The Risk & Rewards Of A Fully Outsourced Clinical Model

By Ed Miseta, Chief Editor, Clinical Leader

For years, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany used a mixed clinical outsourcing model. The company conducted some trials in-house but outsourced others to external service providers. For trials in development around the world, the company had four global CRO providers. For regional Phase 4 and label expansion studies there were as many as 100 different providers, which included niche CROs from around the world.

Merck KGaA, Darmstadt, Germany acquired Serono in 2006. Soon thereafter, the company closed the Serono hub in Geneva, Switzerland, and also decided to outsource the entire trial portfolio to CRO service providers.

A New Strategy And A New Model
“The operations group was asked to come up with a model that would allow us to conduct clinical operations in a manner that was faster, less expensive, high quality, and more efficient than our previous model,” says Jacqueline Curtiss, the company’s global head of clinical trial management, global clinical operations. “We knew it would be a fully outsourced model, but other than that we were given no parameters or restrictions. As a team, we just needed to figure out how to get it done.”

Questions were raised whether this type of outsourcing model would actually save the company money or if the company would maintain adequate accountability over the trials — and whether a CRO could run them better than the sponsor. What would be the efficiency and effectiveness of a fully outsourced model?

The decision ultimately came down to cost and expertise. If the company was in a position where it had to undergo change, then why not find those areas of expertise that could be most easily outsourced? This operational piece was really just one component that would change how the R&D organization operated.

Bring The Right Minds Together
Once the decision was made to outsource all trials, a decision still had to be made regarding the number of outsourcing partners and who those CROs might be. As any operations person will tell you, selecting the right partner is never an easy task.

“The cross-functional team went through a very detailed process that involved dedicating almost a full week’s time to discussing the advantages and disadvantages of a sole provider, and whether that would work for us considering the size of the company and our portfolio, as well as the global reach of the trials we had in development,” said Curtiss.

Some felt outsourcing to one CRO had its advantages, while others were concerned about transferring all trials to one partner. One of the biggest questions that came up during the process was whether the company had a large enough portfolio to justify two CRO partners. Another concern was whether that portfolio would be important enough to two large CROs if it were to be split in half. What resulted was a complex and pointed conversation.

There was a cross-functional group of about 22 people in the room. Clinical operations were a big part of it, but the group also included medics, statisticians, data managers, and representation from the early development team. Every department that could potentially be impacted by the decision had a voice present.

Change management was an important consideration for bringing that large a group together. Management knew that moving forward with a complete outsourcing model would require buy in from key stakeholders at every level of the company. It was clear that this task would be challenging, but with the size of the company and its portfolio, it was a move that made the most sense for the company.

One Development Engine And One CRO
During the decision-making process, Curtiss notes she never believed the company would opt to align itself with just one CRO. However, she knew many pharma companies and their CROs often seem to have overlapping activities. That was something the biopharma business of Merck KGaA, Darmstadt, Germany wanted to avoid.

“Trust is an important element between pharma and CROs,” says Curtiss. “Oftentimes the CRO waits to be told what to do to ensure they get paid for doing it. But when that happens, they do not have any responsibility for what is being done because someone from the sponsor company told them what to do. That dynamic doesn’t work well.”

That is when the team came up with the idea of employing a model where there was a single development engine for the company. The model would ensure there was no duplication of effort and would feature an external development team that functioned as an internal part of the company. There were questions around whether it could actually be done and even if there were a partner that would be willing to participate. Still, Curtiss and many of the team members felt this was something that could work. They also realized there was no way it could work with more than one CRO. No one would see the logic in having a “single” external development engine that consisted of more than one partner.

Show Us What You Can Do
To help with the selection process, the biopharma business of Merck KGaA, Darmstadt, Germany created a bid grid, which helped it define what the company needed. The grid was like a decision tree that created a list of potential service providers that was then winnowed down. Initially there were eight CROs on the list. Because the biopharma business would be fully outsourced from end-to-end, the process of getting down to four CROs was relatively easy. Several of the CROs did not have the desired capabilities and would not be able to help the company with its early planning work. From there it got a bit more difficult. A significant amount of time was spent evaluating the final four CROs.

“Each of the four CROs was sent a profile of one of our molecules,” says Curtiss. “We simply said, ‘Develop this for us.’ No other directions were given. We wanted them to come up with a development plan, whether it was right or wrong. We just wanted to know that they had the expertise and the staff to be able to do this, as well as the commitment to actually sit down and get it done. It also allowed us to see what each CRO considered to be a good clinical development plan in this highly competitive landscape.”

The four CROs were then brought in for a structured, day-long meeting with the cross-functional team. The meetings were run exactly the same for each CRO, and the entire team received a thorough download at the end of the day on the performance of each CRO.

“The mornings were set aside for us to evaluate their development plan,” says Curtiss. “The afternoon featured breakout sessions to determine standard capabilities, such as IT, medical, and regulatory. I was in the session looking at the clinical trial management system (CTMS) to determine how our systems might work together and interface.”

Once the meetings were over, the team unanimously chose to pursue a one-CRO model, with QuintilesIMS being the unanimous choice and the primary partner for trials in Phase 1 to 3 and even some Phase 4 work. (Depending on the scope of the trial, another CRO could be used in some specialty cases, and a very detailed process notes how and when the company can go outside the partnership.)

