Brad Therrell, PhD – NNSGRC Jana Monaco – ACHDNC (parent advocate) W. Harry Hannon, PhD – NNSGRC (CDC) Don Bailey, PhD – RTI (parent advocate) Alaina Harris, MSW, MPH – HRSA Brad Therrell, PhD – NNSGRC Jana Monaco – ACHDNC (parent advocate) W. Harry Hannon, PhD – NNSGRC (CDC) Don Bailey, PhD – RTI (parent advocate) Alaina Harris, MSW, MPH – HRSA Proposed ‘White’ Paper Retention and Use of Residual Dried Bloodspot Material Following Newborn Screening: Guidance from the ACHDNC May 12, 2009 Proposed ‘White’ Paper Retention and Use of Residual Dried Bloodspot Material Following Newborn Screening: Guidance from the ACHDNC May 12, 2009

2005 Publication: “Stability studies show that genomic DNA is stable in dried blood spots stored on filter paper at ambient tropical conditions for at least 11 years. However, DNA quality for amplification of larger DNA fragments decreased when the specimens were stored for longer than 10 years.” DNA Stability in Dried Blood Spots. Chaisomchit S, Wichajarn R, Janejai N, Chareonsiriwatana W. Southeast Asian J Trop Med Public Health Jan;36(1): Publication: “Despite storage for 25 years, at times without air conditioning, all specimens yielded genotyping results. However, the climate in Washington is moderate, and our assays mainly required short amplicons— genotype might not be determinable for all subjects for assays requiring long amplicons.” Newborn Screening Archives as a Specimen Source for Epidemiologic Studies: Feasibility and Potential for Bias. Nielsen SS, Mueller BA, DeRoos AJ, Checkoway H. Ann Epidemiol 2008;18(10): Stability of DNA in Stored DBS Specimens

2009 Publication: “Lightly abrasive contact between DBS resulted in DNA cross- contamination –while contamination was detected, contamination levels were not sufficient to affect most routine molecular genetic assays currently used in NBS.” Assessment of DNA Contamination from Dried Blood Spots and Determination of DNA Yield and Function using Archival Dried Blood Spots. Cordovado SK, Earley MC, Hendrix M, Driscoll-Dunn R, Glass, M, Mueller PW, Hannon WH. Clin Chim Acta 2009;402: Stability of DNA in Stored DBS Specimens 1996 Publication: “Stability of other non-DNA biomarkers for NBS vary with each specific analyte and many start to degrade within a few months.” Guidelines for the Retention, Storage, and Use of Residual Dried Blood Spot Samples after Newborn Screening Analysis: Statement of the Council of Regional Networks for Genetic Services. Therrell BL, Hannon WH, et al., Biochem Molec Med 1996;57:

1996 – CORN Newborn Screening Committee: “Appropriate consent is an important issue. Some legal experts have proposed that proper consent is impossible since it is not possible to adequately inform or educate parents about all potential uses….” Source: Guidelines for the Retention, Storage, and Use of Residual Dried Blood Spot Samples after Newborn Screening Analysis: Statement of the Council of Regional Networks for Genetic Services. Therrell BL, Hannon WH, et al. Biochem Molec Med. 1996; 57: – AAP Task Force Recommendations: “Develop model consent forms and informational materials for parental permission for retention and use of newborn screening samples.” “Develop educational materials for parents that include information regarding the storage and use of residual samples.” Source: Serving the Family from Birth to Medical Home – Newborn Screening: a Blue Print for the Future. Pediatrics. 2000;106 (No. 2 suppl.): Consent - The Issue “Residual NBS dried-blood spots have taken on a new life as a result of developments in genetics and increasing ability of bioinformatics to link DNA information with clinical data. 1” 1 Storing Newborn Blood Spots: Modern Controversies. BM. J Law, Med and Ethics 2004;Winter:

