Environmental influences on Child Health Outcomes (ECHO ... · ECHO-wide Cohort Data Collection Protocol Version 1.2 11 December 2018 3 . Executive Summary . The Environmental influences

ECHO-wide Cohort Data Collection Protocol Version 1.2

11 December 2018 1

Environmental influences on Child Health Outcomes

(ECHO)-wide Cohort Data Collection Protocol

Version Number: 1.2 Date: 11 December 2018 Funding Sponsor: National Institutes of Health (NIH)

ECHO Program Director Matthew W. Gillman, MD, SM

Director, Environmental influences on Child Health Outcomes (ECHO)

Office of the Director, National Institutes of Health

Phone: (301) 402-3388

Email: [email protected]

ECHO Cohort Principal Investigator and ECHO-wide Cohort Data Collection Protocol Development Working Group Co-Chair

Emily Oken MD, MPH

Department of Population Medicine

Harvard Medical School and Harvard Pilgrim Health Care Institute

Phone: (617) 867-4879


Principal Investigator, ECHO Person-Reported Outcome Core (PRO Core) and ECHO-wide Cohort Data Collection Protocol Development Working Group Co-Chair

David Cella, PhD

Department of Medical Social Sciences

Northwestern University Feinberg School of Medicine

Phone: (312) 503-1086



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Principal Investigator, ECHO Person-Reported Outcome Core (PRO Core)

Richard Gershon, PhD


Northwestern University Feinberg School

Phone: (312) 503-3453


Principal Investigator, ECHO Data Analysis Center (DAC)

Corette B. Parker, DrPH

Senior Research Statistician

RTI International

Phone: (919) 541-7122


Principal Investigator, ECHO Data Analysis Center (DAC)

Lisa P. Jacobson, ScD, MS

Professor of Epidemiology

Johns Hopkins Bloomberg School of Public Health

Phone: (410) 502-9770


Principal Investigator, ECHO Coordinating Center (CC)

Brian Smith MD, MPH, MHS

Professor of Pediatrics

Duke Clinical Research Institute

Phone: (919) 668-8951



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Executive Summary The Environmental influences on Child Health Outcomes (ECHO) Program seeks to address the impact of environmental influences on child development and health. The ECHO Program leverages multiple, existing cohort studies that have collected information on various environmental exposures, e.g., physical, chemical, social, behavioral, and biological, to support numerous synergistic, longitudinal studies. These ECHO-supported studies will share standardized data collection methods and focus on five key outcome domains: pre-, peri-, postnatal outcomes; neurodevelopment; upper and lower airways; obesity and obesity-related conditions; and positive health.

The primary objective of the ECHO-wide Cohort Data Collection Protocol is to facilitate the creation of the ECHO-wide Cohort data platform consisting of essential data elements from all ECHO Cohort Awardees and their constituent cohorts, plus recommended data elements from subsets of Cohort Awards. This protocol serves to standardize new data collection across the ECHO Program and to specify what data elements cohorts should collect (new data) and share (both existing data and new data) across the life course, from the prenatal period through adolescence, to create the ECHO-wide Cohort.

ECHO Investigators and the wider scientific community can use the ECHO-wide Cohort data to address innovative, high-impact, solution-oriented research questions that require multiple cohorts and relate a broad range of early environmental influences to child health outcomes.


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Protocol Version and Amendment Tracking

Version No. NIH Approval Date

1.0 18 April 2018

1.1 03 August 2018

1.2 (see Section 11.4 for a summary of changes from Version 1.1 to Version 1.2)

11 December 2018


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Protocol Synopsis

Protocol Version Version 1.2

Protocol Title Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Data Collection Protocol

Objective The ECHO Program seeks to address the impact of a broad array of early environmental influences on child development and health. The ECHO-wide Cohort Data Collection Protocol will facilitate the generation of the ECHO-wide Cohort data platform consisting of essential data elements from all ECHO Cohort Awardees and their constituent cohorts, plus recommended data elements from subsets of the Cohort Awards.

This protocol specifies the data that ECHO cohorts should collect (new data) and share (both existing data and new data) to create the ECHO-wide Cohort data platform. This protocol serves to standardize new data collection across the ECHO Program and will evolve over the course of the ECHO Program.

Study Design The ECHO-wide Cohort Data Collection Protocol will support numerous future longitudinal investigations through the creation of the ECHO-wide Cohort data platform. This data platform will leverage existing cohort studies that share the standardized new data collection methods specified in this protocol.


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Inclusion Criteria and Research Participants

This protocol applies to all participants within constituent cohorts of ECHO Cohort Awards (ECHO cohorts) who meet one of these four criteria for an ECHO-wide Cohort Data Collection Protocol participant:

1. Child enrolled in an ECHO cohort.*

2. Pregnant woman enrolled in an ECHO cohort.*

3. Primary caregiver, preferably the biological mother, where possible, of the child (or children) enrolled in an ECHO cohort. An ECHO cohort that did not previously enroll the child’s primary caregiver will be required to seek their permission for participation under the ECHO-wide Cohort Data Collection Protocol.

4. Biological mother and father of a child (or children) enrolled in an ECHO cohort, if not already enrolled under inclusion criterion #3 above, for the collection of “sample appropriate for DNA” from the biological mother (essential) and biological father (recommended).

* ECHO will follow children and pregnant women for ECHO outcomes of interest, whereas primary caregivers (and biological mothers and fathers, as applicable) will provide valuable exposure/covariate-related data and biospecimens.

ECHO cohorts will seek permission for their participation through the sharing of existing data (where applicable) as well as the collection of new data. Cohorts will also collect data about other individuals who interact with ECHO-wide Cohort Data Collection Protocol participants. These individuals may include biological parents and siblings, non-biological parents and siblings, and other caregivers of the child; and partners, biological parents and siblings, and other children of the pregnant woman.

Exclusion Criteria Participants within constituent cohorts of ECHO Cohort Awards who provide informed consent/assent, as appropriate, are eligible for inclusion in the ECHO-wide Cohort Data Collection Protocol. No further exclusion criteria apply.

Duration of Study Participation

The initial funding period for the ECHO Program is seven years, starting in September 2016 (FY16 funds). Under this cycle, cohorts will collect new data through March 2023.

Number of Cohorts

Currently, there are 31 Cohort Awardees that include approximately 70 cohorts and their associated participating ECHO cohort sites.


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Number of Sites There are approximately 180 participating ECHO cohort sites distributed across the United States, including Puerto Rico. This protocol defines each “site” as a unique combination of Award Principal Investigator, cohort, and institution.

Number of Participants

The number of participants is expected to exceed 50,000 children and almost as many primary caregivers over the course of the ECHO Program.


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Contact Information Cohort Awardees should first contact the NIH ECHO Program Office (via their assigned ECHO Program Officer) for questions regarding the ability (or any limitations) of a cohort to participate in the ECHO-wide Cohort Data Collection Protocol.

Cohort Awardees may direct questions regarding the procedures, processes, or responsibilities described in the ECHO-wide Cohort Data Collection Protocol to:

ECHO-wide Cohort Data Collection Protocol Implementation and Evaluation Committee Faculty Representative Courtney K. Blackwell, PhD

Research Assistant Professor


Northwestern University, Feinberg School of Medicine

Phone: (312) 503-6503


ECHO-wide Cohort Data Collection Protocol Implementation and Evaluation Committee Project Leader Kathleen Trollinger, MSN

Senior Project Leader

ECHO Coordinating Center

Duke Clinical Research Institute

Phone: (919) 668-8380


At the time of publication, all URLs and contact information details within the ECHO-wide Cohort Data Collection Protocol were functional. Please report any broken links or other access issues to [email protected].

mailto:[email protected]




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Table of Contents Executive Summary ................................................................................................................. 3

Protocol Version and Amendment Tracking .......................................................................... 4

Protocol Synopsis ................................................................................................................... 5

Contact Information ................................................................................................................. 8

Table of Contents ..................................................................................................................... 9

List of Tables ...........................................................................................................................11

List of Figures .........................................................................................................................11

Abbreviations ..........................................................................................................................12

ECHO-wide Cohort Data Collection Protocol Glossary ........................................................13

1. Background and Rationale .....................................................................................21

2. Objective and Development of the ECHO-wide Cohort Data Collection Protocol .................................................................................................................................23

2.1 Primary Objective of the ECHO-wide Cohort Data Collection Protocol ...................23 2.2 Development of the ECHO-wide Cohort Data Collection Protocol ..........................23

3. ECHO Program Participant Population .................................................................27 3.1 Inclusion Criteria .....................................................................................................27 3.2 Exclusion Criteria ....................................................................................................27 3.3 Duration of Participation .........................................................................................27 3.4 Number of Participants ...........................................................................................27 3.5 Participant Withdrawal ............................................................................................28

4. ECHO-wide Cohort Data Collection Protocol Design ...........................................28 4.1 ECHO-wide Cohort Data Collection Protocol Design: Data Elements and

Biospecimens .........................................................................................................28 4.1.1 Essential Data Elements and Biospecimens ......................................................28 4.1.2 Recommended Data Elements and Biospecimens .............................................29 4.1.3 Sharing of Existing Data .....................................................................................29 4.1.4 Sharing of Existing Biospecimens ......................................................................29

4.2 ECHO-wide Cohort Data Collection Protocol Design: Measures .............................30 4.2.1 Evaluation of Measurement Harmonization Potential .........................................30 4.2.2 Preferred Measures ...........................................................................................31 4.2.3 Acceptable Measures ........................................................................................31 4.2.4 Alternative Measures .........................................................................................31

5. ECHO-wide Cohort Data Collection Protocol Procedures ...................................32 5.1 Frequency of Data Collection .................................................................................32 5.2 Essential Data Elements for New Data Collection across the Child Developmental

Life Course .............................................................................................................33 5.3 Recommended Data Elements for New Data Collection across the Child

Developmental Life Course ....................................................................................56


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5.4 ECHO-wide Cohort Data Collection Protocol Biospecimens ...................................62 5.4.1 Essential Biospecimens for New Data Collection across the Child Developmental Life Course ........................................................................................................................62 5.4.2 Recommended Biospecimens for New Data Collection across the Child Developmental Life Course ...............................................................................................64

6. Data Management ...................................................................................................65 6.1 Data Submission to the ECHO DAC .......................................................................65 6.2 ECHOPortal and Data Security ...............................................................................65 6.3 Data Quality Assurance ..........................................................................................66 6.4 Data Access ...........................................................................................................67 6.5 Biospecimen Tracking ............................................................................................68 6.6 Record Retention ....................................................................................................68

7. Analysis Proposals .................................................................................................68

8. Study Responsibilities ...........................................................................................68 8.1 ECHO Coordinating Center, Data Analysis Center, and Person-Reported Outcome

Measurement Core Responsibilities .......................................................................68 8.1.1 ECHO Coordinating Center Responsibilities ......................................................68 8.1.2 ECHO Data Analysis Center Responsibilities .....................................................69 8.1.3 ECHO Person-Reported Outcome (PRO) Core Responsibilities ........................69

8.2 ECHO Cohort Investigator Responsibilities .............................................................70

9. Ethical Considerations and Human Subjects Protection .....................................70 9.1 Institutional Review Board/Ethics Committee Review .............................................70 9.2 Informed Consent ...................................................................................................71 9.3 Confidentiality of Participants..................................................................................71 9.4 Authorization for Use and Disclosure of Protected Health Information (HIPAA) ......72 9.5 Risks to ECHO-wide Cohort Data Collection Protocol Participants .........................72 9.6 Reimbursement to ECHO-wide Cohort Data Collection Protocol Participants .........72

10. Regulatory Reporting .............................................................................................72 10.1 Unanticipated Problems Involving Risks to Subjects or Others ...............................72 10.2 Breach Notifications ................................................................................................73 10.3 Reports of Non-compliance ....................................................................................73

11. Appendices .............................................................................................................74 11.1 ECHO-wide Cohort Data Collection Protocol Alternative Measures ........................74 11.2 Essential Data Element Measures for Child Participants 18 to 21 Years of Age .....79 11.3 ECHO Policies ........................................................................................................80 11.4 ECHO-wide Cohort Data Collection Protocol Version 1.1 to Version 1.2: Summary of

Changes .................................................................................................................81


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List of Tables Table 1 Outcome Working Group-Generated Overarching Research Topics and

Questions ..........................................................................................................24

Table 2 ECHO-wide Cohort Data Collection Protocol Development: Life Stages ............26

Table 3 Data Element Measure(s) Assignment Framework ............................................30

Table 4 Essential Data Elements Across the Child Developmental Life Course ..............34

Table 5 Recommended Data Elements Across the Child Developmental Life Course ....56

Table 6 Essential Biospecimens Across the Child Developmental Life Course ...............62

Table 7 Recommended Biospecimens Across the Child Developmental Life Course .....64

Table 8 Essential Data Elements and Associated Alternative Measures Across the Child Developmental Life Course ................................................................................74

Table 9 Discretionary Adult Measures for Child Participants 18 to 21 Years of Age ........79

List of Figures

Figure 1 ECHO Program Organizational Structure ...........................................................22


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Abbreviations ADO Adolescence CAT Computer Adaptive Test CC Coordinating Center CHEAR Children’s Health and Exposure Analysis Resource DAC Data Analysis Center EC Early Childhood ECHO Environmental influences on Child Health Outcomes FISMA Federal Information Security Management Act HIPAA Health Insurance Portability and Accountability Act INF Infancy IRB Institutional Review Board ISPCTN IDeA States Pediatric Clinical Trials Network LMP Last Menstrual Period MC Middle Childhood MOP Manual of Operating Procedures NIH National Institutes of Health NOWS Neonatal Opioid Withdrawal Syndrome (as in “ECHO Cohort Neonatal

Opioid Withdrawal Syndrome (NOWS) Subgroup”) PER Perinatal PHI Protected Health Information PIE ECHO-wide Cohort Data Collection Protocol Implementation and

Evaluation Committee PNA Prenatal PRO Person-Reported Outcome PRO Core Person-Reported Outcome Core QA Quality Assurance QC Quality Control sIRB Single Institutional Review Board UP Unanticipated Problem


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ECHO-wide Cohort Data Collection Protocol Glossary The following table contains a glossary of specialized terminology used within the ECHO-wide Cohort Data Collection Protocol.

Term Definition Acceptable Measure Compared with the preferred measure, measure that

reduces participant and/or researcher burden while maintaining acceptable scientific rigor. Examples may include data abstracted from medical records and short form versions and subscales of longer instruments.

Adolescence Life Stage (ADO) 11 years to 20 years 11 months 30 days Alternative Measure Measure that is a viable alternative to either the

preferred or acceptable measure, as confirmed by evidence of harmonization potential. A cohort may use an alternative measure for new data collection under the ECHO-wide Cohort Data Collection Protocol only if it is a legacy measure for that cohort. The ECHO Alternative Measures Task Force will review alternative measures requests.

Biospecimen Materials taken from the human body, e.g., blood, urine, hair, toenails, stool.

Biospecimens Working Group The ECHO working group charged with developing policies and procedures for biospecimen collection, processing, storage, and utilization, and with exploring novel related methodologies.

Chemical Exposures Working Group

The ECHO working group charged with recommending analyses of chemical exposures..

Children’s Health and Exposure Analysis Resource (CHEAR)

The component of ECHO that provides a focused infrastructure for comprehensive environmental chemical exposure analysis of biological samples: 1. Rigorous assessment of a range of environmental

exposures, xenobiotics, physiological measurements, metabolomics, and other biological indicators of environmental exposure and response.

2. Statistical tools and data science approaches to manage and analyze newly generated datasets pertaining to chemical exposure analysis of biological samples in a cohesive and integrated manner.

Cohorts Longitudinal studies of pregnant women and children that together constitute the ECHO-wide Cohort. There are currently 31 ECHO Cohort Awards comprising approximately 70 constituent cohorts.


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Term Definition Common Data Element Standardized key terms or concepts, used in this

protocol, and generally in research, to enhance data quality so that researchers can use data more effectively across analyses and over time. Common data elements promote data harmonization and comparability across research studies.

Per the ECHO Pediatric Cohorts Request for Applications OD16-004, common data elements in the ECHO-wide Cohort Data Collection Protocol include: a. Demographics (e.g., race, ethnicity, gender,

socioeconomic status, geographic location) b. Typical early development (e.g., growth, milestones,

physical activity, sleep, and optional sub element-microbiome)

c. Environmental exposures (e.g., physical, chemical, in-utero, microbial, psychosocial, natural and built environment)

d. Genetics (genotyping to be provided by the ECHO Genetics Core and optional sub element-epigenetics)

e. Person-reported outcomes.

Coordinating Center (CC) The ECHO component that provides the organizational framework for, and manages, all common ECHO activities.

Data Analysis Center (DAC) The ECHO component that provides the data repository, data management and analysis, study design guidance, and methodological development for ECHO data collected by at least two ECHO Cohort Awardees.

