The State of CRO and Sponsor Relationships

The use of CROs by pharmaceutical sponsors across all therapeutic areas and phases increased 44% between 2007 and 2011, according to the Association for Clinical Research Organizations. Lazard Capital Markets, Life Sciences, noted in 2010 that the largest pharma sponsors outsource nearly 100% of laboratory services (central and bioanalytical), as well as Phase IIIb and Phase IV studies, to CROs and service providers.

With this increased use of outsourced relationships, as well as a growing segment of pharma utilizing strategic relationships with outsourced providers, the need to integrate data, systems, processes, and communications with their CROs is a vital concern. How does the industry balance these needs, as well as achieve their objectives within an outsourced relationship structure?

Applied Clinical Trials took four market research reports that were released in 2013 to assess and evaluate the current state of sponsor and CRO relationships. Those reports are:

• "Strategic Partnerships 2013, Transforming and Unlocking Value in Biopharmaceutical Development," based on third-party research released by Parexel (April 2013).

• ISR Reports, "2013 Phase II/III CRO Quality Benchmarking Report," (April 2013).

• Vantage Partners, "Sponsor-CRO Collaboration Study," (May 2013).

• The Avoca Group, "Quality Consortium, Summit 2013, Optimizing Approaches and Establishing Best Practices in Quality Management of Outsourced Clinical Research, Executive Summary Report," (June 2013).

Reportedly, more and more pharmaceutical sponsors are moving toward more strategic relationships...they contract with less numbers CROs and service providers at any one time; they form closer ties and business integrations to theoretically build efficiencies and save money; and use more shared approaches to expertise, input, and control. However, on the way to this road, there have been barriers and challenges that companies have needed to overcome.

The Vantage Report lists barriers to all outsourced relationships, and the one most cited by CROs is that they are not involved early or deeply enough in the initial trial and protocol design and planning stage.

Execution and expertise

This has been a consistent statement over the years from CROs, that CROs aren't used for their true expertise and are basically the "arms and legs" of the sponsor, when they also want to be the brains. But what do sponsors really want? In the ISR report, currently given their druthers, sponsors want flawless execution. The report asks between flawless execution or drug development design expertise and experience, what do you want from a service provider: 64% go for execution and 36% expertise. When asked what they see three years from now based on their unique development needs, the sponsors' execution needs go down slightly to 59% versus 41% for expertise.

In the Vantage report, the analysts give credit where CRO credit is due in the area of protocol design and study planning and note the following key considerations in planning a clinical trial for which CROs could offer useful insight and information:

• Where are the sites with the highest recruitment potential?

• Which investigators have the best track record, in terms of both recruitment and protocol execution?

• What challenges have other companies run into when executing studies of this type and/or in these regions?

• What are the adverse events that could derail the timeline? How likely are they?

• What has been done in other trials to mitigate or eliminate risks?

Risk agreement

Risk mitigation or risk management in clinical trials is determined and calculated in various ways in project management. For example, most sponsors already have a running list of the Key Risk Indicators (KRIs) in a trial either from a clinical basis or a project management basis...those things that are monitored consistently for a problem. KRIs, and the ability to detect and manage them can be a benchmark or metric by which to assess the performance of a service partner, if they are standardized to compare apples to apples. Some groups, including the Avoca Group, use a standardized list of the KRIs by which agreement and performance between the CRO and sponsor can be the basis.

At the Avoca Quality Summit, Ann Meeker-O'Connell, Acting Division Director for Good Clinical Practice Compliance in the Office of Scientific Investigations, CDER, FDA, spoke via teleconference and noted that it is critical to determine the right partner for each industry activity. And interestingly, effective oversight is a two-way street with communication as its transportation. If sponsors or CROs do not outline activities or identify where risks are, and initiative is not taken, activities can fall through the cracks.

"All standards emphasize communication as an essential part of risk management," Meeker-O'Connell stated. However, there should not be an exhaustive list of issues, rather, it should be about planning efficiently, such as the opportunity to focus resources and keep track of things that aren't being addressed.

