For many pharmaceutical companies engaged in clinical trials, outsourcing is not so much a choice as it is a necessity. Trials being notoriously complex projects, it isn’t often feasible to conduct the whole process in-house, nor does it make sense from a financial perspective. And as the market for contract research organisations (CROs) widens, sponsor companies have an unprecedented opportunity to tap into a wealth of resources.
Some delegate the entire trial to one or more CROs, while others outsource only certain services. Still more will opt for a solution in between the two extremes, harnessing all the benefits of a third party while remaining relatively hands on throughout. But while the specifics vary, all face similar challenges when it comes to selecting a partner.
"If you miss on the CRO selection, it could set you back," says Craig Coffman, senior director of business operations and outsourcing at Endo Pharmaceuticals. "If the relationship does not go well, the study’s going to reflect that – there’ll be communication problems, and probably some trust issues too. You’ve missed selecting a CRO that best meets your study needs."
In an ideal world, CRO and sponsor would work together fruitfully, achieving their goals on time and on budget. Unfortunately, this is not always how matters pan out, with long delays and spiralling costs a very real possibility. In a worst-case scenario, the relationship may need to be terminated midway through the trial, wasting colossal amounts of resources and precious R&D dollars in the process. Third-party selection is therefore a critical part of the clinical trial, and a key determinant of success.
In the past, the prevailing attitude was basically that bigger meant better. Sponsor companies would default to a big name CRO on the basis of scale or reputation, believing that a broad-ranging provider would inevitably have greater know-how. Unfortunately, this strategy was far from foolproof.
"People used to think ‘surely they’ve got the services, and the people and the expertise to do the job’," says Coffman. "But, while they may have all those things, they won’t necessarily be a fit from a cultural perspective. Also, if they’re a very large CRO and you’re a small sponsor, are you getting all the attention you need?"
Mix and match
A US-based pharmaceutical organisation, Endo Pharmaceuticals manufactures drugs for use in pain management. Originally employing the services of a single large provider, the company now uses a centralised outsourcing function. It aims to work with partners who represent the best possible match.
In doing so, it mirrors a general industry trend. As they grow more discerning, sponsors have started to acknowledge that what works for one may not necessarily work for another. Rather than leaning on word of mouth, they are applying clearly defined benchmarks and arriving at their own conclusions. At Endo, the team starts by setting up some selection criteria specific to the study in question. Whether it be therapeutic expertise, geographic reach or an integrated data management system, the company determines the relevant items and decides which of these are most crucial.
"We customise this for every study," says Coffman. "It’s not a template that we just pull out. Working with the clinical team, we determine what elements of CRO selection are most relevant and critical to the success of the study. Once we get our requests for proposal (RFPs), we have a bid defence meeting and rate the CROs that we’ve asked to participate based on the criteria we’ve selected. Frankly, I think if you’re not in an alliance with a particular CRO or preferred provider, this is the best tool to use."
Of course, it isn’t always possible to gauge all relevant factors in advance. While aspects such as geographical presence are easy to confirm, other selection criteria are subject to interpretation – every CRO, for example, will claim to be knowledgeable, punctual and reliable. When it comes to distinguishing between rhetoric and reality, the sponsor is required to perform a difficult balancing act.
"If you ask for references, I’m not saying they’re going to stretch the truth, but they are going to put their best story forward," says Coffman. "It’s one of those things where you need to trust them, but also verify the details as best you can."
For example, if the sponsor is looking to outsource an entire study, it will be keen to ensure that the CRO has significant experience in that field. If a CRO claims it can deliver on time and on budget, but only has one global study to prove this, its track record may prove insufficient. Ultimately, however, this is not an exact science – "Pretty soon you’re just going to get a feel for it," Coffman says.
Another point to bear in mind is the CRO’s corporate culture. One of the most critical pieces of the equation, cultural fit can be instrumental in determining whether a relationship succeeds or fails. And while it might sound like quite a nebulous concept, it is absolutely imperative when it comes to establishing trust.
"We can look at a lot of data about the trials they’ve done and where they’ve got offices, but at the end of the day, these trials are very long term and we’ve got to feel comfortable that we can work with that company over a period of time," says Coffman. "If there’s not a fit, we’re off to a bad start from the beginning."
