Much of the focus these days, especially after the release of ICH E6(R2), has been on how Sponsors can better monitor and oversee the performance of their CRO partners. This discussion, and resulting effort, around CRO oversight is worthwhile and useful, but too often it is narrowly focused on metrics. A holistic approach to successfully partnering with CROs is needed, starting with the initial assessment of outsourcing drivers all the way through to trial completion.
Who partners with CROs?
If you walk through any clinically-focused conference, you can see a multitude of CROs highlighting the services they offer and the value they provide to their clients. CROs have become a standard component of most clinical trials. In an article from August 2017, the Tufts Center for the Study of Drug Development stated that 55 percent of total R&D spending is on services (including CROs and other functional service providers). Additionally, they noted 81 percent of Sponsors are engaged in outsourcing, with nearly half of all Sponsors in a strategic relationship with CRO partners. This prevalence of CRO involvement puts pressure on Sponsors to choose the right partner, create the right framework, and manage the partnership.
Why are you looking to partner?
The first step in any partnership is to create alignment on why you are looking to partner. You don’t partner with a CRO because it benefits them, you partner because it benefits you or fills gaps.
- Does your organization have a capability gap in one particular area (monitoring, data management, etc.) that is preventing optimal trial execution?
- Does your organization want to penetrate a region where you don’t have a footprint?
- Do you have a more robust pipeline than your current headcount can support?
- Do you want to leverage the experience/expertise a CRO has to improve your development plan?
Each of these goals for partnership may influence how you engage, monitor, and evaluate the partnership. As such, it is important to first look ahead.
What does the future look like?
After you have identified your drivers for partnering, the next step is to create alignment on what the future looks like from a process perspective. Some organizations jump too quickly into negotiating, but this can lead to a relationship that hasn’t been adequately thought out — and one that results in unhappiness and many change orders. Instead, it is imperative for both parties to create a shared understanding of the processes and tasks that must occur to effectively run a clinical trial. This isn’t to say we can guarantee a successful trial; solid protocols and promising investigational products are necessary; but aligning to best practice processes that conform to Sponsor expectations sets the stage for smooth trial execution. One pitfall to avoid is trying to assign ownership of tasks at this initial stage. This would set each party up to revert back to ingrained processes instead of striving to create an optimized process.
How do we judge the future?
Once you have defined the future state processes, it is important to identify methods by which you will evaluate the execution of the processes. These methods of evaluation often take the form of metrics and key performance indicators (KPIs). The major categories of metrics I have seen clients focus on are:
- Quality – the extent to which processes/deliverables meet expectations. I have seen clients build corrective and preventive actions, deviations, number of cycles, etc. into their quality evaluation. These are all valid data points as they are quantitative and can be measured. Too often people try to build qualitative judgments into the evaluation process, and that often muddies the water.
- Cycle time – how long it takes to perform an activity. This is one of the most common measures I have seen when evaluating transactional/functional service providers. It is important to have cycle time measures granular enough to evaluate individual parties on their specific process. You want to be able to improve the performance of those groups driving overall delays, and you don’t want to penalize a vendor because your internal teams can’t review a deliverable quick enough.
- Timeliness – did we hit expected milestones? This is the metric most likely to be analyzed by senior leadership at sponsors and CROs. We have all heard the statistics about trial delays and the related costs, so it is understandable that leaders focus on timelines/schedules.
- Cost – are we spending more than we expected? We all know clinical trials are more complex and cost more money every year. We need to be able to evaluate each trial on a continuous basis to confirm the money is being spent efficiently and properly.
Now, just as the processes should be agnostic of the group performing them, we need to strive to make these metrics relevant regardless of who is performing the processes. This is important because it is common for a Sponsor to have studies in various outsourcing models, and we want the same metrics to support evaluating all of the trials consistently. Additionally, we need to create targets/thresholds for each metric to support partner selection and oversight, as well as effective action plans to correct issues if any thresholds are not met.
How do we choose a partner?
