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Study Title and Description

Long-term safety and efficacy of TAK-085 in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized long-term (ORL) study.



Key Questions Addressed
1 RCTs and other Comparative studies
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Primary Publication Information
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TitleData
Title Long-term safety and efficacy of TAK-085 in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized long-term (ORL) study.
Author Tatsuno I., Saito Y., Kudou K., Ootake J.
Country Center for Diabetes, Metabolism and Endocrinology, Toho University Sakura Medical Center, Chiba 285-8741, Japan. Electronic address: ichiro.tatsuno@med.toho-u.ac.jp.
Year 2013
Numbers Pubmed ID: 24314359
14768 (internal)

Secondary Publication Information
UI Title Author Country Year
Efficacy and safety of TAK-085 compared with eicosapentaenoic acid in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized double-blind (ORD) study. Tatsuno I., Saito Y., Kudou K., Ootake J. Center for Diabetes, Metabolism and Endocrinology, Toho University Sakura Medical Center, Chiba 285-8741, Japan. ichiro.tatsuno@med.toho-u.ac.jp -- Not Found --
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Extraction Form: Comparative Studies
Arms
Number Title Description Comments
1 "Fish oil" (DHA+EPA) TAK-085 2 g/day
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2 "Fish oil" (DHA+EPA) TAK-085 4 g/day
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3 EPA EPA-E 1.8 g/day
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Design Details
Question... Follow Up Answer Follow-up Answer
Study Design Trial: Randomized Parallel (Omega-3 vs. Control; Omega-3 + X vs. X)
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What is the name of this study? (e.g. DART, Physician's Health Study) ORL
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Country in which study conducted (where subjects live) Japan
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Funding source Industry funded
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Authors report industry affiliation
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Eligibility Criteria: Outpatients, aged 20 to 74 years undergoing lifestyle modification for hypertriglyceridemia, fasting triglyceride level >=150 mg/dL and < 750 mg/dL at weeks –4 and –2 during the screening period and a variation in fasting low-density lipoprotein cholesterol (LDL-C) level between weeks –4 and –2 of <25% from the highest value. All subjects were advised about lifestyle modifications (dietary or exercise or both) at all visits during the study. The main exclusion criteria were coronary artery disease, an aortic aneurysm, or significant hemorrhagic disease within 6 months before the study; pancreatitis; lipoprotein lipase deficiency, apolipoprotein C-II deficiency, and type III familial hyperlipidemia; Cushing syndrome, uremia, systemic lupus erythematosus, or serum dysproteinemia; type 1 or uncontrolled type 2 diabetes mellitus (hemoglobin A1c $8%); stage III hypertension; and hepatic impairment.
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Comment about Eligibility Criteria: Use of concomitant medications that might affect the evaluation of efficacy was not permitted, such as fish oil supplements (including any other products, medications, or investigational drugs that contained EPA-E or DHA), insulin, androgens, estrogens, progesterones, and systemic steroids. Antihyperlipidemic drugs (with the exception of EPA-E) and antidiabetic drugs (except insulin) were allowed, provided they had been initiated at least 4 weeks before the study and the dose was not changed during the screening or treatment periods.
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Study Population Primary Prevention, Increased CVD Risk (ie, diabetes, metabolic syndrome*, hypertension, dyslipidemia, or chronic kidney disease)
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Duration of Intervention 1 year
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At baseline, did all subjects have (per eligibility criteria)...? ... Define: Dyslipidemia ... fasting triglyceride level >=150 mg/dL and <750 mg/dL at weeks –4 and –2 during the screening period
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Conflict of interest ... Specify Conflict of interest stated ... KK and JO are employees of Takeda Pharmaceutical Company; IT has acted as a consultant to Takeda, YS has acted as a consultant to Astellas and others
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Does the study report a subgroup analysis for an outcome of interest? ... Which subgroups? Yes ... stratified by baseline triglyceride level or concomitant statin use
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Study start date(s) 2009
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Baseline Characteristics
Question "Fish oil" (DHA+EPA) "Fish oil" (DHA+EPA) EPA Total Comments
AnswerFollow-up AnswerFollow-up AnswerFollow-up AnswerFollow-up
Baseline Diseases/Conditions 30.1 33.3 34.4
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Including impaired glucose tolerance. Including impaired glucose tolerance Including impaired glucose tolerance
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59.7 60.5 67.2
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Baseline characteristics, continuous 53.9 55.0 55.6
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10.8 10.5 10.5
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127.4 125.7 130.1
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mg/dL mg/dL mg/dL
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29.1 28.5 30.5
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269.0 277.5 271.8
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mg/dL mg/dL mg/dL
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77.52 97.29 91.53
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26.6 26.3 26.3
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3.7 3.9 3.6
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Male, percent 77.7 74.8 80.5
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Race 100
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Japanese
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Comments about baseline data Low HDL-C (<40 mg/dL) 25.5% Low HDL-C (<40 mg/dL) 22.8% Low HDL-C (<40 mg/dL) 26.9%
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Baseline diet description nd
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Baseline omega-3 intake nd
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Does this study report baseline omega-3 biomarker data? Yes
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Results & Comparisons


