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| ID | Type | Description | Link |
|---|---|---|---|
| U01HG010225 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Human Genome Research Institute (NHGRI) | NIH |
| University of Florida | OTHER |
| Vanderbilt University Medical Center | OTHER |
| Indiana University |
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This study is comprised of three separate pharmacogenetic trials grouped into a single protocol due to similarities in the intervention, the hypotheses, and the trial design. The three trials are the Acute Pain Trial, the Chronic Pain Trial, and the Depression Trial. Participants can enroll in only one of the three trials. All three trials were registered on ClinicalTrials.gov under NCT04445792. In July 2023 each of the three treatment trials was registered under a separate NCT# and NCT04445792 was converted to a screening record per recent guidance on master protocol research programs (MPRPs). This record is specific to the Depression Trial within the ADOPT-PGx protocol.
The Depression Trial is a prospective, multicenter, two arm randomized pragmatic trial. Participants meeting eligibility criteria will be randomly assigned to either immediate pharmacogenetic testing and genotype-guided anti-depressant therapy (Intervention arm) or standard care with 6-month delayed pharmacogenetic testing (Control arm). The investigators will test the hypothesis that pharmacogenetic testing and genotype-guided anti-depressant therapy will reduce depression symptoms in participants who's body processes some anti-depressants faster or slower than normal.
Pain and depression are conditions that impact substantial proportions of the US population. Finding safe and effective drug therapies for both conditions is challenging. In the case of treatment for acute and chronic pain, the challenge is finding effective therapy while minimizing adverse effects or opioid addiction (and the ensuing consequences). For depression, there are few clinically relevant predictors of successful treatment leading to multiple trials of inadequate therapy for some patients. Both opioid and antidepressant prescriptions can be guided by pharmacogenetics (PGx) data based on existing guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC).
This study is designed to evaluate the impact of pharmacogenetic testing and genotype-guided pain or anti-depressant therapy on pain control or depression symptoms in a pragmatic setting.
The rationale for examining a genotype-guided approach to acute and chronic pain management is based on the importance of CYP2D6 for the bioactivation of tramadol, codeine, and hydrocodone and data from a pilot study supporting improved pain control in intermediate and poor CYP2D6 metabolizers in the genotype-guided arm who are taking these drugs at baseline. Similarly, the rationale for examining a genotype-guided approach to depression medication therapy is based on the demonstrated role of CYP2D6 in the bio inactivation and CYP2C19 oxidation of select, commonly used SSRIs. Secondly, data from industry sponsored trials support the hypothesis of improved depression symptom control in a genotype-guided arm.
Study objectives:
Determine if genotype-guided dosing or selection of antidepressants among participants with at least 3 months of depressive symptoms who require new or revised antidepressant therapy leads to improved control of depression, compared to usual care.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Depression - Immediate PGx Testing | Experimental | Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider |
|
| Depression - Delayed PGx Testing | Other | Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pharmacogenetic testing | Other | Genetic testing of CYP2D6 and CYP2C19 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Depression Symptom Control as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System) | The 8-item PROMIS Emotional Distress Depression 8b and PROMIS Pediatric Depression Symptoms 8a questionnaire assess the extent to which participants experience depression symptoms over the past 7 days using a 5-point Likert scale. The responses to the 8 questions are converted to T-scores using the health measures assessment center scoring service. Pediatric T-scores are cross walked to adult T-scores using the cross walk published in Reeve et al 2016. Cross walked T-scores range from 37.1 to 80.9, higher scores correspond with higher levels of depression symptoms. Changes in T-scores from baseline to 3-months range from -43.8 to 43.8. Negative values of change in T-score correspond to symptom improvement, 0 corresponds to no change in depression T-scores, and positive change in depression T-scores correspond to symptom worsening at 3 months compared to baseline. | Baseline to 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Depression Symptomatology as Measured by Patient Health Questionnaire (PHQ-8) | The 8-item PHQ-8 Questionnaire assesses severity of depression over the past 2 weeks using a 4-point scale indicating frequency of depression symptoms: not at all, several days, more than half the days, or nearly every day. The 8 questions are converted to a score ranging from 0 (not at all for all 8 symptoms) to 24 (nearly every day for all 8 symptoms). Changes in PHQ-8 scores from baseline to 3-months range from -24 to 24 and negative values of change in PHQ-8 correspond to improvement in depression at 3 months compared to baseline. |
