Innovation in Regulatory Science Is Meeting Evolution of Clinical Evidence Generation

Lee, Myrto; Ly, Hoan; Möller, Clemens; Ringel, Michael

doi:10.1002/cpt.1354

Cited by 17 publications

(14 citation statements)

References 42 publications

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“…Fox Foundation convened a group of leading experts with the objective of improving the development of therapeutics for PD through the use of reliable digital endpoints. One gap that has been highlighted in the area of DHT is the lack of open-access consensus data standards that have been accepted by the community [34]. A diverse working group of data scientists, pharmaceutical companies, and data standard consortium partners codeveloped a comprehensive roadmap for metadata standards for DHT.…”

Section: Michael J Fox Foundation Digital Health Consortiummentioning

confidence: 99%

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

et al. 2020

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Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease. This poses a major challenge for the development of new therapies and is compounded by the considerable heterogeneity in clinical manifestations across patients and the fluctuating nature of many signs and symptoms of PD. Digital health technologies (DHT), such as smartphone applications, wearable sensors, and digital diaries, have the potential to address many of these gaps by enabling the objective, remote, and frequent measurement of PD signs and symptoms in natural living environments. The current climate of the COVID-19 pandemic creates a heightened sense of urgency for effective implementation of such strategies. In order for these technologies to be adopted in drug development studies, a regulatory-aligned consensus on best practices in implementing appropriate technologies, including the collection, processing, and interpretation of digital sensor data, is required. A growing number of collaborative initiatives are being launched to identify effective ways to advance the use of DHT in PD clinical trials. The Critical Path for Parkinson’s Consortium of the Critical Path Institute is highlighted as a case example where stakeholders collectively engaged regulatory agencies on the effective use of DHT in PD clinical trials. Global regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency, are encouraging the efficiencies of data-driven engagements through multistakeholder consortia. To this end, we review how the advancement of DHT can be most effectively achieved by aligning knowledge, expertise, and data sharing in ways that maximize efficiencies.

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Section: Michael J Fox Foundation Digital Health Consortiummentioning

confidence: 99%

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

et al. 2020

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“…This is particularly key with recent COVID-19-stimulated changes in the regulatory landscape, which supports the need for more flexible approaches. An example is a relatively recent shift of the proportion of the overall pharmaceutical development portfolio from small molecules or antibody-based programs to newer therapeutic modalities, which do not lend themselves well to the timing and comprehensive data requirements of traditional decision-making milestones inherent in development plans anchored in progression from phase I, II, and III [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

The Qualitative Value of Facilitated Regulatory Pathways in Europe, USA, and Japan: Benefits, Barriers to Utilization, and Suggested Solutions

2021

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Background Despite the growing application of facilitated regulatory pathways (FRPs), little attention has focused on assessing the perception of pharmaceutical companies regarding their usefulness beyond increasing timeliness. Objectives The aim of this study was to characterize the perceived value of four key FRPs, based on industry experiences in using these pathways. In addition, we sought to characterize the perceived impact based on benefits and barriers as well as suggested solutions for their use and recommendations as identified by companies, to outline how these FRPs may be further evolved as tools for expediting the development and regulatory review of important medicines. Methods A study was undertaken to characterize the perceived value and impact of US FDA (i.e., Breakthrough Therapy Designation, Fast Track), European Medicines Agency (i.e., PRIME), and Japanese Pharmaceutical and Medical Devices Agency (i.e., Sakigake) FRPs through a comprehensive analysis of strengths, weaknesses, opportunities, and threats (SWOT) as well as suggested solutions based on industry experiences with their use. The finalized survey comprised six questions and was sent to senior management in regulatory affairs departments at 22 multinational pharmaceutical companies in March 2019, with a deadline for completion by April 2019. The responses were analyzed using descriptive statistics. SWOT and free-text responses were reviewed and manually grouped into key themes according to high concordance. Results Survey results were returned by 11 pharmaceutical companies. Based on their perceived value and positive impact, the evaluated FRPs seem to be generally recognized as helpful tools for ensuring timely development and review of important medicines while ensuring multistakeholder involvement. Respondents overwhelmingly felt that the Breakthrough Therapy Designation carried a positive influence, both within and outside their organizations. Following closely with a positive although varied perception was Sakigake, but respondents exhibited more ambivalence about Fast Track and PRIME. Companies felt the impact of the FRPs was generally positive for most stakeholders except for health technology assessors/payers, highlighting the need to better align FRPs with flexible access and reimbursement pathways to expedite the equitable availability of high‐quality, safe, effective medicines. Conclusions This study highlighted common recommendations across all four FRPs (relating to resource optimization, education, alignment, and communication to improve effective use), as well as agency-specific recommendations, some of which are already being addressed by the regulators. Supplementary Information The online version contains supplementary material available at 10.1007/s40290-020-00372-7.

