Clinical trials can be dauntingly complex. The high-stakes culmination of years - sometimes decades - of research, they involve rigorous data requirements, close regulatory scrutiny, intricate logistics, and intense cost pressures. Add the stress of trial outcomes sometimes being a make or break proposition for the sponsor, and it makes sense to hire a professional management team who are experts in delivery execution: a clinical research organization (CRO).
Such an arrangement allows biotech and pharmaceutical companies to concentrate on the science that is their core strength, while leveraging the CRO’s intellectual capital and operational experience. It provides time efficiencies and economies of scale, eliminates the potential for perceived conflicts of interest, and may be useful navigating regulatory roadblocks.
At best, it can be a formidable foundational relationship that powers dozens of trials yet, at worst, if not approached properly, it can doom the trial that it is meant to bolster.
Let’s examine the reasons a Sponsor-CRO relationship may struggle, and a few simple techniques that can ensure it is not only robust, but that it helps advance the success of the trial.
Uncovering the Source of Issues: The Four Fs
Trace almost any Sponsor-CRO upset to its root cause and you will uncover the Four Fs.
If the initial request for proposal (RFP) and planning process are Faulty, the trial’s feasibility assessments are inevitably Flawed. For instance, if the trial is predicated on having 10 patients per site, but more than half the sites have only one patient, then the feasibility assessment was flawed. Or perhaps there are plenty of patients, but the site is meant to process 80 samples a day, yet can only handle 10; again, the feasibility assessment was flawed. Under either circumstance, the site performance Fails, leading the overall project delivery to Founder. And the SponsorCRO relationship bombs (as does, probably, the trial).
Navigating the Sponsor-CRO Relationship
The Sponsor-CRO relationship can be rich, rewarding and long-lived if it is properly established. It can produce time-efficiencies and costsavings, greater commitment and higher-quality delivery. Yet, these things don’t happen by chance. Both the Sponsor and the CRO must toil in tandem to develop clear expectations, well-defined responsibilities, and carefully integrated cultures.
Above all, both sides need to be clear that the CRO is a partner, not a vendor (not even a preferred vendor). Both sides need to forsake transactional exchanges, value collaboration, and embrace shared goals - in fact, they should stop thinking about “sides” and consider themselves to be on the same team. This takes time, hard work and commitment. It also takes constant, steady communication.
That communication starts with open, collaborative dialogue during the planning and feasibility processes, so as to avoid the Four Fs.
Establishing a Solid Foundation
As mentioned earlier, the RFP/planning process sets the foundation for the trial; if it is properly executed many potential obstacles are eliminated.
First, the Sponsor must select a CRO that can be an effective partner. Individual team members and collective attitude are key.
Since the CRO industry is competitive, turnover is high and when employees leave a CRO, they take their hands-on experience and intellectual capital with them. So, Sponsors should spend less time on the credentials of the CRO as a company, and more on the credentials of the individual employees who will be on their trial team. Asking the following questions can help vet a prospective team member, and generate confidence in the contribution they will be able to make to the trial’s success.
- Does the prospective team member have expertise in the therapeutic area and disease indication?
- Have they worked in the countries where the trial may be conducted? What is their experience with that country’s regulatory guidelines, ethical requirements and import-export regulations?
- Do they have experience with trials in out-of-the-ordinary or complex indications?
- Do they have strong critical thinking and problem-solving skills?
- Have they dealt with sites that have never participated in industry-sponsored research? Have they successfully conducted site training?
- How well do the individual team members communicate with each other? Have they worked together before? Does it feel like a good fit with the internal team?
- Do they have the self-assurance to work with key opinion leaders (KOLs), investigators and large academic institutions without feeling intimidated?
Attitude is just as crucial as qualifications. The CRO and the individual team members need to understand that the project is not just about data management or writing queries or monitoring outcomes - it is about the success of the Sponsor organization, about people’s jobs, and about whether a potential treatment moves to the next phase of development.
Give Them the Right Information
Having a well-defined strategy - a clear understanding of your goals, objectives and roles - ensures that the CRO can match its services and expertise with the Sponsor’s specific project needs; it also enables the CRO to help refine project goals and objectives based on their previous operational, regulatory and therapeutic area experience.
This collaboration can and should happen during the planning and feasibility stage. A sound approach is to start with a letter of intent (LOI); engage in one or more working planning sessions during which goals are vetted against what is feasible, what is likely, and what simply won’t work; then finalize the work order based on those discussions.
This sort of collaboration not only clarifies the Sponsor’s overall objectives - do they just need to do the minimum necessary to get an early signal or are they trying to take a drug to market - but also helps create the parameters of the trial.
During this phase, Sponsors and CROs establish the outline of the trial, detail broadly defined responsibilities, and determine who handles each role. This phase also provides an opportunity for team members from both groups to gain clarity into the personalities and corporate cultures they will be working with for the duration of the trial.
