electronic case report form (ecrf) completion …

ELECTRONIC CASE REPORT FORM (eCRF) COMPLETION GUIDELINES RAVE

Infant Bacterial Therapeutics AB IBP-9414-020 INFA133227 Version 4.0 AD-DM-231.03 30-Jul-2017 of 32

1. Project Information

SPONSOR: Infant Bacterial Therapeutics AB (IBT)

PROTOCOL NO.: IBP-9414-020

STUDY TITLE:

A randomized, double blind, parallel-group, placebo controlled study to evaluate the efficacy and safety of IBP-9414 in premature infants 500-1500g birth weight in the prevention of necrotizing enterocolitis – The Connection study

VERSION – DATE OF

DOCUMENT: 4.0 – 24-Jun-2020

2. Signatures

Signature(s) confirm appropriate review has taken place and the document is approved.

Reviewer:

Clinical Manager- Premier Research Date

Approver:

Sponsor Representative – Infant Bacterial Therapeutics

AB

Date

Author:

Lead Data Manager- Premier Research Date

24-Jun-2020 | 12:18:43 EDT

25-Jun-2020 | 03:38:38 EDT

25-jun-2020 | 03:48:10 PDT



3. Version History

All changes made to this document will be listed in this log.

Date of effective Change

Version # Changed by Section # Reason / Description of Change

07-Nov-2018 0.1 Pania Slezak First initial version

14-Nov-2018 0.2 Pania Slezak Updated according to internal team

review

14-May-2019 0.3 Natalia Estévez Updated according to Protocol V5.0

21-May-2019 0.4 Natalia Estévez Updated according to internal team

review

23-May-2019 0.5 Natalia Estévez Section 6 Contacts for Questions

7.3 Screen

Failures

9.6 Medical

History and

9.24

Concomitant

Medications

Updated according to sponsor comments.

Section 6 -Contacts for Questions: Toll

free numbers updated to keep countries

for the study.

7.3 Screen Failures: information to be collected has been updated. Medical History and Concomitant Medications deleted.

9.6 and 9.24 updated to explain that

Concomitant Medication will be collected

since first dose of IP.

04-Jun-2019 0.6 Natalia Estévez 4. Study Title

Death

Adverse

Events

Study title updated according to protocol

version 5.0

Death section updated as new question

was added to the eCRF v 2.0 to confirm

NEC by histopathology.

Adverse event section has been updated

to clarify that events that occur before

first dose will be considered as Medical

History.

05-Jun-2019 0.7 Natalia Estévez 9.26 Adverse Events

Section 9.26 updated to clarify reporting

of reoccurring Adverse Events

06-Jun-2019 1.0 Natalia Estévez Final version release

26-Jun-2019 1.1 Natalia Estévez Section Informed Consent

Reference to countries and protocol

amendment

27-Jun-2019 1.2 Natalia Estévez Informed Consent

After internal review. No comments sponsor

28-Jun-2019 2.0 Natalia Estévez Final version release



Date of effective Change

Version # Changed by Section # Reason / Description of Change

10-Dec-2019 2.1 Natalia Estévez End of Treatment

Reason for treatment discontinuation

‘AE/SAE’ added

12-Dec-2019 3.0 Natalia Estévez Final version release-no changes from

draft 2.1

16-Mar-2020 3.1 Natalia Estévez End of

treatment

Study

Completion

Concomitant

Medication

Clarification added for permanent IP

discontinuation

Clarification added for Date of study

completion

Clarifications added

27-Apr-2020 3.2 Natalia Estévez FUP visit Weight to be collected always

17-Jun-2020 3.3 Natalia Estévez Study

Completion

End of

treatment

Update to include COVID-19 options

and ‘Deterioration of subject’s clinical

condition’ has been removed as ET

reason

Update to include COVID-19 option

COVID-19

Impact Clarifications added for COVID-19

23-Jun-2020 3.4 Natalia Estévez Concomitant

Medication

Nutritional

Intake

Abdominal

Radiograph

After internal review.

24-Jun-2020 4.0 Natalia Estévez Final version release-no changes from

draft 3.4



4. TABLE OF CONTENTS

1. PROJECT INFORMATION ................................................................................................................................ 1

2. SIGNATURES .................................................................................................................................................. 1

3. VERSION HISTORY .......................................................................................................................................... 2

SECTION 6 CONTACTS FOR QUESTIONS .................................................................................................................. 2

4. STUDY TITLE ................................................................................................................................................... 2

9.26 ADVERSE EVENTS ............................................................................................................................................ 2

SECTION INFORMED CONSENT ............................................................................................................................... 2

INFORMED CONSENT ............................................................................................................................................. 2

END OF TREATMENT .............................................................................................................................................. 3

4. TABLE OF CONTENTS .......................................................................................................................................... 4

5. CONTACT INFORMATION ............................................................................................................................... 6

6. CONTACTS FOR QUESTIONS ........................................................................................................................... 6

7. GENERAL CRF COMPLETION INSTRUCTIONS................................................................................................... 7

7.1 ACCESS TO RAVE & LOGGING ON ................................................................................................................................. 7 7.2 STANDARD GUIDELINES .............................................................................................................................................. 8 7.3 SCREEN FAILURES ...................................................................................................................................................... 9 7.4 SITE NUMBER ASSIGNMENT ...................................................................................................................................... 10 7.5 SUBJECT NUMBER ASSIGNMENT ................................................................................................................................ 10 7.6 GENERAL GUIDELINES FOR MEDICAL CODING ............................................................................................................... 10 7.7 ADVERSE EVENT / MEDICAL HISTORY /PRIOR & CONCURRENT PROCEDURES ...................................................................... 11 7.8 MEDICATIONS ........................................................................................................................................................ 12

8. GENERAL RAVE GUIDELINES ......................................................................................................................... 13

IMEDIDATA RAVE ICON KEYS ......................................................................................................................................... 13 FORMS, QUERIES, AND SYSTEM BEHAVIORS ....................................................................................................................... 13 CRF COMPLETION ........................................................................................................................................................ 16 INVESTIGATOR REVIEW AND CERTIFICATION ....................................................................................................................... 16

9. PROTOCOL-SPECIFIC CRF COMPLETION INSTRUCTIONS ............................................................................... 17

