Protocol summary
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Study aim
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The aim of this study is to assess non inferiority of AryoTrust (AryoGEN Pharmed) compared to Herceptin (Roche)
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Design
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This is a Phase III, randomized, two-armed, patient-outcome assessor-data analyzer blinded, parallel active controlled non-Inferiority clinical trial study with a 1:1 allocation
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Settings and conduct
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This trial will be initiated from July 2016 and 108 patients with breast cancer recruit from the 18 centers. All centers implement same protocol and procedures. Variation of evaluation criteria and schemes will be reduced by investigator meetings, training of personnel in advance of the trial, and by careful monitoring during the trial. After confirmation of the eligibility of the patient and signing the informed consent form, the patients will be allocated to treatment groups according to the trial randomization master sheet (created by CRO Trial). Both products are indistinguishable for patients and health care providers and they will be blind to treatment allocation.
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Participants/Inclusion and exclusion criteria
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18-70 years old female patients with HER2+ breast cancer, newly diagnosed stage III (locally advanced) or in-operable stage II are candidates for participation.
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Intervention groups
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This study has two arms with 1:1 allocation. subjects in group I will receive AryoTrust (AryoGen Pharmed) plus Docetaxel every 3 weeks. subjects in group II will receive Herceptin® (Genentech/Roche) plus Docetaxel every 3 weeks. Both groups will receive Doxorubicin + Cyclophosphamid for 4 cycles before randomization.
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Main outcome variables
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Pathologic Complete Response
General information
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Reason for update
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT201606226135N7
Registration date:
2016-06-25, 1395/04/05
Registration timing:
prospective
Last update:
2018-08-16, 1397/05/25
Update count:
2
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Registration date
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2016-06-25, 1395/04/05
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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All expenses of this study including patients’ treatment and medicines, study conduct and performing and research related injuries compensation will be provided by Aryogen pharmed co.
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Expected recruitment start date
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2016-07-02, 1395/04/12
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Expected recruitment end date
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2017-07-03, 1396/04/12
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Actual recruitment start date
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2016-07-09, 1395/04/19
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Actual recruitment end date
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2018-06-11, 1397/03/21
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Trial completion date
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empty
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Scientific title
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A Phase III, randomized, two-armed, patient-outcome assessor-data analyzer blinded, parallel active controlled non-Inferiority clinical trial study of AryoTrust™ (AryogenTrastuzumab) efficacy and safety in Human Epidermal Growth Factor Receptor 2–Positive breast cancer in comparison to Herceptin® (Genentech/Roche) control.
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Public title
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Efficacy and safety in AryoTrust™ (Aryogen trastuzumab) vs Herceptin® (Genentech/Roche trastuzumab), a non inferiority trial
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
18-70 years old female patients
Patients with newly diagnosed stage III(locally advanced) or in-operable stage II (due to sizes larger than 5 cm or high tumor to breast ratio) tumors are candidates for participation
Willing and able to sign an informed consent
Pathological diagnosis of adenocarcinoma of the breast
ECOG status of 0-1
With any ER/PR status
HER2 positive
Exclusion criteria:
Clinical or radiologic evidence of metastatic disease
History of any other malignancy including previous breast cancer, second non-breast malignant disease
History of previous chemotherapy
Left ventricular ejection fraction [LVEF] <55% confirmed by echo cardiogram within 3 months before registration
Any prior myocardial infarction, History of documented congestive heart failure (CHF)
Any prior history of arrhythmia or cardiac vascular disease requiring medications or clinically significant
Current use of medications for treatment of angina pectoris
Current uncontrolled hypertension (diastolic > 100 mmHg or systolic > 200 mmHg)
A severe conduction abnormality (having pacemaker or diagnosed by the ECG) and any other significant cardiovascular disease
Hematologic abnormalities including baseline Absolute NeutrophilCount (ANC) of≤1,500/µL or platelet count ≤ 100,000/µL
Liver dysfunction including : Alanine amino transferase(ALT) and/or aspartate amino transferase (AST) ≥3 Upper Limit Normal (ULN), Alkaline phosphatase (ALP) ≥3 ͯ ULN serum, total bilirubin > 1.5 ULN
Renal dysfunction, defined as serum creatinin ≥2.5 mg/dL
Pregnant, lactating women or women of childbearing potential who are not willing to use adequate contraception
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Age
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From 18 years old to 70 years old
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Gender
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Female
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Phase
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3
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Groups that have been masked
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- Participant
- Care provider
- Investigator
- Outcome assessor
- Data analyser
- Data and Safety Monitoring Board
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Sample size
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Target sample size:
108
Actual sample size reached:
108
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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The randomization is based on blocked randomization. Patient's allocation will be carried on 1:1 allocation ratio by 27 blocks (length of each block is 4). Randomization sequence will be generated using the random generation command in Microsoft Excel (RANDBETWEEN)
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Blinding (investigator's opinion)
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Triple blinded
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Blinding description
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Both trastuzumab products are indistinguishable for patients and health care providers. So it will be possible to make patients blind about the treatment group which they have been allocated to. In addition to this, the outcome evaluators and data managers (data analyzer) will not be aware of patients’ allocations.
