Last year was marked by the COVID-19 pandemic that has changed our lives and the Life Sciences industry. A lot of traditional ways of operation were disrupted, challenging industry professionals and at the same time, providing opportunities for the development of new approaches and strategies.
We spoke with Lisa Comarella, Director of Biostatistics of CROS NT, to understand how the global pandemic has transformed the field of biostatistics and what are the trends that will be shaping the industry in 2021.
Did the COVID-19 crisis have any impact on biostatistical methodologies?
Back in March 2020, European Medicines Agency issued guidelines and points to consider on implications of Coronavirus on methodological aspects of clinical trials. The statistical communities set up working groups to evaluate the impact on statistical methodologies and provided webinars to support the community in finding a common approach to the issues. The top pharma companies established internal task forces to assess the risks related to the COVID-19 and to plan strategies and create solutions to mitigate the risks.
At CROS NT, we also created a special expert group that included statisticians, data managers, clinical specialists, and project managers. The aim of this group is to review continuously the guidelines from the agencies and evaluate the impact of the pandemic on each study we are managing and proactively discuss risk mitigation actions and solutions with sponsors.
What was the impact of the pandemic on your work as a statistician?
In biostatistics, we have to think about how to deal with the increase of missing data, with new intercurrent events, with the increase of protocol deviations, and the presence of heterogeneous populations.
In some cases, we had to revise the statistical analysis plan SAPs to include the evaluation on these topics. In other cases, we performed exploratory analyses of the data to evaluate the impact of COVID-19 on it and supported the sponsor to amend the protocol if required.
Now we are witnessing the rise of interest towards decentralised trials and novel digital endpoints. What are the biggest challenges related to this trend?
The main challenges that we will have to face are related to the increase in missing data. With the increased use of PROs and the rise of telemedicine, we will need to develop new endpoints that will be less objective and more patient orientated and a challenge here can be the possible quality issues related to this type of data.
Did the work from home model affect the way biostatisticians operate?
In the case of CROS NT, I would say no. We are used to smart working – part of our team was already partially or completely home-based when the pandemic started. We also have a very clear organisational structure and processes in place to conduct the activities. I work closely with the team and every member of our biostatistics team has clear work objectives. We also have recurring meetings and revisions to ensure that projects are delivered on time.
Given the range of potential clinical trial disruptions due to COVID-19, how can statisticians and data scientists help to identify potential challenges and complications sponsors may be facing?
The statisticians can support the implementation or improvement of the Risk-Based Monitoring approach to clinical trials. The control of recruitment rate and the drop-out rate is a key aspect to monitor as well.
What are the biggest challenges and decisions to be made regarding the collection, review, and interpretation of data during the pandemic?
Patient safety is paramount, and it is at the heart of every decision. That is why it is important that the investigators continue collecting adverse events and other protocol-specified safety data from the participants through alternative means, such as phone calls, virtual visits, and alternative locations for assessment.
COVID-19 pandemic is likely to cause more protocol deviations than normal, that is why it is paramount to pre-plan how systematic deviations resulting from the measures and individual decisions related to the COVID-19 pandemic are captured and address them in the statistical analysis plan.
Other potential challenges that biostatisticians might face are:
- Increase of missing data
- New intercurrent events that may be generated as a result of the COVID-19 pandemic
- The variability that is likely to increase as a result of reduced data quality
If a DMC is not planned by the protocol, we would advise considering an independent DMC with the responsibilities detailed in the guidelines from the main agencies (EMA and FDA) on implications of COVID-19 on methodological aspects of ongoing clinical trials.