9.1 SCREENED .......................................................................................................................................................... 17 9.2 VISIT DATE ......................................................................................................................................................... 17 9.3 INFORMED CONSENT ........................................................................................................................................ 18 9.4 MEDICAL HISTORY YN? ..................................................................................................................................... 18 9.5 MEDICAL HISTORY ............................................................................................................................................. 18 9.6 DEMOGRAPHY ................................................................................................................................................... 19 9.7 INCLUSION CRITERIA YN ................................................................................................................................... 20 9.8 INCLUSION CRITERIA ......................................................................................................................................... 20 9.9 EXCLUSION CRITERIA YN ................................................................................................................................... 20 9.10 EXCLUSION CRITERIA ...................................................................................................................................... 20



9.11 PATIENT STATUS ............................................................................................................................................. 20 9.12 FAILED .............................................................................................................................................................. 21 9.13 RANDOMIZATION ........................................................................................................................................... 21 9.14 WEEKLY GROWTH MEASUREMENTS .............................................................................................................. 21 9.15 WEIGHT MEASUREMENT ................................................................................................................................ 21 9.16 ABDOMINAL RADIOGRAPH AND LAPAROTOMY ........................................................................................... 22 9.17 STUDY DRUG ADMINISTRATION..................................................................................................................... 23 9.18 NUTRITIONAL INTAKE ..................................................................................................................................... 23 9.19 END OF TREATMENT ....................................................................................................................................... 24 9.20 STUDY COMPLETION ....................................................................................................................................... 25 9.21 DEATH .............................................................................................................................................................. 26 9.22 FOLLOW-UP VISIT ............................................................................................................................................ 26 9.23 CONCOMITANT MEDICATIONS Y/N? .............................................................................................................. 26 9.24 CONCOMITANT MEDICATIONS ....................................................................................................................... 26 9.25 ADVERSE EVENTS Y/N ..................................................................................................................................... 27 9.26 ADVERSE EVENTS ............................................................................................................................................ 28 9.27 COVID-19 IMPACT ........................................................................................................................................... 31



5. Contact Information

Contact Name: Natalia Estévez, LDM Email: [email protected]

Premier Research

Address: Camino de la Zarzuela nº 19, 1ºB 28023 Madrid

Phone: 34 912 157 731 Fax:

6. Contacts for Questions

The first point of contact for eCRF questions is your assigned Clinical Research Associate (CRA). If you are unable to reach your CRA, the following Data Management personnel should be contacted

Natalia Estévez (Lead Data Manager): [email protected]

Technical/database and password-related issues should be directed to Customer Care Help Desk at Medidata. They are available 24 hours a day. Reference project code is INFA133227.

Customer Care Help Desk – Project INFA133227 Medidata: [email protected]

Worldwide Toll-Free Telephone Numbers:

COUNTRY TYPE #

France Toll-Free Number 0805 102 387

Hungary Toll-Free Number 06 800 17376

Israel Toll-Free Number 1 809 214489

Spain Toll-Free Number 800 098 040

United Kingdom Toll-Free Number 0800 001 5212

United States Direct 1 973 659 6780

United States Toll-Free Number 1 866 633 4328

United States Minor Outlying Islands Toll-Free Number 1866 383 1497

mailto:[email protected]



7. GENERAL CRF COMPLETION INSTRUCTIONS

This document is designed to assist site staff with the successful completion of the electronic Case Report Form (eCRF) casebook and thus reduce the number of queries received by the site. The eCRF Completion Guidelines (eCCGs) provides Rave specific system guidance as well as detailed study-specific instructions for the completion of the eCRF casebook. It is essential that these eCCG are followed to ensure consistent reporting of the data across the sites participating in this clinical trial. If assistance or clarification is required when completing the forms, please contact your Clinical Research Associate (CRA).

7.1 Access to Rave & logging on In order to access the RAVE eCRF casebook, the user must have a username and password. To be assigned a username and password, users must receive Rave eLearning that corresponds to the role that they are to perform for the study. This study will use the iMedidata portal www.iMedidata.com for account and eLearning management. iMedidata allows for users to have one personal username/password for all Rave studies, even when the studies are for different sponsors. Initial users will receive an email invitation to join a study group, study, or team. Accounts can be activated by clicking a link in the email sent from iMedidata. Users must create an account by selecting their own personal username, password, and entering an address and phone number (please enter complete address and contact information with specific data for your country and region).

http://www.imedidata.com/



After activating an iMedidata personal account, future invitations to studies can be accepted or declined

in the Invitations pane of the iMedidata home page.

Note: Users that already have an iMedidata.com account must notify their CRA and provide

certificate/documentation of prior training so that they can be set up to receive a study invitation through

their existing iMedidata account.

Upon entering iMedidata, the Study Name for INFA133227 access will be displayed. The study link will

direct the user to the RAVE EDC for the study.

7.2 Standard Guidelines These are general guidelines which apply to all the forms in the eCRF casebook:

All eCRF casebook data fields must be completed.

Data must be entered within 3 to 5 days from the subject’s visit or as soon as source documents are available.

Complete all EDC entries using information from a source document (e.g., medication records, clinic charts, lab reports, etc.). The same type of source should be used consistently throughout the study.

Comment fields in the database can only hold up to 200 characters. Therefore, each comment recorded on the CRF should not be more than 200 characters long, including spaces.

All text fields must be entered in English and spelled correctly. This is particularly important for Concomitant Medications and Adverse Events which must be spelled correctly for coding purposes.

The use of abbreviations and acronyms must be avoided whenever possible. Only use abbreviations that are clear, unambiguous, and standard for medical use.



Ensure that information entered into “Other, Specify” fields does not fit into a more appropriate category or dropdown list.

All dates must reflect the date of the assessments, NOT the date of form completion. Record dates using the following format: DD/MMM/YYYY 2-digit day/ 3 letter month/ 4-digit year (Ex: 05/JAN/2013).

o A complete date is expected for trial assessments and so these do not allow for unknown (UNK) or partial dates.

o Partial dates are allowed for historical dates such as in Medical History, and Concomitant Medications. As much information as possible should be provided. If the Day is unknown but Month and Year are known, the date should be recorded (Ex: UN/SEP/2010). At a minimum a Year must be provided with Month and Day as UNK (Ex: UN/UNK/1998).

All times must be entered using 24-hour clock – see conversion chart below for assistance. For times around midnight, please use 23:59 of the current day or 00:00 of the following day. 00:00 signifies the beginning of the following day. Unknown can be entered (UN:UN) in some cases but times are expected for trial assessments requiring a time.

Do not enter extraneous data into a data field unless it helps to clarify the data point AND the extraneous data is not captured elsewhere on the eCRF casebook.

Do not use ditto marks, arrows or “same as above” notations in data fields. Note: These are not data and hence meaningless for analysis.