Now that we have established the operational expectations (processes and levels of performance) for a partnership, it is time to evaluate potential vendors. As mentioned earlier, there is no shortage of CROs to choose from, so we need to spend the time to narrow down the options. First, you need to look back on the drivers for outsourcing (capability gap, geographic need, scale, etc.) and select the vendors that best align with those drivers. Once you have a short list, it is vital to work with the remaining CROs to brainstorm options for how best to deliver the processes. This will allow the best options to rise to the top while opening the lines of communication with potential partners. Then, query the potential partners on their success in delivering against your desired metrics, knowing not all of the success or failure can be attributed completely to them. Don’t forget to secure proof of compliance in vendor selection and qualification records; inspectors expect direct insights into those decisions and actions. Once you have qualified and selected your preferred CRO vendor, and potentially a backup, it is time to begin creating the contractual framework.
How do we contract for success?
Too often, contracting is handed off to a procurement/outsourcing team that is focused solely on getting the best monetary concessions from their vendors. In the short-term this sounds appealing, but it will result in jilted vendors and a multitude of change orders. A better approach is to have a cross-functional team involved in the contract framing to confirm and affirm the processes and execution expectations of both parties. This confirmation can serve as the basis for the other components of the contract (evaluation criteria, governance, and payment terms). It is important to incentivize good performance based on metrics, not just timelines. Too often the contract payment terms are solely based on milestones/deliverables, while the quality components of the trial are omitted from contracts because it is harder to evaluate them. But a poor-quality component of a trial (database, trial master file, etc.) is problematic, if not useless. In addition to working through the contract details with your CRO partners, it is important to document your oversight and governance approach within the statement of work (or ancillary document such as a vendor management plan).
How do we oversee outsourcing?
Unfortunately, and particularly in fully outsourced models, too many Sponsors believe they can “set and forget” their clinical trial only to return when the timer dings. We know from horror stories that this can be regrettable, emphasized in the principles of ICH E6(R2), which tells us a sponsor is always accountable for the trial:
A sponsor may transfer any or all of the sponsor’s trial-related duties and functions to a CRO, but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor.
As such, it is vital that a Sponsor creates a framework for performing and documenting oversight of their CROs/vendors. Over the years I have seen three main approaches to oversight:
- Passive oversight – Sponsor waits for partner to deliver data/outcomes for review and assessment
- Active oversight – Sponsor performs parallel activities to assess if data/outcomes match those reported by partner
- Balanced oversight — contains elements of both passive and active to drive quality of execution and outcomes. This approach leverages risk-based principles to eliminate redundant activities while keeping the focus on data integrity.
It is not uncommon for Sponsors to start at passive oversight, only to be hit with an issue or inspection finding which causes them to overreact and adopt active oversight. This then results in additional compliance, resourcing, and/or timeline headaches, and they finally settle on balanced oversight. We believe balanced oversight is the optimal approach for Sponsors to both achieve compliance to guidance from regulatory agencies and drive successful trial execution.
How do we continuously evolve the partnership?
In addition to oversight, one of the most important aspects of a Sponsor-CRO relationship, like any relationship, is open communication. This communication needs to be regular and candid — not just status report and stakeholder meetings, but actual conversations between the teams about challenges, opportunities, and areas for improvement. Too often we only hear the negative aspects of a trial (cost overruns, schedule slippages, etc.), but we need to celebrate successes to increase both individual engagement and team cohesion.
Once you have created an environment where open communication is accepted and anticipated, you can leverage the teams to incorporate lessons learned into process improvements, outsourcing model optimization, and metric/KPI evolution.
I urge you to take a step back and think about how you view your partner in clinical trial execution. Are they an adversary you need to spar with or a valuable asset to the trial team that can help bring your product to market better than you could alone? If it is the former, you should go back to basics and create alignment on expectations, because misalignment there is where most issues start. If you view them as an asset, let them know you appreciate all they do for you — and for future patients of your products.
About The Author:
Christopher M. McSpiritt is director of consulting services for the life sciences sector at CGI. He has over 10 years of pharmaceutical industry experience in R&D and has applied his business architecture, business process management, and analytical skills to help pharmaceutical companies improve their conduct of clinical trials. McSpiritt holds a B.A. in psychology from the University of Notre Dame. He is an active member of the Business Architecture Guild, Association of Business Process Management Professionals International, Project Management Institute, and Drug Information Association. He can be reached at email@example.com or on LinkedIn.