POINT Trial Readiness Call Questions and Checklist: CRC, US

HUB: / SPOKE NAME: / DATE:
SPOKE #:
  1. POINT PERSONNEL REGULATORY CHECKLIST SUMMARY

Regulatory Requirements
/ Principal Investigator – A, B, C, D, F, G, H, I, J, K, L,M
Co-Investigator – A, B, C, F, G, H, J, L
Primary Study Coordinator – A, B, C, D, *E, F, G, H, J, K, L
Secondary Coordinator – A, B, C, *E, F, G, H, L
Data Entry (all performing J, K responsibility on DOA log) – B, *E, G,L
Primary Drug Recipient – A, C, L, O
Secondary Drug Recipient – A, C, L, O
Administrator – Requirements based on responsibilities
A: CV
B: HIPAA
C: Medical License (if applicable)
D: POINT Protocol Training
E: POINT Data Training
F: NIHSS Certification / G: HSP
H: ABCD2
I: PI Protocol Signature Page
J: mRS Certification
K: POINT Enrollment Training / L: GCP Training
M: Physician Information Form
N: Shipping & Handling Certification**
O: Pharmacy Training
All team members performing study specific tasks (e.g., performing assessments, obtaining informed consent, abstracting data from patient records) must be included on the DOA Log.
*All team members performing direct data entry must complete the POINT Data Training(J and K responsibility on DOA log).
**Required for at least one study team member if site is participating in the POINT Ancillary Study
  1. POINT DOCUMENTS

Status* / Document / Comments
Protocol Signature Page
CV
Medical License
HIPAA
HSP
Protocol Training
Data Training
Pharmacy Data Training
NIHSS Certification**
ABCD2 Certification**
mRS Certification**
Shipping & Handling Certification
Pharmacy Training
GCP training
Physician Information Form
*C=Complete; I=Incomplete.
**This certification can be waived in WebDCUTM if a team member will not be completing the assessment.

POINT DOCUMENTS (continued)

Status* / Document / Comments
FWA / Facilities covered by this FWA:
Full IRB Application Submission** (current version of the protocol and ICF, Clopidogrel package insert, IND exemption letter, and Subject resource tools if applicable)
IRB ICF Approval
IRB Protocol Approval
Delegation of Authority Log
Institutional Drug Destruction Policy
CAP Certification
ORI Assurance
CLIA Certification
*C=Complete; I=Incomplete
**Documentation should support the following items as submitted to the IRB: current version of the protocol and ICF, Clopidogrel package insert, IND exemption letter, and Subject resource tools (if applicable)

Please discuss the following logistical aspects with your study team before you begin the study.

  1. SITE INFORMATION
  • Confirm the Spoke mailing address and telephone number for shipping study materials other than study drug:

Address: / Phone Number:
  • Has the WebDCUTMClinical Site record been updated with this address and telephone number?

Yes ☐ No ☐

  • Confirm the address and telephone number where subject recruitment and the 90-Day follow-up visits will occur:

Address: / Phone Number:
  1. Study drug control plan
  • Who is the designated Primary Study Drug Recipient?

Name: / Phone Number:
  • Has the Primary Study Drug Recipient completed the Pharmacy Training module available on the NETT website under POINT? Yes ☐ No ☐
  • Are there any other staff at the site who may have access to or dispense study drug (e.g., other coordinators, pharmacy technicians)?

Ensure that all staff involved in study drug handling are indicated on the delegation of authority log.

  • Confirm the address and direct telephone number for shipping study drug:

Address: / Phone Number:
  • Has the WebDCUTMClinical Site record been updated with this address and telephone number?

Yes ☐ No ☐

  • Will the drug be stored at this location after it is received?Yes ☐ No ☐
  • If no, please provide the storage location, address and phone number:

Address: / Phone Number:
  • If no, what are the procedures and associated timelines for transporting the drug from the receiving location to the storage location?
  • Is study drug stored in an Investigational Pharmacy at your site? Yes ☐ No ☐
  • If no, where is study drug stored at your site?
  • If stored in Inpatient Pharmacy: Is study drug kept separate from other drug inventory in your site’s pharmacy? Yes ☐ No ☐
  • What are the hours of operation where the study drug is stored?
  • If the study drug hours of operations are not 24/7, how will the study team access study drug for subjects who might be randomized when the storage facility is closed?

