The World is Watching - Experiences as an IDAC for a COVID-19 Study
I always feel a huge sense of responsibility when involved in an Independent Data Monitoring Committee (IDMC) in any capacity but being the Independent Data Analysis Centre (IDAC) for a recent COVID-19 study certainly amplified those feelings greatly. PHASTAR recently successfully supported a large pharmaceutical company in their IDAC requirements for a COVID-19 study. It was an honour to be involved in such an important piece of work that already has and will continue to save many people’s lives.
Many COVID-19 studies have been set up at breakneck speed and this trial was no different. There are many very good reasons why clinical trials typically take a long time to set up. They require huge levels of detailed thinking, organisation and of course a lot of preparation. But during the pandemic, there has been an urgent need to get treatments to people as quickly as possible whilst maintaining trial integrity and not compromising subject safety. This has not been an easy task. This COVID-19 study (as I’m sure is also true with many others) also had accelerated timelines all round. Whilst a typical IDAC may be given a number of days, or even weeks to prepare the blinded and unblinded package for communication with the IDMC members, in this instance PHASTAR was given only 24 hours in which to turn the analysis around, with the IDMC meetings typically only 2-3 weeks apart.
PHASTAR has two main ways of working when it comes to our IDAC service offerings, ensuring the most flexible approach for our clients. Either we independently programme the blinded and unblinded IDMC package, or we produce the blinded and unblinded IDMC package in PHASTAR’s reporting environment using sponsor code. Each of these have their pros and cons. The independent programming model creates a greater separation between the IDAC and the sponsor, reducing the perceived risk of unblinding, but requires greater resources and introduces the potential for inconsistent results between the IDAC and Clinical Study Report outputs. Using sponsor programmes adds a further level of QC of IDMC packages due to the secondary validation of sponsor’s original code, but any updates to programs require re-working and re-validation.
In this particular COVID-19 study, PHASTAR was instructed to use sponsor programmes. This may, on the face of it, seem like the most straightforward of the two options but when faced with such tight timelines, any issues identified with the programs are all the more complex when the group writing the programs and the group running the programs are different. Careful planning and properly executed dry runs here were imperative to successful statistical and programming activities. The success of this trial heavily relied on the PHASTAR team having the necessary skills to familiarise themselves with complex programs quickly and the professionalism to maintain clear lines of communication with the sponsor. When it came to the efficacy interim analysis, PHASTAR received the programming code just days before the final analysis needed to be run. This was a highly stressful environment at a time when everyone already had greater-than-usual stresses outside of the workplace. But when working on a COVID-19 study, there was an elevated sense of purpose and a sense that everyone needed to pull together to get the job done.
One of the challenges that I am sure many COVID-19 studies have faced is the rapidly changing environment in which these studies are run. Many of the assumptions used to carry out sample size calculations, for example, may not still hold when the study is running. This trial started recruiting in the late summer of 2020 at a time when COVID-19 prevalence in the study population was much lower than it had been just a few months earlier (when the trial was being designed) due to successful restrictions and more favourable weather. This meant that recruitment was much slower than anticipated and was unpredictable. Whilst the whole world was doing all it could to reduce the spread of COVID-19 and bring down case numbers, clinical trials assessing treatments for the virus needed to see cases to have any hope of being able to formally assess differences between treatment groups.
Being involved in a COVID-19 study has given me an increased respect for all the work our doctors and nurses are putting into the fight against this virus (if that was possible). We worked many evenings and weekends to get the job done because every hour longer than necessary quite literally cost numerous lives. But these efforts are miniscule in comparison to the tireless efforts of healthcare professionals around the world. I will always be immensely proud of the small part that I was able to play in the fight against COVID-19.
One thing that always hits me when I take a step back and think about the role IDACs play in clinical trial interim efficacy analyses, is that we are the first people in the world to know if a new indication works. I was one of the first people in the world to see the unblinded interim efficacy data from the trial and see that there was a statistically significant efficacious effect. I was one of the first people in the world to know that we had a new treatment for COVID-19 that worked. I’m not sure I’ll ever forget what it felt like to look at those numbers on my laptop, sat in my kitchen on a Friday evening.