The TOGETHER Trial for COVID-19 therapies, designed by clinical trial specialists at Cytel won the Society for Clinical Trials David Sackett Trial of the Year Award for 2021. I interviewed Hinda Ruton, Research Associate at Cytel, who made significant contributions as Lead Analyst to several studies in TOGETHER Trial.
Hinda has been working as a lead statistician and statistical programmer for clinical trials, and statistician for real world data (RWD) analysis. Prior to joining Cytel, he was the program coordinator of the Rwanda Human Resources for Health program in the Ministry of Health. He coordinated a program of $150 million USD, aiming to build the capacity of health professionals. This was done in collaboration with 25 of the best teaching institutions in the US. Hinda has an academic appointment at the University of Rwanda where he teaches biostatistics and information management systems.
Can you tell us briefly about the TOGETHER Trial?
The TOGETHER Trial is an adaptive platform trial that was launched in July 2020 with a goal to test as many repurposed drugs as possible to identify effective COVID-19 treatment. As of now, TOGETHER has investigated 11 different treatments. In the beginning, the trial was conducted in three sites in South Africa, US, and Brazil. It is now expanding to Pakistan and South Africa, Rwanda, DRC, and Vietnam. So, as you can imagine, the more geographically represented the trial becomes, the stronger the evidence is going to be. We need to be able to say that a certain treatment or repurposed drug is equally effective in any part of the world. On the other hand, if there are any differences, we should be able to explore the cause. Although TOGETHER Trial has been a lot of work, it has been an extremely passionate journey.
What is your role? How has the journey been from the start to now winning the SCT Trial of the Year award?
I got lucky if I may say so! In 2021, I was in an office where there were some people working on this project that seemed to be very interesting and I would have liked to be a part of it. At the time, the lead analyst and data managers of the project were transitioning out of their roles. That gave me the opportunity to join the project as a lead data manager. I had to quickly take full responsibility for creating the DSMB (Data and Safety Monitoring Board) reports and managing the data. I participated in the data analysis for our first publication where we evaluated HCQ and Lopinavir and Ritonavir. Later, I assisted Cytel’s Principal biostatistician, Ofir Harari, as I led the analysis for the subsequent treatments.
What is an adaptive platform trial? Why was it chosen to conduct the TOGETHER TRIAL?
Adaptive Platform Trials are an effective research strategy that allow simultaneous evaluation of multiple interventions for the same condition, such as COVID-19, with flexibilities of allowing new interventions to be added through the trial. Adaptive trials are the new way forward. They are quite different from the traditional two-arm study that takes longer and are not cost-effective. Cytel is one of the leading companies that advocates the adoption of innovative trial designs. It has pioneered many of the most used adaptive design and Bayesian methods for the statistical design of clinical studies.
The power of adaptive designs lies in the fact that they are fast, cost-effective, and more ethical. To illustrate this, I can give you an example from my personal experience of working here at Cytel. Since the time I joined, I have been a part of two adaptive trials, one of which is TOGETHER. Using a multi-arm adaptive platform trial design, Cytel’s statisticians were able to shorten the time it usually takes to secure scientific validity of clinical trial results, without compromising on scientific integrity. Since its launch two years ago, TOGETHER has enrolled over 6000 patients in 22 research sites in Brazil and has evaluated 11 interventions. If we had gone the traditional route, it would have taken a much longer time and costed higher to evaluate 11 different drugs. Hence, selecting an adaptive platform trial design for TOGETHER was a no-brainer as we are dealing with COVID-19 where rapidly identifying cost-effective therapies is a priority.
Is there any research behind why the trial is expanding to Pakistan and South Africa, Rwanda, DRC, and Vietnam? Are there any variations in findings at the country-level, and if so, what might this mean?
As I mentioned, TOGETHER started in three countries including Brazil, USA, and South Africa. In Brazil, we have an amazing partner who was able to achieve high recruitment rate and keep the sites very well organized. Hence, most of our findings were based on results from one country, Brazil. In our initial analysis on HCQ, we found that the data were nearly the same and there seemed to be no country-level difference in findings. However, the reason behind expanding now is to try to ensure that a greater number of low- and middle-income countries (LMICs) are benefiting from scientific development.
Additionally, we know that people are different in terms of their geography, race, and other important social factors. Therefore, this expansion will help to address the diversity and create infrastructure in these new countries that we can continue to use for future infectious diseases. Unfortunately, COVID-19 is probably not the last pandemic we will be facing in the future.
Can you tell us about your recent study on the therapeutic role of Metformin in treating COVID-19?
Out of the 11 interventions that were evaluated by TOGETHER Trial, nine were completed and stopped. The study of Metformin was among the ones that were stopped because it showed no clinical benefit to ambulatory patients with COVID-19 compared to placebo, with respect to reducing the need for retention in an emergency setting or hospitalization due to worsening COVID-19. However, the study did help in removing Metformin from the list of drugs that are being evaluated for COVID-19 treatment.
What is the role of real-world data in global health studies?
That is a very good question. The choice of Ivermectin, one of the treatments we evaluated in TOGETHER Trial, came from an in vitro study which suggested that Ivermectin can help in inhibiting replication of the virus. Currently, the work that we are doing in real world analytics aims to leverage the richness of existing data to identify existing potential drugs that can be tested for COVID-19 treatment. We can use RWD to respond to existing questions using a sophisticated method that we have been developing in Cytel. Additionally, we can use the RWD to indicate the potential use of existing therapies for other types of diseases that do not have any treatment yet.
Hence, real world data in global health is everything. There is rich, unused RWD both in developed nations and LMICs which can be leveraged to create new questions that can be responded to in a more reliable way using adaptive trials.
Are you currently working on anything exciting that you can share with us?
Nothing can match the excitement of the TOGETHER trial. But I am incredibly happy about the various projects I get to be a part of at Cytel. With TOGETHER, I received valuable mentorship and the opportunity to work in a global domain. The work required close collaboration with exceptional biostatisticians at Cytel like Ofir Harari and added to my learnings. At Cytel, you get to work on projects that are exciting as well as find the opportunity to expand your horizons by working globally.
Click below to read Cytel's press release on the SCT awards.
About the Author of Blog:
Mansha Sachdev specializes in content creation and knowledge management. She holds an MBA degree and has over 12 years of experience in handling various facets of marketing, across industries. At Cytel, Mansha is a Senior Content Marketing Manager and is responsible for producing informative content that is related to the pharmaceutical and medical devices industries.