Study drug should be stored at room temperature (25°C/77°F) with excursions permitted within 15-30°C/59-86°F.

  • How will your site monitor and document daily temperature of study drug?
  • Does your site have automated temperature monitoring? Yes ☐ No ☐
  • How will your site monitor and document temperature on the weekends or holidays?
  • Describe the process by which your site handles temperature excursions.
  • How does your site handle temperature excursions on weekends and holidays?
  • Does your institution require that additional labeling be added to the study drug bottle? Yes ☐ No ☐

If yes, please ensure that the randomization number on the bottle is not covered by any additional label.

  • Does your site have SOPs to cover unblinding and dispensing of study drug? Yes ☐ No ☐
  • If planning to use your own, by what date will SOPs be developed?
  • Does your site have the current POINT Study Drug Handling SOP template?

Yes ☐ No ☐

  • Who will be required to complete and maintain the study drug accountability log?

As a reminder, if the POINT Study Drug Accountability is not utilized at your site, please ensure that the accountability log used contains information to document receipt, dispensing, return and destruction respective to each study drug bottle and the person responsible for each of these procedures.

  • Where will returned study bottles be delivered and stored? If these locations are different, please specify and explain the planned procedure for ensuring accountability for each bottle.

Drug will be destroyed on-site following local guidelines at the end of the study. You should retain any returned study bottles until the Site Monitor conducts a visit at your institution or you have been notified by the Monitor that they can be destroyed.

  • Has your site uploadeda copy of your internal SOP for study drug destruction to the database? Yes ☐ No ☐
  • If no, by what date will SOPs be provided?

Ensuring that enrolled subjects are not accidentally prescribed prohibited medications by hospital staff who are not a part of the POINT study has proven challenging at some sites.

  • What steps will be taken at your site to prevent subjects from receiving prohibited medications?
  • Does your site or hospital policy require administration of low-dose anticoagulants for DVT prophylaxis for stroke or TIA patients? Yes ☐ No ☐
  • If yes, please list policy requirements:
  1. Subject enrollment
  • How many hours per day & days per week do you plan to screen subjects?
  • If you are not screening subjects every day:
  • What is the reason for screening subjects on this schedule?
  • Do you have plans to expand the schedule to daily screening?
  • What is your process for identifying/screening potential subjects?
  • How will your study team respond when a potential subject is identified?
  • Does your site have a Stroke Code team and pager system? Yes ☐ No ☐
  • Does your stroke protocol apply for TIA patients as well? Yes ☐ No ☐
  • Do your stroke neurologists come to the ED for the neuro consult? Yes ☐ No ☐
  • Who on the POINT team will be notified when there’s a stroke or TIA patient in the Emergency Department?

Name: / Phone Number:
  • Does your Primary Study Coordinator carry a pager and/or cell phone? Yes ☐ No ☐
  • What is your process for obtaining informed consent?

As part of the consent process and in support of GCP, please be sure to document the discussion within the study files. A sample template for this can be found in the Toolbox on the Resources and Training website. NOTE: Surrogate consent is not permitted in the POINT Trial. Subjects with neurological deficits affecting handwriting should attempt to sign the informed consent form independently. Any illegible writing should be explained in documentation on-site.

  • Where will the consent discussion be noted on site (e.g., EMR, study files, hard copy medical record)?
  • If you are not already participating, would you be interested in learning more about the iPad POINT Trial Consent Supplement Video when consenting patients? Yes ☐ No ☐
  • For reference, we have made the Supplement Consent Video available to site personnel. To access it, please click on the desired link below. If a password is requested, enter “POINTENGLISH” in all caps.

Consent Supplement Video:

English:

Spanish:

Mandarin:

French Canadian:

  1. DOSING REMINDERS

NOTE: Subjects should be given the full loading dose (8 pills) of study drug in the ED even if s/he took a home dose of clopidogrel that day.

Please be sure to document the date and time of the initial loading dose and which member of the study team witnessed the subject taking the loading dose.

  • What is your process for providing the initial (loading) dose of study drug?
  • How will the initial dose of aspirin be administered (i.e., given at the same time as the loading dose of study drug, or at a separate time)?

The dosage range of aspirin during enrollment is 50-325 mg daily, at the discretion of the treating physician.

The strongly recommended dose is 150-200 mg (162 mg in US) daily x 5 daysfollowed by 75-100 mg (81 mg in US) daily for the remainder of the trial.

