gh-lyndonkl-claude/skills/domain-research-health-science/resources/template.md

Domain Research: Health Science - Templates

Workflow

Health Research Progress:
- [ ] Step 1: Formulate research question (PICOT)
- [ ] Step 2: Assess evidence hierarchy and study design
- [ ] Step 3: Evaluate study quality and bias
- [ ] Step 4: Prioritize and define outcomes
- [ ] Step 5: Synthesize evidence and grade certainty
- [ ] Step 6: Create decision-ready summary

Step 1: Formulate research question (PICOT)

Use PICOT Framework to structure precise research question with Population, Intervention, Comparator, Outcome, and Timeframe fully specified.

Step 2: Assess evidence hierarchy and study design

Select appropriate study design for question type using Common Question Types guidance (RCT for therapy, cross-sectional for diagnosis, cohort for prognosis, observational for rare harms).

Step 3: Evaluate study quality and bias

Apply bias assessment using Evidence Appraisal Template with appropriate tool (Cochrane RoB 2 for RCTs, ROBINS-I for observational, QUADAS-2 for diagnostic).

Step 4: Prioritize and define outcomes

Create hierarchy using Outcome Hierarchy Template, prioritizing patient-important outcomes (mortality, QoL) over surrogates (biomarkers), and specify MCID.

Step 5: Synthesize evidence and grade certainty

Rate certainty using GRADE Evidence Profile Template, assessing study limitations, inconsistency, indirectness, imprecision, and publication bias.

Step 6: Create decision-ready summary

Produce evidence summary using Clinical Interpretation Template with benefits/harms balance, certainty ratings, applicability, and evidence gaps identified.

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PICOT Framework

Research Question Template

Clinical scenario: [Describe the decision problem or knowledge gap]

PICOT Components

P (Population):

• Demographics: [Age range, sex, race/ethnicity if relevant]
• Condition: [Disease, severity, stage, diagnostic criteria]
• Setting: [Primary care, hospital, community, country/region]
• Inclusion criteria: [Key eligibility requirements]
• Exclusion criteria: [Factors that make evidence inapplicable]

I (Intervention):

• Type: [Drug, procedure, diagnostic test, preventive measure, exposure]
• Specification: [Dose, frequency, duration, route, technique details]
• Co-interventions: [Other treatments given alongside]
• Timing: [When initiated relative to disease course]

C (Comparator):

• Type: [Placebo, standard care, alternative treatment, no intervention]
• Specification: [Same level of detail as intervention]
• Rationale: [Why this comparator?]

O (Outcome):

• Primary outcome: [Most important endpoint - typically patient-important]
  • Measurement instrument/definition
  • Timepoint for assessment
  • Minimal clinically important difference (MCID) if known
• Secondary outcomes: [Additional endpoints]
• Safety outcomes: [Harms, adverse events]

T (Timeframe):

• Follow-up duration: [How long? Justification for duration choice]
• Time to outcome: [When do you expect to see effect?]

Structured PICOT statement:

"In [population], does [intervention] compared to [comparator] affect [outcome] over [timeframe]?"

Example: "In adults >65 years with heart failure and reduced ejection fraction (HFrEF), does dapagliflozin 10mg daily compared to standard care (ACE inhibitor + beta-blocker) reduce all-cause mortality over 12 months?"

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Outcome Hierarchy Template

Outcome Prioritization

Rate each outcome as:

• Critical (7-9): Essential for decision-making, would change recommendation
• Important (4-6): Informs decision but not decisive alone
• Not important (1-3): Interesting but doesn't influence decision

Outcome	Rating (1-9)	Patient-important?	Surrogate?	MCID	Measurement	Timepoint
All-cause mortality	9 (Critical)	Yes	No	N/A	Death registry	12 months
CV mortality	8 (Critical)	Yes	No	N/A	Adjudicated cause	12 months
Hospitalization (HF)	7 (Critical)	Yes	No	1-2 events/year	Hospital admission	12 months
Quality of life (QoL)	7 (Critical)	Yes	No	5 points (KCCQ)	KCCQ questionnaire	6, 12 months
6-minute walk distance	5 (Important)	Yes	No	30 meters	6MWT	6, 12 months
NT-proBNP reduction	4 (Important)	No	Yes (partial)	30% reduction	Blood test	3, 6, 12 months
Ejection fraction	3 (Not important)	No	Yes (weak)	5% absolute	Echocardiogram	6, 12 months