Results Data
Outcome: lipid      Population: 44385
Time Point Measure "Fish oil" (DHA+EPA) "Fish oil" (DHA+EPA) EPA


0 years

N Analyzed 206 210 195
Mean 45.8 45.7 45.6
SD 9.9 9.9 10.2


12 weeks

N Analyzed 206 210 195
Mean 46.7 47.6 46.2
SD 10.4 11.0 10.7


1 years

N Analyzed 165 170 167
Outcome: lipid      Population: 44386
Time Point Measure "Fish oil" (DHA+EPA) "Fish oil" (DHA+EPA) EPA


0 years

N Analyzed 206 210 195
Mean 127.4 125.7 130.1
SD 29.1 28.5 30.5


12 weeks

N Analyzed 206 210 195
Mean 124.0 123.6 123.3
SD 31.8 29.0 30.5


1 years

N Analyzed 165 170 167
Outcome: lipid      Population: 44387
Time Point Measure "Fish oil" (DHA+EPA) "Fish oil" (DHA+EPA) EPA


0 years

N Analyzed 165 170 167


1 years

N Analyzed 165 170 167
Outcome: lipid      Population: 44388
Time Point Measure "Fish oil" (DHA+EPA) "Fish oil" (DHA+EPA) EPA


0 years

N Analyzed 165 170 167


1 years

N Analyzed 165 170 167
Outcome: lipid      Population: 44389
Time Point Measure "Fish oil" (DHA+EPA) "Fish oil" (DHA+EPA) EPA


0 years

N Analyzed 206 210 195
Mean 269.0 277.5 271.8
SD 77.5 97.3 91.5
Median 254.0 253.7 250.0
25th Percentile 211.3 211.0 208.0
75th Percentile 313.7 316.7 311.3


12 weeks

N Analyzed 206 210 195
Mean 237.5 208.8 238.1
Median 215.5 189.9 213.8
SD 84.0 86.0 99.8
25th Percentile 183.0 159.5 171.0
75th Percentile 271.5 239.3 279.0


1 years

N Analyzed 165 170 167
Mean 214 202 226
SD nd nd nd
Outcome: bp      Population: 44390
Time Point Measure "Fish oil" (DHA+EPA) "Fish oil" (DHA+EPA) EPA


0 years

N Analyzed 165 171 167


1 years

N Analyzed 165 171 167
Outcome: bp      Population: 44391
Time Point Measure "Fish oil" (DHA+EPA) "Fish oil" (DHA+EPA) EPA