Data Collection Form Data collection forms provide specifications for how cohorts will collect related sets of variables (“data elements”) on the ECHO data platform at the form, section, and item level. Data collection forms have associated data dictionaries that describe attributes of each data element (e.g., the element's internal name, data type, caption presented to users, and basic validation information such as range checks), skip logic, and expressions for calculated elements

Early Childhood Life Stage (EC) 12 months to 5 years 11 months 30 days

https://grants.nih.gov/grants/guide/rfa-files/RFA-OD-16-004.html



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Term Definition ECHO Cohort Neonatal Opioid Withdrawal Syndrome (NOWS) Subgroup

An ECHO expert subgroup (led by two co-chairs) with two primary aims: 1. Analyze extant ECHO data and data elements

specific to prenatal opioid exposure, including NOWS, where NOWS is defined as withdrawal syndrome in infants with in utero exposure to opioids.

2. Develop new data elements or items (at the form level) to include in the ECHO-wide Cohort Data Collection Protocol specific to prenatal opioid exposure, including NOWS.

ECHO Manual of Operating Procedures (MOP)

A handbook that supplements the ECHO-wide Cohort Data Collection Protocol to guide study conduct and operations. ECHO cohorts will use the MOP as a reference document for procedures related to the ECHO-wide Cohort Data Collection Protocol.

ECHO-wide Cohort A data platform consisting of essential data elements from all ECHO Cohort Awardees and their constituent cohorts, plus recommended data elements from subsets of Cohort Awards.

ECHO-wide Cohort Analysis An analysis that uses the ECHO-wide Cohort (i.e., uses data from at least two ECHO Cohort Awardees).

ECHO-wide Cohort Data Collection Protocol

The protocol that specifies what data cohorts should collect (new data) and share (both existing data and new data) across the life course from the prenatal period through adolescence. This protocol facilitates the creation of the ECHO-wide Cohort data platform.

ECHO-wide Cohort Data Collection Protocol Development Working Group

The ECHO working group responsible for the development of the ECHO-wide Cohort Data Collection Protocol. Led by two co-chairs, it included members from the ECHO CC, ECHO PRO Core, ECHO DAC, NIH ECHO Program Office, Pediatric Cohort Awards, and six Life Stage Subcommittees. Each Life Stage Subcommittee was co-led by a representative from the ECHO PRO Core and a Cohort PI, and included representatives from the ECHO DAC, from the Biospecimens and Chemical Exposures Working Groups, and from each of the five Outcome Working Groups.


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Term Definition ECHO-wide Cohort Data Collection Protocol Implementation and Evaluation Committee (PIE)

The ECHO committee responsible for improving and evaluating the implementation feasibility of the ECHO-wide Cohort Data Collection Protocol. This group consists of core ECHO-wide Cohort Data Collection Protocol Development Working Group members in addition to four ECHO cohort representatives.

ECHO Cohort Investigator ECHO Cohort Award Principal Investigator or co-investigator

ECHO Program Office The NIH ECHO Program Office consists of the ECHO Director, a Senior Program Officer, additional Program Officers, the Chief of Staff, and administrative personnel. Also coordinates scientific and programmatic input and assistance provided by project scientists from other NIH institutes.

ECHOPortal A gateway for data capture and analysis that provides a collaborative work environment for use of ECHO-wide Cohort data.

Essential Data Element Applies to all constituent cohorts; collection and sharing of essential data elements is required for participation in the ECHO Program. Cohorts must use the preferred measure, or if not feasible, the acceptable measure, for new collection of an essential data element.

Executive Committee Represents the interests of all ECHO components, provides overall direction for the ECHO Program within the vision and rules stipulated by NIH. The Executive Committee proposes strategic decisions regarding overarching program issues, which the Steering Committee considers for ratification. Consists of one to two members from each ECHO component.

Existing Data Cohort data that existed prior to the approval and implementation of the ECHO-wide Cohort Data Collection Protocol. These existing data may contribute to ECHO analyses. If a cohort has previously collected a data element that appears in the ECHO-wide Cohort Data Collection Protocol, either as essential or recommended, they are expected to share these data with the ECHO-wide Cohort data platform.

Exposure A determinant, risk or resilience factor, predictor, or independent variable associated with child health. Exposures can be from a broad range, including physical, chemical, social, behavioral, or biological. ECHO defines the early exposure period from preconception to age 5 years.


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Term Definition Genetics Core The component of ECHO that provides genotyping and

bioinformatics specific to genetics for the ECHO Program. This core may also advise and participate in future genomic studies.

IDeA States Pediatric Clinical Trials Network (ISPCTN)

ECHO component that involves interventional studies. ISPCTN enables access to state-of-the art clinical trials among children from underserved and rural areas. It consists of 17 clinical sites and a Data Coordination and Operations Center. The ECHO-wide Cohort Data Collection Protocol does not apply to this Network.

Infancy Life Stage (INF) 46 weeks post-LMP to 11 months 30 days Legacy Measure A measure that a cohort has previously used and/or is

continuing to use under the cohort’s existing parent protocol. Legacy measures do not include sociodemographic questionnaires or other custom cohort-developed instruments created for sole use by the individual cohort. Use of a cohort’s legacy measure to satisfy a new essential data element collection requirement under the ECHO-wide Cohort Data Collection Protocol is permitted only if the Alternative Measures Task Force has approved the measure, or if this protocol already lists it as an alternative measure.

Life Stage Subcommittees Subcommittees of the ECHO-wide Protocol Development Working Group, composed of experts representing the six developmental life stages investigated across ECHO. Committees also included representation from each outcome domain as well as the Biospecimens and Chemical Exposures Working Groups. Charged with identifying relevant outcomes, exposures, and covariates within each life stage and further identifying valid measurements for inclusion in the ECHO-wide Cohort Data Collection Protocol.

Measure A methodology, often standardized, used to obtain a value or characteristic of a given data element. The ECHO-wide Cohort Data Collection Protocol classifies measures as preferred, acceptable, or alternative.

Middle Childhood Life Stage (MC) 5 years to 11 years 11 months 30 days Neurodevelopment Outcome Domain

The outcome domain focused on neurodevelopmental outcomes (e.g., attention, cognition, emotion, social/language/behavioral development).

New Data Cohort data collected using ECHO or other funding after the approval and implementation of the ECHO-wide Cohort Data Collection Protocol. These new data may contribute to ECHO analyses.


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Term Definition Obesity Outcome Domain The outcome domain focused on obesity and

obesity-related outcomes (e.g., nutrition, metabolic risk factors, and activity level).

Outcome Domains ECHO studies will focus on five key outcome domains that have a high public health impact:

1. Pre-, peri-, postnatal outcomes 2. Neurodevelopment 3. Upper and lower airways 4. Obesity and obesity-related conditions 5. Positive health

Outcome Working Groups Core group of experts representing the five ECHO outcome domains; charged with developing outcome-focused research questions and identifying data elements and appropriate measurements to inform the development of the ECHO-wide Cohort Data Collection Protocol.


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Term Definition Participants The ECHO-wide Cohort Data Collection Protocol defines

eligible research participants as:

1. Children enrolled in ECHO cohorts* 2. Pregnant women enrolled in ECHO cohorts* 3. Primary caregivers, preferably the biological

mother, where possible, of children enrolled in ECHO cohorts. An ECHO cohort that did not previously enroll the child’s primary caregiver will be required to seek their permission for participation under the ECHO-wide Cohort Data Collection Protocol.


* ECHO will follow children and pregnant women for ECHO outcomes of interest, whereas primary caregivers (and biological mothers and fathers, as applicable) will provide valuable exposure/covariate-related data and biospecimens.

ECHO cohorts will seek permission for their participation through the sharing of existing data (where applicable) as well as the collection of new data. Cohorts will also collect data about other individuals who interact with ECHO-wide Cohort Data Collection Protocol participants. These individuals may include biological parents and siblings, non-biological parents and siblings, and other caregivers of the child; and partners, biological parents and siblings, and other children of the pregnant woman.

Perinatal Life Stage (PER) Birth (including presentation for delivery) through the end of 45 weeks post-LMP

Person-Reported Outcomes Core (PRO Core)

The component of ECHO that provides measurement expertise in the development, selection, and validation of self-reported and performance-related measures as assessed from children and proxy participants in the ECHO cohorts.

Positive Health Outcome Domain Outcome domain focused on health assets (biological, functional, behavioral, and experiential) that strengthen an individual’s capacity to adapt, satisfy needs, and fulfill goals.


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Term Definition Preferred Measure Measure that balances innovation with feasibility, burden

with efficiency, and breadth with depth across diverse ECHO cohorts. Cohorts should use the preferred measures if at all possible.

Prenatal Life Stage (PNA) Post-LMP to pre-birth (parental and fetal measures)

Pre-, Peri-, Postnatal Outcome Domain

The outcome domain focused on pre-, peri-, and postnatal outcomes (e.g., birth defects, prematurity, neonatal/infant mortality).

Primary Caregiver A primary caregiver is an individual, such as a family member (biological or non-biological) or guardian, who is responsible for the care of the child.

Recommended Data Element Data elements that ECHO strongly encourages, but does not require, cohorts to collect. If a cohort collects or has previously collected a data element that appears in the ECHO-wide Cohort Data Collection Protocol as recommended, they are expected to share these data with the ECHO-wide Cohort data platform.

Steering Committee Represents the interests of all ECHO components, provides overarching strategic direction for the ECHO Program within the vision and rules stipulated by NIH. Guides the scientific work of the ECHO Program by ratifying key decisions presented by the Executive Committee and by voting on submitted analysis proposals. Consists of one member per Cohort Awardee plus one to two members from each of the other ECHO components.

Team Science Team Science is a collaborative effort to address a scientific challenge that leverages the strengths and expertise of professionals trained in different fields. Team Science allows the whole to be greater than the sum of the parts by facilitating transdisciplinary research.

Transdisciplinary Research Researchers from different disciplines work jointly to develop and use a shared conceptual framework that synthesizes and extends discipline-specific theories, concepts, and methods to create new approaches to address a common problem.

Upper and Lower Airways Outcome Domain

The outcome domain focused on upper and lower airway-related outcomes (e.g., asthma, rhinitis, sleep-disordered breathing).


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1. Background and Rationale In 2016, the NIH established the Environmental influences on Child Health Outcomes (ECHO) Program, an innovative and collaborative research initiative. The overarching scientific goal of ECHO is to advance understanding of the effects of a broad array of early environmental exposures on children’s development and health outcomes with high public health impact. To achieve this goal, the ECHO Program will leverage and expand cohort studies that have collected information on various environmental exposures, e.g., physical, chemical, social, behavioral, and biological, to support multiple synergistic, longitudinal investigations. These ECHO-supported studies will share standardized data collection methods and focus on five key outcome domains: pre-, peri-, and postnatal outcomes; neurodevelopment; upper and lower airways; obesity and obesity-related conditions; and positive health. All cohorts will collect the following standardized, targeted common data elements: demographics, typical early health and development, genetics, environmental factors, and person-reported outcomes (PROs).

The ECHO Program has seven components: the Pediatric cohorts (ECHO cohorts), the Coordinating Center (CC), the Data Analysis Center (DAC), the Person-Reported Outcomes Core (PRO Core), the Children’s Health and Exposure Analysis Resource (CHEAR), the IDeA States Pediatric Clinical Trials Network (ISPCTN), and the Genetics Core. Figure 1 depicts the organizational structure of the ECHO Program, including the ECHO governance structure and the seven ECHO components.


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Figure 1 ECHO Program Organizational Structure

There are currently 31 ECHO Cohort Awardees, comprising approximately 70 constituent cohorts. Over the course of the ECHO Program, these cohorts will include approximately 50,000 children and almost as many primary caregivers. These existing cohorts represent diverse study populations with varying research goals, data collection procedures, measurements, and follow-up schedules, and include preconception, prenatal (over half of the ECHO cohorts are prenatal cohorts), birth, infancy, and early childhood inception cohorts.

Enrollment in these cohorts spans multiple decades, with some recruitment beginning in the early 1980s, while many other ECHO cohorts have ongoing recruitment efforts. ECHO is a nationwide program with approximately 180 participating ECHO cohort sites distributed across the United States, including Puerto Rico, with participants of diverse race/ethnicity (including indigenous populations) and socioeconomic status. The five key outcome domains described above are represented broadly across the ECHO cohorts. This large network of 31 Cohort Awardees, each with diverse inception cohorts, has the promising potential to achieve ECHO’s


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primary scientific goal via the formation of a dynamic ECHO-wide Cohort, which is key to the success of the ECHO Program.

2. Objective and Development of the ECHO-wide Cohort Data Collection Protocol

2.1 Primary Objective of the ECHO-wide Cohort Data Collection Protocol The primary objective of the ECHO-wide Cohort Data Collection Protocol is to facilitate the creation of the ECHO-wide Cohort data platform consisting of essential data elements from all ECHO Cohort Awardees and their constituent cohorts, plus recommended data elements from subsets of Cohort Awards. This protocol serves to standardize new data collection across the ECHO Program and to specify what data elements cohorts should collect (new data) and share (both existing data and new data) across the life course, from the prenatal period through adolescence, to create the ECHO-wide Cohort data platform.

ECHO Cohort Investigators and the wider scientific community can use the ECHO-wide Cohort data platform to address innovative, high-impact, solution-oriented research questions that require multiple cohorts and relate a broad range of early environmental influences to child health outcomes.

2.2 Development of the ECHO-wide Cohort Data Collection Protocol The ECHO-wide Cohort Data Collection Protocol is not intended to address one specific research question, but rather to facilitate the development of a data platform (the ECHO-wide Cohort) that investigators can use to explore numerous innovative, solution-oriented research questions across the five ECHO outcome domains.

The development of this protocol was a transdisciplinary, iterative process guided by the principles of Team Science. It included stakeholders across ECHO, as evidenced by close collaboration between the ECHO-wide Cohort Data Collection Protocol Development Working Group and its Life Stage Subcommittees, the Outcome Working Groups, the Chemical Exposures and Biospecimens Working Groups, CHEAR, the ECHO Executive Committee and Steering Committee, and the NIH ECHO Program Office.

Brief Timeline of ECHO-wide Cohort Data Collection Protocol Development Following the November 2016 ECHO Program Kickoff Meeting, the ECHO Program charged the Outcome Working Groups with developing broad research topics and questions to inform the development of the ECHO-wide Cohort Data Collection Protocol (Table 1). These overarching research questions were intentionally broad to stimulate discussion and were not intended to be specifically addressed by this protocol. However, these questions were vital to the protocol development process, and ultimately, to the generation of the ECHO-wide Cohort data platform.

For ECHO analyses using the ECHO-wide Cohort data platform, writing groups will develop analysis proposals that contain more refined research questions in conjunction with the ECHO DAC (see Section 7). The ECHO Steering Committee will review and approve these analysis


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proposals.

Table 1 Outcome Working Group-Generated Overarching Research Topics and Questions

Outcome Area Overarching Research Topics and Questions Upper and Lower Airways

• Natural History of Asthma – longitudinal analysis • Air pollution on respiratory health • Role of airway and gut microbiota on respiratory health • Integrative -omics and asthma: Regions of the epigenome at

birth will be differentially methylated in relation to prenatal and postnatal exposures that show a relation with childhood asthma

• Effect of viral illness on lung function: What host genomic factors influence the long-term effects of early life respiratory viral illness on later life lung function trajectory and respiratory morbidity?

Neurodevelopment • Which chemical and non-chemical exposures are independently and/or jointly associated with neurodevelopmental outcomes? Are there specific exposure windows of susceptibility? Do any of these exposures play a causal role? Can these exposures explain ethnic/racial and socioeconomic disparities in neurodevelopment and if so, which exposures can be modified to reduce the risk?

• What is the relationship between preconception, prenatal, and perinatal environmental exposures and autism spectrum disorder-related phenotypes?

• Which environmental exposures during the preconception, prenatal and perinatal periods are associated with externalizing and internalizing traits, disorders, and their neurocognitive components?

• Are there high-dimensional biomarkers (e.g., metabolomics, epigenomics, microbiome and other -omics; gene expression) measured in biosamples taken during pregnancy and/or postnatally that predict the neurodevelopmental outcomes and trajectories in the child?


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Table 1 Outcome Working Group-Generated Overarching Research Topics and Questions

Outcome Area Overarching Research Topics and Questions Obesity • To examine the independent and joint associations between

pre-birth and early life exposures and markers/trajectories of childhood obesity, childhood vascular function, and childhood metabolism.

• To explore potential mediators of the prior associations. • Can we use epigenetic data (e.g., DNA methylation, chromatic

remodeling, others) to develop an individual fingerprinting that can be used to reconstruct exposures during sensitive time windows that predict?

Pre-, Peri-, and Postnatal

• What are the exposures, both environmental and maternal, that either individually or combined occur during the prenatal and neonatal period that if modified would improve pregnancy outcomes leading to healthier children?

• What are the paternal-maternal-fetal molecular pathways that mediate, either positively or negatively, the environmental impact on pregnancy outcomes and newborn health?

Positive Health • How does positive health develop during childhood, overall and across the ECHO focus areas?

• How do social environments (family, peers, school) influence the development of wellbeing/global health, overall and by socio-demographic subgroups?

• How do environmental exposures influence sleep function, overall and by socio-demographic subgroups?

