Quality Assurance and Regulatory Compliance (QARC) Present and Future, Adapting to Achieve Best Quality Results

June 2022

The rapid onset and evolution of the COVID-19 pandemic forced quality stakeholders in the clinical research industry, as well as the clients and functional areas they support, to move at an accelerated pace towards the acceptance of digital transformation in quality and compliance setup.

Transition to these standards did not only impact how quality and regulatory entities performed audits. It also led to a full throttle implementation of digital practices where companies like Technical Resources International (TRI) and our clients evolved, embraced change, and became early adopters to be able to comply with the needs of the clients, sponsors, and everyone involved in clinical trials quality oversight execution. Implementing changes like:

• Virtual/video audits


• Remote data verification methods


• File sharing systems to ensure access to digital sources


• Secure remote access to electronic medical records systems


• Digital signatures


• Digital consent processes among many other changes

These and many other modifications to the standard clinical quality verification and auditing processes for Good Clinical Practice (GCP), Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP) and other regulatory and compliance standards of the clinical research industry were part of the digital transformation. It was the natural evolution needed for the industry to adapt or perish, or at least lose its effectiveness.^1,3

This evolution of quality and regulatory practices helped the industry understand the many benefits, and main limitations, of new digital technologies. TRI generated innovative ideas of how to overcome the limitations, which led to new acceptance of technology driven practices. In some cases, the technologies were already available, but the industry previously hesitated to adopt them. Examples of challenges mitigated include:

• Dependence on photography, video, and audio technologies having a high quality and resolution, to allow for evaluation of compliance with physical security and data safety integrity standards for sites, laboratory samples, and paper sources among other aspects used for clinical quality assurance verification. A decrease in audio or image quality would impact the efficacy of an evaluation. This was overcome by TRI by robust remote auditing practices, client and vendor education, and internal training to minimize the impact of technical components in the quality assurance processes.


• Legal and compliance barriers prevented clinical area video tours that were normally standard practice for any audit, limiting the ability of quality and regulatory staff to identify potential non-compliances and/or areas of risk that needed attention to prevent incidents. TRI quality professionals addressed this by applying improvements in communication with the auditee, requesting access by remote/virtual tours before audits, allowing the auditees to plan ahead of time with their site’s staff and facility management to have the areas accessible for the virtual tours, and creating non-disclosure agreements (NDA) and other quality assurance and documentation controls to ensure compliance with the requirements, per example documentation on maintenance of the areas, standards operating and maintenance procedures and their respective evidence of compliance.⁶

• Difficulties in ensuring compliance with HIPAA (Health Insurance Portability Accountability Act) standards of security for PHI (Protected Health Information), as all information documented in paper sources needed to be de-identified, representing a considerable workload for site staff. Understanding that this is a regulatory standard, TRI quality professionals solved or minimized these difficulties by getting approval for remote access to the clinical data, performing over the shoulder verification, going through rigorous approval processes to be able to have direct access to the data to be analyzed or performing quality assurance audits on-site when needed, and using a risk-based approach to identify needs and benefits on a case-by-case basis.^2,4

• In cases of GLP and GMP audits, the remote quality audit process could have diminished the capacity of the auditors to evaluate manufacturing processes, machinery standards and function observation, facility setup, environmental monitoring standards, flow of supplies, proper gowning, quarantine and storage practices, and verification of good laboratory practices. These risks were mitigated by TRI professionals through focused analysis during the audit’s virtual tours, increased emphasis on the review of evidence documentation to determine compliance with standard operating procedures and regulations, and implementing quality assurance techniques such as risk analysis, failure mode analysis, and increasing the samples of the quality review.


• In cases of clinical trial quality assurance oversight, there was limited capacity of direct interaction between auditors and site staff to observe performance of study related activities like physical exams or assessments. This was addressed by TRI quality staff with the implementation of video conferences which allowed the auditors to observe processes at distance and corroborate compliance of these with protocol standards and regulations.⁵

The current state of quality assurance practices is different from the old approach. However, with appropriate risk evaluation, scientifically proven techniques and intelligent quality assurance management, this process of change was a success story for TRI. Our staff ensured there was no impact to the clinical study integrity and human subject protection for the overall success of the clinical trials.

Similar quality assurance methods are being implemented in all aspects of the healthcare and clinical research industries. In the United States and other countries, governments have initiated changes based on quality assurance concepts in the overall healthcare setup. Initiatives that started even before the pandemic, like the US Center for Medicare and Medicaid access (CMS) “Meaningful Measures” initiative, were implemented in the last five years to identify high priority areas of quality and improvement in patient outcomes through standardization, use of quality concepts, adoption of patient-centered practices, and minimization of the burden for providers while fulfilling regulatory requirements.

A new age of quality assurance for healthcare is here. One which aligns aspects of clinical research quality assurance with clinical healthcare quality assurance to provide the best possible outcomes for all stakeholders, starting and ending with patients in mind, within the boundaries of this highly regulated industry.

