Hofmann Precision Psychiatry Research Initiative
One-sentence mission: Investigate whether heterogeneous psychiatric treatment response can eventually be understood through harmonized participant-level evidence, beginning with psilocybin treatment for MDD/TRD.
The Question
Why do some patients respond, remit, relapse, or fail to respond after psychedelic treatment, and is there enough participant-level evidence to identify reproducible treatment-response characteristics?
This question is treatment-neutral. It does not assume that psychedelics outperform conventional antidepressants, psychotherapy, neuromodulation, or other evidence-based treatments.
What We Did
Hofmann Cycle 001 reviewed 45 psilocybin MDD/TRD study records and extracted 41 predictor-evidence relationships into a structured evidence ledger.
Hofmann Cycle 002 deduplicated the publication-level literature into 14 underlying independent cohorts, representing approximately 805 unique participants, and added a patient-level data gap and acquisition audit.
What We Found
Published predictor evidence is currently too sparse, heterogeneous, and exploratory to support meaningful patient-treatment matching. The primary bottleneck appears to be consent-compatible, sponsor-approved, data-dictionary-backed deidentified individual participant data access and cross-study harmonization.
Initial Feasibility Opportunity
EPIsoDE and Zurich were identified as the two highest-priority realistically requestable cohorts. Combined approximate N: 196 participants. This is not sufficient for a clinical prediction system, but it may be useful for an initial harmonization feasibility study.
Proposed Initial Study
Evaluate whether baseline phenotype, treatment, and longitudinal antidepressant outcomes from two independent psilocybin MDD/TRD cohorts can be responsibly harmonized into a common participant-level research schema.
- Establish variable compatibility.
- Quantify missingness.
- Identify measurement inconsistencies.
- Perform descriptive cross-cohort IPD analysis.
- Assess whether future predictor research is statistically and scientifically justified.
No clinical decision system or treatment recommendation is proposed.
What We Are Looking For
We are seeking an academic collaborator/PI with appropriate clinical-research experience and institutional governance who finds the research question scientifically worthwhile and could advise whether the proposed harmonization study merits pursuing through legitimate controlled-data access pathways.
The collaboration sought is scientific, not merely administrative. Independent oversight is important because the core questions involve clinical-trial interpretation, participant privacy, research governance, psychiatric measurement, and biostatistical feasibility.
Current Assets
- structured study registry
- cohort registry
- predictor evidence ledger
- outcome ledger
- provenance ledger
- IPD access audit
- canonical phenotype/harmonization schema
- acquisition priority analysis
- draft EPIsoDE research proposal and variable request
Research Principles
- treatment-neutral
- evidence-driven
- negative findings retained
- no individual treatment recommendations
- no lowering of evidence standards to manufacture predictive signals