A Quick & Easy Guide To Site-Facing Clinical Trial Technologies

By Aurea M. Flores, Ph.D., BS Pharm, CCRP, CHRC, CHC, CHPC, CCEP, PMP, PMI-ACP, RQAP-GCP

Multiple and distinct laws and regulations at the federal, state, and local levels make clinical research one of the most highly regulated industries. States regulate healthcare practices, while drugs under investigation are regulated at the federal level, and federal funding rules, privacy provisions, and medical billing practices, among others, must be complied with. Compliance with these laws and regulations requires documentation of activities, which can be quite a burden. Over the last few decades, technologies have emerged to assist with clinical trial operational compliance. Here is a summary of clinical trial technologies used by clinical research sites, their capabilities, and how sponsors and sites might best evaluate their use in clinical research.

Electronic Health Records

The first technology for widespread use was electronic health records (EHRs), originally developed as computerized provider order entry (CPOE).  However, CPOE transitioned into EHR, whose main purpose was to help comply with Medicare policy and regulations for billing for medical services after the adoption of HIPAA. Since their beginning, EHRs have been used to properly bill medical insurance.

Clinical Trial Management Systems

EHRs have struggled to sufficiently support clinical trial activities. As a result, developers introduced clinical trial management systems (CTMS) to bill trial sponsors and avoid double billing. Other CTMS features include managing trial milestones and budgeting. Some CTMS applications have some degree of nimbleness to assist with other trial operations.

A capable CTMS should be able to:

• Create a coverage analysis
• Create a budget based on the coverage analysis
• Complete trial milestones
• Document completed procedures per participant
• Seamlessly generate invoices to sponsors/sponsor representatives from the completed procedures per participant and trial completed milestones
• Interface with eSource/EHR for participant scheduling

Regulatory Binders

Sponsors are responsible for maintaining trial master files (TMFs) while investigators/sites are responsible for maintaining investigator site files (ISFs). These files are similar but do contain distinct documents needed to comply with each other’s respective regulatory responsibilities.  Maintenance of paper files can pose a great burden, so electronic regulatory binder (eBinder or eReg) applications have been developed to work as document repositories. Some, however, also function as live documents, where regulatory documents can be edited/amended with audit trails to document their activities. The latter is an important feature.

A capable eBinder should be able to:

• Configure a document repository based on the organization’s repository taxonomy and ISF/TMF regulatory requirements
• Generate, complete, and maintain live documents (e.g., Delegation of Authority, Protocol Deviation Log, Adverse Event Log, etc.)

eSource

EHRs contain a lot of information that may or may not apply to the conduct of a clinical trial. Additionally, EHRs are subject to HIPAA regulation, which stipulates that individuals should have access to their medical data (unless this data contains information on their mental health). Data contained in the EHR regarding participation in clinical trials may be held from access by the individual trial participant but eventually must be made available, most likely after the trial has been completed. eSource applications are specifically designed to collect individual data as part of their participation, are not considered EHR, and therefore are not subject to HIPAA regulation. eSource applications are developed for use by investigators/sites and not trial sponsors.

A capable eSource should be able to:

• Interface with EHR, if an organization has an EHR for scheduling purposes and  is billing to third-party medical insurers
• De-identify protected health information (PHI)
• Populate discreet data within the EDC

Quality Management Systems

Every organization should have a way to ensure they are complying with all applicable laws and regulations and to track deviations from compliance with such laws, regulations, and standards. A quality management system (QMS) is a formalized system containing the organization’s business processes, procedures, and responsibilities for complying with applicable laws, regulations, and standards to ensure the quality of the services provided. Maintenance of paper documentation of the activities contained within the QMS, as with many other paper-based activities, can be burdensome.

eQMS assists as a document repository for sharing all applicable documents across the organization in addition to managing policies and procedures documents, versioning, and archiving. Additionally, eQMS can manage live documents, documenting different quality activities such as corrective and preventive action plans, root cause analyses, and internal/external and qualification audits.