7.3 Screen Failures Applicable Screen Failure data will be entered in the EDC database. The following forms will be collected:

Screening Folder: o Visit Date o Informed Consent

12 hour clock 24 hour clock 12 hour clock 24 hour clock

12:00am 00:00 12:00pm 12:00

01:00am 01:00 01:00pm 13:00

02:00am 02:00 02:00pm 14:00

03:00am 03:00 03:00pm 15:00

04:00am 04:00 04:00pm 16:00

05:00am 05:00 05:00pm 17:00

06:00am 06:00 06:00pm 18:00

07:00am 07:00 07:00pm 19:00

08:00am 08:00 08:00pm 20:00

09:00am 09:00 09:00pm 21:00

10:00am 10:00 10:00pm 22:00

11:00am 11:00 11:00pm 23:00



Randomization Folder: o Demography o Inclusion Criteria o Exclusion Criteria o Patient Status o Failed

7.4 Site Number Assignment A site number is assigned to each individual site. The site number contains 4 digits (i.e., 0001, 0002, 0003, 0004, etc.). Please confirm the site number with the assigned Clinical Research Associate (CRA) and/or Premier Research representative before data entry begins.

7.5 Subject Number Assignment Subject ID, assigned by IWRS, automatically appears in Rave as a concatenation of 2 identifiers: site number + screening number (i.e., 00010001, 00010002, etc.)

7.6 General Guidelines for Medical Coding These are guidelines to ensure that medical coding will be performed efficiently and effectively for Medical History, Adverse Events and Concomitant Medications.

Ensure Spelling is correct o Perioneal (unclear if Perineal or Peritoneal) o Ramitidine (unclear if Raniditine or Rimantadine)

Ensure terms are in English. o Musculus Atrofie (enter as Muscle Atrophy)

Avoid entering Conflicting information. o Fever 96.7F (value of 96.7F is inconsistent with Fever) o Motrin (Naprosyn): (ingredient is inconsistent with trade name) o Pepcid with Indication of Embolism (indication is inconsistent with medication)

Avoid using Abbreviations/Acronyms/Truncations. o PE (unclear if Pulmonary embolism or Pleural effusion) o T3 (unclear if Tylenol 3, Triiodothyronine, or other)

Ensure the recorded term specifies no further information is available when specifics cannot be obtained.

o Pain NOS (if specific body site information is not available) (NOS = not otherwise specified) o Unknown CVS Cold Medicine (if trade name/ingredients not available)



When answering a ‘Coding Query,’ ensure the verbatim term or medication name is updated to avoid a re-query.

o AE “Chest pain” queried for type (enter response of “Cardiac” in verbatim AE term, e.g., “Cardiac Chest pain”)

o CM “Prophylaxis” queried for type (enter response of “Thrombosis” in medication name, e.g., “Prophylaxis Thrombosis”)

7.7 Adverse Event / Medical History /Prior & Concurrent procedures

Record Medical History as Medical Conditions, NOT procedures, therapies, outcomes or risk for disease

o Tooth extraction (record reason for procedure, e.g., Impacted Wisdom Tooth) o Hospitalization (enter reason for hospitalization, e.g., Sepsis) o Prematurity, the underlying condition, does NOT need to be entered as medical history.

Medical History conditions should only be recorded as an AE if there has been a worsening in intensity or frequency relative to Baseline. When recording this AE, include descriptor in AE term to reflect the worsening (for example, worsening or increased). Adverse Event recording begins when the subject receives first dose of study medication.

Record AE’s as Medical Conditions, NOT Procedures, Therapies, Outcomes. o Tooth extraction (record reason for procedure, e.g. Impacted Wisdom Tooth) o Cold compresses (enter condition requiring therapy, e.g. Sprained ankle) o Hospitalization (enter reason for hospitalization, e.g. Sepsis) o Death (enter cause of death, e.g. Myocardial Infarction)

If event is at a specific site, include in the verbatim term o Infection (record e.g., Post-op wound site infection)

Record only one sign, symptom, or diagnosis per log line o Urinary bladder obstruction with Cystitis (record each as a separate entry) o Nausea/Fever (record each as a separate entry) o Bruising secondary to blunt trauma (record as a separate entry)

Record a Diagnosis, if available, rather than a list of Signs/Symptoms o Fever/Aches/Cough (e.g., enter influenza or each symptom separately)

Record Investigations as Increased, Decreased, High or Low o Glucose of 40 mg/dL (enter as Glucose decreased or Glucose low) o Heart rate of 120 bpm (enter as Heart rate increased or Heart rate high)

Ensure information is Complete (include Body Site, Type, Event, etc.). o Chest pain (unclear if Cardiac, Pleuritic, Musculoskeletal, etc.). Chest Pain terms must always



include the type. o Pain (Include the body site or type: Head? Arm? Cancer? Catheter site?) o Infection (Postoperative? Kidney? Bacterial? Systemic? Device site?) o Incontinence (Urinary? Fecal?) o Eye events, e.g. Redness (of Eyeball? of Eyelid?)

Ensure information is specific and unambiguous. o Patient felt fuzzy (unclear if Unable to concentrate, Disoriented, Lightheaded, or other) o Eye Problem (unclear if Eye pain, Vision decreased, Retinopathy, or other) o Mouth sore (unclear if Mouth soreness or Sore (i.e. lesion) in the mouth) o Leg Infection (unclear if Skin, Joint, Bone, or Muscle infection of the leg) o Increased Urination (unclear if Increased Urinary Output or Increased Urinary Frequency) o Nasal Sinus Drainage (unclear if Nasal Discharge or Nasal Sinus Drainage Procedure)

7.8 Medications

Record Medications only, NOT procedures or non-drug therapies (transfusions of blood products: Fresh Frozen Plasma, Packed Red Blood Cells, Platelets, White Blood Cells or Whole Blood should not be recorded as a medication)

Record only one Trade Name medication per line o Tylenol/Excedrin (record each as a separate entry)

Record multiple Generics together only when a known combination o Penicillin + Ibuprofen (enter each separately: not manufactured together) o Hydrocodone w/Acetaminophen (okay: manufactured together)

Ensure medication name is Accurate and Complete and include within the verbatim term both Trade name and also Active ingredient(s), if possible, e.g. report “TYLENOL (ACETAMINOPHEN)” or “TYLENOL (Chlorphenamine maleate; Dextromethorphan HBr; Paracetamol; Pseudoephedrine HCL)” o Vicks Sinus Nose Mist (Incorrect: e.g., enter Vicks Sinex Nasal Spray) o Tylenol Cold (Incomplete: e.g., enter Tylenol Cold Multi-Symptom Daytime)

Ensure medication is Specific and Unambiguous o IV Fluids (unclear if Saline, D5NS, Lactated Ringers, or other) o Analgesic (unclear if Aspirin, Hydrocodone, Meloxicam, or other)

Record Drug Indication as a Medical Condition, NOT drug class or type o Antibiotic (record condition drug was used for, e.g., Pneumonia) o Supplement for General health, Cardiac health, Arthritis, Pain, etc.)

