Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care

NCT ID: NCT01431326

Last Updated: 2023-09-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

3520 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-11-30

Study Completion Date

2019-11-30

Brief Summary

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Understudied drugs will be administered to children per standard of care as prescribed by their treating caregiver and only biological sample collection during the time of drug administration will be involved. A total of approximately 7000 children aged \<21 years who are receiving these drugs for standard of care will be enrolled and will be followed for up a maximum of 90 days. The goal of this study is to characterize the pharmacokinetics of understudied drugs for which specific dosing recommendations and safety data are lacking. The prescribing of drugs to children will not be part of this protocol. Taking advantage of procedures done as part of routine medical care (i.e. blood draws) this study will serve as a tool to better understand drug exposure in children receiving these drugs per standard of care. The data collected through this initiative will also provide valuable pharmacokinetic and dosing information of drugs in different pediatric age groups as well as special pediatric populations (i.e. obese).

Detailed Description

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The purpose of this study is to characterize the PK ( Pharmacokinetics) of understudied drugs administered to children per standard of care as prescribed by their treating caregiver. This will be accomplished by the collection of biological samples during the time of drug administration per standard of care as prescribed by the caregiver. The prescribing of drugs to children will not be part of this protocol.

Aim #1: Evaluate the PK of understudied drugs currently being administered to children.

Hypothesis #1: The PK of understudied drugs in children will differ from adults and within children according to pediatric age groups or special population.

Aim #2: Explore the pharmacodynamics (PD) of understudied drugs currently being administered to children.

Hypothesis #2: The PD of targeted drugs in children will differ from adults.

Aim #3: Evaluate the influence of genetic factors, metabolic and protein profiles on therapeutic exposure.

Hypothesis #3: Genetic polymorphisms in drug metabolizing enzymes and metabolic and proteomic profiles will impact drug exposure in children.

Conditions

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Adenovirus Anesthesia Anxiety Anxiolysis Autism Autistic Disorder Bacterial Meningitis Bacterial Septicemia Benzodiazepine Bipolar Disorder Bone and Joint Infections Central Nervous System Infections Convulsions Cytomegalovirus Retinitis Early-onset Schizophrenia Spectrum Disorders Epilepsy General Anesthesia Gynecologic Infections Herpes Simplex Virus Infantile Hemangioma Infection Inflammation Inflammatory Conditions Intra-abdominal Infections Lower Respiratory Tract Infections Migraines Pain Pneumonia Schizophrenia Sedation Seizures Skeletal Muscle Spasms Skin and Skin-structure Infections Treatment-resistant Schizophrenia Urinary Tract Infections Withdrawal Sepsis Gram-negative Infection Bradycardia Cardiac Arrest Cardiac Arrhythmia Staphylococcal Infections Nosocomial Pneumonia Neuromuscular Blockade Methicillin Resistant Staphylococcus Aureus Endocarditis Neutropenia Headache Fibrinolytic Bleeding Pulmonary Arterial Hypertension CMV Retinitis Hypertension Chronic Kidney Diseases Hyperaldosteronism Hypokalemia Heart Failure Hemophilia Heavy Menstrual Bleeding Insomnia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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The POPS study is collecting PK data on children prescribed the following drugs of interest per standard of care:

Intervention Type DRUG

Other Intervention Names

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cidofovir ciprofloxacin methylprednisolone tobramycin alfentanil clozapine haloperidol lurasidone molindone pentobarbital warfarin (oral) ziprasidone amikacin cefepime nafcillin piperacillin-tazobactam rocuronium vecuronium vancomycin aminocaproic acid bosentan fosfomycin labetalol nifedipine oxycodone sevelamer carbonate spironolactone tranexamic acid zolpidem

Eligibility Criteria

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Inclusion Criteria

* 1\) Children (\< 21 years of age) who are receiving understudied drugs of interest per standard of care as prescribed by their treating caregiver

Exclusion Criteria

* 1\) Failure to obtain consent/assent (as indicated)
* 2\) Known pregnancy as determined via interview or testing if available.
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role collaborator

Daniel Benjamin

OTHER

Sponsor Role lead

Responsible Party

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Daniel Benjamin

Professor of Pediatrics

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Chi Hornik, PharmD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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Alaska Native Medical Center

Anchorage, Alaska, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

University of California at San Diego Medical Center

La Jolla, California, United States

Site Status

Axis Clinical Trials

Los Angeles, California, United States

Site Status

University of California, Los Angeles Medical Center

Los Angeles, California, United States

Site Status

The Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Yale New Haven Children's Hospital

New Haven, Connecticut, United States

Site Status

Alfred I. DuPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Florida Jacksonville Shands Medical Center

