In 2020, the SARS-CoV-2 coronavirus has infected millions and resulted in death for hundreds of thousands. It has also negatively impacted clinical trials of all types, including medical device trials. Traditionally, clinical trials collect data at physical healthcare facilities. In-person data collection is challenging when travel restrictions are in place and if participants and staff are fearful of contact with others. This situation is likely to continue past the height of the present crisis as restrictions and behaviors change permanently, and will lead to protocol deviations for in-progress studies.
As a crisis response, many sponsors applied decentralized and hybrid clinical trial technology where possible to support remote interactions, including using telemedicine to conduct remote visits to replace those previously done at a site. They also used tactics such as mailing equipment (e.g., pulse oximeters and spirometers) to participants for home data collection.
Sponsors discontinued or suspended many trials not feasible to continue. If you continue your trial during this time, you need to pay even more attention than usual to how you capture data to ensure it is high quality. This article discusses how.
It’s all about the data quality
Data quality directly impacts the success of a clinical research study. Common data quality issues in clinical research data collection include lack of data standardization, missing or incomplete clinical data, and incompatible representations of data types and elements. Protocol deviations can cause many of these data quality issues and are more plentiful in a crisis in a disrupted environment.
Review study endpoints as a first tactic when rethinking study design through a crisis. Defer any less critical endpoints if they require in-person visits or travel. You create a higher risk for protocol deviations when you do not streamline study protocols appropriately.
Protocol deviations complicate the picture
A protocol deviation is any change from the approved study design or protocol that is under the investigator’s control and not authorized by the IRB/ethics board, so long as it does not affect the participant’s safety, rights, or welfare and the completeness, accuracy, and integrity of the study data. A protocol violation, by contrast, may affect the participant in those negative ways and is considered much more severe.
If the protocol is updated appropriately for the current conditions, you should have fewer protocol deviations long term. Proper site training and preparation also reduce the number of deviations by helping to ensure that participants and staff follow the protocol. However, the environment changes dramatically in a crisis when travel, social distancing requirements, and the introduction of new technology all increase the probability of a deviation.
Protocol deviations that may occur with global travel restrictions and social distancing guidelines in place include:
- Failure to show up for a scheduled visit
- Failure to provide adequate samples (such as blood)
- “Out of window” visits, meaning the participant did not show up within the required timeframe
If a deviation occurs, report the deviation to the IRB/ethics board on the Deviation Summary Log and submit it at the time of continuing review. The IRB reviews the Deviation Log to determine if there is ongoing noncompliance. Remember that the sponsor must investigate potential adverse effects and decide whether or not they might be related to the study drug before reporting to the IRB.
The FDA issued updated guidance on dealing with reporting of protocol deviations caused by the crisis. However, it is unclear how or if the guidance will adjust to the still-uncertain situation.
Three data considerations for continuing studies in progress
Quickly assess if you need to make protocol changes to ensure participant safety. If you do not change the protocol to accommodate participants, there may be an increased risk of missing data and participant dropout.
Consider if it is safe, feasible, and reliable to collect endpoints remotely. With the data you need, can patients self-assess and report results electronically, or must a clinical professional be present? For example, collecting data for an endpoint of worsening heart failure might require a high level of clinical judgment, and cannot be self-assessed by a participant.
Understand the regulatory considerations of in-home data collection. FDA regulations allow for expedited changes when submitting amendments to IRBs for active study protocols that relate to immediate hazards to human subjects.
Your data quality action plan
Keep these data collection quality best practices in mind as you move forward through this crisis and beyond:
- Streamline the data you need to capture
- Use a modern electronic data capture system
- Keep a flexible mindset — make more rapid and agile adjustments
- Allow longer lead times for planning and study start-up
- Consider a study design update that makes full use of participant-facing data-capture technology
- Simplify your data capture forms
- Use remote monitoring instead of sending monitors to a site
- Re-evaluate your data quality framework
Rethink – for now, and the post-crisis world
It’s not easy to stay on track with compliant data for a clinical research study at regular times. In a crisis, it is even more challenging. Be prepared: rethink your study design for the future, find new ways to collect and monitor data, and commit to decentralized or hybrid clinical trial technology as a way to stay flexible.