Expanded Newborn Screening:ACMG/HRSA Report

APHL Annual MeetingJune 27, 2005

Bill Becker, DO, MPHMedical Director

Ohio Dept of Health Laboratory

Newborn Screening: Towards a Uniform Panel and System

Contract No. 240-01-0038

ContractorAmerican College of Medical Genetics

SPONSORMaternal and Child Health Bureau

Genetic Services BranchHealth Resources and Service Administration

0

2

4

6

8

10

12

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43

20042004

No.

of S

tate

s

No. of conditions

<55-10

11-20>20

% USBirths20%42%12%27%

From NNSGRC(updated 9/8/04)

0

2

4

6

8

10

12

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43

20022002N

o. o

f Sta

tes

No. of MANDATED conditionsNo. of MANDATED conditions

No. of conditions

<55-10

11-20>20

% USBirths30%66%0%5%

5-10(20%)

<5(20%)

5-10(66%)

<5(30%)

3 Disorders (1)

More than 8 Disorders (32) [More than 30 Disorders (14)]

7 Disorders (4)6 Disorders (4)5 Disorders (2)4 Disorders (6)

8 Disorders (2)U.S. Newborn Screening

Mandated Disorders – Jan 2005 (Note: Other disorders may be offered but are

not mandated)

>30

>30 26>30

>30

9>30

>30

>30

>30>30

26

40

14

29

9

9

>30

29

19

9

10

21

>30

13 10

>30>30

27

DC

>30

>30>30

NBS in the United States TODAY is–Not UNIVERSAL

• Only PKU, CH, and GAL (related conditions)

–Not FAIR or UNIFORM• Limited pilot programs• Left to consumer initiative

State of Newborn ScreeningTODAY

• Lack of uniformity is pervasive and affects:

– Decision-making (no national process)

– Analytical quality

– Interpretation of results

– Outcome data collection

General Goals of HRSA/ACMG Contract

• Develop uniform panel of conditions– a decision-making tool for program expansion or

contraction• Develop minimum standards, policies &

procedures for NBS programs• ID appropriate health outcomes to be

incorporated into evaluation protocols• Consider value of a national process for QA and

oversight of NBS

Process (1)

• Steering Committee formed:– Major organizations with interest and

involvement• AAP, CDC, MOD• Genetic Alliance• NIH, HRSA

• Expert Group formed:– Broadly representative of interest groups but

focused on scientific expertise

Process (2) – Input From:

• 24 experts in NBS & public policy

• 75 recognized experts (US & International)

• (3) Public comment opportunities

• Input requested from many interest groups (APHL, SIMD, ASTHO, consumers, others)

• Literature review

Assessing the Evidence: Issues

Incidence/Prevalence Data

• General population data is best

• Mostly rare diseases

• Multiple genetic etiologies

• Splitting conditions in multiple groups

The Evidence Base

• Systematic review of sources– Clinical evidence– Cost/economic evidence and modeling– E-references (Medline, PubMed)– Reference Texts– Health technology assessment (HTA)– Professional guidelines

• Review of Epidemiologic studies– Study design– Subjects, outcome– Effectiveness of treatment

Criteria and Scoring SystemCriteria and Scoring System• Incidence of conditions• Identifiable at birth• Burden of disease• Availability of test• Test characteristics• Availability of treatment• Cost of treatment• Efficacy of treatment• Early intervention• Early identification• Mortality prevention• Diagnostic confirmation• Acute management• Simplicity of therapy

No ResponsesNo Responses

8455

4032

39

International 22Not provided 2

8959

4235

43

International 22Not provided 2

292 Survey Responses

1,106

International 353Not provided 2

323 326

776 1,0351,110

International 353Not provided 2

3,939 Disease Profiles

326 328

780 1,040120

International 60Not provided 2

585 Respondent Profiles

178

53 68

79125

International 60Not provided 2

184

58 71

85

Sorting of Survey Scores

Amino acids

OA FAO AA

IVA MCAD PKU SCA HYPOTHGA-I VLCAD MSUD Hb S/ Th BIOTHMG LCHAD HCY Hb S/C CAHMCD TFP TYR I G6PD * GALTMUT CUD ASA HEAR

Cbl A,B CIT CF3MCCPROPBKT

MS/MSAcylcarnitines

UNIFORM PANEL

Hematology Others(9)(9) (5)(5) (6)(6) (4)(4) (6)(6)

Amino acids

Cbl C,D M/SCHAD Hyper-PHE Variant Hb GALE2M3HBA SCAD TYR-II GALK

IBG MCKAT BIOPT (BS)2MBG GA-II TYR-III3MGA CPT-IA ARGMAL CPT-II BIOPT (REG)

CACT METDE REDUCT CIT-II

OthersOA FAO AA

MS/MSAcylcarnitines

Hb Pathies

Secondary Markers

CONDITION

>1,200 <1,0001,000-1,200

NoNBS

Is therea TEST

available?

Is natural history

well understood?

REPORTONLY

No

No

SURVEYSCORE

Yes

Yes

Are all detected patients

affected?

CORE PANEL

FULL NBS PROGRAM

Yes

Yes

Is Condition part of a differential diagnosis for a core condition?

Yes

Is treatment available and/or necessary?

No

To be reconsidered based on:1) New screening methods2) New treatments3) Knowledge of natural history

Survey consensus:Mean score >100Median score =200

Survey consensus:Mean score <100Median score <200

No Is Condition still detected as part

of a multiplex profile?

Yes

No

NOSome patients

are carriers

Evaluation Flow Chart

Other HRSA Activities

• Confirmatory algorithms

• Action “Act” sheets for patient management/referral

• Regional collaboratives

• Ongoing evidence review

OK – So What Happened to the ACMG/HRSA Report?

• 2004 HHS Secretary Thompson appointed an Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children

• SAC has reviewed the report and recommended it to the Secretary HHS

Status of the ACMG/HRSA Report

• Open comment period – closed May 8th

– Encouraged input from all• Next – all comments will be reviewed by

the SAC for further recommendations• Internally – all interested agencies within

HHS will review & comment

SAC Purpose

• Title XXVI of the Children’s Health Act of 2000 Screening for Heritable Disorders

• Establishes a program to improve the ability of States to provide newborn & child screening for heritable disorders

• A possible mechanism for federal funding?

SAC Activities

• Has established subcommittees– Laboratory standardization– Education & training– Follow up

• Cross cutting issues – financing, information technology, new testing technologies & review of the core panel for additions/deletions

Decision to Expand

• Widespread interest– clinical experts– public groups– private groups– political groups

Public Health

Centralized Program was felt to be the most important Goal

• Newborn screening is more than just testing

• Must be an integrated system

• Linking the babies, parents, hospitals & physicians with the health department and regional centers

Providers

Genetic & Sickle Cell Centers

Program

The End !