Jacksonville, Florida, United States

Site Status

Kapiolani Womens and Childrens Medical Center

Honolulu, Hawaii, United States

Site Status

Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Riley Hospital for Children at Indiana University

Indianapolis, Indiana, United States

Site Status

University of Kansas Medical Center

Fairway, Kansas, United States

Site Status

Children's Mercy Hospital and Clinics

Kansas City, Kansas, United States

Site Status

Wesley Medical Center

Wichita, Kansas, United States

Site Status

Norton Children's Hospital

Louisville, Kentucky, United States

Site Status

Tulane University Health Science Center

New Orleans, Louisiana, United States

Site Status

Ochsner Baptist Clinical Trials Unit

New Orleans, Louisiana, United States

Site Status

University of Maryland

Baltimore, Maryland, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

University of Montana

Missoula, Montana, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

University of New Mexico, Health Sciences Center

Albuquerque, New Mexico, United States

Site Status

UNC Hospital Neonatal-Perinatal Medicine

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center (PICU / NICU)

Durham, North Carolina, United States

Site Status

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Akron Children's Hospital

Cleveland, Ohio, United States

Site Status

Board of Regents of the University of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of South Carolina

Columbia, South Carolina, United States

Site Status

University of Utah Hospitals and Clinics

Salt Lake City, Utah, United States

Site Status

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status

University of Virginia Children's Hospital

Charlottesville, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

West Virginia University Hospital

Morgantown, West Virginia, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Manitoba Institute of Child Health

Winnipeg, Manitoba, Canada

Site Status

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Hospital Sainte-Justine

Montreal, Quebec, Canada

Site Status

Assaf Harofeh Medical Center

Zerifin, Tel Aviv, Israel

Site Status

Schneider Children's Medical Center of Israel

Petah Tikva, , Israel

Site Status

KK Women's and Children's Hospital Pte Ltd

Singapore, , Singapore

Site Status

Southampton General Hospital

Southampton, Hampshire, United Kingdom

Site Status

Alder Hey Children's Hospital

Liverpool, Merseyside, United Kingdom

Site Status

Countries

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United States Canada Israel Singapore United Kingdom

References

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Tremoulet A, Le J, Poindexter B, Sullivan JE, Laughon M, Delmore P, Salgado A, Ian-U Chong S, Melloni C, Gao J, Benjamin DK Jr, Capparelli EV, Cohen-Wolkowiez M; Administrative Core Committee of the Best Pharmaceuticals for Children Act-Pediatric Trials Network. Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design. Antimicrob Agents Chemother. 2014 Jun;58(6):3013-20. doi: 10.1128/AAC.02374-13. Epub 2014 Mar 10.

Reference Type RESULT
PMID: 24614374 (View on PubMed)

Gonzalez D, Melloni C, Yogev R, Poindexter BB, Mendley SR, Delmore P, Sullivan JE, Autmizguine J, Lewandowski A, Harper B, Watt KM, Lewis KC, Capparelli EV, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act - Pediatric Trials Network Administrative Core Committee. Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents. Clin Pharmacol Ther. 2014 Oct;96(4):429-37. doi: 10.1038/clpt.2014.134. Epub 2014 Jun 20.

Reference Type RESULT
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Gonzalez D, Melloni C, Poindexter BB, Yogev R, Atz AM, Sullivan JE, Mendley SR, Delmore P, Delinsky A, Zimmerman K, Lewandowski A, Harper B, Lewis KC, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act--Pediatric Trials Network Administrative Core Committee. Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots. Bioanalysis. 2015;7(9):1137-49. doi: 10.4155/bio.15.38.

Reference Type RESULT
PMID: 26039810 (View on PubMed)

Hornik CP, Benjamin DK Jr, Smith PB, Pencina MJ, Tremoulet AH, Capparelli EV, Ericson JE, Clark RH, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act-Pediatric Trials Network. Electronic Health Records and Pharmacokinetic Modeling to Assess the Relationship between Ampicillin Exposure and Seizure Risk in Neonates. J Pediatr. 2016 Nov;178:125-129.e1. doi: 10.1016/j.jpeds.2016.07.011. Epub 2016 Aug 10.

Reference Type RESULT
PMID: 27522443 (View on PubMed)

Gonzalez D, Delmore P, Bloom BT, Cotten CM, Poindexter BB, McGowan E, Shattuck K, Bradford KK, Smith PB, Cohen-Wolkowiez M, Morris M, Yin W, Benjamin DK Jr, Laughon MM. Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2888-94. doi: 10.1128/AAC.03086-15. Print 2016 May.

