As the COVID-19 pandemic made in-person visits difficult or impossible, sponsors and CROs turned to remote visits and remote assessments to keep trials running. This is an approach to which several regulators have signaled interest and VeraSci has endorsed. After careful consideration, we’ve moved forward with transitioning multiple on-going trials to remote assessments.
Increasingly, however, we’ve noticed a trend with some in our industry suggesting remote assessments can be added as an option in protocols to use any time a resurgence of COVID-19 happens to avoid missed visits or protocol deviations. These suggestions and recommendations ignore the complexities of implementing remote assessments in a way that will be acceptable by regulatory guidelines. While regulators have shown a willingness to be flexible during the pandemic, the validity of the data must be maintained. Downplaying the complexities involved in properly implementing remote assessments creates a risk that your trial data will not be considered acceptable to regulators.
How to Decide If Assessments Are Appropriate for Remote Administration
Not all assessments are suitable for remote administration. Each assessment needs to be considered individually in the context of the trial, and some may require modifications. Patient Reported Outcomes (PROs) can almost always be administered remotely because, by definition, they require patients to provide responses without external support. Many clinical interviews with patients and observers that do not involve any physical assessments are also appropriate for remote assessment based on reasonable clinical judgment. For some assessments, such as those that involve the assessment of non-verbal emotional expression, video is essential for an accurate assessment. In other cases, these can be completed by phone. In all cases, the appropriateness of remote assessment of clinical interviews relies on participants having a private space for completing the interview.
Traditional performance-based assessments (PerfOs) such as tests of cognition, motor function, and functional capacity can often be administered remotely, but typically require some modification. The level of modification varies widely, ranging from none needed for a completely verbal assessment to extensive modifications for assessments involving manipulation of objects. In some cases, the need for object manipulation makes remote administration impossible. Specific timing needs can also impact the feasibility of remote assessment. It may be necessary to send materials to subjects in advance of the session or to have someone with the subject to assist with administration. Similar to clinical interviews, these assessments often require videoconferencing. These assessments also require the subject to have a private space free of distraction and have the additional burden of the electronic equipment and often the data plan.
Scales involving a physical exam that include touching the subject, such as assessing rigidity or strength, are the most significant challenge for remote administration. For scales that include these elements, it may be possible to do a partial administration that does not include these items. For example, proxy scales for the assessment of medication side effects have been utilized by eliminating items that require hands-on assessment. Decisions regarding remote administration of scales with these elements are the most complex and require thorough consideration of the protocol, importance of those measurements, and the impact of not assessing them on the scale’s validity.
The appropriateness of remote administration of any assessment may require input from those who developed the instrument. During the COVID-19 era, some authors of tests or rating scales have weighed in on the appropriateness of their scales for remote administration. Some authors have provided specific suggestions for modification, and some have provided specific guidance indicating that their scale is not appropriate for remote administration. We always recommend consulting with the authors of an assessment to get their input on any modifications under consideration. A thorough literature search may also be necessary to determine whether there is any precedent for remote administration and if any validation research has been completed.
Switching Between Modes of Administration
We’ve also seen recommendations to allow individual subjects “ping-pong” between remote and in-clinic assessments, meaning that they could move back and forth between remote and in-clinic assessments multiple times based on conditions at the time of each visit. Although no rule currently exists, there is no regulatory precedent which introduces some risk for sponsors moving forward with this approach. Switching back and forth between remote and in-person assessments would require a thoughful justification for the multiple changes to allow for data interpretability in the context of, among others, the ICH E9 addendum framework.
It will be essential for investigators to document why they chose to use remote assessments because many remote assessments are not supported by good evidence of equivalency with the original measures.
Assessments Needed to Demonstrate Safety
Assessments which are designed to detect safety signals require special attention. When it comes to safety related assessments, it is likely better to err on the side of collecting incomplete data rather than collecting no data. Even if an assessment could only be partially administered or would rely on a patient to tell the clinician about something the clinician would normally observe directly, it may be better than receiving no safety information at all.
Data Analysis Considerations
Finally, when it comes time to analyze the data, special care must be taken to account for changes in the mode of administration appropriately. Sponsors will still be expected to follow existing regulatory guidance for the statistical analysis of clinical trial data, particularly as it relates to intercurrent events, estimands, and intent-to-treat principles as well as proper handling of missing data.
Do you have questions about adding remote assessments to a new or on-going trial? Contact us to discuss and get support in designing your trial.