Institute Effective Governance
Regular planned assessments are an essential component of any strong working relationship. These may include weekly check-ins, more formal monthly meetings, and evaluations at each milestone. Sponsor and CRO senior management need to be involved regularly, both to convey the importance of the project and to provide occasional impartial oversight. Their more objective (and, perhaps, more seasoned) view can help spot potential complications before they become problematic, enabling the team to trouble-shoot more effectively and keep the trial on a smooth course.
Set Shared Goals
The best way to ensure that everyone is pulling in the same direction is to align their goals as well as their expectations. If the Sponsor is a small or mid-sized company, the trial may be testing its only asset, with the success of the company (and all its employee’s jobs) riding on the outcome; the CRO needs to understand that it’s not just data they are managing, but the company’s future - and they need to fight for it as hard as if it were their own.
Risk-sharing can be an effective means of tying financial motivation to a common goal, and making the final success be a true reward for all. However, any financial incentive should be tied to metrics and outcomes that the CRO actually can exert control over. It is neither fair nor helpful to insist on specific results or even milestones that can only be achieved with significant contributions from other parties.
Likewise, there can be no finger-pointing: if the CRO is failing maybe the Sponsor is doing something wrong and if the Sponsor is failing maybe the CRO is doing something wrong. It doesn’t matter. At any juncture, the two groups need to work hand in glove, unconcerned with who is at fault, simply identifying the root cause and wholly focusing on how to solve any problem - prospective or current - together. Success, after all, is their shared goal.
Securing Success: Commitment to the 3 Ds
Of all the fundamental strategies underlying a strong Sponsor-CRO relationship, the most powerful is communication. I call it C3D: “The Commitment to Dialogue creates the Direction which ultimately makes the Difference in the relationship.”
Start with real dialogue. This means two or more people talking, preferably in person though over the phone or web is acceptable; email, in which both tone and meaning are easily misunderstood, is not acceptable. In our global work culture with offices spread around the world, we rely heavily on email. But sometimes, and more often than one may believe, people don’t get the right message - which can have serious repercussions.
Worse, without regular bi-directional communication, sometimes the message is never conveyed. The Sponsor assumes that the CRO knows they signed a contract in France and declined the one in the Czech Republic - but the CRO doesn’t know and is relying on recruiting patients in Prague.
This dialogue must be bi-directional. The Sponsor cannot simply talk at the CRO (or vice-versa). The CRO needs to feel free to challenge assumptions and share advice based on the experience the Sponsor has already ascertained that they have. For instance, if the CRO has conducted four other trials over the past three years with a similar indication and design, they should never be reluctant to tell the Sponsor that a certain path is unlikely to be successful. Conversely, the CRO should always listen closely to the Sponsor, filtering everything though their known needs and drivers.
That is true for individuals, too. Some people like to hear themselves talk; some people process out loud; some are alarmists; some epitomize ‘calm, cool and collected.’ All team members - both Sponsor and CRO - must learn and remember how each team member best communicates, and keep that in mind whenever someone speaks. As they say, consider the source and always understand your audience.
All this work will pay off not only in the final trial result, but at every stage along the way. It will produce better results, creating the sort of relationship where either side can pick up the phone and say, ‘We messed up; here's what we're going do about it.’ It will also make the months working together smoother and more enjoyable, by building the trust that is an essential factor in a strong partnership. In short, open bi-directional dialogue can really change the Sponsor-CRO relationship.
Building a Long-Term Relationship
Of course, no CRO is going to be the perfect fit for every trial a Sponsor ever runs. Yet, establishing a solid long-term relationship that spans multiple trials creates efficiencies for both sides. The CRO team has the chance to internalize the Sponsor’s key needs and drivers, so responding with those in mind becomes instinctual. The Sponsor learns precisely what to expect - and what to deliver - at each milestone. The team as a whole builds a comfortable working relationship based on highly effective communication and a trust that everyone has each other’s back. Lessons learned from one trial are easily applied to the next. Transitions are smooth, expectations are appropriate, planning is seamless.
To that end, Sponsors who want to ensure a long-term relationship with a CRO should be sure to provide visibility into their upcoming plans, so that the CRO is prepared and free to participate. Otherwise, the CRO may anticipate team member availability and take on other projects - leaving them unavailable to manage the Sponsor’s Phase 3 trial; the shared learnings from the Phase 2 trial wasted; and both sides sorry that the strong relationship they have built cannot continue.
This comes back to the fundamental premise: the best Sponsor-CRO relationship is a collaborative partnership, not a transactional employeremployee affiliation. Every aspect and every interaction should be crafted with that in mind. Both the Sponsor and CRO should be in continuous, ongoing dialogue about how to advance the partnership, and how to develop their organizations in tandem. Indeed, the goal is not just to build a partnership, but to build a very intimate and long-term partnership.
When such an enterprise succeeds, it delivers far more than commitment and comfort. Shared knowledge begets streamlined operations and the resultant time- and cost- efficiencies. Shared expectations support high-quality delivery with no surprises. Above all, a shared outlook helps each side reinforce the other in the drive to success.