Notes:

• Prioritize patient-important outcomes (mortality, symptoms, function, QoL) over surrogates (biomarkers)
• Surrogates only acceptable if validated relationship to patient outcomes exists
• MCID = Minimal Clinically Important Difference (smallest change patients notice as meaningful)

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Evidence Appraisal Template

Study Identification

Citation: [Author, Year, Journal] Study design: [RCT, cohort, case-control, cross-sectional, systematic review] Research question type: [Therapy, diagnosis, prognosis, harm, etiology] Setting: [Country, healthcare system, single/multi-center] Funding: [Government, industry, foundation - assess for conflict of interest]

PICOT Match Assessment

PICOT Element	Study Population	Your Population	Match?
Population	[Study's population]	[Your patient/question]	Yes/Partial/No
Intervention	[Study's intervention]	[Your intervention]	Yes/Partial/No
Comparator	[Study's comparator]	[Your comparator]	Yes/Partial/No
Outcome	[Study's outcomes]	[Your outcomes of interest]	Yes/Partial/No
Timeframe	[Study's follow-up]	[Your timeframe]	Yes/Partial/No

Applicability: [Overall assessment - can you apply these results to your question/patient?]

Risk of Bias Assessment (RCT - Cochrane RoB 2)

Domain	Judgment	Support
1. Randomization process	Low / Some concerns / High	[Was allocation sequence random and concealed?]
2. Deviations from intended interventions	Low / Some concerns / High	[Were participants and personnel blinded? Deviations balanced?]
3. Missing outcome data	Low / Some concerns / High	[Loss to follow-up <10%? Balanced across groups? ITT analysis?]
4. Measurement of outcome	Low / Some concerns / High	[Blinded outcome assessment? Validated instruments?]
5. Selection of reported result	Low / Some concerns / High	[Protocol pre-specified outcomes? Selective reporting?]

Overall risk of bias: Low / Some concerns / High

Key Results

Outcome	Intervention group	Control group	Effect estimate	95% CI	p-value	Clinical interpretation
Mortality	[n/N, %]	[n/N, %]	RR 0.75	0.68-0.83	<0.001	25% relative risk reduction
QoL change	[Mean ± SD]	[Mean ± SD]	MD 5.2 points	3.1-7.3	<0.001	Exceeds MCID (5 points)

Absolute effects:

• Risk difference: [e.g., 5% absolute reduction in mortality]
• Number needed to treat (NNT): [e.g., NNT = 20 to prevent 1 death]

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GRADE Evidence Profile Template

Evidence Summary Table

Question: [PICOT question] Setting: [Clinical context] Bibliography: [Key studies included]

Outcomes	Studies (Design)	Sample Size	Effect Estimate (95% CI)	Absolute Effect	Certainty	Importance
Mortality (12mo)	5 RCTs	N=15,234	RR 0.75 (0.70-0.80)	50 fewer per 1000 (from 60 to 40)	⊕⊕⊕⊕ High	Critical
HF hospitalization	5 RCTs	N=15,234	RR 0.70 (0.65-0.76)	90 fewer per 1000 (from 300 to 210)	⊕⊕⊕○ Moderate¹	Critical
QoL (KCCQ change)	3 RCTs	N=8,500	MD 5.2 (3.1-7.3)	5.2 points higher (MCID=5)	⊕⊕⊕○ Moderate²	Critical
Serious adverse events	5 RCTs	N=15,234	RR 0.95 (0.88-1.03)	15 fewer per 1000 (from 300 to 285)	⊕⊕⊕○ Moderate³	Critical

Footnotes:

1. Downgraded for inconsistency (I²=55%, moderate heterogeneity across studies)
2. Downgraded for indirectness (QoL instrument not validated in all subgroups)
3. Downgraded for imprecision (confidence interval includes no effect)

