A New Approach to an Old Problem – Speeding Study Startup

Launching a new clinical study is an exciting stage of product development. There is tremendous hope that a new drug will cure illness or bring relief to patients. Inspired, the team jumps in with a sense of urgency – but as documents and tasks pile up, bottlenecks emerge that delay getting actual research started, threatening the team’s ability to meet key study milestones for product registration. 

Study startup has many moving parts with numerous activities happening among multiple parties in parallel. The protocol is written; investigator sites are evaluated and selected; clinical trial applications are prepared; ethics committee submissions are developed; investigators and clinical trial team members are trained; investigational product is formulated and packaged – and the list goes on. To further complicate matters, different regulatory requirements must be met across the globe and various disciplines and stakeholders (i.e., researchers, physicians, lawyers, regulators, ethicists, investigators, scientists, and monitors) are involved in the process. As is so often the case today, many team members are added to the mix in support of the study – CROs, labs, technology vendors, and others. 

The study “Benchmarking the Study Initiation Process” published in Therapeutic Innovation & Regulatory Science collaborated with 11 pharmaceutical and biotechnology companies to examine 105 global clinical trials and confirms this inefficiency. “Due to the volume of activities required at study startup,” the researchers reported, “many companies have recognized this phase as a bottleneck and are looking specifically at the study initiation process as a key improvement area.”¹

So Much Paper, So Little Time

The life sciences industry continues to rely heavily on paper-based processes and low-tech systems to share and collaborate on critical study startup materials. Documents or disks are mailed or couriered across the globe, and spreadsheets are used to track and manage progress. When a typical Phase III study requires hundreds or even thousands of patients to confirm efficacy, many international investigator sites are needed, each with local regulatory and institutional site initiation requirements.  With this volume and complexity, it’s not surprising that clinical research teams struggle to make progress using Excel spreadsheets to manage their work.

In addition to being inherently slow, these manual processes prevent all stakeholders or process participants from overseeing progress or tracking status. The problem is compounded with international teams as regional groups often maintain their own records, which may not correspond with records at headquarters. Almost no one on the study team has real-time visibility, forcing organizations to be reactive – looking back at problems instead of taking preventative action. This situation creates many opportunities for error, exposes companies to risk, and plays a direct role in study setbacks. 

One flaw in current technology solutions for study startup is that they provide a detailed picture of either the documents or the operational data, but not both at the same time. While some solutions help because they enable the team to see and access all needed documents in one place, they don’t connect the documents with operational information the team needs to efficiently initiate the study. Existing systems often do not help manage the work processes involved, either. Automating simple workflows, such as routing documents for approval or quality control, can have a large impact on time to first patient and time to first visit.

There are a handful of specific study startup applications on the market today, but spreadsheets and clinical trials management systems (CTMS) are the most commonly leveraged tools across the industry. Spreadsheets don’t provide global team visibility, create version control issues, and require manual effort for entry, updating, and checking. The CTMS offers functionality for planning and tracking, but this type of system can be complex and inflexible to manage the local requirements in a global study startup process. The CTMS provides limited ability to manage or process documents.

Some specific study startup solutions endeavor to combine operational data from different systems and provide a very clear visualization of the startup process in one place so everyone can see where progress is lagging and where they need to take corrective action. If the data is updated in real time, this can help, but delays in integrating data can cause inefficiency for study teams. And, although the data are visible, these systems don’t link the data to the documents the team needs in order to take action immediately.  

“Many sponsors and CROs have traditionally used unsophisticated, disparate, and incompatible proprietary and customized approaches and eClinical solutions to manage study startup and initiation activities,” says Ken Getz, associate professor at CSDD Tufts University School of Medicine. “This has contributed to the historically high level of inefficiency and inconsistency that we’ve observed in investigative site engagement and activation.”²

Bring Documents and Data Together

Through the evolution of study startup solutions – from paper and Microsoft Excel tracking sheets to dedicated software applications that capture and leverage metadata as users create, review, and distribute content within the system – it is now possible to bring documents and data together. As a result, all team members across geographies can see what documents or data that is missing from the TMF without toggling to different sources or emailing various people. It’s all in one place, which also enables the team to then immediately take action. Sponsors, CROs, and local study team members can update documents and operational data at that central source and manage workflows and work processes, ensuring version control, enabling planning, and speeding the activities of study startup. 

Often, because of the complexity in the clinical study process, team members don’t have the information they need to prioritize their work. They need to know which activities are most vital for keeping study start up on the path, and which occurrences will delay the projected study start date. Integrated solutions improve communication among team members spread across the enterprise as well as between sponsors and CROs, which increases visibility of all tasks, eliminates redundancies, and enables the team to move forward at a faster pace. 

Awareness of the problems with study startup is very high and a number of efforts to solve them are underway. Many organizations have created new positions solely with the objective to oversee and improve the startup process. Accelerating the time to first patient is seen as key to driving study efficiencies. 

Additionally, many industry groups are also focusing on simplifying and speeding the time it takes to begin research. TransCelerate BioPharma Inc., a coalition of large pharmaceutical companies, has launched a program focused on speeding study startup timelines by developing standard criteria for recognition of good clinical practice (GCP) training and site qualification.³ The TMF Reference Model, maintained by an industry group of almost 200 life sciences companies, provides standard structure and taxonomy for maintaining a GCP-compliant trial master file (TMF), which includes many of the documents collected during study startup. And, the Metrics Champions Consortium has outlined a number of activities related to site activation as part of their Clinical Trial Performance Metrics Set.⁴

These types of industry-wide collaboration are essential and pave the way for meaningful transformation of the study startup process. Consistent processes and industry-wide standards help sites, CROs, sponsors, and regulatory authorities work together more effectively. The application of new technologies represents the other side of the solution. Linking documents and data for a complete view of the startup process, and then being able to act on that information provides a new opportunity to solve the study startup challenge, once and for all.

References

1. “Benchmarking the Study Initiation Process,” by Lamberti, Brothers, Manak, and Getz, Therapeutic Innovation & Regulatory Science (2013) 47: 101. For more: http://dij.sagepub.com/content/47/1/101
2. FDA, "Frequently Asked Questions-Statement of Investigator (Form FDA 1572)," (2010). For more: http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm214282.pdf
3. "TransCelerate Initiatives," by TransCelerate BioPharma Inc., (2013). For more: http://transceleratebiopharmainc.com/?4a17eb50
4. "J&J, Lilly, Merck Plan Clinical Trial Site Database," by D. Beasley, Reuters, (2012). For more: http://www.reuters.com/article/2012/11/15/us-pharmaceuticals-trials-idUSBRE8AE0XS20121115.

Jennifer Goldsmith is the Vice Presisent of Veeva Vault and can be reached at jennifer.goldsmith@veeva.com