1. The Methods section states that “no changes occurred in panel composition” and that all 17 experts remained eligible throughout. However, the Results report 11 respondents (64.7%) in Round 1 and 13 respondents (76.5%) in Round 2. If the panel composition was stable, how did the number of active respondents increase by two in the second round? If two experts who missed Round 1 were allowed to vote in Round 2, this introduces unanchored perspectives mid-process, violating standard Delphi methodology. Please clarify the exact respondent flow and justify this deviation.
2. Recommendation 12 restricts MTB access to patients who have “exhaustion of standard therapeutic lines.” Recommendation 13 creates an exception for patients with “significant evidence of molecular actionability” even before first-line therapy. Since the MTB is the authoritative body responsible for determining molecular actionability, this creates a gatekeeping paradox: a referring physician must independently identify “significant evidence of actionability” to bypass the exhaustion criterion and access the MTB, yet they may lack the specialized expertise to do so without the MTB. How is this operationalized without creating a catch-22 for referring clinicians?
3. The Discussion acknowledges that “bioinformaticians, health informatics specialists, and health economists” were not represented in the panel. However, the panel proceeded to vote on and establish consensus for highly technical operational guidelines, including Recommendation 5 (technological decision-support systems), Recommendation 9 (NGS laboratory logistics/outsourcing), and Recommendation 10 (specific bioinformatics database curation). How can the authors claim a valid, comprehensive “consensus” on these specific technical and infrastructural domains without including the primary experts who design, fund, and execute them?
4. Recommendation 3 mandates a global TAT of 28 days from testing to therapy recommendation. Yet, Recommendation 9 explicitly permits outsourcing NGS to external certified laboratories. In real-world European healthcare settings, outsourced comprehensive genomic profiling (CGP) routinely exceeds 28 days due to tissue shipping, centralized batch processing, and bioinformatic analysis. Did the panel review empirical TAT data from outsourced European laboratories before endorsing this 28-day target, or is this an arbitrary ideal that risks rendering the recommendation non-compliant in routine practice?
5. Table 1 reveals that 52.9% of the expert panel (9 out of 17) are from Italy and Germany. Given the vast heterogeneity in healthcare funding, genomic infrastructure, and regulatory frameworks across Europe (e.g., Eastern vs. Northern Europe), a consensus driven primarily by two Central/Southern European countries may merely reflect the specific operational realities and resource availability of those nations. How do the authors justify generalizing these findings as a harmonized “European” implementation framework?