Reference Type RESULT
PMID: 26926644 (View on PubMed)

Autmizguine J, Melloni C, Hornik CP, Dallefeld S, Harper B, Yogev R, Sullivan JE, Atz AM, Al-Uzri A, Mendley S, Poindexter B, Mitchell J, Lewandowski A, Delmore P, Cohen-Wolkowiez M, Gonzalez D; the Pediatric Trials Network Steering Committee. Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01813-17. doi: 10.1128/AAC.01813-17. Print 2018 Jan.

Reference Type RESULT
PMID: 29084742 (View on PubMed)

Le J, Poindexter B, Sullivan JE, Laughon M, Delmore P, Blackford M, Yogev R, James LP, Melloni C, Harper B, Mitchell J, Benjamin DK Jr, Boakye-Agyeman F, Cohen-Wolkowiez M. Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates. Ther Drug Monit. 2018 Feb;40(1):103-108. doi: 10.1097/FTD.0000000000000466.

Reference Type RESULT
PMID: 29271816 (View on PubMed)

Dallefeld SH, Atz AM, Yogev R, Sullivan JE, Al-Uzri A, Mendley SR, Laughon M, Hornik CP, Melloni C, Harper B, Lewandowski A, Mitchell J, Wu H, Green TP, Cohen-Wolkowiez M. A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):419-430. doi: 10.1007/s10928-018-9576-y. Epub 2018 Feb 12.

Reference Type RESULT
PMID: 29435949 (View on PubMed)

Hornik CP, Gonzalez D, van den Anker J, Atz AM, Yogev R, Poindexter BB, Ng KC, Delmore P, Harper BL, Melloni C, Lewandowski A, Gelber C, Cohen-Wolkowiez M, Lee JH; Pediatric Trial Network Steering Committee. Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children. J Clin Pharmacol. 2018 Aug;58(8):1092-1104. doi: 10.1002/jcph.1116. Epub 2018 Apr 20.

Reference Type RESULT
PMID: 29677389 (View on PubMed)

Drolet BA, Boakye-Agyeman F, Harper B, Holland K, Lewandowski A, Stefanko N, Melloni C; Pediatric Trials Network Steering Committee (See Acknowledgments for a listing of committee members.). Systemic timolol exposure following topical application to infantile hemangiomas. J Am Acad Dermatol. 2020 Mar;82(3):733-736. doi: 10.1016/j.jaad.2019.02.029. Epub 2019 Feb 18. No abstract available.

Reference Type RESULT
PMID: 30790601 (View on PubMed)

Hornik CP, Yogev R, Mourani PM, Watt KM, Sullivan JE, Atz AM, Speicher D, Al-Uzri A, Adu-Darko M, Payne EH, Gelber CE, Lin S, Harper B, Melloni C, Cohen-Wolkowiez M, Gonzalez D; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents. J Clin Pharmacol. 2019 Dec;59(12):1606-1619. doi: 10.1002/jcph.1499. Epub 2019 Jul 17.

Reference Type RESULT
PMID: 31317556 (View on PubMed)

Maharaj AR, Gonzalez D, Cohen-Wolkowiez M, Hornik CP, Edginton AN. Improving Pediatric Protein Binding Estimates: An Evaluation of alpha1-Acid Glycoprotein Maturation in Healthy and Infected Subjects. Clin Pharmacokinet. 2018 May;57(5):577-589. doi: 10.1007/s40262-017-0576-7.

Reference Type RESULT
PMID: 28779462 (View on PubMed)

Maharaj AR, Wu H, Zimmerman KO, Speicher DG, Sullivan JE, Watt K, Al-Uzri A, Payne EH, Erinjeri J, Lin S, Harper B, Melloni C, Hornik CP; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis. J Clin Pharmacol. 2020 May;60(5):636-647. doi: 10.1002/jcph.1562. Epub 2019 Dec 8.

Reference Type RESULT
PMID: 31814149 (View on PubMed)

Thompson EJ, Wu H, Melloni C, Balevic S, Sullivan JE, Laughon M, Clark KM, Kalra R, Mendley S, Payne EH, Erinjeri J, Gelber CE, Harper B, Cohen-Wolkowiez M, Hornik CP; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Population Pharmacokinetics of Doxycycline in Children. Antimicrob Agents Chemother. 2019 Sep 9;63(12):e01508-19. doi: 10.1128/AAC.01508-19. Epub 2019 Sep 23.

Reference Type RESULT
PMID: 31548185 (View on PubMed)

Ge S, Mendley SR, Gerhart JG, Melloni C, Hornik CP, Sullivan JE, Atz A, Delmore P, Tremoulet A, Harper B, Payne E, Lin S, Erinjeri J, Cohen-Wolkowiez M, Gonzalez D; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Population Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescents. Clin Transl Sci. 2020 Nov;13(6):1189-1198. doi: 10.1111/cts.12803. Epub 2020 May 27.

