In the race to approve vaccines and therapies during the COVID-19 pandemic, the most vulnerable individuals—those at the highest risk of severe SARS-CoV-2 infection— were left out of the pandemic related clinical trials. While we’re all hoping that the pandemic was a once in a lifetime experience, scientists are not waiting around to find out. They’re actively working to understand viral evolution, predict strains that might lead to another pandemic, as well as devising strategies to create the infrastructure necessary to contain infection and ensure better inclusivity when it comes to developing treatment strategies.
In a recent Clinical Infectious Diseases article, scientists and physicians from Fred Hutch, the University of Washington and Seattle Children’s that are part of the Cancer Consortium, teamed up to highlight a major gap in our public health response during the pandemic: the exclusion of immunocompromised individuals from clinical trials. The authors, including Drs. Michael Boeckh, Joshua Hill, Steven Pergam and Larry Corey, also identify ways to ensure inclusion in future clinical trials, whenever the next pandemic inevitably strikes.
When it came to testing the efficacy and safety of therapies and prevention strategies for SARS-CoV-2, speed was understandably the priority, however it came it at the cost of excluding populations most vulnerable to infection. Dr. Joshua Hill, a physician and Associate Professor at Fred Hutch, states that the “COVID-19 pandemic underscored the vulnerability of highly immunocompromised cancer and other patients to new epidemic and existing endemic infectious diseases. Their exclusion from participation in most of the trials for therapeutics to prevent and treat SARS-CoV-2 provides a clarion call to address this major gap in our public health response, and responsibility, to individuals across our society.” The exclusion was not without a reason. Dr. Larry Corey, Professor and previous Fred Hutch President and Director who helped design these national trials, explains the challenges of including immunocompromised individuals. These patients “take a lot of concomitant medications and change therapies often, all of which confound the accuracy and attribution to the vaccines versus their underlying disease and medication.” Because of this, these patients need to be studied separately, and unfortunately “they fell through the cracks. Why? Because there was no clinical trials program nationwide that was large enough to effectively organize this effort. This is an issue not just in pandemics. It’s an everyday issue and it needs rectifying,” Dr. Corey states.
“The experience during the COVID-19 pandemic is a reflection of the historical reality that most vaccines and other infectious disease therapeutics have not been rigorously studied in immunocompromised patients, who are often the most likely to benefit,” the authors note. Adding that the new RSV vaccines are a great example of this, as “there are currently no data about the immunogenicity and efficacy of this vaccine in immunosuppressed individuals, which impacts access and insurance coverage.” Including immunocompromised individuals in clinical trials requires additional considerations and resources since this population may differ in their response to therapies. And “although these are highly addressable issues, the activation threshold to include them in trials is higher, and some companies do not see an opportunity for a return on investment. This is why a dedicated Network with the necessary expertise will be critical to lowering the burden of studying interventions in this patient population,” Dr. Hill explains.
To address these challenges, the authors propose several key recommendations on how to develop a robust infrastructure to ensure inclusion of immunocompromised individuals in clinical trials. These considerations include mandating parallel clinical trials that are conducted for immunocompromised patients alongside healthy populations, developing a designated Network that will help conduct these trials and securing sustainable funding to create this infrastructure. “This is a neglected but relatively large and rapidly growing sector of the population whose quality of life continues to be substantially impacted by SARS-CoV-2 and other infectious diseases. We as a society can and should do better to generate the data to guide evidence-based recommendations for patients and their providers,” the authors state. Furthermore, to continue advocating for immunocompromised patients to be included in clinical trials and find a path forward for this vision, Dr. Hill adds that they have organized an upcoming workshop to discuss building an infectious disease treatment and prevention clinical trials Network in immunocompromised individuals. This unique gathering will be held next month in Washington DC and bring together leaders across academia, governmental organizations (including the NIH and FDA), industry, and patient advocates.
Fred Hutch/UW/Seattle Children’s Cancer Consortium members Drs. Michael Boeckh, Joshua Hill, Steven Pergam, Larry Corey and Janet Englund contributed to this work.
Boeckh M, Pergam SA, Limaye AP, Englund J, Corey L, Hill JA. How Immunocompromised Hosts Were Left Behind in the Quest to Control the Covid-19 Pandemic. 2024. Clinical Infectious Disease.
Science Spotlight writer Rachel Lex is a postdoctoral researcher in the Beronja lab at Fred Hutch. She studies what makes certain tissue regions more susceptible to cancer and looks at this from the angle of stem cell-microenvironment interactions in the skin.