Michael Brinkley is the Vice President for Quality at Endocyte. Endocyte is a small company specialising in small molecule drug conjugates primarily targeted at oncology applications. He is responsible for all aspects of GXP compliance, meaning GMP for the manufacturing sides, GLP for laboratory practices, as well as GCP for clinical practices. Additionally, he’s also responsible for good distribution practices, pharmacovigilance, and for distribution.
Working within a small sized company, Brinkley deals with a multitude of issues surrounding CRO management. In this interview, Brinkley provides insight on how he overcomes these issues and offers advice to similarly small companies.
Clinical Trials Arena: To what extent are CAPAs (corrective and preventative action) and deviations a challenge you commonly face?
Michael Brinkley: As a small company, we rely heavily on third party CROs for the monitoring of our clinical trials, primarily in the US, but we have conducted studies worldwide. When you deal with CROs, they have an ever changing population of CRAs and getting consistency of both monitoring and deviation definitions across CRAs that may or may not be consistent through the life of the study or across the site is difficult. So what one CRA might identify as a deviation at one site, another might not draw the same conclusion at another site that has the same practices.
CTA: Is this a specific issue that’s unique to smaller companies that depend heavily on the services of CROs?
MB: Yes, I think this is specific to all small companies that rely on CROs that don’t have direct oversight and access to the CRAs. While we have influence over the training on our particular protocol, we don’t have a lot of historical background on the training for the CRAs, specifically as it relates to general deviation documentation and assessment.
CTA: How have you gone about ensuring that CRAs and everyone on the CRO side are on the same page when it comes to, not only identifying deviations, but conducting the trial in general?
MB: We have weekly telephone conferences with the CRO, which includes the lead CRAs at the sites, where we go over all the deviations that have been identified by the CRAs during that week. We place particular emphasis on whether this deviation is likely to occur, or have been the result of an action, at a single site or whether this deviation has the potential to be systemic across all sites.
For instance, we had a protocol where we specified certain labs be drawn; these labs were outside of what a site would normally order for blood work. So we had a site that missed a couple of the lab time points because this wasn’t a test they traditionally ordered as part of their monitoring. We informed the CRAs and they identified that a number of other sites had missed these particular labs as a result of those being fairly specialised labs and not part of the normal bank of blood work that would be ordered. By discussing that in an open (weekly) forum, we were able to inform the sites making them aware of the potential this could occur across the study and not just at a single site.
CTA: It’s no secret that CRA turnovers are high within CROs. As a small company, how do you mitigate turnovers to limit the impact on a trial?
MB: It’s a major problem for us and, honestly, we’ve been struggling to come up with an adequate solution. We are implementing a co-monitoring requirement that compels all CRAs to go out for their first visit – preferably their first two visits – with either an Endocyte trained quality clinical monitor or a clinical trials manager prior to being able to audit the sites on their own. This is primarily to gauge their level of training and experience, but also so that we can answer any questions that are protocol specific while they’re reviewing the actual source documentation for the first time.
The high turnover rate in general is a huge burden for us because as a small group we have three clinical trial monitors overseeing eight different clinical protocols and we have a quality staff dedicated to the clinical side of only two people. So, when you start to get a large influx of new CRAs, it puts a burden on a small organization that has limited personnel resources to be able to go out and do co monitoring and training. We’re not a Merck or GSK, so when your population is in the single digits it makes it difficult to train six, eight new monitors at a time.
CTA: What advice would you give fellow professionals in small sized companies?
MB: When it comes to deviations, develop an internal strategy that’s consistent from the beginning of the study ensuring you communicate that through the clinical trial managers, the CRAs and the sites. With deviations, the worst thing you can do is attempt to change your course mid-trial. Therefore, so it’s important you identify upfront how you classify them (e.g. major, minor and critical) and make sure that when you’re training the sites during your site initiation visits and you’re training CRAs during their initial training that you emphasise this and that you’re consistent throughout the study.
*Michael Brinkley is the Vice President, Quality at Endocyte