研究证据与方法评估

references/evidence_hierarchy.md

Traditional Evidence Hierarchy (Medical/Clinical)

This is a teaching shorthand for some intervention questions, not a universal ranking. Choose designs for the question: prevalence, prognosis, diagnostic accuracy, harms, and mechanisms have different evidence needs. A review synthesizes its underlying studies; meta-analysis alone does not increase certainty. Reporting quality, risk of bias, applicability, and certainty must be assessed separately. Current sources are recorded in review_sources.md.

Level 1: Systematic Reviews and Meta-Analyses

Description: Comprehensive synthesis of all available evidence on a question.

Strengths:

• Combines multiple studies for greater power
• Reduces impact of single-study anomalies
• Can identify patterns across studies
• May quantify a pooled effect if studies and estimands can meaningfully be combined

Weaknesses:

• Quality depends on included studies ("garbage in, garbage out")
• Publication bias can distort findings
• Heterogeneity may make pooling inappropriate
• Can mask important differences between studies

Critical evaluation:

• Was search comprehensive (multiple databases, grey literature)?
• Were inclusion criteria appropriate and prespecified?
• Was study quality assessed?
• Was heterogeneity explored?
• Were missing studies/results sought in registries and protocols? If funnel-plot methods were appropriate, were alternative explanations for asymmetry considered? Fail-safe N is not a reliable assessment of missing-evidence bias.
• Were appropriate statistical methods used?

Level 2: Randomized Controlled Trials (RCTs)

Description: Experimental studies with random assignment to conditions.

Strengths:

• Strong design for estimating intervention effects when implemented and analysed appropriately
• Balances prognostic factors in expectation, not necessarily in each realized sample
• Minimizes selection bias
• Enables causal inference

Weaknesses:

• May not be ethical or feasible
• Artificial settings may limit generalizability
• Often short-term with selected populations
• Expensive and time-consuming

Critical evaluation:

• Was randomization adequate (sequence generation, allocation concealment)?
• Was blinding implemented (participants, providers, assessors)?
• Was sample size adequate (power analysis)?
• Was intention-to-treat analysis used?
• Was attrition rate acceptable and balanced?
• Are results generalizable?

Level 3: Cohort Studies

Description: Observational studies following groups over time.

Types:

• Prospective: Follow forward from exposure to outcome
• Retrospective: Look backward at existing data

Strengths:

• Can study multiple outcomes
• Establishes temporal sequence
• Can calculate incidence and relative risk
• More feasible than RCTs for many questions

Weaknesses:

• Susceptible to confounding
• Selection bias possible
• Attrition can bias results
• Causal interpretation requires explicit identification assumptions and sensitivity analysis

Critical evaluation:

• Were cohorts comparable at baseline?
• Was exposure measured reliably?
• Was follow-up adequate and complete?
• Were potential confounders measured and controlled?
• Was outcome assessment blinded to exposure?

Level 4: Case-Control Studies

Description: Compare people with outcome (cases) to those without (controls), looking back at exposures.

Strengths:

• Efficient for rare outcomes
• Relatively quick and inexpensive
• Can study multiple exposures
• Useful for generating hypotheses

Weaknesses:

• Usually cannot estimate absolute incidence from sampled case/control counts alone
• Susceptible to recall bias
• Selection of controls is challenging
• Causal interpretation depends on the sampling design and control of relevant biases

Critical evaluation:

• Were cases and controls defined clearly?
• Were controls appropriate (same source population)?
• Was matching appropriate?
• How was exposure ascertained (records vs. recall)?
• Were potential confounders controlled?
• Could recall bias explain findings?

Level 5: Cross-Sectional Studies

Description: Snapshot observation at single point in time.

Strengths:

• Quick and inexpensive
• Can assess prevalence
• Useful for hypothesis generation
• Can study multiple outcomes and exposures

Weaknesses:

• Cannot establish temporal sequence
• Cannot determine causation
• Prevalence-incidence bias
• Survival bias

Critical evaluation:

• Was sample representative?
• Were measures validated?
• Could reverse causation explain findings?
• Are confounders acknowledged?

Level 6: Case Series and Case Reports

Description: Description of observations in clinical practice.

Strengths:

• Can identify new diseases or effects
• Hypothesis-generating
• Details rare phenomena
• Quick to report

Weaknesses:

• No control group
• Descriptive uncertainty may be estimable; uncontrolled counts do not identify a comparative effect
• Highly susceptible to bias
• Cannot establish causation or frequency

Use: Primarily for hypothesis generation and clinical description.

Level 7: Expert Opinion

Description: Statements by recognized authorities.

Strengths:

• Synthesizes experience
• Useful when no research available
• May integrate multiple sources

Weaknesses:

• Subjective and potentially biased
• May not reflect current evidence
• Appeal to authority fallacy risk
• Individual expertise varies

Use: Lowest level of evidence; should be supported by data when possible.