Ensure Drug Indication is Complete (include type of prophylaxis/pre-med)



o Prophylaxis (Pain, Thrombosis, Infection, Allergic reaction, etc.) o Pre-Medication (Sedation, Nausea, Salivation, Dehydration, etc.)

Ensure that Medical History and/or Adverse Events that are associated with the medication are reported appropriately.

8. GENERAL RAVE GUIDELINES

iMedidata RAVE Icon Keys

Forms, Queries, and System Behaviors

Password information: Each user will have a UNIQUE username and password – DO NOT SHARE (per 21CFR Part11). See Standard Guidelines section for details on initial access to the study. The database passwords have the following rules:

Passwords expire every 90 days, and will require the use of the “I forgot my username and password” link

to reset the password for access. If a user does not access the study database within 120 days, the user’s

account will become invalid.

o Passwords are case sensitive and must be at least 8 characters in length and required to contain:

at least one uppercase letter



one lowercase letter, and one number or punctuation character

o For iMedidata access assistance contact Medidata Solutions World Wide Support (refer to section 5 for Medidata Helpdesk’s phone number) and select 2=iMedidata

o MEDIDATA cannot assist with the following: study specific or protocol related questions potential issues with database such as: forms not publishing as expected, queries that

appear incorrect or any system error messages

create a screen shot (so date/timestamp is captured), provide a clear description of the issue and send by email to the LDM with CRA copied.

o To update passwords for iMedidata, either, click the name at the top of the Home page, or click Account Details from the My Information pane. Then update the password or other information as needed.

Field Types: There are multiple types of fields in Rave: o Drop-down lists – These have pre-defined values to choose from to enter the necessary data. o Radio buttons – These are circles by which clicking on the circle will answer the question on

the form. Only ONE answer is allowed to be chosen. If a response must be removed, the response should be clicked on so that the circle is now empty and then the field should be saved.

o Check boxes – These are boxes by which clicking on the box will indicate the item is checked.

Note: After the page is saved, the pencil icon must be selected to select or check a different box.

o Free-text fields – These are boxes which allow the entry of different types of data. These are

sometimes small and only allow entry of numbers and some are larger, which allow both alpha and numeric text. These larger free-text boxes usually have a maximum of 200 characters.

Note: All free-text fields have defined maximum character limits – the system will prompt

with a Non-conformant data flag if this character limit has been exceeded. If this flag appears, the data must be edited to meet character limits. If it is impossible to edit the information without losing necessary detail, please contact your CRA to notify Clinical Data Management of a potential need to update field length. This is ONLY possible if the length is shorter than 200 characters.

Saving data o Once data have been entered onto a page, SAVE should be clicked at the bottom of the form

prior to leaving the page, in order to save all the data. Reminders:

o If data is not saved prior to the inactivity timeout, the information entered will be lost. o When attempting to navigate away from the page, a warning pop-up will be provided to save

the form. If “Leave” is selected from the pop-up, the information entered will be lost.



Not Done, Not Applicable, or Unknown: If the data requested is Not Done (ND), Not Applicable (NA), or Unknown (UN:UN, UN/UNK), and the field is NOT a date, time, radio button, or drop down list, please enter the appropriate response.

Comments: Free text comments can be entered within the Audit tab of any item or form. Comments are not included in the analysis of the clinical data, but it can provide additional clarification during off-site review of the data. Please notify the CRA if a Comment is added to the database, as the system will not automatically notify the CRA of the Comment.

Changing Data: A reason for change MUST be provided in order to change previously entered data on the eCRF. The Reason for Change defaults to “Data Entry Error”; however, please select the most appropriate response:

o Data Entry Error o Per Query Resolution o New Information

Protocol Deviations: These will not be entered into the RAVE clinical database.

Editing Data: Changing data is achieved by different methods based on the activity and type of form. o To change data the Pencil icon must be used. It is located on the far right of the screen next

to each item or at the top of the form to edit all fields. o If any row within a log needs to be deleted, select the “inactivate” hyperlink. This link is

located next to the “add a new log line” at the bottom of the logged section. A dropdown box will then appear that contains a list of log line #’s. Choose the log line # that should be inactivated and click the inactivate button again. Then click SAVE. A line or strikethrough will be created across the data in the data in the inactivated row.

o If a log line is inactivated in error, the line may be re-activated. To reactivate a log line, click the “reactivate” hyperlink at the bottom of the logged section. A dropdown box will then appear that contains a list of log line #’s. Choose the log line # that should be reactivated and click the reactivate button again. Then click SAVE. The selected line will no longer have a line through the data.

Types of Data Entry forms: o Log-style forms: When multiple records of the same forms are needed (e.g. previous visits,

Concomitant Medications, Adverse Events, etc.), a Log Form is used. Click on “Add new log



line” at the bottom of the form to add new log entries. o Add Event: There is a dropdown located at the bottom of the Subject’s “home screen” (the

screen available upon first clicking on a subject number) with the choice of:

Queries: There are different types of queries but all must be addressed. An open query is demoted

in the form by Red-question mark and a pink highlighted field on the form. All queries will appear in red text under the item in question and at the end of the query text the category type of query will be noted.

o Site from System – programmed into Rave to check the data at the time of entry for correctness and consistency. Open queries may be resolved in either of the following manners:

If the data is entered in error, it may be changed and if the new data meets form criteria the query will auto-close once the data is submitted/SAVED.

If the data correct as entered then the query MUST be responded to within the text box below the query text.

o Site from CRA or Site from DM – are considered Manual Queries. These are queries that will be placed in the system by different functional personnel. These queries behave similarly to auto queries with the only difference being that they will not auto-close when data is updated. All manual queries MUST have a text response. The project tram will review database updates and query responses and close if update or response is deemed acceptable.

Note: Data changes MUST be made in the data field. Data updates only provided in the query text box will result in a re-query.

