The revolution of immune checkpoint inhibitors (ICIs) in cancer treatment has been phenomenal. However, their success comes with a unique set of side effects called immune-related adverse events (irAEs).

Our understanding of these events is still evolving, and current practices of reporting and analyzing these side effects within clinical trials are hindering progress. This blog post examines this issue in depth, offering insights for healthcare professionals and caregivers concerned about the safety of immunotherapy.

The Challenge of Incomplete Reporting

One main problem is incomplete reporting of adverse events (AEs) during clinical trials. Many trials focus only on AEs that are pre-determined treatment-related, leading to a biased picture. 

Unexpected toxicities might remain hidden because of their unusual nature or the time it takes to develop after starting immunotherapy.

This lack of comprehensive reporting makes it difficult for clinicians and patients to establish links between certain AEs and immunotherapy, even if those connections might become apparent in real-world practice or years later.

Everyone needs better, more transparent information to make informed decisions about these cutting-edge therapies.

Lack of Standard Terminology and Methods

Another hurdle arises from consistency in how AEs are collected, coded, and reported.

Some studies use the Medical Dictionary for Regulatory Activities (MedDRA), while others rely on the Common Terminology Criteria for Adverse Events (CTCAE) or don’t specify a dictionary. This patchwork system hinders comparison across trials.

Further, publications often ignore AEs that don’t meet a certain frequency threshold within a trial. This can mask side effects that, while less common, could be clustered within a specific group or have a common underlying cause.

If these AEs are artificially diluted due to reporting methods, they might be overlooked, leading to potentially severe consequences for some patients.

Confounding Factors in Analysis

Finally, traditional methods used to analyze AEs often don’t account for crucial parameters like the length of follow-up for individual patients or competing risks (like death) that might skew the data.

Let’s use an example: If a study reveals more severe blood count abnormalities in patients receiving chemotherapy with immunotherapy versus chemotherapy alone, it’s easy to conclude that immunotherapy is to blame.

However, the immunotherapy group also has drastically improved survival. In that case, it’s more likely that these patients simply experienced more of the usual side effects of chemotherapy due to more prolonged treatment exposure.

The Case for Change

How we report and analyze adverse events in immunotherapy trials needs urgent attention. Here’s what we should consider:

  • Transparent and Comprehensive Reporting: Reporting every single AE, not just those assumed to be immunotherapy-related, is crucial for the long-term understanding of immunotherapy’s safety profile. Only then can we identify unexpected toxicities and establish cause-and-effect relationships.
  • Harmonized Standards: Adopting universal standards for AE data collection and coding across all trials would streamline research and make comparing different therapies much easier.
  • Advanced Statistical Methods: Using statistical techniques that account for follow-up time and competing risks would give us a clearer picture of the actual risk and timing of AEs. This is particularly important for immunotherapy, where side effects can be diverse and have unpredictable timelines.

The Path to Improving Patient Care

The Path to Improving Patient Care - Safe Therapeutics

These changes might seem small, but their impact would be huge. Stakeholders across the board – regulators, sponsors, researchers, publishers, and clinicians – all have a role in refining how AEs are reported and analyzed. Why is this so important?

  • Understanding the Bigger Picture: Complete and precise AE data is the crucial first step towards understanding the full spectrum of immunotherapy’s effects on the body – both beneficial and harmful.
  • Empowering Clinical Practice: Healthcare professionals making treatment decisions and patients weighing the risks and benefits of immunotherapy need comprehensive information for accurate risk assessment.
  • Driving Future Research: Better AE data will facilitate research into the long-term safety of immunotherapy, more targeted therapies, and personalized treatment approaches to minimize side effects.

It’s time to rethink our approach to adverse events in immunotherapy trials. By embracing transparency, consistency, and advanced analysis methods, we can unlock immunotherapy’s full potential while prioritizing patient safety.