New guide open for public comment: Capturing Investigational Study Vaccination Data in IIS

Prior to the COVID-19 pandemic, investigational study vaccinations were not typically reported to the IIS for several reasons, one of which includes the strict patient-blinding policies in clinical trial protocols. However, the COVID-19 pandemic has thrust the role of vaccine clinical trials and their vaccinated participants into a new spotlight. There is a need to share participant investigational study vaccination data with appropriate entities, including the participant and those responsible for the care of the participant. Immunization information systems (IIS) can capture and include investigational study vaccines, including COVID-19, in participants’ comprehensive vaccination records. IIS can be accessed by a variety of health care providers, making IIS an ideal tool for clinical decision support. Although we recognize that investigational study vaccinations might not be able to be reported to the IIS until after the trial concludes and is unblinded, this document summarizes the importance of reporting investigational study vaccination data to the IIS and outlines technical and other important considerations for partner organizations working on this topic. 

Why do investigational study vaccines need to be included in IIS?

• For real-time, clinical decision support (CDS) for vaccinating providers
• For school entry, work, travel, or social gathering purposes requiring proof of vaccination status
• For payors to ensure their members are protected from vaccine-preventable diseases
• For broader vaccine safety studies and post-monitoring surveillance

What are some important technical considerations for IIS?

Code set considerations

• There is no standardized process for recording investigational study vaccines in the electronic health record (EHR).
• Investigational study vaccines do not have a CVX (vaccine administered code set) assigned during the study period.[1]
• Investigational study vaccines do not have a National Drug Code (NDC) number until the U.S. Food and Drug Administration (FDA) approves a Biologics License Application (BLA) or Emergency Use Authorization (EUA).1
• Investigational study vaccines have different expiration dates during the trial process.

Timing considerations

• Investigational study vaccinations might not be able to be reported to the IIS until after the trial concludes and has been unblinded.

Data field considerations

• Consistent documentation of investigational study vaccines is critical, including a variable or field indicating if the vaccine was administered as part of a vaccine investigational study.
• Considerations would need to be made for IIS capturing the following data fields:
• Active comparator[2] vaccines administered to the placebo-controlled group. Would IIS want to capture this data assuming accurate NDC codes are reported?
• Individuals receiving true placebos (i.e., no antigen given to the placebo-controlled group). Would the IIS want to capture patients having received a true placebo?

Data quality considerations

• Data quality considerations would need to be undertaken regarding the various scenarios that can occur with reporting investigational study vaccine data to the EHR or IIS:
  • Investigational study vaccines get reported as an existing vaccine (i.e., misuse of NDC and/or CVX code).
  • The incorrect vaccine is reported for the placebo-controlled group (e.g., MMR vaccine is being studied, but placebo-controlled group is given varicella which incorrectly gets reported as MMR due to the study topic).
• As reported with COVID vaccines, some jurisdictions found that, if an investigational study site was contained within a major hospital system or academic institution that was already connected to the IIS, doses were automatically reported to the IIS without the immunization program’s awareness. This most likely occurred after the EUA was issued for the COVID vaccine.
• IIS may want to capture vaccination data from trials that are never approved.
• In cases where the manufacturer does not submit the candidate vaccine to FDA (e.g., due to safety data, market concerns, etc.), this information is still important to capture in the EMR and report to the IIS. This information has implications for clinical decision support and overall medical history. Convening necessary stakeholders (e.g., IIS jurisdictions, vaccinating providers, immunization programs) to determine what information would be beneficial to capture is an important next step.

What are other important considerations?

• Contract research organizations (CROs) provide support to pharmaceutical companies in the form of research services outsourced on a contract basis, which includes management of the investigational study.
  • CROs benefit from connecting with an IIS by reducing some administrative burden when accessing investigational study participants’ vaccine history and increasing the accuracy in documenting vaccination history, both before and during the study.
  • Contracts with the CRO may need to specify that vaccination data must be reported to the IIS.
  • Requiring reporting to the IIS may have financial implications.
  • If investigational study participants are issued a vaccine card at the end of the trial, reporting to the IIS could be included as part of the closeout process.
• Further analysis is needed to determine the extent to which CROs are reporting data to IIS, in what way the CROs are reporting data, and the HL7 capabilities of the investigational study data systems.

What is AIRA doing?

• Hosting stakeholder meetings to raise awareness, identify issues related to reporting, and discuss solutions
• Developing resources, including:
• Considerations for IIS programs and investigational study sites that are planning to exchange vaccination data:
• Clinical Trial Data: A Pathway to IIS Guidance
• Technical mechanism for constructing a message for investigational study vaccination events:
• Guidance on Indicating Clinical Trial Vaccines

What is still needed?

• Guidance and input from partner organizations, such as the Advisory Committee on Immunization Practices (ACIP) and FDA
• Additional data to determine the magnitude of the problem for all age groups and vaccines
• Landscape analysis of investigational study software
• Landscape analysis on the prevalence and types of use of IIS by CROs
• Translation of the current Guidance on Indicating Clinical Trial Vaccines into the IIS Health Level 7 (HL7) National Implementation Guide
• Indicating a vaccine is from an investigational study via HL7
• Possible need to record a true placebo for HL7 so it is not mistaken for a clinical treatment
• Funding to fully support the work on this topic
• Consideration for this topic when working on the overall data-modernization effort 

 If interested in collaborating on this topic, please contact Jody Dial.