Using these overarching topics and questions to guide their discussions, the Life Stage Subcommittees identified the most relevant exposures, outcomes, and covariates for cohorts to measure in their respective life stages. For the purposes of protocol development, the childhood life course is organized across distinct developmental life stage categories as summarized in Table 2. For heuristic purposes, the ECHO Program assigned specific age bands to each life stage based on consensus of pediatric developmental experts. Several of these life stages intentionally overlap, as there is age-variability in normal maturation and development.


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Table 2 ECHO-wide Cohort Data Collection Protocol Development: Life Stages

Life Stage Age Span

Prenatal Post-LMP to pre-birth (parental and fetal measures)

Perinatal Birth (including presentation for delivery) through the end of 45 weeks post-LMP

Infancy 46 weeks post-LMP to 11 months 30 days

Early Childhood 12 months to 5 years 11 months 30 days

Middle Childhood 5 years to 11 years 11 months 30 days

Adolescence 11 years to 20 years 11 months 30 days See Section 5.1 for details regarding the frequency of data collection in each life stage. Note: The ECHO Manual of Operating Procedures (MOP) provides instructions regarding any required measure-specific age adjustments for preterm infants (defined as <37 completed weeks of gestation at birth) through age 2 years. The ECHO Steering Committee ratified Version 1.0 of the protocol in November 2017 (NIH ECHO Program Office approved version dated 18 April 2018). In February 2018, ECHO convened the ECHO-wide Cohort Data Collection Protocol Implementation and Evaluation Committee (PIE), whose primary objective was to inform Version 1.1 of the protocol. This committee evaluated ECHO-wide Cohort Data Collection Protocol data elements and/or biospecimens that could be refined, reclassified, or removed from the protocol to reduce burden and improve the feasibility of implementation across diverse ECHO cohorts. The PIE Committee engaged with experts across the ECHO community, including the ECHO DAC, ECHO PRO Core, Outcome Working Groups, ECHO cohort representatives, and the NIH ECHO Program Office to create a comprehensive change proposal for the generation of the ECHO-wide Cohort Data Collection Protocol Version 1.1, ratified by ECHO Steering Committee 20 July 2018. In addition, the PIE Committee consulted with the ECHO Cohort Neonatal Opioid Withdrawal Syndrome (NOWS) Subgroup to confirm that the protocol contains the data elements, items (at the form level), and biospecimens that would potentiate the identification of children exposed to opioids in utero, thereby ensuring that future ECHO analyses can address this emerging public health crisis.

In November 2018, the PIE Committee performed a reconciliation activity between protocol Version 1.1 and all developed study materials (e.g., forms), resulting in the generation of a clarification amendment and, consequently, protocol Version 1.2 (dated 11 December 2018).


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3. ECHO Program Participant Population

3.1 Inclusion Criteria

This protocol applies to all participants within constituent cohorts of ECHO Cohort Awards (ECHO cohorts) who meet one of these four criteria for an ECHO-wide Cohort Data Collection Protocol research participant:

1. Child enrolled in an ECHO cohort.

2. Pregnant woman enrolled in an ECHO cohort.

3. Primary caregiver, preferably the biological mother, where possible, of the child (or children) enrolled in an ECHO cohort. An ECHO cohort that did not previously enroll the child’s primary caregiver will be required to seek their permission for participation under the ECHO-wide Cohort Data Collection Protocol.


3.2 Exclusion Criteria Participants within constituent cohorts of ECHO Cohort Awards who provide informed consent/assent, as appropriate, are eligible for inclusion in the ECHO-wide Cohort Data Collection Protocol. No further exclusion criteria apply.

3.3 Duration of Participation The initial funding period for the ECHO Program is seven years, starting in September 2016 (FY16 funds). Under this cycle, cohorts will collect new data through March 2023.

3.4 Number of Participants The ECHO Program consists of 31 Cohort Awardees that comprise approximately 70 cohorts, and their associated participating ECHO cohort sites (approximately 180 sites). The number of participants is expected to exceed 50,000 children and almost as many primary caregivers over the course of the ECHO Program.


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3.5 Participant Withdrawal Participants can withdraw from participation (i.e., discontinue participation) in the ECHO-wide Cohort Data Collection Protocol at any time and for any reason, without consequence. In cases of participant withdrawal, ECHO study staff will record withdrawal-related information, including the reason(s) for withdrawal. Participant data and biospecimens collected prior to a participant’s withdrawal will be used for purposes related to the ECHO-wide Cohort Data Collection Protocol (unless otherwise specified by the participant).

4. ECHO-wide Cohort Data Collection Protocol Design The ECHO-wide Cohort Data Collection Protocol serves to standardize new data collection (sharing of existing data is discussed in Section 4.1.3 and sharing of existing biospecimens is described in Section 4.1.4).

This protocol will support numerous future longitudinal analyses through the creation of the ECHO-wide Cohort data platform. This data platform will leverage existing cohort studies that will apply standardized new data collection methods.

4.1 ECHO-wide Cohort Data Collection Protocol Design: Data Elements and Biospecimens

The ECHO-wide Cohort Data Collection Protocol features two categories of data elements and biospecimens, essential (Section 4.1.1) and recommended (Section 4.1.2).

These two data element categories differentiate, and therefore ensure, the robust collection of data elements and biospecimens that are essential to analyses using the ECHO-wide Cohort data platform, while they also identify important, recommended data elements and biospecimens that will further enrich the depth, breadth, and innovation of the ECHO-wide Cohort data platform.

The essential and recommended data elements and biospecimens featured in this protocol encompass, but are not limited to, the targeted common data elements specified in the Request for Applications OD16-004, including demographics, typical early development, environmental exposures, genetics, and PROs.

4.1.1 Essential Data Elements and Biospecimens The ECHO Program requires that cohorts collect and share essential data elements and biospecimens (Section 5.2 and Section 5.4.1, respectively); this requirement applies to all ECHO constituent cohorts. The ECHO Program expects that cohorts will collect all essential data elements and biospecimens from all willing participants in each life stage their cohort participants (pregnant women and children) enter during the period of their ECHO funding support. Any deviations from this expectation will be determined by the NIH ECHO Program Office. Before the implementation of this protocol, if a cohort did not collect an essential data element or biospecimen during the life stage window specified for collection, then the cohort is exempt from the collection requirement.




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4.1.2 Recommended Data Elements and Biospecimens To allow for innovation across ECHO, this protocol also contains a diverse array of recommended data elements and biospecimens (Section 5.3 and Section 5.4.2, respectively). ECHO encourages, but does not require, cohorts to collect recommended data elements and biospecimens. However, during new data collection, if a cohort collects a data element that appears in the ECHO-wide Cohort Data Collection Protocol as recommended, ECHO expects them to share these data with the ECHO-wide Cohort data platform.

4.1.3 Sharing of Existing Data For all data elements in the ECHO-wide Cohort Data Collection Protocol (both essential and recommended), if a cohort has previously collected them (existing data), ECHO expects the cohort to share them on the ECHO-wide Cohort data platform, irrespective of the specific measure or methodology previously used for data collection. Cohorts will share participant data per the most recently signed informed consent associated with the sharing of these data. The ECHO Data Sharing Policy describes the specific policies and practices governing the sharing of existing data.

4.1.4 Sharing of Existing Biospecimens The ECHO Program expects cohorts to share existing biospecimens (including those collected previously with non-ECHO funding as well as those collected in pursuit of ECHO-funded cohort specific aims) that appear in this protocol in accordance with the ECHO Biospecimen Utilization Policy. Cohorts will share participant biospecimens per the most recently signed informed consent associated with the sharing of these biospecimens.

Cohorts will also share existing cohort data derived from biospecimens with the ECHO-wide Cohort data platform upon approval of an analysis proposal that incorporates those data (see Section 4.1.3 for sharing of existing data).


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4.2 ECHO-wide Cohort Data Collection Protocol Design: Measures The ECHO-wide Cohort Data Collection Protocol defines measures for each essential data element as either preferred (Section 4.2.2), acceptable (Section 4.2.3), or alternative (Section 4.2.4)1. The protocol further identifies preferred measures for recommended data elements. Table 3 summarizes the organizational framework for the assignment of measures to data elements.

Table 3 Data Element Measure(s) Assignment Framework

Data Element

Measure Assignment

New Data Collection Preferred Acceptable Alternative

Essential ≥1 measure Could be ≥1 measure

Could be ≥1 measurea

Required to use the preferred measure or, if not feasible, the acceptable measure

Recommended ≥1 measure Not Applicable

Not Applicable

Strongly encouraged to use the preferred measureb

a Substitution of an alternative measure (Section 4.2.4) in lieu of the preferred or acceptable measure is permitted only if the Alternative Measures Task Force has approved the measure, or if this protocol already lists it as an alternative measure and it is the cohort’s legacy measure.

b While ECHO encourages cohorts to collect the preferred measure, they may choose instead to use their legacy measure or a more rigorous or innovative measure.

4.2.1 Evaluation of Measurement Harmonization Potential To ensure the ability to analyze essential data elements across diverse ECHO cohorts, the preferred and acceptable measures must demonstrate harmonization potential at one of the two following harmonization levels (from most to least stringent):

1. Identical: The two measures are identical in content and collection mode. 2. Comparable: The two measures capture the same data concept(s), but use different

units, scoring, or collection modes (e.g., administered via a self-administered survey versus an interview). A mathematical relationship exists between comparable measures. This relationship can include score linking or other mathematical conversions (e.g., weighting coefficients), high correlations, or linking across the different instrument collection modes.

1 This measurement assignment framework does not apply to biospecimens (Section 5.4). The collection of biospecimens included in this protocol will adhere to the ECHO Biospecimen Collection, Processing, and Storage Processes. Biospecimens that the ECHO Program considers essential and recommended for new collection under this protocol are described in Sections 5.4.1 and 5.4.2, respectively.


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4.2.2 Preferred Measures Preferred measures are those that sufficiently balance innovation with feasibility, burden with efficiency, and breadth with depth across diverse ECHO cohorts.

The ECHO-wide Cohort Data Collection Protocol assigns all data elements (both essential and recommended) at least one preferred measure. The ECHO Program expects cohorts to collect preferred measures if at all possible.

4.2.3 Acceptable Measures If the collection of the preferred measure is not feasible, cohorts may instead use the acceptable measure. Compared with the preferred measure, the acceptable measure reduces participant and/or researcher burden while maintaining acceptable scientific rigor. Examples may include data abstracted from medical records and short form versions and subscales of longer instruments.

The ECHO-wide Cohort Data Collection Protocol may include at least one acceptable measure for each essential data element; however, for some data elements, the acceptable measure is the same as the preferred measure.

4.2.4 Alternative Measures Alternative measures may be included in the ECHO-wide Cohort Data Collection Protocol if they are viable alternatives to either the preferred or acceptable measure, as confirmed by evidence of harmonization potential per the criteria in Section 4.2.1. Alternative measures already included in the protocol are listed in Table 8.

A cohort may use an alternative measure (in lieu of the preferred or the acceptable measure) for new data collection of an essential data element only if it is the cohort’s legacy measure. The ECHO Program defines a legacy measure as a measure a cohort has previously used and/or is continuing to use under their parent study protocol under local IRB approval. Use of a cohort’s legacy measure to satisfy a new essential data element collection requirement under the ECHO-wide Cohort Data Collection Protocol is permitted only if the Alternative Measures Task Force has approved the measure, or if this protocol already lists it as an alternative measure.

Alternative Measure Request Process The ECHO Program acknowledges that cohorts may have legacy measures historically used to assess an essential data element that are not listed as an alternative measure in the ECHO-wide Cohort Data Collection Protocol. In these cases, if cohorts wish to use their legacy measures to satisfy the new data collection requirements, they may submit a formal request to the ECHO Alternative Measures Task Force (composed of ECHO DAC, ECHO PRO Core, and ECHO cohort experts). In collaboration with the ECHO Data Harmonization Working Group, this Task Force will then adjudicate whether the legacy measure is a viable alternative (i.e., whether it can be harmonized to the ECHO-wide Cohort per the criteria in Section 4.2.1) and advise the cohort applicant of their decision and any further recommendations.

If the legacy measure submitted for review cannot be harmonized, collection of this measure will not satisfy the essential data element collection requirement, and the cohort will be required to collect the essential data element using the preferred measure, if possible, and the acceptable measure if not.


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5. ECHO-wide Cohort Data Collection Protocol Procedures The following sections apply to new data collection and describe the essential and recommended data elements and associated measures that ECHO cohorts should collect (biospecimens are discussed separately in Section 5.4). Note, for all data elements in the ECHO-wide Cohort Data Collection Protocol (both essential and recommended), if a cohort has previously collected them (existing data), ECHO expects the cohort to share them with the ECHO-wide Cohort data platform (see Section 4.1.3).

The data elements and associated measures included in the ECHO-wide Cohort Data Collection Protocol are organized across the child developmental life course, from the prenatal period through adolescence (see Table 2). Research participants associated with a pregnant woman or child will be followed according to the associated pregnant woman’s or child’s study schedule. For a child participant in an overlapping developmental life stage (e.g., a 5-year-old falls in both early childhood and middle childhood), each cohort will determine and document which data elements and associated measures it plans to collect during that window of observation.

In this protocol (Table 4 and Table 5), child self-report measures generally start at age 8, with primary caregiver versions for younger children. If a child self-report option is available and developmentally appropriate for the cohort’s specific study sample, cohorts should use the child self-report version. However, additional considerations, such as reading ability, comprehension, and cognitive ability may necessitate primary caregiver questionnaires at older ages.

In this protocol (Table 4, Table 5, and Table 9), some PROMIS measures can be administered as computer-adaptive tests (CATs) in lieu of short forms. CATs increase measurement precision with minimal burden on participants by determining which item should be administered next based on the respondent’s prior answers. CATs adapt to an individual’s level of the latent trait being measured and the CATs included in this protocol can be completed in 4 to 6 items. Measures that can be administered as a CAT are noted with the convention “/CAT” in the aforementioned tables.

Many of the data elements presented in the following sections can be outcomes, exposures, or covariates depending on the specific analysis; therefore, data elements are not organized by outcome, exposure, or covariate status. For future specific analyses performed using the ECHO-wide Cohort, writing groups will specify data elements as exposures, outcomes, or covariates in question-specific analysis proposals (see Section 7).

5.1 Frequency of Data Collection The ECHO Program expects that each cohort will collect life stage-specific measures at least once in each life stage (see Table 2) their cohort participants (pregnant women and children) enter during the period of their ECHO funding support. Furthermore, given the rapid developmental changes during some life stages (e.g., the prenatal period) and the long duration of others (e.g., the 10-year span of the adolescence period), the ECHO Program also encourages repeated collection within these life stages, to the extent possible.

Some data elements are not life stage-specific and are denoted as “collect once” in this protocol


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(see Section 5.2). Cohorts are expected to collect these data elements at least once over the course of the ECHO Program (unless a cohort has previously collected them, i.e., existing data).

5.2 Essential Data Elements for New Data Collection across the Child Developmental Life Course

The ECHO MOP provides detailed information regarding the data collection procedures under the ECHO-wide Cohort Data Collection Protocol. Table 4 summarizes essential data elements (and their associated preferred and acceptable measures) under the following concepts: Sociodemographics, Child and Family Health Histories, Pregnancy-related , Caregiver Psychosocial, Built/Physical Environment, Home/Social Environment, Child Physical Health and Functioning, Child Neurodevelopmental Health and Functioning, Child Health Behaviors/Lifestyle-related Data Elements, Child Social Role Performance and Functioning, Child Sleep Health, and Child Well-being.

The following guidance supports the interpretation of Table 4:

• “Concepts” are overarching organizational constructs that encompass numerous related data elements; within concepts, data elements are generally organized chronologically across the child life course.

• “Collect Once” indicates that the collection of that essential data element is required at least once during ECHO-wide Cohort Data Collection Protocol participation; cohorts may collect these elements in any appropriate life stage (per associated measure administration instructions, see the ECHO MOP for details).

• An “X” in a given life stage indicates that the data element is essential in that life stage. An “X(R)” in a given life stage indicates that the data element is recommended in that life stage, but is essential in another life stage. In some instances, the preferred and acceptable measures for a given data element differ in the life stages indicated for collection (e.g., one measure is “Collect Once” and the other is life stage-specific). In these cases, the “X” is superscripted with “XPref” or “XAccpt” to clarify the life stage for collection of the preferred and acceptable measures.

• Some essential data elements also have alternative measures listed (denoted by the alpha symbol “α”); these alternative measures are presented by data element in Table 8.

• Cohorts are expected to collect essential data elements in the adolescence life stage per Table 4, with the following two considerations:

o Where corresponding adult versions of pediatric measures are available, cohorts with adult child participants, defined as those aged 18 to 21 years, may use, at their discretion, either the pediatric measures (provided in Table 4) or the discretionary adult versions (provided in Table 9).

o In cases where there is no corresponding adult version of a pediatric measure for adult child participants, or the data element itself is not relevant for adolescents (see Table 4 footnotes), the essential data element is recommended (as appropriate).


