When Strong Recommendations Rest on Weak Evidence: Lessons From Therapeutic Apheresis Guidelines

The American Society for Apheresis (ASFA) guidelines serve as a global standard for therapeutic apheresis practice. However, our analysis of the 2023 guidelines reveals discordance between the strength of recommendation and the quality of evidence. Among 166 indications, one-third carry strong recommendations, yet only 8% are supported by high-quality evidence. Over half (55%) are informed by low- or very-low quality evidence. This mismatch is most pronounced for Category I indications, where apheresis is considered first-line therapy: nearly one-third are based on low-quality data, yet 89% receive strong recommendations. Weak evidence is nine times more likely to prompt a strong recommendation for Category I versus Category III indications. This misalignment risks overutilization of apheresis, introduces ethical hurdles for clinical trials by diminishing equipoise, and may mislead patient expectations during informed consent. We advocate for greater transparency by stating the rationale underlying strong recommendations despite low-quality evidence, acknowledgment of uncertainty where applicable, and suggested research to strengthen the evidence.