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| ID | Type | Description | Link |
|---|---|---|---|
| Pro00045542 | Other Identifier | DUHS IRB |
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| Name | Class |
|---|---|
| David Grant U.S. Air Force Medical Center | FED |
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The purpose of this study is to examine if using genetics can improve statin adherence in patients who should be taking statins but are not because of prior side effects. This study will assist physicians/providers in making a personalized health care plan for prevention of cardiovascular disease.
Hydroxy-methylglutaryl-coenzyme A (HMG Co-A) reductase inhibitors ("statins") are commonly prescribed to lower low density lipoprotein cholesterol (LDLc) and to prevent cardiovascular disease (CVD), a leading cause of morbidity and mortality. Long-term adherence to statins in the primary care environment is challenging; consequences of statin non-adherence include higher LDLc levels, hospitalizations, costs, and death due to CVD.
Medication non-adherence is complex and multifactorial and can be associated with a number of factors including medication cost, complexity of medication regimen, poor provider-patient relationship / communication, and adverse side effects. For statins, side effects such as muscle aches, cramping, and pain (referred to broadly as statin-related myopathy) are a frequent cause of non-adherence. These symptoms are non-specific and are frequent reasons for stopping statin therapy, due to patient or provider concern about the possibility of statin-related myopathy. Many patients may be needlessly deprived of the cardiovascular benefits of long-term statin use.
A genetic risk factor for statin myopathy and subsequent non-adherence has recently been identified. In a genome-wide association study, a genetic variant (named SLCO1B1*5) was a main contributor of statin myopathy. It was demonstrated that the SLCO1B1*5 variant is not only a predictor of myopathy, but also of premature statin discontinuation. The risk with the *5 allele is statin specific: greatest with simvastatin and atorvastatin use, the least with pravastatin or rosuvastatin. Therefore, the SLCO1B1*5 variant is common, can predict myopathy, subsequent non-adherence, and due to its statin-specific effects creates a novel research paradigm for personalizing statins to an individual's genetic profile. Carriers of the SLCO1B1*5 variant may do best on rosuvastatin, pravastatin, or fluvastatin whereas non-carriers may be treated with any statin.
The objective of this study is to conduct a randomized trial comparing two strategies:
The overall hypothesis is that genetically guided statin therapy will lead to greater statin adherence and lower LDLc when compared to a non-guided strategy. The design of this trial will randomize primary care patients within Duke University Health System (DUHS) and travis Air Force Base (TAFB) clinics that are nonadherent to statins due to prior side-effects in an unblinded, 1:1 fashion, stratified by SLCO1B1*5 genotype.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Genotype results plus usual care | Experimental | SLCO1B1*5 allele testing, results reported at randomization: genetic testing for SLCO1B1*5 allele and reporting of results to patient and provider at randomization. |
|
| Usual care only | Active Comparator | SLCO1B1*5 allele testing, results reported at end of study: genetic testing for SLCO1B1*5 allele and reporting of results to patient and provider at end of study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SLCO1B1*5 allele testing, results reported at randomization | Genetic | Genetic testing for SLCO1B1*5 allele and reporting of results to patient and provider at randomization |
|
| Measure | Description | Time Frame |
|---|---|---|
| Morisky Medication Adherence Scale (MMAS) Score | The Morisky Medication Adherence Scale (MMAS) is a self-reported measure of adherence, collected at baseline for general medication and at 3 and 8 months of followup for statin specific adherence. The eight-item MMAS survey will be used. This is a modified version of the original four-item MMAS capturing further aspects of adherence behavior. The survey includes 8 yes/no items that are summed to create an overall adherence score ranging from of 0 to 8, with higher scores indicating better adherence. The primary hypothesis is that the genetically guided statin therapy leads to greater adherence of statin therapy, corresponding to a higher MMAS score. | 3 months and 8 months |
| Measure | Description | Time Frame |
|---|---|---|
| Low Density Lipoprotein Cholesterol (LDLc) at Baseline, Month 3 and Month 8 | The continuous outcomes LDLc will be modeled as a linear regression with arm and baseline LDL as predictors. | Baseline, Month 3, Month 8 |
| Medication Possession Ratio (MPR) From Baseline to Last Patient Follow-up |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Deepak Voora, MD | Duke University | Principal Investigator |
| Henry Lau, MD | David Grant US Air Force Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| David Grant US Air Force Medical Center | Travis Air Force Base | California | 94535 | United States | ||
| Duke University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30354330 | Derived | Peyser B, Perry EP, Singh K, Gill RD, Mehan MR, Haga SB, Musty MD, Milazzo NA, Savard D, Li YJ, Trujilio G, Voora D. Effects of Delivering SLCO1B1 Pharmacogenetic Information in Randomized Trial and Observational Settings. Circ Genom Precis Med. 2018 Sep;11(9):e002228. doi: 10.1161/CIRCGEN.118.002228. | |
