Among the multitude of healthcare practices impacted by the COVID-19 outbreak, previous clinical trial procedures are evolving rapidly to accommodate new approaches to the pharmaceutical R&D lifecycle that will sustain trial continuity in the new global healthcare environment.
In part 2 of this three-part blog series, I discussed strategies underlying the four pillars that drive the continuation of clinical trials, and key essential steps that keep the trials going despite all the barriers of COVID-19 globally.
In the series’ final installment, I look at the emerging, pandemic-driven need to adjust the focus of a clinical trial’s monitoring approach so it clearly addresses patient safety and data integrity.
The monitoring stage is a tactical element of clinical trials. While there may be a range of factors to monitor when conducting a trial, at the end of the day, what is critical is to extract well-founded data in order to generate and submit a strong clinical study report (CSR) that addresses the efficacy and safety of that trial.
As COVID-19 has steadily begun to permeate the healthcare environment, our experience is revealing that we have to move quickly to mobilize resources and connections across the portfolio of trials currently underway.
There are three considerations for heading back into the field.
1. Assess risk
From the initiation of a trial study, you have to continuously assess risk in a multitude of fashions. You have to look at the sites – what are their specific needs? Where are the risks for varying types of patient populations? As you can expect, it varies by therapeutic area. For instance, oncology studies and patients are of prime concern, and we want to identify any risks to those protocols that stem from delay of patient visits, assessments, investigational product administration, or follow-up treatment.
Risk assessments also include identifying the locations of patients, as well as the location of clinical research associates. With current travel restrictions, you may be limited in who can leave their local jurisdiction, and you may have to work within that city to identify a resource or work via virtual means.
Other questions that are critical to consider include:
- What are the risks related to the trial timeline and trial milestones?
- Are there strict deadlines related to submissions and customer expectations that have to be met in order for the investigational product to move forward for approval?
A final risk to consider surrounds the type of investigational medicinal product (IMP) you have and whether it poses any unique risks due to delivery needs. Is it an infusion that has to be monitored? Does it have to be transported under refrigerated conditions? Can a courier deliver and track it? Can you maneuver and arrange trial logistics to allow for trial continuation?
Understanding and documenting these and other risks helps you to plan the appropriate mitigation strategies for your studies. This allows the study team and sponsor to plan for trial continuity, patient safety and data integrity. Understanding and acting upon these risks early has been essential in the COVID-19 response.
2. Go remote
One of the most important mitigation responses has been the ability to “go remote.” As sites have shut down or reduced access due to COVID-19, the ability to conduct remote clinical research associate (CRA) visits to continue contact with the principal investigator and study site staff has been integral to addressing key critical study risks, and ultimately ensure as much continuity as possible. This remote visit option has enabled the CRA to establish vehicles to ensure patient safety is verified, to validate and coordinate that IMP is delivered to the patient’s home, that assessments can continue remotely if needed, and that study visits and data collected can be reviewed to validate that good clinical practices (GCP) has been followed.
This remote approach can be conducted via telephonic visits, Skype, Microsoft Teams, or other similar methods using IT-secure interfaces to perform data reviews where permitted by regulators. In some cases, it may be a visit where the CRA does a “look-over-the-shoulder review,” addressing process and training. This allows for good communications with site staff and with investigators, really important elements when visits are conducted remotely.
3. Let analytics do the driving
The third consideration for effective trial continuity monitoring, post-COVID-19, builds upon the first—risk-based monitoring. This gets to the third pillar I discussed in my previous blog, taking a much more predictive analytics-driven approach to monitoring.
As you can imagine, with an increasing number of investigative sites beginning to re-open for a multitude of pharmaceutical and biotech companies, sites face the very real potential of inundation; they will struggle to accept everybody coming back in. It will be necessary to take a risk-based monitoring approach where you are able, employing analytics to determine which sites are the most problematic, and which therapeutic indications and protocols pose the greatest risk. You will want to identify the highest-risk sites quickly and re-engage with them with that data in hand.
In order to prioritize sites, you should identify critical data, critical trials and critical subjects, which will enable the CRA team to focus on those patients, sites, and trials with the most urgent needs and require the most intervention either remotely or on-site.
Consider maintaining a new approach to monitoring going forward
As we begin to gradually emerge in a post-COVID-19 environment, we are beginning to see some countries open up, permitting patients back into clinical sites and allowing CRAs to conduct on-site monitoring visits. The path for everyone in healthcare will be slow. As such, it is very likely that remote strategies will continue to be employed for quite some time as each country resumes its previous clinical practices at a different pace and by different design.
The reality may be that remote visits never fully cease as our understanding of how to support both current and new clinical trials during a pandemic continues to evolve. We do know that we will have to continue to assess risks with new trials and sustain a state of COVID-19 readiness by employing remote patient monitoring and trial continuity if needed. We also are seeing some convergence of clinical trial and real-world technologies and strategies that are enabling that continuity and resilience to happen as we address those risks.
Additionally, the newfound flexibility of the regulators to allow for the remote monitoring and clinical continuity direct to patient approaches has certainly supported the way forward given the COVID-19 challenges. All of this can certainly create an overall new normal that could drive exponential change in our industry and advance the future of clinical trials for the better for patients and families.