Some Got It, Others Didn’t
The evaluation team knew the CRO selected would have to offer end-to-end services. On the back end, they would have to understand the needs of regulatory submissions. But that is the easy part. On the front end, the partner would have to help the company determine the clinical development plan based on their operational feasibility, understand the indication, know what countries to work in, and how to best develop the asset. That was the more challenging part.

“We felt there were few CROs with the capability to bring that end-to-end offering to the table,” notes Curtiss. “Our meetings really forced us to test them on that early development piece. We needed to know if they could provide the operational expertise necessary to develop the molecule. But we also needed to know if they had the global reach to pull it off. There are not many CROs that can run a large global Phase 3 trial in the number of countries where we operate. Third-party vendors play a role in the clinical process. The CRO would be allowed to pick those vendors but would also have to be competent enough to manage them throughout the course of the trial.”

When it came to demonstrating its capabilities to develop a molecule, some CROs seemed to understand the assignment while others did not. Curtiss notes some CROs brought the wrong people to the meeting. Others brought a team that attempted to make a sales presentation. This did not allow the cross-functional team to see what they had to offer or if they would be able to embrace a different way of thinking that involved doing a lot of the planning rather than simply following direction.

“We started this process in 2012 and made our final decision in 2013,” says Curtiss. “It takes a significant amount of time and energy for a true partnership to begin to deliver benefits. Your portfolio, teams, and the industry will all undergo changes. In addition, you need to be willing to adjust your model as the situation changes. This includes a continued need for sponsor oversight and associated applicable regulatory requirements. It’s important to give these partnerships time to mature.”

SIDEBAR

Inside A Massive Outsourcing Shift

When the biopharma business of Merck KGaA, Darmstadt, Germany made the decision a few years ago to outsource all of its clinical trials to QuintilesIMS, it created a challenge Jacqueline Curtiss and her colleagues would have to solve. Curtiss is the global head of clinical trial management at the Biopharma business of Merck KGaA, Darmstadt, Germany and was part of the team tasked with overseeing the process of moving all trials, including those being conducted internally and at other CROs, to its new partner.

Moving just a single trial from one CRO to another can be a challenge, but Curtiss notes moving all of your ongoing trials to that one provider required a tremendous undertaking. A clinical trial cannot be moved overnight, and transitioning those trials to the new service provider took approximately two years to complete.

“The first thing we did was perform a gap analysis to determine if it would be feasible to transition all trials in progress,” says Curtiss. “We had studies that were close to completion, either in-house or at another CRO. If it made sense to finish rather than transfer them, that’s what we did. The main priority was maintaining proper treatment for patients involved in the studies and ensuring there were no disruptions. All other concerns, including cost and time, were secondary. When a patient showed up at their site for a visit with their physician, we wanted that to be a seamless experience for them.”

The first trials transferred were the ones most recently launched or in the process of being launched. Transition teams at both companies were created to ensure the transfers were conducted smoothly and properly. The process was complex and often required the company to pay the new CRO for work that was already completed by another provider.

“This was a massive effort,” states Curtiss. “Contracts that were already in place needed to be changed. Documents had to be refiled with regulatory authorities in all of the countries where we operate, and sites needed to be notified. Some of those documents were very complex, which contributed to the challenge of the transition.”

Maintain The Right Skill Sets

Throughout the process, retaining top talent was a priority — qualified people to continue the work during this transition. At the same time, QuintilesIMS needed to make sure it had staff available and prepared to take on the additional work. Finally, the individuals maintained internally also had to have the right skill sets. For example, someone who was leading a trial in-house might not have the skills and experience to manage a study that was outsourced. Curtiss notes this was a critical part of the conversion effort, as the two jobs require entirely different skill sets.

“Managing a CRO is not as simple as saying, ‘I know what work needs to be done, so I am capable of telling someone else what they need to do,’’’ adds Curtiss. “Teaching people how to lead and ensure proper vendor oversight versus performing the work yourself is a hugely underestimated training need. These are two very different jobs. Once we opt to outsource a trial that had been done in-house, we need to release control (but not accountability) of the study to the CRO and let them do what they do best. Our job at that point is to provide oversight and set the strategic direction. We have to be able to demonstrate to regulators that we are maintaining control over the trial and ensuring patient safety, while also releasing some of the day-to-day activities and tasks to the CRO. That can be a very delicate balance.”

As noted earlier, a primary goal was maintaining treatments to patients. There were approximately 15 trials that had to be transitioned to the new CRO. While a lot was changing in the background, including contracts and the CRO representative at the investigative sites, there were no gaps in treatment for the patients, and most would not have known a change in CRO even took place.

Do What You Do Best

Although the biopharma business of Merck KGaA, Darmstadt, Germany has a large and competent legal team in house, it opted to have its new CRO partner do most of the contract work with sites due to the huge increase of workload during the transition. The pharma company provided QuintilesIMS with language it found acceptable and asked that new contracts be negotiated using that language.

Allowing the chosen CRO to do things its own way was a new way of working. The two companies had to develop a plan for how to work together, which Curtiss notes was another important focus area.

“We realized quickly that change management was key to the success. Leveraging the skills and expertise of both companies and bringing them together to create one team allowed us to really optimize the strategic intent of the partnership. Change isn’t easy, but everyone has made a concerted effort to make this collaboration a success for patients.”