Jang (2022)

Relapsed/refractory multiple myeloma

Oncology • Other Data • South Korea

Study Metrics
Total Sample 138
Treatment Group 69
Control Group 69
Covariates 9
PICO Comparisons 28
Quality Indicators
Transparency High
DAG Usage No
QBA Performed No

Study Information

First Author: Jang
Publication Year: 2022
DOI: https://doi.org/10.3390/ijerph192013560
Preprint: No preprint

Institution & Funding

Institution Type: Academic
Institutions: College of Pharmacy and Research Institute of Pharmaceutical Sciences at Seoul National University, and Department of Internal Medicine at Seoul National University Hospital
Funding: Declared: Public
Funding Institutions: This research was supported by a grant (2020MFDS171) from the Ministry of Food and Drug Safety in 2020.

Study Context

Disease: Relapsed/refractory multiple myeloma
Disease Category: Oncology
Data Type: Other
Number of Data Sources: 2
Geography: South Korea
Eligible Sample: 263.0
Number of Treatments: 2

Analytical Methods

Matching Method: PS Matching, 1:1 matching
Analysis Method: Cox PH
Estimand: Not defined

Quality Methods

Directed Acyclic Graph (DAG) Not Used
Quantitative Bias Analysis (QBA) Not Performed

Target Trial Information

Target Trial Name: ASPIRE
Registration Number: NCT01080391
Target Trial DOI: https://doi.org/10.1056/nejmoa1411321

TTE vs RCT Comparisons

Detailed comparison between Target Trial Emulation results and corresponding Randomized Controlled Trial outcomes.

Acute kidney injury
EMPA-REG OUTCOME
OR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Acute kidney injury

RCT Result

0.78

95% CI: [0.63, 0.96]


vs
TTE Result

0.70

95% CI: [0.59, 0.82]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Acute renal failure
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Acute renal failure

RCT Result

1.19

95% CI: [0.70, 2.00]


vs
TTE Result

1.30

95% CI: [0.53, 3.16]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
All cause death
EMPA-REG OUTCOME
HR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

All cause death

RCT Result

0.68

95% CI: [0.57, 0.82]


vs
TTE Result

0.78

95% CI: [0.67, 0.91]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Coronary revascularization
EMPA-REG OUTCOME
HR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Coronary revascularization

RCT Result

0.86

95% CI: [0.72, 1.04]


vs
TTE Result

0.94

95% CI: [0.87, 1.02]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Cough
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Cough

RCT Result

1.94

95% CI: [1.37, 2.72]


vs
TTE Result

1.04

95% CI: [0.45, 2.45]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Diabetic ketoacidosis
EMPA-REG OUTCOME
OR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Diabetic ketoacidosis

RCT Result

1.99

95% CI: [0.20, 17.80]


vs
TTE Result

1.09

95% CI: [0.72, 1.64]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Diarrhea
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Diarrhea

RCT Result

1.44

95% CI: [1.08, 1.92]


vs
TTE Result

1.03

95% CI: [0.52, 1.99]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Dyspenia
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Dyspenia

RCT Result

1.38

95% CI: [0.94, 2.00]


vs
TTE Result

2.27

95% CI: [1.24, 4.16]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Fracture
EMPA-REG OUTCOME
OR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Fracture

RCT Result

0.98

95% CI: [0.76, 1.27]


vs
TTE Result

0.94

95% CI: [0.87, 1.03]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Genital infection
EMPA-REG OUTCOME
OR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Genital infection

RCT Result

3.74

95% CI: [2.70, 5.19]


vs
TTE Result

1.49

95% CI: [1.35, 1.65]

Concordance Assessment
Confidence Interval Overlap: No
CIs do not overlap
Direction Agreement: Same Direction
Both point to similar conclusion
Heart failure
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Heart failure

RCT Result

1.59

95% CI: [0.83, 3.02]


vs
TTE Result

1.45

95% CI: [0.61, 3.48]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
hospitalization for heart failure
EMPA-REG OUTCOME
HR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

hospitalization for heart failure

RCT Result

0.65

95% CI: [0.50, 0.85]


vs
TTE Result

0.85

95% CI: [0.75, 0.95]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Hospitalization for unstable angine
EMPA-REG OUTCOME
HR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Hospitalization for unstable angine

RCT Result

0.99

95% CI: [0.74, 1.34]


vs
TTE Result

0.94

95% CI: [0.88, 1.01]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Hypertension
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Hypertension

