Key Considerations For Working With CROs
By Stacey Erickson and Laurie Stone, Clarkston Consulting
Drug development is a complex process that needs a lot of attention and resources that many pharma and biotech companies do not have. By outsourcing elements of the clinical trial to contract research organizations (CROs), sponsors can save time and resources while leveraging the CROs' experience and knowledge to improve the quality and efficiency of the clinical trial process. CROs can also play a key role in ensuring regulatory compliance and ethical conduct of clinical trials, which is important for protecting patient safety and maintaining public trust in the clinical research enterprise.
Selecting A CRO
When deciding on a CRO specializing in clinical research, sponsors will find a wide range of choices, from global players who cover every part of the clinical trial process, including all therapeutic areas, to those smaller niche players who specialize in a specific disease area. Too often, needless worry goes into selecting the right CROs and second-guessing those choices when the focus should instead turn to the importance of collaboration.
Sponsors should evaluate CROs on three key measures: 1) a strong track record, 2) good communication strategies, and 3) effective quality control measures. Once the outsourcing contracts have been executed, the emphasis should turn to collaboration and transparency. Regardless of whether you are working with a small or large CRO, if you do not set clear expectations and maintain very open communication through the trial process, your study is going to struggle.
Even with the best plan, almost every clinical trial has unexpected complications and challenges as well as unforeseen risks. There is a reason we do not often see CROs exceeding expectations other than those cited in a rare white paper or case study. Sponsors sometimes forget that outsourcing parts of the operation to a CRO does not take away accountability. Understanding and knowing the potential pitfalls ahead of time can potentially save your company time and money and, more importantly, ensure your drug development will not be impacted because of your decision to outsource with a CRO.
Mitigating Common Challenges While Working With CROs
There are several challenges associated with working with contract research organizations. However, getting ahead of these challenges can help you to mitigate the risks.
Sponsor Involvement/Communication
Effective communication between the sponsor and the CRO, as well as within the CRO team and the study sites participating in the clinical trial, is essential for a successful trial. Sponsors need to know what is going right, what is going wrong, and what study tasks may require additional training or clarification. However, language barriers, cultural differences, or even time zone differences may hinder clear and timely communication.
Having a communication plan that incorporates roles, responsibilities, governance, escalation, frequency, and types of communication methodologies and tools is crucial. Sponsors that manage according to a solid plan with the CRO ensure the project operations are clearly defined and made available to all stakeholders. Of course, communication plans are multifaceted. They must incorporate sponsors’ visibility and connectedness to investigators, study coordinators, and participants and their support systems (i.e., family and advocacy groups). It is important to have several touchpoints to allow everyone involved to feel heard.
The plans also must include the expectations of the CRO. The CRO should ensure the sponsor knows how the study is performing, what additional training might be needed, or any required amendments or process revisions. CROs should encourage sponsors to communicate directly with the sites and monitor teams in a coordinated and transparent manner.
Quality Issues
CROs are expected to deliver high-quality services, but quality issues such as poor data quality, inadequate site oversight, or inadequate staff training may arise, leading to delays or incomplete results.
Sponsors should take the time to develop key performance indicators (KPIs) (e.g., cycle times, error rates, deviations, and change orders) as standardized metrics to ensure quality and performance during the clinical trial and clear expectations with their CRO. These KPIs should be communicated at the time of contract negotiations so the CRO has transparency into these performance metrics throughout the project. It is important to ensure the KPIs are metrics you can sustain, consistently measure, and regularly report on over time as part of this performance monitoring.
Staff Turnover
One very real risk in outsourcing with a CRO is the potential for turnover. CROs historically have struggled with a high turnover rate, leading to a lack of resources, gaps in knowledge transition, and a possible disconnect between bid and execution of team members. This, of course, can create delays in the project or potential quality issues. One way to address this up front is to ask the CRO for staffing metrics before signing the outsourcing agreement. Having an open and transparent conversation up front about any historical employee turnover helps reduce the risk for both parties and ultimately allows the sponsor to plan accordingly. Staff turnover rate can also be part of the KPIs that are being measured and reported on both internally for the sponsor and in performance reviews with the CRO.
Regulatory Compliance
Both the sponsor and the CRO need to ensure that the clinical trial complies with applicable regulations and guidelines. However, the CRO may not have the same level of familiarity with the sponsor's operating procedures, leading to potential non-compliance issues. When contracting with a CRO, the sponsor should first ensure it has a compliance plan that includes the following elements: an initial compliance audit, a method to track any violations and monitoring for compliance, a dedicated compliance team, implementation of company policies and procedures, an efficient policy management system, regular compliance training for all employees, and continual improvement of regulatory compliance.
When a CRO is responsible for an obligation under 21 CFR 312, your first step to regulatory compliance starts with a comprehensive “prequalification” audit to ensure that the CRO can provide the services with the necessary quality results, establish a compliance baseline for delivery, and help to identify any potential problem areas early in the process. Once the legal agreement is established with the CRO, the sponsor should ensure a Transfer of Regulatory Obligations (TORO) is completed, clearly outlining who is responsible for each activity. The sponsor retains ultimate responsibility for the program regardless of the duties and functions delegated to the CRO with the TORO, and so regular audits will be critically important. The audits should be conducted multiple times during the trial to ensure the quality of the program stays consistent, including an audit to be conducted near the end of the program to ensure proper closure. The audits should focus on the strengths and weaknesses of the CRO’s capabilities, considering everything from security policies to risk management procedures.
Working With CROs To Deliver Effective, High-Quality Clinical Trials
CROs are important and critical to the success of clinical trials, but there are also challenges that must be managed, especially in the areas of communication, quality performance, regulatory compliance, and staff turnover. You can spend time up front managing these risks during your CRO selection process by looking for CROs that have a proven track record, a quality-first culture, and high employee engagement. As the relationship progresses, here are some questions to consider when assessing your CRO partnership: Is the CRO performing as you expected? Meeting timelines? Staying within budget? Is the quality of the CRO’s deliverables up to your company’s standards? Do your sites enjoy working with the CRO staff? And if not, do you understand why? It is vitally important that this is a dynamic relationship, closely managed throughout the project. Without CROs, the fast-paced nature of drug development would not be possible, so it is best to embrace the challenges and work with them to see success in delivering an effective, high-quality clinical trial.
About the Authors
Stacey Erickson, client solutions executive at Clarkston Consulting, has more than 25 years of experience in operations, supply chain, sourcing, and procurement within the life sciences and medical device industries.
Laurie Stone, director at Clarkston Consulting, has more than 20 years of experience in clinical operations across different stages of development, providing expertise in quality, management, and compliance in the biotech, pharma, and medical device industries.