By Christopher M. McSpiritt, director of R&D consulting, Paragon
Study startup is a continual focus because it has such an impact on clinical trials — and not usually a positive one. Problems with the startup, more than any other phase of a clinical trial, have the greatest potential to increase timelines and budgets. Research has shown it takes eight months on average to move from pre-visit through site initiation.1 In particular, site feasibility takes on average six to eight weeks.2 For a prolonged oncology study this may not seem outrageous, but for a more common Phase III trial, which lasts between two and three years, startup is a significant portion of the timeline. Of note, contract and budget negotiations and approval are responsible for 49 percent of study delays.3 In addition to the timeline implications, startup delays directly impact the budget of clinical trials. Specifically, problems in site selection can increase the cost of clinical trials by at least 20 percent.4
As such, organizations are always looking to optimize the startup process so they can bring products to market quicker — getting potentially lifesaving drugs into the hands of patients is the primary goal — while also reducing each study budget so more products can be pursued to help other patient groups.
What Do We Look For When We Conduct Study Startup?
Site selection and contract/budget negotiations are not the only components of study startup that need to be optimized to improve outcomes. Before we delve into the components, let’s talk about the goals of optimized study startup. Based on our interactions with sponsors and CROs, there are two main drivers for improving study startup:
#1 — Getting The Best Sites For Their Studies
First and foremost, organizations are looking to get the best sites and investigators. They are competing with other organizations for a limited pool of qualified sites — those that can recruit patients, protect patient safety, and collect/document clinical data points to support analysis. Meeting this goal involves conducting more efficient and effective site feasibility to identify the best sites for the study.
#2 — Getting Those Sites Activated Quickly
Once you have selected the sites you think are most appropriate for your study, the next step is to activate the sites so they can begin to enroll patients and conduct the study. This involves securing contracts, collecting documents necessary for regulatory compliance, training the sites on the protocol, and getting approval from international review boards (IRBs).
What Can Be Done To Improve Study Startup?
By focusing on the specific objectives for each component of startup, we can position our studies for success.
There are two key aspects of site selection to improve for both the prospective sites and our study team. The first aspect is data collection rate and timelines, a key pain point for site personnel, while the second is the amount of information our study teams, or specialized startup team, have available to make decisions.
Improve Data Collection Rates/Timelines
Data collection rates can be improved by implementing technologies that make it easier for sites to provide their qualifications and rationale for study participation. We have seen great progress over the years in moving from paper surveys (which are mailed/faxed to sites, completed, and then returned to the sponsor) to electronic documents that can be completed/emailed back, and finally to online survey tools that allow sites to quickly provide info for sponsors’ immediate access. However, even with online surveys we have room for improvement. First, we need to make sure the surveys improve the site experience, lest they revert to old habits or, worse yet, refuse to participate. We can implement tools that remove unnecessary/redundant data entry by prepopulating surveys with information from existing data sources (clinical trial management systems, investigator databases, purchased site information) and from previous survey responses from that site. Additionally, we can reduce the number of questions sites must process by leveraging technology that displays only relevant questions based on answers to previous questions.
Increase The Amount Of Information Study Teams Have
Now that we have improved one key site aspect, it is time to help the study teams and make sure they are able to select the most appropriate sites. Historically, study teams relied on tribal knowledge to identify potential sites and then managed the selection process with individual spreadsheets for each study. Today, sponsors are increasingly using investigator databases that provide a more comprehensive view of sites, their capabilities, and their historical study performance. One key is to broadly assess intra-site performance using a study comparison as well as individual site performance against initial feasibility targets. Protocol complexity is a common cause of sites underperforming against expectations.
Investigator databases help remove politics from the identification of potential sites, especially if there is tension between sponsor and CRO, and helps improve transparency. They also help replace decisions based on perceptions with ones based on significant performance/capability information.
Once you have identified potential sites and received their survey responses, it is beneficial to leverage programmatic ranking of sites using scoring/algorithms. This helps ease the decision-making process for your clinical teams. To achieve this, look for a survey tool that provides built-in reporting capabilities and configure your survey to use weighting/scoring for answers that are most appropriate for your study.
