Building A Stronger Community For Site-Based Research

By Matthew Roe, M.D., Duke Clinical Research Institute (DCRI); Kaitlin Malone, Amgen; and Gerrit Hamre, Clinical Trials Transformation Initiative (CTTI)

Leading a clinical trial at a research site as an investigator is a challenging task. Running a successful study requires the ability to manage budgets, coordinate the activities of support teams, efficiently allocate limited time and resources, and navigate the complexities of regulations and reporting obligations.

Lately, there has been growing concern that these challenges are leading to a shrinking pool of experienced site investigators. A 2015 Tufts survey found that roughly half of the world’s clinical investigators in 2013 were relatively inexperienced first-time trialists, and turnover rates even among experienced investigators appear to be growing.¹ More recently, the Clinical Trials Transformation Initiative (CTTI), a public-private partnership co-founded by Duke University and the U.S. Food and Drug Administration (FDA), reviewed information housed in the FDA’s Bioresearch Monitoring Information Systems (BMIS) database that suggests attrition rates may be especially high for U.S.-based site investigators. Taken together, these developments have serious implications, because the success of U.S. clinical research depends on a healthy supply of experienced, knowledgeable site investigators and support staff.

In response to these concerning trends, CTTI created the Investigator Community Project to examine factors that contribute to investigators deciding to leave or remain engaged in research and identify opportunities for strengthening and supporting the community of site investigators and their staff.

Why Are Investigators Leaving Research?

To get a clearer picture of the challenges facing site investigators, CTTI conducted a series of interviews and surveys to explore what it saw as the most significant barriers to staying engaged in clinical research. “One-and-done” investigators — that is, those who stopped participating after just one trial — consistently described four key issues as the most significant barriers to their continued engagement in clinical trials:

• Issues related to trial finances and budgeting;
• Time required for trial implementation and execution;
• Burdens associated with data and safety reporting; and
• Difficulties in balancing trial workloads with clinical obligations.

However, more than 40 percent of “one-and-done” investigators indicated that they were still interested in participating in clinical trials, but had a hard time finding appropriate trials after their initial trial experience.²

CTTI also interviewed investigators who had been involved with multiple clinical trials to identify attributes that might contribute to sustained participation as a site investigator. These “stayer” investigators consistently invoked personal commitment, institutional support, and experienced, well-trained staff as being particularly important to their ongoing participation in clinical trials.

Strengthening The Investigator Community

Based on these findings, as well as a consensus that emerged from a multi-stakeholder expert meeting convened to tackle the problem of investigator turnover, CTTI developed a set of Recommendations for Strengthening the Investigator Site Community. Below, we list these major recommendations and describe some of the actions that should be considered by investigators, sites, health systems, sponsors, and CROs to support and grow the community of site investigators:

• Develop supportive infrastructure for site-based research. This includes hiring qualified research coordinators and support staff whose knowledge and expertise encompass the many complex tasks and processes essential to conducting successful trials. Providing continuous training and career development for staff and creating clear, consistent SOPs are also important parts of sustaining the necessary infrastructure for site investigators.
• Optimize trial execution and conduct. Sponsors can help facilitate and stimulate enrollment in clinical trials by developing protocols that take into account the real-world environment of clinical practice and by planning carefully and realistically for patient recruitment. In both cases, incorporating input and perspectives from all stakeholders during protocol development can greatly enhance the likelihood of a successful study. Meanwhile, sites and investigators can contribute to a better experience by carefully reviewing protocols and recruitment plans and by saying “no” to trials that are not a good fit for them.
• Improve efficiency and transparency of budget and contract negotiations. Budgets and contracts are a frequent source of friction in clinical research. By encouraging transparent communication between investigators, sponsors, and CROs — and by ensuring that investigators and key support staff have a clear understanding of budget and payment schedules and how to effectively address concerns — budgeting and contracting processes can be made more efficient. Sponsors can also expedite contracting processes by using master agreements with sites that clearly spell out key contract elements that can be used for multiple projects. Finally, CROs and sponsors can help educate investigators and site staff regarding how fair market value calculations are applied when determining site payments and budgets.
• Help investigators identify opportunities for leading site-based research. Matching highly motivated investigators with opportunities for trial participation is an obvious way to boost interest in clinical trials, but surprisingly, many investigators report difficulties in locating trials that are right for them. Professional organizations representing site investigators and site research personnel may be able to play an important role in helping to create “matchmaking” services for investigators and CROs; meanwhile, physicians interested in conducting research should not hesitate to reach out to sponsors to ask about possible opportunities.