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Inclusion Criteria:
Depression Trial
Exclusion Criteria
Trial-wide:
Depression Trial
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| Name | Affiliation | Role |
|---|---|---|
| Hrishikesh Chakraborty | Duke University | Study Director |
| Josh F. Peterson, MD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nemours Children's Health System | Wilmington | Delaware | 19803 | United States | ||
| University of Florida - Gainesville |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38860639 | Background | Hines LJ, Wilke RA, Myers R, Mathews CA, Liu M, Baye JF, Petry N, Cicali EJ, Duong BQ, Elwood E, Hulvershorn L, Nguyen K, Ramos M, Sadeghpour A, Wu RR, Williamson L, Wiisanen K, Voora D, Singh R, Blake KV, Murrough JW, Volpi S, Ginsburg GS, Horowitz CR, Orlando L, Chakraborty H, Dexter P, Johnson JA, Skaar TC, Cavallari LH, Van Driest SL, Peterson JF; IGNITE Pragmatic Trials Network. Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression. Clin Transl Sci. 2024 Jun;17(6):e13822. doi: 10.1111/cts.13822. | |
| 42090156 |
| Label | URL |
|---|---|
| Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression | View source |
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There were 1572 participants consented into the Depression trial. 112 consented participants were not randomized into the trial and were not assigned to a treatment arm. The 1460 randomized participants will be described moving forward.
This record is specific to the Depression Trial within the ADOPT PGx protocol. It only contains the participants consented to the Depression Trial.
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| ID | Title | Description |
|---|---|---|
| FG000 | Depression - Immediate PGx Testing | Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 23, 2024 |
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| OTHER |
| Icahn School of Medicine at Mount Sinai | OTHER |
Immediate vs. delayed pharmacogenetic testing and genotype-guided pain or depression therapy
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| Clinical decisions support | Other | Prescribing recommendations to the provider based on the pharmacogenetic testing results |
|
| Baseline to 3 months |
| Side Effect Burden | An 8-item survey was developed to assess the severity of 8 depression medication side effects, using a 4-point scale for rating severity of the side effect: none, mild, moderate, severe. The 8 questions are converted to a side effect burden score ranging from 0 (none for all 8 side effects) to 24 (severe for all 8 side effects). Higher values correspond with more side effects and with higher severity. | 3 months |
| Medication Non-Adherence as Measured by the Voils Medication Adherence Survey | Medication adherence level, non-adherent / adherent, derived from the Voils Medication Adherence survey. Reported as the number of participants who were non-adherent. | 3 months |
| Number of Participants With Depression Remission as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System) | Remission is defined as whether or not the summed raw responses to the PROMIS emotional distress depression survey is ≤ 16, corresponding to a participant respond "rarely" or "never" to most or all questions. | 6 months |
| Number of Participants With Depression Remission as Measured by the Patient Health Questionnaire (PHQ-8) | The PHQ-8 scores range from 0 to 24 and remission is defined as having a PHQ-8 score of ≤ 4. | 6 months |
| Number of Participants With 50% Reduction in Patient Health Questionnaire (PHQ-8) Score | 3 months |
| Number of Participants With Drug-gene Concordance | Concordance defined as agreement between the PGx phenotype and SSRI medications reported. | 3 months |
| Gainesville |
| Florida |
| 32610 |
| United States |
| Nemours Children's Health System | Jacksonville | Florida | 32207 | United States |
| University of Florida - Jacksonville | Jacksonville | Florida | 32209 | United States |
| Nemours Children's Health System | Orlando | Florida | 32827 | United States |
| Eskenazi Health | Indianapolis | Indiana | 46202 | United States |
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| The Institute for Family Health | New York | New York | 10035 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Sanford Health | Fargo | North Dakota | 58104 | United States |
| Meharry Medical College | Nashville | Tennessee | 37208 | United States |