Once you have selected the appropriate sites for your study, it is imperative that you focus on improving how you move selected sites through the process to become activated sites. Like site selection, a key theme here is to reduce painful/redundant work from sites and the study team. The other theme is improving visibility into the process so any needed adjustments can be quickly identified and corrected.
Reduce Painful/Redundant Site Work
Repeating the same training for various sponsors is consistently one of the biggest complaints about site activation. We have seen great progress from sponsors and TransCelerate on creating standards for GCP training that allow sites to be “one and done.” This is a good start, but it needs to be combined with making training as accessible as possible for sites by leveraging online/self-paced training.
Training inefficiencies are compounded by sponsors asking sites for the same documentation over and over for each new study — and doing it in an inefficient manner. Like feasibility surveys, we have seen a transition from mail/fax to electronic systems for activation documentation submission/review. This is a good start, but too often these systems are little more than electronic mailboxes. The technology exists to automate more activation documentation processes via pre-population of information, requesting documents via automated tasks, and approvals via workflows and electronic signatures.
Coming back to a common theme, we are seeing more and more clients replace unlinked Excel workbooks with sophisticated systems that centralize data important to study teams and provide the teams with the ability to act on the data. These purpose-built systems provide status of site activation activities and include information about regulatory/IRB approvals that can alert study teams when sites will potentially be able to enroll patients. Having information is important, but what is more important is the ability to act upon this information. The more sophisticated systems allow updates to plans and initiate contact with sites to instigate action. This allows the study team to more accurately manage the study activation process.
How Do You Improve Startup At Your Organization?
Now that we have identified the available tools and the outcomes they support, it is important to understand how you can implement the new technologies and processes. The first step is to work with leadership to understand the key drivers and desired operating model. If your future involves outsourcing all activities to a CRO partner, the future processes/technology needs differ from those of an organization which plans to manage study startup in-house.
Once you have identified the high-level operating model, it is important to identify and optimize the processes that support the future state. This involves identifying the steps as well as who is going to perform the tasks within each process.
After you have alignment on the processes, it is time to select the appropriate technologies you will leverage to support startup. This may involve investing in/implementing technology within your organization, leveraging toolsets of partners, or adopting industry-led systems (like the TransCelerate Shared Investigator Platform). After the technology solution has been configured, it is most important to ensure all impacted stakeholders are willing and able to use the tools to improve the current state. Too many organizations focus on technology and don’t allocate sufficient effort to change management and training. The best system provides no value if nobody uses it.
The Future Is Brighter
We are confident the increased focus on study startup will lead to improvement. The industry has begun to reach agreement on how startup can be improved and to invest in supportive technologies. Now we must keep pushing our peers in the industry to not become complacent, to leverage new systems, and to continue to drive optimized study startup.
Morgan, C., “The Need For Speed In Clinical Study Startup”, Clinical Leader, 2015, www.clinicalleader.com/doc/the-need-for-speed-in-study-startup-0001
Brennan, Z., “Trial Site Feasibility Platform Looks to End Onerous Paper Questionnaires”, Outsourcing-Pharma.com, 2013, www.outsourcing-pharma.com/Commercial-Services/Trial-Site-Feasibility-Platform-Looks-to-End-Onerous-Paper-Questionnaires
Farfel, G. and Neuer, A., “Faster study start-up and reduced costs through the use of clinical document exchange portals”, IntraLinks , 2009, https://www.intralinks.com/sites/default/files/file_attach/wp_faster_study_startup.pdf
Grom, T., “Unclogging the patient recruitment bottleneck”, PharmaVOICE, 2011, www.pharmavoice.com/article/2182/
About The Author:
Chris McSpiritt is a director in Paragon’s Research and Development Consulting Practice. Chris has over 10 years of pharmaceutical industry experience in R&D and has applied his business architecture, business process management, and analytical skills to help pharmaceutical companies improve their conduct of clinical trials. Chris holds a B.A. in psychology from the University of Notre Dame. He is an active member of the Business Architecture Guild, Association of Business Process Management Professionals, Project Management Institute, and Drug Information Association.