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Table 4 Essential Data Elements Across the Child Developmental Life Course

Data Element(s)

Measure

New Data Collection Window

Collect Once

Life Stage

Preferred Acceptable PNA PER INF EC MC ADO

Concept: Sociodemographics

Lifetime/updated residential address

Residential Address Historya

Same as Preferred X X X X Xb

Caregiver and partner occupation Caregiver Occupation and Employment

Same as Preferred X X X X X

Household income, Receipt of federal assistance, Financial strain

Income, Assistance, and Financial Strainc


Household primary language spoken, Household primary language read

Language and Acculturationc


Household composition, Caregiver relationship

Household Compositionc Same as Preferred X X X X Xb

Early care and education Early Care and Education Same as Preferred X X

K12 Education Child K12 Education Same as Preferred X X Xd

Gender identity Gender Identity Same as Preferred X X

Adolescent occupation Adolescent Occupation and Employment

Same as Preferred X


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Data Element(s)

Measure


Collect Once

Life Stage


Child demographics Demographics of Child Same as Preferred X (collect once after the birth of the child)

Biological family demographics Demographics of Biological Familye

Same as Preferred X

Rearing family demographics Demographics of Primary Caregiver Familye

Same as Preferred X

Concept: Child and Family Health Histories

Caregiver and child health insurance status

Health Insurance Coverage Same as Preferred X X X X X

Lifetime/updated first degree relative family medical conditionsf

Medical History – Biological Family

Same as Preferred X X X X X

Child medical historyf Child Medical History Note: Separate forms for INF, EC, MC/ADO

Child Medical Record Abstraction X X X X

Child birth information Child Birth Medical Record Abstraction

Child Birth Information X


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Data Element(s)

Measure


Collect Once

Life Stage


Concept: Pregnancy-related Data Elements (Biological Mother)

Maternal food contaminants in pregnancy

Maternal Food Source and Preparation

Same as Preferred X

Maternal diet in pregnancy National Cancer Institute (NCI) Diet History Questionnaire Third Edition (DHQ III)g

Dietary Screener Questionnaire –Self-Reporth

X

Maternal sleep health in pregnancy

Maternal Sleep Health in Pregnancy

Same as Preferred X

Maternal sleep quality in pregnancyα

PROMIS v1.0 - Sleep Disturbance 4a/CAT

Same as Preferred

X

Maternal sleep-related impairment in pregnancy

PROMIS v1.0 - Sleep-Related Impairment 4a/CAT

Same as Preferred

X


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Data Element(s)

Measure


Collect Once

Life Stage


Maternal weight and height (includes pre-pregnancy weight)

Prenatal: Maternal Medical Record Abstraction

Prenatal: Maternal Weight and Height – Measuredi

or

Pregnancy Weight Gain – Prenatal Self-Reportj

XPref XAccpt

All other life stages: Maternal Weight and Height – Measuredk

All other life stages: Total Pregnancy Weight Gain – Self-Reportl

X(R) X(R) X(R) X(R)

Total pregnancy weight gain (includes pre-pregnancy weight)

Maternal Medical Record Abstraction

Total Pregnancy Weight Gain – Self-Reportl

X

Maternal substance use in pregnancy


Lifestylem,n X

Maternal supplements in pregnancy


Maternal Supplementsm,n X

Maternal pregnancy-related conditions/medical interventions


Pregnancy Medical Conditions and Interventionsm,o

X


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Data Element(s)

Measure


Collect Once

Life Stage


Laboratory and screening test results (including Zika virus)

Maternal Medical Record Abstraction Same as Preferred

X

Pregnancy dating X

Receipt of prenatal care X

Serial pregnancy measurements (including recent travel [self or partner] in pregnancy)

X

Ultrasound results X


11 December 2018 39


Data Element(s)

Measure


Collect Once

Life Stage


Concept: Caregiver Psychosocial-related Data Elements

Global health PROMIS v1.2 - Global Health Scale

PROMIS v1.2 - Global Health Mental 2a and PROMIS v1.2 - Global Health Physical 2a

X X X X X

Depressive symptomsα PROMIS v1.0 - Depression 8a/CAT

Same as Preferred X X X X(R) X(R)

Perceived stressα Perceived Stress Scale 10-itemp

Perceived Stress Scale 4-item X X X X(R) X(R)

Social supportα PROMIS v2.0 - Emotional Support 4a/CAT, and

PROMIS v2.0 - Informational Support 4a/CAT, and

PROMIS v2.0 - Instrumental Support 4a/CAT

Same as Preferred X X X X(R) X(R)


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Data Element(s)

Measure


Collect Once

Life Stage


Stressful life events in adulthood (age ≥18 yrs)α

Crisis in the Family Systems - Revised (CRISYS - R)

Stressor Checklistq X X X X(R) X(R)

Discriminationα The Everyday Discrimination Scale

The Everyday Discrimination Scale (Short Version)

X X(R) X(R) X(R) X(R)

Caregiver IQα NIH Toolbox Cognition Battery (all constituent tasks were v2.1 at time of protocol finalization)

NIH Toolbox Picture Vocabulary Test v2.1 X

Stressful life events in childhood (age <18 yrs)α

Childhood Trauma Questionnaire

Adverse Childhood Experiences – Adult Primary Versionr or Adverse Childhood Experiences – Adult Alternate Versionr

X


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Data Element(s)

Measure


Collect Once

Life Stage


Concept: Built/Physical Environment-related Data Elements

Chemical exposures (encompasses indoor air pollution)

Household Chemical Exposure – Pre-pregnancy and Pregnancym,s

Same as Preferred X

Household Chemical Exposure – Recallm

Same as Preferred Xt Xt

Household Chemical Exposure – Currentm

Same as Preferred X X Xb

Household exposure to secondhand smoke

Household Exposure to Secondhand Smoke – Pre-pregnancy and Pregnancym, s

Same as Preferred

X

Household Exposure to Secondhand Smoke – Recallm

Same as Preferred Xu

Household Exposure to Secondhand Smoke – Currentm

Same as Preferred X X X Xb

Maternal and paternal work exposures

Maternal and Paternal Occupation Exposuresm,v

Same as Preferred X


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Data Element(s)

Measure


Collect Once

Life Stage


Concept: Home/Social Environment-related Data Elements

Caregiving quality and behaviorα Child 0 to 5 yrs: National Institute of Child Health and Human Development (NICHD) Direct Observation - Caregiver - Child Free Play

Child 5 to 7 yrs: Parenting Scale

Child 8+ yrs: Alabama Parenting Questionnaire Parent Form or Child Formw

Child 9 mos to 5 yrs: Parenting Scale Child 5 to 7 yrs: Same as Preferred

Child 8+yrs: Alabama Parenting Questionnaire 9-item Parent Form or Child Formw

X X X Xx


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Data Element(s)

Measure


Collect Once

Life Stage


Family relationships Child 0 to 5 yrs: Family Environment Scale (FES) – Family Cohesion Subscale

Child 5 to 7 yrs: PROMIS v1.0 - Family Relationships 8a - Parent Proxy/CAT

Child 8+ yrs: PROMIS v1.0 - Family Relationships 8a – Pediatric/CAT

Child 0 to 5 yrs: Same as Preferred

Child 5 to 7 yrs: PROMIS v1.0 - Family Relationships 4a - Parent Proxy/CAT

Child 8+ yrs: PROMIS v1.0 - Family Relationships 4a – Pediatric/CAT

X X X Xx

Child negative life eventsα Child 1 to 11.9 yrs: Adverse Childhood Experiences – Parent Report

Child 12 to 17.9 yrs: Adverse Childhood Experiences – Child Self-Report

Same as Preferred

X X Xy

Concept: Child Physical Health and Functioning-related Data Elements

Child length at birth, Child weight at birth

Child Anthropometry and Physical Examinationz

Child Medical Record Abstraction or Birth Information

XAccpt XPref


11 December 2018 44


Data Element(s)

Measure


Collect Once

Life Stage


Child head circumference at birth Child Anthropometry and Physical Examinationz

Child Medical Record Abstraction XAccpt XPref

Child length (child 0 to <2 yrs)

Child Anthropometry and Physical Examinationz

Child Medical Record Abstraction

X X

Child head circumference (child 0 to <3 yrs)

X X

Child weight X X X X

Child blood pressure X X X X

Child height/stature (child 2+ yrs) X X X

Child resting heart rate X X X X

Child waist circumference (child 2+ yrs)

Same as Preferred X X X

Child body compositionα Dual-energy X-ray Absorptiometry (DXA)

X X X X


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Data Element(s)

Measure


Collect Once

Life Stage


Airways-related health outcomesaa

Asthma impactbb

Asthma impactbb

Airways Questionnaires

Note: There are separate questionnaires for use in INF for infants aged 9 to 12 mos, and in EC, MC, and ADO

Same as Preferred

X X X X

Child 5 to 7 yrs: PROMIS v2.0 - Asthma Impact 8a - Parent Proxy/CAT

X

Child 8+ yrs: PROMIS v2.0 - Asthma Impact 8a – Pediatric/CAT

X Xcc

Child pubertal developmentα Child 9+ yrs: Pubertal Development Scale

Same as Preferred X Xcc


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Data Element(s)

Measure


Collect Once

Life Stage


Concept: Child Neurodevelopmental Health and Functioning-related Data Elements

Child developmental milestonesα Ages and Stages Questionnaire

Same as Preferred X X

Temperamentα Child 3 to 12 mos: Rothbart Infant Behavior Questionnaire Revised Very Short Form (Ages 3-12 Months)

Child 13 to 36 mos: Rothbart Early Childhood Behavior Questionnaire Very Short Form (Ages 13-36 Months)dd

Child 3 to 5 yrs: Rothbart Childhood Behavior Questionnaire Very Short Form (Ages 3-5 Years)

Same as Preferred

X X


11 December 2018 47


Data Element(s)

Measure


Collect Once

Life Stage


Emotional and behavioral functioningα

Child 1.5 to 5 yrs: Child Behavior Checklist (CBCL) for Ages 1.5 to 5

Child 6 to 18 yrs: Child Behavior Checklist (CBCL) for Ages 6 to 18

Strengths and Difficulties Questionnaire (SDQ)ee

X X Xy

Child general cognitionα Child 3 to 6 yrs: NIH Toolbox Early Cognition Battery (all constituent tasks were v2.1 at time of protocol finalization)

Child 7+ yrs: NIH Toolbox Cognition Battery (all constituent tasks were v2.1 at time of protocol finalization)

Child 3 to 6 yrs: NIH Toolbox Dimensional Change Card Sort v2.1 and NIH Toolbox Picture Vocabulary Test v2.1

Child 7+ yrs: Same as Preferred

X X (complete the NIH Toolbox

Cognition Battery once in

MC or ADO)

Child social cognition Child 18 mos to 4 yrs: Social Responsiveness Scale - Second Edition (SRS-2) Preschool

Child 4 to 18 yrs: Social Responsiveness Scale - Second Edition (SRS-2) School Age

Same as Preferred

Xy,ff


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Data Element(s)

Measure


Collect Once

Life Stage


Child perceived stress Child 5+ yrs: PROMIS v1.0 - Psychological Stress Experiences 4a - Parent Proxy/CAT or Child 8+ yrs: PROMIS v1.0 - Psychological Stress Experiences 4a - Pediatric/CAT

Child 8 to 12 yrs: Perceived Stress Scale 10-item - Parent Report (Ages 8-12)gg

Child 13 to 17 yrs: Perceived Stress Scale 10-item - Self-Report (Ages 13-17)gg

X(R) X Xy

Concept: Child Health Behaviors/Lifestyle-related Data Elements

Infant feeding and introduction to solids

Infant Feeding Practiceshh Same as Preferred X

Infant feeding history Complementary Feeding History (note: complete as early as possible in EC)

Same as Preferred X

Child food contaminants Child Food Source and Preparation

Same as Preferred X X


11 December 2018 49


Data Element(s)

Measure


Collect Once

Life Stage


Child diet Child 2 to 7 yrs: Block Questionnaire for Ages 2-7 - Kids 2-7 FFQii

Child 8 to 17 yrs: Block Questionnaire for Ages 8-17 - 2004 FFQii

Child 2 to 10 yrs: Dietary Screener Questionnaire - Parent Reporth

Child 11+ yrs: Dietary Screener Questionnaire –Self Reporth

X X Xy

Child physical activity Child 5 to 7 yrs: PROMIS v1.0 - Physical Activity 8a - Parent Proxy/CAT

Child 8+ yrs: PROMIS v1.0 - Physical Activity 8a - Pediatric/CAT

Same as Preferred

X(R) X Xcc

Child sexual behavior Youth Risk Behavior - Sexual Behaviorjj

Same as Preferred X

Child substance use Youth Risk Behavior - Substance Usejj

Same as Preferred X


11 December 2018 50


Data Element(s)

Measure


Collect Once

Life Stage


Concept: Child Social Role Performance and Functioning-related Data Elements

Academic ability and performanceα

Child 2 to 5 yrs: Early Academic Competencies - Parent Reportkk

Child 6+ yrs: Healthy Pathways Academic Performance Scale – Parent Report or Healthy Pathways Academic Performance Scale – Child Reportll

Same as Preferred

X X Xcc

Peer relationships Child 3 to 7 yrs: NIH Toolbox v2.0 - Positive Peer Interactions - Parent Report (Ages 3 to 12)

Child 8+ yrs: PROMIS v2.0 - Peer Relationships 8a - Pediatric/CAT

Same as Preferred

X X Xy


11 December 2018 51


Data Element(s)

Measure


Collect Once

Life Stage


Concept: Child Sleep Health-related Data Elements

Child sleep health Child 0 to 12 mos: Sleep Health of Infants

Child 12 mos to 17 yrs: Sleep Health of Children and Adolescents - Parent Report

Child 8+ yrs: Sleep Health of Children and Adolescents – Self-Report

Same as Preferred

X X X Xy

Child sleep quality Child 2 to 7 yrs: PROMIS v1.0 - Sleep Disturbance 4a - Parent Proxy/CAT

Child 8+ yrs: PROMIS v1.0 - Sleep Disturbance 4a - Pediatric/CAT

Same as Preferred

X X Xy


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Data Element(s)

Measure


Collect Once

Life Stage


Child sleep-related impairment Child 5 to 7 yrs: PROMIS v1.0 - Sleep-Related Impairment 4a - Parent Proxy/CAT

Child 8+ yrs: PROMIS v1.0 - Sleep-Related Impairment 4a - Pediatric/CAT

Same as Preferred

X(R) X Xy

Concept: Child Well-being-related Data Elements

Child global health Child 0 to 4 yrs: Child Global Healthmm

Child 5 to 7 yrs: PROMIS v1.0 - Global Health Scale 7 + 2 - Parent Proxy

Child 8+ yrs: PROMIS v1.0 - Global Health Scale 7 + 2 - Pediatric

Same as Preferred

X X X Xy


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Data Element(s)

Measure


Collect Once

Life Stage


Child well-being - life satisfaction Child 5 to 7 yrs: PROMIS v1.0 - Life Satisfaction 8b - Parent Proxy/CAT

Child 8+ yrs: PROMIS v1.0 - Life Satisfaction 8b - Pediatric/CAT

Same as Preferred

X(R) X Xy

Child well-being - meaning and purpose

Child 10+ yrs: PROMIS v1.0 - Meaning and Purpose 8a - Pediatric/CAT

Same as Preferred X Xy

Abbreviations: ADO, adolescence; EC, early childhood; INF, infancy; MC, middle childhood; mos, months; PER, perinatal; PNA, prenatal; yrs, years. a There are two versions of the residential address history form, one for use in the prenatal life stage and one for use in childhood. The pregnant woman should

complete the prenatal version as late as possible in pregnancy (ideally in the third trimester). The child participant’s primary caregiver should complete the child version during the infancy through adolescence life stages per form instructions (note: if the adolescent participant is no longer living within the caregiver home, he/she should answer for his/her primary dwelling).

b If the adolescent participant is no longer living within the caregiver home, he/she should answer for his/her primary dwelling. c There is one version for use in the prenatal life stage and one for use in childhood. d Measure not appropriate if the adolescent participant is no longer in school. e ECHO cohorts are expected to collect demographic information related to the ECHO child’s biological family members; however, in cases where biological

family members are not the primary caretakers of the child (e.g., child is adopted, biological caregivers deceased), this information may not be available. In these cases, capturing the child’s rearing family demographics is critical. If the rearing family is different than the biological family, ECHO cohorts should strive to collect both biological family and rearing family demographics to the extent possible.

f Regarding medical histories: If the adolescent participant is ≥18 years old, he/she can complete the “Medical History – Biological Family” and the “Child Medical History – Middle Childhood and Adolescence” preferred measures him/herself. For child medical histories, collect child medical history information using the preferred or acceptable measure as late in each life stage as possible (in order to maximize coverage of each life stage).

g The DHQ III is a freely available, web-based tool. Collect the DHQ III, past month with portion size version, once at any point during pregnancy.

https://epi.grants.cancer.gov/dhq3/index.html


11 December 2018 54

h Adapted from the National Health and Nutrition Examination Survey (NHANES) Dietary Screener Questionnaire (DSQ) 2009-10. For child participants, adolescents may complete the Dietary Screener Questionnaire– Self Report for themselves, or the primary caregiver may complete the Dietary Screener Questionnaire- Parent Report for them.

i Measure weight on the pregnant participant at least once during pregnancy, ideally within 4 weeks of the expected delivery date. If collecting more than once during the prenatal life stage, measure weight at each encounter. Maternal height is only required once.