0 years

N Analyzed 165 171 167


1 years

N Analyzed 165 171 167

Adverse Events
Arm or Total Title Description Events (n) At Risk (N) Follow-up time Comments
"Fish oil" (DHA+EPA) Nasopharyngitis 57 165 1 year
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"Fish oil" (DHA+EPA) 43 171 1 year
EPA 42 167 1 year
"Fish oil" (DHA+EPA) Pharyngitis 14 165 1 year
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"Fish oil" (DHA+EPA) 15 171 1 year
EPA 15 167 1 year
"Fish oil" (DHA+EPA) Bronchitis 9 165 1 year
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"Fish oil" (DHA+EPA) 7 171 1 year
EPA 9 167 1 year
"Fish oil" (DHA+EPA) Gastroenteritis 5 165 1 year
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"Fish oil" (DHA+EPA) 3 171 1 year
EPA 5 167 1 year
"Fish oil" (DHA+EPA) Influenza 3 165 1 year
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"Fish oil" (DHA+EPA) 5 171 1 year
EPA 3 167 1 year
"Fish oil" (DHA+EPA) Seasonal allergy 6 165 1 year
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"Fish oil" (DHA+EPA) 6 171 1 year
EPA 9 167 1 year
"Fish oil" (DHA+EPA) Diabetes mellitus 3 165 1 year
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"Fish oil" (DHA+EPA) 9 171 1 year
EPA 9 167 1 year
"Fish oil" (DHA+EPA) Hypoesthesia 7 165 1 year
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"Fish oil" (DHA+EPA) 1 171 1 year
EPA 2 167 1 year
"Fish oil" (DHA+EPA) Headache 1 165 1 year
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"Fish oil" (DHA+EPA) 5 171 1 year
EPA 3 167 1 year
"Fish oil" (DHA+EPA) Conjunctivitis allergic 4 165 1 year
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"Fish oil" (DHA+EPA) 0 171 1 year
EPA 3 167 1 year
"Fish oil" (DHA+EPA) Upper respiratory tract inflammation 12 165 1 year
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"Fish oil" (DHA+EPA) 19 171 1 year
EPA 14 167 1 year
"Fish oil" (DHA+EPA) Rhinitis allergic 2 165 1 year
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"Fish oil" (DHA+EPA) 2 171 1 year
EPA 5 167 1 year
"Fish oil" (DHA+EPA) Oropharyngeal pain 1 165 1 year
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"Fish oil" (DHA+EPA) 4 171 1 year
EPA 1 167 1 year
"Fish oil" (DHA+EPA) Diarrhea 8 165 1 year
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"Fish oil" (DHA+EPA) 9 171 1 year
EPA 9 167 1 year
"Fish oil" (DHA+EPA) Periodontitis 6 165 1 year
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"Fish oil" (DHA+EPA) 5 171 1 year
EPA 7 167 1 year
"Fish oil" (DHA+EPA) Gastritis 1 severe TAK-085 4-g group; a higher incidence in both the TAK-085 2-g and TAK-085 4-g groups than in the EPA-E 1.8-g group 6 165 1 year
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"Fish oil" (DHA+EPA) 6 171 1 year
EPA 4 167 1 year
"Fish oil" (DHA+EPA) Dental caries 2 165 1 year
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"Fish oil" (DHA+EPA) 9 171 1 year
EPA 3 167 1 year
"Fish oil" (DHA+EPA) Reflux esophagitis 5 165 1 year
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"Fish oil" (DHA+EPA) 2 171 1 year
EPA 4 167 1 year
"Fish oil" (DHA+EPA) Constipation a higher incidence in both the TAK-085 2-g and TAK-085 4-g groups than in the EPA-E 1.8-g group 3 165 1 year
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"Fish oil" (DHA+EPA) 6 171 1 year
EPA 0 167 1 year
"Fish oil" (DHA+EPA) Enterocolitis 2 165 1 year
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"Fish oil" (DHA+EPA) 4 171 1 year
EPA 3 167 1 year
"Fish oil" (DHA+EPA) Hepatic function abnormal 3 165 1 year
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"Fish oil" (DHA+EPA) 5 171 1 year
EPA 6 167 1 year
"Fish oil" (DHA+EPA) Eczema a higher incidence in both the TAK-085 2-g and TAK-085 4-g groups than in the EPA-E 1.8-g group 5 165 1 year
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"Fish oil" (DHA+EPA) 7 171 1 year
EPA 2 167 1 year
"Fish oil" (DHA+EPA) Urticaria 4 165 1 year
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"Fish oil" (DHA+EPA) 2 171 1 year
EPA 5 167 1 year
"Fish oil" (DHA+EPA) Back pain 7 165 1 year
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"Fish oil" (DHA+EPA) 8 171 1 year
EPA 12 167 1 year
"Fish oil" (DHA+EPA) Arthralgia 2 165 1 year
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"Fish oil" (DHA+EPA) 4 171 1 year
EPA 4 167 1 year
"Fish oil" (DHA+EPA) Myalgia 1 165 1 year
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"Fish oil" (DHA+EPA) 5 171 1 year
EPA 3 167 1 year
"Fish oil" (DHA+EPA) Pain in extremity 1 165 1 year
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"Fish oil" (DHA+EPA) 5 171 1 year
EPA 1 167 1 year
"Fish oil" (DHA+EPA) Osteoarthritis 4 165 1 year
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"Fish oil" (DHA+EPA) 0 171 1 year
EPA 2 167 1 year
"Fish oil" (DHA+EPA) Blood creatine phosphokinase raised 13 165 1 year
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"Fish oil" (DHA+EPA) 7 171 1 year
EPA 18 167 1 year
"Fish oil" (DHA+EPA) Liver function test abnormal a higher incidence in both the TAK-085 2-g and TAK-085 4-g groups than in the EPA-E 1.8-g group 10 165 1 year
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"Fish oil" (DHA+EPA) 7 171 1 year
EPA 6 167 1 year
"Fish oil" (DHA+EPA) Blood uric acid raised 5 165 1 year
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"Fish oil" (DHA+EPA) 4 171 1 year
EPA 4 167 1 year
"Fish oil" (DHA+EPA) g-Glutamyltransferase raised 7 165 1 year
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"Fish oil" (DHA+EPA) 3 171 1 year
EPA 3 167 1 year
"Fish oil" (DHA+EPA) Contusion 4 165 1 year
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"Fish oil" (DHA+EPA) 4 171 1 year
EPA 6 167 1 year
"Fish oil" (DHA+EPA) Fall 1 165 1 year
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"Fish oil" (DHA+EPA) 4 171 1 year
EPA 3 167 1 year
"Fish oil" (DHA+EPA) Road traffic accident 1 165 1 year
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"Fish oil" (DHA+EPA) 1 171 1 year
EPA 4 167 1 year
"Fish oil" (DHA+EPA) subarachnoid hemorrhage 1 severe in TAK-085 4-g group nd 165 1 year
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"Fish oil" (DHA+EPA) nd 171 1 year
EPA nd 167 1 year
"Fish oil" (DHA+EPA) pneumonia 1 severe in the EPA-E 1.8-g group nd 165 1 year
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"Fish oil" (DHA+EPA) nd 171 1 year
EPA nd 167 1 year
"Fish oil" (DHA+EPA) AEs that led to discontinuation of treatment 9 165 1 year
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"Fish oil" (DHA+EPA) 17 171 1 year
EPA 16 167 1 year
"Fish oil" (DHA+EPA) Serious AEs All except 2 (sleep apnea syndrome with TAK-085 2 g and subarachnoid hemorrhage with TAK-085 4 g) had resolved by the end of the study. 5 165 1 year
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"Fish oil" (DHA+EPA) 10 171 1 year
EPA 7 167 1 year
"Fish oil" (DHA+EPA) Bleeding overall no increased bleeding risk was seen with TAK-085 nd 165 1 year
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"Fish oil" (DHA+EPA) nd 171 1 year
EPA nd 167 1 year

