A proposal regarding reporting of in vitro testing results

Area of Science:

• Oncology
• Pharmacology
• Drug Development

Background:

• High rates of negative clinical trials suggest issues with current preclinical testing methodologies.
• In vitro studies frequently employ clinically irrelevant concentrations, particularly for anticancer agents like sorafenib, vorinostat, and metformin.
• Protein binding in serum can create a significant difference between in vitro and in vivo effective concentrations.

Discussion:

• Claims of anticancer activity for sorafenib are often based on in vitro micromolar concentrations that are not achievable in human plasma due to high protein binding.
• Vorinostat and metformin studies have reported in vitro activity at concentrations exceeding human pharmacokinetic data, despite available human data.
• This discrepancy between in vitro and in vivo concentrations can lead to misleading conclusions about drug efficacy.

Key Insights:

• Clinically irrelevant concentrations in preclinical drug testing contribute to the high failure rate of clinical trials.
• Accurate reporting of in vitro drug concentrations relative to human pharmacokinetics is crucial for reliable drug development.
• Failure to consider protein binding and achievable plasma concentrations can result in erroneous claims of drug activity.

Outlook:

• Journal editors and reviewers should prioritize the scrutiny of clinically relevant concentrations in in vitro drug testing reports.
• A focus on patient-relevant preclinical data can redirect research efforts toward more promising therapeutic strategies.
• Improved evaluation of in vitro data will enhance the likelihood of successful clinical trials and better cancer treatments.