Welcome: Dr. Darren Michael, Program Manager, Newborn Screening, CDPHE

Program Updates: Dr. Darren Michael, Program Manager, Newborn Screening, CDPHE

Repeat—Vision for CO NBS LaboratoryNew HPLC System

Discussion of Follow-up & Reference Ranges (CLIR)Summary of Quarterly Outreach & Contract Monitoring

Summary of New Disorders Meeting (Bethesda, June 21-23)Electronic Access to NBS Data—IDS & CIIS

New Staff Member—Abena Watson-Siriboe

Planning: Margaret Ruttenber, Future Stakeholder Meetings & CCHD Update—(Questions)

Colorado Newborn Screening Stakeholders’ Committee Meeting

June 27, 2017

Vision for the CO Newborn Screening Laboratory

April 27, 2017

Darren J. Michael, PhD, CC (NRCC), SC (ASCP)

Comprehensive Review

• What do we do?• Why do we do it?• Is there a better way to do it?• Where are the systemic risks?• Meeting one-on-one and in small

groups with clients and stakeholders—stress that CDPHE is willing to listen & consider change

Vision for the Future• Improve the flow of information throughout the CO

NBS program• Identify best practices and spread them—put peers in

front of peers• Data-driven decisions—expand analytics capabilities

within CDPHE’s NBS laboratory• Activate other state resources—local public health

authorities, Office of Information Technology• Establish boundaries for the state’s obligation in NBS

testing and follow-up• Bring new technologies to CDPHE’s NBS laboratory,

e.g. NextGen sequencing, HPLC, LC-MS/MS• Expand our expertise—focus on molecular biology

(one new hire)

Program Updates:New HPLC System

June 27, 2017

Darren J. Michael, PhD, CC (NRCC), SC (ASCP)

Installation & User TrainingBioRad VARIANTnbs System

• Installed on June 19

• Initial training for staff—June 20-22

• Additional training at BioRad’s training facility—July 10-12

Some Initial Data

BioRad VARIANTnbs System

FADC Marker

F

A

D C

CLIA, FDA & Validation PlansBioRad VARIANTnbs System

• FDA cleared for identification of six Hb variants—F,A,S,D,C,E

• Not cleared as a quantitative method—requires a different validation pathway (laboratory-developed test or LDT)

• 1st Validation Study—Verify FDA-cleared method; no later than 7/31/2017

• 2nd Validation Study—establish parameters for detecting and reporting Hb Bart’s (alpha thalassemias); no later than 9/15/2017

CLIA: Verifying vs Establishing Performance Parameters§493.1253 Standard: Establishment and verification of performance specifications.(a) Applicability. Laboratories are not required to verify or establish performance specifications for any test system used by the laboratory before April 24, 2003.(b)(1) Verification of performance specifications. Each laboratory that introduces an unmodified, FDA-cleared or approved test system must do the following before reporting patient test results:(i) Demonstrate that it can obtain performance specifications comparable to those established by the manufacturer for the following performance characteristics:(A) Accuracy.(B) Precision.(C) Reportable range of test results for the test system.(ii) Verify that the manufacturer's reference intervals (normal values) are appropriate for the laboratory's patient population.(2) Establishment of performance specifications. Each laboratory that modifies an FDA-cleared or approved test system, or introduces a test system not subject to FDA clearance or approval (including methods developed in-house and standardized methods such as text book procedures), or uses a test system in which performance specifications are not provided by the manufacturer must, before reporting patient test results, establish for each test system the performance specifications for the following performance characteristics, as applicable:(i) Accuracy.(ii) Precision.(iii) Analytical sensitivity.(iv) Analytical specificity to include interfering substances.(v) Reportable range of test results for the test system.(vi) Reference intervals (normal values).(vii) Any other performance characteristic required for test performance.(3) Determination of calibration and control procedures. The laboratory must determine the test system's calibration procedures and control procedures based upon the performance specifications verified or established under paragraph (b)(1) or (b)(2) of this section.(c) Documentation. The laboratory must document all activities specified in this section.