Quality Dimensions
Dimension Value Notes Comments
Was the allocation sequence (RANDOMIZATION METHOD) adequately generated? Low
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Was ALLOCATION adequately concealed (prior to assignment)? High Open-label trial
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Were PARTICIPANTS adequately BLINDED? High Open-label trial
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Were OUTCOME ASSESSORS adequately BLINDED? High Open-label trial
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Incomplete outcome data (ATTRITION BIAS) due to amount, nature or handling of incomplete outcome data Low
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Is there evidence of SELECTIVE OUTCOME REPORTING bias (Yes/No)? Yes Subgroup analysis results not shown.
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INTENTION-TO-TREAT analysis? (Yes/No) Yes
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Group SIMILARITY AT BASELINE (**GENERAL**) Low
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Was there incomplete COMPLIANCE with interventions across groups? Low
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Group SIMILARITY AT BASELINE (**OMEGA-3**) Low
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Additional Bias: Bias due to problems not covered elsewhere in the table.
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If outcome assessor blinding risk of bias is different for different outcomes (eg, lipids vs. MI), choose HIGH risk of bias and describe in Notes
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If attrition risk of bias is different for different outcomes (eg, lipids vs. MI) or different time points (eg, 1 year vs. 5 years), choose HIGH risk of bias and describe in Notes
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Quality Rating
No quality rating data was found.