Research Determination

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Attachment C - Pilot Online Data Collection for SMA PT Research Determination

Print Date: 5/15/20

Title:

Pilot PT Program for Spinal Muscular Atrophy (SMA)

Project Id:

0900f3eb81b383d2

Accession #:

NCEH-DLS-4/30/20-383d2

Project Contact:

Ding_Yan (Shirley) (yad6)

Organization:

NCEH/ATSDR/DLS

Status:

Pending Clearance

Intended Use:

Project Determination

Estimated Start Date:

04/13/2020

Estimated Completion Date:

04/03/2021

CDC/ATSDR HRPO/IRB Protocol #:
OMB Control #:
Source System #:

2020-0076

Determinations
Determination

Justification

Completed

Entered By & Role

HSC:
Does NOT Require HRPO
Review

Not Research

5/15/20

Davis_Stephanie I. (sgd8) CIO HSC

5/15/20

Davis_Stephanie I. (sgd8) CIO OMB / PRA

PRA:
PRA Applies

Description & Funding
Description
Priority:

Standard

Date Needed:

05/30/2020

Determination Start Date:

04/30/20

Description:

The goal of this project is to pilot test an SMA proficiency testing program with partner domestic newborn screening
programs. The MQIP team has developed a protocol to make dried blood spot materials that are needed by
newborn screening labs in support of SMA testing including: 1) SMA-like specimens that are homozygous for the
SMN1 exon 7 deletion 2) SMA- carrier specimens that have one normal SMN1 exon 7 and one deletion of SMN1
exon 7 3) “Negative” or normal specimens that will amplify the SMN1 exon 7 4) UNSAT samples that have no
amplification These materials will be sent to partner newborn screening labs that have agreed to assist MQIP in
testing the logistics of the PT program. This pilot will evaluate the shipping logistics and processes related to the
send out of PT materials, the data collection tool, data receipt, analysis and report generation process by CDC as
well as the data reporting and results receipt within domestic newborn screening programs prior to full PT
implementation. The MQIP team will work closely with NSQAP’s data management team with the above processes.

IMS/CIO/Epi-Aid/Chemical Exposure
Submission:

No

IMS Activation Name:

Not selected

CIO Emergency Response Name:

Not selected

Epi-Aid Name:

Not selected

Assessment of Chemical Exposure Name:

Not selected

Goals/Purpose

MQIP is dedicated to supporting state screening programs in their effort to identify newborns with Spinal Muscular
Atrophy (SMA). An integral component of this support is the development, preparation and distribution of quality
assurance materials that can be used by newborn screening labs to meet their quality and regulatory needs. The
MQIP team has been developing and testing a protocol to make dried blood spot materials that are needed by
newborn screening labs in support of SMA testing. MQIP has validated these materials as fit for purpose for
newborn screening of SMA. We now propose the establishment of a pilot of an SMA PT program in domestic
newborn screening programs.

Objective:

In 2018, SMA was added by the HHS Secretary to the recommended uniform screening panel (RUSP) for newborn
screening and currently 22 domestic public health programs have begun routine screening. It is expected that all
U.S. newborn screening laboratories will adopt SMA screening in the next few years. Infants born with infantile or
type 1 SMA become incapacitated and typically die within 2 to 4 years of life. However, if SMA is diagnosed and
treated prior to onset of symptoms with an FDA approved drug, children with Type 1 SMA can avoid severe,
deleterious effects of the disease and may retain the ability to live relatively normal lives. Newborn screening for
SMA allows for early detection of affected infants that may appear normal at birth and early treatment can halt
irreversible neuronal damage. Newborn screening programs count on CDC’s quality assurance program for dried
blood spot materials to help them assure that their assays are accurately detecting babies affected with SMA. If a
child is missed, the baby would die unnecessarily. In addition, public health programs rely on CDC for PT challenges
to comply with their clinical testing regulatory requirements.

Activities or Tasks:

Purchase, Use, or Transfer of Information, Data, Biospecimens or Materials

Target Populations to be
Included/Represented:

Other

Tags/Keywords:

DLS 2020-0076, SMA, pilot, real time PCR, , Laboratory Proficiency Testing

CDC's Role:

CDC is provider of materials/services TO an institution, CDC is recipient of private data/specimens FROM an
institution

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Attachment E - Pilot of Online Data Collection for SMA PT Research Determination
Method Categories:

QA/QI

Methods:

Quality assurance materials that will be used for the pilot PT were created from samples received from two sources
including: de-identified patient samples collected by the Sequoia Foundation in collaboration with the California
Department of Public Health that represent an SMA patient sample (ie homozygous SMN1 exon 7 deletion), an SMA
carrier sample (ie heterozygous SMN1 exon 7 deletion) and an SMA unaffected sample (ie intact SMN1 exon 7
region); and leukodepleted blood from Tennessee Blood Services. These quality assurance materials will be fully
validated by the following criteria with the MQIP quality representative: 1) Transduced cell confirmation relative to
initial blood received - microsatellite analysis a. Results must match those obtained from initial patient donor blood
sample and master bank cells 2) Homogeneity testing - real-time PCR assay that detects the RPPH1 gene a. DNA
concentrations are used to evaluate homogeneity and must return a “Yes” result when using the SAS program
described in NSMB-B/C-LABOP.014 3) Fit for purpose testing - real-time PCR triplex assay that detects SMN1 (exon
7)/TREC/RPP30 a. Assay run on different instruments using different DNA extraction methods and be within
expected ranges MQIP will develop forms, templates, Excel macros and SAS programs as needed for 1) PHL data
collection and instructions; 2) CDC data receipt from PHL and aggregation programs; 3) data analysis programs
and SOPs; 4) report templates and lab verification pages (along with needed SAS programs). NSQAP will
incorporate SMA into the CRM system including: 1) all information and documentation associated with a new PT
program; 2) develop shipping materials and logistics plans; 3) develop system to receive data via Excel data
collection forms and 3) develop system to vet final reports, assure 508 compliance and report dissemination to
PHLs.