FDA-cleared method

FDA-modified or laboratory-developed method

Program Updates:Discussion of Follow-up and Reference Ranges

(Collaborative Laboratory Integrated Reports—CLIR)

June 27, 2017

Darren J. Michael, PhD, CC (NRCC), SC (ASCP)

Sample Collection (Nurses, Midwives,

Physician Assistants)

Submitters(Hospitals/Quest,

Midwives, Pediatricians)

Transportation (Courier, USPS,

PO Box, Wyoming)

CDPHE NBS LaboratoryReceiving(CDPHE)

5:00-7:00AM

Sorting/Processing(CDPHE)[‘Mail’]

5:30AM-8:00AM

Punching(CDPHE)

8:00AM-9:00AM

Testing(CDPHE)

10:00AM-11:59PM

Reviewing of Results(CDPHE)

8:00AM-6:00PM

Reporting of Results(CDPHE)8:00AM-6:00PM

‘Normal’(USPS)

Linking—Match 1st & 2nd Screen(CDPHE)

4:00PM-5:00PM

Borderline(Alert PCP)

Critical(Connect to Care)

Contract Monitoring/Case Reporting

Accessioning(CDPHE)

8:00AM-12:00PM

WorkflowFax, Email, Phone

Medical Consultants

Submitters & PCP’s

Electronic Portal(s)CIIS, IDS v2

Follow-up Tool: Bill Vertrees (CDPHE)

Follow-up Data: Aggregate Data

Time Period Flags for Call Out Unique Accession Numbers1/1/2017-3/31/2017 689 6031/1/2017-6/27/2017 1318 1159

Follow-up Data: Quarterly and YTD Activity (with Unsats)

Follow-up Data: Quarterly and YTD Activity (w/o Unsats)

CLIR: Collaborative Laboratory Integrated Reports• International effort to improve interpretation of clinical test results

• Based at Mayo Clinic—Piero Rinaldo, M.D., Ph.D.

• Derived from the Region 4 Stork Collaborative Project [R4S]

• Region 4—IL, IN, KY, MI, MN, OH, WI

• Goal—define disease ranges, normal ranges and target ranges for numerous clinical conditions and diseases using data from laboratories around the world (increases the sample size [n] for rare disorders)

• Approved to submit data—Legal & compliance review by Ann Hause (CDPHE)

• Initial goal—submit 5,000-10,000 data sets from normal bloodspots

• Long-term goal—establish site-specific post-analysis tools which incorporate significant co-variates including age in hours, birth weight, sex, gestational age*

• Gestational age—available through electronic birth certificate database (leverage state resources)

Courtesy of Piero Rinaldo, Mayo Clinic

CLIR

Courtesy of Piero Rinaldo, Mayo Clinic

Program Updates:Follow-up Contracts

June 27, 2017

Darren J. Michael, PhD, CC (NRCC), SC (ASCP)

• Congenital Hypothyroidism—Rocky Mountain Pediatric Endocrinology* (first time there’s been a competitive bidding process for a follow-up contract)July 1, 2017-June 30, 2018

• Various Metabolic Conditions—University of Colorado Medicine (CU Medicine)July 1, 2017-June 30, 2018

• Hemoglobinopathies—University of Colorado Medicine (CU Medicine)July 1, 2017-December 31, 2017(resume 1-year award on January 1, 2018)

• Severe Combined Immunodeficiency (SCID)—National JewishJuly 1, 2017-September 30, 2017(resume 1-year award on October 1, 2017)

Follow-up Contracts

Program Updates:Summary of Quarterly Outreach & Contract Monitoring

June 27, 2017

Darren J. Michael, PhD, CC (NRCC), SC (ASCP)

• Lyn Elliott and others, March of Dimes (telephone call and in-person meeting)

• Visit by Wyoming Department of Health (Carleigh Soule and Christina Taylor)

• Visit by NewSTEPs 360 (Joshua Miller, Sarah McKasson and Marci Sontag)

• Visit to hemoglobinopathy follow-up contractor (Donna Holstein)

• Email exchange with Piero Rinaldo (R4S & CLIR)

• Title V Calls (Karen Trierweiler; AK, CO, DE, IA, LA, MT, ND, NM, NY, SD, TN, UT)

