We work with some outstanding Sponsors who utilize their internal resources to manage and monitor their studies. Several years ago, the trend was that small-to-medium sized sponsors typically outsourced their clinical operations because they had limited resources to handle functions such as scientific writing, data management, project management, monitoring, and overall clinical development.
Over the past several years, however, we have seen this pendulum swing to the effect where many small-to-medium sized sponsors are pulling this work in-house…for several different reasons.
I believe CROs are an extremely important piece of our industry’s puzzle. Because the regulatory environment is becoming more stringent, the best strategies for companies not having internal expertise in scientific disciplines such as clinical operations, project management and regulatory may be to outsource their clinical studies to a CRO.
And in many cases I have seen sponsor partnerships with CROs to be highly effective…but I believe all of us have heard horror stories with these engagements as well.
As an example, we have been engaged with a terrific Small Pharma that has managed their early phase projects in-house for the past 6 years. They have done a terrific job and have consistently had about a dozen early phase studies running across North America at any given time.
Last year this Sponsor launched their first large-scale global Phase III project. Because they didn’t have the infrastructure to manage the study across different countries, they decided to outsource this Phase III study to a CRO. The experience was not a good one…the CRA attrition was extremely high, the sites were not happy (nor compliant in many cases), the data quality did not meet expectations and the project manager admitted to me that she felt bullied by the CRO’s project team.
As they dug into the root cause of the problem, they realized that even though they had a quality agreement in place with this CRO, they had no idea how the CRO was performing against that quality agreement. Further, they admitted they really didn’t have a plan in place to measure how well the CRO was performing…
And they are not alone. I recently saw the results of a survey of ClinOps Leaders which indicated that only 34% of them felt they had successfully achieved their planned CRO Goals. Said differently, roughly only a third of sponsors using CROs were happy with the outcome.
And as many of you are aware, when it comes to successfully monitoring studies, a large number of 483 findings cite “Failure to ensure proper monitoring of the study” as the cause (see current FDA Inspection Observations).
Now let’s talk ICH guidelines. In Section 5.2 of ICH E6(R2), it is clear that sponsors may transfer their responsibilities to CROs (according to certain parameters) and of course, this section also states the CROs are responsible for complying with all ICH requirements related to those sponsor responsibilities which have been delegated to them. Note, however, the 2016 R2 amendment added that “The sponsor should ensure oversight of any trial-related duties and functions carried out on its behalf, including trial-related duties and functions that are subcontracted to another party by the sponsor’s contracted CRO(s).” (Section 5.2.2 in ICH E6(R2). Based on this amendment, one can interpret that not only are sponsors responsible for appropriate oversight, but evidence of the oversight needs to be maintained.
So how does a sponsor do that? How do you measure against the quality agreement? When it comes to onsite monitoring, this can easily be established by adding an Oversight CRA. The typical role of a Sponsor Oversight CRA includes on-site assessment visits where the Sponsor’s CRA assesses the CRO’s CRA.
It’s a brilliant idea. Many of you have heard of the Hawthorne Effect which shows that individuals alter their behavior because they know they are being observed. Having an Oversight CRA in place is an extremely proactive approach to managing the quality agreement you have with your CRO and from our experience, has been shown to make a HUGE difference to the outcome of the study.
The Cost? One Oversight CRA can (on average) assess 10 monitors / 100 sites, therefore taking this approach is much more cost effective compared to the cost of a poorly monitored trial.
The Method? Establish an Oversight plan where the “What to Measure” and “How to Measure” questions are clearly defined (we can help you with this).
The Competency? Ensure the Oversight CRA has a strong background in monitoring. The CRA should not only be an expert in regulatory and quality assurance but should also have experience in the creation and management of CAPA plans. The CRA should also have significant experience in identifying data trends, creating and executing training programs as well as being able to re-engineer processes.
Final Words: Given the increasing rate Sponsors are outsourcing to CROs, it isn’t surprising that ICH E6(R2) has become more stringent as it relates to setting the oversight expectations of both Sponsors and CROs. When it comes to establishing a plan to adhere to this new addendum, an Oversight Monitoring plan may be a great solution.
Our firm is unique in that we specialize in the placement of CRAs; therefore, helping our clients to implement programs such as an Oversight CRA strategy is common for us. For more information on this key role and how it may be a help to your organization, please feel free to reach out and we will be glad to help.
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