John Hopkins University

John Hopkins University

clinicaltrials.gov

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With the COVID-19 pandemic sweeping the world, our working and personal lives have been transformed. As we adapt to a new, albeit temporary reality, and governments, healthcare providers and researchers around the world battle to mitigate the effects of the outbreak, the clinical trial landscape is also changing.  The FDA and EMA have both released guidelines for conducting clinical trials during the COVID-19 pandemic, while the WHO has released R&D blueprint trial synopses to support researchers developing COVID-19 treatments.

Veramed is working on protocol developments and statistical analysis planning for two clinical trials in COVID-19.  Both are trials exploring COVID-19 as a new indication for drugs already in development. The sponsors have reason to believe their treatments could be effective in specific subsets of COVID-19 patients.  

Naturally, developing a new protocol and setting up a trial in this new environment poses several critical challenges that we have needed to address in partnership with our clients.

Working with the unknown

One of the major challenges in this space is that COVID-19 is a new indication, and there is no direct historical data available for trial planners to draw on. Therefore, trial designs may need to incorporate exploratory or ‘pilot’ stages to build the necessary knowledge as outlined in the blueprint synopsis developed by the WHO we reference above. The WHO has also proposed a new ordinal endpoint for COVID-19 research and sponsors will need to carefully consider how to interpret the data and outcomes. 

Fast Set-Up

Typically, the process of developing a protocol and setting up a trial ready for the first patient first dose takes many months. However, with the urgent need to find safe, effective treatments for COVID-19 patients in advance of an available vaccine, COVID-19 trials need to initiate in a matter of weeks rather than months. For this reason, working in the fast-moving COVID-19 environment requires our statisticians to have a flexible mindset. As well as significantly faster set-up, trial durations are shorter and decision-making at any interim analysis needs careful planning to ensure that the next steps can be determined swiftly and accurately.  Because so much is unknown, statistical analysis plans need to be more flexible than usual to account for new information as it becomes available.

Make data collection easy

Investigators will be extremely stretched, treating patients and managing the effects of the pandemic.  Therefore, ease of data collection for sites by, for example, setting up a simple CRF is vital. However, this cannot mean sacrificing data integrity. Perhaps more than ever, the stakes are high, and it is essential to ensure usable data that is fit for analysis at the end of the trial.

Flexibility

Operational flexibility is crucial to enable fast set-up, study conduct, and analysis. Therefore some activities that are traditionally sequential such as database set up and beginning data collection may need to take place in tandem.

How can we enable success in COVID-19 research?

These are challenging times but as statisticians and clinical researchers we can play our part by putting our best foot forward to influence positive research outcomes. Here are some of our thoughts from this experience so far: 

• Be proactive, ask questions and challenge assumptions to ensure the best possible design and analysis.  
• While COVID-19 is a new indication, we can still apply our knowledge of related respiratory diseases and their analysis methods.  In supporting these trials, Veramed is harnessing extensive respiratory experience and technical statistics knowledge to inform the protocol development and propose statistical methods to analyse the incoming data.  
• Our customers have been impressively agile in mobilising the initiation of these trials. As a niche CRO, Veramed has been well-placed to match this agility and speed.

Looking ahead

Despite the circumstances, it is encouraging to see how quickly sponsors and the broader research community has been able to mobilise and get vital trials underway in record time. The impressive collaboration between global healthcare stakeholders gives hope for a resolution to the crisis.  At a more personal level, in the face of global uncertainty, our Veramed colleagues have been uplifted by the opportunity to apply their analytical abilities and contribute positively to the crisis through working on COVID-19 trials.