KEY HIGHLIGHTS
- Frontier Science Scotland (FSS) commissioned to monitor all study phases of a proof-of-concept phase II randomised clinical study in Norway
- Our risk-based approach to monitoring provided much needed flexibility
- Monitor had a strong background in data management practices which helped to ensure accurate and complete data
- Fostered ALCOA (attributable, legible, contemporaneous, original and accurate) documentation practices and helped the site conform to Good Clinical Practice
THE SITUATION
In simple terms, this clinical trial tested the efficacy of cetuximab, a type of targeted cancer drug, in reducing neuropathic pain.
This was a proof-of-concept phase II randomised clinical study (15 patients at a single study site in Norway) which consisted of two blinded treatment periods followed by open label cetuximab for all patients. The investigator-led clinical trial aimed to determine the difference in average neuropathic pain score reduction between patients with defined neuropathic pain, using cetuximab and a placebo administered in a blinded crossover design.
THE CHALLENGE
Among other tasks, FSS was appointed to monitor the full study lifecycle, from protocol development to publication, working in collaboration with the study investigators. We created a risk assessment and developed a tailored monitoring plan. The appointed monitor from FSS then conducted a mix of in-person and remote visits to the clinical trial site.
Although it was a small study, with only 15 patients randomised, it had a complex study design. Most of the data collected and analysed was from patient-reported pain questionnaires where the patient’s first language was not English. Patient medical notes were electronic, and questionnaires were completed on paper and entered into the clinical database by the study nurse.
During the first onsite monitoring visit, our monitor conducted Source Data Verification (SDV) on the first two patients and identified a high volume of discrepancies. The study was further complicated by the trial site lacking study-specific documentation and a change in pharmacy triggering a review of the drug accountability process.
OUR SOLUTION
FSS had initially been tasked with carrying out SDV only on critical variables. As our monitor raised queries about the source data discrepancies both during and after their initial visit, we switched to 100% SDV to ensure adequate and accurate data. To improve the data quality, we provided extra onsite staff training on using the Electronic Data Capture (EDC) system, plus web-based training and eCRF guidelines. The combination of these approaches enabled all discrepancies to be resolved.
To ensure complete data, we created and shared a Data Management Plan with the trial site. This outlined a data entry schedule that enabled timely data cleaning. Our monitor had a strong background in data management, so they were able to guide the client on effective data handling solutions.
By providing tailored study site documentation for the site to follow, we fostered ALCOA (attributable, legible, contemporaneous, original and accurate) documentation practices and helped the site conform to Good Clinical Practice.
THE OUTCOME
Thanks to the data management experience of our monitor and quality expertise within the wider FSS team, we ensured that all issues picked up during monitoring were quickly addressed. This resulted in a complete and accurate database for the final analysis.
FSS worked closely with the site, taking risk-based decisions to ensure that all activities conformed to Good Clinical Practice. As well as increasing the SDV level after the initial site visits, we also split the close-out visit into two parts to accommodate site staff and final checks related to the Clinical Study Report.
Our monitor developed an excellent working relationship with the site staff, enjoying a good rapport with the nursing staff and the investigators. This was particularly helpful when source records had to be translated from Norwegian to English so the monitor could review them. We carried out all study activities on time, to a tight deadline.
As well as handling the monitoring, we provided other services for this clinical trial, including protocol development, Case Review File design, database build, randomisation, data management, Trial Master File management and statistical programming and analysis.
