It is well known in the clinical trial industry that the start-up phase of clinical studies can be very challenging. It is at this stage of development that clinical trials must lay the groundwork for success, and good intelligence gathering must be integrated into every aspect of strategy, from site identification to patient enrollment.
In this post I will discuss the some of the approaches to streamlining study start-up, and the new technologies that are being utilized, in order to achieve the greatest possible efficiency at this challenging phase of clinical trials design.
One aspect of the start-up phase that has evolved over recent years is the use of workflow management systems. This approach, involving the use of techniques such as CPM and Lean Six Sigma methodologies, allows study teams to improve their ability to manage key start-up steps, and to move away from an overreliance on simple data tracking. The aim of these systems is to create global visibility and promote better communication to create more seamless transitions between the different stages of study start-up.
Today, companies are building databases which enable CROs and sponsors better anticipate the future based on past project experience. In using this information, new protocols and products can be evaluated according to their overall design and composition. This more easily enables the prediction and therefore avoidance of risks that may occur along the same path.
However, the use of broad comparisons with past trials, even of a similar type and at the same phase, to predict a project timeline, is inadequate. For aspects of study start-up with high levels of complexity, it is vital that intelligence databases allow study teams to enter multiple unique parameters to generate the designs that are most likely to result in predictability around timelines.
Fundamental to the appropriate management of timelines is the ability to measure against baseline performances, and in order to establish realistic start-to-finish goal at the beginning of a project, key deliverables must be tracked against a baseline plan. While inevitable changes in circumstances, that alter a timeline, can be incorporated into a new projection, the initial baseline should always remain. This ensures that the appropriate data is available, and when delays occur and allows information gathering that will lead to swifter mitigation strategies, leading to greater timeline predictability.
The identification of high performing sites and investigators is crucial for positive research outcomes. Choosing an appropriate site correlates with faster patient recruitment, and therefore success in reaching overall enrollment goals, superior data quality, fewer queries, and better patient retention.
However, the selection of poor clinical trials sites continues to be a problem, and it leads to an increase in the cost of clinical trials. Inappropriate site selection is principally due to lack of knowledge of relevant clinical investigators, and many sponsors predominantly rely on established connections with previously used sites, to find suitable investigators.
When recruiting sites, sponsors and CROs typically first identify regions in which the targeted patient population is more commonly located, and then determine whether the protocol is suitable. These initial assessments must be combined with information from regulatory intelligence databases to determine country and site feasibility. This should form the foundation when exploring locations to conduct trials.
Study start-up efficiency can also be improved by the use of enrollment modeling. This technology allows enrollment data, as well as intelligence regarding specific protocols, countries, and sites to be viewed in parallel. This enables study teams to predict the speed at which enrollment targets can be met using a set number of sites, and provides a means of measuring recruitment as the study progresses.
Over the past decade, there have been considerable advancements in global reporting systems and technologies for use in clinical development. This has gone some way to shift study teams’ workloads from the onerous tasks of compiling Excel spreadsheets, towards approaches that incorporate more real-time data and reporting. This has muerous advantages, such as enabling queries from regulators and ethical committees to sites in several countries to be shared worldwide, in real-time.
While digital methods of communication between investigators are becoming increasingly common, site implementation of web-based tools for the exchange of clinical document, remains slow. In 2011 a global survey found that traditional methods of communication, such as e-mail, fax, and courier, were the principal tools being used for the exchange of clinical trial documents in 73% of sites.  This is despite the fact that most investigators have access to tablets and smartphones.
It is the responsibility of CROs and sponsors to utilize these tools. Application of these technologies could be used, for example, to electronically distribute questionnaires, or predictable, pre-populated documents, to investigators. They could then be completed on a handheld device and signed with an electronic signature, helping to speed up the overall start-up process and reduce timelines.
Another area in which technology is affecting a more streamlined approach to study start-up, is through the use of online clinical document exchange portals. These can be used to simplify the task of tracking study start-up activities for several sites. Online portals enable the generation of reports, increasing the transparency of the status of a site’s progress. They also provide the capability to streamline communication, making for a clearer, user-friendly, and regulatory-compliant method for sites and sponsors to track and collaborate on operational data. Finally, these smart workflow technologies also make it easier for study teams to deliver real-time status updates to management, enabling the identification of bottlenecks and optimization of resources.
It is important to acknowledge that, as with the adoption of any new technology, the implementation of digital portal systems can be a challenge, requiring the creation of new SOPs, additional staff training, often at site already burdened with a heavy workload. However, it is vital that the clinical trial environment keeps pace with improving technologies, to manage competing demands, and to remain competitive and continue to increase efficiency.
New strategies and technologies, to streamline onerous and time-consuming start-up procedures, show potential. However, while the implementation of integrated data systems and digital document management remain uneven, challenges in estimating start-up timelines and identifying potential bottlenecks will continue. It is therefore essential that companies continue the process of collecting and compiling data, together with the use of appropriate systems to share that intelligence, in order to achieve ever-greater predictability in study start-up.
- Schimanski, M. Kieronski, “Streamline and improve study start-up,” Applied Clinical Trials, Vol. 22, Number 9, September 2013.
- Bio-IT World, “IntraLinks Survey Highlights Need for e-Clinical Document Exchange Tools,” (2011), http://www.bio-itworld.com/news/06/14/2011/IntraLinks-survey-need-clinical-document-exchange.html.