| Title: |
Impact of retrospective data verification to prepare the ICON6 trial for use in a marketing authorization application |
| Authors: |
Embleton-Thirsk, A; Deane, E; Townsend, S; Farrelly, L; Popoola, B; Parker, J; Rustin, G; Sydes, M; Parmar, M; Ledermann, J; Kaplan, R |
| Source: |
Clinical Trials , 16 (5) pp. 502-511. (2019) |
| Publisher Information: |
SAGE PUBLICATIONS LTD |
| Publication Year: |
2019 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Data verification; quality; independent review; data entry; monitoring; error rate |
| Description: |
Background: The ICON6 trial (ISRCTN68510403) is a phase III academic-led, international, randomized, three-arm, double-blind, placebo-controlled trial of the addition of cediranib to chemotherapy in recurrent ovarian cancer. It investigated the use of placebo during chemotherapy and maintenance (arm A), cediranib alongside chemotherapy followed by placebo maintenance (arm B) and cediranib throughout both periods (arm C). Results of the primary comparison showed a meaningful gain in progression-free survival (time to progression or death from any cause) when comparing arm A (placebo) with arm C (cediranib). As a consequence of the positive results, AstraZeneca was engaged with the Medical Research Council trials unit to discuss regulatory submission using ICON6 as the single pivotal trial. / Methods: A relatively limited level of on-site monitoring, single data entry and investigator’s local evaluation of progression were used on trial. In order to submit a license application, it was decided that (a) extensive retrospective source data verification of medical records against case report forms should be performed, (b) further quality control checks for accuracy of data entry should be performed and (c) blinded independent central review of images used to define progression should be undertaken. To assess the value of these extra activities, we summarize the impact on both efficacy and safety outcomes. / Results: Data point changes were minimal; those key to the primary results had a 0.47% error rate (36/7686), and supporting data points had a 0.18% error rate (109/59,261). The impact of the source data verification and quality control processes were analyzed jointly. The conclusion drawn for the primary outcome measure of progression-free survival between arm A and arm C was unchanged. The log-rank test p-value changed only at the sixth decimal place, the hazard ratio does not change from 0.57 with the exception of a marginal change in its upper bound (0.74–0.73) and the median progression-free survival benefit ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10082929/1/Embleton_ClinicalTrials_rev2.pdf; https://discovery.ucl.ac.uk/id/eprint/10082929/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10082929/1/Embleton_ClinicalTrials_rev2.pdf; https://discovery.ucl.ac.uk/id/eprint/10082929/ |
| Rights: |
open |
| Accession Number: |
edsbas.809FD548 |
| Database: |
BASE |