| 24918167 | Derived |
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Eight participants that signed a consent either withdrew consent, were lost-to follow up, or were screen-failures and thus were not randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Genotype Results Plus Usual Care |
Reporting for SLCO1B1*5 allele at randomization: Reporting of genetic test results to patient and provider at randomization Genetic testing for SLCO1B1*5 allele: Blood test for SLCO1B1*5 allele |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| SLCO1B1*5 allele testing, results reported at end of study | Genetic | Genetic testing for SLCO1B1*5 allele and reporting of results to patient and provider at end of study |
|
| Genetic testing for SLCO1B1*5 allele | Genetic | Blood test for SLCO1B1*5 allele |
|
Medication possession ratio will be calculated based on number of statin medication refills over time from randomization to end of follow up. MPR is calculated as follows: 1.Sum of the days' supply of all statin medications is the sum of the number of pills dispensed for each statin prescription during follow up (taken from 3-month, 4-month and 8-month statin utilization review) 2.Sum of the days of follow up = date of 8-month follow up survey - date of randomization 3.MPR = #1/#2 MPR will be modeled as a linear regression with arm, genotype, and site as predictors. |
| Baseline to Last patient follow-up in study (3 months or 8 months) |
| Number of Participants Reporting New Statin Prescriptions | The number of new prescriptions is binary and will be modeled with logistic regression with arm, genotype, and site as predictors. Any variables imbalanced between arms will also be included as covariates. | Baseline, Month 3, Month 8 |
| Brief Pain Inventory (BPI) Score - Pain Severity at Month 3 and Month 8 | Brief Pain Inventory data will be taken from 3 and 8-month follow up Patient Surveys. Pain severity and pain interference will be compared between groups. Both of these measures will be modeled as a linear regression with arm, genotype, and site as predictors. Transformations of the response may be explored depending on the distribution of the regression residuals. Baseline pain scores will also be included as a covariate to account for baseline variability. Scores range from 0-10. Higher scores indicate higher pain severity. | Month 3 and Month 8 |
| Brief Pain Inventory (BPI) Score - Pain Interference at Month 3 and Month 8 | Brief Pain Inventory data will be taken from 3 and 8-month follow up Patient Surveys. -Pain severity and pain interference will be compared between groups -Both of these measures will be modeled as a linear regression with arm as predictor. Baseline pain scores will also be included as a covariate to account for baseline variability. Scores range from 0-10. Higher scores indicate higher pain interference with daily activities. | Month 3 and Month 8 |
| Change in Short Form -12 Item (SF-12) Health Survey - Physical Component (PC) | Month 3 and Month 8 SF12 scores for mental and physical health will be compared. Both of these measures will be modeled as a linear regression with arm as predictor. Baseline SF-12 scores will also be included as a covariate to account for baseline variability. Ranges from 0 to 100, where a zero score indicates the lowest level of physical health measured by the scales and 100 indicates the highest level of physical health | Baseline, Month 3, Month 8 |
| Change in Short Form -12 Item (SF-12) Health Survey - Mental Component (MC) | Month 3 and Month 8 SF12 scores for mental and physical health will be compared. Both of these measures will be modeled as a linear regression with arm as predictor. Baseline SF-12 scores will also be included as a covariate to account for baseline variability. Ranges from 0 to 100, where a zero score indicates the lowest level of mental health measured by the scales and 100 indicates the highest level of mental health. | Baseline, Month 3, Month 8 |
| Physical Activity Scale Score | Activity levels will be compared at the end of 8-months. Activity levels are defined by a five-level ordinal variable (0-4; higher level corresponding to higher activity). which was calculated based on survey answers. An ordinal logistic regression model will be used with arm as predictor. The assumption of proportional odds will be checked, and if it is not met, a multinomial regression model will be used. -Baseline physical activity will also be included as a covariate to account for baseline variability. Scale score (0-4): 0 - Inactivity, 1 - Ligh-intensity activity, 2 - moderate-intensity activity, 3 - Hard-intensity activity, 5 - very hard-intensity activity | Baseline and Month 8 |
| Beliefs About Medications (BMQ) Score at Baseline, Month 3 and Month 8 |
Higher score corresponds to higher thought necessity and higher thought concerns about taking the medication. The higher the necessity score, the more the patient believed statins necessary for their health. The higher the concerns score, the more the patient was concerned about taking stains (side effects). | Baseline, Month 3, Month 8 |
| Durham |
| North Carolina |
| 27710 |
| United States |
