By Laurie Halloran, founder, president, and CEO, Halloran Consulting Group
Almost two years ago, the FDA issued a draft guidance document “letting us off the hook” from what had been standard practice in most registrational clinical trials: source document verification (SDV), the procedure commonly called “100% of 100%,” or in layman’s terms, a complete verification of every data point for every patient in every clinical trial where data is included to support approval. SDV requires significant resources in terms of time and cost. It tends to be the key activity of CRAs (clinical research associates) or monitors during routine site visits, although there is widespread agreement it should be only part of a monitor’s focus to ensure a high-performing site. Reducing the practice to a quantitative risk-based model would free up monitors’ time so they may more effectively manage the activities that often cause a research site to veer off track from a regulatory perspective.
The FDA recognizes that SDV requires significant time and resources, and that finding ways to reduce the time required allows the monitor to pay closer attention to other important aspects of a study so that the study stays within regulatory guidelines. While the FDA’s guidance sanctions a risk-based approach, and the time and cost savings seem to be potentially significant for sponsors, the adoption of the new practices has been surprisingly slow.
Why The Slow Adoption Rate?
What is behind such lukewarm implementation of a much-needed efficiency, particularly one which has been suggested by the FDA? To find out, I have spoken about the guidance’s tepid reception with hundreds of sponsor stakeholders from CRAs to CMOs. There is reticence to “be the first,” a behavior that I noticed even 20 years ago when I was a monitor. I noticed the risk-averse conduct at the time, but after seeing it still in use decades later, it is apparent that this hesitation to strike out and be first is the reason for slow acceptance of new methods of efficiency. Senior management sees the potential for cost savings in a risk-based model, so many executives issue an edict. But others have their vision clouded; they see only risk, and they want someone other than themselves to act and make definitions all the way down to the level of a procedure. My observations of clouded vision are confirmed every time I present on this topic, and there are questions from the audience that prove that no one wants to take the first plunge off the dock. After witnessing so much hesitation, I see it as imperative we stop quibbling. Get on with it, and take a leap! There is so much to be gained and so much which has proved to reduce efficiency to be lost, that there is no need not to embrace this new mode of operating.
Risk Management Prerequisites For Success
Well-adopted risk management practices can be applied to clinical trials with a quantitative and qualitative model established and deployed to enable study management decision making on both protocol and siteby- site levels. What does it take to effectively and accurately implement risk management? The goal is to use a right-sized approach based on the ongoing performance of the individual sites. The role of clinical compliance within sponsor companies is relatively new, and it will ultimately be a critical one to ensure quality control is managed in real time. Additionally, there should be an individual on the study management team who makes an ongoing assessment of the potential risks based on the data being collected through EDC (electronic data collection) and modified with input gathered during the CRA’s site management activities, including visits. Another key component to making a risk-based approach successful is to partner with outsourcing providers, and there are two reasons for this: to develop a study-specific monitoring plan and to build a strong feedback loop so the sponsor is involved in sanctioning changes to the frequency and intensity of monitoring as it occurs.
What To watch Out For
The process can be complicated by several factors, the first of which is to be mindful of how the CRO proposes the budget and scope. Research sites with infrastructure and highly skilled staff are crucial to fully realize the cost savings, but they are often not identified as such when the project budget is initially defined. The gulf between many sponsors and CROs having an open dialogue built on trust may prevent a collaborative approach that is essential to defining the budget because there are many variables that can give the vendors concern about scope issues once the project begins.
I recognize there are companies out there trying a risk-based approach, and I applaud them for their willingness to update their procedures. But there won’t be widespread adoption until lessons learned by those who’ve tried it can be shared publicly to demonstrate how well it works to appease those who are too nervous to take the plunge. Risk-based monitoring is not a panacea and not a one-size-fitsall solution. However, CRAs can and should be teachers, problem solvers, and compliance managers, not data point verifiers and box checkers.