RCT Result

2.23

95% CI: [1.38, 3.62]


vs
TTE Result

1.32

95% CI: [0.73, 2.40]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Hypoglycemic adverse event
EMPA-REG OUTCOME
OR Safety
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Hypoglycemic adverse event

RCT Result

1.00

95% CI: [0.89, 1.11]


vs
TTE Result

0.70

95% CI: [0.59, 0.84]

Concordance Assessment
Confidence Interval Overlap: No
CIs do not overlap
Direction Agreement: Different Direction
Different conclusions
Hypokalemia
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Hypokalemia

RCT Result

2.46

95% CI: [1.69, 3.57]


vs
TTE Result

1.91

95% CI: [0.62, 5.87]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Ischemic heart disease
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Ischemic heart disease

RCT Result

1.28

95% CI: [0.68, 2.42]


vs
TTE Result

1.00

95% CI: [0.34, 2.92]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Different Direction
Different conclusions
MACE (major adverse cardiovascular events)
EMPA-REG OUTCOME
HR Safety
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

MACE (major adverse cardiovascular events)

RCT Result

0.86

95% CI: [0.74, 0.99]


vs
TTE Result

0.87

95% CI: [0.79, 0.96]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Muscle spasm
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Muscle spasm

RCT Result

1.36

95% CI: [0.97, 1.89]


vs
TTE Result

5.12

95% CI: [1.05, 15.00]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Myocardial infarction
EMPA-REG OUTCOME
HR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Myocardial infarction

RCT Result

0.87

95% CI: [0.70, 1.09]


vs
TTE Result

0.91

95% CI: [0.76, 1.08]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Pyrexia
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Pyrexia

RCT Result

1.52

95% CI: [1.08, 2.11]


vs
TTE Result

1.79

95% CI: [0.97, 3.24]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Stroke
EMPA-REG OUTCOME
HR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Stroke

RCT Result

1.18

95% CI: [0.89, 1.56]


vs
TTE Result

0.89

95% CI: [0.75, 1.05]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Different Direction
Different conclusions
Thrombocytopenia
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Thrombocytopenia

RCT Result

1.40

95% CI: [1.02, 1.94]


vs
TTE Result

1.84

95% CI: [1.10, 3.06]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Thromboembolic event
EMPA-REG OUTCOME
OR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Thromboembolic event

RCT Result

0.75

95% CI: [0.42, 1.31]


vs
TTE Result

0.92

95% CI: [0.80, 1.05]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Transient ischemic attack
EMPA-REG OUTCOME
HR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Transient ischemic attack

RCT Result

0.85

95% CI: [0.51, 1.42]


vs
TTE Result

0.88

95% CI: [0.74, 1.04]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Upper respiratory tract infection
ASPIRE
RR Efficacy
Population

Korean patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years

Intervention

KRd (carfilzomib, lenalidomide, and dexamethasone)

Comparison

Rd (lenalidomide and dexamethasone)

Outcome

Upper respiratory tract infection

RCT Result

1.68

95% CI: [1.19, 2.33]


vs
TTE Result

1.43

95% CI: [0.59, 3.56]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Urinary tract infection
EMPA-REG OUTCOME
OR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Urinary tract infection

RCT Result

0.99

95% CI: [0.87, 1.13]


vs
TTE Result

0.87

95% CI: [0.81, 0.94]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Same Direction
Both point to similar conclusion
Volume depletion
EMPA-REG OUTCOME
OR Efficacy
Population

Adult patients (≥18 years) with type 2 diabetes mellitus and established cardiovascular disease in Korean population

Intervention

Empagliflozin

Comparison

Sitagliptin

Outcome

Volume depletion

RCT Result

1.04

95% CI: [0.82, 1.30]


vs
TTE Result

0.84

95% CI: [0.76, 0.94]

Concordance Assessment
Confidence Interval Overlap: Yes
CIs overlap, suggesting concordance
Direction Agreement: Different Direction
Different conclusions

Transparency Indicators

Protocol Registration Available
Data Sharing Not Available
Code Sharing Not Available
Overall Transparency Score:
High Transparency - This study meets good transparency standards.

Conflicts & Funding

Conflicts of Interest: Declared: None
Funding Source: Declared: Public
Funding Institutions: This research was supported by a grant (2020MFDS171) from the Ministry of Food and Drug Safety in 2020.