• APHL webinar—Alpha Thalassemia and Newborn Screening

• Met with LIMS vender for LSD/CDPHE—ChemWare/Horizon (live ~1/1/2018)

• Calls with Quest, Kaiser Permanente and HealthOne—aid with flow of information in the NBS system

• Two site visits by Perkin Elmer—hardware, software, reagents and support

• Invited to speak at Wyoming Newborn Screening Conference—June 29, 2017

Program Updates:Summary of New Disorders Meeting

(Bethesda, MD—June 21-23)

June 27, 2017

Darren J. Michael, PhD, CC (NRCC), SC (ASCP)

• Organized by APHL/NewSTEPs

• Health Resources and Services Administration (HRSA) grant

• Focused on three conditions recently added to the Recommended Uniform Screening Panel (RUSP): Pompe, Mucopolysaccharidosis Type I [MPS-I], X-linked Adrenoleukodystrophy (X-ALD)

• Lysosomal disorders—Pompe and MPS-I

• Peroxisomal disorder—X-ALD (no known correlation between genotype and phenotype); accumulation of long-chain fatty acids; might need to engage endocrinology partners to design follow-up

• Complicated follow-up routines (difficult to reach an endpoint quickly with some of these conditions; when is the state finished?)

• Pseudodeficiency with Pompe—low enzymatic activity but no clinical significance

• Testing platforms—digital microfluidics ($1/test/condition for 4-plex; FDA approved) or MS/MS (cost estimate not yet available; LDT)

• Do we need 2nd tier tests before we initiate testing?

Program Updates:Electronic Access to NBS Bloodspot Data

(IDS v2 and CIIS)June 27, 2017

Darren J. Michael, PhD, CC (NRCC), SC (ASCP)

Colorado Newborn Screening Statute

Colorado Revised Statutes: 25-4-1001 to 25-4-1006

25-4-1004—Provides statutory authority to collect NBS bloodspot data in Colorado Immunization Information System (CIIS)

….The results of any testing or follow-up testing pursuant to section 25-4-1004.5 may be sent to the immunization tracking system authorizedby section 25-4-2403 and accessed by the physician or other primaryhealth care provider…..

Colorado Immunization Information System (CIIS)

IDS v1—Different track

IDS v2—Developed and Maintained by CDPHE through CHED

Integrated Data System (IDS)

• (IDS v1) https://www.healthinformatics.dphe.state.co.us/

• (IDS v2) https://www.phi.dphe.state.co.us/nonauthenticated/default.aspx?ReturnUrl=%2f

• Potential to integrate several data sources, e.g. electronic birth certificate data (“golden record”), immunization records, newborn screening results for bloodspot

Electronic Birth Certificate Record(lag of ~2 weeks)

Colorado Immunization Information System(CIIS)

NBS Bloodspot Results(Perkin Elmer LIMS)

IDS v2(integrate data sets)

(who hasn’t been screened)

Future Meetings of CNBSSC

Tuesday, September 19, 2017 (need room)

Tuesday, October 3, 2017 (here)

Tuesday, November 7 or 14, 2017 (here)

AcknowledgementsColorado Newborn Screening Laboratory

Colorado Dept. of Public Health & Env.(main campus)

Laboratory Services Division

Accessioning GroupBrandon Gambrall

Gabriel PlessDominique Stewart

Kristin OndreikoTracy Bliss

Colorado Newborn Screening Stakeholders’ Committee

Finance GroupOlga IvanovaKristi GambleJaqui Maharaj

Office of IT (OIT)

Mark DymerskiGreg Bonn

Marilyn HeilCory Porter

Abena Watson-Siriboe

Paula BrallierKay Reilly

Rachel RodriguezKyle Senger

Kirida SinJulia GrayAmy Davis

Cynthia ForemanJyoti KochharJalene RochaAlicia Castro

Hugh Maguire, Ph.D.Dana Erpelding

Lauren Farnsworth

Brenda SmithJustin Nucci

Vickel Maharaj

Larry Wolk, M.D.Tista Ghosh, M.D.

Margaret RuttenberKaren Trierweiler

Ann HauseJoni KoenigBill Vertrees