KEY HIGHLIGHTS
- This study had a complicated trial set up, with two protocols and two distinct databases merged into one consolidated database
- Over 1800 patients were involved, from 420 centres across 23 countries (United States and Rest of World)
- There were multiple trial partners, so working in collaboration was key
- The study results led to treatment intervention being approved by regulators across the globe, including the FDA, PMDA and EMA
THE SITUATION
The trial was a placebo-controlled, double-blind randomised trial of an investigational product in treating patients with genetic BRCA mutations. The trial also tested the outcomes for patients with high-risk breast cancer following therapy. Over the course of five years, more than 14,000 patients were screened and over 1800 patients recruited from 420 centres in 23 countries.
This was a collaborative project, with two sponsors, a clinical cooperative group, an academic research group and two Frontier Science offices (Scotland and United States) working together to run the trial. Frontier Science Scotland (FSS) was commissioned to:
- Manage the data for the Rest of World (RofW)
- Create a consolidated database to merge RofW and United States (US) data
- Generate CDISC-compliant analysis files
- Conduct the statistical analysis.
THE CHALLENGE
The trial had two separate Rave databases for collating study data. The RofW data was managed by FSS, and the US data was managed by the clinical cooperative group in accordance with National Cancer Institute (NCI) principles. Together, we had to ensure the Case Report Forms (CRFs) and CRF completion guidelines were consistent and the same or equivalent edit checks were used during the study build. We also merged and standardised the data from both databases into a single consolidated database for analysis.
OUR SOLUTION
Check the consistency of the data
To ensure data collection, cleaning and management were standardised across all organisations, we performed various consistency checks:
- Comparison of electronic Case Report Forms and their mapping to the consolidated database, plus eCRF completion guidelines and edit checks
- Coding for both RofW and US
- Where possible, the same rules around missing data were used for both electronic data captures.
Ensure high data quality
To ensure high quality data, we performed various data quality control checks on both sets of data:
- In-house bespoke data quality software was created and run on the consolidated database. The checks were defined collaboratively between our data management and programming teams
- Partial dates: lists were provided to both data management teams to try to get complete dates where possible. Partial dates were reviewed by our statistical team to assess their impact on the analysis
- Lab data: checks were made to ensure lab results were within specified limits
- Prior chemotherapy data: a clinical science review was conducted to ensure all data reported met the trial’s eligibility criteria.
THE OUTCOME
The results of the trial were submitted to all major regulatory authorities, resulting in the investigational product being approved as a treatment for early breast cancer.
Collaboration and excellent communication between the two data management teams, plus stringent data quality procedures, ensured the data across the two distinct data capture systems was consistent and high quality.
At database lock, 99.98% of lab issues and 99.99% of data queries were resolved and anything remaining was risk-assessed by the wider study team as having minimal or no impact on the consolidated database. The study was inspected by the FDA and the PMDA, who found zero data management issues.
The ability of our team to be flexible and accommodate many changes during the study was one of the contributing factors to its success, as well as the bespoke and robust data review process we developed.
Frontier Science Scotland provides adaptable data management and biostatistics solutions for clinical trials. To find out more, get in touch.