  • What dose of aspirin will your site administer with the loading dose of study drug?
  • Please discuss how your site plans to handle those subjects who have already taken aspirin for that day. (See recommendations below).

The study recommends the following when a subject has already taken aspirin on Day 1 of enrollment:

  • Supplement the aspirin up to recommended dose of 150-200 mg if the patient has already taken a dose of aspirin that day.
  • If a subject has taken a dose of 75-100 mg within 12 hours of presentation to the ED, the subject can be given another 75-100 mg.
  • If a subject has already taken more than 200 mg within 12 hours, s/he does not need to get another dose until the following day.
  • If it has been more than 12 hours since a subject prior dose of aspirin, then the subject should be given a full dose (suggested 150-200mg).
  • Please consult the Pharmacy Study Drug Handling SOP for details on supplementing aspirin based on timing and/or dosage taken on the first day.
  • Following the Day 1 loading dose,what dose of aspirin will your site prescribe for the next 4 days?
  • What dose of aspirin will your site prescribe for the remaining days?
  • If the patient is admitted to your institution, how will you administer study drug on Day 2 and up to discharge?
  • How will subjects be provided with study drug at discharge?
  • Aspirin is not provided by the study. Will you provide aspirin to the subjects prior to discharge (give them a bottle or a prescription) or instruct subjects to obtain aspirin over-the-counter?
  1. SERIOUS ADVERSE EVENTS AND CLINICAL OUTCOME REPORTING
  • All SAEs/Clinical Outcomes occurring until participation in study has ended are recorded on the online SAE/Clinical Outcome Reporting Form (CRF 19) through WebDCUTM.
  • All SAEs/Clinical Outcomes will require an Event Packet to be uploaded to the database. This packet should include copies of discharge summaries, neurology, cardiology or other consultation notes, head imaging reports, appropriate laboratory values, and a narrative summary, plus any supplemental documentation based upon adjudication category assigned to the event, with all unique identifiers removed.
  • An investigator will document his/her determination of all components of the SAE including severity, seriousness, outcome, relationship to study drug, and resolution date. This documentation will be reviewed by a monitor at site visits.
  • Who will be responsible for entering the SAEs into the database and updating information as needed? *All data entry must take place within 5 days of discovery of the event.*

Name: / Phone Number:
  • All SAEs will be reported to the local IRB by the site and all related IRB correspondence must be uploaded into the regulatory database as “POINT IRB Modification Notifications”.
  1. MAINTENANCE OF RESEARCH RECORDS
  • Describe how source documents will be stored at your site.
  • Explain how research records will be managed electronically, if applicable.
  • Describe how research records will be protected against inappropriate use, disclosure, or accidental loss.
  1. ANCILLARY STUDY BLOOD DRAW
  • Is your site participating in the biomarker substudy? Yes ☐ No ☐ (If no, proceed to SectionIX.)
  • If yes, has the WebDCUTMBiomarker Study Site table been updated (contact person, shipping address)?

Yes ☐ No ☐

What is the kit shipping address, contact name, email, and telephone numberof the person responsible for receiving and ordering biomarker kits and supplies? Please include any room or suite numbers.

Name: / Email:
Address: / Phone:
  • Is your site participating in DNA only, or DNA and plasma? DNA only ☐ DNA and plasma ☐
  • Are you familiar with the lab manualon the POINT NETT website? Yes ☐ No ☐
  • Would your site like to receive additional training on the biomarker substudy? Yes ☐ No ☐
  • If yes, who should be contacted?

Name: / Email: / Phone Number:

DNA Only:

If your site is participating in DNA only, specimens must be stored in a 4°C refrigerator and shipped on Cool Packs within 4 daysfrom date of blood draw. Specimens can be shipped Monday through Thursday ONLY.

  • Does your site have a 4°C refrigerator to store specimens for 4 days: Yes ☐ No ☐

DNA and Plasma:

  • Does your site have a centrifuge that operates at 1000g? Yes ☐ No ☐
  • Does your site have access to both of the following types of freezers:

-20°C, -30°C or -40°C freezer ☐ -70°C or -85°C freezer ☐

If you are using a -20°C, -30°C or -40°C freezer, specimens must be shipped on dry ice within

4 days from blood draw. Example: If blood drawn on a Thursday, the specimen must be shipped no later than Monday.

