Phase I/II study in cancer patients showcases eClinical effectiveness.
Complex study designs are fast becoming the norm—but integrated clinical trial technology can make even the more complicated of data collection requirements a breeze.
IDDI worked on a Phase I/II trial for people with cancer who were ineligible for induction chemotherapy.
High risk participants, complex protocol design, and COVID-19 risk mitigation were among the multiple challenges faced by the sponsor, but all were overcome thanks to the utilization of a range of eClinical tools.
In this case study, we look at how integrated eClinical tools can accelerate study implementation, help to determine a recommended dose safely and accurately, and reduce burden on site staff. We will also look at how to foster effective collaborative partnerships with clinical monitoring teams during a study.
The trial was a Phase I/II open-label, dose-finding, safety, efficacy study, in patients with cancer who were ineligible for induction chemotherapy. It ran across six centers for a total of 32 months.
Phase I, which involved 18 subjects, consisted of dose exploration, and escalation strategies were used to establish the recommended Phase II dose and schedule.
Phase II enrolled 175 patients on an open-label 2:1 randomized design, to evaluate the effect of treatment at the recommended dose.
Participants in both phases were adults. In Phase II, additional constraints were added the eligibility criteria.
Sponsors were faced with a multitude of challenges conducting this dose exploration trial.
To protect participant safety and quickly move from Phase I to Phase II, the team needed to rapidly access all captured data from a variety of sources. These included the electronic case report forms (eCRF), laboratory reports, randomization, and trial supply management (RTSM), and a range of external systems.
This was a complex protocol design. During Phase I, subjects were started on an initial dose of the targeted drug in combination with another product. The dose was then escalated and evaluated for the occurrence of events, using a standard 3+3 dose escalation protocol.
In addition, specific data collection requirements included the dose-escalation algorithm, and tumor and radiological assessments. All of this posed a huge potential to place additional burden on sites, and sponsors wanted to ease the
Implementation during COVID-19 was another challenge for the team, who were aware that the pandemic could result in missed visits and missing data. They wanted a robust mechanism, which recognized the importance of risk-based monitoring, to ensure study goals could still be met.
The sponsor selected IDDI as its biometric partner, and we provided our fully integrated eClinical suite, which features electronic data capture (EDC) and RTSM, as well as data collection, data cleaning, and data analysis. Using a single vendor to provide these tasks and services, the client felt, ensured data quality and coherence with trial design.
The solution helped overcome many of the traditional challenges of EDC, delivering data according to the protocol, collecting only those data necessary for the statistical analysis, and collecting data in an accessible format during study analysis.
In terms of tumor assessment, investigators simply entered information such as lesion type and location at the screening visit, and this information was systematically copied over into the relevant response assessment visits. This allowed investigators to accurately follow tumor evolution throughout
Another vendor was selected to perform clinical and medical monitoring, which enabled a clear separation of tasks.
The eClinical suite is fully integrated, removing the need for repetition of tasks in multiple systems. Date of birth, for example, need only be entered once, and is then displayed across systems. This reduces site burden and the potential for error, while streamlining the process and protecting data quality and integrity.
This approach enabled the sponsor to implement the complex dose-escalation algorithm into the eCRF, which contributed to the rapid and accurate determination of the recommended Phase II dose.
Tumor and radiological assessments were accessible within the eCRF. Calculation functionalities within the system copied the target and non-target lesions, documented at baseline, into post-treatment visits. This ensured consistency in lesion identification across the entire study and reduced data entry.
Linking the RTSM to eCRF and payment sheets to schedule visits also reduced administrative burden, and the creation of precise edit checks limited time-consuming, expensive data cleaning.
The team applied a monitoring plan to the EDC, which guided site staff through source data verification to avoid missed data, and were given rapid access to data via ad-hoc reports, based on their own study element and timeline interests.
While joint working was imperative, it was also important to keep a clear separation between the IDDI’s biometry and the monitoring vendor’s team for a number of reasons. First, it enabled each to focus on their own areas of expertise and gave the biometry CRO the ability to act as an unbiased, independent partner when conducting statistical monitoring and data quality assessment.
This balance was achieved in several ways. For example, while the clinical data management (CDM) and biostatistics services were linked, monitoring data was kept separate to give each vendor an independent view of the information. In addition, key data management and biostatistics milestones were integrated into the planning to enable effective co-working. It meant, for example, that the CDM team was able to start programming the study data tabulation model (SDTM), as soon as the eCRF had been finalized as per the analysis data mode datasets (ADaM).
The protocol amendment process was also carefully managed. The lead CDM, biostatistician, and sponsor managing director all reviewed the protocol to make sure everyone knew the schedule of assessments and the data to be collected. Once the protocol was finalized and eCRF had been developed, the biostatisticians carried out another review, to make sure all endpoints had been included, and that all captured data could be
IDDI’s integrated eClinical suite and expert team successfully were able to rapidly implement this study design in just three months, and then quickly and accurately determine the recommended Phase II dose.
Key to this achievement were the weekly coordination meetings with the CDM and biostats departments. As a result, resources were planned on almost real-time trial status, thus reducing time- and resource-wasting activities.
It´s also worth noting that CDM staff do not always have the necessary understanding to ensure the data being collected is appropriate to meet study endpoints. This can jeopardize an entire trial, but we were able to assure appropriate data collection by having the eCRF reviewed by a statistician.
Serge Bodart, MS, Chief Commercial Officer, IDDI Group