j The Pregnancy Weight Gain – Prenatal Self-Report should be completed by the pregnant participant if unable to collect the Maternal Weight and Height – Measured (see footnote “i” above) during pregnancy. Administer as late as possible during pregnancy, ideally within 4 weeks of the expected delivery date.

k Recommend collecting maternal weight in INF, EC, MC, and ADO. Maternal height is only required once. l This should be completed by the woman enrolled in an ECHO cohort or by the biological mother of a child enrolled (if different). m Adapted from The Early Life Exposures Assessment Tool (ELEAT) © The Regents of the University of California, Davis campus. n This can be collected concurrently during the prenatal life stage using the “Pre-pregnancy and Pregnancy” version. For repeat collection during pregnancy

(optional), use the subsequent “Pregnancy Incremental” version. This data element can also be collected via recall using the “Recall" version, considered valid until the child reaches 8 years of age. If cohorts collect this information during pregnancy, they must also complete infancy portion on the “Recall” version for complete data collection.

o Collect “Pregnancy Medical Conditions and Interventions” once for each pregnancy resulting in a child (or children) enrolled in an ECHO cohort, if the biological mother is available to provide the information. If the pregnancy does not result in a live birth, cohorts should seek this information from the pregnant woman enrolled where possible. The form should be completed in the INF (ideally after the child is at least 3 months of age), EC, or MC life stage (recall considered valid until the child reaches 8 years of age).

p Available through the NIH Toolbox Fixed Form v2.0 – Perceived Stress (Ages 18+) © 2006-2017 National Institutes of Health and Northwestern University. q Complete the Life Stressor Checklist at first administration, for subsequent administrations to the same individual, complete the 12-Month Stressor Checklist. r The Adverse Childhood Experiences - Adult Primary Version maintains individual items, while the Adverse Childhood Experiences - Adult Alternate Version

groups sensitive items related to physical and emotional abuse with less sensitive/non-reportable items. It is at the individual cohort’s discretion to determine the most appropriate version for its setting.

s This can be collected concurrently during the prenatal life stage using the “Pre-pregnancy and Pregnancy” version. For repeat collection during pregnancy (optional), use the subsequent “Pregnancy Incremental” version.

t If “Recall” version is not collected in INF, collect once in EC or MC. Recall is considered valid until the child reaches 8 years of age. u If not collected concurrently during the prenatal life stage, complete the “Recall” version once in INF, EC, or MC. Recall is considered valid until the child

reaches 8 years of age. v This can be collected concurrently during the prenatal life stage using the “Pre-pregnancy and Pregnancy” version. This can also be collected via recall using

the “Recall" version, considered valid until the child reaches 8 years of age. If cohorts collect this information during pregnancy, they must also complete infancy portion on the “Recall” version for complete data collection.

w The child form of the Alabama Parenting Questionnaire or the Alabama Parenting Questionnaire 9-item is recommended for children 13+ years (cohort discretion).

x If the adolescent participant is no longer living within the caregiver home, this data element is not essential, but is recommended as relevant/applicable (cohort discretion).

y See Table 9 for the corresponding adult measure (cohort discretion). z There is one child anthropometry and physical examination form for use in PERI with newborns, one for use in INF and EC with children 0 to 2 yrs old, and

one for use in EC, MC, and ADOL with children >2 yrs old.


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aa The ECHO Program expects each cohort to collect life stage-specific measures at least once in each life stage (see Section 5.1); however annual collection of the life stage-specific Airways Questionnaires (or collections at each point of contact) are strongly encouraged.

bb Assess asthma impact only if child has a “yes” response to the item “Has a doctor or other healthcare provider ever diagnosed the child with asthma?” on the Middle Childhood or Adolescence Airways Questionnaires.

cc There is no corresponding adult version of this measure. Therefore, this data element is not essential in adolescent participants aged 18 to 21, but is recommended as relevant/applicable (cohort discretion).

dd Per the developer “The ECBQ is the best choice for the 13 to 17 month age range, since several IBQ items do not appear to be appropriate for children older than one year. Exceptions to this rule include use with samples with developmental delays or use by researchers who wish to directly compare their results at 13-17 months to data obtained with 3- to 12-month-olds.”

ee For the SDQ, there are different parent report versions for children 2 to 4 years, 4 to 10 years, and 11 to 17 years. There is also a child-self report version for children aged 11 to 17 years and an adult self-report version for children aged 18+ years. Complete the age appropriate version in each life stage indicated for collection (cohort discretion whether to use the parent or child-self report version in participants aged 11 to 17 years).

ff Collect the SRS-2 once between early childhood and adolescence, but in the earliest of these life stages in which the cohort sees a participant (i.e., do not postpone collection).

gg Available through the NIH Toolbox Perceived Stress Parent Report Ages 8-12 v2.0 and Fixed Form Ages 13-17 v2.0 © 2006-2017 National Institutes of Health and Northwestern University.

hh Adapted from the Infant Feeding Practices Study II postnatal questionnaires available at http://www.cdc.gov/breastfeeding/data/ifps/questionnaires.htm. ii Block Food Frequency Questionnaires are proprietary and are available in paper or electronic format. The Block Questionnaire for Ages 2-7 - Kids 2-7 FFQ

includes approximately 90 questions (6 month recall, portion sizes only asked for beverages) and would take a caregiver or interviewers approximately 30 minutes to complete. The Block Questionnaire for Ages 8-17 - 2004 FFQ includes 77 food items (with portion size, pictures provided to improve accuracy) and takes approximately 25 minutes to complete.

jj Adapted from the Center for Disease Control and Prevention 2017 Youth Risk Behavior Surveys (YRBS) for Middle and High School. The YRBS is part of the CDC Youth Risk Behavior Surveillance System (https://www.cdc.gov/healthyyouth/data/yrbs/index.htm).

kk Adapted from the 2016 National Survey of Children’s Health conducted by the United States Census Bureau, US Department of Health and Human Services. ll Cohorts may choose to administer the Healthy Pathways Academic Performance Scale - Child Report beginning when the child is aged 8+ years (cohort

discretion). mm Adapted from PROMIS Parent Proxy Scale v1.0 - Global Health 7 plus 2.

https://research.bowdoin.edu/rothbart-temperament-questionnaires/frequently-asked-questions/#Answer7

http://www.cdc.gov/breastfeeding/data/ifps/questionnaires.htm

https://www.nutritionquest.com/assessment/list-of-questionnaires-and-screeners/

https://www.cdc.gov/healthyyouth/data/yrbs/index.htm


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5.3 Recommended Data Elements for New Data Collection across the Child Developmental Life Course

The ECHO MOP provides detailed information regarding the data collection procedures under the ECHO-wide Cohort Data Collection Protocol.

Table 5 summarizes recommended data elements and their associated preferred measures across the child developmental life course. An “R” in a given life stage indicates that the data element is recommended for new data collection in that life stage. Note, some data elements are recommended in certain life stages and essential in others, these data elements are described in Table 4 above.

Table 5 Recommended Data Elements Across the Child Developmental Life Course

Data Element(s) Preferred Measure


Collect Once

Life Stage

PNA INF EC MC ADO

Child-related Data Elements

Child death Child Death Certificate R

Home screen media access and use

Child 0 to 12 yrs: Child Media Use – Parent Reporta

Child 13+ yrs: Child Media Use – Self Reportb

R R R R

Sleep ecology Child 0 to 12 mos: Infant Sleep Ecology Questionnaire

Child 12 mos to 17 yrs: Child and Adolescent Sleep Ecology Questionnaire - Parent Report

Child 8+ yrs: Child and Adolescent Sleep Ecology Questionnaire - Child Self-Report

R R R R

Neighborhood capital Neighborhood Collective Efficacy - Caregiver (PhenX #210801) R R R R

Perceived neighborhood conditions

Neighborhood Safety – Caregiver (PhenX #210901) and Physical Activity - Neighborhood Environment – Caregiver (PhenX #151201)

R R R R


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Collect Once

Life Stage

PNA INF EC MC ADO

Adaptive behavior Vineland Adaptive Behavior Scales, Third Edition (Vineland - 3) R

Autism spectrum disorder (ASD) screener

Child 16 to 30 mos: Modified Checklist for Autism in Toddlers Revised (M-CHAT-R)

R

Caregiver feeding practice and style

Child 18 mos to 6 yrs Comprehensive Feeding Practices Questionnaire and/or Child 3 to 6 yrs: Children's Eating Behaviour Questionnaire

R

Information processing speed

NIH Toolbox Pattern Comparison Test v2.1 R

Academic achievement School records, report cards of standardized achievement testsc R R R

Anxiety Child 5 to 7 yrs: PROMIS v2.0 - Anxiety 8a - Parent Proxy/CAT

Child 8+ yrs: PROMIS v2.0 - Anxiety 8a - Pediatric/CAT

R R R

Attention problems Child 4 to 7 yrs: Conners Kiddie Continuous Performance Test Second Edition (Conners K-CPT 2) and Conners 3 Parent Report Attention-Deficit /Hyperactivity Disorder (ADHD) Index

Child 8+ yrs: Conners 3 Parent Report ADHD Index and Conners 3 Self-Report ADHD Index

R R R


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Collect Once

Life Stage

PNA INF EC MC ADO

Depressive symptoms Child 5 to 7 yrs: PROMIS v2.0 - Depressive Symptoms 6a - Parent Proxy/CAT

Child 8+ yrs: PROMIS v2.0 - Depressive Symptoms 8a - Pediatric/CAT

R R R

Device- measured physical activity

Accelerometer – Childc

R R R

Home food and activity environment

Assessment of your Home Health Environmentd R R R

Motor function NIH Toolbox Motor Battery (all constituent tasks were v2.0 at time of protocol finalization)e

R R R

Nutrient and energy Child 2+ yrs: Automated Self-Administered 24-Hour (ASA24) Dietary Assessment Toolf

R R R

Positive affect Child 5 to 7 yrs: PROMIS v1.0 - Positive Affect 8a - Parent Proxy

Child 8+ yrs: PROMIS v1.0 - Positive Affect 8a - Pediatric/CAT

R R R

Professional dental care Professional Dental Care - Parent or Self-Report (PhenX #081301)g R R R

Bullying Child 8+ yrs: Healthy Pathways Bullying Scales R R

Caffeine use Caffeine Intake - Parent or Self-Report (PhenX #050300)h

R R

Lung function testing Child 6+ yrs: Spirometry - Child (PhenX #091602)

R R

Product use Child Product Use - Parent or Self-Reporth R R


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Collect Once

Life Stage

PNA INF EC MC ADO

Social support Child 8+ yrs: NIH Toolbox v2.0 - Emotional Support - Self-Report (Ages 8-17)

R R

Social-emotional competencies

Social-Emotional Student Competenciesi R R

Student engagement Child 8+ yrs: School Engagementi R R

Teacher connectedness Child 8+ yrs: Teacher-Student Relationshipsi R R

Pregnancy-related Data Elements (Biological Mother)

Maternal nausea/ vomiting in pregnancy

Pregnancy-Unique Quantification of Emesis (PUQE-24) Scale R

Maternal nutrient and energy in pregnancy

Automated Self-Administered 24-Hour (ASA24) Dietary Assessment Toolf R

Maternal sexual behavior

Sexual Risk Behavior - Female (PhenX #101702) R

Device-measured physical activity in pregnancy

Accelerometer – Maternalc

R

Physical activity in pregnancy

Pregnancy Physical Activity Questionnaire

R

Neighborhood capital Neighborhood Collective Efficacy – Pregnant Woman (PhenX #210801)

R

Perceived neighborhood conditions

Neighborhood Safety – Pregnant Woman (PhenX #210901) and Physical Activity - Neighborhood Environment - Pregnant Woman (PhenX #151201)

R


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Collect Once

Life Stage

PNA INF EC MC ADO

Primary Caregiver-related Data Elements

Caregiver ASD-related phenotype

Social Responsiveness Scale (SRS-2) - Adult (Relative/Other Report) R

Caregiver externalizing spectrum

Achenbach System of Empirically Based Assessment (ABESA) - Adult Self Report (ASR)

R

Caregiver anger PROMIS v.1.1 - Anger 5a/CAT R R R R R

Caregiver anxiety PROMIS - Anxiety 8a/CAT R R R R R

Caregiver-partner relationship

Conflict Tactics Scale for Partner and Spouse R R R R R

Caregiver wellbeing - life satisfaction

PROMIS v1.0 - General Life Satisfaction 5a/CAT R R R R R

Caregiver wellbeing - meaning and purpose

PROMIS v1.0 - Meaning and Purpose 8a/CAT R R R R R

Caregiver sleep health Sleep Health of Adults R R R R

Caregiver sleep quality PROMIS v1.0 - Sleep Disturbance 4a/CAT R R R R

Caregiver sleep-related impairment

PROMIS v.1.0 - Sleep-Related Impairment 4a/CAT R R R R

Family conflict Family Environment Scale (FES) - Family Conflict Subscale R R R Rj

Parenting sense of competency

Parenting Sense of Competence Scale R R R R

Abbreviations: ADO, adolescence; ADHD, attention deficit/hyperactivity disorder; ASD, autism spectrum disorder; EC, early childhood; INF, infancy; MC, middle childhood; mos, months; PNA, prenatal; yrs, years. a Modified from Zero to Eight: Children’s Media in America 2013 Report and Common Sense Census: Media Use

by Kids Ages Zero to Eight Report. © Common Sense Media Inc., 2013; 2017; The Common Sense Census: Plugged-In Parents of Tweens and Teens Report © Common Sense Media Inc., 2016.


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b Modified from the Common Sense Census: Media Use by Tweens and Teens Report. © Common Sense Media Inc., 2015; Social Media, Social Life: Teens Reveal Their Experiences, 2018 Report. © Common Sense Media Inc., 2018.

c Refer to the ECHO MOP (Chapter 3) for further data collection details. d This measure must be completed in the home or dwelling where the child lives. If the adolescent participant is no

longer living within the caregiver home, he/she should answer for his/her primary dwelling. e The NIH Toolbox Motor Battery for ages 7+ yrs includes five core measures (9-Hole Pegboard Dexterity Test,

Grip Strength Test, Standing Balance Test, 4-Meter Walk Gait Speed Test, 2-Minute Walk Endurance Test). For ages 3 to 6 years, the NIH Toolbox Early Childhood Motor Battery excludes the 4-Meter Walk Gait Speed Test (but includes the other four core tests).

f Complete the Automated Self-Administered 24-Hour (ASA24) Dietary Assessment web-based tool 2 to 3 times over the course of 1 month.

g This measure is parent-report for early and middle childhood, and adolescence or the adolescent can complete the child self-report.

h This measure is parent-report for middle childhood and child self-report for adolescence. i These measures are adapted from Panorama Education’s Student Survey instrument. There are different

versions for children 3rd to 5th grade and children 6th to 12th grade. This measure is not appropriate if the adolescent participant is no longer in school. The Social-Emotional Student Competencies form includes five scales - Grit, Growth Mindset, Self-Management, Social Awareness, and Self-Efficacy.

j The FES is validated for child self-report in children 11 years and older (cohort discretion).

https://epi.grants.cancer.gov/asa24/

https://www.panoramaed.com/social-emotional-learning


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5.4 ECHO-wide Cohort Data Collection Protocol Biospecimens The following sections describe biospecimens that are essential (Section 5.4.1) and recommended (Section 5.4.2) for collection under the ECHO-wide Cohort Data Collection Protocol. The ECHO Biospecimen Collection, Processing, and Storage Policy describes the policies and processes for the collection, processing, and storage of biospecimens.

Biospecimens collected under the ECHO-wide Cohort Data Collection Protocol will be stored in the ECHO physical biorepository. Fisher Bioservices will serve as the biorepository vendor for the ECHO Program. They will be responsible for providing specimen collection kits and acquiring, processing, storing, and distributing ECHO biospecimens.

5.4.1 Essential Biospecimens for New Data Collection across the Child Developmental Life Course

Table 6 summarizes essential biospecimens across the child developmental life course.

• An “X” in a given life stage indicates that the biospecimen is essential for collection in that life stage.

• An “X(R)” in a given life stage indicates that the biospecimen is recommended for collection in that life stage, but essential in another life stage.

• “Collect Once” indicates that the collection of that essential biospecimen is required at least once during ECHO-wide Cohort Data Collection Protocol participation. Cohorts may collect these biospecimens in any life stage.

