Open relationship – the importance of post-trial reviews

In essence, clinical trials are a process of reviewing something with the aim of improving it. Reviews and critiques are an essential part of the process of making sure something is the best it can be. So how do we decide what needs to stay and what needs to go?

The use of contract research organisations (CROs) by pharmaceutical sponsors across all therapeutic areas and phases increased by 44% between 2007 and 2011. A study by a consulting company discovered that, in 2010, the largest pharma sponsors outsourced nearly 100% of laboratory services to CROs and service providers. This is a huge level of cooperation based on mutual trust and an understanding that it will get the job done. Without these relationships, it is unlikely that pharma companies and other organisations would be able to undertake the level of clinical trials they do.

So how can a sponsor foster a healthy working relationship that addresses any faults or problems while also being able to ascertain if this long-term partnership could work? Or, if it turns out not to be the best fit, what is the best way to sever ties and seek new partners that can better deliver what you need? It’s a difficult task.

Nancy Meyerson-Hess, Grünenthal’s head of clinical operations and compliance, has over 30 years’ experience in the industry and is well versed in the topic.

“Outsourcing initiatives are targeted to fulfil a need,” she begins. “A company opts to approach CRO management for many reasons, such as resource constraints or seeking expertise that’s not available within the organisation.

“Establishing a relationship involves investment in getting to know each other, explaining and understanding expectations on both sides and at the conclusion of the activities, assessing the success and outcome. All of this requires a people focus.”

Great expectations

There are several issues that recur with these partnerships, and especially in those where the process is ongoing and covers several projects. The first is the culture clash when two established teams come together to learn how to operate as a unit. Managers and senior leaders need to understand that the dynamics and interpersonal relations of a partnership determine whether it endures or fails in the long run – and if a company is coming to the stage where it may have to renew, it can become difficult.

Meyerson-Hess sees this as an opportunity to learn. “Undertaking an exchange of what went well and what did not sets the foundation for a continued relationship. Obviously, when there are many negative outcomes, especially in meeting agreed-to deliverables, this puts the relationship in question for further collaboration.

“Seeking a new partner – if the partner has not yet collaborated with the sponsor – is associated with starting from scratch and establishing a new relationship. I sometimes liken this to going on a blind date, where you need to get to know the person.”

Another challenge many face is the timelines once decisions are made. Companies need to maintain their internal expertise in order to be able to build up that external expertise but, at the same time, it is necessary to verify that outside expertise matches up with the internal team, especially when it comes to quality.

It seems like a lot of the issues associated with deciding whether to stay with a vendor arise from trying to balance expectations. Meyerson-Hess sees several factors being required to sustain a successful relationship between the two companies.

“It is crucial to be clear, and define in writing, what the expectations are, especially in terms of the deliverables in scope, timing, quality and budget,” she says. “It is important to closely discuss and document the agreed-to activities, to make certain that it is clearly understood and to periodically check that this is taking place. This supports the operational teams carrying out the activities and provides them with feedback.”

One unfortunate by-product of a poor working relationship is that management sometimes wants to move a project to a CRO before the two teams have adequately transferred the required knowledge and technology. In these situations, one of the hardest parts of the job can be remaining objective – there are always going to be times when you have to be an advocate for one side or the other, but trying to have everyone hold off making the outsourcing move until both sides are ready is definitely a challenge.

Meyerson-Hess believes that teams that run together need to be streamlined, and that heavy use of constructive debate is healthy to get the best out of a partnership. “Feedback should be primarily through the operational focus; however, the formal outsourcing team’s involvement must run in parallel,” she says.

“These individuals review the relationship and are available for escalation when issues are not solved at an operational level. Management from the sponsor and the CRO must remain involved in the oversight process.”

Speak easy

It is clear that discipline and communication are two ways to manage a CRO team and maintain a healthy relationship that can go forth in the next project, but how can companies avoid poor ongoing relationships between sponsors and vendors during a project?

“Poor relationships are detrimental to the success of a contracted activity and must be quickly addressed,” says Meyerson-Hess. “It can become an issue when the vendor is niche – perhaps providing geographic expertise or [when] there are cultural sensitivities that must be taken into account.

