Population Gap Detector

Reference Module Integration

The references/ directory is not optional background material. It defines the operational rules that must be actively used while running this skill.

Use the reference modules as follows:

• references/population-axis-framework.md → use when mapping the relevant subgroup dimensions in Section B.
• references/subgroup-gap-typology.md → use when classifying the specific type of subgroup gap in Section D.
• references/meaningful-vs-cosmetic-stratification-rules.md → use when deciding whether a subgroup gap is genuinely important in Section E.
• references/evidence-depth-by-population.md → use when auditing subgroup evidence depth and validation status in Section F.
• references/population-priority-rules.md → use when selecting the strongest next-step subgroup focus in Section G.
• references/research-translation-rules.md → use when converting the selected subgroup gap into a study-ready direction in Section H.
• references/output-section-guidance.md → use as the section-level formatting and content control standard for Sections A–J.

If any output section is generated without using its corresponding reference module, the output should be treated as incomplete.

Input Validation

Valid input: one or more of the following:

• a disease area with suspected heterogeneity
• a biomarker, treatment, mechanism, target, pathway, or phenotype plus a concern about subgroup undercoverage
• a research direction where representation, transportability, or subgroup specificity is uncertain
• a broad topic where the user wants to know which population is most overlooked
• a disease, endpoint, or use case where age, sex, geography, ancestry, comorbidity, disease stage, or molecular subtype may matter

Examples:

• "Which populations are under-studied in immunotherapy response biomarker research for lung cancer?"
• "Find subgroup gaps in blood biomarker studies for Alzheimer’s disease."
• "What patient groups are poorly represented in real-world anticoagulation studies?"
• "Which molecular subtypes are still weakly resolved in this disease area?"
• "Are there ancestry or geography gaps in current studies on this target?"
• "Identify the most overlooked study population in this research direction."

Out-of-scope — respond with the redirect below and stop:

• requests for direct patient-specific medical advice or subgroup treatment decisions
• requests for a full disease review without a subgroup-gap purpose
• requests to invent subgroup opportunities without evidence mapping
• non-biomedical segmentation or marketing-style audience analysis

"This skill is designed to detect population and subgroup gaps within biomedical evidence. Your request ([restatement]) is outside that scope because it requires [patient-specific medical advice / a full evidence review without subgroup-gap analysis / non-biomedical audience segmentation]."

Sample Triggers

• "Which populations are missing in current studies on this topic?"
• "Find overlooked subgroups in this disease area."
• "Are existing studies pooling together patients who should be separated?"
• "Which subgroup gap would be strongest for a focused next-step study?"
• "Check whether ancestry, sex, age, or disease-stage gaps exist in this literature."
• "Identify meaningful population undercoverage, not just general under-studied topics."

Core Function

This skill should:

1. define the topic unit precisely before looking for subgroup gaps
2. identify the subgroup axes that are plausibly relevant
3. audit how the evidence base actually handles each subgroup axis
4. classify the kind of subgroup gap that is present
5. distinguish meaningful subgroup gaps from cosmetic stratification
6. assess evidence depth and validation status by subgroup
7. rank the most defensible overlooked population or subgroup
8. translate the strongest subgroup gap into a research-ready direction

This skill should not:

• act like a general topic gap finder
• treat any subgroup mention as meaningful subgroup coverage
• equate underrepresentation alone with a valuable research opportunity
• overstate precision relevance when subgroup evidence is thin or poorly justified
• recommend subgroup splitting that has no plausible biological or clinical consequence

Decision Logic

Step 1 — Define the topic unit

Identify the working topic unit as precisely as possible.

This may be:

• a disease area
• a disease-stage-specific question
• a treatment-response context
• a biomarker use case
• a target or pathway
• a mechanism or molecular phenomenon

Do not begin subgroup-gap detection before the topic unit is clear.

Step 2 — Map candidate population axes

Identify the population axes that could matter for this topic.

Possible axes include:

• age
• sex
• geography
• ancestry
• comorbidity
• disease stage
• treatment line
• exposure history
• molecular subtype
• tissue context
• care setting
• special populations

Only include axes that are plausibly relevant to the topic. Use references/population-axis-framework.md to structure this step.

Step 3 — Audit existing coverage by population axis

Assess how the current evidence base handles each candidate population axis.

Determine whether each axis is:

• absent
• thinly represented
• descriptively reported only
• analyzed but weakly interpreted
• repeatedly evaluated
• externally validated
• clinically meaningful and decision-relevant

Do not confuse subgroup reporting with subgroup evidence.

Step 4 — Classify the type of population gap

For each important subgroup axis, classify the gap.

Possible gap types include:

• missing population
• underrepresented population
• pooled-but-unresolved subgroup
• inconsistent subgroup findings
• subgroup without independent validation
• subgroup with biological relevance but weak evidence depth
• subgroup with clinical plausibility but weak study targeting

State clearly what kind of gap is present. Use references/subgroup-gap-typology.md here.

Step 5 — Separate meaningful gaps from cosmetic stratification

Not every underrepresented subgroup is a strong research opportunity.

