BERYL
The impact of natural disasters on clinical research
A week without power. Large trees toppled seemingly everywhere one turned. Massive disruption to organizations and communities. Such is the memory of Hurricane Beryl, a storm that hit Houston in early July.
Though Beryl was “only” a Category 1 hurricane, the storm’s specific trajectory, wind pattern, timing, and combination with heavy rain caused extreme damage to vegetation that complicated restoration of electricity. Mid-summer is not the most enjoyable time to be without electricity in Gulf coast Texas; nor is it the safest for populations with unique healthcare considerations. Many of the losses attributed to the storm event are resultant of lack of electricity for a week or, in some parts of greater Houston, longer.
Hope Biosciences Research Foundation (HBRF) lost power for five days. While we are pleased to share that our people and facility are fully intact, our operations are not without impact. Like all organizations, natural disasters affect resources of time, energy, and money. Like any healthcare entity, there are very real effects on people, especially patients, who typically constitute a vulnerable healthcare population. Unique to clinical research organizations (CROs) are possible implications on the data. In the spirit of easing minds and providing answers to any questions our community may hold, we will take this opportunity to explain the ramifications of a natural disaster on clinical research generally, and specific to HBRF.
By the book: The FDA
HBRF conducts research authorized by the United States Food and Drug Administration (FDA).
When a clinical trial is submitted to the FDA, study design specifies at what periodicity and over what timeline patients are to be treated. Any deviation from the approved protocol, including changes in timeline administration due to natural disaster, requires diligent and voluminous documentation and, as appropriate, approval by the designated Institutional Review Board (IRB). One significant effect of a natural disaster on clinical research, then, is an exponential increase in administrative manpower required to re-schedule necessary elements of the clinical trial, including in-house logistics and patient communication; document and submit changes; and negotiate any significant changes with FDA. At HBRF, currently running multiple Phase II trials, the task of administratively recovering from Hurricane Beryl will constitute hundreds of many hours.
FDA published “Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies” in September 2023, intended to assure safety, maintain compliance with Good Clinical Practice (GCP), and minimize risk to trial integrity. The publication contains “nonbinding recommendations” developed by a host of participating federal policy and research entities, covering such diverse circumstances as hurricanes, earthquakes, military conflicts, infectious disease outbreaks, or bioterrorism. Chief among discussion points is whether to halt existing trials affected by natural disasters, or to continue them with modifications.
In the course of translating FDA’s guidelines into actionable events, three key questions occupy us:
First, can participants remain safe?
Is our clinical trial site physically safe to welcome patients? In the context of Beryl, that means ensuring downed trees are cleared, the roof is intact, electricity is established and stable, and similar considerations common to any large building. Most of the equipment in our infusion suite is manual, runs on batteries, or is mobile and plugged in when needed, so was unplugged when the storm hit. We must, however, consider the state of computers and other technology — was anything damaged in a power surge when the power returned? Do our copiers and printers work? While these may sound like minor inconveniences if the answer is “no,” the administrative load of conducting FDA-authorized research quickly piles up. We are pleased to share that our facility rode out the storm well, with no damage to building or equipment.
Also related to safety, if a clinical trial is halted, delayed, or paused for any reason, a CRO must ask whether the investigational product can be safely administered to patients given the changed timeline. HBRF specializes in adult cell therapy with a specific type of stem cell, so fortunately, the answer is a straightforward “yes” in our field. We have treated hundreds of patients safely and effectively over the course of the last four years, at a wide array of periodicities. At this stage, our research primarily asks not whether the drug is safe and effective, but at what periodicity, over what span of time, and in what quantities is the drug most effective. Restarting, then, does not constitute a safety problem in our current research suite.
Can the trial logistically continue?
Recovering from closure due to natural disaster is not as simply as turning on an “open” sign. Delays can be compounded by the need to freshly manufacture the investigational product and potential supply chain disruption, as well as difficulty in patient travel, especially for those who evacuated to ensure medical safety.
In the restart process, decisions must be made about how to accommodate and compress the need to reschedule patients. At HBRF, for example, an appointment is about 4 hours and there are a set number of chairs available and a certain number of clinical staff. Clinical research also relies on principal investigators, which in many CROs are physicians still actively practicing medicine in other places; they may be urgently engaged in hospital or other medical settings as part of disaster recovery and have constrained availability for some time after the disaster. Each piece of the puzzle must be thoughtfully addressed.
Can the key objectives still be met?
An FDA-authorized study lays out a specific plan for clearly articulated examination of a defined healthcare condition. Depending on the nature of the investigational product and how dramatic the impact is to timeline, closures due to natural disasters may create variables that must be philosophically and empirically accounted for during data analysis. If the study seeks to validate the periodicity of drug administration, it may now be more difficult to determine whether efficacy, or lack thereof, is a reflection of the drug or of the changed timeline. Conversely, a change in timeline could validate hypothesized results — if, for example, an otherwise improving patient declines over the course of a forced delay, such an experience could be considered validation that the drug is most efficacious when administered over a more condensed, regimented timeline.
Considerations of data capture, review, and interpretation are both discrete, such as means of statistical analysis, and more subjective, such as the patient’s lived experience during the natural disaster. Were there any changes to patient status as a result of hardships brought about by the disaster, such as the stress of living without energy or perhaps even necessary medical equipment? While FDA does provide a clear path for documenting so-called “adverse events,” under which such experiences would fall, they can unduly affect patient- or caregiver-reported quality of life data or affect how the patient’s system utilizes the investigational product. There are also unknown impacts to patient psyche, as they deal with the natural disaster, as well as their own emotions at changes to the clinical research experience. Most frustratingly of all, patients experiencing improvement face a delay in receiving an investigational product that is helping them.
Bottom line
In clinical research, recovery from a natural disaster can be a complex process. Sometimes, however, disasters force innovation. Such was the case with the COVID pandemic, which prompted authorization and, in the years that followed, increasingly widespread adoption of virtual administration — that is, administration of the investigational produce in the patient’s home, with virtual monitoring by the clinical trial site. HBRF was among the first granted FDA authorization to conduct virtual administration and continues to do so today, enabling us to open clinical research participation to an array of individuals who would otherwise never have an opportunity to possibly benefit.
HBRF’s solution — calmly make one decision at a time, with people (both patients and our team) front of mind at all times. Document everything. Clearly communicate the measured and supposed impact of delays on the data. Be prepared to learn things we did not expect to learn, and delight in them when we do.
In short — keep it moving, with hope.
