THE NASH Tsunami audience got to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – discuss what has improved in the intervening time period, and what has not. The group suggest that researchers are making progress in reducing screen fail rates, but not in the critical issues of accessibility and equity.
Improving NASH Clinical Trials By Reducing Screen Fail Rates
As the conversation begins, Jörn harkens back to the 2020 paper and reflects on improvements in cost-effectiveness and duration of the trial process since. “The way we use biomarkers and AI to augment outcomes has changed the field dramatically.” Yet, clinical trials are still reliant on the same endpoint. A surrogate is required for conditional drug approval. Roger asks for the most important improvements that have resulted from conversations around patient selection for a trial. Jörn recalls the past reliance on biopsies and compares today’s focus on non-invasive techniques (NITs).
Stephen joins to highlight improvements in the way practices utilize VCTE (FibroScan) and other NITs to mine data in real time and refer patients to the proper clinical trial. One idea Stephen mentions: evaluating NIT values during the recruiting process to reset cutoff levels. He also discusses expanding screening criteria to include non-hepatic metabolic risk factors such as obesity and diabetes. Both approaches to patient refinement are contributing to more successful studies and limiting unnecessary biopsies. With fewer screen failures, sites remain engaged. Louise Campbell agrees that mitigating screen fail rate is key to fighting study fatigue.
The conversation shifts to the issue of finding patients for these trials. Stephen notes that major metropolises still do not have access to NASH clinical trials. For example, “we’re putting almost zero NASH patients in clinical trials out of a city as large as Chicago that has high rates of obesity, diabetes and metabolic syndrome.” NITs like the FibroScan are largely unavailable across the country. Where available, a lack of education around NASH diagnostics tests remains a barrier. Jörn adds that hurdles at multiple levels also prevent patients from accessing NASH trials in socialized healthcare systems. Roger believes the US system may have a better shot than Europe at broadening recruitment processes because the technology developed under larger U.S. budgets means that some pivotal technologies are more widely available geographically.
Next, Roger comments that for as long as screen fail rate has been discussed on this podcast, we had never discussed the idea of mid-trial adjustments. Stephen gives an example of adjusting FibroScan thresholds to boost the number of patients who could enter the trial. In response to a question, Jörn shares his belief that use of NITs outside the formal qualification criteria has helped reduce screen fail rates.
Stephen shifts focus to a bigger issue: equity in representation of underserved patients in these trials. There is an issue of decentralized trials, whereby at-risk groups are under-referred due to several factors. Stephen outlines potential solutions. Roger suggests tertiary care research universities that have their own primary practice as suitable to become an accessible point of referral. He notes this may not translate to the European system and Louise agrees.
What is there to look forward to in this space in 6 months to a year? Louise is looking for the approval of FibroScan for primary care in the UK. Jörn is hoping for an opportunity to offer health care services through referral systems. Stephen says we’ll hopefully be a step closer to getting a drug approved. Roger finishes with a Stephen quote: is the juice worth the squeeze? The juice takes forms in cash and optimism, and the juice will be worth the squeeze if a drug sees successful development.