GRADE Certainty Assessment

Outcome	Study Design	Risk of Bias	Inconsistency	Indirectness	Imprecision	Publication Bias	Upgrade Factors	Final Certainty
Mortality	RCT (High)	No serious (-0)	No serious (-0)	No serious (-0)	No serious (-0)	Undetected (-0)	None	⊕⊕⊕⊕ High
HF hosp	RCT (High)	No serious (-0)	Serious (-1)	No serious (-0)	No serious (-0)	Undetected (-0)	None	⊕⊕⊕○ Moderate
QoL	RCT (High)	No serious (-0)	No serious (-0)	Serious (-1)	No serious (-0)	Undetected (-0)	None	⊕⊕⊕○ Moderate

Certainty definitions:

• High (⊕⊕⊕⊕): Very confident true effect is close to estimate
• Moderate (⊕⊕⊕○): Moderately confident; true effect likely close but could differ substantially
• Low (⊕⊕○○): Limited confidence; true effect may be substantially different
• Very Low (⊕○○○): Very little confidence; true effect likely substantially different

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Clinical Interpretation Template

Evidence-to-Decision

Benefits:

• [List benefits with certainty ratings]
• Example: Mortality reduction (RR 0.75, GRADE: High) - clear benefit

Harms:

• [List harms with certainty ratings]
• Example: Serious adverse events (RR 0.95, GRADE: Moderate) - no significant increase

Balance of benefits vs harms: [Favorable / Unfavorable / Uncertain]

Certainty of evidence: [Overall certainty across critical outcomes]

Patient values and preferences: [Are there important variations? Uncertainty?]

Resource implications: [Cost, accessibility, training required]

Applicability: [Can these results be applied to your setting/population?]

• PICO match: [Assess similarity]
• Setting differences: [Trial setting vs your setting]
• Feasibility: [Can intervention be delivered as in trial?]

Evidence gaps: [What remains uncertain? Need for further research?]

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Systematic Review Protocol Template

Protocol Information

Title: [Systematic review title] Registration: [PROSPERO ID if applicable] Review team: [Names, roles, affiliations] Funding: [Source - declare conflicts of interest]

Research Question (PICOT)

[Use PICOT template above]

Eligibility Criteria

Inclusion criteria:

• Study designs: [RCTs, cohort, etc.]
• Population: [Specific PICO elements]
• Interventions: [What will be included]
• Comparators: [What will be included]
• Outcomes: [Which outcomes required for inclusion]
• Setting/context: [Geographic, time period]
• Language: [English only? All languages?]

Exclusion criteria:

• [Specific exclusions]

Search Strategy

Databases: [MEDLINE, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science]

Search terms: [Key concepts - population AND intervention AND outcome]

• Population: [MeSH terms, keywords]
• Intervention: [MeSH terms, keywords]
• Outcome: [MeSH terms, keywords]

Other sources: [Clinical trial registries, grey literature, reference lists, contact authors]

Date limits: [From XXXX to present, or all dates]

Selection Process

• Screening: Two reviewers independently screen titles/abstracts, then full text
• Disagreement resolution: Discussion, third reviewer if needed
• Software: [Covidence, DistillerSR, or other]
• PRISMA flow diagram: Document screening at each stage

Data Extraction

Information to extract:

• Study characteristics: Author, year, country, setting, sample size, funding
• Population: Demographics, condition details, inclusion/exclusion criteria
• Intervention: Specifics of intervention (dose, duration, delivery)
• Comparator: Details of comparison
• Outcomes: Results for each outcome (means, SDs, events, totals)
• Risk of bias domains: [RoB 2 or ROBINS-I elements]

Extraction tool: Standardized form, piloted on 5 studies

Duplicate extraction: Two reviewers independently, compare and resolve discrepancies

Risk of Bias Assessment

Tool: [Cochrane RoB 2 for RCTs, ROBINS-I for observational studies, QUADAS-2 for diagnostic accuracy]

Domains assessed: [List specific domains from chosen tool]

Process: Two independent reviewers, disagreements resolved by discussion

Data Synthesis

Quantitative synthesis (meta-analysis): [If appropriate]