A capable eQMS should be able to:

• Configure a document repository based on an organization’s policies and procedures taxonomy to comply with regulatory requirements
• Generate, complete, and maintain live documents (e.g., CAPAs, RCAs, audit reports, organizational policy/procedure deviations) across all functional units

Electronic Data Capture

Electronic data capture (EDCs) are applications that collect, manage, and store data from clinical trials in digital format. EDCs are mostly used by sponsors or sponsor representatives designated to perform data analysis and submit to regulatory agencies.

A capable EDC should be able to:

• Accommodate building different types of CRFs
• Intuitively build trial protocols as well as complete data entry
• Interface with EHR/eSource to populate discreet data

EHR/eSource To EDC Application

More recently, applications that can seamlessly transfer discreet data from the EHR/eSource to the EDC have come onto the market. These applications aim to reduce the time and effort of clinical trial staff responsible for data entry. These activities can be time-consuming and require verification (e.g., quality control activities) to ensure the accuracy of the data entered in the EDC. These applications can be valuable for busy investigator sites but may not be cost-effective for smaller sites. In most cases, sponsor/sponsor representatives contract these applications on behalf of the sites.

A capable EHR/eSource to EDC application should be able to:

• Integrate with the most highly used EHR/eSource and EDC applications

Investigational Medicinal Product Management Systems

These are web-based applications that assist investigator sites to manage investigational medicinal products (IMP)s used in trials. These applications can assist in documenting trial status,      IMP receipt, quarantined IMP inventory, lot numbers and expiration dates, IMP dispensing, and IMP returns by trial participants.

Additionally, they can track participant enrollment, IRB expiration, and trial team members. These applications are valuable in research institutions conducting many clinical trials. Smaller investigator sites may not find that these applications are cost-effective.

A capable IMP management system should be:

• Intuitive for end users to be able to build the trial in the application
• Supportive of the listed activities above
• Easy for end users to enter data

eConsent

Obtaining informed consent from prospective participants to join a clinical trial is more than a document that is provided to prospective participants to read and sign. It’s a process.

The development of electronic applications to support informed consent have been more challenging and only became a priority as a result of the COVID-19 pandemic. At the time, investigators could not obtain informed consent in person due to the physical distance requirements. Unfortunately, some vendors’ idea of eConsent was to replace a paper informed consent form (ICF) with an electronic version, without fully understanding the actual process to obtain consent.

A capable eConsent application should be able to:

• Support the organization’s procedure to obtain informed consent, e.g., who is delegated
• Support video recording of consent information (e.g., informed consent document)
• Support voice recording of informed consent information (for vision-impaired individuals who do not know Braille)
• Include a glossary of terms and web links to assist individuals
• Document how long an individual spends reviewing the materials
• Support a wide variety of options to provide the signed/dated informed consent to participants
• Allow  trial staff delegated to obtain informed consent to document informed consent procedure in a clinical note (and allow for the clinical note to populate in either the EHR/eSource)

About The Author:

Aurea Flores is a clinical research professional with over 25 years of experience.  She is a licensed pharmacist and was awarded a Ph.D. in pharmacology & toxicology with an emphasis on drug metabolism and chemical carcinogenesis. She has conducted/supported clinical trials in a variety of areas (oncology, cardiology, neurology, gastroenterology, bariatrics, pediatrics, and others) with an emphasis on patient safety, operations, quality, and regulatory compliance. She is a Certified Clinical Research Professional (CCRP-SoCRA), Project Management Professional (PMP-PMI), and Agile Project Manager (PMI-ACP), and is Certified in Healthcare Research Compliance (CHRC-HCCA), Certified in Healthcare Compliance (CHC-HCCA), Certified in Health Privacy Compliance (CHPC-HCCA). She is also a Certified Compliance & Ethics Professional (CCEP-SCCE) and a Registered Quality Assurance Professional in Good Clinical Practice (RQAP-GCP/SQA). She is a speaker at national meetings and consults in areas of clinical research operations, project management, healthcare and research compliance, and quality assurance.