplexe Anforderungen an Sponsoren und beteiligte Zentren. In den letzten 2 Jahrzehnten delegieren Sponsoren regulatorische sowie organisatorische Studienaufgaben zunehmend an medizinische Auftragsinstitute (engl. Clinical Research Organisation [CRO]). In der Regel sind diese Unternehmen die Hauptschnittstelle für die Zusammenarbeit mit den beteiligten Studienzentren. Hauptzweck der Mitwirkung ist die Unterstützung der Studienzentren zur Erzielung einer maximalen Studienqualität. Die in der Arbeitsgemeinschaft DOG Klinische Studienzentren verbundenen Studienzentren beobachten unterschiedliche Erfahrungen in der Zusammenarbeit mit CROs. Solche Erfahrungen sollen künftig systematisch an den beteiligten Zentren erfasst und vom Leiter der klinischen Studie ausgewertet werden. Die Spiegelung dieser Erfahrungen an die jeweiligen Auftragsinstitute und die sie beauftragenden Sponsoren kann in der Zukunft zur Qualität der Unterstützung durch CROs und damit zur Studienqualität beitragen. Die vorliegende Arbeit stellt vor, welche Bereiche der Zusammenarbeit im Fragebogen erfasst und analysiert werden.Abstract Clinical trials with pharmaceuticals or medical devices make complex demands on sponsors and participating centers. During the past two decades, sponsors have increasingly delegated regulatory and organizational tasks to clinical research organizations (CRO). As a rule, these companies are the main interface for the collaboration with the participating study centers. The main purpose of the participation is the support of the study centers for achieving an optimal study quality. The study centers involved in the DOG working group on clinical study centers perceived varying experiences in the collaboration with CROs. In the future these experiences will be systematically assessed at the participating study centers and analyzed by the coordinating investigator. Reflecting these experiences to the respective CROs and the delegating sponsors will contribute to the quality of support by CROs and herewith to the quality of clinical trials. This paper presents which areas of collaboration will be assessed and analyzed

Zusammenarbeit mit klinischen Auftragsforschungsinstituten

Clinical trials with pharmaceuticals or medical devices make complex demands on sponsors and participating centers. During the past two decades, sponsors have increasingly delegated regulatory and organizational tasks to clinical research organizations (CRO). As a rule, these companies are the main interface for the collaboration with the participating study centers. The main purpose of the participation is the support of the study centers for achieving an optimal study quality. The study centers involved in the DOG working group on clinical study centers perceived varying experiences in the collaboration with CROs. In the future these experiences will be systematically assessed at the participating study centers and analyzed by the coordinating investigator. Reflecting these experiences to the respective CROs and the delegating sponsors will contribute to the quality of support by CROs and herewith to the quality of clinical trials. This paper presents which areas of collaboration will be assessed and analyzed

Zusammenarbeit mit klinischen Auftragsforschungsinstituten

ZusammenfassungKlinische Studien mit Arzneimitteln oder Medizinprodukten stellen zunehmend komplexe Anforderungen an Sponsoren und beteiligte Zentren. In den letzten 2 Jahrzehnten delegieren Sponsoren regulatorische sowie organisatorische Studienaufgaben zunehmend an medizinische Auftragsinstitute (engl. Clinical Research Organisation [CRO]). In der Regel sind diese Unternehmen die Hauptschnittstelle für die Zusammenarbeit mit den beteiligten Studienzentren. Hauptzweck der Mitwirkung ist die Unterstützung der Studienzentren zur Erzielung einer maximalen Studienqualität. Die in der Arbeitsgemeinschaft DOG Klinische Studienzentren verbundenen Studienzentren beobachten unterschiedliche Erfahrungen in der Zusammenarbeit mit CROs. Solche Erfahrungen sollen künftig systematisch an den beteiligten Zentren erfasst und vom Leiter der klinischen Studie ausgewertet werden. Die Spiegelung dieser Erfahrungen an die jeweiligen Auftragsinstitute und die sie beauftragenden Sponsoren kann in der Zukunft zur Qualität der Unterstützung durch CROs und damit zur Studienqualität beitragen. Die vorliegende Arbeit stellt vor, welche Bereiche der Zusammenarbeit im Fragebogen erfasst und analysiert werden.</jats:p