• Statistical method: [Random-effects or fixed-effect]
• Effect measure: [Risk ratio, odds ratio, mean difference, standardized mean difference]
• Software: [RevMan, R, Stata]
• Heterogeneity assessment: [I², Cochran's Q test]
• Subgroup analyses: [Pre-specified]
• Sensitivity analyses: [Exclude high risk of bias, publication bias adjustment]

Qualitative synthesis: [If meta-analysis not appropriate]

• Narrative summary organized by [outcome, population, intervention]

Certainty of Evidence

GRADE assessment: Rate certainty (high, moderate, low, very low) for each critical outcome

Summary of findings table: Create evidence profile with absolute effects and certainty ratings

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Common Question Types

Therapy Question

PICOT: Population with condition → Intervention vs Comparator → Patient-important outcomes → Follow-up Best study design: RCT (if feasible); cohort if RCT not ethical/feasible Bias tool: Cochrane RoB 2 (RCT), ROBINS-I (observational) Key outcomes: Mortality, morbidity, quality of life, adverse events Statistical measure: Risk ratio, hazard ratio, absolute risk reduction, NNT

Diagnosis Question

PICOT: Population with suspected condition → Index test vs Reference standard → Diagnostic accuracy → Cross-sectional Best study design: Cross-sectional with consecutive enrollment Bias tool: QUADAS-2 Key outcomes: Sensitivity, specificity, positive/negative predictive values, likelihood ratios Statistical measure: Sensitivity, specificity, diagnostic odds ratio, AUC

Prognosis Question

PICOT: Population with condition/exposure → Prognostic factors → Outcomes → Long-term follow-up Best study design: Prospective cohort Bias tool: ROBINS-I or PROBAST (for prediction models) Key outcomes: Incidence, survival, hazard ratios, risk prediction performance Statistical measure: Hazard ratio, incidence rate, C-statistic, calibration

Harm Question

PICOT: Population exposed to intervention → Adverse outcomes → Timeframe for rare/delayed harms Best study design: RCT for common harms; observational for rare harms Bias tool: Cochrane RoB 2 (RCT), ROBINS-I (observational) Key outcomes: Serious adverse events, discontinuations, organ-specific toxicity Statistical measure: Risk ratio, absolute risk increase, number needed to harm (NNH)

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Quick Reference

Evidence Hierarchy by Question Type

Therapy: Systematic review of RCTs > RCT > Cohort > Case-control > Case series Diagnosis: Systematic review > Cross-sectional with consecutive enrollment > Case-control (inflates accuracy) Prognosis: Systematic review > Prospective cohort > Retrospective cohort > Case-control Harm: Systematic review > RCT (common harms) > Observational (rare harms) > Case series

GRADE Domains

Downgrade certainty for:

1. Risk of bias (study limitations)
2. Inconsistency (unexplained heterogeneity, I² > 50%)
3. Indirectness (PICO mismatch, surrogate outcomes)
4. Imprecision (wide confidence intervals, small sample)
5. Publication bias (funnel plot asymmetry, selective reporting)

Upgrade certainty for (observational studies):

1. Large effect (RR > 2 or < 0.5; very large RR > 5 or < 0.2)
2. Dose-response gradient
3. All plausible confounders would reduce effect

Effect Size Interpretation

Risk Ratio (RR):

• RR = 1.0: No effect
• RR = 0.75: 25% relative risk reduction
• RR = 1.25: 25% relative risk increase

Minimal Clinically Important Difference (MCID) - Common Scales:

• KCCQ (Kansas City Cardiomyopathy Questionnaire): 5 points
• SF-36 (Short Form Health Survey): 5-10 points
• VAS pain (0-100): 10-15 points
• 6-minute walk test: 30 meters
• FEV₁ (lung function): 100-140 mL

Sample Size Considerations

Adequate power: ≥80% power to detect MCID Typical requirements:

• Mortality reduction (5% → 4%): ~10,000 per arm
• QoL improvement (MCID): ~200-500 per arm
• Diagnostic accuracy (sensitivity 85% → 90%): ~300-500 patients