Costs for drug development have never been higher. A critical component of the drug development roadmap includes human clinical trials. Many sponsors of new biopharma/device products are typically small, lean running companies which rely on clinical research organizations (CROs) to help them scale up the human capital required to set up and manage these large complex projects. Even larger major pharma companies must partner with CROs to fill resource gaps. There is intensive pressure on sponsors to make sure the selected CRO can deliver clinical trials that are completed with a high level of quality and performance. How can sponsor companies effectively evaluate and select these crucial business partners?
Sponsors can pay for expensive webinars that opine on CRO selection, offer “evaluation checklists” or other “evaluation metrics”, but we thought to get real with an actual clinical research professional.
I spoke with Joaquin Sosa, RN, MBA who is the Director of Clinical Systems and Trial Management for Cidara Therapeutics. Joaquin is especially well versed on selecting and working with CROs since his career includes positions at several of the largest CROs in the USA. He just completed a large Phase III clinical trial utilizing SureClinical’s ETMF software application.
A common theme in evaluating and selecting a CRO is transparency. The best indication that the CRO may be a reliable partner starts at the beginning. CROs that are candid and transparent when responding to Requests for Proposal (RFP) set a great table for a successful partnership. When moving to the bid defense stage of CRO evaluation, ask the CRO to provide unitized costs e.g. there will be 10 site selection visits (SSV) and the unit cost of each SSV is $XXX. Joaquin added, “This helps sponsors compare apples to apples when evaluating CROs for a new project.”
To effectively manage clinical trials, electronic clinical trial data systems are now required since we’ve moved past the paper era. If the sponsor cannot or chooses not to select and pay for the data systems directly, they must ensure the CRO’s systems are validated and compliant. Ask for the validation documentation. Most importantly, do not allow the CRO to put add on charges to software systems. Ask for the system-provider invoice and do not pay any “admin” or “overhead fee”. Unauthorized reselling of software is not legal and can get sponsors as well as CROs in unwanted trouble.
Mind the Details
A seasoned clinical research professional makes certain assumptions about the scope of the work and tasks involved with proper monitoring of clinical trials. You may think a unit of site monitoring by a CRO includes laboratory checking, deviation tracking, and regulatory document review but unless it is in writing on the CRO bid, it may not happen. Additionally, you could be facing extra “out of scope” charges. “Large change orders are extremely painful and some require Board Approval,” explained Joaquin. As busy as clinical trial managers are, it is extremely important to spend the time to hammer out all expectations up front and get costs before you sign on the contract. Some changes in scope are inevitable with long complex clinical trials, but there should not be surprises around the basic tasks.
Partnerships in Information
When a CRO and sponsor sign a Transfer of Regulatory Obligations (TORO) they become one on the same team. A successful trial depends on clear and constant communication between the team. The CRO serves as the eyes and ears of the clinical trial, but the Sponsor holds overall responsibility. “A major component in the CRO partnership is helping the Sponsor to identify any gaps and CROs must have processes and documentation to make our sponsor oversight responsibilities easier to manage,” said Joaquin.
Much of the clinical trial information is now housed in cloud-based data systems. If sponsors do not have direct access to clinical trial information systems (eTMF, CTMS, etc), the CRO should be able to provide easily interpretable reports from validated systems with audit trails that show where the clinical study data is coming from and how it is reconciled.
Another important factor in a successful partnership with a CRO includes progress reporting. Joaquin recommends well-established expectations. He added, “A CRO should provide meaningful key performance indicators (KPIs) to ensure the sponsor that things are going correctly.” KPIs, if well designed, can ensure proactive analysis of data and performance to head off problems. The CRO must be ready to report those issues and have remediation plans in place.
Joaquin added a real-world example when things did not go to plan. He’s been on both ends of the “CRO-Switch”, where a sponsor fires a CRO and adds a new rescue CRO. Many of the tasks and responsibilities were smoothly transitioned, but he cautioned about data migration. “Migrating data from one EDC or eTMF to a new vendor platform is serious business and can be a quality nightmare.” Systems pharmacovigilance is a new necessary. The FDA is asking a lot of questions about eClinical system compliance, implementation timing, validation, and audit trails. Documentation needs to be at the ready. This suggests that sponsors should be in control of their clinical systems and data; they should not rely on the CRO to select and implement systems unilaterally.
A successful clinical trial depends on a solid partnership with a CRO. Some factors to consider when making this important selection decision include:
- Transparency in costs and deliverables
- Details of tasks and expectations
- Well developed systems for gap analysis and key performance indicators
- Ensure that all electronic systems are validated, compliant and contain audit trails
When asked what makes a CRO a “Fabulous CRO”, Joaquin quipped, “Do what you say you are going to do and hit your marks!”