CRF Completion

The Principal Investigator (PI) must delegate individuals that are responsible for making entries in the CRF. These individuals must sign the List of Signatures of Study Personnel Log. (The signatures of the PI, Sub-Investigator(s) (Sub-Is), Study Coordinator(s), and other assigned staff must also be included on this form.)

o The log will be maintained in the Regulatory Binder and should be updated when changes in study site personnel and/or responsibilities occur.

Investigator Review and Certification

The PI must sign and date the Investigator’s Statement page (CRF page 21) to certify that he has reviewed the information in the CRF and that it is accurate and complete.

The CRF should not be signed until all monitoring review has occurred and all corrections have been applied.

Steps for completing signature:

The forms available for signature are indicated by the ‘requires signature’ icon and PI is unable to sign on a form unless all data points are showing as such.



Log-in as Investigator role.

Navigate to the subject you wish to sign.

To Sign the entire subject click on the ‘Sign and Save’ button located below the Visit tree on the subjects level screen.

To sign on an individual form, navigate to the form and click the ‘Sign and Save’ button.

9. PROTOCOL-SPECIFIC CRF COMPLETION INSTRUCTIONS

9.1 SCREENED All screened data are collected by IWRS. Therefore, if data modification is required, the update request should be sent to IWRS, as per instructions in the IWRS user guide. Screen ID

o This is a non-enterable field. The screen ID will automatically be populated via IWRS integration. Secondary Screen ID

o This is a non-enterable field. The Secondary screen ID will automatically be populated via IWRS integration.

Screen Date o This is a non-enterable field. The screen Date will automatically be populated via IWRS integration.

9.2 VISIT DATE Visit Date

o Enter a complete date in DD/MMM/YYYY format only in Day 1 folder. Once the Day 1 visit date is entered, the remaining folders will automatically appear based on subject’s age and expected participation in the study (to be completed when subject reaches 34 weeks + 6 days post-menstrual age/PMA) and the applicable visit dates will also automatically be populated.



9.3 INFORMED CONSENT Date informed consent signed by the legal representative

o This is a non-enterable field. The date of informed consent will automatically be populated via

IWRS integration. If date of informed consent is incorrect, please contact IWRS to request for a

data change.

Protocol version o Select from the available list to indicate the current approved protocol version at country/site,

under which the subject was screened for. Date of birth

o This is a non-enterable field. The date of birth will automatically be populated via IWRS integration.

Time of birth o This is a non-enterable field. The time of birth will automatically be populated via IWRS integration.

Gestational age: weeks o This is a non-enterable field. The gestational age (weeks) will automatically be populated via IWRS

integration.

Gestational age: days o This is a non-enterable field. The gestational age (days) will automatically be populated via IWRS

integration.

9.4 MEDICAL HISTORY YN? Any medical history reported?

o Select ‘Yes’ or ’No’ to indicate if the subject experienced any Medical History items. o If ‘No’, this section is completed. o If ‘Yes’, complete ‘Medical History’ form

9.5 MEDICAL HISTORY Record any relevant or major illnesses (at investigator’s discretion) present before the screening visit, except for prematurity (the underlying condition for this study). Verbatim term

o Provide any past and/or current diseases or past surgeries (one per row). Avoid using ambiguous terms, special characters, and abbreviations.

Start Date

o Enter the start date of the medical history illness.

Start time

o Enter the Start time of the medical history illness. This should be entered in 24-hour format. Ongoing?

o Mark if the medical history illness is ongoing.



End Date

o Enter the end date of the medical history illness. End time

o Enter the End time of the medical history illness. This should be entered in 24-hour format.

Note: Additional rows can be added by selecting the Add a new Log line link. If additional rows are added in error, they can be inactivated by selecting the Inactivate link after the form has been saved. If already inactivated rows need to be added again, they can be reactivated by selecting the Reactivate link after the form has been saved.

9.6 DEMOGRAPHY Gender

o Select Male or Female. Ethnicity

o Select one response from the available list. This is the patient’s self-reported ethnicity.

Hispanic or Latino is considered a person of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture of Non-European origin, regardless of race.

Ethnicity is required to be entered since incidence of NEC can be influenced by ethnicity.

Race (check all that apply)

o Select the patient’s race based on the following definitions:

American Indian or Alaska Native: A person having origins in any of the original peoples of North and South America (including Central America), and who maintain tribal affiliation or community attachment.

Asian: A person having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent, including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, or Vietnam.

Black or African American: A person having origins in any of the black racial groups of Africa.

Native Hawaiian or Other Pacific Islander: A person having origins in any of the original peoples of Hawaii, Guam, Samoa, or other Pacific Islands.

White or Caucasian: A person having origins in any of the original peoples of Europe, the Middle East, or North Africa.

Unknown: A person with unknown race.

Race is required to be entered since incidence of NEC can be influenced by race. Delivery method

o Select the method of delivery (vaginal or cesarean). 1 minute Apgar score (0-10)

o Select the score of Apgar test. 5 minute Apgar score (0-10)

o Select the score of Apgar test. 10 minute Apgar score (0-10) (optional)



o Select the score of Apgar test. o This score is optional if Apgar score is not assessed at 10 minutes as part of the standard

practice at site Weight at birth (g)

o Enter the weight at birth (in grams). Head circumference at birth (cm)

o Enter head circumference at birth (in centimeters).

9.7 INCLUSION CRITERIA YN Does the patient meet all inclusion criteria?

o Select ‘Yes’ or ‘No’ to indicate if the patient met inclusion eligibility criteria. o If ‘Yes’, the section is complete. o If ‘No’, provide further detail on Inclusion criteria form.

9.8 INCLUSION CRITERIA INCLUSION criterion number(s) not met:

o Select the Inclusion criteria. o Add a new log line for each additional criterion.

9.9 EXCLUSION CRITERIA YN Does the subject meet any exclusion criteria?

o Select ‘Yes’ or ‘No’ to indicate if the patient met exclusion eligibility criteria. o If ‘No’, the section is complete. o If ‘Yes’, provide further detail on Exclusion criteria form.

9.10 EXCLUSION CRITERIA EXCLUSION criterion number(s) met:

o Select the Exclusion criteria. o Add a new log line for each additional criterion.

9.11 PATIENT STATUS Is patient Randomized or Screen Failed?

o This is a non-enterable field. The screen ID will automatically be populated via IWRS integration.



9.12 FAILED This eCRF will only appear if the subject status is deemed as screen failed by IWRS. Failed Date

o This is a non-enterable field. The screen ID will automatically be populated via IWRS integration.

9.13 RANDOMIZATION Date of randomization

o This is a non-enterable field. The Randomization date will automatically be populated via IWRS

integration.