Nuances and Limitations of Traditional Hierarchy

When Lower-Level Evidence Can Be Strong

1. Well-designed observational studies with:

   • Large effects that plausible bias cannot explain (size alone does not establish this)
   • Dose-response relationships
   • Consistent findings across contexts
   • Biological plausibility
   • Explicitly justified confounding and selection assumptions, with sensitivity analyses

2. Multiple converging lines of evidence from different study types

3. Natural experiments approximating randomization

When Higher-Level Evidence Can Be Weak

1. Poor-quality RCTs with:

   • Inadequate randomization
   • High attrition
   • No blinding when feasible
   • Design, conduct, or reporting problems associated with sponsor influence

2. Biased meta-analyses:

   • Publication bias
   • Selective inclusion
   • Inappropriate pooling
   • Poor search strategy

3. Not addressing the right question:

   • Wrong population
   • Wrong comparison
   • Wrong outcome
   • Too artificial to generalize

Alternative: GRADE System

GRADE assesses certainty in a body of evidence for a specified outcome and comparison. Choose the relevant GRADE application, target population and decision threshold; retain effect estimates and uncertainty alongside domain judgments. The current GRADE Book is being released progressively; consult its updated chapters and the handbook only for sections not yet replaced.

For intervention effects, the traditional approach starts randomized evidence at high and non-randomized evidence at low certainty. When using the ROBINS-I-integrated approach, start at high and assess bias from confounding/selection explicitly, usually rating down substantially. Do not penalize lack of randomization twice. Specify the approach before rating. Consider risk of bias, inconsistency, indirectness, imprecision, and missing-evidence bias, and justify any large-effect, dose-response, or opposing-confounding considerations.

These levels are judgments about certainty, not numerical probabilities or recommendation strength:

High Certainty

Definition: High confidence that the effect is on the specified side of a threshold or within the target range.

Characteristics:

• No important unresolved concerns across the applicable certainty domains
• Neither an RCT label nor a large effect alone establishes high certainty

Moderate Certainty

Definition: Moderate confidence in that target; the effect could be in another range.

Downgrades from high:

• Some risk of bias
• Inconsistency across studies
• Indirectness (different populations/interventions)
• Imprecision relative to the specified threshold/range of important effects
• Publication bias suspected

Low Certainty

Definition: Limited confidence in that target; the effect may be in a different range.

Downgrades:

• Serious limitations in above factors
• Observational studies without special strengths

Very Low Certainty

Definition: Very little confidence in that target; substantial uncertainty remains about the effect's range.

Characteristics:

• Very serious limitations
• Evidence may be too sparse or indirect to support an effect estimate at all; do not invent a numerical estimate or GRADE rating for an unsupported opinion
• Multiple serious flaws

Document threshold magnitudes and their rationale. For intervention decisions use absolute effects with an appropriate baseline risk and its uncertainty. Rate down/up only when a concern changes confidence in the target range; do not double-count the same underlying problem across domains. Have independent assessors reconcile formal judgments.

Study Quality Assessment Criteria

Internal Validity (Bias Control)

Questions:

• Was randomization adequate?
• Was allocation concealed?
• Were groups similar at baseline?
• Was blinding implemented?
• Could missingness depend on the unobserved outcome? Low or balanced attrition alone does not establish low risk of bias.
• Was intention-to-treat used?
• Were all outcomes reported?

External Validity (Generalizability)

Questions:

• Is sample representative of target population?
• Are inclusion/exclusion criteria too restrictive?
• Is setting realistic?
• Are results applicable to other populations?
• Are effects consistent across subgroups?

Statistical Conclusion Validity

Questions:

• Was sample size adequate (power)?
• Were statistical tests appropriate?
• Were assumptions checked?
• Were effect sizes and confidence intervals reported?
• Were multiple comparisons addressed?
• Was analysis prespecified?

Construct Validity (Measurement)

Questions:

• Were measures validated and reliable?
• Was outcome defined clearly and appropriately?
• Were assessors blinded?
• Were exposures measured accurately?
• Was timing of measurement appropriate?

Critical Appraisal Tools

For Different Study Types

RCTs:

• Cochrane RoB 2 — recommended for randomized trials in Cochrane intervention reviews; assess a result, use the correct parallel/cluster/crossover variant, and retain reasons
• PEDro Scale — used for physiotherapy trials; its score is not interchangeable with RoB 2
• Legacy RoB 1 and Jadad ratings in older reviews should be identified as such

Observational Studies:

• ROBINS-I applies to non-randomized intervention effects, not every observational question. Specify the 2016 version or November 2025 ROBINS-I V2 draft for follow-up/cohort studies; do not combine version-specific signalling questions or domains.
• Newcastle-Ottawa Scale has cohort and case-control forms; record the chosen form and item judgments, not an unexplained universal good/poor star cutoff.

Diagnostic Studies:

• QUADAS-3 (current tool v1.2, published February 2026) assesses bias and applicability for individual accuracy estimates against defined synthesis questions and an ideal test accuracy trial. QUADAS-2 is the previous version.