Collection of Info, Data or Biospecimen:

Materials will be shipped via FedEx along with instructions (pdf) and an Excel data collection form to participating
state public health laboratories (PHLs) for evaluation. PHLs will run their routine SMN1 detection assay(s) to assess
if any of the five pilot PT specimens give a result that suggests the sample is at risk for SMA. The PHLs will input
the following information on to the data collection form: 1) Lab code number; 2) Type of screening method; 3)
Method of DNA extraction; 4) SMN1 assay primer and probe information; 5) Reference gene assay primer and
probe information; and 6) Clinical assessment based on presence or absence of SMN1 exon 7. Once complete, the
PHLs will return their evaluations to NSQAP DMT for assessment. The MQIP team will perform the evaluation on the
submitted data and generate an SMA program newsletter with individual laboratory assessments, which will be
returned to the participants by email.

Expected Use of Findings/Results:

In 2018, SMA was added by the HHS Secretary to the recommended uniform screening panel (RUSP) for newborn
screening and currently 22 domestic public health programs have begun routine screening. It is expected that all
U.S. newborn screening laboratories will adopt SMA screening in the next few years. Infants born with infantile or
type 1 SMA become incapacitated and typically die within 2 to 4 years of life. However, if SMA is diagnosed and
treated prior to onset of symptoms with an FDA approved drug, children with Type 1 SMA can avoid severe,
deleterious effects of the disease and may retain the ability to live relatively normal lives. Newborn screening for
SMA allows for early detection of affected infants that may appear normal at birth and early treatment can halt
irreversible neuronal damage. Newborn screening programs count on CDC’s quality assurance program for dried
blood spot materials to help them assure that their assays are accurately detecting babies affected with SMA. If a
child is missed, the baby would die unnecessarily. In addition, public health programs rely on CDC for PT challenges
to comply with their clinical testing regulatory requirements. The results of this Pilot SMA PT event will not be
disseminated to the public; although, respondent labs will be notified of their own performance results as part of
the pilot of methods and procedures. CDC will use these results to finalize the SMA PT methods.

Could Individuals potentially be identified
based on Information Collected?

No

Funding

Funding Type

Funding Title

CDC Funding Intramural

Project Funding and Partners

Funding #

Original Budget Yr

# Years Award

Review Attributes

Quality Assurance / Improvement

Regulation and Policy
Do you anticipate this project will be
submitted to the IRB office

No

Estimated number of study participants

Population - Children
Population - Minors
Population - Prisoners
Population - Pregnant Women
Population - Emancipated Minors
Suggested level of risk to subjects Do you anticipate this project will be exempt research or non-exempt research

Requested consent process waviers
Informed consent for adults

No Selection

Children capable of providing assent

No Selection

Parental permission

No Selection

Alteration of authorization under HIPPA
Privacy Rule

No Selection

Requested documents of informed consent
Informed consent for adults

No Selection

Children capable of providing assent

No Selection

Parental permission

No Selection

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Attachment E - Pilot of Online Data Collection for SMA PT Research Determination
Consent process shown in an understandable language
Reading level has been estimated

No Selection

Comprehension tool is provided

No Selection

Short form is provided

No Selection

Translation planned or performed

No Selection

Certified translation / translator

No Selection

Translation and back-translation to/from
target language(s)

No Selection

Other method

No Selection

Clinical Trial
Involves human participants

No Selection

Assigned to an intervention

No Selection

Evaluate the effect of the intervention

No Selection

Evaluation of a health related biomedical or
behavioral outcome

No Selection

Registerable clinical trial

No Selection

Other Considerations
Exception is requested to PHS informing
those bested about HIV serostatus

No Selection

Human genetic testing is planned now or in
the future

No Selection

Involves long-term storage of identfiable
biological specimens

No Selection

Involves a drug, biologic, or device

No Selection

Conducted under an Investigational New
Drug exemption or Investigational Device
Exemption

No Selection

Institutions & Staff
Institutions
Name

FWA #

FWA Exp Date

Centers for Disease Control & Prevention

FWA00001413

10/31/24

IRB Title

IRB Exp Date

Funding #

Staff
Staff
Member

SIQT Exp.
Date

John
Bernstein

09/26/2021

Kristina
Mercer

09/17/2021

CITI Biomedical
Exp. Date

CITI Social &
Behavioral Exp. Date

CITI Good Clinical
Practice Exp. Date

11/02/2021

Staff
Role

Email

Phone

Organization

Project
Officer

770-4880973

NEWBORN SCREENING
BRANCH

Project
Officer

404-4980866

NEWBORN SCREENING
TEAM 3

Data
DMP
Proposed Data Collection Start Date:

4/13/20

Proposed Data Collection End Date:

4/3/21

Proposed Public Access Level:

Non-Public

Non-Public Details:
Reason For Not Releasing Data:

Other - QA/QC

Public Access Justification:

QA/QC

How Access Will Be Provided for Data:

Project data is not public health data

Plans for Archival and Long Term
Preservation:

Spatiality

Spatiality (Geographic Locations) yet to be added .....

Dataset
Dataset Title

Data
Publisher/Owner

Public
Access
Level

Public Access
Justification

External
Access URL

Download
URL

Type of Data
Released

Collection
Start Date

Collection
End Date

Dataset yet to
be added...

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Attachment E - Pilot of Online Data Collection for SMA PT Research Determination

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