Date of randomization o This is a non-enterable field. The randomization time will automatically be populated via IWRS

integration. Randomization number

o This is a non-enterable field. The randomization number will automatically be populated via IWRS

integration.

9.14 WEEKLY GROWTH MEASUREMENTS Head circumference (cm) should be recorded weekly (every 7 ± 2 days). Timepoint

o Select the week of head circumference measurement Was head circumference measurements assessed?

o Select Yes or No indicating if the assessment was done. Reason not done

o Enter a reason why the assessment was not completed. Date of assessment

o Enter a complete date in DD/MMM/YYYY format. Head circumference (cm)

o Enter head circumference (in centimeters).

9.15 WEIGHT MEASUREMENT Weight (g) should be recorded daily.

Was weight measurement assessed? o Select Yes or No indicating if the assessment was done.

Reason not done



o Enter a reason why the assessment was not completed. Date of assessment

o Enter a complete date in DD/MMM/YYYY format. Weight (g)

o Enter weight measurement (in grams).

9.16 ABDOMINAL RADIOGRAPH AND LAPAROTOMY All clinical signs of NEC must be entered along with the indication if abdominal radiographs and laparotomy are performed. Was there any clinical sign of NEC?

o Select Yes or No to indicate any clinical sign of NEC.

If there are any clinical signs please select YES. If Yes, complete the rest of this eCRF page. Please

ensure also to report corresponding adverse event on AE CRF page, if applicable. If there are no

clinical signs of NEC on that day, please select NO. If ‘No’ is selected no other questions will be

displayed on this page.

What were the clinical signs of NEC? o Tick any items which apply. If Other is selected, specify in the space provided.

Were abdominal radiographs taken for clinical signs of NEC? o Select Yes or No to indicate if abdominal radiographs were taken for clinical sign of NEC.

Date abdominal radiographs taken o Enter the date when the abdominal radiograph(s) was/were taken. Date should be in

DD/MMM/YYYY format. Time abdominal radiographs taken

o Enter the time when each abdominal graph was taken. This should be entered in 24-hour format. Was intestinal pneumatosis and/or portal venous gas observed on these radiographs by the local radiologist?

o Select Yes or No to indicate pneumatosis and/or portal venous gas observed on these radiographs

by the local radiologist.

Have all abdominal radiographs taken for clinical signs of NEC been transferred to central reader? o Select Yes or No to indicate if transfer occurred.

Was laparotomy performed? o Select Yes or No to indicate if laparotomy was performed.

Date laparotomy performed o Enter the date when the laparotomy was performed. Date should be in DD/MMM/YYYY format.

Time laparotomy performed o Enter the time when the laparotomy was performed. This should be entered in 24-hour format.

Was necrotizing enterocolitis observed during laparotomy? o Select Yes or No to indicate necrotizing enterocolitis was found at laparotomy. If this has not

been reported as AE, please make sure that e corresponding entry is made on the AE CRF page.

If yes, Were necrotic surgical specimens sent to pathology for evaluation?



o Select Yes or No to indicate necrotic surgical specimens sent to pathology for evaluation.

If yes, Did pathologist confirm presence of intestinal necrosis? o Select Yes or No to indicate pathologist confirmed presence of intestinal necrosis.

9.17 STUDY DRUG ADMINISTRATION The study drug must be administered within 3 hours of preparation. IP should be given once daily. Was study drug administered?

o Select ‘Yes’ or ’No’ to indicate if the study drug was administered. o If ‘No’, complete the reason.

Reason dose was not administered o Enter the reason indicating why the study drug was not administered.

Date of study drug administration o This is a non-enterable field. Date of study drug administration will be auto-populated once the

“Was study drug administered?” is entered as Yes. Time of study drug administration

o Enter the time when the study drug was administered. This should be entered in 24-hour format. Volume of study drug administered

o Enter volume of study drug administered (in milliliters).

If volume of study drug administration is not per protocol, please comment o If volume of study drug administered (in milliliters) is not per protocol (0.5 ml) please enter a

comment.

9.18 NUTRITIONAL INTAKE Total daily enteral feeding volume (ml)

o Enter total daily feeding volume (in milliliters). Enter total feeding volume during 24 hours calendar day.

Date of enteral feeding volume o Enter the Date of enteral feeding volume in DD/MMM/YYYY format.

Was any parenteral nutrition (i.e. amino acids and/or lipids) given? o Select Yes or No to indicate subject received parenteral nutrition.

Was any amount of human milk given?

o Select Yes or No to indicate if human milk was given. Were there clinical signs of feeding intolerance?

o Select Yes or No to indicate if there were clinical signs of feeding intolerance.] o Note: Clinical signs of feeding intolerance should be reported in the Adverse Event page or in less

common cases, in the Medical History page depending on the clinical sign onset date. What were the clinical signs of feeding intolerance?

o Select what were clinical signs of feeding intolerance. Select all the appropriate check box(s) for clinical signs



9.19 END OF TREATMENT

I

Did the subject complete the study drug administration until PMA 34 weeks + 6 days? o Select ‘Yes’ or ‘No’ to indicate if the subject completed the study drug administration.

Date of last study drug administration o Enter the Date of last study drug administration in DD/MMM/YYYY format. o Date of last study drug administration should be the Date when the subject reaches 34 weeks + 6

days PMA, or until treatment is permanently discontinued if earlier. Reason for early discontinuation of study drug administration (choose primary reason)

o Select one option from the available list: Adverse Event(AE)/Serious Adverse Event (SAE) Caregiver/Legal representative withdrawal of consent Death Subject was discharge.

If Subject was discharged the following questions will appear in the eCRF Was the subject discharged home or to other hospital care?

o Select ‘Home’ or ‘Other Hospital Care’ to indicate where subject was discharged.

Date of discharge o Enter the Date of discharge in DD/MMM/YYYY format.

COVID-19 Other

If COVID-19, please specify If Other, please specify

o If subject’s reason for discontinuation is ‘Other’, enter the reason. If AE, SAE please specify number

o If AE,SAE please select AE/SAE number from dynamic search list.



9.20 STUDY COMPLETION The subject will complete the study once the subject complete Follow-up visit, 40weeks ± 7days PMA.

Did the subject complete the study, including the Follow up visit? o Select ‘Yes’ or ‘No’ to indicate if the subject completed the study.

