November 09 2022
Written by the NRG Oncology Quality Control & Communications Working Group
The purpose of this is to provide a general best practice document. If the protocol states otherwise, the protocol overrides the information within this document
- No protocol waivers will be granted for eligibility criteria.
- All eligibility criteria must have supporting source documents for verification
- The enrolling investigator should sign and date the protocol specific eligibility criteria, prior to registration of a subject. Follow institutional guidelines for others that also need to verify eligibility (ie: research nurse or research coordinator). Some sites require 2 to 3 signatures as verification of eligibility.
- Consider creating a stratification worksheet for the enrolling physician to also sign indicating the pertinent stratification factors. Alternatively, the registration worksheet from CTSU may be used if available.
- When counting between visits to determine protocol windows, start the count with Day 0. For Example: If a bone scan was done on 1/1/2022 then day 7 would be 1/8/2022.
- Protocol windows include calendar days
- Windows for treatment are counted from the actual (or expected) date of treatment/assessment, not the scheduled date of treatment. The day treatment is given could also be considered the “actual” date but may differ from the protocol expected date if windows are used.
- Windows for disease/response assessment (ex. CT scans) are counted from the scheduled date of assessment. Consider creating an imaging tracker to ensure scans are completed within protocol required assessment period.
Medical History & Physical Examinations:
- Any missed assessment is to be documented within the participant medical record and should include the rationale for the missed assessment and/or delay.
- To define physical examination, this means a physical exam includes assessment and documentation of the following unless a protocol specifies differently: performance status, a 12 point review of systems to include general, eyes, ent, nose, respiratory, skin, cardiovascular, gastrointestinal, urinary, neurologic, psychiatric/behavioral, musculoskeletal, vital signs.
- Ensure you are using the correct version of the PRO.
- Hard copy (paper) PRO’s are to include subject’s assigned identification number, date of completion, and applicable study visit at the time of completion.
- Any missed protocol required PRO must be documented in the medical record and include the rationale.
- A cover sheet for the PRO needs completed within RAVE for any PRO assessment time point regardless of whether the PRO was completed or not.
- Multiple missed PRO assessments and/or a missed PRO at the baseline visit for a research subject may be considered major noncompliance or deviation.
- Many trials are utilizing electronic versions of PROs called e-PRO. A detailed e-PRO FAQs sheet can be found on NRG Oncology website within the Data Management Resources section. A few recommendations are listed below:
When protocols require a medical history, the expectation is that the following information will be assessed and recorded:
a. prior malignancies
b. prior chemotherapy as well as other anticancer agents (lines of treatment with start and stop date as well as response is most helpful).
c. surgical history
d. radiation treatment (as applicable)
e. social history (including tobacco and alcohol use)
f. any other information the medical provider determines to be pertinent to medical history
- Training is required for staff in order to get access to the Patient Cloud in iMedidata Rave and it is the CRA’s responsibility to register the patient to the patient cloud. The CRA should complete the training as soon as possible.
- Always refer to the protocol for details and contact the protocol specific data manger if questions arise.
- If technical issues arise and the patient is unable to complete the electronic PRO, then the patient can complete a paper PRO version, as an alternative. Recommend having a paper copy available at the research visits, as a backup in case any technical issues prevent the use of e-PRO completion.
- The data from ePRO’s will automatically populate after the patient completes and submits the electronic QOL and does not require manual entry into the case report form like required when paper PRO’s are completed.
- Verify in Rave that the patient was able to complete and submit the appropriate PRO/QOL. Address any issues or discrepancies if present.
- All PO medications, required for NRG trials, require the use of drug diaries for each type of PO medication included in the study intervention, even if the study agent(s) is from a commercial supply.
- If the protocol does not provide a drug diary for PO medication compliance, consider creating one or use a generic institutional medication diary or progress note to record. As a reminder all patient facing documents need IRB approval before use.
- Concomitant medication(s) is defined as any agent administered/taken from the time of informed consent through the time of study completion, unless otherwise noted within the protocol. This includes supportive medication(s).
- Concomitant medications are to be documented on a Con Medication log or within the participant medical record.
- Medication administration details (ie: drug, dose, route, date and time given) are to be documented within the participant medical record.
- Any dose modification or treatment delays are to be documented and explained within the participant medical record.
- Prescriptions are to be signed by an investigator with an active CTEP ID for all investigational agents, per the CTMB Audit Guidelines.
- Radiation therapy administration records to verify protocol compliance are to be included within the subject’s research chart. The source document to verify radiation therapy administration is the signed radiation oncology treatment summary.
Withdrawal of consent:
- NRG Oncology has a Consent Withdrawal Guidance document available for reference.
- If a research subject withdraws from study participation, there must be documentation to clearly explain if the patient does or does not continue to allow data to be collected and reported.
- If a patient revokes consent, data can be reported for the time on study until the time of withdrawal.
- Consider creating a withdrawal of consent document which clearly outlines patient choices to be used if necessary.
Patients lost to Follow Up:
- See the Data Management section on the NRG website to view “NRG Oncology Data Management Lost to Follow-up Guidance Document.Some key points included in the Guidance Document: A patient will be deemed to be lost to follow-up only if the site has been unable to get ANY vital statistics information related to the patient for 2 continuous years. Attempts to locate the patient are expected to continue during this 2-year period
- Several different contact strategies are recommended: contact the study participant by phone, search medical records, contact the study participant’s primary care physician if permitted, search registries for their region as appropriate, contact the study participant by registered or certified letter, contact the study participant by email or other electronic means if permitted and search public websites such as the Social Security Index.
- Reminder: You are still required to make attempts to get information on your patient after being made Lost to Follow-up.
See the Adverse Event section on the NRG website to view “Guidance for Routine Adverse Event Reporting” document (June 10, 2020). Some key points included in the Guidance Document:
- Always refer to the protocol document for protocol-specific adverse event reporting.
- Adverse event reporting encompasses all aspects of protocol treatment which can include radiation therapy, surgery, device, and drug.
- As part of good clinical practice (ICH E3; ICH E6) NRG recommends that an AE log be part of the source documentation inclusive of start and end dates by grade change, decision making regarding expedited reporting, etc.
- If the start date is unknown, the date of the clinic visit at which the event was discovered may be used.
- All events reported via CTEP-AERS still need to be added to the routine AE forms in RAVE.
Laboratory abnormalities and changes in vital signs (outside of reference ranges) are considered adverse events if resulted in any of the following:
- discontinuation or interruption of study treatment.
- clinically significant per investigator assessment.
- require therapeutic medical intervention.
- meet protocol specific criteria (see toxicity management in protocol)
- if the investigator considers them to be adverse events.