Blood Donor Written Statement of Understanding Introduction Orieji Illoh, MD Office of Blood Research and Review CBER/FDA Blood Products Advisory Committee April 29, 2011

Outline Introduction Issues to be considered Donor consent: Current status FDA requirements or recommendations AABB standards ACBSA recommendations “Written statement of understanding” (WSU) Elements as outlined in the 2007 proposed rule Public comments to the proposed rule Elements of the written statement of understanding Educational material Risks and hazards of blood donation Questions for the committee Speakers and topics

Introduction About 10 million allogeneic donors provided ~17 million donations of Whole Blood and Red Blood Cells in 2008. The blood donation process is highly safe but adverse reactions can occur. FDA has regulations for donor consent in Source plasma, plateletpheresis and plasmapheresis donors. The practice of donor consent for whole blood donors varies. 3

Blood donation process 1 2 3 4 Registration Donor provides identification and demographic information Donor reads information about blood donation (Educational material) Donor consents to blood donation Health history and limited physical examination Health history questions asked by blood center staff Blood pressure, pulse and hemoglobin levels are checked Donation Arm is cleansed Blood is drawn (6-10 minutes) Needle is removed Recovery Rest ~ 15mins Snacks Average donation process takes just under one hour

Issues for consideration Proposed “Written Statement of Understanding” for Whole Blood donors Content How to administer When to administer Does not include informed consent for research studies. Including collection of repository samples.

Donor consent: Current status

FDA requirements or recommendations Source Plasma 21CFR 640.61 “Guidance on Informed Consent Recommendations for Source Plasma Donors Participating in Plasmapheresis and Immunization Programs” Plateletpheresis and plasmapheresis 21 CFR 640.21(c) and 21CFR 640.31(b) “Guidance for Industry and FDA Review Staff: Collection of Platelets by Automated Methods” Apheresis red blood cell donations “Guidance for Industry: Recommendations for Collecting Red Blood Cells by Automated Apheresis Methods

AABB Standard for Donor Consent Obtained on the day of donation and presented in understandable terms Information provided regarding: Risks of the procedure. Tests performed to reduce the transmission of infectious diseases to the allogeneic recipient. An opportunity provided to ask questions and to give or refuse consent for donation. AABB. Standards for Blood Banks and Transfusion Services. 27th ed.

Advisory Committee for Blood Safety and Availability: December 2008 Donor consent is generally adequate but lacks consistency. Include in consent forms The effects of repeat donation on the donor population. The gender specific effects of iron deficiency on donors. The effects of collecting blood from anemic men using current donation thresholds. The disproportionate prevalence of adverse events in the youngest donors. Consider The method and frequency of effective informed consent for repeat donations

FDA Proposed Rule: Written Statement of Understanding

“Written Statement of Understanding” - definition The term “Written Statement of Understanding” is used as a general term to differentiate it from informed consent for research as defined in 21CFR 50.25

2007 Proposed Rule: WSU The donor has received and reviewed the educational material. The donor agrees not to donate if the donation could result in a potential risk to the safety, purity, or potency of the blood supply. A sample of the donor’s blood will be tested for specified relevant transfusion-transmitted infections and for syphilis.

2007 Proposed Rule: WSU If any of the tests is reactive, the sample of blood will be tested further. If the donation is determined to be not suitable or if the donor is deferred from donation, the donor’s record must identify the donor as ineligible to donate and the donor must be notified. The hazards and risks of the donation procedure are explained. The donor has the opportunity to ask questions and withdraw consent at any time.

2007 Proposed Rule: WSU Blood establishments would need to provide and ensure that the written statement to the donor: Is read and signed before each donation. Is written in clear terminology. Does not include language that would waive any of the donor's legal rights. FDA rulemaking is not intended to preempt state laws regarding donor consent for minors.

Proposed Rule: WSU Representative comments from industry Agreement that donors should be adequately informed about the blood donation process and that there should be documentation that the donor has been so informed. Concern about how signature will be obtained. Consider electronic acknowledgement. Provide guidance that provides recommendations for compliance with this rule.

Proposed Rule: Written Statement of Understanding: Selected elements Educational materials Risks and hazards of donation

WSU: Educational materials AABB introduced educational materials in 1984. Current FDA recommendations for HIV education published in the 1992 memorandum. Incorporated into the AABB educational materials. AABB educational material version 1.3

WSU: Educational materials Information about the behaviors that increase risks of relevant transfusion-transmitted infections. Signs and symptoms of such infections, and the consequent risk to the safety of the blood and blood component. Instructions for donors to self-defer if they determine that they have participated in an increased-risk behavior for, or show signs or symptoms of that relevant transfusion-transmitted infection.

WSU: Educational materials This information may be provided in oral, written, or multimedia form in a manner designed to be understood by the donor. FDA may provide additional guidance in the future.

WSU: Risks and hazards of Blood donation About 3 – 10% of blood donors will experience an adverse reaction Eder A et al. Transfus Med Rev. 2009 Jul;23(3):205-20. Severe adverse donor reaction rate in 2008 = 0.09% collection procedures Whitaker BI et al. The 2009 National Blood Collection and Utilization Survey (presented at the 2010 AABB meeting)

Risks and hazards of Whole Blood donation Minor Major Long term Dizziness Presyncope Bruises Hematomas Allergic Syncope with loss of consciousness or injury Nerve damage Arterial puncture Iron deficiency with or without anemia

Risks and hazards of blood donation Study: Post donation interview of 1000 Whole Blood donors % donor reaction rate AEs = Adverse effects Arm injuries Systemic reactions Total AEs Bruise Sore arm Hematoma Sensory changes Fatigue Vasovagal Nausea and vomiting 36.1 22.7 10.0 1.7 0.9 7.8 5.3 1.1 Newman et al. Transfusion. 2003 May;43(5):598-603

American Red Cross: 2006 hemovigilance data Rates of complications associated with allogeneic Whole Blood donation ~ 6 million whole blood donations ~ 349 complications/ 10,000 donations Major reaction rate (7.4/10,000) Most complications were minor Hematomas (~75/10,000) Presyncopal (~258/10,000) Eder et al. Transfusion. 2008 Sep;48(9):1809-19

Blood donor fatalities FDA donor fatality reports: FY 2005 through FY 2009. In 2009, Whole blood fatalities 2 cases - donation ruled out 1 case - donation not ruled out but no causal relationship http://www.fda.gov/BiologicsBloodVaccines/Safety Availability/ReportaProblem/TransfusionDonationFatalities

Questions for the committee Please comment on the seven proposed elements of the written statement of understanding as listed in FDA’s 2007 proposed donor eligibility rule. Does the Committee agree that the data support a need for minimum standards for the explanation of the risks and hazards of Whole Blood donation to the donor? Please comment on what methods are acceptable for presenting the written statement of understanding to the donor, and how the donor should acknowledge receipt of this statement.

Questions for the committee Please comment: When should blood establishments administer the written statement of understanding? Before donor questions? Before physical examination? Before phlebotomy? Please comment: How often should blood establishments administer the written statement of understanding to Whole Blood donors?

Speakers Christine Grady, MSN, PhD : National Institutes of Health. Clinical Center An overview of informed consent Beth Shaz, M.D.: New York Blood Center Evaluation of informed consent forms for adults and minors for whole blood donation used by United States blood centers. Ronald Domen, M.D.: Penn State Milton S. Hershey Medical Center The informed consent process in whole blood donation.