| Nashville General Hospital | Nashville | Tennessee | 37208 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Derived |
| Blake KV, Hines LJ, Liu M, Myers RA, Baye JF, Cavanaugh KL, Duong BQ, Hulvershorn LA, Mathews CA, Murrough JW, Orlando LA, Petry NJ, Tillman EM, Sadeghpour A, Voora D, Block SL, Cicali EJ, Clermont S, Elwood EN, Harris EC, Nguyen KA, Ramos MA, Rosenman MB, Shroff N, Shuman S, Wyatt C, Horowitz CR, Volpi S, Singh R, Rider RA, Chakraborty H, Dexter PR, Johnson JA, Skaar TC, Cavallari LH, Peterson JF; IGNITE Pragmatic Trials Network. Genotype-Guided Antidepressant Prescribing for Patients With Depression: A Randomized Clinical Trial. JAMA Netw Open. 2026 May 1;9(5):e2610609. doi: 10.1001/jamanetworkopen.2026.10609. |
| FG001 |
| Depression - Delayed PGx Testing |
Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 |
| COMPLETED |
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| NOT COMPLETED |
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ITT refers to the Intent To Treat population, while mITT, a subset of ITT, refers to the modified Intent To Treat population. The mITT population is the primary analytical population for the Depression Trial and includes participants who have a CYP2D6 PM, UM or NM-UM phenotype or a CYP2C19 PM, RM, or UM phenotype.
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| ID | Title | Description |
|---|---|---|
| BG000 | Depression - Immediate PGx Testing | Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider |
| BG001 | Depression - Delayed PGx Testing | Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Intent to Treat Population | Count of Participants | Participants |
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| Age, Categorical | Modified Intent to Treat Population | Count of Participants | Participants |
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| Sex: Female, Male | Intent to Treat Population | Count of Participants | Participants |
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| Sex: Female, Male | Modified Intent to Treat Population | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Intent to Treat Population | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Modified Intent to Treat Population | Count of Participants | Participants |
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| Race (NIH/OMB) | Intent to Treat Population | Count of Participants | Participants |
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| Race (NIH/OMB) | Modified Intent to Treat Population | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| 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 | Change in Depression Symptom Control as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System) | The 8-item PROMIS Emotional Distress Depression 8b and PROMIS Pediatric Depression Symptoms 8a questionnaire assess the extent to which participants experience depression symptoms over the past 7 days using a 5-point Likert scale. The responses to the 8 questions are converted to T-scores using the health measures assessment center scoring service. Pediatric T-scores are cross walked to adult T-scores using the cross walk published in Reeve et al 2016. Cross walked T-scores range from 37.1 to 80.9, higher scores correspond with higher levels of depression symptoms. Changes in T-scores from baseline to 3-months range from -43.8 to 43.8. Negative values of change in T-score correspond to symptom improvement, 0 corresponds to no change in depression T-scores, and positive change in depression T-scores correspond to symptom worsening at 3 months compared to baseline. | Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with completed PROMIS Depression surveys at both baseline and 3 months are included. Participants with missing PROMIS depression surveys at either baseline or 3-months are excluded. | Posted | Mean | Standard Deviation | T-score | Baseline to 3 months |
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| Secondary | Change in Depression Symptomatology as Measured by Patient Health Questionnaire (PHQ-8) | The 8-item PHQ-8 Questionnaire assesses severity of depression over the past 2 weeks using a 4-point scale indicating frequency of depression symptoms: not at all, several days, more than half the days, or nearly every day. The 8 questions are converted to a score ranging from 0 (not at all for all 8 symptoms) to 24 (nearly every day for all 8 symptoms). Changes in PHQ-8 scores from baseline to 3-months range from -24 to 24 and negative values of change in PHQ-8 correspond to improvement in depression at 3 months compared to baseline. | Modified ITT population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with completed PHQ-8 surveys at both baseline and 3 months are included. Participants with missing PHQ-8 surveys at either baseline or 3-months are excluded. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 3 months |