NOTE: Specimens can be shipped Monday through Thursday ONLY.

If you are using a -70°C or colder freezer,specimens may be stored in the freezer for up to

3 months and then shipped on dry ice to LabCorp.

NOTE: Specimens can be shipped Monday through Thursday ONLY.

NOTE: Once a specimen is stored at one freezer temperature, it cannot be transferred to the other.

  • Has your site received biomarker kits? Yes ☐ No ☐
  • If no, an initial shipment of5 kits will arrive on: ______(If unknown, Sponsor will provide estimated date during Readiness Call)
  • Who holds Shipping and Handling Certification at your site?

Name: / Location:
  • Do you have a single consent or 2 separate forms covering both the main POINT study and the Ancillary Biomarker Study? Single consent form☐ 2 separate consent forms ☐
  • Documentation such as calibration, maintenance, and temperature records verifying that the equipment is functioning as needed will be reviewed during monitoring visits.

A list of Ancillary Study FAQs is available in the Toolbox on the NETT website.

  1. RANDOMIZATION REMINDERS
  • When screening subjects, please document that both inclusion and exclusion criteria were reviewed by the PI or a Co-I in the subject’s source notes.
  • Subjects must be randomized within 12 hours of time the participant was last known to be free from new ischemic symptoms and should receive their loading dose of study drug as soon thereafter as possible, ideally within the 12 hours of time last known free of new ischemic symptoms.
  • Time between randomization and treatment should be minimized: treatment should be considered STAT.
  • A letter to the subject’s Primary Care Physician, Prohibited Medication List, Study Medication Information Sheet, and Study Medication Calendar are available in the Toolbox here: Sites should obtain IRB approval for these materials before distributing them to subjects.
  • Sites should contact the study hotline at 1-866-94-POINT (1-866-947-6468) should a subject need to be unblinded.
  • The NETT and CRC are blinded, so subject treatment status should not be communicated to them, and should be limited among study team members. A blinded study team member will need to conduct the follow-up visits.
  • Once randomized, always analyzed. Subjects should still receive the 7-day and 30-day follow up phone calls and come in for the 90-day visit, even if they discontinue taking study drug, whenever possible.
  • How many patients do you expect to enroll in a 60 day period? ____
  • Do you have competing trials? Yes ☐ No ☐
  • If yes, which trial(s)?
  • If yes, what is the process for allocating potential subjects between trials?
  1. Randomization Procedure Reminders
  • To minimize crossover during randomization, a link for a Randomization Verification Form (RVF) will be on the completed Randomization Form 10 in WebDCUTM. This form includes the subject randomization number and should be printed and taken to the pharmacy or study drug dispensing location. The Study Drug ID number on the Verification Form should be compared against the ID number on the bottle of study medication, and the form itself should be signed by study personnel, ideally the Study Coordinator and the dispensing pharmacist. The signed form should be kept in the study files on site; it does not need to be submitted to WebDCUTM, but monitors will review it during site visits.
  • For every subject randomization, the site will also receive a follow-up email.
  • For emergency clinical questions regarding enrollment eligibility or emergency unblinding, call the 24-hour POINT study hotline at 1-866-94-POINT (1-866-947-6468).
  • Press 1 for urgent clinical questions related to enrollment eligibility, or for emergency unblinding.
  • Press 2for the WebDCUTM Emergency Randomization Hotline for questions related to technical issues during randomization.
  1. Data Entry Reminders
  • Please make and document several attempts to contact subjects before considering them Lost to Follow-Up, including phone, email, and certified letter. If subjects are unable or unwilling to return for the 90-day visit, please gather as much information as possible over the phone. The coordinator should also request that the subject return the study drug bottle to the site. Subjects will be considered lost to follow-up when the site is unable to collect reliable information about the status of a subject up to 150 days after randomization. Dates of attempts to contact the subject and alternative contact (if applicable) must be entered into the General Comments section of F17: End of Study in WebDCUTM.
  • For data management support during working hours (9 am to 5 pm US Eastern Time), please contact your Site Manager/Monitor.
  1. Source Documentation

Sites are expected to maintain appropriate source documentation. These are the original documents/materials where clinical information (subject case history) is recorded to support data reported for the study. Examples of source documents include, but are not limited to, electronic medical records, hard copy medical records, imaging reports, study worksheets, lab reports, discharge notes.