Muriel Berthier and Denis McMillan, PAREXEL, discuss the key factors for achieving more reliable feasibility in clinical trials
Muriel Berthier and Denis McMillan, PAREXEL
Clinical trial complexity is placing a greater emphasis on — and creating a critical need for — study feasibility. A key success factor is ensuring the planning and design is correct from the beginning to avoid re-work and delays, which requires moving away from opinion-based decisions and adopting a more sophisticated data-driven approach. Whilst there is more and more data available to support this approach, the challenge remains in selecting and analysing the right data that can help select the right countries, sites and patients.
Feasibility refers to the identification and quantification of risks in clinical trial planning, including: protocol (regulatory, scientific, medical, statistical), country and site, patient, resourcing, quality, financial or contractual. It also involves the assessment of drug supply risk, a critical evaluation factor for investigators.
Feasibility is a complex team activity requiring high levels of open collaboration between sponsor, CRO, investigator and patient. As a discipline, it sits within risk management and plays an integral role in the planning and design process, as well as in ensuring reliable delivery. It is a continuum — programme, protocol, country, site and patient recruitment — with a feedback loop to the start of the next project. To be effective, it requires large volumes of data from a wide variety of sources, as well as feasibility-orientated technology platforms.
Data-driven country and site selection
Technology platforms combine dynamic and sophisticated analysis of data with best-in-class visualisations to generate key insights to optimise protocols, country placement, site selection and proactive recruitment and contingency plans. Aggregating and mastering data across both in-house and third-party databases produces a more comprehensive and therefore clearer picture of prior performance, current variables and future trends.
Informed country placement evaluates a full range of factors, including medical, clinical, financial, regulatory and operations/logistics, which helps reduce risk to acceptable levels. Looking at only one or two factors would create a bias; therefore, technology is required to efficiently analyse and score country suitability and create insightful visualisations. Country-allocation technology enables CROs to be more influential and transparent with recommendations, in turn driving more efficient and effective conversations with the sponsor.
Site selection remains an important part of the successful delivery of trials. But just how much do we know about primary investigators (PIs) and investigative sites? With too much siloed data for clinical decision makers to analyse, they end up relying on survey data and an impression of past performance. Technology can help consolidate the information from CTMS, IVR, Labs, QA, imaging and third-party databases. Automatic analysis and insightful visualisations are essential; however, the lack of unique investigator identifiers makes this a difficult task.
Increased accuracy of recruitment forecasts
Self-estimated recruitment numbers have traditionally driven most investigators’ planning decisions while set-up and recruitment timelines are missed more often than not, causing the majority to miss their recruitment target. Access to electronic medical records (EMR) data can help increase the accuracy of investigator estimates. In addition to quantifying the impact of individual inclusion and exclusion criteria on the general population, combining all criteria can create a more comprehensive understanding of the pool of eligible patients for a specific trial. The often-missed consideration, however, is the opinion of the patients. How do they feel about their current treatment? How is their disease impacting their everyday life? How willing are they to participate in a clinical trial and accept all the requirements of the protocol with its advantages and constraints? Whilst information is more widely available to patients, the industry still relies on investigators to comment on patient opinion. Patient feasibility surveys introduce the patient voice and are becoming instrumental in accurately forecasting recruitment rates, as well as in developing the right patient material to drive successful recruitment.
As important as it is to identify the risks involved, decision makers need to be appraised of the size of the problem (likelihood of occurrence and the size of the impact). The subsequent operational strategy must then help mitigate the risk and provide prudent contingency to ensure delivery. Industry-leading feasibility is only possible when expertise, experience and technology are closely aligned. Feasibility is, however, part of a continuous risk management process and should not sit in isolation. The combination of scientific and clinical knowledge, along with advanced technological capabilities, all within a single point of accountability is the path towards more reliable feasibility.