Reference Type RESULT
PMID: 32324313 (View on PubMed)

Maharaj AR, Wu H, Zimmerman KO, Autmizguine J, Kalra R, Al-Uzri A, Sherwin CMT, Goldstein SL, Watt K, Erinjeri J, Payne EH, Cohen-Wolkowiez M, Hornik CP. Population pharmacokinetics of olanzapine in children. Br J Clin Pharmacol. 2021 Feb;87(2):542-554. doi: 10.1111/bcp.14414. Epub 2020 Jul 5.

Reference Type RESULT
PMID: 32497307 (View on PubMed)

Commander SJ, Wu H, Boakye-Agyeman F, Melloni C, Hornik CD, Zimmerman K, Al-Uzri A, Mendley SR, Harper B, Cohen-Wolkowiez M, Hornik CP; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Pharmacokinetics of Hydrochlorothiazide in Children: A Potential Surrogate for Renal Secretion Maturation. J Clin Pharmacol. 2021 Mar;61(3):368-377. doi: 10.1002/jcph.1739. Epub 2020 Oct 7.

Reference Type RESULT
PMID: 33029806 (View on PubMed)

Wu YSS, Cohen-Wolkowiez M, Hornik CP, Gerhart JG, Autmizguine J, Cobbaert M, Gonzalez D; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. External Evaluation of Two Pediatric Population Pharmacokinetics Models of Oral Trimethoprim and Sulfamethoxazole. Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0214920. doi: 10.1128/AAC.02149-20. Epub 2021 Jun 17.

Reference Type RESULT
PMID: 33903114 (View on PubMed)

Maharaj AR, Wu H, Zimmerman KO, Muller WJ, Sullivan JE, Sherwin CMT, Autmizguine J, Rathore MH, Hornik CD, Al-Uzri A, Payne EH, Benjamin DK Jr, Hornik CP; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Pharmacokinetics of Ceftazidime in Children and Adolescents with Obesity. Paediatr Drugs. 2021 Sep;23(5):499-513. doi: 10.1007/s40272-021-00460-4. Epub 2021 Jul 23.

Reference Type RESULT
PMID: 34302290 (View on PubMed)

Gerhart JG, Carreno FO, Ford JL, Edginton AN, Perrin EM, Watt KM, Muller WJ, Atz AM, Al-Uzri A, Delmore P, Gonzalez D; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Use of physiologically-based pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity. CPT Pharmacometrics Syst Pharmacol. 2022 Jun;11(6):778-791. doi: 10.1002/psp4.12793. Epub 2022 May 2.

Reference Type RESULT
PMID: 35491971 (View on PubMed)

Karatza E, Ganguly S, Hornik CD, Muller WJ, Al-Uzri A, James L, Balevic SJ, Gonzalez D. External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data. Front Pharmacol. 2022 Mar 17;13:817276. doi: 10.3389/fphar.2022.817276. eCollection 2022.

Reference Type RESULT
PMID: 35370711 (View on PubMed)

Smith MJ, Gonzalez D, Goldman JL, Yogev R, Sullivan JE, Reed MD, Anand R, Martz K, Berezny K, Benjamin DK Jr, Smith PB, Cohen-Wolkowiez M, Watt K; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Pharmacokinetics of Clindamycin in Obese and Nonobese Children. Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02014-16. doi: 10.1128/AAC.02014-16. Print 2017 Apr.

Reference Type RESULT
PMID: 28137820 (View on PubMed)

Hornik CP, Wu H, Edginton AN, Watt K, Cohen-Wolkowiez M, Gonzalez D. Development of a Pediatric Physiologically-Based Pharmacokinetic Model of Clindamycin Using Opportunistic Pharmacokinetic Data. Clin Pharmacokinet. 2017 Nov;56(11):1343-1353. doi: 10.1007/s40262-017-0525-5.

Reference Type DERIVED
PMID: 28290120 (View on PubMed)

Related Links

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Other Identifiers

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IND 113645

Identifier Type: OTHER

Identifier Source: secondary_id

IND 114369

Identifier Type: OTHER

Identifier Source: secondary_id

IND 114531

Identifier Type: OTHER

Identifier Source: secondary_id

IND 118358

Identifier Type: OTHER

Identifier Source: secondary_id

HHSN20100006

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HHSN27500020

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HHSN27500027

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HHSN27500043

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HHSN27500049

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Pro00029638

Identifier Type: -

Identifier Source: org_study_id

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