Putting Recommendations Into Practice

As site investigators and stakeholders for clinical trials put these recommendations into practice, it’s important to realize that many can build on existing programs or initiatives. For instance, many CROs already have programs in place to recognize the contributions of site investigators and staff; such programs can be reviewed for opportunities for improvement or expansion. Similarly, the use of streamlined approaches to study start-up has been gaining traction in recent years; leveraging these efforts by providing additional education in best practices for invoicing and capturing study milestones can make processes more efficient and expedite payment — both of which will benefit sites. Finally, sponsors, CROs, physicians, and medical schools can all play roles in providing training, mentoring, and a career path for physicians interested in site-based clinical research.

Building For The Future

Aligning training, communication, and infrastructure in ways that sustain and support investigators and study staff, while at the same time anticipating and reducing logistical and organizational burdens, will help create a more welcoming, sustainable, and efficient environment for conducting clinical research. As these approaches are implemented, it will be essential to continue to gather insights into challenges facing investigators and seek evidence-based, collaborative solutions that ensure the long-term health of U.S. clinical research.

References:

1. Tufts Center for the Study of Drug Development. High turnover and protocol noncompliance continue to plague the global investigative site landscape. January 15, 2015. Available at: http://csdd.tufts.edu/news/complete_story/pr_ir_jan_feb_2015.
2. Corneli A, Pierre C, Hinkley T, et al. One and done: Reasons principal investigators only conduct one FDA-regulated trial. Contemp Clin Trial Comm. 2017; 6:31-8.

About The Authors:

Matthew T. Roe, M.D., is a cardiologist with extensive experience as principal investigator in numerous phase II-IV cardiovascular clinical trials. He has also served in leadership roles for observational registries focusing on patients with acute myocardial infarction, patients undergoing percutaneous coronary intervention, and patients with familial hyperlipidemia. Dr. Roe is the DCRI Fellowship Program Director and served as faculty director of the Global Megatrials group at the DCRI from 2013 to 2017. He is the co-principal investigator of the ADAPTABLE trial (the first, large-scale pragmatic trial being conducted in the PCORnet network). He has published over 400 articles in high-tier journals.

Kaitlin Malone has been with Amgen over a decade and is currently a clinical trial oversight manager within Amgen’s Global Study Operations team with oversight of the clinical trial contracts, budgets, and payments. While she is located at Amgen’s headquarters in Thousand Oaks, CA, Kaitlin also supports global teams with the development of training tools and support resources to ensure consistency and quality. She has enjoyed partnering with CTTI on the Investigator Community initiative since 2016. Malone holds a bachelor’s degree in law and sociology from the University of California, Santa Barbara.

Gerrit Hamre manages the development and implementation of CTTI projects. In collaboration with team leaders, he creates project plans and budgets, and manages the implementation of project plans. Prior to joining CTTI, he worked in the U.S. Food and Drug Administration’s (FDA) Office of Legislation, followed by the FDA’s Center for Drug Evaluation and Research, Office of Policy for Pharmaceutical Quality. His primary areas of focus at the FDA were the drug approval process, antibacterial drug development, manufacturing quality, and generic drugs. Before joining the FDA, Gerrit worked on pharmaceutical science or healthcare delivery administration issues in corporate, federal government and non-government organization (NGO) sectors, domestically and internationally.