Systematic Reviews:

• AMSTAR 2 appraises systematic reviews of healthcare interventions; assess critical weaknesses rather than calculating a total score.
• PRISMA 2020 assesses reporting completeness; it is not a risk-of-bias instrument.

Design-specific general appraisal:

• CASP supplies separate checklists for supported study designs; select the matching one. Do not assume every design has the same domains or numerical score.

Domain-Specific Considerations

Basic Science Research

Consider together, without imposing a fixed ranking:

1. Multiple convergent lines of evidence
2. Mechanistic understanding
3. Reproducible experiments
4. Established theoretical framework

Key considerations:

• Replication essential
• Mechanistic plausibility
• Consistency across model systems
• Convergence of methods

Psychological Research

Additional concerns:

• Replication crisis
• Publication bias particularly problematic
• Small effect sizes often expected
• Cultural context matters
• Measures often indirect (self-report)

Strong evidence includes:

• Preregistered studies
• Large samples
• Multiple measures
• Behavioral (not just self-report) outcomes
• Cross-cultural replication

Epidemiology

Causal inference frameworks:

• Bradford Hill criteria
• Rothman's causal pies
• Directed Acyclic Graphs (DAGs)

Strong observational evidence:

• Dose-response relationships
• Temporal consistency
• Biological plausibility
• Specificity can inform interpretation but is not necessary for causation
• Consistency across populations
• Large effects assessed against plausible confounding and selection mechanisms

Social Sciences

Challenges:

• Complex interventions
• Context-dependent effects
• Measurement challenges
• Ethical constraints on RCTs

Strengthening evidence:

• Mixed methods
• Natural experiments
• Instrumental variables
• Regression discontinuity designs
• Multiple operationalizations

Synthesizing Evidence Across Studies

Consistency

Strong evidence:

• Multiple studies, different investigators
• Different populations and settings
• Different research designs converge
• Different measurement methods

Weak evidence:

• Single study
• Only one research group
• Conflicting results
• Publication bias evident

Biological/Theoretical Plausibility

Strengthens evidence:

• Known mechanism
• Consistent with other knowledge
• Dose-response relationship
• Coherent with animal/in vitro data

Weakens evidence:

• No plausible mechanism
• Contradicts established knowledge
• Biological implausibility

Temporality

Essential for causation:

• Cause must precede effect
• Cross-sectional studies cannot establish
• Reverse causation must be ruled out

Specificity

Moderate indicator:

• Specific cause → specific effect strengthens causation
• But lack of specificity doesn't rule out causation
• Most causes have multiple effects

Strength of Association

Strong evidence:

• Large effects with plausible confounding, selection, and measurement explanations examined
• Dose-response relationships
• All-or-none effects

Caution:

• Small effects may still be real
• Large effects can still be confounded

Red Flags in Evidence Quality

Study Design Red Flags

• No control group
• Self-selected participants
• No randomization when feasible
• No blinding when feasible
• Very small sample
• Inappropriate statistical tests

Reporting Red Flags

• Selective outcome reporting
• No study registration/protocol
• Missing methodological details
• No conflicts of interest statement
• Cherry-picked citations
• Results don't match methods

Interpretation Red Flags

• Causal language from correlational data
• Claiming "proof"
• Ignoring limitations
• Overgeneralizing
• Spinning negative results
• Post hoc rationalization

Context Red Flags

• Industry funding without independence
• Single study in isolation
• Contradicts preponderance of evidence
• No replication
• Published in predatory journal
• Press release before peer review

Practical Decision Framework

When Evaluating Evidence, Ask:

1. What type of study is this? (Design)
2. How well was it conducted? (Quality)
3. What does it actually show? (Results)
4. How likely is bias? (Internal validity)
5. Does it apply to my question? (External validity)
6. How does it fit with other evidence? (Context)
7. Are the conclusions justified? (Interpretation)
8. What are the limitations? (Uncertainty)

Making Decisions with Imperfect Evidence

Certainty does not itself authorize changing practice or policy. A high-certainty estimate may show negligible benefit or important harm. Low-certainty evidence may still inform a decision when delay or alternatives carry costs. A separate evidence-to-decision process considers absolute benefits/harms, values, resources, equity, acceptability, and feasibility. State whose decision and setting are involved; an appraisal is not an individual clinical recommendation. Identify the information most likely to change the decision.

When Evidence is Conflicting

Strategies:

1. Weight by study quality
2. Look for systematic differences (population, methods)
3. Consider publication bias
4. Update with most recent, rigorous evidence
5. Conduct/await systematic review
6. Consider if question is well-formed

Communicating Evidence Strength

Avoid:

• Absolute certainty ("proves")
• False balance (equal weight to unequal evidence)
• Ignoring uncertainty
• Cherry-picking studies

Better:

• Quantify uncertainty
• Describe strength of evidence
• Acknowledge limitations
• Present range of evidence
• Distinguish established from emerging findings
• Be clear about what is/isn't known