Is it difficult for CROs and sponsors to agree on risk? The Avoca Group asked sponsors: In general how difficult is it to gain agreement between your company and your clinical service provider partners about the probability and importance of various risks associated with clinical trial conduct? Only 4% said very difficult, 21% said easy. The remainder was weighted toward slightly difficult and somewhat difficult.

When asking CROs the same questions, 6% said very difficult, and 16% said easy. Again the remainder was in the area of slightly to somewhat difficult, not by large margins of difference.

The Parexel survey noted that the outsourcing relationship today has barriers and the top was limited alignment of goals and objectives (which could be construed as risk) and the last barrier a lack of information sharing. However, it noted that "as strategic partnerships evolve, the model will provide biopharmaceutical companies and CROs with a strong foundation to address these concerns. The hallmark of well-executed strategic partnerships is how efficiently these dynamics are managed through the partnership infrastructure."

Partner attributes and metrics

The Strategic Partnerships 2013 was a first stab at assessing the state of strategic partnerships, a business model that only came into being within the past five years. So what attributes among CROs are needed for that strategic partnership? Listed in order of importance:

• History of quality

• Cultural fit

• Partnership approach/philosophy

• Cost

• Geography

• Assurance of supply

• Technology

• Innovation

The ISR Benchmarking Report asked the most important service provider attributes-overall, not just strategic-with the following chosen as most important: overall value, prior positive experience with that provider, project manager quality, therapeutic expertise and contingency planning, and risk management.

When given a full choice of attributes that are gaining importance in the past 12 months, the report noted low cost jumps to number two, and global footprint to number five. However, any attribute related to metrics such as metrics for site start-up, for sites or recruitment, database lock timelines, or turnover metrics, the numbers were quite low. The analysts for this report said: "One thing that strikes us about the selection data is how far down on the list the 'metrics' based attributes are. As important as these attributes are to the success of a project...we would expect a CRO's ability to demonstrate a successful track record in these to be more important in the selection process."

Interestingly, the discussion of metrics is fluid in the chosen reports. As noted above, ISR analysts were surprised that metrics weren't rated higher. The Vantage report includes a discussion that one metric, first person in, became so over-concerning on both parties, that other focuses fell by the wayside. So Vantage recommends: Measure what matters-avoid the temptation to measure too many things, or focusing on what is easy to measure. Think carefully about which measures ought to be captured at which levels of the relationship. Consider starting by looking at the data currently captured by both sponsor (for in-house trials) and CRO (for its own purposes and for other sponsors). Most of the important data will be on such a list, and it is just a matter of filtering through it.

Truly there is more to talk about in CRO and sponsor relationships than can fit in any one article. These reports range from 18 to 245 pages, some are free and others available for purchase. Beyond the pages of our magazine and website, many venues discuss the state of these relationships in the clinical trials industry including CBI's CRO and Sponsor Business Process Integration, and the annual IIR Partnerships conference. However, most will agree that the foundation of any relationship is trust, and getting to a point where companies can trust each other to look out for their best interests is hallmark of outsourcing.

Lisa Henderson is Editor-in-Chief of Applied Clinical Trials, e-mail: lhenderson@advanstar.com.

References

1. "Strategic Partnerships 2013, Transforming and Unlocking Value in Biopharmaceutical Development," based on third-party research released by Parexel, (April 2013), http://www.parexel.com/etc/strategic-partnerships-report-2013/.

2. ISR Reports, "2013 Phase II/III CRO Quality Benchmarking Report," (April 2013), |~http://www.isrreports.com/product/2013-cro-quality-benchmarking-phase-iiiii-service-providers/.

3. Vantage Partners, "Sponsor-CRO Collaboration Study," (May 2013), http://www.vantagepartners.com/researchandpublications/viewpublications.aspx?id=12858.

4. The Avoca Group, "Quality Consortium, Summit 2013, Optimizing Approaches and Establishing Best Practices in Quality Management of Outsourced Clinical Research, Executive Summary Report," (June 2013), http://www2.theavocagroup.com/content/documents/files/Summit_2013_Executive_Summary1.pdf.