Clinical trials are the bridge to medical innovation. Most people don't think about the origins of the drug they receive or the medical procedures they undergo on a regular basis. Yet every drug, diagnostic test, surgical procedure – medical treatment in any shape or form – finds its origins in a single source: research.
Over many years, innovations evolve, graduating through the different stages of development: basic research, translational research, and clinical research. Clinical research is the last critical stage, designed to test the safety and efficacy of new innovations in real patients. Unfortunately, the process of clinical research is not only long and bureaucratic; it is also experiencing diminishing returns. According to a recent study by KPMG, within the pharmaceutical industry, the return on R&D expenditure has fallen from an industry average of approximately 20 percent 20 years ago, to 10 percent now, highlighting the need for greater innovation. Without further innovation, pressures on clinical development – including an aging population, smaller target disease pools, and increased market competition – will only further erode the ROI on research.
Studies estimate that it costs somewhere between $161 million and $2 billion to bring a new drug to market, which translates into daily revenue losses in the range of $1 million to $8 million, resulting from delayed market entry. According to the study cited above (sponsored by the US Department Health and Human Services), the average length of time from clinical development to marketing is on the rise over the last decade and currently stands at about 7.5 years. Longer timelines further increase costs and decrease revenues. As a result, there is intense pressure to speed clinical trials and restrain costs, but inefficiencies tied to complicated protocols, globalization, and paper-based methods have stalled these efforts.
In an effort to confront these issues the industry has been evolving from its slow paper-based methods and standalone spreadsheets towards automated, cloud-based systems. There has always been a strong focus on study conduct and quality. But as stakeholders are increasingly aware that better study startup (SSU) processes are linked to shorter clinical timelines, the emphasis is shifting in that direction.
According to research conducted by the Tufts Center for the Study of Drug Development (CSDD), it takes an average of 17 months to get from protocol approval to 100% approved sites initiated for a clinical trial. Site activation costs $1,500 per site per month, or approximately $25,000 on average to get one site up and running. Since, on average, phases II to IV studies have 82 sites per study, this can mean a total study startup cost of over $2 million. For every day that is eliminated from study startup, sponsors and Contract Research Organizations (CRO) not only save valuable time, they also gain enormous savings.
Study Startup Complexity
Study startup is the multistep practice of selecting and preparing investigative sites required to conduct clinical trials. It is a collaboration of stakeholders: sponsor, CRO, site, institutional review board (IRB) or ethics committee (EC), and a variety of outsourced providers. The study startup phase for clinical trials has historically been a time-consuming, labor intensive and costly process that consists of a number of related activities:
- Site identification and activation/initiation
- Conducting investigator meetings/site training
- Regulatory document completion and IRB/EC approval
- Negotiations of contracts and budgets
- Planning for patient recruitment
- Managing/tracking regulatory documents, including:
- Site feasibility survey forms
- Investigator brochures
- Site contracts
- Budget worksheets
- Patient recruitment plans
- Informed consent forms
- Advertising materials
- Drug accountability
- Provision of supplies and test article
Improving SSU efficiency is imperative to a sponsor's bottom line and to accelerating trials, with deep process-based issues that can't be addressed by simply increasing human capital alone.
Manual Processes in Study Startup
Technology has allowed big advances in clinical trial efficiency, ranging from entry of clinical trial data via electronic data capture (EDC) to managing study documents in the electronic trial master file (eTMF). But, up until the last few years, the SSU portion of clinical trials has not benefited from these innovations, essentially remaining manual or heavily rooted in Excel spreadsheets. These manual processes have long hampered efforts in study startup, with valuable resources diverted from more critical tasks to the manual routing and tracking of forms. For example, a survey on clinical trial budgeting, a standard SSU activity, found that 57% of respondents claim to still be building their study budgets in Excel, and as a result, 65% reported that the review and revision cycle for a single study was taking more than five weeks, while nearly one-third (31%) required more than nine weeks.
Today, sponsors and CROs must perform a number of specific activities related to documents, submissions, contracts, and visits scheduled across multiple studies, being undertaken in multiple countries. With Phase II to Phase IV studies, on average, having 82 sites per study the complexity is self-evident – How are all these documents tracked? Where are we in the process? Where are the bottlenecks and inefficiencies? Where are these documents stored? And, who has access? Furthermore, ensuring that the most recent versions of these documents are used can be challenging, if not a daunting task, especially if there are multiple versions and amendments.
