By Audrey Rossow
When a pharma or biotech sponsor company engages with a contract research organization (CRO) and other service providers, it develops a list that details which organization is responsible for each task to be conducted. The degree to which a small to midsize sponsor has the expertise and the resources internally to manage a task, as well as budgetary constraints, will dictate which tasks it delegates and which it keeps in-house.
This article will focus on two tasks in particular: monitor oversight and investigative site relationship management. As sponsors get more involved in these two critical tasks, there are pros and cons to consider in terms of how the tasks are executed and how they are documented. Because if it isn’t documented, it didn’t happen.
The regulatory responsibilities of sponsors are found in 21 CFR 312, subpart D (Responsibilities of Sponsors and Investigators).1 Although there are approximately 19 tasks listed, those most relevant to this article are (1) selecting monitors who are qualified by training and experience to monitor the progress of the investigation and (2) ensuring proper monitoring of the investigation.
The usual methods sponsors use to select appropriate monitors include review of CVs, phone or in-person interviews, clinical research associate (CRA) training opportunities, and accompanying the monitor on site visits. Does the sponsor resource tasked with this oversight have experience being a CRA? If not, it would be ideal to hire a contract senior CRA or CRA manager for this task. First, it seems to follow that a person tasked with ensuring that a monitor is qualified through training and experience should themselves be qualified to do so through training and experience.
Second, sponsors do not always appreciate the incredible number of detailed tasks a CRA is responsible for and the knowledge of federal, state, and local regulations they must possess. There is also a tremendous amount of documentation the monitor reviews, collects, and generates, over and above the monitoring visit reports, confirmation letters, and follow-up letters. In addition, CROs often have their own electronic clinical trial management systems (CTMSs) that monitors must keep up to date for their managers to oversee metrics and report on them to the sponsor and the CRO’s senior management. Finally, there is the task of ensuring all documentation undergoes a quality check and associated workflow management before it gets filed in the trial master file (TMF).
Sponsors tend to have a bird’s eye view of what the CRO and the monitors do on a day-to-day basis and do not always appreciate the volume of paperwork and documentation behind that work. It is not glamorous, but it is required. If you want to take on oversight of monitors, you must have the same knowledge base they have. Are you willing to commit to that level of engagement, expertise, and “paperwork”?
Investigative Site Relationship Management
In a CenterWatch press release regarding top sponsors as rated by investigative sites, it was noted that “Investigators have raised their expectations for sponsor performance. In response, sponsor companies have made strengthening their relationships with investigative sites a top priority in recent years and have created a wide range of initiatives designed to incorporate investigator viewpoints into improving clinical development processes and easing site burdens.”2
In an Applied Clinical Trials article, the author noted, “The subject of improving sponsor-site relations as a way to improve performance has been a topic of discussion since the late 1990s. At that time, articles and surveys highlighting the frustrations of investigative sites and their opinions of various sponsors started appearing in the literature. What is different this time is that sponsors are responding by making strong commitments of time and manpower in a way they have not done before.”3
So, what does this relationship management look like in action? I have witnessed an increase in sponsors interacting with their sites on an ongoing basis long after the investigators’ meeting is complete. These interactions take the form of site visits, regional meetings, symposia, or meetings coinciding with scientific conferences. There is incredible value in these visits if the sponsor keeps the site and the patients as a primary focus of discussion, versus “How can you enroll more subjects?” or “When will you answer your outstanding queries?” This time is about listening to the site personnel and hearing their perspectives, which will maximize the interaction. After all, “Having someone who listens is a great gift, but to be truly heard is a treasure.”
― Tatjana Urbic, author
Similar to the concept of monitor oversight above, who at the sponsor company is tasked with relationship-building with its sites? A visit from the CEO or CMO is certainly meaningful and appreciated. However, there are so many tasks that site personnel must manage for the study (in addition to their workload on studies for other sponsors) that to be able to speak the same language is very helpful. Or, bring along a colleague who can discuss budgets, contracts, essential documents, data entry, central labs, drug accountability, and so forth (not to mention all the technology supporting these tasks).
Sponsor visits to sites with or without the monitors have a high value. However, a visit does not fulfill sponsor oversight obligations if (1) it was not an oversight visit and (2) it was not documented.
What is a sponsor to do? First, create a sponsor oversight plan that includes a minimum of:
- A list of all vendors and their roles
- A list of whose SOPs are governing which tasks
- Confirmation review of team members’ curricula vitae, expertise, and training
- Location of the trial master file
- A list of all manuals and plans being used in the study with versions, authors, reviews, and approvers listed
- A list of quality oversight activities across each sponsor functional area department, including task, timing/ frequency, owner, and process
- A template sponsor monitor oversight visit report with instructions
- A template sponsor site visit documentation form with instructions
- Site and vendor audit history
Second, ensure that you have resources who have the training and the time to execute the plan before the first subject is enrolled. In another Applied Clinical Trial article, the authors noted, “Small sponsors who do not have a qualified internal resource to serve as the project manager to provide adequate vendor oversight should seriously consider hiring an experienced contractor to supplement their team.”4
Third, avail yourself of resources such as TransCelerate, the AVOCA Group, and the Clinical Trials Transformation Initiative.
Finally, and probably most critical, decide early on who in the organization is responsible to lead the oversight effort: quality assurance or clinical operations. Clear ownership and process mapping will save a good deal of time and resources in the long run.
About The Author:
Audrey Rossow is the owner of A Rossow Consulting, LLC located in Central Massachusetts. She has 25+ years’ experience in pharmaceutical and biotech clinical development, Phases 1 – 3b. Her core work is in project management and clinical operations. She is passionate about site engagement and support, patient recruitment and retention, and sponsor oversight of their CROs. She can be reached at firstname.lastname@example.org and her website is http://www.arossowconsulting.com.