An open book

Successful clinical trials are the result of a relationship between sponsors and solution providers, and, as in any relationship, open and honest communication is essential. A company that has worked hard and invested its resources and reputation in a new therapy must ensure that the process under which it is validated is conducted thoroughly, efficiently and to the highest possible standards, yet many trials are simply handed over to contract research organisations (CROs) only to run into problems down the line.

The reason for this is not that CROs lack technical capacity or the appropriate standards to achieve the required results. All too often, it is that the sponsor has not selected the right CRO for its specific needs, or that the necessary oversight and monitoring has been lacking.

For one company, which develops cellular therapies to target various types and stages of cancer, the correct approach relies on more than statistical analysis and requests for proposals. It begins with informal human contact and interaction.

“Before the process of selecting the CRO for a specific project, we use conferences, training events or any meeting of solutions providers – CROs or electronic data capture (EDC) providers – to evaluate the company and team mentality, and to identify who to contact,” says Jessica Cordes, director of clinical opperations at Medigene. “The relationship management begins before any project is in the pipeline. We take those first steps before a project, so that we are not starting from scratch.”

Give and take

Medigene is a publicly listed biotechnology company headquartered in Martinsried, near Munich. It focuses its efforts on the development of personalised T-cellbased immunotherapies, and currently has candidates in clinical and preclinical development. The company has T-cell receptor-modified T-cell (TCR-T) therapy MDG1011 for indications with a high unmet medical need, like AML, MM and MDS at the clinical phase I/II trial stage, and also dendritic cell (DC) vaccines in ongoing clinical phase I/II trials.

As Medigene is currently engaged in these trials, and is looking ahead to phase III trials, it has worked hard to devise a template for engagement with CROs and EDCs that emphasises clarity and communication – from its own side and that of the solution provider.

“We provide timelines, milestones – which are very important – and expectations of quality, performance and risk management,” explains Cordes. “We aim to be as clear as possible from the beginning. Everything is based on facts in the request for information process, but this only comes after step zero, which is meeting people to get a good first impression.”

“From that we get an idea of who might be capable partners in oncology, cell therapy and so on, and who might be able to work with a small biotech company like ours. We also tell CROs who their competitors are in the process. That is part of our transparent communication process. They must understand our project and our expectations in order to mitigate budget problems.”

Soft skills and hard facts

For Medigene, a transparent process for selecting clinical trial partners is key to setting off on the right foot. It enables the bid defence process to be carried out with candour and clear lines of accountability.

“We clearly define how we select a CRO,” says Cordes. “We score on each of our criteria, and we score by vendor. The criteria have different weightings. Expertise is important, but so is the composition of the team and the chemistry within that team. The experience of the team members is very important, but so is how distributed that team is around the world and whether they are connected or dissociated.

“We also want to know how involved senior management is. Is the project manager experienced enough to do the job or will senior management be stepping in frequently? We have to look at the team empowerment, its experience and how it operates internally,” she adds.

The bid defence is usually the last hurdle for a CRO to clear in the selection process. This intense face-to-face meeting is intended to give sponsors the clarity and certainty they need before pushing the start button on the trial itself, but there are frequent reports of gaps in understanding that open up after these meetings. It is clear that, in some cases, sponsors and CROs leave these meetings with different ideas of what processes and outcomes are expected further down the line.

At the bid defence stage, CROs should have a clear idea of what the sponsor requires of them, and sponsors will be looking to finalise their impression of the CROs capabilities, whether it’s the make-up of the team, the company’s reputation, its commitment and engagement or any other key factors. For Cordes, there are more than the usual boxes to tick, however, and soft skills are high on the list of priorities.

“We look at how they act within their team and with us,” says Cordes. “There is a soft skills review of the people and how they interact with each other. The mentality of the CRO team is not linked to the size of the company. The important thing is that the mentality of the CRO must fit with that of the sponsor.”

“Project success comes from team mentality,” she adds. “So, you could end up with a good CRO but the wrong team for your company, in which case the trial will not be a success. A perfect fit is when the CRO’s corporate mentality and the team mentality fit perfectly with your mentality as the sponsor. But if I had to prioritise, I would choose the mentality of the team. It is more about the individuals than the organisation. That is why it is important to have the whole team attend the bid defence meeting, not just the project manager.”

Two-way street

For Cordes, setting out the chain of command and the lines of communication are essential steps for the sponsor. Equally important, however, is verifying that the oversight process and the project outcomes have been clearly expressed.

“The people who are handling specific areas, such as the clinical operations process, must be clearly identified,” notes Cordes. “The clinical trials manager is in charge. As the sponsor, you have to clearly communicate your KPIs so that there are no surprises for your partners. If you do that, the CRO can say if it is not comfortable with what you require, and it can choose not to send a quote.

“Complete transparency at the beginning is the key step,” she adds. “It is also important to ask the CRO to summarise what they have heard from the sponsor about its expectations to ensure that they have interpreted everything in the right way. That is just as important in an outsourcing model with external partners as it would be with internal colleagues.”

For Medigene, the governance structure is a key part of detailed discussion that takes place to mitigate potential issues early on. Reports to the clinical trial manager happen once a week, then Cordes herself meets once a month with her counterpart at the CRO, and Medigene’s chief medical officer is involved twice a year or when an issue arises that needs to be escalated.

“There needs to be a clear escalation process in place and the governance structure needs to be shared early on,” Cordes remarks. “The sponsor has full responsibility, so we have to keep track of the activities of the CRO and have the right governance process in place. We can’t pass the overall responsibility to the CRO.

“I have seen projects run like that in the old days, and the result was that the data was not good enough for full statistical analysis because the CRO did not do a good-enough job. If you have a good fit with a really proactive partner then the governance process just becomes about ticking the boxes, but I have not seen that work in practice yet. There is always a need to step in temporarily and put the process back on track.”

Balance time and transparency

What Cordes describes is an extensive planning process that involves putting in place all of the necessary assessments – from the technical to the personal – and getting to know the individuals involved. This can be a lengthy process, and time is not a luxury of which there is an endless supply.

“It does take time, and for us there is not usually much time to spare,” she explains. “It is sped up by sharing all of the details of the project up front. They are already part of the initial contract, then we negotiate the master service agreement and generate the work order. We agree the allocation of responsibilities as a key part of that, not just as a footnote, so that it is not left until the project planning phase. We do that as a mitigation, so that there is less change in the scope of the project.”

To achieve this, the sponsor must know its own mind and express its aims clearly.

“We have set KPIs about quality, performance and so on, and the CRO can see our thresholds, which are an appendix to the work contract, not the later project plan,” adds Cordes. “The job profiles for key personnel at the solution provider are also part of the contract. There, we specify that people must have certain experience. That way, the CRO can determine if it is capable of handling the project for you.”

The thorough process that Cordes describes is not common in the industry. What seems obvious in terms of planning and transparency to mitigate potential problems before they arise is not the norm.

“We are innovative in our approach, and we get good feedback about our approach from CROs,” she remarks. “For instance, CROs do not normally know who else is competing for the project. But what we are doing is allowing them to be a real partner because we are not only clear about our expectations, but we also listen to what they say to us. What we hear from CROs is that they feel sponsors usually just throw them an RFP. So, sponsors need to adapt, too. After all, it is a collaboration.”

It is easy to say that communication and oversight are important for clinical trials, but it is harder to put those words into practice. Effective communication is not just about setting clear parameters that partners must meet, it is also about listening to what solution providers need.