And recent research conducted by Tufts CSDD in 2016, examining practices and inefficiencies in site selection, study start and site activation, indicates not much has changed. The research shows that, despite advancements in technology, researchers are not conducting SSU any faster today than they did 20 years ago. Site activation cycle time (the amount of time it takes to identify a site and get it activated) was found to average around 14 months.
Site contract cycle times are contributing to this stagnation in SSU duration. KMR Group, a leader in analyzing R&D performance data for the biopharmaceutical R&D industry, recently concluded an assessment of global industry site contract cycle times. The study evaluated 20,000 recently-executed contracts for Phase II and III trials from leading biopharmaceutical companies. KMR Group's Site Contracts Study found that overall site contract cycle times have doubled from an industry median of about 1.5 months in 2010-2011 to over 3 months in 2014-2015. Even contracts conducted in North America, traditionally a top performer, have increased from 1.3 months in 2010-11 to 2.4 months in 2014-15.
Widespread use of Excel contributes to SSU inefficiencies with its lack of critical features necessary for data sharing and collaboration. Issues with Excel are numerous and systemic, as it was simply not designed for use in documenting, tracking and analyzing clinical trial data. Specifically, Excel lacks:
- Project management capabilities
- Regulatory compliance features
- Features to protect data security and integrity
- Automated data entry
- Version control or centralization
- Automated workflows and documentation management
- Tools to facilitate easy communication amongst stakeholders
- Transparency which facilitates effective oversight and partner selection
- Integration between related business processes often tracked in separate files
- Ability to facilitate accurate real-time reporting
Manual processes and archaic tools like Excel have mired SSU performance, resulting in cost overruns, timeline delays, rescue studies or worst – study derailments – with poor site selection alone cited as increasing cost of trials by 20 percent or more. A paradigm shift is needed in order to eliminate the three evil "e's" – email, Excel, and e-meetings (teleconferences with remote study team members) – long associated with starting clinical trials. To meet these daunting challenges, companies are now turning to and leveraging technology to fill the gaps in their SSU process.
Improving SSU Efficiency with Technology
With all the inefficiencies introduced into clinical trials by the three evil e's, there is a growing acceptance that smart workflow technologies are a better choice for streamlining SSU processes, with the potential to ultimately reduce timelines and improve data quality. Companies are moving away from the tedious job of compiling Excel spreadsheets in favor of technology that allows for the reporting of real-time data. With these new purpose-built tools, study teams can access real-time status updates to quickly identify process bottlenecks, helping decision makers intervene immediately or before a major setback has occurred, instead of after the fact – actions that are simply not possible with Excel.
Time isn't wasted assembling and discussing status updates; instead, all stakeholders view this information in real-time via their technology solution, well ahead of any scheduled status meetings. Real-time reporting negates the need for "status" meetings, where dated, manually prepared reports are reviewed for budget and timeline compliance. All stakeholders can view dashboards and progress reports, without the need for a dedicated resource to update progress and status. This empowers the decision making process, as clinical study managers can now access automated, at-a-glance status.
SSU software tools provide alerts, intelligent document routing, version control and status reporting, which reduce the number of handoffs, errors, and downtime events that can occur during the startup phase of clinical trials. The use of a dedicated SSU tool allows for the seamless sharing and visibility of documents and associated information in real-time – globally – facilitating handoffs. Delays due to documents sitting in siloed email boxes is eliminated as role management ensures continuity in the absence of a team member.
Excel has been pushed beyond its limits in the clinical trial environment. Fortunately, technology for SSU has advanced to the point that current solutions can do what Excel never will—automatically trigger workflows as a clinical trial unfolds. It has also become possible to set and track milestones, improve communications among partners, act as a central repository for study documents, and integrate the flow of information from various data sources in a compliant manner—functions that are critical to successful site activation process as clinical trials become more global and complicated. In addition to markedly increasing the speed of study startup, there is also a significant reduction in risk. Why? Because organizations are able to drastically minimize the amount of institutional knowledge spread around in difficult to search, unstructured repositories, such as Excel, email and e-meetings.
Article originally published in Applied Clinical Trials, September 2016