They call it the “One and Done” phenomenon, a relatively new occurrence in clinical research. It was first noted during a study by Duke University and the FDA showing a high percentage of principle investigators leaving clinical trials altogether after conducting just one FDA-related drug trial.
Maintaining strong site relationships is key to keeping projects on time, but that’s almost impossible if those relationships never have an opportunity to grow. And recent research from the Tufts Center for Drug Development indicates a significant upward trend in completely new sites, making up almost 30% of all engaged sites. This places the next new trial on precarious footing right at the start.
At the core of every trial should be the patient, and along with the patient the cooperation and support of PIs who are their direct link. It’s no easy task, though, as investigators commit to taking on the complex planning of a project in addition to balancing their already taxing workload. It can become draining. Something usually gives, either quality or the investigator themselves. Neither option – burnout or a drop in quality – is acceptable as the need to bring new drugs to patients grows globally every year.
Not to mention the impact on trials themselves. According to the Tufts Center, “The overall site initiation cycle time is 9.9 weeks shorter for repeat or familiar sites, compared to new sites.” So, it’s imperative to keep experienced, dependable principle investigators in trials, and to do that we must take a look at what is causing them to reconsider participating in the first place.
The Duke University and FDA study indicated a 54.2% turnover rate among principal investigators, many of whom departed after just one study.
The survey sheds some light on the primary causes of departure:
- 63.8% – Workload balance.
- 63.4% – Time required to initiate and implement the trial (in particular PI and site staff time)
- 56.5% – Responsibility and time requirements for data and safety reporting
- 46.0% – A general dissatisfaction with finance-related issues.
The many multifaceted burdens of clinical research continue to take their toll at the point when drug studies can be at their most vulnerable. Where once the methodologies were more basic, the sheer complexity of drug trials has exploded. This is in addition to other factors like the overall size, extended duration, and widening globalization within those trials.
So while clinical trials have continued to grow and span the world to include a larger patient pool and bring more potential cures to patients, it also means new regulatory processes, time differences, and language barriers. It can be daunting for principal investigators to juggle all these various factors and still feel that the convoluted process would be worthwhile to repeat.
The Burden of Research
Clinical trials have continued to increase in complexity. According to a study conducted by The Tufts Center in 2016, a typical Phase 3 protocol now consists of an average of 167 procedures. This is 60% more than at the start of 2000.
It also noted that the process of identifying a viable site through getting that site initiated takes an average of 7-8 months at large institutions, though the turnaround time may be quicker at research centers and private institutions. That’s in addition to conducting the actual study. Unfortunately, this cycle has not improved in the last decade.
Almost half that time (6-8 weeks) is just spent on sending out feasibility questionnaires and waiting for them to be returned. That’s if they are even returned, which wastes even more valuable time.
Another issue for principal investigators may be that their first experience with a clinical trial did not go as planned. Even minor mistakes such as filling out a form incorrectly can suddenly mean a mound of paperwork to explain the deviation. Suddenly, the site is swamped with additional paperwork, meaning longer hours and a growing lack of patience.
Simply finding time to run a complex clinical trial remains an overall issue for investigators. In order to run both the clinical trial along with maintaining normal practices at the site, new innovations and resourceful practices need to be discovered. As an industry, we need to find new ways to balance the process that recognizes those issues and work with them to find the best means of fitting into their schedules while also impressing upon them the deadlines everyone is working towards.
Kim Meyer, a Site Identification Specialist at PSI CRO understands that well. “The PI’s and support staff are generally very busy with routine patients and have very little time allocated to research. It is up to the CRO to help the sites as much as possible and to make the study process less cumbersome. This includes, but is not limited to, offering to complete study documents on behalf of the sites in order to speed up the start-up process and setting up routine calls with sites to go over what the study needs are and what their timelines dictate.”
Other methods include collecting accurate data, promoting increased efficiency throughout the study and discovering new ways to automate as much as possible by relying on technology. However, reducing the amount of excess work while still maintaining data quality remains challenging. Discovering the means to save time and make actions more efficient may lead to developing and maintaining those good relationships necessary to bring a trial to a successful conclusion.
Applied Clinical Trials suggests that “pursuits in data collection and analysis much now focus on the underlying dimensions unique to an individual country or site being targeted for clinical research. This is particularly important amid the rapid globalization of drug development, where access to the right intelligence during study start-up is critical.” Other means of streamlining can include checking for redundancy in the process, paperwork, etc., as well as finding ways to standardize processes as much as possible.
The Duke-FDA study also noted that 44.4% of principal investigators were interested in conducting another trial but found there were no opportunities available to them. Therefore, the second obstacle is providing ample opportunities to those willing to continue with further trials. One way to keep abreast of current trials is to reach out to colleagues who are already involved in clinical trials. They may know if additional sites are needed for participation. Other ways of keeping well-informed of prospects come from Judy Stone, M.D. in Conducting Clinical Research: A Practical Guide for Physicians, Nurses, Study Coordinators, and Investigators.
- Use the internet to conduct your own research on areas of interest. Physicians living in rural communities can still easily reach out.
- Register with online sites listing services such as CenterWatch, Research Investigator’s Source, Inclinix, or Site Management Solutions.
- Stay current on therapeutic areas.
- Utilize online pharma news sources like FiercePharma and by using Google News Alerts.
- Attend conferences that are specialty or disease-specific
- Become published in your field or arrange to be a co-author.
Every day the contributions made by the medical community, and all those involved in the clinical trial right down to the patients themselves, make success possible by providing and collecting the necessary data. Make no mistake, the methods are complex and trying to maintain a delicate balance remains strenuous. No one is a machine, least of all doctors. But a balance is possible.
“Maintaining meaningful relationships with sites is the key to a CRO’s success,” says Meyer. “The ability to contact the same sites year after year because we know their successes is priceless.” Only by keeping the lines of communication open and reducing (and acknowledging) the burden of workload balance can we keep both CROs and principal investigators working together to achieve positive results and create long-standing, beneficial relationships.