Changing standard of care during a randomized trial: examples, considerations and guidelines

Area of Science:

• Oncology
• Clinical Trials Methodology
• Evidence-Based Medicine

Background:

• Randomized clinical trials (RCTs) are crucial for evaluating new cancer treatments.
• The validity of RCTs relies on control arms reflecting the current standard of care (SOC).
• Rapid advancements in cancer therapy lead to frequent changes in SOC during ongoing trials.

Purpose of the Study:

• To examine the impact of a dynamic standard of care (SOC) on ongoing randomized clinical trials (RCTs).
• To provide recommendations for designing and conducting RCTs in the context of evolving cancer treatment landscapes.
• To ensure the continued clinical relevance and accurate interpretation of RCT findings.

Main Methods:

• Review of common scenarios where the standard of care (SOC) changes during randomized clinical trials (RCTs).
• Analysis of the potential impact of dynamic SOC on trial conduct and interpretation.
• Development of prospective strategies for trial design to mitigate SOC-related challenges.

Main Results:

• Changing standard of care (SOC) during randomized clinical trials (RCTs) can introduce bias and affect outcome interpretation.
• The accelerating pace of cancer treatment innovation exacerbates the challenge of maintaining a relevant SOC in control arms.
• Proactive trial design is essential to address the impact of evolving SOC on RCT validity.

Conclusions:

• Dynamic standard of care (SOC) poses a significant challenge to the integrity of ongoing randomized clinical trials (RCTs).
• Implementing adaptive trial designs and prospective strategies can help mitigate the effects of changing SOC.
• Addressing these methodological issues is vital for generating reliable evidence for cancer treatment advancements.