Date of study completion/ET o Enter the Date of subject completion/discontinuation in DD/MMM/YYYY format. o Date of study completion should be the same as Follow up visit Date if the subject completes the

study per protocol. Reason for Early Termination (choose primary reason)

o Select one option from the available list: Adverse Event Caregiver/Legal representative withdrawal of consent Lost to follow-up COVID-19 Death Other

If Other, please specify o If subject’s reason for discontinuation is ‘Other’, enter the reason.

If reason for early termination is Lost to follow-up, specify date of last contact o If subject’s reason for discontinuation is ‘Lost to follow-up’, enter the date of last known contact

with the subject in DD/MMM/YYYY format. If reason for early termination is COVID-19, please specify the reason

o Select one option from the available list: Subject infected with COVID-19 Parent decision Site closed Study delayed/cancelled Other

If COVID-19 reason is other, specify o If subject’s reason for discontinuation is ‘Other’, enter the reason.

Was the subject discharged home during the study?

o Select ‘Yes’ or ‘No’ to indicate if subject was discharged home. Date of discharge

o Enter the Date of discharge in DD/MMM/YYYY format.



9.21 DEATH If both clinical and autopsy results are available, please enter the autopsy information in this form. Date of death

o Enter the date of death. Date should be in DD/MMM/YYYY format. Was primary cause of death determined by autopsy or clinically?

o Select from the available options: autopsy or clinically. Primary cause of death

o Select an option to indicate the primary cause of death. o If Other is selected, specify in the space provided.

Was secondary cause of death determined by autopsy or clinically? o Select from the available options: autopsy or clinically.

Secondary cause of death o Select an option to indicate the secondary cause of death. o If Other is selected, specify in the space provided.

Was necrotizing enterocolitis observed at autopsy? o Select from the available options: Yes, No or Autopsy not performed.

If yes, Was necrotizing enterocolitis confirmed by histopathology? o Select Yes or No to indicate if necrotizing enterocolitis was confirmed by histopathology.

9.22 FOLLOW-UP VISIT Type of follow-up visit

o Select Clinical Visit or Phone call to indicate type of follow-up.

Weight o Weight should be collected at FU visit, regardless if Clinical Visit or Phone call.

9.23 CONCOMITANT MEDICATIONS Y/N? The followings should be recorded:

Any existing medications ongoing at the time of screening visit.

Any changes to existing medications (such as changes in route or indication) during the course of the clinical trial.

Any new medications received by the subject since the screening visit. Are there any concomitant medications to report?

o Select ‘Yes’ or ’No’ to indicate if a medication was taken. o If ‘No’, form is complete. o If ‘Yes’, complete the ‘Concomitant Medication’ form.

9.24 CONCOMITANT MEDICATIONS Concomitant medications will be recorded from first dose of IP.



NOTE: Record only ONE medication per line. Medication/Therapy

o Enter the name of each Concomitant Medication taken by the patient. Medication names should be spelled out, avoid using ambiguous terms, special characters, acronyms and abbreviations. If combination medication needs to be entered refer to the Medications section in Standard Guideline.

Indication o List the diagnosis or symptom for which the subject took medication. Be consistent with

terminology as the indications will be cross-referenced to medical condition eCRFs (Medical History and/or Adverse Events). Any medication administered due to an adverse event must also be recorded on the adverse events eCRF.

Route o Select the appropriate route from the available list.

Start Date o Enter the date concomitant medication was started. Date should be in DD/MMM/YYYY format. o If a complete date is unknown, see General CRF Completion Instructions section for instructions

on how to enter a partial date. Ongoing?

o Check this box if Medication is Ongoing. o When the ‘Ongoing’ box is checked, the ‘End Date’ is not be required. o If the medication does not have an end date at time of study discontinuation, death, or if the

patient is lost to follow up or withdraws consent, the ‘Ongoing’ box has to be checked. End Date

o Enter the date concomitant medication was discontinued. Date should be in DD/MMM/YYYY format.

o At least the year should be provided. See General CRF Completion Instructions section for instructions on how to enter a partial date.

Note: Additional rows can be added by selecting the Add a new Log line link. If additional rows are added in error, they can be inactivated by selecting the Inactivate link after the form has been saved. If already inactivated rows need to be added again, they can be reactivated by selecting the Reactivate link after the form has been saved.

9.25 ADVERSE EVENTS Y/N An AE is any symptom, sign, illness, or experience that develops or worsens in severity during the course of the study. Abnormal results of diagnostic procedures are considered to be AEs if the abnormality:

Results in study withdrawal.

Is associated with a serious adverse event (SAE).

Is associated with clinical signs or symptoms.

Leads to additional treatment or to further diagnostic tests.



Is considered by the Investigator to be of clinical significance.

Are there any AEs to report? o Select ‘Yes’ or ’No’ to indicate if the patient experienced any Adverse Events. o If ‘No’, this section is completed. o If ‘Yes’, complete ‘Adverse Events’ form. o IMPORTANT NOTE: Please review patient charts carefully for any AEs. Many of these events are

related to the condition of prematurity, but they are still considered adverse events and need to be reported accordingly.

9.26 ADVERSE EVENTS All Adverse Events will be recorded from the time of first dose of study medication to the end of study treatment follow-up. Any event that happens before first dose will be considered as Medical History. All Adverse Events, regardless of seriousness or relationship to study drug treatment, are to be recorded. A pre-existing condition should be recorded as an AE only in the case of worsening or the event became serious during the study. The responsible investigator decides how to define the start and end of an AE episode in accordance with

sound clinical judgment. Should an AE of the same character recur, the AE episode may be defined as

equivalent in time to the cumulated treatment duration e.g. multiple erythrocyte transfusions may be

within the duration of a single AE episode. Similarly recurring thrombocytopenia may be noted as one AE

episode.

If an Adverse Event resolves and is experienced again, a new AE log line should be created. If an Adverse Event changes in severity or seriousness without first resolving, a new row should be added to the existing AE form to record the change in grade. When new rows are added to capture change in grade of an existing AE, ensure start and end dates of each line collapse correctly. Death should not be recorded as an Adverse Event. If an Adverse Event results in Death, enter the AE diagnosis that led to death with the outcome recorded as ‘Fatal’. Hospital stays for elective procedures should not be listed as Adverse Event. Adverse Event Term

o Enter the diagnosis, if known, instead of presenting signs/symptoms. o If the adverse event is under current clinical evaluation and a diagnosis has not yet been

established, enter the sign or symptom. If multiple signs and/or symptoms are present and a diagnosis has not yet been

established, enter each sign and/or symptom on a separate AE form. Please avoid the addition of ‘suspected’ to any diagnoses.

o For changes in laboratory values, every attempt should be made to capture the clinical diagnosis of the adverse event, rather than the laboratory term when reporting the adverse event (e.g. anemia versus low hemoglobin value).



o Adverse Event terms should be as specific as possible (e.g., for Pain, include the Site in the term; for Cold, specify either a Head Cold or Feels Cold).

o One Adverse Event should be entered on a form. If a patient has 2 terms (i.e. muscle weakness/fatigue or nausea/vomiting), these should be recorded as 2 separate Adverse Events. If 2 terms are recorded together, a query will be generated to split the Adverse Event terms

to allow for coding. o Adverse Event terms should be spelled out to avoid ambiguity, do not use abbreviations (e.g.,

enter ‘Peripheral Artery Disease’ instead of PAD), acronyms or special characters (i.e. @, #, &, <, >).