Table 6 Essential Biospecimens Across the Child Developmental Life Course

Biospecimen Collection Window

Collect Once

Life Stage

PNA PER INF EC MC ADO

Maternal Biospecimens (Pregnant Woman/Biological Mother)

Sample appropriate for DNAa X

Whole bloodb Xc X(R)

Hair Xd

Urinee Xc

Toenails Xf


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Table 6 Essential Biospecimens Across the Child Developmental Life Course


Collect Once

Life Stage


Child Biospecimens

Sample appropriate for DNAa X

Hair X(R) X(R) X X X

Toenails X X X X

Urinee X(R) X X X

Whole blood/Blood Spot X(R)g X(R)g X(R)b Xb Xb

Shed teethh X X

Abbreviations: ADO, adolescence; EC, early childhood; INF, infancy; MC, middle childhood; PER, perinatal; PNA, prenatal. Note: Per 45 CFR § 46.110[f,2] and 21 CFR § 56.110[f,2], for minimal risk research purposes, the collection of blood by finger stick, heel stick, ear stick, or venipuncture from children and pregnant women should not exceed the lesser of 50 mL or 3 mL/kg in an 8 week period and may not occur more frequently than twice per week. Total blood collection for clinical, ECHO-wide Cohort, and cohort-specific purposes should not exceed the limits described. a Blood (buffy coat) is the preferred DNA source; saliva is an acceptable alternative. b Venipuncture is preferred, but a blood spot is an acceptable alternative if venipuncture is not possible (collection

of both blood spot and venipuncture is optimal). Cohorts should plan to collect 15 mL of blood specifically for the ECHO-wide Cohort, to be stored as aliquots of whole blood, buffy coat, plasma, serum, and red blood cells, and 1 dried blood spot (250 µl). Refer to the Blood and Blood Spot Collection, Processing, and Storage Documents in the ECHO MOP.

c The protocol indicates collection at least once during the prenatal life stage, however, collections during each trimester are recommended where possible. Pregnancy trimesters are defined as: first, 0 to 13 weeks; second, 14 to 26 weeks; third, 27 to 40 weeks (or the end of pregnancy).

d Collect maternal hair in the prenatal or perinatal life stage (perinatal is preferred). For prenatal sampling, collect as late in pregnancy (as close to delivery) as possible. For perinatal sampling, collect as close to delivery as possible (preferably prior to hospital discharge).

e Refer to the Urine Collection, Processing, and Storage Documents in the ECHO MOP for recommended urine volumes.

f Collect maternal toenails as late in pregnancy (as close to delivery) as possible. g Recommend collection of a child blood spot in the perinatal and infancy life stages. h Collect shed teeth (typically occurring from 5 to 13 years of age) from middle childhood through adolescence.


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5.4.2 Recommended Biospecimens for New Data Collection across the Child Developmental Life Course

Table 7 summarizes recommended biospecimens across the child developmental life course. An “R” in a given life stage indicates that the biospecimen is recommended for collection in that life stage.

Table 7 Recommended Biospecimens Across the Child Developmental Life Course

Biospecimen


Collect Once

Life Stage


Maternal Biospecimens (Pregnant Woman/Biological Mother)

Stool R

Placenta R

Breast milk Ra

Child Biospecimens

Cord blood R

Meconium R

Nasal mucus Rb Rc

Stool Rb Rc R R

Paternal Biospecimens (Biological Father)

Sample appropriate for DNAd R

Abbreviations: ADO, adolescence; EC, early childhood; INF, infancy; MC, middle childhood; PER, perinatal; PNA, prenatal. a Collect a breast milk sample once at the first post-partum visit. b Repeated sampling at 1 month and 6 months of age is recommended. c Repeated sampling at 1 year and 3 years of age is recommended. d Blood (buffy coat) is the preferred DNA source; saliva is an acceptable alternative.


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6. Data Management

6.1 Data Submission to the ECHO DAC The ECHO Program expects cohorts to transfer all existing and newly collected essential and recommended data elements included in the ECHO-wide Cohort Data Collection Protocol to the ECHO DAC in a manner consistent with the ECHO Data Sharing Policy.

Cohorts will submit all data to the ECHO DAC through ECHOPortal.org, the main hub for data-centered ECHO-wide Cohort activities. At the outset, the DAC will associate each user of ECHOPortal with organizational levels within the ECHO Program (e.g., cohort award, cohort within award, site within cohort within award) that set the default access that the user has to view data. In addition, each user will be assigned one or more authorization groups or roles (e.g., data manager, study coordinator) that govern the access granted for various utilities and modules on ECHOPortal.

Cohorts will transfer existing data in encrypted format using the “Data Upload” utility available to users with approved uploading privileges..

There are several approaches cohorts may use to collect and submit new data:

• The ECHO DAC will provide an electronic data capture system for the new collection of all essential and recommended data elements included in the ECHO-wide Cohort Data Collection Protocol through “REDCap Central” on ECHOPortal. REDCap (Research Electronic Data Capture) is a metadata-driven electronic data capture software for web-based application developed by Vanderbilt University. The ECHO DAC will customize the system for the measures targeted for collection by a specific cohort. Data entered by the cohort into this system will be captured in real-time in a central secure database at the ECHO DAC. The ECHO Program will permit the use of alternative measures under certain circumstances (see Section 4.2.4), but the ECHO DAC-developed data capture system will not provide tools for collecting these measures.

• A cohort may update their own data capture system to accommodate the collection of the specific measures targeted for collection, and submit these data in batch via the ECHOPortal Data Upload utility, just as they will for existing data.

• A cohort may use their own data capture system for data they already collect, in combination with the ECHO DAC data capture system for newly collected data elements (i.e., a hybrid system).

6.2 ECHOPortal and Data Security ECHOPortal is a web portal to a High-Performance Computing infrastructure developed and maintained by the ECHO DAC to receive, host, analyze, and control access to data. ECHOPortal provides access to numerous tools, including a metadata catalog of data collected by each cohort, a participant registration system, data capture and processing systems, a biospecimen tracking system, and tools for the analysis of ECHO-wide Cohort data.

ECHO cohorts will collect data under the ECHO-wide Cohort Data Collection Protocol and enter


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or transfer these data through ECHOPortal. The system and tools available through ECHOPortal that cohorts will use to collect data under this protocol comply with the Federal Information Security Management Act (FISMA) low-level information security requirements for federal information security systems.

Data will be processed, stored and analyzed at the ECHO DAC under FISMA moderate security controls. FISMA moderate security requires that the ECHO DAC use extensive security procedures and controls as well as regular vulnerability scans of the computers and related systems. Compliance with the requirements is evaluated by a government-accredited third-party assessor prior to the issuance of an Authority to Operate. The following required security measures decrease the risk of a breach or data leak:

• Multiple network firewalls and an Intrusion Prevention/Detection system protect all network communication in and out of the moderate network. The network implements a "default deny" rule that drops all traffic not explicitly permitted. The ECHO DAC monitors network traffic for malicious behavior and other specific attack signatures.

• Access to the moderate network is controlled through a virtual private portal that requires multi-factor authentication using a software token and a PIN. All connections to the moderate network require an encrypted virtual private network connection that securely encrypts all network traffic and data in transit.

• Telnet, File Transfer Protocol, Simple Mail Transfer Protocol, Network Basic Input/Output System, and other clear-text (not encrypted) transmissions to the Internet are not permitted.

• All outbound emails from a FISMA moderate security network are limited to 50KB in size and emails cannot include attachments. The ECHO DAC FISMA moderate environment will not provide an outbound email capability.

• There is no direct Internet access into or out of the moderate network.

• Users cannot take information from the environment and paste it into an external system or application.

Within ECHOPortal, data are encrypted when not being used. Data transmissions from the ECHO cohorts will be encrypted and captured in a secure data lake that is also encrypted within the ECHOPortal environment. The ECHO Data Lake is a write once, then read-only data storage, allowing the data to be tracked exactly as submitted, including information regarding when the data was submitted and by whom.

6.3 Data Quality Assurance The ECHO DAC, the ECHO CC, the ECHO PRO Core, and other involved ECHO components will follow written standard operating procedures documented in the ECHO MOP to ensure that cohorts collect data in compliance with the ECHO-wide Cohort Data Collection Protocol. The ECHO DAC (and other involved ECHO components) will also employ quality assurance (QA) and quality control (QC) procedures to assure that the data and reported results are credible


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and accurate. Quality assurance activities refer to steps taken prior to collection of data, and QC activities refer to steps taken during and following data collection to ensure unified data collection standards across cohorts.

The QA/QC procedures for data collected under this protocol include the following:

• Development of the ECHO-wide Cohort Data Collection Protocol, data collection forms, data dictionaries, and the manual of operating procedures (MOP).

• Development of an electronic data capture system available to cohorts that is specific to each cohort’s implementation of the ECHO-wide Cohort Data Collection Protocol and that includes automated edit checks to identify potential errors at the point of entry, participant scheduling, and reporting needs.

• Thorough testing of the data capture system capabilities and functioning, and establishment of change control processes, issue tracking, and load testing;

• Training and certification of cohort staff in measurement and data collection procedures; and

• Regular communication between the ECHO DAC and cohort staff to review progress and to address questions and concerns.

The QC metrics for data collected under this protocol include the following:

• Numbers of children and pregnant women enrolled and completeness of follow-up by cohort, cohort award, and ECHO-wide.

• Number and percent of variables that are missing, outside of accepted ranges, or inconsistent between-variables. Depending upon the review outcome, specific data will move forward for additional processing and editing or for data harmonization and use in analysis.

• Comprehensive quality (e.g., illogical values, unexpected distributional properties) and completeness (at item and form level) assessment.

6.4 Data Access Data that are individually unique and pose a theoretical risk of participant re-identification may be accessed only by select ECHO DAC staff (e.g., data analysts, system administrators) within a secure FISMA moderate virtual computing enclave that includes two-factor authentication (i.e., identity must be proven in two different ways before a user can gain access).

The policies and procedures for obtaining access to ECHO-wide Cohort data for the purposes of conducting analyses for a Steering Committee-approved analysis proposal are described in the ECHO Data Sharing Policy, the ECHO Publications Policy, and the ECHO MOP.

The ECHO DAC may revoke any and all access for a user if s/he is found to be in violation of the policies, principles, and procedures of the NIH and the ECHO Data Sharing Policy. This policy ensures that security controls meet government standards and security risks have appropriate mitigation strategies. Security controls in place include access control, physical and


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environmental protection, personnel security, accountability and audit, and system/information integrity.

6.5 Biospecimen Tracking The ECHOPortal Biospecimen Tracking system (Bio-Track) will manage biospecimens and their associated metadata. Within this system, cohort staff enter information about the collection, processing and storage steps taken with each biospecimen at their local facilities and link the biospecimen to a participant and to their location in local storage facilities. In addition, they enter relevant information collected about the participant (e.g., time since the participant last ate). Authorized users can perform specimen container and sample management, prepare shipment manifests, and finalize shipments using Bio-Track. Shipment information, containing only de-identified sample, container and shipping information is securely transmitted to the central repository’s Laboratory Information Management System (LIMS) using Bio-Track.

6.6 Record Retention Data transmitted or entered via ECHOPortal under the ECHO-wide Cohort Data Collection Protocol will be maintained at the ECHO DAC for the duration of the ECHO DAC grant. Near the end of the grant, the ECHO DAC will transfer the data to a repository consistent with the ECHO Data Sharing Policy.

7. Analysis Proposals The objective of this protocol is to standardize data collection and sharing across the ECHO Program. The overarching outcome-specific research questions posed in Table 1 were intentionally broad to stimulate the identification of essential and recommended data elements and biospecimens, and the preferred and acceptable measures of those data elements for inclusion in this protocol; not necessarily to drive any specific analysis plans.

Separate, research question-specific analysis proposals will describe future analyses of data collected under the ECHO-wide Cohort Data Collection Protocol (i.e., analyses of the ECHO-wide Cohort data). Both ECHO Cohort Investigators and outside investigators will develop these analysis proposals in close collaboration with the ECHO DAC, and the ECHO Steering Committee will review and approve them (see the ECHO Publications Policy for more information).

8. Study Responsibilities

8.1 ECHO Coordinating Center, Data Analysis Center, and Person-Reported Outcome Measurement Core Responsibilities

8.1.1 ECHO Coordinating Center Responsibilities The ECHO CC will provide the overall coordination and support of activities and communications accruing to the conduct of the ECHO-wide Cohort Data Collection Protocol.


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The ECHO CC is responsible for maintaining the current version of the ECHO-wide Cohort Data Collection Protocol, and will make any protocol revisions available to the cohorts for follow-up with involved IRBs.

In addition, the ECHO CC will:

• Serve as the main point of contact between the ECHO single institutional review board (sIRB) and the cohort sites, and facilitate event reporting from the cohort sites and the ECHO DAC to the ECHO sIRB.

• Develop and maintain the ECHO MOP.

• Facilitate the ECHOPortal access request process.

• Collaborate with the ECHO DAC, the ECHO PRO Core, experienced ECHO cohorts, and the ECHO Biorepository to provide protocol training.

• Review cohort-specific informed consent documents to ensure the required ECHO-wide Cohort Data Collection Protocol consent language is incorporated.

• Review cohort-specific protocols to ensure inclusion of ECHO-wide Cohort Data Collection Protocol measures as reported to the DAC for inclusion on the ECHO-wide Cohort data platform.

• Collaborate with the ECHO DAC and the ECHO PRO Core regarding data quality assurance.

8.1.2 ECHO Data Analysis Center Responsibilities The ECHO DAC is responsible for developing and maintaining an environment to host, analyze, and control access to ECHO-wide Cohort data. The environment is accessible through a web portal (ECHOPortal.org) that provides capabilities to receive data from ECHO cohorts using secure transmission protocols; capture newly collected individual-level data using web-based data collection tools; and query, visualize, and analyze harmonized ECHO-wide Cohort data. The DAC is also responsible for tracking biospecimens and their associated metadata in the ECHOPortal Biospecimen Tracking system (Bio-Track).

8.1.3 ECHO Person-Reported Outcome (PRO) Core Responsibilities The ECHO PRO Core is responsible for efforts to enable, curate, and, where needed, enhance existing or develop new PROs, where the term “PRO” refers broadly to any information about exposures, covariates, and outcomes obtained through self- or proxy-report, observation, performance-based testing, or personal sensor devices. The ECHO PRO Core will conduct quality checks on PRO data.


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8.2 ECHO Cohort Investigator Responsibilities It is the responsibility of the ECHO Cohort Investigator or designee with oversight for any contributing cohort to:

• Provide all study personnel under their supervision with copies of the ECHO-wide Cohort Data Collection Protocol and access to all information provided by the ECHO CC, and to ensure that they are fully informed about the conduct of the processes within the protocol.

• Ensure that a properly constituted IRB has reviewed and approved the ECHO-wide Cohort Data Collection Protocol prior to the initiation of any protocol-related procedures.

• Ensure that prior to the initiation of any protocol-related procedures, research staff have engaged each participant or legal guardian in an informed consent process that involved full and adequate information about the protocol, and that the participant or legal guardian has signed and dated an informed consent (or assent, as appropriate) form, as required by the IRB of record.

• Retain source documents including, but not limited to, the signed and dated informed consent document, study-related progress notes, completed interviews, and questionnaires, study or participant-specific correspondences, records of files created and submitted to the ECHO DAC, according to the IRB of record/institution and NIH policies regarding record retention.

• Collect and share data with the ECHO-wide Cohort data platform under the ECHO-wide Cohort Data Collection Protocol. Separate Cohort-specific Operational Plans will document the cohort-specific processes and procedures that cohorts will conduct to collect the data elements in this protocol.

9. Ethical Considerations and Human Subjects Protection

9.1 Institutional Review Board/Ethics Committee Review A properly constituted IRB of record, formally designated to review and monitor research involving human subjects, will be accountable for compliance with regulatory requirements for the ECHO-wide Cohort Data Collection Protocol at participating cohort sites. The choice of IRB authority model, either the ECHO sIRB or the local IRB (this could be the sole local IRB for single site awards or the established sIRB of record for Cohort Awards with multiple sites), is at the discretion of the ECHO Cohort Awardee. Participating sites will then rely on the IRB of record to satisfy the regulatory requirements relevant to the IRB review. The participating sites will maintain essential required documentation of IRB reviews. Where applicable, a reliance agreement will be required between the ECHO sIRB and participating sites.

The designated IRB of record will review this protocol and all informed consent/assent forms, HIPAA Authorization forms, recruitment materials, and other relevant information prior to the initiation of any ECHO-wide Cohort Data Collection Protocol-related procedures or activities. The IRB of record will also review any amendments to this protocol prior to their implementation.


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9.2 Informed Consent The ECHO MOP provides detailed information regarding the ECHO-wide Cohort Data Collection Protocol informed consent process.

ECHO Cohort Investigators (or their designated study personnel) will obtain written informed consent from ECHO-wide Cohort Data Collection Protocol participants who are at least 18 years of age (or following any state-specific regulations), or from a parent/legal guardian, along with child assent for those participants who are younger than 18 years of age (or following any state-specific regulations). Investigators should inform potential participants about the nature and purpose of the protocol, participation and withdrawal conditions, and the risks and benefits of participation, before initiating any ECHO-wide Cohort Data Collection Protocol-related procedures or activities. The informed consent will specify that participants may choose not to participate in a specific component, biospecimen collection, questionnaire, individual question, or genetic testing at any time and that they may stop participation in the study at any time.

The Investigator will record written informed consent/assent on the properly constituted IRB approved consent/assent/HIPAA form(s). The informed consent process and form will conform to US regulations (45 CFR § 26, the “Common Rule”) and to institutional requirements for informed consent. If applicable, the informed consent form will be provided in translation for non-English-speaking participants. Investigators will provide a copy of the final signed consent/document to the participant (or the parent/legal guardian).

The ECHO Program will collect brief demographic information (e.g., age, race, ethnicity, and sex) about pregnant women and children participating in cohorts who are eligible for the ECHO-wide Cohort Data Collection Protocol but who do not consent. This will allow the Program to better understand trends and consider any biases in the resulting data.

