Conducting clinical trials during a global pandemic

Today is International Clinical Trials Day. This day of recognition provides the medical research community with the opportunity to raise awareness of clinical trials among the greater public.

COVID-19 has significantly affected workplace practices over the last few months and as a research organisation that specialises in clinical trials, The George Institute has been uniquely affected.

We asked The George Institute’s Global Project Operations Director, Helen Monaghan how conducting clinical trials have been affected by COVID-19, how things have changed and what this means for the future.

What is a clinical trial?

The World Health Organization (WHO) definition of a clinical trial is

‘any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes’.

Clinical trials help us to determine the safety and effectiveness of new and standard interventions including drugs, vaccines, medical devices, health service changes, preventive care strategies and educational interventions.

How are clinical trials usually conducted? Can you tell us what the normal process for this is?

At The George Institute, clinical trials involve a multi-disciplinary team of researchers, project operations staff, data managers and statisticians. This team will typically be responsible for the design and conduct of the trial including developing the protocol, acquiring sufficient funding, developing the data capture system and creating the trial plans and manuals.

Trial sites will be selected to recruit participants who provide informed consent to be part of the trial (in some trials consent is delayed or waived). The trial team will ensure appropriate oversight and management of study progress including monitoring to ensure that trial processes and procedures are followed; the safety of trial participants is maintained, and that trial data is complete and accurate.

Prior to the final analysis of the data, a Statistical Analysis Plan will be written and approved by the project team and then a primary manuscript will be written to document the description of the trial and the trial results, which will then be submitted for publication.

Most countries around the world are currently several months into social distancing due to COVID-19. How has this affected the way in which clinical trials are run?

Various adaptations have been made to ensure that the trials conducted by The George Institute can continue following the protocol as closely as possible. In some cases, protocol amendments have been undertaken to capture changes to the conduct of the study – these have involved decisions being made by the study Management or Steering Committees to ensure the trial can continue without affecting the overall integrity and ensure the rights, safety and well-being of trial participants is maintained. Potential changes include:

• Suspending recruitment
• Adjusting trials assessments when visiting the clinic is not possible e.g. visits conducted by telephone, medication sent via courier, use of local laboratory results
• Amending visit window periods to allow for an extension of visit time periods
• Implementing remote and centralised monitoring as visits to trial sites cannot take place
• Using an electronic consenting process as per regulatory guidelines 

Every trial conducted at The Institute has put in place COVID-19 contingency plans that detail how risks and changes will be mitigated and managed.

How do you predict this change in the way the trials are run will affect the outcome?

In general, trials run by The Institute will take longer to complete, especially if recruitment has been suspended or has slowed down significantly. Other trials where recruitment has been completed, have been able to quickly adapt their follow-up strategies to ensure all participants are contacted as per the protocol schedule and study outcomes are captured remotely.

For some Intensive Care Unit trials, recruitment has generally been allowed to continue, however the rate has decreased significantly and it is therefore going to take longer to complete these trials. Each study presents its own challenges, but there are also opportunities. Project teams are reviewing progress regularly to ensure minimal disruption to trial conduct. We will be looking at and measuring how trial outcomes are impacted by the necessary changes and we can see if there are new opportunities for trial implementation in the future.

What does this change mean longer term, how has this pandemic changed practices for the future even if things go back to normal?

At The George Institute, we have already been giving a lot of thought as to how to conduct our trials more efficiently and the COVID-19 pandemic has heightened our focus on this. There are opportunities to engage trial participants differently via apps and other digital functionality throughout the life of a trial and to more fully involve them in the research process. Monitoring of trial data is essential to ensure the accuracy and integrity of the trial results.

Traditional on-site monitoring, which may involve source data verification, review of study documents and staff training, has had to adapt during COVID-19 and this change is likely to prevail. On-site monitoring is very time-consuming and expensive and although it’s still an important component of ensuring data integrity, it’s not possible in the current environment so remote centralised monitoring is being utilised. Once on-site visits to trial sites are resumed, we will look at how they can be streamlined and limited to ensure they’re more focused on elements that are critical to quality and outcomes.

Another aspect will be to consider resilience and agility in trial management and to structure teams in such a way that enables maximum productivity in the event of unexpected changes.

Today on International Clinical Trials day, why is it important to recognise and celebrate clinical trials?

The results of clinical trials have led to significant changes in the way that health conditions are managed. Without them, we wouldn’t be able to make advances or improvements to the lives of millions of people around the world. It is important to remember that every pill you take, medical procedure you undergo or any other intervention clinicians use, is only effective because of the evidence provided from a clinical trial to support its implementation in the wider community. 

^{Contributors: Erika Dempsey, Ruth Freed, Allison Humphries, Serena Knowles, Mallikarjuna Kunigari, Sharon Micallef, Dorrilyn Rajbhandari}