Protocol summary
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Study aim
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Effect of probiotic administration to women at risk of preterm birth on some of the neonatal and maternal outcomes
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Design
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A randomized, double-blind, placebo-controlled clinical trial with two parallel arms: 72 participants will be equally allocated into the probiotic or placebo groups using stratified (recruited center [health center/hospital], singleton/twin pregnancy) block randomization referring to a computerized program.
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Settings and conduct
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Eligible women at risk of preterm birth covered by the health centers and those hospitalized in the department of high-risk mothers of Al-Zahra Medical Teaching Hospital in Tabriz will be studied, after obtaining written informed consent. Participants, those recruiting participants, care providers, outcome assessors, and analyzers will not be aware of which group each person is placed in.
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Participants/Inclusion and exclusion criteria
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1. Women with a gestational age of 22 to 26 weeks based on ultrasonography below 12 weeks or LMP
2. Being at risk of preterm birth or having a history of hospitalization with symptoms of threatening preterm labor during the current pregnancy, provided suppression of the symptoms with tocolytic drugs.
Exclusion criteria:
1. Pregnancy after in vitro fertilization
2. Premature rupture of membranes
3. Known important medical problems
4. Acute symptoms of premature labor
5. Known major fetal abnormalities
6. Known abnormalities of the female uterus
7. Regular consumption of probiotics or sensitivity to probiotics
8. Drug or alcohol addiction
9. Triplets or more
10. Inflammatory bowel disease
11. Participation in another trial
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Intervention groups
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The women at risk of preterm birth will receive a supplemental capsule of probiotic or placebo daily from the time of the allocation (22-26 weeks of pregnancy) until 6 weeks after delivery.
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Main outcome variables
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Intrauterine age of newborns, Postpartum depression score
General information
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Reason for update
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Due to the challenge of recruiting eligible pregnant women at risk of preterm birth and the extended sampling period, the Research Council approved a reduction in the sample size from 144 to 72.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20100414003706N43
Registration date:
2022-11-26, 1401/09/05
Registration timing:
prospective
Last update:
2024-02-08, 1402/11/19
Update count:
1
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Registration date
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2022-11-26, 1401/09/05
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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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Expected recruitment start date
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2022-12-22, 1401/10/01
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Expected recruitment end date
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2023-12-20, 1402/09/29
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Actual recruitment start date
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2022-12-30, 1401/10/09
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Actual recruitment end date
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2024-01-04, 1402/10/14
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Trial completion date
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2024-07-04, 1403/04/14
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Scientific title
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Effect of probiotic administration to women at risk of preterm birth on some neonatal and maternal outcomes: a randomized controlled clinical trial
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Public title
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Effect of probiotic administration to women at risk of preterm birth on some neonatal and maternal outcomes
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Purpose
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Prevention
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Inclusion/Exclusion criteria
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Inclusion criteria:
Gestational age of 22 to 26 weeks based on ultrasound under 12 weeks or LMP
Being at risk of preterm birth, ie, having at least one of the following characteristics: history of preterm birth under 37 weeks or fetal loss after 16 weeks of pregnancy, cervical length less than 25 mm according to ultrasound results, twin, aged under 17 or over 35 years, cervical cerclage in the current pregnancy, smoking, less than 6 months interval between pregnancy and previous delivery, pre-pregnancy body mass index > 30 or < 18.5 kg/m2 and above, bacteriuria in the current pregnancy; or a history of hospitalization with symptoms/signs of threatened preterm birth, provided that suppression of the symptoms with tocolytic drugs (such as magnesium sulfate/nifedipine) in the current pregnancy.
Exclusion criteria:
Pregnancy after in vitro fertilization
Premature rupture of membranes (PROM)
Known important medical problems such as chronic hypertension, diabetes, diseases of the thyroid or liver
Acute symptoms of premature labor
Known major fetal abnormalities
Known abnormalities of the woman uterus
Regular consumption of probiotics or having a history of sensitivity to probiotics
Drug or alcohol addiction
Triplets or more
Inflammatory bowel disease (as diagnosed by a specialist)
Participation in another trial
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Age
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From 17 years old to 45 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
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Sample size
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Target sample size:
72
Actual sample size reached:
72
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Women at risk of preterm birth will be equally allocated into the probiotic or placebo groups using stratified (recruited center [health center/hospital], singleton/twin pregnancy) block randomization (with block sizes of 4 & 6) referring to a computerized program.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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Identical, opaque, sequentially numbered bottles containing probiotic/placebo capsules will be utilized to conceal the allocation and ensure blinding. The sequence generation and preparation of the bottles will be done by a person not involved in the recruitment, the prescription, and data collection. The investigators, health care providers, outcome assessors, and statistical analysts will be blinded.
