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The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. In this conversation, the panelists explore issues around clinical trial design, focusing specifically on the value of Phases 2a and 2b and whether improvement in patient self-management during trials is a research artifact or a replication of reality.

This conversation addresses two issues in clinical trial design. First, Roger Green draws on the Session 9 discussion of failed trials to ask which is the right way to proceed when a drug in a Phase 2b trial fails to reach its primary endpoint but a subanalysis reveals a second possible path to Phase 3. He notes that this was the case with elafibranor, one of the Session 9 case studies, as well as obeticholic acid, a drug whose Phase 3 trials met its efficacy endpoints but is not yet approved due to regulators’ seeming perception that it lacks an acceptable cost:benefit ratio. The group points to reasons these may have been solid decisions before noting that the market and scientific community both expect higher performance from drugs today than they did several years ago. Mazen Noureddin asks whether exceptionally promising drugs might consider moving directly from Phase 1b to Phase 3; the group agrees that Phases 2a and 2b will have value for virtually every drug at this time. 

The final question comes from Roger, who asks whether improvements in patients’ diet and lifestyle during the clinical trial constitute a “Hawthorne effect,” as some stated on Saturday morning. He notes that in the literature, a Hawthorne effect is a change that might affect clinical trial results but will have no meaning in day-to-day practice. By that standard, improvements in patients’ diets and lifestyles do not constitute a Hawthorne effect since we want to effect these behaviors in all patients. Mazen Nouredin disagrees, noting that after trials, patients’ behaviors tend to revert to pre-trial levels, thus making improved behavior a confounding factor in analyzing trial results. The group comes to no clear consensus on this issue.

This episode is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.