The future is here:

With the unprecedented situation that the COVID-19 pandemic represented, technology enthusiasts and the technology industry saw an opportunity to finally increase their presence in this field, providing new tools to help healthcare stakeholders evolve.¹⁰

Some of the technologies applicable to clinical research and healthcare quality assurance scenarios that are on the horizon or are already being tested today, are:

• Artificial Intelligence (AI): AI could help quality assurance professionals with many tasks, including quality control and intelligent process automation of clinical research database generation, statistical analysis, data management, automated distribution to clinical research stakeholders, automated source verification, and trend analysis for signal identification. This technology is also potentially applicable to clinical quality assurance for laboratory management, inventory management, resource analysis, manufacture of medical devices and medications, clinical assessments for research, automated testing, autocalibration for equipment, and robotic support.⁷



• Blockchain technologies:The blockchain may be instrumental for quality assurance, as it has the potential to be used for database automation, verification of data integrity and security, and verification of clinical research data. It could provide the opportunity to address common threats to the integrity of data collected in clinical trials and ensure the analysis of these data is compliant with prespecified plans. This technology could also act as a secure method for sharing private data such as PHI and genomic data in clinical research. Providing blockchain-based dynamic consent architecture could address some of the barriers that inhibit clinical research data sharing for decentralized clinical trials or DCTs—also termed “direct-to-participant trials” or “virtual” studies, which are characterized by less dependence on traditional research facilities or specialist intermediaries for data collection.^8,9



• Face and Voice recognition:These two readily available technologies are gaining traction and they may soon be used in the clinical research and quality assurance industry. Potential applications include informed consent management. This may include facial identification of subjects/patients that will be part of a study or simple have a procedure at a hospital. This process could be verified on the distance video recording and the Face and Voice recognition software could be validated. These technologies may be used for analysis of compliance of informed consent reading to the subjects, ensuring that all key aspects and risks have been discussed with the patient. It could be used to document trainings, consents, audit reports, compliance records or other activities that require identification. This may eventually eliminate the need for a wet or electronic signature by changing this for an electronic facial or voice recognition record.¹¹



• Virtual reality: This fast-evolving technology is already being used for simple quality tasks like Virtual Audit tours, virtual environment evaluation for vendor qualifications, and virtual planning and design. The possibilities of its use go beyond this initial approach. The current literature describes the possibility of using this technology for proper risk analysis, quality by design, as a preventive measurement for evaluation of potential outcomes, and more. This, in combination with the artificial intelligence and coding technologies, will serve to increase the quality of every aspect of clinical quality in research, allowing improvement of root cause analysis by implementation of preventive virtual measures, testing and differential analysis of algorithms for issue resolution. All of these are applicable to every aspect of the clinical quality spectrum, from process standardization all the way to statistical analysis of results, going through all aspects involved in the generation scientifically sound and well designed, executed and overseen clinical studies.¹¹

At the fast pace that technologies have progressed, many new innovations are already ongoing. The fact that digital healthcare and modern technologies are becoming increasingly accessible to all levels of society, only makes the application of them to clinical quality and compliance more important in the evolution of QARC.

At TRI, we will continue to track and apply innovative technologies to all activities. We are always researching and looking to make the best use of all available tools and technologies to improve the speed and quality of our work for our clients. We support the magnificent work being done in the clinical research and healthcare industry to provide best in class quality outcomes, and through them, improve the health of the world population.

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About the Author

Dr. Elias Querales is and International M.D., MPH, CCRP with over 15 years of combined leadership and managerial experience in US and international clinical research in both the private and federal sectors. His experience includes safety and pharmacovigilance, healthcare quality, service quality applied to the clinical environment, and program management in the medical device and pharma development industry. He has worked all over America and supported creation and implementation of quality management systems and quality assurance methods in healthcare and clinical research businesses in the US, Canada, and Latin America.

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Footnotes

1. U.S. Food and Drug Administration. (2013). Oversight of Clinical Investigations. A Risk-Based Approach to Monitoring.
   https://www.fda.gov/regulatory-information/search-fda-guidance-documents/oversight-clinical-investigations-risk-based-approach-monitoring


2. U.S. Food and Drug Administration. (2013). Part 11, Electronic Records Electronic Signatures. Scope and Application
   https://www.fda.gov/regulatory-information/search-fda-guidance-documents/part-11-electronic-records-electronic-signatures-scope-and-application
   


3. GDPR.EU. (2018). General Data Protection Regulation.
   https://gdpr.eu/?cn-reloaded=1
   


4. International Council for Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use. (2016). ICH (International Conference on Harmonization) harmonized guideline integrated addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2)ICH Consensus Guideline. https://ichgcp.net/
   


5. Branch, E. (2016, April 30). Ways to Lower Costs of Clinical Trials and How CROs (Clinical Research Organization) Help. American Pharmaceutical Review.
   https://www.americanpharmaceuticalreview.com/Featured-Articles/185929-Ways-to-Lower-Costs-of-Clinical-Trials-and-How-CROs-Help/
   


6. U.S. Food and Drug Administration. (2020). FDA (Food and Drug Administration) Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency.
   https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19-public-health-emergency


7. The Emergence of Artificial Intelligence/Machine Learning Tools to Enhance Risk Management in Clinical Trials.
   https://www.tech-res.com/TRIbune/Fall-2021/TRIbune-Fall-2021-Article1.aspx


8. Using Blockchain Technology to Manage Clinical Trials Data: A Proof-of-Concept Study.
   https://pubmed.ncbi.nlm.nih.gov/30578196/


9. Decentralized Clinical Trials: The Future of Medical Product Development?
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093545/


10. Conducting Clinical Research During the COVID-19 Pandemic Protecting Scientific Integrity.
    https://jamanetwork.com/journals/jama/fullarticle/2766778


11. Saved by Automation! How Technology and Innovative Thinking Significantly Increased Productivity of the MSK Clinical Research (CR) Audit Program, Jacqueline Simpronio Susan Puleio, CCRP, ACRP-CP Memorial Sloan Kettering Cancer Center.
    https://www.aaci-cancer.org/Files/Admin/CRI/2021/42-How-Technology-and-Innovative-Thinking-Increased-Productivity-of-MSK-CR-Audit-Program.pdf
    

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