An observational study in Neoplasms (Cancer / Tumors), Colorectal Neoplasms and Lung Neoplasms, sponsored by Harvard Medical School (HMS and HSDM). Not yet recruiting at 1 site in United States. Per ClinicalTrials.gov, last updated 2026-09-11.
Sponsored by Harvard Medical School (HMS and HSDM) · Observational
Many clinical trials evaluating cancer treatments require patients to undergo testing for specific molecular markers as part of eligibility screening, typically using immunohistochemistry or sequencing. Because relatively few patients may carry a required marker, trial investigators often test large numbers of patients to identify the few who may ultimately qualify for enrollment.
Pathology laboratories routinely produce hematoxylin-and-eosin (H\&E) slides during cancer diagnosis. Pathology foundation models-large neural networks pretrained on millions of histology images-have shown promise in predicting molecular characteristics from these slides. Researchers can use these models to build classifiers that predict specific molecular markers and prioritize patients for confirmatory testing.
This study evaluates FATHOM (Facilitating Accrual through Tumor Histology and Omics Matching), an autonomous research system powered by large multimodal models. Its agents read registered clinical trial records, identify molecular markers used as enrollment criteria, build prediction models using pathology foundation models, select the individual models or model combinations that best meet prespecified criteria, set their decision thresholds, and determine whether to deploy them. Together, a prediction model, its decision threshold, and the decision to deploy it constitute an AI prediction policy.
Before FATHOM runs, the investigators preregister the clinical trial records that its agents may read, the cutoff date that defines which trial information they may use, the rules governing the agents, and the analysis plan. The system timestamps and locks each policy immediately after an agent produces it. The investigators then apply the policies to archived patient slides and compare their predictions with existing molecular marker results.
The primary outcome is the proportion of prespecified evaluation scenarios in which an agent-generated policy, compared with universal molecular testing, either enriches the population selected for confirmatory testing with marker-positive patients or safely spares patients from confirmatory testing while meeting prespecified performance criteria.
This study analyzes existing pathology images and clinical trial records only. It does not enroll or contact patients, influence patient care, or affect participation in any clinical trial.
WHAT IS REGISTERED. This study evaluates screening policies generated by autonomous research agents using archived pathology slides and existing molecular marker profiles. The study does not prospectively enroll or contact patients. The investigators register the clinical trial corpus that the agents may read, the trial-record cutoff date, the information that the agents may access, the rules governing their work, and the methods used to score their policies.
THE AGENTS. Each agent may access the registered clinical trial corpus, published literature, out-of-fold performance estimates for its own classifiers, and any development data identified in its manifest. The agent receives no results from any sealed evaluation cohort. For visual recognition, each agent uses pathology AI models as feature extractors and trains classifiers on the extracted features. The agent determines which molecular markers to model, which model to use, how to set each operating threshold, and whether to deploy the resulting policy. The agent records each decision and its rationale.
THE MANIFEST. Each agent run produces a timestamped manifest listing every policy generated and each policy's final deployment decision. On the study start date, the investigators designate the autonomous-agent approach and its comparators for the primary evaluation.
TRIAL DEMAND CUTOFF. Trials first posted before January 1, 2026, define retrospective trial demand. Trials first posted on or after January 1, 2026, are used for the temporal generalization evaluation.
SEALED ANALYSIS RULE. Each policy result corresponds to an evaluation scenario, defined as one cohort paired with one molecular marker. For each scenario, the study logs and publishes the date on which investigators first compare any model output with the ground-truth marker result.
COHORTS. The study uses archived institutional and consortium cohorts containing routine diagnostic H\&E slides linked to molecular profiles. No clinician uses model output from this study to make patient-care decisions.
10,818 studies on the registry are indexed under Neoplasms; 2,324 are open to participants now.
This study's planned enrollment of 30,000 is above the median of 200 across 2,638 observational studies indexed under Neoplasms.
Browse Neoplasms studies →Harvard Medical School (HMS and HSDM) is the lead sponsor of 55 studies on the registry; 14 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patient records from archived, multi-institutional cohorts of patients with histologically confirmed cancers, relevant molecular profiling results, and at least one diagnostic hematoxylin and eosin (H\&E) whole-slide image. For the evaluation of a given policy, patients whose slides were used to train that policy's classifier are excluded. No patients are enrolled or contacted; enrollment counts refer to patient records analyzed.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patient records and data from archived multi-institutional cohorts with routine H\&E whole-slide images and molecular profiles. No intervention is assigned, and no patient is contacted.
Proportion of prespecified evaluation scenarios in which an AI-generated deployment policy demonstrates effective screening enrichment or rule-out performance
An evaluation scenario consists of one molecular marker evaluated in one study cohort. For each prespecified scenario, the study assesses whether the AI system generates a policy that either prioritizes patients more likely to carry the marker for confirmatory testing or identifies patients who may safely be spared testing, compared with testing everyone. The outcome is the proportion of scenarios in which the policy meets these performance criteria.
Time frame: Periprocedural (at the time of pathology slide evaluation)
Per-scenario performance of each AI-generated deployment policy
For each evaluation scenario, the study reports sensitivity, negative predictive value, positive predictive value, the proportion of patients spared confirmatory testing, and the applicable enrichment or depletion ratio with its confidence interval.
Time frame: Periprocedural (at the time of pathology slide evaluation)
Temporal generalizability for trials first posted on or after January 1, 2026
Among trials first posted on or after January 1, 2026 that require a molecular biomarker for enrollment, the study evaluates: (1) the proportion of biomarkers and trials for which the agentic AI screening approach is useful; and (2) the estimated number of patients who would benefit from AI-guided screening compared with universal molecular testing. Estimates are based on model performance and biomarker prevalence observed in the evaluation cohorts.
Time frame: Periprocedural (at the time of pathology slide evaluation)
Temporal performance for trials first posted on or before December 31, 2025
Among trials first posted on or before December 31, 2025, that require a molecular biomarker for enrollment, the study evaluates: (1) the proportion of biomarkers and trials for which the agentic AI screening approach is useful; and (2) the estimated number of patients who would benefit from AI-guided screening compared with universal molecular testing. Estimates are based on model performance and biomarker prevalence observed in the evaluation cohorts.
Time frame: Periprocedural (at the time of pathology slide evaluation)
Proportion of evaluation scenarios in which a non-default AI-generated deployment policy demonstrates effective screening enrichment or rule-out performance
Among scenarios in which the deployed policy is not the default strategy of testing everyone, the study assesses whether the AI system generates a policy that either prioritizes patients more likely to carry the marker for confirmatory testing or identifies patients who may safely be spared testing, compared with testing everyone. The outcome is the proportion of these scenarios in which the policy meets these performance criteria.
Time frame: Periprocedural (at the time of pathology slide evaluation)
Plan to share: No
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This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Harvard Medical School (HMS and HSDM)