What's Right and Wrong in Preclinical Science: A Matter of Principled Investigation

Area of Science:

• Neuroscience
• Psychiatry
• Clinical Trials

Background:

• The discovery of treatments for neuropsychiatric conditions is hindered by systemic issues in scientific research.
• Preclinical studies, particularly in neuroscience, exhibit a significant positive bias in reported results.
• Existing efforts to mitigate bias have been largely ineffective due to insufficient attention and systemic pressures.

Purpose of the Study:

• To highlight the detrimental impact of positive bias in preclinical research on the development of neuropsychiatric treatments.
• To advocate for fundamental changes in the scientific system to address pervasive bias.
• To propose specific reforms that promote research integrity and improve the reliability of findings.

Main Methods:

• Analysis of the current scientific system and its contribution to research bias.
• Identification of key factors driving positive bias in preclinical studies.
• Proposal of systemic reforms focusing on research methodology and reporting standards.

Main Results:

• A strong positive bias in preclinical neuroscience studies contributes to clinical trial failures.
• Current scientific and competitive pressures incentivize biased reporting rather than bias mitigation.
• Lack of meaningful change despite recognition of bias indicates a need for systemic intervention.

Conclusions:

• Urgent systemic changes are required to counteract positive bias in scientific discovery.
• Shifting focus from statistical significance and clean narratives to a priori power calculations is crucial.
• Individual scientists must adopt responsible practices in research planning, analysis, and presentation to reinforce these systemic changes.