9.3 Confidentiality of Participants The ECHO DAC will maintain the confidentiality of human subject data obtained from ECHO-wide Cohort Data Collection Protocol participants throughout the duration of the ECHO DAC initial funding period. Near the end of the funding period, the ECHO DAC will transfer data to a repository consistent with the ECHO Data Sharing Policy.

The data files submitted by ECHO cohorts may include personal identifiers, including Protected Health Information (PHI), such as date of birth and residential address. The ECHOPortal environment provides an infrastructure to share data and information while respecting and protecting ECHO participant confidentiality. The alignment of different ECHO roles (e.g., cohort data manager, ECHO DAC analyst) with access to different ECHOPortal functions (e.g., data submission, data analysis) will help to safeguard participant privacy and data confidentiality. Some functions will require having a combination of the correct role and fulfillment of additional requirements, including ECHO Steering Committee approval of an analysis proposal and IRB approval for an Investigator leading an analysis proposal.

The ECHO-wide Cohort data platform will include two types of data: anonymized data that have a very small risk of participant identification, and non-anonymized data (prior to application of


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statistical disclosure limitation techniques). Only ECHO DAC analysts will have access to the non-anonymized data, and they will conduct analyses (or re-run analyses initially done on anonymized data by a non-ECHO DAC analyst) that require access to non-anonymized data. Additional stipulations may apply for special populations, including tribal nations.

A Federal Certificate of Confidentiality has been obtained for the ECHO-wide Cohort Data Collection Protocol. The certificate will help protect against disclosures of study-related information by Federal, State or local civil, criminal, administrative, legislative, or other proceedings, although it will not guarantee that data cannot be released. Participants will be informed about the certificate during the informed consent process.

9.4 Authorization for Use and Disclosure of Protected Health Information (HIPAA) ECHO Cohort Investigators will ensure that the use and disclosure of PHI obtained under this protocol complies with the Health Insurance Portability and Accountability (HIPAA) Privacy Rule.

9.5 Risks to ECHO-wide Cohort Data Collection Protocol Participants The ECHO-wide Cohort Data Collection Protocol defines the collection of observational data. It does not include interventional procedures (e.g., the use of drugs, medical devices or procedures, vaccines, or changes of the participants’ health practices). The measures and assessments in this protocol conform to the definition of minimal risk in the federal regulations (45 CFR § 46.102[i]; the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests). A properly constituted IRB of record will review the measures and assessments in this protocol under 45 CFR § 46.404, where no greater than minimal risk is identified, and provisions are made for obtaining assent from children and the permission of their parents or guardians.

9.6 Reimbursement to ECHO-wide Cohort Data Collection Protocol Participants ECHO cohorts may reimburse participants for their time to participate in the ECHO-wide Cohort Data Collection Protocol. The degree of participant reimbursement will be at the discretion of each ECHO cohort (and commensurate with participant burden).

10. Regulatory Reporting Refer to the ECHO MOP for detailed regulatory reporting instructions.

10.1 Unanticipated Problems Involving Risks to Subjects or Others The US department of Health and Human Services, Office of Human Research Protections defines research-related unanticipated problems (UPs) as:

• Events that are unanticipated and related (or possibly related) to research participation; or

• Any event that, in the opinion of the investigator, puts the participant at greater risk than

https://www.hhs.gov/ohrp/regulations-and-policy/guidance/reviewing-unanticipated-problems/index.html#backtotop


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was previously known or recognized.

ECHO Cohort Investigators (or their designated study personnel) are responsible for reporting research-related UPs according to the IRB of record/institution processes. In addition, all research-related UPs should be reported to the ECHO CC within one business day of discovery. Unanticipated problems reported to the ECHO CC will be tracked and summarized in the sIRB continuing review.

10.2 Breach Notifications ECHO Cohort Investigators (or their designated study personnel) are responsible for immediately notifying the ECHO DAC and the ECHO CC of any breach in privacy and security (e.g., compromise of user account, significant virus/malware infection, or accidental inclusion of direct identifiers on records uploaded to ECHOPortal) as it may impact confidentiality, integrity, or availability of ECHOPortal data and resources. ECHO Cohort Investigators (or their designated study personnel) must also report any privacy breach according to the IRB of record/institution processes and to their appropriate institutional authorities. The ECHO CC will notify the NIH ECHO Program Office within three business days of receiving the final IRB of record decision and may also notify the ECHO Steering Committee.

The ECHO DAC is responsible for notifying the ECHO CC, within one business day, of any breaches of privacy and security in their databases (i.e., breaches of data housed in ECHOPortal). The ECHO CC will report the breach to the ECHO sIRB and affected ECHO Cohort Investigators within one business day of breach notification. The ECHO CC will notify the NIH ECHO Program Office within three business days of receiving the breach report and may also notify the ECHO Steering Committee. The ECHO CC will disseminate sIRB decisions to the ECHO DAC and affected ECHO Cohort Investigators for required actions and institutional reporting.

10.3 Reports of Non‐compliance The ECHO Program defines non-compliance as the failure to follow the determinations or requirements of the IRB-approved protocol. ECHO Cohort Investigators (or their designated study personnel) are responsible for reporting protocol non-compliance to the ECHO CC within one business day of discovery and to the IRB of record/institution according to institutional and/or IRB policies.


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11. Appendices

11.1 ECHO-wide Cohort Data Collection Protocol Alternative Measures Table 8 provides a by-data element summary of the alternative measures included in Version 1.2 of the ECHO-wide Cohort Data Collection Protocol. The inclusion of an alternative measure for a given essential data element is denoted by use of the “α” symbol in Table 4 (see the guidance that accompanies Table 4).

Active links to supporting references/documentation have been included to provide context for each alternative measure, but the specific instruments are not available in the ECHO MOP or the centralized data collection system (see Section 6.1), as the use of an alternative measure to satisfy ECHO-wide Cohort Data Collection Protocol requirements may occur only if it is a cohort’s legacy measure under current local IRB authority/approval.

Table 8 Essential Data Elements and Associated Alternative Measures Across the Child Developmental Life Course

Data Element(s) Alternative Measure


Collect Once

Life Stage


Concept: Pregnancy-related Data Elements (Biological Mother)

Depressive symptoms

Edinburgh Postnatal Depression Scale (EPDS)

The following measures can be linked to the PROMIS Depression metric (see PROsettaStone.org for more information on score linking):

• Adult Self-Report (ASR) Achenbach System Depression Problems Syndrome Scale

• Beck Depression Inventory II (BDI-II)

• Brief Symptom Inventory (BSI)

• Center for Epidemiological Studies Depression Scale (CES-D)

• Kessler 6 Mental Health Scale (K6)

• Patient Health Questionnaire (PHQ-9)

• SF-36 Health Survey (Mental Health Summary scores)

X X X X(R) X(R)

https://www.ncbi.nlm.nih.gov/pubmed/3651732


http://www.prosettastone.org/LinkingTables1/AngerAnxiety%20DepressionPositive%20Affect/Pages/default.aspx


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Collect Once

Life Stage


Maternal sleep quality in pregnancy

Pittsburgh Sleep Quality Index

X


Perceived stress Perceived Stress Scale 14-item X X X X(R) X(R)

Social support ENRICHD Social Support Instrument (ESSI) X X X X(R) X(R)

Stressful life events in adulthood (age ≥18 yrs)

Life Experiences Survey

Traumatic Life Events Questionnaire

X X X X(R) X(R)

Discrimination Experiences of Discrimination (EOD) X X(R) X(R) X(R) X(R)

Caregiver IQ Peabody Picture Vocabulary Test (PPVT)

Stanford-Binet Intelligence Scales

Wechsler Abbreviated Scale of Intelligence (WASI)

Wechsler Adult Intelligence Scale (WAIS)

X

Stressful life events in childhood (age <18 yrs)

Behavioral Risk Factor Surveillance System (BRFSS) ACE Module

CDC-Kaiser ACEs Module

WHO ACE International Questionnaire (ACE-IQ)

X


http://www.psy.cmu.edu/%7Escohen/








https://www.pearsonclinical.com/language/products/100000501/peabody-picture-vocabulary-test-fourth-edition-ppvt-4.html

https://www.pearsonclinical.com/language/products/100000501/peabody-picture-vocabulary-test-fourth-edition-ppvt-4.html

https://www.wpspublish.com/store/p/2951/sb-5-stanford-binet-intelligence-scales-fifth-edition

https://www.pearsonclinical.com/education/products/100000593/wechsler-abbreviated-scale-of-intelligence-wasi.html


https://www.pearsonclinical.com/psychology/products/100000392/wechsler-adult-intelligence-scalefourth-edition-wais-iv.html


https://www.cdc.gov/violenceprevention/acestudy/ace_brfss.html




http://www.who.int/violence_injury_prevention/violence/activities/adverse_childhood_experiences/questionnaire.pdf?ua=1

http://www.who.int/violence_injury_prevention/violence/activities/adverse_childhood_experiences/questionnaire.pdf?ua=1


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Collect Once

Life Stage


Concept: Home/Social Environment-related Data Elements

Caregiving quality and behavior

The Home Observation for Measurement of the Environment (HOME)a

X X

Child negative life events

Adverse Childhood Events Expanded (ACEs-E)

Traumatic Event Screening Inventory Child Report Form - Revised (TESI – CRF-R) Traumatic Event Screening Inventory - Parent Report Revised (TESI – PRR)

Yale-Vermont Adversity in Childhood Scale (Y-VAC) Parent Report and Child Report

X X X


Child body composition

Bioimpedence analysis (provide body fat mass [kg], total lean mass [kg])

Magnetic Resonance Imaging (MRI)

PeaPod/BodPod (provide body fat mass [kg], total lean mass [kg])

X X X X

Child pubertal development

Tanner’s stages of puberty in girls

Tanner’s stages for male genitalia development

X X

https://onlinelibrary.wiley.com/doi/full/10.1046/j.1475-357X.2003.00073.x





https://www.ptsd.va.gov/professional/assessment/documents/TESI-C.pdf



https://www.ptsd.va.gov/professional/assessment/documents/tesi-parent.pdf










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Collect Once

Life Stage


Concept: Child Neurodevelopmental Health and Functioning-related Data Elements

Child developmental milestones

Battelle Developmental Inventory, Second Edition (BDI-2)

Bayley Scales of Infant and Toddler Development

Mullen Scales of Early Learning

Parents Evaluation of Developmental Status (PEDS)

X X

Temperament Laboratory Temperament Assessment Battery (Lab-TAB) Prelocomotor (6 month) Tasks

Laboratory Temperament Assessment Battery (Lab-TAB) Locomotor (12 month) Tasks

Laboratory Temperament Assessment Battery (Lab-TAB) Preschool Tasks

X X

Emotional and behavioral functioning

Anxiety Dimensional Observation Schedule (Anx-DOS)b

Behavior Assessment System for Children (BASC) Berkeley Puppet Interview (BPI)

Disruptive Behavior Diagnostic Observation Schedule (DB-DOS)b

Infant Toddler Social Emotional Assessment (ITSEA)

Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB)b

X X X

https://www.hmhco.com/programs/battelle-developmental-inventory

https://www.hmhco.com/programs/battelle-developmental-inventory

https://www.pearsonclinical.com/childhood/products/100000123/bayley-scales-of-infant-and-toddler-development-third-edition-bayley-iii.html

https://www.pearsonclinical.com/childhood/products/100000123/bayley-scales-of-infant-and-toddler-development-third-edition-bayley-iii.html

https://www.pearsonclinical.com/childhood/products/100000306/mullen-scales-of-early-learning.html

https://www.ncbi.nlm.nih.gov/pubmed/?term=12659386


http://www.uta.edu/faculty/jgagne/labtab/desc_pre-loco_Lab-TAB.htm



http://www.uta.edu/faculty/jgagne/labtab/desc_loco_Lab-TAB.htm



http://www.uta.edu/faculty/jgagne/labtab/desc_preschool_Lab-TAB.htm





https://www.pearsonclinical.com/education/products/100000658/behavior-assessment-system-for-children-second-edition-basc-2.html

https://www.pearsonclinical.com/education/products/100000658/behavior-assessment-system-for-children-second-edition-basc-2.html










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Collect Once

Life Stage


Child general cognition

Differential Ability Scales, Second Edition (DAS-II) Stanford-Binet Intelligence Scales

A Developmental NEuroPSYchological Assessment II (NEPSY-II)

Wechsler Adult Intelligence Scale (WAIS)c

Wechsler Intelligence Scale for Children (WISC)

Wechsler Preschool and Primary Scale of Intelligence Fourth Edition (WPPSI IV)

Wechsler Abbreviated Scale of Intelligence (WASI)

X

X

(complete once in MC or

ADO)

Concept: Child Social Role Performance and Functioning-related Data Element

Academic ability and performance

School records or report cards (subject area grades, unweighted GPA)

X X

Abbreviations: ADO, adolescence; EC, early childhood; INF, infancy; MC, middle childhood; PER, perinatal; PNA, prenatal; yrs, years. a The HOME is an alternative measure only for 0 to 5-year-olds. b Alternative measure only for the internalizing scales of the CBCL and the SDQ. c Applicable only to adolescents 18+ yrs old.

https://www.pearsonclinical.com/education/products/100000468/differential-ability-scales-ii-das-ii.html

https://www.pearsonclinical.com/education/products/100000468/differential-ability-scales-ii-das-ii.html

https://www.wpspublish.com/store/p/2951/sb-5-stanford-binet-intelligence-scales-fifth-edition

https://www.pearsonclinical.com/psychology/products/100000584/nepsy-second-edition-nepsy-ii.html





https://www.pearsonclinical.com/psychology/products/100000310/wechsler-intelligence-scale-for-children-fourth-edition-wisc-iv.html

https://www.pearsonclinical.com/psychology/products/100000310/wechsler-intelligence-scale-for-children-fourth-edition-wisc-iv.html

https://www.pearsonclinical.com/psychology/products/100000102/wechsler-preschool-and-primary-scale-of-intelligence--fourth-edition-wppsi-iv.html






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11.2 Essential Data Element Measures for Child Participants 18 to 21 Years of Age Cohorts with child participants who are 18 to 21 years (late in the adolescence life stage) may use the pediatric measures identified in Table 4 or they may use (at their discretion), the corresponding adult measures where appropriate (Table 9).

Table 9 Discretionary Adult Measures for Child Participants 18 to 21 Years of Age

Essential Data Element Adult Measures for Child Participants 18 to 21 years

Child negative life events Adverse Childhood Experiences – Adult Primary Version - 18-21 yr olds or Adverse Childhood Experiences – Adult Alternate Version - 18-21 yr oldsa

Emotional and behavioral functioning Strengths and Difficulties Questionnaire (SDQ) S18+

Child social cognition Social Responsiveness Scale (SRS-2) - Adult - 18-21 yr olds

Child perceived stressα Perceived Stress Scale 10-item - 18-21 yr oldsb or Perceived Stress Scale 4-item - 18-21 yr olds

Child diet National Cancer Institute (NCI) Diet History Questionnaire Third Edition (DHQ III)c

Peer relationships PROMIS v2.0 - Companionship 6a – 18 to 21 yr olds

Child sleep health Sleep Health of Adults - 18-21 yr olds

Child sleep quality PROMIS v1.0 - Sleep Disturbance 4a - 18-21 yr olds/CAT

Child sleep-related impairment PROMIS v1.0 - Sleep-Related Impairment 4a - 18-21 yr olds/CAT

Child global health PROMIS v1.2 - Global Health Scale - 18-21 yr olds or

PROMIS v1.2 - Global Health Mental 2a- 18-21 yr olds and PROMIS v1.2 - Global Health Physical 2a- 18-21 yr olds

Child well-being - life satisfaction PROMIS v1.0 - General Life Satisfaction 5a- 18-21 yr olds/CAT

Child well-being - meaning and purpose

PROMIS v1.0 - Meaning and Purpose 8a - 18-21 yr olds/CAT

α The Perceived Stress Scale 14-item is a viable alternative measure for both the 4- and 10-item Perceived Stress Scales. A cohort may use this alternative measure for new data collection under the ECHO-wide Cohort Data Collection Protocol only if it is a legacy measure for that cohort.

a The Adverse Childhood Experiences - Adult Primary Version maintains individual items, while the Adverse Childhood Experiences - Adult Alternate Version groups sensitive items related to physical and emotional abuse with less sensitive/non-reportable items. It is at the individual cohort’s discretion to determine the most appropriate version for its setting.

b Available through the NIH Toolbox Fixed Form v2.0 – Perceived Stress (Ages 18+)© 2006-2017 National Institutes of Health and Northwestern University.

c The DHQ III is a freely available, web-based tool. Collect the DHQ III, past month with portion size version.

http://www.psy.cmu.edu/%7Escohen/

https://epi.grants.cancer.gov/dhq3/index.html


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11.3 ECHO Policies All current ECHO Policies are located in the ECHO Program Manual under “Program Information and Governance”, “Policies”. The policies cited in the ECHO-wide Cohort Data Collection Protocol include:

• ECHO Publications Policy

• ECHO Biospecimen Collection, Processing, and Storage Policy

• ECHO Biospecimen Utilization Policy

• ECHO Data Sharing Policy

https://flow.dcri.org/sites/echo/Pages/ECHOProgramManual.aspx


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11.4 ECHO-wide Cohort Data Collection Protocol Version 1.1 to Version 1.2: Summary of Changes

Sections Affected Summary of Change Reason for Change ECHO-wide Cohort Data Collection Protocol Version 1.1 to Version 1.2 (Amendment 2): Dated 11 December 2018

Entire Protocol (global in all instances)

Changed references of Version 1.1 to Version 1.2 and updated the version dating. Added Version 1.2 to the Protocol Version and Amendment Tracking. Added the Summary of Changes from Version 1.1 to Version 1.1 as Section 11.4.

