Rethinking Risk in Clinical Trials: Why Patient Safety Must Come First and Risk-Based Training

In the fast-evolving landscape of clinical research, there’s no room for complacency, especially when it comes to patient safety. Recent discussions with Darshan Kulkarni , a regulatory expert and recurring guest on my "Fraud Pod" podcast segment, have shed light on the critical issues facing clinical trial sites. One of the most glaring topics was around a warning letter issued to a site where significant dosing errors occurred in a pediatric trial. The incident highlighted the need for the industry to rethink how risk mitigation is approached in my opinion.

Patient Safety First

Clinical research is fundamentally about advancing science to benefit human health, but I think we can all agree that mission must never come at the expense of patient safety. During the podcast, Darshan and I discussed how, all too often, Sponsors, via their training methods particularly when it comes to site activation, focus on the wrong priorities. We see an imbalance where data entry processes and administrative tasks like e-diaries are given the same weight as patient dosing and drug safety. This skewed focus could lead to devastating consequences, such as the dosing error we discussed, where a pediatric patient received ten times the intended dose. The potential for severe adverse effects in such cases is staggering.

As a site owner and former CRA, I’ve participated in hundreds of Site Initiation Visits (SIVs). From my experience, the first principle of any clinical trial site undertaking a new study should be: Do no harm. Yet, in many SIVs, the training on patient safety is not given the attention it deserves. Yes, it’s covered, but it’s often treated as just another checklist item, not as the core foundation of what we do. Patient safety should be the first and most important element in risk mitigation, and it should dictate the structure of the entire SIV process. Oftentimes, the "why" of adverse events of special interest, or concomitant medication contraindications are omitted entirely from the training slides. From my experiences, this "why" has helped research staff understand the important safety considerations for any particular Investigational Product or trial undertaken.

The Business of Clinical Research

While sponsors and CROs may prioritize data integrity and adherence to protocols, patient safety should never take a backseat. In clinical trials, especially those involving complex drugs like monoclonal antibodies, or drugs with novel mechanisms of action, the risks associated with dosing errors can be life-threatening. For instance, as we discussed in the podcast, even seemingly small oversights—like not properly calculating a patient’s BMI before administering an injection—can have disastrous outcomes, particularly when it comes to dose selection and IP preparation.

The challenge lies in balancing the business side of clinical trials with ethical responsibilities, both from the side of the Sponsors as well as the Sites. Sites are frequently scrapped for resources and understandably attempt to make a profit from the studies they undertake while Sponsors are naturally concerned with the quality of data and minimizing delays, as well as garnering further exploratory insights into their drug's mechanism of action, as their IP portfolios' success hinges on those factors. However, as a site owner, I believe there needs to be a fundamental shift in how we structure our risk mitigation hierarchy. Patient safety should be at the top, followed by protocol adherence, and finally, data integrity. If patient safety is ensured, the rest will follow.

Training and Risk Mitigation: What Needs to Change

One of the most practical solutions is better, more focused training for site staff. Currently, training sessions at SIVs often bombard coordinators and PIs with a flood of information that prioritizes everything equally—data entry, compliance, drug dosing, etc. However, the reality is that not all tasks are equally critical. Entering data incorrectly, while problematic, is fixable. A life-threatening dosing error is not. Randomizing a patient prior to washing out a particular concomitant medication is not. There are countless other such potential pitfalls which must be mitigated. We have implemented risk-based monitoring, why not risk-based training?

Moreover, sponsors and CROs need to emphasize the "why" behind every protocol and dosing guideline. This is especially crucial for sites staffed by medical assistants or coordinators who may not have an in-depth medical background. When staff understand the reasons behind exclusion criteria, contraindicated medications, or proper dosing schedules, they are much more likely to follow the rules rigorously. While PIs certainly understand safety implications, the majority of the work at the Site is done by coordinators, so focusing on the "why" when it comes to highlighting certain study assessments is paramount for a Site Director or Site's CRA to routinely emphasize in order to effectively communicate the message to the study coordinators and other research staff.

Concluding Thoughts

The clinical research industry is complex and high-stakes, with countless variables that need to be managed. However, patient safety must always be the priority. By rethinking how we approach risk mitigation and by placing greater emphasis on training and understanding the “why” behind protocols and certain assessments or safety markers, we can prevent the kinds of errors that lead to devastating consequences. Clinical trials are ultimately about helping people, and that means ensuring that no patient is harmed along the way.

For those who are involved in clinical research, whether as a sponsor, CRO, or site owner, I urge you to reconsider your priorities during SIVs and throughout the study. Let’s make sure we’re focusing on what truly matters—protecting the patients who entrust us with their health.

To watch the entire podcast with Darshan Kulkarni please see below and thank you very much for your time.