Core Concepts
Developing effective NAFLD treatments faces challenges due to trial failures and limitations in trial design and measurement methods.
Abstract
The content discusses the challenges faced in developing treatments for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). It highlights the reasons behind the failure of investigational treatments, trial design limitations, the impact of new guidelines, and the importance of identifying high-risk patients for referral to hepatology. The discussion also touches on the need for noninvasive testing, the role of histologic evaluation, and the potential impact of clinical practice guidelines on clinical trials.
Reasons for Treatment Failures
- Investigational products for NAFLD often fail to progress to phase 3 trials.
- Some drugs were stopped due to negative phase 2 trial results or changes in drug companies' priorities.
Trial Design Limitations
- Phase 2 trials may lack efficacy due to sample size or duration issues.
- Histologic evaluation methods have limitations, leading to uncertainty in assessing drug efficacy.
Noninvasive Testing and Trial Design
- Integrating digital pathology into trials could provide more sensitive and reliable tools for assessing histologic effects.
- Noninvasive testing could speed up recruitment and improve the reliability of trial outcomes.
Impact of New Guidelines
- Updated guidelines may indirectly impact clinical trials by increasing awareness and diagnostic rates.
- Clinical practice guidelines help in patient management but may not directly influence trial efficiency.
Referral Pathways and Patient Identification
- Referral pathways focus on identifying high-risk patients with significant fibrosis for consultation.
- Tailoring therapeutics towards high-risk patients may pose challenges in delivering medication to a larger patient population.
Stats
"It is estimated as much as 40% of the world could be affected by nonalcoholic fatty liver disease (NAFLD)".
"Most of these investigational products do not progress to phase 3 trials".
"It is also clear that some of these compounds were rushed into later phases of development without having gone through a very thorough demonstration of their efficacy in well-conducted, earlier-phase trials".
Quotes
"It is eliminating the uncertainty around the histologic reading that will be progress".
"Improvements in efficacy will be incremental".