A site must be registered first, but only once, at uscovidplasma.org, and then each physician/PI must be registered. Following that, they can consent and subsequently register patients for EAP enrollment. After receiving confirmation of patient enrollment, the treating physician will be authorized to contact their hospital blood bank to request convalescent plasma from their regular blood supplier.
For hospitals that do not have a regular blood supplier, Blood Centers of America (BCA), which operates a national resource sharing network, has implemented a toll-free number to help hospitals order convalescent plasma.
Hospitals that need to order convalescent plasma from an outside provider, can contact:
Phone: 844-633-3226 (844-NEEDABO)
After you administer the plasma product, you will need to complete several, short additional forms: a 4-hour post infusion data form capturing the essential data on serious adverse events that are required by the Sponsor and US Government; and two additional short, data forms at days 7 and 30 if your patient(s) remain hospitalized. It takes only a few minutes to complete each of the forms, which ensures that the expanded access program remains safe and potentially efficacious for all involved.
In collaboration with the U.S. Food and Drug Administration and the Mayo Clinic, it was decided that the Mayo IRB would be the Central IRB for the United States for the expanded access program (EAP). The FDA has waived certain requirements to allow the EAP to proceed as quickly as possible as exceptions to policy (e.g., the use of REDCap which is not 21 CFR Part 11 compliant and the use of typical written reliance agreements).
As such, we ask institutions wanting to participate as sites to agree to: 1) rely upon us by checking the box on the site and physician/PI registration forms; 2) abide by all U.S. and State regulations and the Principles in the Belmont report; 3) use the approved consent form; and 4) not require other written agreements.
The local institution/IRB can add a cover sheet to the consent form to include information unique to their operations, including:
- Local site name
- Local physician/PI name
- Local IRB and/or research advocate phone number and/or additional contact information
- Local instructions unique to the center and IRB operations
- Unique identifying information i.e., bar code that allow you to assist the physician/PI in tracking the consent forms and maintaining storage, digitally or in paper.
- Additional language which does not alter the risk/benefits section or the main consent language in any material manner.
The consent forms are available in English, Spanish and Arabic (uscovidplasma.org/#consent). If you have a local patient who speaks a different language, the treating physician/PI may elect to have it verbally read to the patient and certified that the reading is an exact translation before the patient signs the English version.
Yes, it is possible to participate in the Expanded Access Program and other clinical trials concurrently.
Information about additional emerging clinic trials at various institutions can be found at ccpp19.org.
The current guidelines for plasma donation developed by the American Red Cross in collaboration with the FDA are available here.
For more information about the location of blood donation centers and the donation process, please visit the American Red Cross website or contact your local blood donation center.
The US Food and Drug Administration asked Mayo Clinic to be the Central IRB for the US Expanded Access Program protocol. This request was intended to reduce the administrative burden on other institutions and the FDA by essentially allowing the use of the same product in the same manner in an already established and reviewed EAP that would be available from multiple eIND submissions. In this way it would potentially reduce the time to initiation of treatment.
Local IRB approval of the protocol is not necessary if you use and rely on the Mayo Clinic IRB which is AAHRPP accredited. In fact, the expanded access protocol is managed by a single, academic IRB to allow for quick dissemination nationally during the COVID-19 pandemic to give hospitals and medical centers access to the expanded use protocol as quickly as possible. Local IRB approval is not necessary from our standpoint but you can check with your local IRB to determine their requirements and policies.
Another option for your physicians if these terms are not acceptable is for your IRB and institution to assist them in applying for an emergency IND and use your own product and protocol. Refer to the FDA website for more information.
Each individual medical facility within a health system should be registered separately.
The Mayo Clinic IRB is serving as the IRB of record for this Expanded Access Program (EAP), sometimes colloquially referred to as 'compassionate use' at the request of the U.S. Government. An EAP is the mechanism by which access to certain investigational new drugs (IND) are made available outside of clinical trials. The focus of an EAP is to provide treatment whereas a clinical trial is focused on research. An EAP is sometimes necessary when the presence of a disease is classified as life threatening or severe and there is no current or readily available off-label intervention. In these instances, an EAP can be combined with an Investigational New Drug (IND) application to quickly make available a desired therapy to qualifying medical centers throughout the United States.
Using the specifically supplied inform consent form for the EAP found at uscovidplasma.org, the treating physician or anyone designated by the physician who is qualified to obtain clinical consent may perform and document the informed consent process. This process should follow institutional, local and federal (FDA) requirements as applicable.
The survey to complete the FDA 1572 Form will be emailed to the PI at the email address they provided in the patient enrollment form 24 hours after submitting the form. Please continue to proceed with Expanded Access Program protocol as you wait for this form. This form must be completed.
The U.S. Food and Drug Administration asked Mayo Clinic to serve as the Central IRB for the U.S. Expanded Access Program. The FDA and Mayo legal counsel discussed at length how to streamline the typical reliance agreement process to match the urgency of the situation. We settled on the mechanisms that are on the website, which requires hospitals/medical centers to check a box on the patient enrollment form indicating their agreement to rely upon the Mayo Clinic IRB, agree to follow all applicable regulations, follow the protocol and adhere to the principles of the Belmont Report.
We ask institutions wanting to participate as sites to agree to (1) rely upon Mayo Clinic IRB by checking the box on the site and Physcian/PI enrollment form, (2) abide by all US and state regulations and the Principles in the Belmont report, (3) use our approved consent form and (4) not ask for any other written agreements. The FDA has waived certain requirements for us to allow the EAP to proceed as quickly as possible as exceptions to policy. The use of REDCap is one example. The use of typical written reliance agreements are another.