| Ramsey LB, Johnson SG, Caudle KE, Haidar CE, Voora D, Wilke RA, Maxwell WD, McLeod HL, Krauss RM, Roden DM, Feng Q, Cooper-DeHoff RM, Gong L, Klein TE, Wadelius M, Niemi M. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014 Oct;96(4):423-8. doi: 10.1038/clpt.2014.125. Epub 2014 Jun 11. |
| Usual Care Only |
Reporting for SLCO1B1*5 allele at the end: Usual care recommendations provided to patient and provider at randomization. Genotyping results provided at the end of study. Genetic testing for SLCO1B1*5 allele: Blood test for SLCO1B1*5 allele |
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Genotype Results Plus Usual Care |
Reporting for SLCO1B1*5 allele at randomization: Reporting of genetic test results to patient and provider at randomization Genetic testing for SLCO1B1*5 allele: Blood test for SLCO1B1*5 allele |
| BG001 | Usual Care Only |
Reporting for SLCO1B1*5 allele at the end: Usual care recommendations provided to patient and provider at randomization. Genotyping results provided at the end of study. Genetic testing for SLCO1B1*5 allele: Blood test for SLCO1B1*5 allele |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Morisky Medication Adherence Scale (MMAS) Score | The Morisky Medication Adherence Scale (MMAS) is a self-reported measure of adherence, collected at baseline for general medication and at 3 and 8 months of followup for statin specific adherence. The eight-item MMAS survey will be used. This is a modified version of the original four-item MMAS capturing further aspects of adherence behavior. The survey includes 8 yes/no items that are summed to create an overall adherence score ranging from of 0 to 8, with higher scores indicating better adherence. The primary hypothesis is that the genetically guided statin therapy leads to greater adherence of statin therapy, corresponding to a higher MMAS score. | Only participants who re-initiated statin use were eligible to do statin specific MMAS and included in the analysis. | Posted | Mean | Standard Deviation | units on a scale | 3 months and 8 months |
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| Secondary | Low Density Lipoprotein Cholesterol (LDLc) at Baseline, Month 3 and Month 8 | The continuous outcomes LDLc will be modeled as a linear regression with arm and baseline LDL as predictors. | All subjects with available data were included in the analysis. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Month 3, Month 8 |
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| Secondary | Medication Possession Ratio (MPR) From Baseline to Last Patient Follow-up | Medication possession ratio will be calculated based on number of statin medication refills over time from randomization to end of follow up. MPR is calculated as follows: 1.Sum of the days' supply of all statin medications is the sum of the number of pills dispensed for each statin prescription during follow up (taken from 3-month, 4-month and 8-month statin utilization review) 2.Sum of the days of follow up = date of 8-month follow up survey - date of randomization 3.MPR = #1/#2 MPR will be modeled as a linear regression with arm, genotype, and site as predictors. | Only subjects who re-initiated statin medication and reported statin medication refills were included in the analysis. | Posted | Mean | Standard Deviation | ratio | Baseline to Last patient follow-up in study (3 months or 8 months) |
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| Secondary | Number of Participants Reporting New Statin Prescriptions | The number of new prescriptions is binary and will be modeled with logistic regression with arm, genotype, and site as predictors. Any variables imbalanced between arms will also be included as covariates. | Only subjects reporting new prescriptions were included in the analysis. | Posted | Count of Participants | Participants | Baseline, Month 3, Month 8 |
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| Secondary | Brief Pain Inventory (BPI) Score - Pain Severity at Month 3 and Month 8 | Brief Pain Inventory data will be taken from 3 and 8-month follow up Patient Surveys. Pain severity and pain interference will be compared between groups. Both of these measures will be modeled as a linear regression with arm, genotype, and site as predictors. Transformations of the response may be explored depending on the distribution of the regression residuals. Baseline pain scores will also be included as a covariate to account for baseline variability. Scores range from 0-10. Higher scores indicate higher pain severity. | Only subjects that completed the Brief Pain Inventory surveys were included in the analysis. | Posted | Mean | Standard Deviation | units on a scale | Month 3 and Month 8 |
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| Secondary | Brief Pain Inventory (BPI) Score - Pain Interference at Month 3 and Month 8 | Brief Pain Inventory data will be taken from 3 and 8-month follow up Patient Surveys. -Pain severity and pain interference will be compared between groups -Both of these measures will be modeled as a linear regression with arm as predictor. Baseline pain scores will also be included as a covariate to account for baseline variability. Scores range from 0-10. Higher scores indicate higher pain interference with daily activities. | Only subjects that completed the Brief Pain Inventory surveys were included in the analysis. | Posted | Mean | Standard Deviation | units on a scale | Month 3 and Month 8 |
