We recently wrote about the first two special meetings of the Innovative Technologies Working Group of the International Society for CNS Clinical Trials and Methodology (ISCTM) to discuss challenges related to implementing remote assessments in CNS clinical trials in the context of COVID-19 precautions. These calls provided an open forum for discussion between FDA, industry, academia, and clinical trial sites. There has since been a third call, which also included participants from EMA sharing their views. The call focused on three key topics.

Statistical Considerations for Trials Using Two Different Assessment Methods (In-person vs. Remote)

The first key topic was a discussion of statistical analyses in trials using both in-person and remote assessments. The working group noted that in most cases, remote and in-person assessments could not be considered interchangeable. This discussion addressed the following aspects of this challenge:

    • Making adjustments based on the heterogeneity remote assessments add to the data
    • Adjusting the sample size because of the heterogeneity remote assessments add to the data
    • Handling inter-site variability in the percentage of assessments conducted remotely
    • Whether to stay with remote assessments or transition to in-person assessments once restrictions ease for trials where baseline assessments were administered remotely
    • Missing data handling for assessments that cannot be done remotely

Panelists on the call stressed the difficulty of making universal recommendations for study design and statistical analysis plans and urged sponsors to work directly with regulators on specific program plans. This applies to the two other topics discussed on the call as well. They also noted the importance of documenting what data was missing or collected differently.

Acceptability of Revising Some Elements of Performance-Based Outcome Measures to Allow for Remote Assessment

The second topic was a discussion about the acceptability of changing some elements of outcome measures, like cognitive tasks or motor skills tasks, to allow for remote assessment. The following points were covered:

    • Whether protocol amendments are needed to address issues resulting from the COVID-19 situation, such as capturing new mental health problems not included in the original protocol?
    • Whether amendments are needed to allow the use of remote assessments that have been shown to correlate adequately with the original measures
    • The necessity of amending scales to reflect the effect of social distancing measures during the COVID-19 period
    • The process and data requirements for the validation of remote assessment tools intended to be used instead of in-person assessment
    • Whether imputation methods can be used to account for the effect of the COVID-19 pandemic on primary objectives
    • Whether a treatment effect in the absence of the COVID-10 pandemic can be used

Methodological Considerations Related to the Effects of COVID-19 on Patient Symptoms

The final topic was a discussion of methodological considerations related to the effects of COVID-19, such as isolation, psychosocial stressors, and changes in routine, on patient symptoms like mood and anxiety. The issues covered included:

    • If certain patient symptoms (e.g., mood, anxiety) should be considered an increase or a new baseline
    • Using separate assessments for pre-COVID and post-COVID periods
    • Including testing and COVID-19 status of to substantiate differences in observed results
    • Whether guidance can be provided to raters for completion of assessments in which clearly COVID-19 related factors are excluded and how these results would be used in a sensitivity analysis
    • Incorporating scales that specifically measure the impact of life events into clinical trials

A recording of the full discussion is available here.

The ISCTM Innovative Technologies Working Group is co-chaired by Mike Davis, FDA Division of Psychiatry Products Office of New Drugs, and Rich Keefe, CEO at VeraSci.

On Tuesday, September 22, ISCTM will hold a Virtual Hot Topics session from 10:30-11 ET on “Regulatory viewpoints from EMA and FDA on contemporary challenges and strategies for conducting and analyzing clinical trials in the COVID-19 era.” The session will be chaired by Dr. Keefe from VeraSci and Dr. Davis and Dr. Valentina Mantua from FDA. It will include several panelists from FDA and EMA.

Do you have questions about using remote assessments for your ongoing study?

VeraSci is offering sponsors a complimentary consultation to discuss options for remote assessment as well as other challenges related to the impact of COVID-19 on their studies.