somewordstoolate/Q2CRBench-3 huggingface dataset:
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD double combination therapy
Outcome: Pain (follow up: 1 year; assessed with: VAS 0-100 (Lower values – > benefit) (MCID -11.9)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population with moderate to high disease activity.
Imprecision: result: SERIOUS
rationales: Downgraded by one level due to serious imprecision. Low sample size.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: CSDMARD double therapy: 36
CSDMARD monotherapy: 69
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.05 higher (10.89 lower to 10.99 higher)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD double combination therapy
Outcome: Serious adverse events (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population with moderate to high disease activity.
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence intervals includes both values suggesting benefit and values suggesting harm. Small sample size, very low number of events.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: CSDMARD double therapy: 0/36 (0.0%)
CSDMARD monotherapy: 3/69 (4.3%)
Effect: Relative Effect (95% CI): RR 0.27 (0.01 to 5.09)
Absolute Effect (95% CI): 32 fewer per 1,000 (from 43 fewer to 178 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD double combination therapy
Outcome: Withdrawal due to lack of efficacy (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment in both studies, high risk of attrition bias in one of the two studies.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population with moderate to high disease activity.
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence intervals includes both values suggesting benefit and values suggesting harm. Small sample size, very low number of events.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: CSDMARD double therapy: 4/104 (3.8%)
CSDMARD monotherapy: 15/206 (7.3%)
Effect: Relative Effect (95% CI): RR 0.53 (0.18 to 1.56)
Absolute Effect (95% CI): 34 fewer per 1,000 (from 60 fewer to 41 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD double combination therapy
Outcome: Withdrawal due to adverse events (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment in both studies, high risk of attrition bias in one of the two studies.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirectness. The evidence is based on a population with moderate to high disease activity.
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence intervals includes both values suggesting benefit and values suggesting harm. Small sample size, very low number of events.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: CSDMARD double therapy: 14/104 (13.5%)
CSDMARD monotherapy: 28/206 (13.6%)
Effect: Relative Effect (95% CI): RR 0.99 (0.54 to 1.79)
Absolute Effect (95% CI): 1 fewer per 1,000 (from 63 fewer to 107 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD triple combination therapy
Outcome: Disease activity (follow up: 3 months; assessed with: DAS 44 (Lower values --> benefit)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: SERIOUS
rationales: Downgraded by one level due to serous imprecision. Small sample size.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: MODERATE
No of participants: csDMARD triple therapy: 89
csDMARD monotherapy: 90
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.35 lower (0.64 lower to 0.06 lower)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD triple combination therapy
Outcome: Remission (follow up: 3 months; assessed with: DAS 44 <1.6)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence interval includes both values suggesting benefit and values suggesting harm. Small sample size.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: csDMARD triple therapy: 38/89 (42.7%)
csDMARD monotherapy: 28/90 (31.1%)
Effect: Relative Effect (95% CI): RR 1.37 (0.93 to 2.03)
Absolute Effect (95% CI): 115 more per 1,000 (from 22 fewer to 320 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD triple combination therapy
Outcome: Disability (follow up: 3 months; assessed with: HAQ-DI (Lower values --> benefit) (MCID -0.22)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: SERIOUS
rationales: Downgraded by one level due to serious imprecision. Small sample size.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: MODERATE
No of participants: csDMARD triple therapy: 78
csDMARD monotherapy: 78
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.03 lower (0.2 lower to 0.14 higher)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD triple combination therapy
Outcome: Serious adverse events (follow up: 3 months)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence interval includes both values suggesting benefit and values suggesting harm. Small sample size.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: csDMARD triple therapy: 4/89 (4.5%)
csDMARD monotherapy: 6/90 (6.7%)
Effect: Relative Effect (95% CI): RR 0.67 (0.20 to 2.31)
Absolute Effect (95% CI): 22 fewer per 1,000 (from 53 fewer to 87 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD triple combination therapy
Outcome: Withdrawal due to Adverse events (follow up: 3 months)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence interval includes both values suggesting benefit and values suggesting harm. Small sample size.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: csDMARD triple therapy: 0/93 (0.0%)
csDMARD monotherapy: 3/97 (3.1%)
Effect: Relative Effect (95% CI): RR 0.15 (0.01 to 2.84)
Absolute Effect (95% CI): 26 fewer per 1,000 (from 31 fewer to 57 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs exposed RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD triple combination therapy
Outcome: Disease activity (follow up: 6 months; assessed with: DAS 28-ESR (Lower values – > benefit) (MCID -1.17)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirecteness. The population has moderate disease activity.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: MODERATE
No of participants: csDMARD triple therapy: 132
csDMARD monotherapy: 379
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.64 lower (0.95 lower to 0.33 lower)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs exposed RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD triple combination therapy
Outcome: Disease activity (follow up: 6 months; assessed with: ACR 20)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirecteness. The population has moderate disease activity.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: MODERATE
No of participants: csDMARD triple therapy: 73/132 (55.3%)
csDMARD monotherapy: 150/379 (39.6%)
Effect: Relative Effect (95% CI): RR 1.40 (1.15 to 1.70)
Absolute Effect (95% CI): 158 more per 1,000 (from 59 more to 277 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs exposed RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD triple combination therapy
Outcome: Disease activity (follow up: 6 months; assessed with: ACR 50)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirecteness. The population has moderate disease activity.
