Eileen Daniel has spent over 25 years working in the clinical trials industry. During those years, there were times when she became quite disillusioned. Daniel, now the executive director of clinical operations at Nektar Therapeutics, always felt there were ways the clinical trial planning process could be improved.
"I always felt there could be fewer intermediaries between the site and the sponsor,” she says. “When the clinical trials team at Nektar came up with the idea of implementing good human practices (GHP), we knew we were doing something that would benefit the relationships between sponsors, CROs, sites, and most importantly, patients. I think we are already seeing good results from our efforts.”
Daniel notes the core of GHP involves doing the right thing for people as well as the project, an idea that is not new to pharma companies but requires dedication to keep it in focus. The whole push throughout the implementation process has been to figure out how to stay as close as possible to the people who are working hard on each study.
“For all intents and purposes, we should never be more than two layers removed from our sites, or even two layers removed from our patients,” she states. “It is much more difficult for a sponsor to have a great depth of oversight if they are distant from the site and patient. By applying simple, GHP principles to day-to-day activities, from pre-start-up through to the end of the trial, we end up with an inspection-ready oversight plan that allows the executive director of clinical operations to have in-depth conversations with sites on a much more frequent basis. This allows them to learn more about how studies are operating and adopt a more adaptive-learning approach.”
A NEW WAY TO INTERACT WITH CROs
The value of better communication with sites became clear to Daniel when she received a call from a site coordinator. The coordinator was requesting information on a medicine that one of her patients took as part of a trial. After looking into the request, Daniel found the drug had been approved and would be imminently available for use by the patient. Unfortunately, the coordinator was never notified of the results.
The clinical team at Nektar decided it was time to implement some additional processes and practices that could enhance interactions with sites. The goal was to streamline the flow of information from the sponsor, to a project manager with the CRO, to a manager at the site, and then back up the chain of command. Depending on the size of the companies and the trials being conducted, such communications are not always one-to-one and frequently occur via emails or database queries.
It was evident communication could be enhanced, and one person who was instrumental in this effort was Craig Coffman, Nektar’s executive director of clinical business operations & outsourcing.
“We knew we had to start at the very beginning,” says Daniel. “That meant thinking about how we engaged with CROs. We felt that one of the first things to be addressed should be the initial presentation from a CRO. The majority of those presentations cover subjects including capabilities, structure, SOPs, compliance, and bandwidth. As we already had a process in place to evaluate those factors, we felt the presentations were somewhat unnecessary.”
Instead of a presentation, Daniel and Coffman asked potential CRO partners to come in and talk to them about how they would tackle the program. They felt this approach was the best way for individuals from both companies to get to know each other as potential fellow team members, as the most important consideration for the Nektar team was how both sides would interact. During the conversations, Nektar representatives presented their thinking in regard to a trial and inquired as to how the CRO could adapt its organization and teams in order to make it happen.
“It’s definitely a different kind of CRO engagement and selection process,” Daniel notes. “Once they are on board and have a taste of what we are trying to do, we move on to the next stage, which is a kick-off meeting. We take a very different approach to that as well. We let them know that they are our partner, that this is a study team, and that we are all in it together. We also emphasize the fact that the relationship is more inclusive than just Nektar and the CRO. It must also include representatives from all the other service providers that are needed in the study, which could number from seven to 10 different providers on a complex study.”
WHAT ARE ALL THESE PEOPLE DOING HERE?
At a typical kick-off meeting, a CRO will go through the entire contract, making sure all of their management hours and project management buckets are aligned. Nektar delays that part of the process until after a study team meeting that is a bit more difficult. During that meeting all parties walk through Nektar’s protocols from the perspective of the site and then again from the patient’s point of view.
A key concern for Daniel is having the right number of appropriate team members on hand to engage in conversations around the various aspects of the protocol.
As a result, a typical study team launch meeting can get pretty crowded. At one such meeting, there were more than 50 people sitting in a room for two days.
“It is hard to describe,” she says. “We had whiteboard walls. We involved people from data management who would be creating the databases. Many of these folks had probably never been involved in one of these discussions before, yet here they were learning important details about the study and what their role in it would entail.”
Needless to say, some CROs are a bit taken aback by the approach. When one CRO hosting the meeting heard what Nektar wanted to do, the response was, “You want to do what?”
This novel process certainly took some getting used to, especially on the part of the CROs. “When a meeting is scheduled, the first thing a CRO usually does is send out an agenda,” notes Daniel. “Throughout this process, one of the things we tried to do was fight the regular, SOP-driven agenda templates that are common. Most CROs have an SOP for conducting a kickoff meeting, and we would encourage them to disregard that template and start from scratch. By setting aside predefined processes, we were able to brainstorm and come up with new ways of tackling issues.”
This example also illustrates why it is so important to have a good relationship with partners. Daniel will press CROs for what her team wants and notes that most CROs will also press back on certain issues that are important to them. During conversations with the CRO, she will often ask if a certain request will prevent them from doing their job, or if a particular procedure they have in place is necessary to perform a task that was delegated to them and for which they will be held accountable.
"We should never be more than two layers removed from our sites, or even two layers removed from our patients."
Executive Director of Clinical Operations, Nektar Therapeutics
UNDERSTAND THE FIRST CONTACT
Since one of Nektar’s primary goals was developing strong relationships with sites, everyone knew the first contact with a site would be very important. Daniel wanted to know what that first contact between the CRO and the site would look like, what was being said, whether Nektar’s name would be included in the correspondence, and if the proper message was being conveyed. When site management is outsourced, this messaging can be left up to the CRO, but Nektar felt it was important to get deeply involved in the process.
When the CRO formed a team to engage the start-up process and start sending letters, emails, and faxes to sites, Nektar opted to work with them to decide who would make the first contact and what the messages would say. To illustrate the importance Nektar placed on this step, Daniel also insisted on driving the communications, not just having input to them. To do so, an internal communication platform was set up that could also be accessed by CROs and service providers.
“We now have the ability to directly communicate with sites and distribute news, study documents, and protocols via this platform,” says Daniel. “Sites are also using the platform to provide us with comments on documents and feedback on protocols. Some CROs voiced concerns, but so far things are working well. We get to manage our own communications platform, and the CROs are providing us with material to send or simply uploading the documents themselves.”
One of the harder things Nektar had to work through was its mission to become more electronic and modern and eliminate paper throughout the trial process According to Daniel, one of the challenges was in getting service providers to understand that Nektar did not want them to turn into a print-and-ship shop.
“The amount of paper that circulates in a clinical trial is extraordinary and can be hard to manage,” she states. “We have seen CROs design a form and blast email it or do a mass print run and send it to study sites. With the number of stakeholders participating in a trial, sometimes things can happen without you knowing it. Those actions can send a different message to a site than intended by the trial coordinator. By working closely with our CROs, we are doing a good job of managing that process.”
Daniel and the Nektar team already have feedback from sites, and so far it is looking good. “The feedback has been very positive,” she adds, “and they have been nothing short of gushy about the entire experience. Even when offering critiques about things that did not work well, they are still overwhelmingly positive. I think that is a positive sign for us going forward. They feel comfortable enough to tell us where we need to improve because they know they are a trusted partner in the process.”