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| Secondary | Side Effect Burden | An 8-item survey was developed to assess the severity of 8 depression medication side effects, using a 4-point scale for rating severity of the side effect: none, mild, moderate, severe. The 8 questions are converted to a side effect burden score ranging from 0 (none for all 8 side effects) to 24 (severe for all 8 side effects). Higher values correspond with more side effects and with higher severity. | Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with completed medication side effect surveys at 3 months are included. Participants with missing side effect surveys at 3-months are excluded. | Posted | Mean | Standard Deviation | score on a scale | 3 months |
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| Secondary | Medication Non-Adherence as Measured by the Voils Medication Adherence Survey | Medication adherence level, non-adherent / adherent, derived from the Voils Medication Adherence survey. Reported as the number of participants who were non-adherent. | Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with 2 or more Voils survey questions completed at 3 months are included. Participants with fewer than 2 completed Voils survey questions are excluded. | Posted | Count of Participants | Participants | 3 months |
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| Secondary | Number of Participants With Depression Remission as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System) | Remission is defined as whether or not the summed raw responses to the PROMIS emotional distress depression survey is ≤ 16, corresponding to a participant respond "rarely" or "never" to most or all questions. | Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with a completed PROMIS depression survey at 6 months are include. Participants with an incomplete PROMIS depression survey are excluded. | Posted | Count of Participants | Participants | 6 months |
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| Secondary | Number of Participants With Depression Remission as Measured by the Patient Health Questionnaire (PHQ-8) | The PHQ-8 scores range from 0 to 24 and remission is defined as having a PHQ-8 score of ≤ 4. | Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with a completed PHQ-8 survey at 6 months are include. Participants with an incomplete PHQ-8 survey are excluded. | Posted | Count of Participants | Participants | 6 months |
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| Secondary | Number of Participants With 50% Reduction in Patient Health Questionnaire (PHQ-8) Score | Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with a completed PHQ-8 survey at baseline and 3 months are included. Participants with an incomplete PHQ-8 survey at either baseline or 3 months are excluded. | Posted | Count of Participants | Participants | 3 months |
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| Secondary | Number of Participants With Drug-gene Concordance | Concordance defined as agreement between the PGx phenotype and SSRI medications reported. | Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with a completed medication review at 3 months are included. Participants without a medication review at 3 months are excluded. | Posted | Count of Participants | Participants | 3 months |
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Up to 6 months
Per the study protocol, only Adverse Device Effect (ADE) events suspected to be related to the specimen collection, laboratory assay genotyping results, and phenoconversion recommendations from the Best Practice Alerts (BPAs)/Consult notes were reported to the IRB. Reportable ADEs or unanticipated Adverse Device Effect (UADEs) events including unanticipated study related deaths will be collected in the study database per IRB reporting policies. Medication side effects were not collected.
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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 | Depression - Immediate PGx Testing | Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider | 1 | 727 | 0 | 727 | 0 | 727 |
| EG001 | Depression - Delayed PGx Testing | Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period | 2 | 733 | 0 | 733 | 0 | 733 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hrishikesh Chakraborty, PhD | Duke University | 919-668-1238 | hrishikesh.chakraborty@duke.edu |
| Apr 25, 2025 |
| Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 14, 2023 | Nov 14, 2023 | ICF_000.pdf |
| ID | Term |
|---|---|
| D003863 | Depression |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D000071185 | Pharmacogenomic Testing |
| ID | Term |
|---|---|
| D005820 | Genetic Testing |
| 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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| Between 18 and 65 years |
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| >=65 years |
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