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| Secondary | Change in Short Form -12 Item (SF-12) Health Survey - Physical Component (PC) | Month 3 and Month 8 SF12 scores for mental and physical health will be compared. Both of these measures will be modeled as a linear regression with arm as predictor. Baseline SF-12 scores will also be included as a covariate to account for baseline variability. Ranges from 0 to 100, where a zero score indicates the lowest level of physical health measured by the scales and 100 indicates the highest level of physical health | Only subjects that completed the SF-12 Health Survey were included in the analysis. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Month 3, Month 8 |
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| Secondary | Change in Short Form -12 Item (SF-12) Health Survey - Mental Component (MC) | Month 3 and Month 8 SF12 scores for mental and physical health will be compared. Both of these measures will be modeled as a linear regression with arm as predictor. Baseline SF-12 scores will also be included as a covariate to account for baseline variability. Ranges from 0 to 100, where a zero score indicates the lowest level of mental health measured by the scales and 100 indicates the highest level of mental health. | Only subjects that completed the SF-12 Health Survey were included in the analysis. | Posted | Mean | Standard Deviation | units on a scale 0 to 100 | Baseline, Month 3, Month 8 |
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| Secondary | Physical Activity Scale Score | Activity levels will be compared at the end of 8-months. Activity levels are defined by a five-level ordinal variable (0-4; higher level corresponding to higher activity). which was calculated based on survey answers. An ordinal logistic regression model will be used with arm as predictor. The assumption of proportional odds will be checked, and if it is not met, a multinomial regression model will be used. -Baseline physical activity will also be included as a covariate to account for baseline variability. Scale score (0-4): 0 - Inactivity, 1 - Ligh-intensity activity, 2 - moderate-intensity activity, 3 - Hard-intensity activity, 5 - very hard-intensity activity | Only subjects that completed the Physical Activity survey were included in the analysis | Posted | Mean | Standard Deviation | units on a scale | Baseline and Month 8 |
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| Secondary | Beliefs About Medications (BMQ) Score at Baseline, Month 3 and Month 8 |
Higher score corresponds to higher thought necessity and higher thought concerns about taking the medication. The higher the necessity score, the more the patient believed statins necessary for their health. The higher the concerns score, the more the patient was concerned about taking stains (side effects). | Only subjects that completed the Beliefs About Medications questionnaire were included in the analysis. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Month 3, Month 8 |
|
Baseline through Month 8
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Genotype Results Plus Usual Care |
Reporting for SLCO1B1*5 allele at randomization: Reporting of genetic test results to patient and provider at randomization Genetic testing for SLCO1B1*5 allele: Blood test for SLCO1B1*5 allele | 1 | 83 | 4 | 83 | 1 | 83 |
| EG001 | Usual Care Only |
Reporting for SLCO1B1*5 allele at the end: Usual care recommendations provided to patient and provider at randomization. Genotyping results provided at the end of study. Genetic testing for SLCO1B1*5 allele: Blood test for SLCO1B1*5 allele | 0 | 76 | 6 | 76 | 0 | 76 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Liver function testing abnormality | Hepatobiliary disorders | Systematic Assessment |
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| Chest Pain | Cardiac disorders | Systematic Assessment |
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| Hospitalization for bleeding | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Respiratory Distress | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Nausea, vomiting, abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Suspected MRSA bacteremia | Infections and infestations | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | Systematic Assessment |
| ||
| Renal Failure | Renal and urinary disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stroke | Vascular disorders | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Deepak Voora | Duke University | 919-668-1755 | Deepak.vorra@duke.edu |
| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| D055118 | Medication Adherence |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010349 | Patient Compliance |
| D010342 | Patient Acceptance of Health Care |
| D000074822 | Treatment Adherence and Compliance |
| D015438 | Health Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D005820 | Genetic Testing |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |
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| Male |
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| Black/African American |
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| Other |
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| MMAS Score 8 Months |
|
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| 0.57 |
| Slope |
| -0.2468 |
| Standard Error of the Mean |
| 0.4315 |
| 2-Sided |
| Equivalence |
Month 8 |
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| Units | Counts |
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