Due to increasing regulatory demand for data illustrating the effect of a drug on a patient’s blood pressure, more and more clinical trial sponsors are including ambulatory blood pressure monitoring (ABPM) endpoints in their protocols.
When a sponsor chooses ABPM to collect blood pressure data, they need to consider the many important factors that impact whether or not the data they capture will be useful and valid.
In many cases, sponsors can rely on their cardiac safety partner’s expertise to ensure the ABPM data they collect meets regulatory expectations and helps them achieve their clinical objectives.
However, sponsors should still be aware of the most common factors that determine whether or not ABPM will be effective for their trial, which we review here.
1. Making the ABPM Decision: Patient / Trial Fit
Sponsors should consider the study’s patient population and whether they can tolerate ABPM. Collecting ABPM data requires the patient to wear a blood pressure cuff on the upper arm ─ while conducting daily activities, including sleeping ─ for 24 hours or more. The cuff is programmed to inflate, tighten and deflate a few times every hour, which can be inconvenient and uncomfortable.
Patients that may have a lower tolerance for ABPM include:
- Elderly patients with thinner, sensitive skin
- Obese patients, who may experience longer cuff inflation times
- Sick patients, who may struggle with office visits to retrieve and return the cuff
2. Ensuring Patient ABPM Compliance
Poor patient compliance is a common problem with continuous BP monitoring. Typically, sites that have more ABPM experience achieve higher patient compliance rates. But, with the latest FDA guidance suggesting sponsors monitor blood pressure during clinical development, it’s expected that more non-experienced sites will be asked to collect ABPM data, so it’s important to acclimate site personnel to appropriate procedures for successful outcomes.
Regardless of site experience, the most important factor in patient compliance is patient training and coaching. Site coordinators who manage patient expectations about ABPM and communicate with patients about any issues they run into while wearing the cuff can achieve more usable data. One easy way for site coordinators to better empathize with the patient experience is to ask them to wear the ABPM cuff for 24 hours themselves before the first study patient is screened.
Because enrollment numbers are often a concern, site coordinators may not want to give up on a patient who struggles with ABPM compliance during the screening period. Therefore, sponsors should consider a longer screening period, allowing for repeated ABPM visits so that sites can coach and resolve compliance issues before a patient is enrolled in the study.
When a monitoring session produces poor quality data, consider giving the patient a few days off before repeating the test so they can mentally and physically recharge. Many experts recommend not collecting ABPM data from a patient multiple days in a row and we see that compliance becomes harder to achieve when the monitoring period extends beyond 24 hours.
3. Collecting High Quality ABPM Data
Before the trial begins, sponsors should consider:
- Which visits will include ABPM
- Which countries and patients will participate in ABPM collection
- Inflation timing and frequency
- Define day versus night hours for ABPM collection of 24 hours or longer
- Number of inflations per hour for each period
- ABPM quality criteria
- What is practical for the population and study?
- What do regulators expect to see?
- Define requirements, e.g. % of valid inflations across 24 hours, how many missing hours allowed, etc.
- Whether to plan for repeat ABPM visits to mitigate poor quality
- Which arm will be used for cuff placement – consistency across a subject is critical
- Which cuff sizes are needed at each site – the patient’s upper arm can be measured early in the screening process to allow for time to order more cuffs if needed
- Patient activity restrictions during the monitoring period, such as exercise
Addressing these factors well before a study starts helps to avoid protocol addendums later on, and ensures sponsors collect consistent, valid data that accurately depicts the drug’s effect on blood pressure.
4. Reacting to Poor ABPM Data Trends
If sponsors receive results that indicate low compliance or ABPM failure, they should work with their partners and site coordinators to review the data and investigate patient and site trends.
There are many potential issues that can negatively impact ABPM data. Partnering with all parties involved in the trial can help a sponsor determine the problem’s root cause and whether it’s related to the device battery, software, or patient error.
Communicating performance trends to sites and offering retraining when needed can help mitigate these issues. As trials go on, data quality and compliance rates are likely to improve as sites and patients learn more about ABPM.
5. Identifying Other ABPM Needs
In addition to some of the concerns listed above, sponsors may face other issues related to ABPM implementation, including site training burden and the up-front cost of investing in ABPM devices.
Choosing ABPM as the blood pressure endpoint for a trial is a decision that requires careful consideration. If you’re planning to use ABPM, or think it might be the right fit for an upcoming study, schedule a conversation with ERT and learn how to best address these factors to ensure the ABPM data collected helps you meet your clinical objectives.
Patricia Castellano is a Senior Director of Product Management at ERT.
With contributions by Juan Iurato, Clare Howell, and Miarka Edwards, ERT.