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“…In the study of Ohno[20]and Dennis[ 24 ], pulmonary artery perfusion in malignant lesions was higher than in benign lesions, which was consistent with our findings. Some studies [ 25 – 27 ]have found that pulmonary malignant lesions were mainly bronchial blood supply, benign lesions were mainly pulmonary artery blood supply. This was contrary to our results, maybe our study selected lung lesions larger than 2 cm in diameter, leading to an increase in pulmonary artery blood supply.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary lesions: correlative study of dynamic triple-phase enhanced CT perfusion imaging with tumor angiogenesis and vascular endothelial growth factor expression

et al. 2021

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Background To investigate value of the quantitative perfusion parameters of dynamic triple-phase enhanced CT in differential diagnosis of pulmonary lesions, and explore the correlation between perfusion parameters of lung cancer with microvessel density (MVD) and vascular endothelial growth factor (VEGF). Methods 73 consecutive patients with lung lesions who successfully underwent pre-operative CT perfusion examination with dynamic triple-phase enhanced CT and received a final diagnosis by postoperative pathology or a clinical follow-up. The cases were divided into malignant and benign groups according to the pathological results. CT perfusion parameters, such as Median, Mean, Standard deviation (Std), Q10, Q25, Q50, Q75, Q90 of pulmonary artery perfusion (PAP), bronchial artery perfusion (BAP), perfusion index (PI) and arterial enhancement fraction (AEF) were obtained by performing computed tomography perfusion imaging (CTPI). Computed tomography perfusion (CTP) parameters were compared between malignant and benign lesions. The receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of CTP parameters in diagnosing malignant lesions. The correlations between CTP parameters with MVD and VEGF were analysed in 36 lung cancer patients who had extra sections be used for immunohistochemistry staining of CD34 and VEGF. Results BAP (Mean, Std, Q90) and PI Std of benign lesions were higher than malignant lesions (p < 0.05), and PAP (Q10, Q25), PI (Median, Mean, Q10, Q25, Q50) of malignant lesions were higher than the benign (p < 0.05). The area under the ROC curve of PI Mean, PI Q10 and PI Std was 0.722 (95% CI = [0.595–0.845]), 0.728 (95% CI = [0.612–0.844]) and 0.717 (95% CI = [0.598–0.835]) respectively. Partial perfusion parameters of BAP and AEF Q10 were positively correlated with MVD (p value range is < 0.001–0.037, ρ value range is 0.483–0.683), and partial perfusion parameters of PI were negatively correlated with MVD (p value range is 0.001–0.041,ρvalue range is − 0.523–− 0.343). Partial perfusion parameters of BAP and AEF Q10 were positively correlated with VEGF (p value range is 0.001–0.016, ρvalue range is 0.398–0.570), meanwhile some perfusion parameters of PAP and PI were negatively correlated with VEGF (p value range is 0.001–0.040, ρ value range is − 0.657–0.343). Conclusions Quantitative parameters of dynamic triple-phase enhanced CT can provide diagnostic basis for the differentiation of lung lesions, and there were connection with tumor angiogenesis and vascular endothelial growth factor expression.

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Innovation in Regulatory Science Is Meeting Evolution of Clinical Evidence Generation

Cited by 17 publications

References 42 publications

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

The Qualitative Value of Facilitated Regulatory Pathways in Europe, USA, and Japan: Benefits, Barriers to Utilization, and Suggested Solutions

Pulmonary lesions: correlative study of dynamic triple-phase enhanced CT perfusion imaging with tumor angiogenesis and vascular endothelial growth factor expression

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