Provided the patient meets eligibility criteria, the Expanded Access Program may provide a more streamlined process that allows multiple centers to enroll multiple patients with a centralized source of compliance and safety support. The emergency IND (eIND) process is still active; please visit the FDA website for additional information.
The Expanded Access Program is not directly involved in obtaining serologic testing for COVID-19. If you are interested in obtaining serologic testing, the test would need to be ordered by your local medical provider. This test is being processed at a small number of laboratories across the country.
To ensure compatibility with blood type and the requirement to adhere to strict guidelines for participating in this treatment program, directed donations are not permitted.
The Mayo Clinic REDCap database resides behind multiple layers of physical security. Additionally, when a user submits a form, it is transmitted with a secure HTTPS-encrypted connection. All inbound network traffic is monitored 24 hours per day; and any web traffic without the proper, secure token is immediately blocked. This has been approved by the FDA.
Your site/ medical center can designate one physician/PI for this Expanded Access Program or multiple physicians/ PIs can register for each site.
A site administrator will typically register the site. The treating physician or the PI is responsible for physician/PI registration, patient consent, patient registration completion of Form FDA 1572 survey (one for each site they will be treating patient(s) at under the EAP), completion of follow-up information, and reporting of adverse events.
We understand that it may be too difficult or challenging to obtain written informed consent in person, especially if the patient is critically ill and not able to provide consent. If the treating physician/PI is unable to be physically in the room with the patient at the time of written informed consent, they or their designee trained to get informed consent can speak with the patient via a telemedicine or telephone device, and ask the patient to sign the consent form. The patient or his/her family member or health care worker can photograph the consent form and email it with signature to the physician/PI.
If the LAR/designee is unable to be physically in the room with the patient at the time of written informed consent, the Physician/PI or their designee trained to get informed consent can speak with the LAR via a telemedicine or telephone device, and ask them to sign the consent form. They can photograph the consent form and email it with signature to the physician/PI.
You can also email us at firstname.lastname@example.org for additional discussion.
This is a situation where we are asking medical centers to take the protocol and consent form as is or they are not eligible to participate. This was a joint decision by officials at US FDA and ourselves. We apologize if it seems brusque. It is not intended in that manner, but rather to ensure safety and efficacy.
No, the Expanded Access Program (EAP) does not require a certificate in order for hospital blood banks to obtain convalescent plasma, which may be required for other programs such as eINDs.
Number of Units:
The Expanded Access Program (EAP) protocol enables physicians to administer 1 or more units of COVID-19 convalescent plasma to any eligible and enrolled patient in the EAP. The volume of plasma to be transfused should be at least one unit (approximately 200 mL) and based on the patient’s weight and clinical comorbidities (e.g., patients with impaired cardiac function and heart failure may require less volume or prolonged transfusion times).
In general, it is expected that most patients will receive 1-2 units, but larger quantities are allowed if the treating physician determines that additional units and/or re-treatment are clinically justified. Transfusions may occur at any time throughout the hospitalization including multiple doses on non-sequential days.
Compatibility of Plasma:
ABO-compatible convalescent plasma will be transfused preferentially. If ABO-compatible convalescent plasma is not available, investigators may follow their institution’s guidelines for administration of incompatible plasma with respect to ABO mismatch, titer and volume limits. For example, in the absence of ABO-compatible plasma, some institutional guidelines include that patients may receive as a second choice either Group A plasma or low anti-A titer Group O plasma, as available.
Rate of transfusion:
Physicians should transfuse each unit of convalescent plasma at an infusion rate that adheres to institutional guidelines and best clinical practice.
If transfusion of plasma does not occur, please complete the Initial Data Collection Form, citing the reason(s) the transfusion did not occur.
One Initial Data Collection Form should be completed for each plasma transfusion.
If transfusing one unit of plasma: The Initial Data Collection Form should start with the beginning of the transfusion period and include the 4-hour window following the transfusion. Thus, if the transfusion requires 1.5 hours for completion, the Initial Data Collection Form represents a 5.5-hour period.
While the EAP program prefers the attending physician/PI complete the initial data collection form, any required form can be completed by the delegate the physician/PI chooses. The only regulatory requirement is that all forms be completed and submitted at the appropriate time.
Notably, the physician/PI is required to complete the physician/PI registration and FDA 1572 Form.
Serious adverse events (SAEs) associated with this EAP need to be reported on the 4 hour post-transfusion form for events that occur during and up to 4 hours post-transfusion, and on the Serious Adverse Event Report form for events that occur after 4 hours post-transfusion through day 7 post-transfusion. This is a regulatory requirement. The physician must report:
- Transfusion related acute lung injury (TRALI)
- Transfusion related circulatory overload (TACO)
- Transfusion related infection
- Severe allergic transfusion reaction (requiring medical intervention other than antihistamines)
- Severe hemolytic transfusion reaction (requiring medical intervention)
- Severe anaphylactic reaction
- VF ventricular arrhythmia requiring treatment
- VT ventricular arrhythmia requiring treatment
- Atrial arrhythmia requiring treatment
- Atrial fibrillation requiring treatment
- Cardiac arrest
- Need for ECMO or ventricular assistance
- Need for ICU transfer (since transfusion)
- Need for increased oxygen support (since transfusion)
- Need for mechanical ventilation (since transfusion)
- Development of sustained low blood pressure (SBP < 80 or need for IV pressure support in estimation of treating physicians)
ABO-compatible convalescent plasma will be transfused preferentially. If ABO-compatible convalescent plasma is not available, investigators may follow their institution’s guidelines for administration of incompatible plasma with respect to ABO mismatch, titer and volume limits.