Administrative changes required due to versioning from Version 1.1 to Version 1.2.

Updated number of Cohort Awardees (31), constituent cohorts (approximately 70), and number of sites (approximately 180). Added definition of “sites” at first reference, in synopsis: This protocol defines each “site” as a unique combination of Award Principal Investigator, cohort, and institution.

Updated to align with cohorts that transitioned from UG3 to UH3 awards..

Synopsis, Glossary, Section 3.1 (Inclusion Criteria)

Revised inclusion criteria to include fourth criterion “Biological mother and father of a child (or children) enrolled in an ECHO cohort, if not already enrolled under inclusion criterion #3 above, for the collection of “sample appropriate for DNA” from the biological mother (essential) and biological father (recommended).” Removed references to "primary" participant but defined those participants followed for ECHO outcomes of interest versus those providing exposure/covariate data. Revised all instances of "index child" to "child".

Revised to ensure cohorts seek samples appropriate for DNA per-protocol and to comprehensively define all ECHO-wide Cohort Data Collection Protocol research participants.

Synopsis, Section 1 (Background and Rationale) and Section 3.4 (Number of Participants)

Removed "and pregnant women" from: The number of participants is expected to exceed 50,000 children and almost as many primary caregivers and pregnant women over the course of the ECHO Program.

Revised to remove inaccurate estimate.

List of Abbreviations Added term “CAT” for “Computer Adaptive Test” and “PRO” for “Person Reported Outcome.

Added to due to associated protocol revisions (CAT) and to add previously omitted term (PRO)..


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Sections Affected Summary of Change Reason for Change Glossary, Section 8.1.1 (ECHO Coordinating Center Responsibilities), Section 8.2 (ECHO Cohort Investigator Responsibilities).

Removed all references “Cohort Measurement Identification Tool (CMIT)”.

Revised to remove specific references tool nomenclature, CMIT is defined in more granular terms in the MOP.

Glossary, Section 1 (Background and Rationale)

Added language for the now established ECHO Genetics Core. Revised to reflect the establishment of the ECHO Genetics Core.

Glossary, Table 3 (Data Element Measure(s) Assignment Framework), Section 4.2.4 (Alternative Measures)

Expanded upon definition of legacy to clarify that a cohort may use a legacy measure as an alternative measure if the Alternative Measures Task Force has approved the measure, or if this protocol already lists it as an alternative measure and to clarify that legacy measures do not include sociodemographic questionnaires or other custom cohort-developed instruments created for sole use by the individual cohort.

Revised to elaborate upon previous definition.

Section 2.2 (Development of the ECHO-wide Cohort Data Collection Protocol)

Revised content to remove references to Version 1.1 and added language to describe the development of Version 1.2.

Changes required due to versioning from Version 1.1 to Version 1.2.

Section 3.5, Participant Withdrawal

Revised language to further define participant withdrawal and to clarify that in cases of participant withdrawal, ECHO study staff will record withdrawal-related information.

Revised for clarity.

Section 4.1.3 (Sharing of Existing Data), Section 4.1.4 (Sharing of Existing Biospecimens)

Added language to allow for the sharing of previously collected data/biospecimens outside of ECHO-wide Cohort Data Collection Protocol consent, where the parent study consent allows for the sharing of those data/biospecimens.

Revised to clarify data/biospecimen sharing language.

Section 4.2.4 (Alternative Measures, Alternative Measures Process)

Revised alternative measures process language to reflect the Alternative Measures Task Force having approval capacity of alternative measures.

Revised to align with update in the alternative measures process.


11 December 2018 83

Sections Affected Summary of Change Reason for Change Section 5.0 (ECHO-wide Cohort Data Collection Protocol Procedures)

Added guidance language concerning the administration of child self-report measures and the administration certain PROMIS measures as Computer Adaptive Measures (CATs). Added language to define CATs and the benefits of their use.

Revised to provide procedural guidance regarding the administration of age and developmentally appropriate child self-report measures and regarding the administration of CATs.

Section 5.2 (Essential Data Elements for New Data Collection across the Child Developmental Life Course)

Revised text to remove reference to translations, added bulleted guidance text regarding considerations for adolescent data collection, and revised “Collect Once” guidance.

Guidance about translations is available in the Manual of Operating Procedures. Revised to clarify requirements and considerations for adolescent data collection. Revised to clarify that cohorts should “Collect Once” in an appropriate life stage, and to reference the MOP for associated measure administration instructions.


11 December 2018 84

Sections Affected Summary of Change Reason for Change Changes to Table 4: Essential Data Element Across the Child Developmental Life Course The following rows do not include changes to Table 4 due to updated form naming conventions, revisions to table formatting, or miscellaneous changes to table footnote content.

Table 4 (global in all instances) Updated measure naming conventions to align with developed forms where applicable.

Revised for consistency with developed study materials and systems.

Added the suffix “/CAT” to all PROMIS measures that can be administered as a Computer Adaptive Test (CAT).

Added to denote the PROMIS measures that ECHO cohorts may administer as CATs.

Specified version numbers for all NIH Toolbox battery tasks. Revised to provide specificity and continued protocol standardization.

Concept: Sociodemographics Added footnote to “Residential Address History” to specify the 2 distinct versions of the associated form and to specify data collection requirements.


Removed data element “Acculturation” from Table 5 (Recommended Data Elements) and merged acculturation measure (PhenX Acculturation [#180101]) with “Household Language” form in Sociodemographics. Added footnote to specify there is one version for use in the prenatal life stage and one for use in childhood.


Removed unique row for “Prenatal Household Composition”, added an “X” in the prenatal life stage to “Household Composition”. Added footnote to specify there is one version for use in the prenatal life stage and one for use in childhood.

Revised to streamline protocol and mirror presentation for Language and Acculturation.

Added a unique row for “Child Demographics” as Collect Once after the birth of the child to ensure that child demographics are collected consistently across ECHO cohorts.



11 December 2018 85

Sections Affected Summary of Change Reason for Change Concept: Child and Family Health Histories

Revised data element “Caregiver health insurance status” to “Caregiver and child health insurance status”.

Revised as the developed form will collect both caregiver and child health insurance status.

Applied the following footnote to the Biological Family and Child Medical History data elements: If the adolescent participant is ≥18 years old, he/she can complete the “Medical History – Biological Family” and the “Child Medical History – Middle Childhood and Adolescence” preferred measures him/herself. For child medical histories, collect child medical history information using the preferred or acceptable measure as late in each life stage as possible (in order to maximize coverage of each life stage).

Revised to clarify and for consistency with developed study materials and systems.

Concept: Pregnancy-related Data Elements

The acceptable measures previously associated with the data elements “Maternal gestational weight gain”, “Maternal height”, and “Maternal weight” were replaced with 3 newly developed forms. These new forms were footnoted to clarify data collection requirements. The protocol now contains one row for ”Maternal Height and Weight (includes pre-pregnancy weight)” and one row for “Total pregnancy weight gain (includes pre-pregnancy weight)”.

Revised to clarify protocol data collection requirements and associated data collection forms for maternal height, weight, and gestational weight gain.

Revised the footnotes associated with the acceptable measures of “Maternal Medical Conditions/Interventions”, “Lifestyle”, and “Maternal Supplements” to reflect revised data collection paradigms and developed measures.



Revised the data collection paradigm for the “Stressor Checklist”. Added footnote: Complete the Life Stressor Checklist at first administration, for subsequent administrations to the same individual, complete the 12-Month Stressor Checklist.



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Sections Affected Summary of Change Reason for Change Concept: Built/Physical Environment-related Data Elements

Updated the presentation of the preferred measures of “Chemical exposures” and “Household exposure to secondhand smoke” to reflect revised data collection paradigm and developed measures, updated associated footnotes accordingly.


Revised the footnote associated with the preferred measure of “Maternal and paternal work exposures” to reflect revised data collection paradigm and developed measure.



Added the following footnote associated with all instances of "Child anthropometry and physical examination": There is one child anthropometry and physical examination form for use in PERI with newborns, one for use in INF and EC with children 0 to 2 yrs old, and one for use in EC, MC, and ADOL with children >2 yrs old.


Added infancy data collections of “Child blood pressure” and “Child resting heart rate”.

Revised for consistency with developed anthropometry data collection forms.

Added appropriate child age to the preferred measure of “Child pubertal development” (Child 9+ yrs).

Revised to clarify.

Concept: Child Health Behaviors/ Lifestyle-related Data Elements

Removed the Version 1.1 footnote associated with the preferred measure of “Infant feeding and introduction to solids”, the “Infant Feeding Practices Study - II (IFPS - II) Questionnaires”.

IFPS II footnote is no longer required as the developed form is now applicable to the entire infancy life stage.

Removed the acceptable measure of “Infant feeding and introduction to solids” the “WHO Infant and Young Child Feeding Practices (IYCFP)” from the protocol.

Removed to streamline protocol and standardize data collection (low projected cohort adoption and measure not appropriate for US-based sample).

Added the following notation adjacent to the "Complementary Feeding History": note: complete as early as possible in EC.

Revised to clarify recommended timing for data collection.


11 December 2018 87

Sections Affected Summary of Change Reason for Change Concept: Child Health Behaviors/ Lifestyle-related Data Elements

Added the following footnote in all instances of the "Dietary Screener Questionnaire": Adapted from the National Health and Nutrition Examination Survey (NHANES) Dietary Screener Questionnaire (DSQ) 2009-10. For child participants, adolescents may complete the Dietary Screener Questionnaire– Self Report for themselves, or the primary caregiver may complete the Dietary Screener Questionnaire Parent Report for them.

Revised to align with developed form completion instructions.

Removed the acceptable measure of “Child sexual behavior” “PhenX Sexual Risk Behavior - Female (#101702) or PhenX Sexual Risk Behavior - Male (#101701)” from the protocol.

Removed to streamline protocol and standardize data collection (low projected cohort adoption).

Removed the acceptable measure of “Child substance use” “PhenX Patterns of Substance Use - Adolescents (#510303)” from the protocol.


Changes to Table 5: Recommended Data Element Across the Child Developmental Life Course The following rows do not include changes to Table 5 due to updated form naming conventions, revisions to table formatting, and miscellaneous changes to table footnote content. Table 5 (global in all instances) Updated measure naming conventions to align with developed

forms where applicable. Revised for consistency with developed study materials and systems.



Specified version numbers for all NIH Toolbox battery tasks. Revised to provide specificity and continued protocol standardization.

Recommended Data Elements: Child-related

Removed the data element “Indoor air pollution” and the associated measure “PhenX Air Contaminants in the Home Environment (#061101)” from the protocol. Added notation to the essential “Chemical exposures data” element that this encompasses indoor air pollution.

Streamlining protocol. Removed as measure is largely redundant with the already essential chemical exposures preferred measure.


11 December 2018 88

Sections Affected Summary of Change Reason for Change Recommended Data Elements: Child-related

Added "Child 3 to 6 yr" age band adjacent to the “Children's Eating Behaviour Questionnaire”. Added “Child 18 mos to 6 yrs” age band adjacent to the “Comprehensive Feeding Practices Questionnaire”

Revised to clarify and align with the associated form-specified age bands.

Revised age range for parent report of “Child Media Use” measure to Child 0 to 12 yrs, Child Self-Report changed to 13+yrs.

Revised based on evidence that children 8 to 12 years do not provide reliable self-report media use data.

Added rows for the data elements “Neighborhood capital” and “Perceived neighborhood conditions”, as measured by their respective PhenX measures, to the Child-related concept area as these measures target the child (not the caregiver) during childhood (infancy through adolescence).

Revised to clarify data collection and the respective target for these measures.

Removed the Adaptive Behavior Assessment System Third Edition (ABAS-3), a measure of the data element “Adaptive behavior”, from the protocol.


Removed the data element “Executive function” and the associated measures (Baby Stroop Task and Five Boxes Task, and the EF Touch Battery Tasks) from the protocol.

Removed data element and measures as executive function is captured under NIH Toolbox Early Childhood Cognition Battery on the essential list.

Removed recommended data collections of NIH Toolbox Pattern Comparison Test (a measure of the data element “Information processing speed”) from middle childhood and adolescence, retain in early childhood.

Revised to clarify. The NIH Toolbox Cognition Battery is essential in middle childhood or adolescence (the pattern test is an element of the cognition battery).

Added footnote associated with the "Assessment of your Home Health Environment": This measure must be completed in the home or dwelling where the child lives. If the adolescent participant is no longer living within the caregiver home, he/she should answer for his/her primary dwelling.

Revised to clarify measure completion instructions.


11 December 2018 89

Sections Affected Summary of Change Reason for Change Recommended Data Elements: Child-related

Removed follow-up interview portion of the Modified Checklist for Autism in Toddlers Revised (M-CHAT-R).

Removed as follow-up interview is only applicable to a subset of children screening positive on the M-CHAT-R and requires much more specific expertise in early childhood development and autism to administer.

Added footnote to “Professional dental care”: This measure is parent-report for early and middle childhood, and adolescence or the adolescent can complete the child self-report”. Added footnote to “Caffeine use”, and “Product use”: This measure is parent-report for middle childhood and child self-report for adolescence.

Revised to provide specific data collection guidance.

Added child age range to “Bullying” measure (Child 8+ yrs: Health Pathways Bullying Scales).

Revised to provide specific data collection guidance.

Recommended Data Elements: Pregnancy-related

Added rows for the data elements “Neighborhood capital” and “Perceived neighborhood conditions” as measured by their respective PhenX measures, to the Pregnancy-related concept area as these measures target the pregnant woman during the prenatal life stage (removed these rows from “Primary Caregiver-related Data Elements”).

Revised to clarify data collection and the respective target for these measures.

Recommended Data Elements: Caregiver-related

Removed the Adult Behavior Checklist (ABCL) as a recommended measure of “Caregiver externalizing spectrum”.



11 December 2018 90

Sections Affected Summary of Change Reason for Change Table 6: Essential Biospecimens Removed the following language from above Table 6: For many

biospecimens, e.g., prenatal blood and urine and child urine, the protocol indicates collection at least once in the life stage(s) specified; however, for many assays for which these biospecimens will be used, multiple collections in the life stage(s) specified may be advantageous (e.g., by trimester during pregnancy). Clarified repeat collection recommendations by adding footnotes to Table 6 that prenatal blood and urine are required once per protocol, but by-trimester collections are recommended.

Revised to provide specimen-specific guidance regarding repeat collections for the purposes of biospecimen budgeting, tracking, and storage.

Section 6 (Data Management) and Section 8.1.2 (ECHO Data Analysis Center Responsibilities)

Refreshed content to reflect continued development of data management infrastructure and responsibilities.

Updated due to continued development of infrastructure and responsibilities.

Section 8.1 (ECHO Steering Committee)

Removed Section 8.1, ECHO Steering Committee Removed for Version 1.2 as this version is not under ECHO Steering Committee ratification. The Steering Committee is defined in the glossary for reference.

Section 9.2 (Informed Consent) Added language: The ECHO Program will collect brief demographic information (e.g., age, race, ethnicity, and sex) about pregnant women and children participating in cohorts who are eligible for the ECHO-wide Cohort Data Collection Protocol but who do not consent. This will allow the Program to better understand trends and consider any biases in the resulting data.

Added to specify that the ECHO Program will collect these demographic variables from these individuals to better understand trends..

Section 10 (Regulatory Reporting)

Made minimal revisions to regulatory reporting language to align with developed reporting procedures (as described in the ECHO MOP, Chapter 1).

Revised to align with developed materials.

Table 8: Essential Data Elements and Associated Alternative Measures Across the Child Developmental Life Course

Add "X" to infancy life stage for "PeaPod" as an alternative measure of infant “Child body composition”.

Revised to correct inadvertent omission of infancy data collection for this alternative measure.


11 December 2018 91

Sections Affected Summary of Change Reason for Change Table 9: Discretionary Adult Measures for Child Participants 18 to 21 Years of Age

Updated measure naming conventions to align with developed forms where applicable.


Added the following post-table footnote "α ": The Perceived Stress Scale 14 item is a viable alternative measure for both the 4- and 10-item Perceived Stress Scales. A cohort may use this alternative measure for new data collection under the ECHO-wide Cohort Data Collection Protocol only if it is a legacy measure for that cohort.

Revised to align with allowing the 14-item scale as an alternative measure in adult participants (per Table 8, Essential Data Elements and Associated Alternative Measures Across the Child Developmental Life Course).



Section 11.3 (ECHO Policies) Removed policy version numbers. Removed version numbers as the current versions are noted in the hyperlinked ECHO Program Manual.