Different ranibizumab dosages for retinopathy of prematurity: 5-year follow-up data of the randomised, controlled CARE-ROP Study

Background Data on long-term outcomes of antivascular endothelial growth factor therapy in retinopathy of prematurity (ROP) are still rare. We present 5-year post-treatment ophthalmological and paediatric outcomes of the prospective, multicentre, randomised, double-blinded, controlled pilot study CARE-ROP (Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity).Methods 14 patients (28 eyes) completed the ophthalmologic and 5 patients completed the paediatric 5-year follow-up assessment. The ophthalmological assessment included best-corrected visual acuity (BCVA), orthoptic status, slit lamp examination, intraocular pressure and funduscopy. The paediatric examination followed the German Neonatal Network protocol and covered cognitive, motor and sensory development.Results 17 of 28 eyes exhibited at least one ocular abnormality, such as optic disc pallor or atrophy of the optic nerve head, retinal pigment epithelium (RPE) pigment changes, persistent tortuosity or macular hypoplasia. Despite this, 19 of 26 eyes demonstrated a logarithm of the Minimum Angle of Resolution (logMAR) BCVA of 0.3 or better. Mean refractive error was −0.9 D (±3.4 D) with only two eyes of one infant having high myopia of &lt; −5 D. The neurodevelopmental results were within the expected range for a population of preterm infants with treatment-warranting ROP but need to be interpreted with caution due to the low number of five patients.Conclusion The 5-year ophthalmologic and paediatric outcomes of the CARE-ROP study confirm the previous results and add important additional information on long-term safety of 0.12 and 0.20 mg ranibizumab for the treatment of ROP. The ophthalmologic functional outcome regarding BCVA and refraction is promising. These exploratory long-term data, however, need to be interpreted with caution due to the low patient number both in the ophthalmologic and paediatric assessment

Assessment of retinopathy of prematurity regression and reactivation using an artificial intelligence–based vascular severity score

IMPORTANCE One of the biggest challenges when using anti-vascular endothelial growth factor (VEGF) agents to treat retinopathy of prematurity (ROP) is the need to perform long-term follow-up examinations to identify eyes at risk of ROP reactivation requiring retreatment. OBJECTIVE To evaluate whether an artificial intelligence (AI)-based vascular severity score (VSS) can be used to analyze ROP regression and reactivation after anti-VEGF treatment and potentially identify eyes at risk of ROP reactivation requiring retreatment. DESIGN, SETTING, AND PARTICIPANTS This prognostic study was a secondary analysis of posterior pole fundus images collected during the multicenter, double-blind, investigator-initiated Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) randomized clinical trial, which compared 2 different doses of ranibizumab (0.12 mg vs 0.20 mg) for the treatment of ROP. The CARE-ROP trial screened and enrolled infants between September 5, 2014, and July 14, 2016. A total of 1046 wide-angle fundus images obtained from 19 infants at predefined study time points were analyzed. The analyses of VSS were performed between January 20, 2021, and November 18, 2022. INTERVENTIONS An AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images. MAIN OUTCOMES AND MEASURES Analysis of VSS in infants with ROP over time and VSS comparisons between the 2 treatment groups (0.12 mg vs 0.20mg of ranibizumab) and between infants who did and did not receive retreatment for ROP reactivation. RESULTS Among 19 infants with ROP in the CARE-ROP randomized clinical trial, the median (range) postmenstrual age at first treatment was 36.4 (34.7-39.7) weeks; 10 infants (52.6%) were male, and 18 (94.7%) were White. The mean (SD) VSS was 6.7 (1.9) at baseline and significantly decreased to 2.7 (1.9) at week 1 (P < .001) and 2.9 (1.3) at week 4 (P < .001). The mean (SD) VSS of infants with ROP reactivation requiring retreatment was 6.5 (1.9) at the time of retreatment, which was significantly higher than the VSS at week 4 (P < .001). No significant difference was found in VSS between the 2 treatment groups, but the change in VSS between baseline and week 1 was higher for infants who later required retreatment (mean [SD], 7.8 [1.3] at baseline vs 1.7 [0.7] at week 1) vs infants who did not (mean [SD], 6.4 [1.9] at baseline vs 3.0 [2.0] at week 1). In eyes requiring retreatment, higher baseline VSS was correlated with earlier time of retreatment (Pearson r = -0.9997; P < .001). CONCLUSIONS AND RELEVANCE In this study, VSS decreased after ranibizumab treatment, consistent with clinical disease regression. In cases of ROP reactivation requiring retreatment, VSS increased again to values comparable with baseline values. In addition, a greater change in VSS during the first week after initial treatment was found to be associated with a higher risk of later ROP reactivation, and high baseline VSS was correlated with earlier retreatment. These findings may have implications for monitoring ROP regression and reactivation after anti-VEGF treatment