2004 Publication: “ In light of growing use of DBSs and their potential secondary applications, proactive solutions should be envisaged to ensure proper protection of choice, consent, and the privacy and confidentiality of genetic information. Transparency, supervision, strict rules for scientific study and informed consent requirements, are rules that a properly regulated biobank should live by.” Source: Storing Newborn Blood Spots: Modern Controversies. Kharaboyan L, Avard D, Knoppers BM. J Law, Med and Ethics. 2004; Winter: Newspaper Article: “Medical privacy advocates, ethicists say parents should be asked for consent before newborns’ screening samples are kept.” Source: Austin American Statesman, Sunday, February 22, Consent - The Issue “Residual NBS dried-blood spots have taken on a new life as a result of developments in genetics and increasing ability of bioinformatics to link DNA information with clinical data.” 1 1 Storing Newborn Blood Spots: Modern Controversies. BM. J Law, Med and Ethics 2004;Winter:

Thesis: Dried-blood specimens that remain after newborn screening is completed are valuable resources that should be carefully and thoughtfully preserved and used for public health benefit. Approach: To develop a national guidance policy for retaining and using dried blood specimens that remain after newborn screening is completed.

Reported Residual Bloodspot Storage – 5/1/2009 (Ascending Order) Years Residual Dried Bloodspots Stored Program Location 1 mo Indefinitely 3 mo6 mo 4 mo6 wk ~ 46% Newborn Pop. Stored for ≤ 3 yrs. ~ 54% Newborn Pop. Stored for ≥18 yrs.

Scientific Issues (1 of 3) Blood volume (number of spots available) Specimen quality (uniform collection and rejection practices) Biomarker stability (variability affecting detectability) 1. Physical Limitations

Scientific Issues (2 of 3) Permission (information to parents; consent or dissent process) (note: only 12 programs mention storage in educational materials) Definition of Purpose –Primary (program quality assurance; program improvement) –Secondary (family needs; program research; non-program research) Retention Conditions (temperature; humidity; controls) 2. Retention Process

Scientific Issues (2 of 3) Retention Duration (defined period of time; additional permission?) Space Requirements (dependent on size of specimen; container size) Accessibility (system – computerized ; non- computerized) Disposal (identifiers removed; no hazard identification) 2. Retention Process (cont)

Scientific Issues (3 of 3) Program – need (true cases; general population – quality improvement; method validation) Parental request (process; evaluation) Research –Identified (IRB review) –De-identified (models) 3. Usage Process

Scientific Issues (3 of 3) Accountability (released to whom; tracking; property of whom; return or disposal) Legal request (court order – forensic; other) 3. Usage Process (cont)

Policy Issues (1 of 4) 1. General interest Questions to be answered Policy maker responsibility –Public trust –Transparency Privacy protection –Parent advocacy –Legal requirements

Policy Issues (2 of 4) 2. State responsibility Policy maker responsibility –Public trust –Transparency Privacy protection –Parent advocacy –Legal requirements

Policy Issues (3 of 4) 3. Federal responsibility ACHDNC Federal agencies

Policy Issues (4 of 4) 4. Policy guidance Published information and policies – APHL – ACMG Model working repositories (honest broker) – MI – SC – Others?

Financial Issues Education (value; process) Blood spot collection kit modifications (retention and use) Storage (program; research) Access (including computerized process, if appropriate) Shipping (research use) Storage (researcher - confidentiality)

Legal and Ethical Issues Ownership Stewardship (15 states address storage/use in statute) Privacy protections Awareness and education (parents and public) Consent/dissent communication (sensitive; understandable – education, culture) Legal back-up (government attorney – aware; educated; available)

Recommendations 1.Parent education materials [model(s) for state use] 2.Consent/dissent process [model(s) of forms and procedures for state use] 3.Public/private partnerships – public health departments, advocacy groups, researchers, companies 4.National repositories (virtual and/or real – state, multi-state, regional, national)

References