It can be seriously disruptive when the site investigator for your trial leaves or decides to step down, but new recommendations from the Clinical Trials Transformation Initiative (CTTI) aim to mitigate that risk.
The organization says its new guidance was prompted by high rates of turnover among investigators who lead clinical trials at research sites, which it says is generally caused by “difficulty balancing workload, time requirements to conduct trials, data and safety reporting burdens, and financial issues.”
That can result in a phenomenon known as “one and done,” referring to the high proportion of principal investigators—more than half, according to recently published research by a team led by Duke University’s Matthew Roe, M.D.—who for various reasons choose never to conduct a second trial.
That’s a big problem for drug developers, as it takes a lot of resources to train investigators, and high attrition rates increase the cost of clinical research whilst potentially having an impact on the quality and efficiency of the trial.
Some of the comments received by Roe and his colleagues over the course of that study highlight the issue starkly. “Too much effort, without enough help, with too much bureaucracy, for no recognition (no authorship on paper, no kudos or appreciation from my section chief, etc.),” says one. “Conducting research costs me money, the time and effort is not paid and takes me away from the financially rewarding parts of my job. There is constant paperwork, site visits, protocol amendments, and need to re-consent. All time sucking,” goes another.
It has also emerged from Roe’s research that there is a big, as-yet-untapped pool of potential investigators out there. “A large proportion of investigators wanted to conduct more FDA-regulated drug trials but had not had an opportunity to do so,” write Roe and his co-authors in the research paper.
So what’s to be done? The white paper from CTTI—an organization set up by Duke and FDA in 2007—sets out what it says are practical solutions to tackle the administrative, financial and logistical burdens that are causing investigators to abandon clinical research.
It’s inevitably a combination of many things. Hiring and retaining experienced research coordinators, providing continuous training for research staff and adopting good clinical practice standard operating procedures are all actions sites can take to ameliorate the problem. For sponsors, it is important to recognize the value of investigators—a “thank you” goes a long way—and offer to include them as co-authors in publications.
A failed or problematic trial can be a big factor in attrition, so sponsors should take care that their trial designs and protocols have scientific validity and don’t cause logistical issues with patient enrollment, data collection or reporting. And sites should also be selective and decline studies that aren’t a good fit, says the paper, which also gives recommendations for site budget and contract negotiations and encouraging matchmaking between investigators and sponsors.
“The problem is that leading a trial is complex and the learning curve is steep. If you’re new to the field or you don’t have mentors, training, and infrastructure to support you, the burdens can quickly become overwhelming,” said Roe.
“Then the imperfect cycle begins again with a new investigator.”