The landscape for clinical trials is ever evolving.1 Adaptive trial designs, decentralized, and hybrid trials are becoming more prevalent, particularly in light of the COVID-19 pandemic.2 Regulatory changes in the US and abroad are constant and inevitable.
As clinical trials change, the relationships between contract research organizations (CROs) and sponsors have evolved as well. Both entities have needed to respond to the trends noted above, and deal with issues such as staffing challenges, remote work, and multiple vendors (e.g., electronic data capture, central labs, core imaging labs, etc.).
Throughout it all, the relationships between sponsors and CROs remain critical to clinical trial success.3,4 Although there are many environmental, technological, and regulatory changes occurring in the clinical trial space, the basics of CRO and sponsor relationships still apply.
From the perspective of the CRO, the optimal sponsor client is friendly, engaged, responsive, respectful, and communicative. In fact, it is in the CRO’s best interest to ensure that the sponsor relationship is healthy and productive.
Conversely, sponsors choose their CRO partners very carefully. Oftentimes, they send out requests for proposal (RFPs) to several vendors and have a process for narrowing down to their chosen CRO. As with CROs, sponsors want to work with those partners who are capable, communicative, and responsive.
Unsurprisingly, CROs regularly perform systematic internal reviews of their clients’ projects. Often included in these reviews are assessments of the relationships with the sponsor client. One component of project reviews done at former CROs engaged internal discussions around a list of “warning signs.” These signs were meant to give a heads-up to management of factors that either make the project difficult to execute or point to the possibility of the CRO losing the project or client.
These warning signs can be instructive for how sponsors and CROs interact.
1. New type of product or study
Part of the appeal of medical device clinical research is working with cutting-edge products. Because these devices are so innovative, there may be no similar devices on the market and, therefore, the CRO understandably has not worked with thetherapy or product class. This can require creative thinking with study design and conduct (within regulatory requirements) and perhaps with the FDA itself, but such resourcefulness can appear to the sponsor that the CRO staff are inexperienced.
While the sponsor should be the expert on their therapeutic area and product, very often (especially with startups) they are not experts in clinical research. Part of the CRO’s job is to educate clients in compliant study conduct.
2. Difficult contract negotiations
It’s been the author’s (hard-earned) experience that clients who show a win-lose mentality while negotiating the consulting agreement extend that same attitude to relationships during the project. It becomes difficult when the sponsor continues to be overly demanding during the clinical study. The CRO should be looking out for the best scientific and regulatory interests of the sponsor, but this can be misinterpreted as obstructionist.
Conversely, difficult contract negotiations with the CRO can foreshadow a team that is rigid in their thinking and performing in a “cookie cutter” manner.
3. Customer not fully funded
CROs, like any business, need a steady revenue stream to survive. Startup organizations are often key customers for CRO services, since many lack the necessary talent and experience in the clinical research area. Startups are sometimes tenuously funded, and it is important for the CRO to keep an eye on accounts payable as well as work with the company to find the most efficient and less costly way for execution to keep the costs within the company’s budget.
Of course, sponsors need to perform due diligence not only on the financial health and track record of a prospective CRO partner, but on appropriate staffing levels and historical performance.
4. Client timelines expectations vs realistic timelines
More often than not, sponsors push the deadlines for their clinical trials onto the CRO based on business needs and promises to investors rather than a realistic timeline for the respective trial. The study timelines depend on several factors that might not be in the CRO’s control, such as site contract negotiations and enrolling the right participants. It is important during the bid, as well as throughout the study duration, to keep track of project timelines and communicate any changes to the sponsor while mitigating any potential delays and risks.
Conversely, CROs may need to calibrate their expectations. While the CRO may have the ability and motivation to move quickly, the sponsor may have constraints (e.g., budget, manufacturing, etc.) that prevent moving full speed into their clinical study.
5. Client questioning invoices/overly cost conscious
To be clear, clients should scrutinize their CRO invoices carefully, as clinical studies are a huge investment. It becomes excessive, however, when every line item and expense is questioned, and the CRO needs to put aside work to answer excessive questions. In an optimal relationship, the level of invoice detail should be reached early in the process and hopefully questions can be minimal.
As an analogous situation, a CRO’s over-reliance on frequent change orders can test the sponsor relationship. It is natural for project scopes to creep, and documented changes should be able to be billed to the sponsor. How refreshing it would be, however, if all CROs responded to RFPs with realistic study budgets instead of the lowest number in order to win the business. CROs also need to communicate typical reasons for change orders with their clients and think about how often they send them; perhaps changes in scope can be saved for quarterly updates.
6. Changes in client or CRO management
Personnel change is an unfortunate reality of life. It’s fair to expect a strong working relationship can be established over time between the CRO and sponsor teams. When this balance is upset, it can be for the better, but very often, it is for the worse. New sponsor managers frequently want to establish themselves in their company and often the CRO is an easy target.
Not only do sponsors despise (and rightly so) changes to management in the CRO, but changes to the project team members are equally disliked, due to the retraining and onboarding of new study staff. It is incumbent upon CRO management to create working environments that help with employee retention, but also to keep a project team together for as long as possible. When change is necessary, a clear plan and communication with the sponsor is critical.