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Placebo
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Used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2022-10-30, 1401/08/08
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Ethics committee reference number
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IR.TBZMED.REC.1401.708
Health conditions studied
1
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Description of health condition studied
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Preterm birth
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ICD-10 code
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O60
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ICD-10 code description
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Preterm labor
2
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Description of health condition studied
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Postpartum Depression
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ICD-10 code
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F32.8
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ICD-10 code description
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Other depressive episodes
Primary outcomes
1
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Description
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Intrauterine age of newborn
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Timepoint
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at birth
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Method of measurement
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Assessment of mother/infant medical record
2
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Description
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Postpartum depression
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Timepoint
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Before the intervention (baseline), one month of the intervention, 40-45 days after delivery
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Method of measurement
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Using the Edinburgh Postpartum Depression Scale
Secondary outcomes
1
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Description
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Infant birth weight
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Timepoint
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At birth
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Method of measurement
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Using a digital scale
2
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Description
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Phototherapy of the newborn
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Timepoint
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40-45 days after the childbirth
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Method of measurement
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Examining the infant's medical record or asking the mother
3
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Description
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Duration of newborn phototherapy (hours)
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Timepoint
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During neonatal period or 40-45 days after the childbirth
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Method of measurement
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Examining the infant's medical record or asking the mother
4
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Description
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Duration of infant hospitalization
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Timepoint
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at 40-45 days after the childbirth
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Method of measurement
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Examining the infant's medical record or asking the mother
5
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Description
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Infant weight gain in 40-45 days after birth
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Timepoint
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At birth, 40-45 days after birth
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Method of measurement
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Using a digital scale
6
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Description
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The composite variable of occurrence of serious problems in hospitalized newborns (including dysplasia, bronchopulmonary, sepsis, necrotizing enterocolitis, and retinopathy of prematurity)
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Timepoint
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7-10 days and 40-45 days after birth
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Method of measurement
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Diagnosed by neonatologist and ophthalmologist based on clinical and para-clinical assessments (Retinopathy of prematurity will be assessed by an ophthalmologist after 28 days of infancy)
7
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Description
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The composite variable of occurrence of some neonatal problems including Apgar score less than 7 in the fifth minute, hospitalization in NICU, use of surfactant, intubation, mechanical ventilation, and use of Continuous Positive Air Pressure (CPAP)
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Timepoint
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For infants who have been hospitalized for more than 48 hours, during neonatal hospitalization; for the rest, 40-45 days after childbirth
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Method of measurement
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For infants who have been hospitalized for more than 48 hours, by examining the infant's medical record and asking the neonatologist, if needed; for the rest, by asking mothers
8
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Description
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Appropriate weight gain of women during pregnancy
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Timepoint
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At baseline, maximum 10 days before delivery
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Method of measurement
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Weighting using a digital scale and comparison of the weight gain with the recommended one
9
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Description
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Anxiety
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Timepoint
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At baseline, one month of the intervention, 40-45 days after delivery
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Method of measurement
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Using the Beck Anxiety Scale
10
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Description
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Occurrence of mastitis in the woman
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Timepoint
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40-45 days after birth
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Method of measurement
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Using the mastitis scale
Intervention groups
1
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Description
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Women in the intervention group will receive probiotic supplements, in 500 mg capsules, containing the microorganisms Lacticaseibacillus paracasei subsp. Paracasei and Bifidobacterium lactis (animals) at a dose of 3×109 CFU/g of each strain (supplied by Hansen Company), daily from recruitment (22- 26 weeks) until six weeks after delivery.
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Category
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Prevention
2
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Description
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Control group: Women in the control group will receive starch-containing placebo , in 500 mg capsules, daily from recruitment (22- 26 weeks) until six weeks after delivery.
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Category
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Prevention
1
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Sponsor
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Grant name
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70598
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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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Tabriz University of Medical Sciences
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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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Public
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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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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Yes - There is a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Yes - There is a plan to make this available
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Data Dictionary
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Yes - There is a plan to make this available
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Title and more details about the data/document
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The requested data will be provided to researchers for statistical analysis (meta-analysis) of the submitted proposals.
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When the data will become available and for how long
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Starting immediately after the publication of the study results
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To whom data/document is available
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Data will be available to researchers working at academic organizations, as well as to the chief editor (and reviewers) of the journal of the submitted manuscript/s if requested.
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Under which criteria data/document could be used
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The data will be available to researchers upon request and submission of a proposal to perform a meta-analysis using IPD data after being unidentified. Also, in exceptional cases, data will be made available to the journal of the submitted manuscript/s for checking the accuracy of the data.
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From where data/document is obtainable
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Refer to the email address (alizades@tbzmed.ac.ir; mhammadalizadehs@gmail.com)
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What processes are involved for a request to access data/document
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The requests will be sent by email and data will be available within a week.
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Comments
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