Start Date o Enter the start date of the Adverse Event in DD/MMM/YYYY format. o If there’s a change in severity, enter as a new line.

Start time o Enter the time the adverse event began. This should be entered in 24-hour format.

End Date o Enter the end date of the Adverse Event in DD/MMM/YYYY format. o An ‘End Date’ should be provide when an AE resolves, changes in severity, or seriousness changes. o Adverse Events that result in death, an End Date is required and should match date of death on

Subject Disposition page. o Adverse Events ongoing at time of death that do not result in death, End Date should be left blank

and mark Ongoing as Yes. o If an AE Outcome = Not Recovered or Not Resolved, Unknown or Recovering/Resolving then the

End Date should be blank. End time

o Enter the time the adverse event ended. This should be entered in 24-hour format. Outcome

o Select Outcome of the Adverse Event: Recovered or Resolved

Select ‘Recovered or Resolved’ for any AE that resolves. Recovered or Resolved with Sequelae

Select ‘Recovered or Resolved with Sequelae’ for any AE that resolves with sequelae or any effects that remain.

Recovering or Resolving Select ‘Recovering or Resolving’ for any AE that is resolving at the time of study

discontinuation or death. Not Recovered or Not Resolved

Select ‘Not Recovered or Not Resolved’ when an AE changes grade or seriousness and the AE does not resolve or for any AE which is ongoing (unresolved) at time of study discontinuation or for any AE ongoing at time of death if the AE did not lead to the death.

Fatal Select ‘Fatal’ for AE which results in a patient's death.

Unknown Select ‘Unknown’ for any AE whose outcome is not known, not observed, not

recorded, or the outcome report is refused by the patient.



Severity o Select Severity of Adverse Event from the available list:

Mild The AE is easily tolerated and does not interfere with daily activity.

Moderate The AE interferes with daily activity, but the subject is still able to function.

Severe The AE is incapacitating and requires medical intervention.

Serious o Select ‘Yes’ or ‘No’ to indicate if Adverse Event met Serious criteria. o If ‘Yes’, ensure SAE report is submitted to Premier Research Safety department according to safety

reporting guidelines for this study.. o When the AE is no longer considered ‘Serious’ but is still ongoing, a new row should be added with

‘Serious’ as ‘No’. o If adverse is serious, indicate:

Death Tick to indicate if Adverse Event caused death.

Life Threatening? Tick to indicate if Adverse Event is life threatening.

Hospitalization or prolonged hospitalization Tick to indicate if Adverse Event led to inpatient hospitalization or prolongation of an

existing hospitalization Persistent or significant disability or incapacity?

Tick to indicate if Adverse Event caused persistent or significant disability or incapacity

Associated with a congenital anomaly or birth defect? Tick to indicate if Adverse Event caused congenital anomaly or birth defect.

Other medically important event? Tick to indicate if Adverse Event caused medically important event.

Is this an anticipated or unanticipated event? Select from the available list: anticipated or unanticipated.

Relationship to study medication

Select applicable option to indicate the relationship of the Adverse Event to study drug: o Definite

Distinct temporal relationship with drug treatment. Known reaction to agent or chemical group, or predicted by known

pharmacology. Event cannot be explained by subject’s clinical state or other factors.

o Probable Reasonable temporal relationship with drug treatment. Likely to be known reaction to agent or chemical group, or predicted by known

pharmacology. Event cannot easily be explained by subject’s clinical state or other factors.

o Possible



Reasonable temporal relationship with drug treatment. Event could be explained by subject’s clinical state or other factors.

o Unlikely Poor temporal relationship with drug treatment. Event easily explained by subject’s clinical state or other factors.

o Unrelated Event occurring before dosing. Event or intercurrent illness due wholly to factors other than drug treatment.

Action taken with study medication Select the action taken with study drug for this Adverse Event from the available list:

o Drug interrupted o Drug withdrawn o Dose not changed o Not applicable

If more than one action taken applies, select the final action taken with study treatment. Other action taken: None

Tick to indicate if AE required no other action taken. Other action taken: Concomitant Medication

Tick to indicate if AE required concomitant medication. Other action taken: Abdominal surgical procedures

Tick to indicate if AE required abdominal surgical procedures. If Abdominal surgical procedures, indicate:

If additional action was taken related to abdominal surgical procedures, select from the available

option: Laparotomy, Drain placement or Other. If Other, specify in the space provided.

Diagnostic measure: Blood cultures taken Tick to indicate if AE required blood cultures. If Blood cultures taken, were there any positive cultures?

Select ‘Yes’ or ‘No’ to indicate if positive cultures were observed. If yes, enter the identified strain

in the space provided.

Did the adverse event cause the subject to be discontinued from the study? o Select ‘Yes’ or ‘No’ to indicate if AE caused study discontinuation.

Note: This form is set as a table. In order to view the table with all Adverse Events entered, the “Complete View” link, at the top of the page, can be used to review and switch between the entries.

Please note, additional rows can be added in ‘Complete View’ by selecting the Add a new Log line link. If additional rows are added in error, they can be inactivated by selecting the Inactivate link after the form has been saved. If already inactivated rows need to be added again, they can be reactivated by selecting the Reactivate link after the form has been saved

9.27 COVID-19 IMPACT This page must be completed at any time a study visit or protocol procedure has been impacted by the



COVID-19. Visit impacted by COVID-19

o Select the visit that was impacted by COVID-19 Missed?

o Please tick if the visit was missed Visit Date

o Enter a complete date in DD/MMM/YYYY format Procedures missed?

o Select ‘Yes’ or ‘No’ to indicate if any procedures was missed Weight measurements

o Please tick if the measurement was missed Head measurement

o Please tick if the measurement was missed IP administration

o Please tick if the IP administration was missed

electronic case report form (ecrf) completion …

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