Evaluation of Clinical Trials in Onco-haematology: A New Method Based on Risk Analysis and Multidisciplinarity.

BACKGROUND: European member states are increasingly vying with one another to recruit patients for clinical trials (CTs). The French national agency for medicines (ANSM) now receives an ever-growing number of CTs, extending response times. The aim of the new methodology presented herein is to reduce assessment times below the national mandatory timeframe of 60 days and to improve patient safety. MATERIALS AND METHODS: Based on an analysis of the criteria defining CTs, 4 key points were identified (safety, fragile population, loss of opportunity, design complexity) to build a criticality score which would determine evaluation type. This score also determines the resources needed (complete evaluation, multidisciplinary advice, ad hoc evaluation) and the timeframe required for appropriate analysis. All post-phase I CTs were analysed from the implementation of the new assessment method, on 01/02/2018 through to 31/12/2019. RESULTS: 447 CTs were analysed (63% industry and 37% academic sponsors). Based on a criticality scale, 27% of the CTs received a type A evaluation (complete), 37% a type B (multidisciplinary evaluation), 23% a type C evaluation (ad hoc evaluation) and 13% a type D evaluation (fast evaluation). From 2014 to 2017, 37% of the CTs were analysed within the mandatory timeframe, with a mean of 68 days, reaching a maximum of 102 days in 2017. Using this new assessment method, 92% of CTs respected the mandatory timeframe in 2019; the mean time in 2018-2019 was 34 days; Grounds for Non-Acceptance (GNA) were raised for 66% of the CTs (69% from academic sponsors and 65% from industrial firms). 3 CTs were refused. CONCLUSION: Here, we demonstrate the feasibility of risk analysis and multidisciplinarity method, which resulted in a dramatic improvement of assessment times.

Impact of coronary plaque morphology as assessed by IVUS computer-aided analysis on mechanisms of balloon angioplasty and stenting.

This study was performed in order to quantitate structural coronary plaque modifications after balloon angioplasty and stenting and to evaluate the impact of plaque morphology on the mechanisms of lumen enlargement during angioplasty. Plaque morphology was studied by computer-aided analysis of 60 cross-sectional intravascular ultrasound (IVUS) images of the target lesion in 20 patients undergoing percutaneous coronary angioplasty. Based on a computer-aided video densitometry classification of plaque morphology, three groups of plaques were defined based on the slope value of a fifth polynomial regression of the plaque gray-level distribution. In groups A and B, balloon angioplasty provided significant increases in lumen area (P < 0.0001) and vessel area (P < 0.05) without a reduction in plaque area; neither parameter increased in group C. In group A, stenting was associated with an additional lumen enlargement (P < 0.0001) due to plaque reduction (P < 0.05). In groups B and C, stenting further increased lumen area (P < 0.0001) by improving vessel area (P < 0.001) but without plaque reduction. Balloon angioplasty and stenting provided a significant decrease in plaque area in group A as compared to groups B (P < 0.05) and C (P < 0.01). Finally, vessel area improvement was greater in group B than in groups A (P < 0.01) and C (P < 0.05). The mechanisms underlying lumen enlargement after coronary angioplasty are highly dependent on plaque morphology as defined by an IVUS computer-aided analysis and may differ between balloon angioplasty and stenting.