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: MODERATE
No of participants: csDMARD triple therapy: 41/132 (31.1%)
csDMARD monotherapy: 73/379 (19.3%)
Effect: Relative Effect (95% CI): RR 1.61 (1.16 to 2.24)
Absolute Effect (95% CI): 117 more per 1,000 (from 31 more to 239 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs exposed RA and low disease activity receive csDMARD monotherapy or csDMARD combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs exposed RA and low disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD triple combination therapy
Outcome: Disease activity (follow up: 6 months; assessed with: ACR 70)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: NOT_SERIOUS
Inconsistency: result: NOT_SERIOUS
Indirectness: result: SERIOUS
rationales: Downgraded by one level due to serious indirecteness. The population has moderate disease activity.
Imprecision: result: SERIOUS
rationales: Downgraded by one level due to serious imprecision. Confidence interval includes both values suggesting no effect and values suggesting harm. Low number of events.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: csDMARD triple therapy: 11/132 (8.3%)
csDMARD monotherapy: 13/379 (3.4%)
Effect: Relative Effect (95% CI): RR 2.43 (1.12 to 5.29)
Absolute Effect (95% CI): 49 more per 1,000 (from 4 more to 147 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive csDMARD monotherapy or combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA who have moderate to high disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD double combination therapy
Outcome: Disease activity (follow up: 1 year; assessed with: DAS 44 (Lower values – > benefit) (MCID -1.2 based on the EULAR criteria)
Importance: CRITICAL

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment in both studies, high risk of attrition bias in one of the two studies.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: MODERATE
No of participants: csDMARD double therapy: 104
csDMARD monotherapy: 206
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.3 lower (0.57 lower to 0.02 higher)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive csDMARD monotherapy or combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA who have moderate to high disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD double combination therapy
Outcome: Disability (follow up: 1 year; assessed with: HAQ-DI (Lower values – > benefit) (MCID -0.22)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment in both studies, high risk of attrition bias in one of the two studies.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: NOT_SERIOUS
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: MODERATE
No of participants: csDMARD double therapy: 104
csDMARD monotherapy: 206
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.01 lower (0.16 lower to 0.14 higher)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive csDMARD monotherapy or combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA who have moderate to high disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD double combination therapy
Outcome: Pain (follow up: 1 year; assessed with: VAS 0-100 (Lower values – > benefit) (MCID -11.9)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: SERIOUS
rationales: Downgraded by one level due to serious imprecision. Low sample size.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: LOW
No of participants: csDMARD double therapy: 36
csDMARD monotherapy: 69
Effect: Relative Effect (95% CI): -
Absolute Effect (95% CI): MD 0.05 higher (10.89 lower to 10.99 higher)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive csDMARD monotherapy or combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA who have moderate to high disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD double combination therapy
Outcome: Serious adverse events (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence intervals include both values suggesting benefit and values suggesting harm. Small sample size, very low number of events.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: csDMARD double therapy: 0/36 (0.0%)
csDMARD monotherapy: 3/69 (4.3%)
Effect: Relative Effect (95% CI): RR 0.27 (0.01 to 5.09)
Absolute Effect (95% CI): 32 fewer per 1,000 (from 43 fewer to 178 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio
Guideline: 2021 ACR RA
Clinical question: Should patients with MTX-naïve and non-MTX csDMARDs naïve RA and moderate to high disease activity receive csDMARD monotherapy or combination (double or triple) therapy?
Population: Patients with MTX-naïve and non-MTX csDMARDs naïve RA who have moderate to high disease activity
Intervention: csDMARD monotherapy
Comparator: csDMARD double combination therapy
Outcome: Withdrawal due to lack of efficacy (follow up: 1 year)
Importance: IMPORTANT

Evidence assessment:
GRADE: Risk of bias: result: SERIOUS
rationales: Downgraded by one level due to serious risk of bias. Lack of allocation concealment in both studies, high risk of attrition bias in one of the two studies.
Inconsistency: result: NOT_SERIOUS
Indirectness: result: NOT_SERIOUS
Imprecision: result: VERY_SERIOUS
rationales: Downgraded by two levels due to very serious imprecision. Confidence intervals include both values suggesting benefit and values suggesting harm. Small sample size, very low number of events.
Other considerations: result: none
Study design: Randomized Controlled Trial
Certainty: VERY LOW
No of participants: csDMARD double therapy: 4/104 (3.8%)
csDMARD monotherapy: 15/206 (7.3%)
Effect: Relative Effect (95% CI): RR 0.53 (0.18 to 1.56)
Absolute Effect (95% CI): 34 fewer per 1,000 (from 60 fewer to 41 more)
Abbreviations: CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio