Local Treatment Strategies for Brain Metastases of Colorectal Cancer (COLBRAIN)

Local Treatment Strategies for Brain Metastases of Colorectal Cancer: An International Observational Multicenter Retrospective Cohort Study (COLBRAIN)

COLBRAIN trial is an international (2 countries) observational, multicenter (15 centers) retrospective cohort study designed to investigate local treatment strategies for brain metastases of colorectal cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer; Brain Metastases, Adult
• Intervention / Treatment: Procedure: Neurosurgical Resection (NRS): En-bloc (EBR), Total piecemeal (TPR), Subtotal (SPR) or Partial (PPR); Radiation: Radiotherapy (RT): Stereotactic Radiosurgery/Radiotherapy (SRS/SRT), Whole-Brain Radiotherapy (WBRT); Other: Combined Local Treatment Modalities; Other: No Local Treatment

Detailed Description

Brain metastases (BM) from colorectal cancer (CRC) are a rare event, reported in less than 3% of patients with CRC. This course is associated with a dismal prognosis, and treatment of these patients remains challenging. The rarity of the event complicates research into both the effectiveness of local treatment methods and long-term oncological outcomes. Published studies are largely limited to single-center series with non-representative small patient cohorts, making it difficult to assess the reasons for such unsatisfactory treatment results.

Despite its rarity, there is growing evidence that the incidence of BM from CRC is increasing. Although direct epidemiological data are limited, many experts believe the detection rate has risen over the past quarter-century. This trend is likely multifactorial, attributed to advances in neuroimaging techniques and improved life expectancy due to the evolution of systemic therapy strategies.

However, this increase in detection has not translated into improved outcomes. Central nervous system (CNS) involvement in CRC remains associated with a dismal prognosis; median overall survival from the time of progression ranges from 2 to 5 months and has not substantially improved over recent decades. The aggressive disease course and the unmet clinical need for effective therapeutic strategies highlight the importance of large-scale, real-world data.

The primary objective of this study is to evaluate, in a large multi-institutional real-world cohort, the effectiveness of the following local treatment modalities for CRC BM:

1. Neurosurgical resection (NRS):

   • En-bloc resection (EBR)
   • Total piecemeal resection (TPR)
   • Subtotal (SPR) or partial piecemeal resection (PPR)
   • Extent of resection unknown

2. Radiotherapy (RT):

   • Stereotactic radiosurgery (SRS)
   • Staged stereotactic radiosurgery (stSRS)
   • Stereotactic radiotherapy (hypofractionated) (SRT)
   • Whole-brain radiotherapy (WBRT)

3. Combined local treatment modalities:

   • NRS with postoperative WBRT
   • NRS with postoperative SRT/SRS
   • Preoperative SRS followed by NRS
   • Combination radiotherapy (SRS and WBRT, SRT and WBRT, SRS and SRT)
4. No local treatment

Investigators from a multi-institutional consortium of 15 major cancer centers across Russia and Belarus have initiated a collaborative effort to create, to the best of our knowledge, the largest and most comprehensive retrospective dataset of patients with CRC BM described to date. This dataset will pool clinical, pathological, and treatment-related data from patients diagnosed over the past quarter-century (2000-2025). Data to be collected for each patient will include:

1. Demographics and Baseline Characteristics

   • Sex (male/female)
   • Age at primary cancer diagnosis (years, median with range)
   • Age at BM diagnosis (years, median with range)

2. Primary Tumor Characteristics

   • TNM classification (T, N, M categories with subcategories, including X when unknown)
   • Disease stage at initial diagnosis (I-II, III, IV, unknown)
   • History of primary tumor resection (yes/no/unknown)

   • Primary tumor sidedness:

     • Right-sided (cecum, ascending colon, hepatic flexure, transverse colon)
     • Left-sided (splenic flexure, descending colon, sigmoid colon, rectosigmoid junction, rectum)
     • Unknown
   • Primary tumor location (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, sigmoid colon, rectosigmoid junction, rectum, multiple tumors of colon, unknown)

3. Extracranial Disease Burden:

   • At initial cancer diagnosis:

     • Number of extracranial organ sites involved (1, 2, ≥ 3, unknown)
     • Location of extracranial metastases (liver, lung, peritoneum, bone, adrenal glands, soft tissues, distant lymph nodes, other; with specification of exclusive vs. combined involvement)

   • At the time of BM diagnosis:

     • Presence of extracranial metastases (yes/no/unknown)
     • Number of extracranial organ sites involved (1, 2, ≥ 3, unknown)
     • Location of extracranial metastases (liver, lung, peritoneum, bone, adrenal glands, soft tissues, distant lymph nodes, other; with specification of exclusive vs. combined involvement; including "brain-exclusive" disease)
     • Activity of extracranial disease (stable, progressing, brain-exclusive, unknown)

4. Intracranial Tumor Characteristics

   • Number of BM at diagnosis (median with range; categorized as solitary vs. ≥ 2)
   • Location relative to the tentorium (supratentorial, infratentorial, both)
   • For solitary BM: specific localization (frontal, temporal, parietal, occipital lobe; cerebellum; left/right hemisphere; unknown)
   • Cumulative intracranial tumor volume (CITV) (cm³, median with range; categorized into clinically relevant volume groups)
   • Largest intracranial tumor volume (LITV) (cm³, median with range; categorized into clinically relevant volume groups)
   • Maximum diameter of the largest intracranial tumor (cm, median with range; categorized into clinically relevant diameter groups)
   • Radiological features (present/absent/unknown): Perifocal edema, Mass effect, Dislocation syndrome, Ventricular compression (lateral, III, IV), Brainstem compression, Intratumoral hemorrhage, Intratumoral necrosis, Leptomeningeal disease (LMD), Occlusive hydrocephalus, Bone destruction, Cerebellar tonsil herniation

5. Clinical Presentation

   • Timing of BM diagnosis:

     • Synchronous (within 60 days of primary tumor diagnosis or as initial presentation)
     • Metachronous (> 60 days after primary tumor diagnosis)
     • Unknown
   • Neurological symptoms at BM diagnosis (symptomatic, asymptomatic, unknown)
   • Presence of neurological deficit at BM diagnosis (yes/no/unknown)
   • Neurological syndromes at BM diagnosis (global cerebral symptoms (headache, nausea, vomiting, dizziness), aphasic, dysarthric, pyramidal, sensory, extrapyramidal, cerebellar/vestibulo-ataxic, bulbar, pseudobulbar, paroxysmal, cognitive, brainstem, visual, meningeal, occlusive, behavioral, unknown)
   • ECOG performance status at BM diagnosis (0-1, 2-3, unknown)

6. Molecular Profile (where available)

   • Primary tumor:

     - RAS status (mutant/wild-type/unknown; specify codon if available)

     - BRAF status (mutant/wild-type/unknown; specify mutation if available)

     • dMMR/MSI status (MSI/MSS/unknown)
     • HER2 status (positive/negative/unknown)

   • Brain metastases:

     - RAS status (mutant/wild-type/unknown; specify codon if available)

     - BRAF status (mutant/wild-type/unknown; specify mutation if available)

     • dMMR/MSI status (MSI/MSS/unknown)
     • HER2 status (positive/negative/unknown)

7. Treatment-Related Data

   ◾ Lines of systemic therapy prior to BM diagnosis (number; categorized as 0, 1, 2, 3, 4, ≥ 5, unknown)

   • Lines of systemic therapy after first local treatment (number)
   • First local treatment modality (see detailed list below)
   • Number of local treatments per patient (median with range)

   • For radiotherapy:

     • Radiation therapy device (Leksell Gamma Knife, Accuray CyberKnife, Varian TrueBeam/Novalis Tx, non-stereotactic linac, other)
     • Biologically effective dose (BED) (Gy, median with range)
     • Equivalent dose (EQD2) (Gy, median with range)

8. Institutional and Period Data

   • Institution type (federal center, reference center, regional center)

   • Treatment period (by year of primary cancer diagnosis):

     - 2000-2010

     • 2011-2020
     • 2021-2025

Primary Endpoints:

1. Overall Survival (OS): Defined as the time from the date of brain metastasis (BM) diagnosis to the date of death from any cause or last follow-up (censored).

2. Time to Intracranial Progression (TTIP): Defined as the time from the date of initial colorectal cancer (CRC) diagnosis to the date of first BM detection. Based on this interval, patients will be categorized into two groups:

   - Synchronous BM: BM diagnosed either prior to or within 2 months (≤ 60 days) of the primary tumor diagnosis.

   - Metachronous BM: BM diagnosed more than 2 months (> 60 days) after the primary tumor diagnosis.

3. Central Nervous System Progression-Free Survival (CNS-PFS): Defined as the time from the date of first local treatment for BM to the date of subsequent intracranial progression or last instrumental follow-up (censored). Subsequent intracranial progression includes:

   • Continued growth of the treated lesion (≤ 6 months thereof);
   • Local recurrence of the treated lesion (> 6 months thereof);
   • Development of new distant intracranial lesions.

Secondary Endpoints:

1. Overall Survival from Initial Diagnosis: Time from initial CRC diagnosis to death from any cause or last follow-up.
2. Cancer-Specific Survival: Time from BM diagnosis to death from cancer progression (intracranial and/or extracranial), accounting for death from other causes as a competing event.
3. Cumulative Incidence of Death from Intracranial Progression: Death directly attributable to neurological complications resulting from progressive intracranial disease, analyzed using competing risks methodology with death from other causes as competing events.
4. Cumulative Incidence of Death from Extracranial Progression: Death attributable to systemic disease progression in the presence of controlled intracranial disease, analyzed using competing risks methodology.
5. Cumulative Incidence of Death from Other Causes: Death from causes unrelated to cancer progression, analyzed using competing risks methodology.

6. Cumulative Incidence of Repeat Local Interventions: The cumulative proportion of patients undergoing any additional local treatment (neurosurgery or radiotherapy) for intracranial disease progression following initial local therapy. This endpoint captures the total burden of repeat procedures required for recurrent or new intracranial lesions during follow-up. Death without a repeat intervention is treated as a competing event in the analysis.

   Statistical Analysis. All statistical analyses will be performed using IBM SPSS Statistics (version 29.0) and STATA (version 17.0, StataCorp LLC). A two-sided p-value < 0.05 will be considered statistically significant.

   - Descriptive Statistics. Categorical variables will be presented as absolute frequencies (n) and relative frequencies (%). Continuous variables will be assessed for normality. Normally distributed variables will be presented as mean with standard deviation (SD); non-normally distributed variables will be presented as median with interquartile range (IQR) or full range. The frequency of missing data will be reported for each variable. Where appropriate, multiple imputation using chained equations (MICE) will be considered to address missing data and minimize bias.

   - Survival Analysis. Survival curves will be estimated using the Kaplan-Meier method. Median survival times with 95% confidence intervals (CI) will be reported. Comparison of survival curves between groups will be performed using the log-rank test and, where appropriate, the Breslow-Wilcoxon test.

   For analyses of cause-specific death, competing risks methodology will be employed to estimate the cumulative incidence of death from intracranial progression, extracranial progression, and other causes, with death from competing causes treated as a competing event.

   - Univariable and Multivariable Analysis. Univariable analysis will be performed to identify potential prognostic factors associated with survival outcomes. For categorical variables, the log-rank test will be used. For continuous variables, univariable Cox proportional hazards regression will be performed.

   Variables with p < 0.10 on univariable analysis, as well as clinically relevant factors regardless of significance, will be entered into multivariable Cox proportional hazards regression models to identify independent prognostic factors. The proportional hazards assumption will be tested. Results will be presented as hazard ratios (HR) with 95% CI.

   - Preplanned subgroup analyses will be performed based on key variables such as local treatment modality, molecular profile, primary tumor sidedness, timing of brain metastases (synchronous vs. metachronous), and presence of extracranial disease.

   Specific Analyses:

   • Analysis of growth kinetics: In patients with available serial imaging, volumetric growth rate (VGR, cm³/day) and volume doubling time (VDT, days) will be calculated. These parameters will be correlated with clinical, molecular, and outcome variables.
   • Radionecrosis analysis: In patients receiving radiotherapy, the cumulative incidence and time to radionecrosis (TTRN) will be assessed and correlated with treatment modality, dose, volume, and molecular profile.
   • Temporal trends: Outcomes and treatment patterns will be compared across three time periods (2000-2010, 2011-2020, 2021-2025) to assess changes in practice and survival over time.
   • Institutional analysis: Outcomes will be compared across institution types (federal, reference, regional centers) to explore potential disparities in care.
   • GPA index validation: The prognostic accuracy of established Graded Prognostic Assessment (GPA) indices will be evaluated in this cohort and compared with any novel prognostic models developed from this data.

   Handling of Missing Data. The proportion of missing data will be reported for all variables. Patterns of missingness will be explored. Where appropriate and assuming data are missing at random, multiple imputation using chained equations (MICE) will be performed to impute missing values for key variables in multivariable models.

   The results of this large-scale, international study aim to provide high-level evidence to guide clinical decision-making and pave the way for personalized treatment approaches for this rare but challenging patient population.

• Study Type: Observational
• Enrollment (Actual): 700

Contacts and Locations

Study Locations

• Belarus
  • Homyel, Belarus, 246012
    • Gomel Regional Clinical Oncology Dispensary (OKOD)
• Russia
  • Kaliningrad, Russia, 236016
    • Kaliningrad Regional Clinical Oncology Center
  • Krasnogorsk, Russia, 143442
    • Moscow Regional Oncology Hospital No. 62
  • Moscow, Russia, 125284
    • P.A. Hertsen Moscow Oncology Research Institute
  • Moscow, Russia, 111123
    • A.S. Loginov Moscow Clinical Scientific Center
  • Moscow, Russia, 115446
    • S.S. Yudin City Clinical Hospital, Oncology Center No. 1
  • Moscow, Russia, 115478
    • Blokhin's Russian Cancer Research Center
  • Moscow, Russia, 115478
    • OncoStop CyberKnife Center
  • Moscow, Russia, 117303
    • Moscow Multidisciplinary Clinical Center "Kommunarka"
  • Moscow, Russia, 125047
    • Gamma Knife Center Moscow
  • Moscow, Russia, 125047
    • N.N. Burdenko National Medical Research Center of Neurosurgery
  • Moscow, Russia, 129090
    • N.V. Sklifosovsky Research Institute for Emergency Medicine
  • Saint Petersburg, Russia, 197758
    • N.N. Petrov National Medical Research Center of Oncology
  • Tyumen, Russia, 625062
    • Federal Center of Neurosurgery
  • Ufa, Russia, 450054
    • Republican Clinical Oncology Dispensary (RCOD)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients (≥ 18 years) with histologically confirmed colorectal adenocarcinoma and radiologically ± histologically documented brain metastases.

Patients with synchronous or metachronous multiple primary tumors confined to the colon or rectum are eligible. Patients referred after initial local treatment for brain metastases are included provided that complete documentation of the first treatment modality is available.

Description

Inclusion Criteria:

• Male and female patients aged 18 years or older;
• Histologically confirmed epithelial malignancy of the colon or rectum (colorectal adenocarcinoma). Patients with synchronous or metachronous multiple primary tumors within the colon or rectum are eligible;

• Radiologically ± histologically confirmed brain metastases, including:

  • Solid brain parenchymal metastases
  • Leptomeningeal disease (LMD)
  • Both solid metastases and LMD

Exclusion Criteria:

• Synchronous or metachronous multiple primary malignancies (MPM) involving sites other than the colon or rectum
• Primary tumor located outside the gastrointestinal tract;
• Histologically confirmed non-epithelial gastrointestinal malignancy (e.g., neuroendocrine tumors, sarcoma, gastrointestinal stromal tumor, lymphoma);
• Isolated spinal cord involvement without brain parenchymal metastases;
• Incomplete medical records precluding assessment of at least one primary endpoint (OS, TTIP, or CNS-PFS). Patients with available data for any primary endpoint are eligible, even if other clinical details are missing.
• Prior local treatment for brain metastases at an outside institution with no available records, precluding determination of the first local treatment modality

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Eligible Patients; Adult patients (≥ 18 years) with histologically confirmed colorectal adenocarcinoma and radiologically ± histologically documented brain metastases

Procedure: Neurosurgical Resection (NRS): En-bloc (EBR), Total piecemeal (TPR), Subtotal (SPR) or Partial (PPR); Patients in this cohort underwent neurosurgical resection as the primary local treatment for brain metastases. Surgical approaches include: En-bloc resection (EBR): gross-total removal of the tumor as a single, intact specimen with no residual disease on postoperative MRI;; Total piecemeal resection (TPR): gross-total removal of the tumor in multiple fragments with no residual disease on postoperative MRI; Subtotal (SPR) or partial (PPR) piecemeal resection: incomplete removal of the tumor, with macroscopic residual disease on postoperative MRI. This includes:Subtotal resection: 75-90% of tumor volume removedPartial resection: 30-75% of tumor volume removed; Extent of resection unknown: surgical resection performed, but the precise extent could not be determined from available records; Radiation: Radiotherapy (RT): Stereotactic Radiosurgery/Radiotherapy (SRS/SRT), Whole-Brain Radiotherapy (WBRT); Patients in this cohort received radiotherapy as the primary local treatment modality for brain metastases. Treatment modalities include: Stereotactic radiosurgery (SRS): single-fraction, high-precision radiation with a prescribed dose > 12 Gy;; Staged stereotactic radiosurgery (stSRS): radiosurgery delivered in 2-3 stages, typically 2-4 weeks apart, allowing for tumor volume reduction between stages;; Stereotactic radiotherapy (hypofractionated) (SRT): stereotactic radiation delivered in multiple fractions, including:3 fractions (single dose 7-9 Gy, total dose 21-27 Gy);5 fractions (single dose 6-7 Gy, total dose 30-35 Gy);7 fractions (single dose 5 Gy, total dose 35 Gy).; Whole-brain radiotherapy (WBRT): conventional fractionated radiation to the entire brain.; Other: Combined Local Treatment Modalities; Patients in this cohort received a combination of local treatment approaches. This includes: NRS with postoperative WBRT;; NRS with postoperative SRT/SRS;; Preoperative SRS followed by NRS;; Combination radiotherapy (SRS and WBRT, SRT and WBRT, SRS and SRT); Other: No Local Treatment; Patients in this cohort did not receive any local treatment for their brain metastases. This may include patients receiving best supportive care (BSC) (typically includes the administration of corticosteroids for symptomatic control of peritumoral edema and neurological symptoms) or systemic therapy alone. Reasons for not receiving local treatment may include poor performance status, extensive intracranial disease, or patient preference.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from the date of brain metastasis diagnosis to the date of death from any cause or last follow-up (censored)	From date of brain metastasis diagnosis until death or last contact, assessed up to 5 years (censored)
Time to Intracranial Progression (TTIP)	Time from the date of initial colorectal cancer diagnosis to the date of first brain metastasis detection. Based on this interval, patients will be categorized as synchronous (≤ 60 days from primary diagnosis) or metachronous (> 60 days).	From date of initial cancer diagnosis until first brain metastasis detection, assessed up to 10 years
Central Nervous System Progression-Free Survival (CNS-PFS)	Time from the date of first local treatment for brain metastases to the date of subsequent intracranial progression or last instrumental follow-up (censored). Intracranial progression includes: continued growth of treated lesion (≤ 6 months after treatment), local recurrence of treated lesion (> 6 months after treatment), or development of new intracranial lesions.	From the date of first local treatment for BM until subsequent intracranial progression or last imaging follow-up, assessed up to 5 years (censored)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival from Initial Diagnosis	Time from the date of initial colorectal cancer diagnosis to the date of death from any cause or last follow-up.	From date of initial cancer diagnosis until death or last contact, assessed up to 5 years
Cancer-Specific Survival	Time from brain metastasis diagnosis to death from cancer progression (intracranial and/or extracranial), with death from other causes treated as a competing event	From date of brain metastasis diagnosis until death or last contact, assessed up to 5 years
Cumulative Incidence of Death from Intracranial Progression	Death directly attributable to neurological complications resulting from progressive intracranial disease, analyzed using competing risks methodology with death from other causes as competing events.	From date of brain metastasis diagnosis until death or last contact, assessed up to 5 years
Cumulative Incidence of Death from Extracranial Progression	Death attributable to systemic disease progression in the presence of controlled intracranial disease, analyzed using competing risks methodology with death from other causes as competing events.	From date of brain metastasis diagnosis until death or last contact, assessed up to 5 years
Cumulative Incidence of Death from Non-cancer Causes	Death from causes unrelated to cancer progression, analyzed using competing risks methodology with cancer-related deaths as competing events.	From date of brain metastasis diagnosis until death or last contact, assessed up to 5 years
Cumulative Incidence of Repeat Local Interventions	The cumulative proportion of patients undergoing any additional local treatment (neurosurgery or radiotherapy) for intracranial disease progression following initial local therapy. This endpoint captures the total burden of repeat procedures required for recurrent or new intracranial lesions during follow-up. Death without a repeat intervention is treated as a competing event in the analysis	From date of first local treatment until the date of second local intervention or last follow-up, assessed up to 5 years (censored)

Collaborators and Investigators

• Sponsor: Blokhin's Russian Cancer Research Center
• Investigators: Study Chair: Alexey Tryakin, MD, professor, Blokhin's Russian Cancer Research Center; Study Chair: Ali Bekyashev, MD, professor, Blokhin's Russian Cancer Research Center; Principal Investigator: David Khalafyan, MD, Blokhin's Russian Cancer Research Center

Publications and helpful links

General Publications

• 33P Molecular-genetic concordance of the primary tumor and brain metastases of colorectal cancer (GENCONCOR-1). Khalafyan, D. et al. ESMO Open, Volume 9, 103779
• 484P. Molecular-genetic concordance of the primary tumor and brain metastases of colorectal cancer (GENCONCOR-1): second interim analysis. Halafyan, D. et al. Annals of Oncology, Volume 35, S1582

Helpful Links

• Comparison of Molecular-Genetic Concordance of the Primary Tumor and Brain Metastases of Colorectal Cancer (GENCONCOR-1)

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: February 19, 2026
• First Submitted That Met QC Criteria: February 28, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 28, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Cohort study; Colorectal cancer; Rectal cancer; Radiotherapy; Observational study; Hypofractionated radiotherapy; WBRT; Neurosurgery; OS; CNS; Colon cancer; SRS; Stereotactic radiosurgery; Overall survival; Stereotactic radiotherapy; SRT; Whole-brain radiotherapy; Real-world data; Brain metastases; GPA; Brain metastasis; Retrospective study; Local treatment; RWD; Piecemeal resection; Central nervous system metastases; En-bloc resection; Staged stereotactic radiosurgery; Time to intracranial progression; TTIP; CNS-PFS; RANO-BM
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Nervous System Neoplasms; Central Nervous System Neoplasms; Rectal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Brain Neoplasms; Therapeutics; Radiotherapy
• Other Study ID Numbers: 1155221705

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data collected for this study, including data dictionaries, will be available upon reasonable request from the corresponding author beginning 6 months after publication and ending 5 years following article publication. Data will be shared with researchers who provide a methodologically sound proposal for use approved by an independent review committee. Proposals should be directed to the corresponding author.
• IPD Sharing Time Frame: Individual participant data and supporting information will become available 6 months after publication of the primary results and will remain available for 5 years following article publication.
• IPD Sharing Access Criteria: Access will be granted to qualified academic researchers who submit a methodologically sound research proposal for use approved by an independent review committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No