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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Secondary Ids
1
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Registry name
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clinicaltrial.gov
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Secondary trial Id
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NCT03425656
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Registration date
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2018-06-02, 1397/03/12
Ethics committees
1
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Ethics committee
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Approval date
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2016-06-22, 1395/04/02
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Ethics committee reference number
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ir.tums.rec.1395.2730
2
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Ethics committee
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Approval date
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2016-07-17, 1395/04/27
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Ethics committee reference number
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IR.MUI.REC.1395.4.041
Health conditions studied
1
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Description of health condition studied
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breast cancer patients with HER2-positive
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ICD-10 code
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C50
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ICD-10 code description
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Malignant neoplasm of breast
Primary outcomes
1
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Description
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pathologic Complete Response (pCR)
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Timepoint
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following completion of neoadjuvant systemic therapy
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Method of measurement
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the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes
Secondary outcomes
1
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Description
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clinical Complete Response (cCR)
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Timepoint
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after completion of neoadjuvant systemic therapy
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Method of measurement
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Disappearance of lesions in imaging. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm
2
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Description
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clinical Partial Response (cPR)
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Timepoint
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after completion of neoadjuvant systemic therapy
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Method of measurement
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At least a 30% decrease in the sum of diameters of target lesions through imaging
3
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Description
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clinically Stable Disease (cSD)
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Timepoint
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after completion of neoadjuvant systemic therapy
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Method of measurement
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Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD through imaging
4
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Description
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clinical Progressive Disease (cPD)
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Timepoint
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after completion of neoadjuvant systemic therapy
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Method of measurement
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at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm through imaging
5
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Description
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clinical Objective Response(cOR)
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Timepoint
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after completion of neoadjuvant systemic therapy
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Method of measurement
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cOR= cCR+ cPR
6
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Description
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breast conservation rate
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Timepoint
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After surgery
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Method of measurement
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number of mastectomy or Breast conservative surgery
7
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Description
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Immunogenicity
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Timepoint
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Week 10, 13, 19 and 26
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Method of measurement
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Laboratory results
8
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Description
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Adverse events
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Timepoint
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Every cycle
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Method of measurement
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Laboratory data and patient assessments
Intervention groups
1
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Description
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Intervention group: All patients are scheduled to receive Doxorubicin + Cyclophosphamide/Docetaxel+AryoTrust regimen as detailed bellow: Doxorubicin + Cyclophosphamide phase: (Cycle length: 14 days.Total cycles: 4) CyclesDoxorubicin, 60 mg/m2 IV + Cyclophosphamide,600 mg/m2 IV. Docetaxel + AryoTrust™ phase: (Cycle length: 21 days.Total cycles: 4 cycles) Docetaxel, 100 mg/m2 IV, AryoTrust™(Produced by AryoGEN Pharmed) 8 mg/kg IV loading dose (at cycle 1), followed by 6 mg/kg at subsequent cycles
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Category
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Treatment - Drugs
2
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Description
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Control Group: All patients are scheduled to receive Doxorubicin + Cyclophosphamide/Docetaxel+Herceptin regimen as detailed bellow: Doxorubicin + Cyclophosphamide phase: (Cycle length: 14 days.Total cycles: 4) CyclesDoxorubicin, 60 mg/m2 IV + Cyclophosphamide,600 mg/m2 IV. Docetaxel + Herceptin phase: (Cycle length: 21 days.Total cycles: 4 cycles) Docetaxel, 100 mg/m2 IV, Herceptin (Produced by Roche) 8 mg/kg IV loading dose (at cycle 1), followed by 6 mg/kg at subsequent cycles
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Aryogen pharmed Company
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Proportion provided by this source
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100
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Industry
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available