7. More than one decision-maker
In any client/consulting relationship it is always easier to work with one point of contact. In reality, many sponsors have a group with which the CRO team works. It becomes problematic (going both ways) when a member of the sponsor team overrules a previous decision, or multiple decisions are handed down. The best way to mitigate this situation is to establish communication pathways and document it early in the process, hopefully at the project kick-off meeting.
Due to the nature of the sponsor-CRO relationship, the CRO most likely will guide the sponsor (if necessary) on decisions related to the study. From the sponsor side, it is critical, however, that there is one ultimate point of contact at the CRO, and a route for escalation of any issues that may arise.
8. Client/CRO slow to respond/unresponsive, or missing deadlines
As in any relationship, if one side is too busy or slow to respond to requests, questions, or action items, it can make progress on the project impossible. A meeting of all stakeholders can be helpful. Sometimes, however, for good reasons, the sponsor is genuinely too busy to give attention to the CRO. Understanding the sponsor’s situation can go a long way, and perhaps the CRO can be granted greater decision-making authority. However, the sponsor is ultimately responsible for the study and, thus, it is desired that both sides agree to the course of action, or even more critical in case of risk mitigations.
Slow and/or unresponsive can indicate a CRO that is having trouble attracting or retaining staff or has taken on more work than they can handle. The author has experience working in organizations with high rates of attrition, making those who stay responsible for shouldering an ever-increasing burden while trying (at times, desperately) to hire more staff. It can be a vicious cycle of CRO staff burnout and poor performance for their clients.
9. Client/CRO micromanaging the project
Micromanaging is the opposite of the previous issue. This is a detrimental situation that can undermine the success of the project because it indicates a lack of trust in the CRO. If the sponsor doesn’t trust the CRO, they may be planning to find another. Also, if not mitigated promptly, this can have downstream effects on CRO staff who may feel disempowered to do their jobs. As with other situations, a frank meeting with stakeholders and management can sometimes help this situation by finding out the root cause of the sponsor distrust and CRO addressing the sponsor’s concerns.
CROs are not generally able to micromanage their clients, but this could manifest itself in an overly detailed project timeline. If a CRO has this tendency, they could be documenting every perceived misstep, and become excessively defensive about who was responsible for any missed milestones (and ultimately costing more money as the CRO bills for this time).
10. Client/CRO not disclosing or discussing information
As with the situation noted above, hiding key information (such as product performance issues) from the CRO staff indicates a lack of trust.
Also noted, the optimal sponsor-CRO partnership is one of regular communication and updates. Some sponsors, want to “throw the study over the wall” to the CRO and not engage with them during the study at all. On the other hand, some CROs assume that any questions or communication from the sponsor constitutes “meddling” in their business. The best way to avoid problems of this nature is for sponsors to engage with the CRO and require regular team meetings and/or status reports.
11. Client/CRO not listening to advice
When a CRO project manager recommends sound courses of action (perhaps on a good clinical practice or site management issue) and sponsor repeatedly does the exact opposite, it signals a lack of trust, which makes progress on a project difficult.
It is the CRO’s job to do what the client wants, as long as it complies with the principles and requirements of good clinical practice. Difficulties can arise when there is disagreement between the parties of what constitutes compliance. CROs, while mandated to conduct ethical and valid research, need to listen to the unique needs of each of their sponsors.
Having reviewed the warning signs from both perspectives, here are five suggestions to establish trust and enhance the sponsor-CRO relationship.
- Realistic statements of work. Many issues around invoices, payments, and change orders can be mitigated upfront with a proposal or statement of work that accurately reflects the assumptions, tasks, and budget needed to accomplish the study.
- Expectations around roles and responsibilities. These should be confirmed and documented at the kickoff meeting to avoid any gaps or duplication of effort. These can be revisited periodically throughout the study.
- Communication. It’s important to establish communication channels early in the project. Not only how to communicate, but how often (hourly, daily, or weekly). Communication promotes trust.
- Timelines. Should be established early and documented. Anything that could affect the timeline should be communicated transparently by each stakeholder.
- Clear expectations on invoice level of detail. A sample invoice should be provided to the sponsor around the time of study kickoff. Hopefully any changes can be resolved prior to the first invoice.
In summary, the principles noted above point to the need, as with any relationship, for the early establishment of clear communication and trust. The ability to work together in good faith and clearly communicate when issues arise is critical.
James Moat, Director, Clinical Operations, MEDIcept, Inc.
- Bhatt A. Evolution of Clinical Research: A History Before and Beyond James Lind. Perspect Clin Res. 2010. 1 (1), :6-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149409/
- Clinical Research Trends & Insights for 2023. WCG. https://www.wcgclinical.com/clinical-research-trends-insights-for-2023/
- Henderson, L. The State of CRO and Sponsor Relationships Applied Clinical Trials. October 1, 2013. https://www.appliedclinicaltrialsonline.com/view/state-cro-and-sponsor-relationships
- Halloran, L.Measuring the Health of CRO-Sponsor Relationships. Life Science Leader. May 9, 2017. https://www.lifescienceleader.com/doc/measuring-the-health-of-cro-sponsor-relationships-0001