Common ground
When the CRO and sponsor operate from similar starting points, drawing on a nexus of shared values, it becomes far easier for the sponsor to harness the new intellectual capital at its disposal. The two are less likely to work at cross purposes, and more likely to honour their goals.
Conversely, where the two parties are fundamentally misaligned, there is an extra layer of complication in the mix. In the absence of trust, the sponsor may be tempted to micromanage, which can stand in the way of success. There’s a fine line between micromanaging and providing good oversight to the process. Micromanaging a CRO really reduces the benefits of outsourcing. It will take both parties working side by side to meet the stipulated time line and budget.
So, how can the sponsor determine these matters from the outset? Above all, communication is key. Rather than assuming anything, it is critical that both parties lay out their expectations and clarify any areas of confusion. Transparency is the watchword, for sponsors and CROs alike.
"Expectations need to be set up and put on the table very early in the process," says Coffman. "As a sponsor, I need to be clear in what I’m trying to accomplish, and the CRO needs to speak up and push back if they think I’ve got some erroneous expectations. At the same time, we need our CRO partners to give us the benefit of their knowledge and institutional capital, and we’ve got to be willing to accept some of that."
The last thing a sponsor needs is a CRO who falls into line unheedingly.
"I don’t need somebody to say, ‘Yeah, yeah, yeah, that sounds good’," adds Coffman. "I need somebody to say, ‘That sounds good, but it’s been our experience that it will take six months longer to set up sites in that country than it’s worth’. By the same token, if I have a particular interest in that country and do want to conduct my trial there, they need to be told about that."
If the sponsor wishes to benefit fully from the CRO’s expertise, it is important to initiate this dialogue as soon as possible. This should be a relationship of equals – a collaborative, rather than hierarchical, approach – and it will not function optimally if the CRO is drafted in too late. What is more, early engagement with a CRO can help the sponsor gain a clearer idea of how the trial will work in practice.
"Once we have an indication that we’re going to move forward with a particular study, we like to engage, even though we may not have a synopsis available," says Coffman. "The CRO may help us flesh out what the study design would look like."
An open dialogue
Of course, since the wrong choice of CRO can be ruinous to a trial, there is little to gain from making a knee-jerk selection. Endo, therefore, talks to two or three possible contenders, disclosing its aims for the trial and asking how they would put those aims into action. Only once these preliminary conversations have taken place will the CROs move onto the more formalised RFP process.
"A proposal’s going to be three prongs really – budget, timeline and strategy," says Coffman. "We try not to constrain them on strategy. We’re hiring them because they’ve got the experience, and if we ignore that we’re not going to get the benefit of it. We’re looking for them to tell us how they can operationalise the study on our behalf, and we’ll have some dialogue back and forth throughout."
The sponsor company will then review matters internally and assess the proposals against its predefined selection criteria. While strategy is examined thoroughly, budget and time frame tend to be relegated to the sidelines: budgets will be fairly close in range providing the assumptions are the same, and can be negotiated following the selection. Likewise, time lines need to be accurate as opposed to ambitious. Overly optimistic proposals can raise suspicions.
In fact, a benefit of engaging several CROs is that spotting outliers becomes easier. If one of the candidates makes vastly different predictions to the others, the sponsor can delve further and find out why. Are the assumptions the same? Is the CRO being unrealistic? If you only had one CRO on your hands, it would be hard to determine any discrepancies. What is more, three proposals means three sets of ideas to pick from.
"We can start to pick and choose what we think are the key elements," says Coffman. "Then, we have the benefit of what’s out there, and can put it to good use and select a CRO partner that can best operationalise the study for success."
Ultimately, this is a team endeavour, for the good of the sponsor and the CRO. Both parties need to remain fully accountable throughout, aware that the more upfront they are, the better for all concerned. After all, clear communication doesn’t just help with CRO selection; it also helps the two companies work as an integrated whole.
"If we’re all sitting in a room, and we allow them to look through the keyhole, the only thing they can see is the other side of the room," says Coffman. "But if we open the door and share everything with them, they get the whole landscape – which benefits us in the end."
It is incumbent on the sponsor to open that door and invite their CRO to look around.