Assessment of Retinopathy of Prematurity Regression and Reactivation Using an Artificial Intelligence–Based Vascular Severity Score

ImportanceOne of the biggest challenges when using anti–vascular endothelial growth factor (VEGF) agents to treat retinopathy of prematurity (ROP) is the need to perform long-term follow-up examinations to identify eyes at risk of ROP reactivation requiring retreatment.ObjectiveTo evaluate whether an artificial intelligence (AI)–based vascular severity score (VSS) can be used to analyze ROP regression and reactivation after anti-VEGF treatment and potentially identify eyes at risk of ROP reactivation requiring retreatment.Design, Setting, and ParticipantsThis prognostic study was a secondary analysis of posterior pole fundus images collected during the multicenter, double-blind, investigator-initiated Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) randomized clinical trial, which compared 2 different doses of ranibizumab (0.12 mg vs 0.20 mg) for the treatment of ROP. The CARE-ROP trial screened and enrolled infants between September 5, 2014, and July 14, 2016. A total of 1046 wide-angle fundus images obtained from 19 infants at predefined study time points were analyzed. The analyses of VSS were performed between January 20, 2021, and November 18, 2022.InterventionsAn AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images.Main Outcomes and MeasuresAnalysis of VSS in infants with ROP over time and VSS comparisons between the 2 treatment groups (0.12 mg vs 0.20 mg of ranibizumab) and between infants who did and did not receive retreatment for ROP reactivation.ResultsAmong 19 infants with ROP in the CARE-ROP randomized clinical trial, the median (range) postmenstrual age at first treatment was 36.4 (34.7-39.7) weeks; 10 infants (52.6%) were male, and 18 (94.7%) were White. The mean (SD) VSS was 6.7 (1.9) at baseline and significantly decreased to 2.7 (1.9) at week 1 (P &amp;amp;lt; .001) and 2.9 (1.3) at week 4 (P &amp;amp;lt; .001). The mean (SD) VSS of infants with ROP reactivation requiring retreatment was 6.5 (1.9) at the time of retreatment, which was significantly higher than the VSS at week 4 (P &amp;amp;lt; .001). No significant difference was found in VSS between the 2 treatment groups, but the change in VSS between baseline and week 1 was higher for infants who later required retreatment (mean [SD], 7.8 [1.3] at baseline vs 1.7 [0.7] at week 1) vs infants who did not (mean [SD], 6.4 [1.9] at baseline vs 3.0 [2.0] at week 1). In eyes requiring retreatment, higher baseline VSS was correlated with earlier time of retreatment (Pearson r = −0.9997; P &amp;amp;lt; .001).Conclusions and RelevanceIn this study, VSS decreased after ranibizumab treatment, consistent with clinical disease regression. In cases of ROP reactivation requiring retreatment, VSS increased again to values comparable with baseline values. In addition, a greater change in VSS during the first week after initial treatment was found to be associated with a higher risk of later ROP reactivation, and high baseline VSS was correlated with earlier retreatment. These findings may have implications for monitoring ROP regression and reactivation after anti-VEGF treatment.</jats:sec