“In such a situation, it is imperative to either engage professionals familiar with collaboration or to provide specific training to your team targeted to interact with the vendor. This also comes down to expectations and communication, and, therefore, to a clear understanding of the deliverables contracted.”

Again, setting up the communication and escalation paths upfront should avoid a poor ongoing relationship. Obviously, if the situation becomes critical and there is no way to rectify the situation, one must consider termination.”

Meyerson-Hess sees ways of avoiding this though – the other aspects of a partnership that are vital to maintaining a working relationship and wanting to partner again for future projects are fairly easy to understand. “Partnership means understanding the needs of each party. When a solid working relationship has been established, it is easy to involve the partner upfront in providing strategic input and best practice based upon their experience.”

“Many companies enter into preferred-provider relationships in order to streamline this approach, but it is still possible to involve your vendor in early-phase feedback,” she adds. “CROs are interested in repeat business and being involved in strategic input; repeat-business situations provide a good basis for quickly starting up activities, especially if there is something like a Master Service Agreement in place.

“Based on my experience,” she continues, “through partnering and repeated business, both parties can benefit: the sponsor in receiving cost savings through special arrangements, sometimes assigning a sponsor operational team meaning that the CRO team is aware of the client’s way of working; for the CRO, looking to the future for further outsourced activities, being involved early on in the strategic planning.

Necessary expertise

“Some sponsors also arrange that the CRO provides experts who are embedded in the organisation for specific functions. This creates an environment of trust and familiarity for both sides.”

“Of great importance is that both parties see their collaboration as a team – not them versus us – and treat each other with respect.”

It seems that the trend for collaborations with CROs will continue. Meyerson-Hess attributes this to the ubiquitous need for specific areas of expertise common across all clinical trials and, of course, cost.

“Laboratory services are an example of an expertise that is used in almost all trials. As such, the establishment of an in-house laboratory or specific imaging service would require a significant financial investment in materials and personnel for the sponsor in order to provide a similar service [as a CRO].”

And does she think there are more pros or cons? “I don’t see this as any different to the overall outsourcing of activities. Outsourcing of clinical-research-related activities involves people; staff relationships are the foundation for success,” she says, adding that differing workplace cultures are a big deal but can easily be overcome with the desire to communicate.

“We sometimes see that the teams do not immediately relate to each other,” she explains. “This is not unusual and can be addressed through various initiatives. This is a global industry and, consequently, people bring their specific cultural profiles with them. It is very important to be aware of these profiles upfront in order to avoid offending someone.

“It is also important to accept feedback from the vendor on potential cultural influences, such as understanding the role of the family in supporting a patient in a clinical trial.”

If you want to define a relationship and have it be an ongoing one, then this should always be at the forefront from the very beginning.

“When beginning discussions over a potential collaboration, have a list of tasks, and which group or person is responsible, and the scope of the task in terms of time, quality and budget. Review this with both parties, making certain that this is understood. This is the basis for the collaboration. Agree on how to review the progress – be it weekly, monthly, via a status report, metrics or a dashboard.

“There is no right or wrong,” she adds. “It all has to be suited to the activities and scope of the outsourced work. Ongoing feedback from both sides, with an emphasis on respecting each other, is very important.

So those are the problems with cultural clash or expectations of workloads that could cause a partnership to end, but what of regulatory challenges that could make it harder to stay with one CRO?

“This is a rare challenge. Sponsors need to select a vendor according to their company qualification process. This process must reflect the business needs, and fulfil the regulatory and GCP/GLP, for instance. The outcome of the selection process is documented, and we are all working towards the goal of always being ready to be inspected by a regulatory agency.”

Talk it through

Above all, Meyerson-Hess believes that communication, established from the beginning, is the best way to nurture and shepherd an ongoing relationship between sponsors and vendors through a thorough post-trial review of the clinical operations.

“The sponsor must provide sufficient detail that allow questions on the requested activities to be outsourced prior to awarding the work,” she says. “From that point on, a well-defined plan of communication for how both parties are to work and interact must be followed.

“Close contact, face-to-face meetings and the establishment of steering committees allows the operational teams to collaborate and move forward. Conflicts or misunderstandings that cannot be solved by the operational teams can then be escalated.

“All should strive for repeat business as this provides a streamlined approach to the next project after the integration of any lessons learned.”