Determine whether the subgroup gap is likely to matter because it may affect:

• disease biology
• diagnosis
• prognosis
• treatment response
• risk modeling
• implementation
• transportability of findings

Do not elevate cosmetic slicing into a meaningful precision-research opportunity. Use references/meaningful-vs-cosmetic-stratification-rules.md here.

Step 6 — Audit evidence depth and interpretability

Assess whether the subgroup has enough evidence to support a real gap claim.

Distinguish:

• subgroup not studied
• subgroup mentioned but not analyzed
• subgroup analyzed but underpowered
• subgroup signal reported without replication
• subgroup pattern supported across studies
• subgroup-specific effect plausibly important but still incompletely resolved

Do not overstate subgroup certainty when evidence is thin. Use references/evidence-depth-by-population.md for this step.

Step 7 — Prioritize the most defensible population gap

Rank the best candidate subgroup gaps using:

• biological plausibility
• clinical relevance
• evidence thinness
• likely impact of resolving the gap
• feasibility of follow-up study design
• expected value over generic broad-cohort repetition

Recommend the strongest next-step population focus, not just the longest list of possible gaps. Use references/population-priority-rules.md here.

Step 8 — Translate the population gap into a research-ready direction

Convert the strongest subgroup gap into a study-ready framing.

This should include:

• the candidate population
• why that population matters
• what is currently missing
• what kind of next study would close the gap
• what the likely value of resolving the subgroup gap would be

Use references/research-translation-rules.md for this step.

Mandatory Output Structure

Always output the following sections.

A. Topic Scope

State the exact topic unit used for the analysis.

B. Candidate Population Axes

List the population axes considered and explain which ones are most relevant.

C. Population Coverage Audit

Summarize how existing evidence handles each major subgroup axis.

Use a table only when multiple axes or subgroup categories need side-by-side comparison.

D. Population Gap Classification

Identify which subgroup gaps are present and what type of gap each represents.

E. Meaningful vs Cosmetic Gap Judgment

Explain which subgroup gaps are likely to be meaningful and which are weak, cosmetic, or poorly justified.

F. Evidence Depth and Validation Status

Explain how much subgroup-specific evidence actually exists and where interpretation remains weak.

G. Priority Population Gap

Name the single strongest or most defensible population gap for next-step research, or a short ranked list if several are similarly strong.

H. Research Translation Framing

Reframe the selected population gap into a more precise research direction.

I. Risk Review

Briefly state:

• the strongest part of the subgroup-gap argument
• the weakest assumption
• the main risk of overcalling the gap
• the easiest way this gap could turn out to be low value

J. References

List only real and relevant references when available.

If citation certainty is limited, explicitly say so.

Formatting Expectations

Use short, clean sections.

Use tables only when they materially improve comparison across subgroup axes, candidate populations, or evidence-depth categories.

Do not force tables when a short explanatory paragraph is more precise.

Keep the report focused on decision value:

• who is missing
• why that matters
• whether the gap is real
• whether it is worth targeting

Hard Rules

1. Always distinguish the topic unit before detecting population gaps.
2. Never confuse subgroup mention with subgroup evidence.
3. Never treat underrepresentation alone as a meaningful research opportunity.
4. Always separate demographic, clinical, molecular, and context-defined subgroup axes.
5. Do not inflate cosmetic stratification into precision relevance.
6. Do not treat thin subgroup analyses as robust subgroup evidence.
7. Always distinguish descriptive subgroup reporting from validated subgroup-specific findings.
8. Prioritize subgroup gaps that could plausibly change interpretation, biology, utility, or implementation.
9. Do not assume that every poorly represented population is equally important.
10. When several subgroup gaps are possible, rank them rather than presenting them as equivalent.
11. Never fabricate references, PMIDs, DOIs, cohort properties, subgroup definitions, ancestry labels, validation status, or study findings.
12. Never present vague field beliefs as literature-backed conclusions.
13. If subgroup evidence is uncertain, thin, or inconsistently defined, label it explicitly as limited, unresolved, or evidence-thin.
14. Do not claim precision-medicine relevance unless the subgroup distinction could plausibly matter biologically or clinically.
15. Treat the report as incomplete if it does not identify both the subgroup gap and the reason that subgroup gap matters.

What This Skill Should Not Do

This skill should not:

• act like a general literature summarizer
• produce a generic diversity statement without evidence mapping
• equate “not enough data” with “good research opportunity”
• recommend subgroup analyses with no plausible biological or clinical importance
• confuse study design weakness with population-gap evidence
• invent subgroup relevance where the literature does not support it

Quality Standard

A high-quality output should:

• define the topic scope precisely
• identify the most relevant subgroup axes rather than every possible one
• distinguish real subgroup undercoverage from superficial subgroup mention
• separate meaningful gaps from cosmetic subgroup slicing
• recommend a focused, defensible next-step study population
• remain evidence-grounded and explicit about uncertainty
• avoid fabricated literature or exaggerated subgroup claims