CLINICAL TRIALS - Quality Matters in an Evolving Clinical Trial Landscape

INTRODUCTION

The strive to deliver the very best outcomes sits at the heart of clinical research. Arguably the mechanism for delivering that “perfect” outcome rests squarely on the shoulder of a single key principle – quality. Quality in all areas from study design to data collection to successful publication and many more.

The concept of quality encompasses a vast array of perspec­tives gained from the evolution of trends in the development of quality management practices. Good Clinical Practice (GCP) is regarded as the ethical and scientific quality standard for con­ducting a trial and applies to all steps in the process that bring a trial to a successful conclusion. GCP’s role is to ensure that the clinical trial data and reported results are credible and accurate and that the rights, integrity, and confidentiality of the trial subjects are protected.

As clinical research becomes more and more complex, small nuances potentially have a big impact on outcomes. Globaliza­tion, outsourcing, and increasing regulatory demands are all af­fecting clinical trials and their quality. Artificial Intelligence (AI) and machine learning (ML) are contributing new ways of discov­ering and acting on data management in clinical trials, including discovering any anomalies in the data.

Concurrently, wearables and mobile technologies along with cloud technology and related platforms enable the collection of frequent, specific, and multidimensional data but can pose new challenges to collecting and distributing quality clinical trial infor­mation. Clinical trial participants are often using these devices in a remote way that requires diligent work on the part of the clini­cian to ensure data is properly classified and disseminated throughout the appropriate channels. Social media is a rapidly increasing data source for clinical research, but the quality and ultimate validity of the information reported continues to be con­cern for many.

Investigator sites and Institutional Review Boards (IRBs) have been under increasing scrutiny by the US Food and Drug Administration, the European Medicines Agency (EMA), and the UK’s Medicine and Healthcare Products Regulatory agency (MHRA) when it comes to quality. To meet the regulatory expectations, sponsors and Clinical Research Organizations (CRO) need to im­prove quality by developing systems with specific standards for each clinical trial process.

This article will review best practices for achieving quality by addressing chal­lenges focused on the all-important but growing complexity of managing the dis­tribution of critical safety documents and the processing of Individual Case Study Reports (ICSRs) and aggregate reports to sites, Ethic Committees (ECs), IRBs, and others in the reporting chain.

Quality systems have many touch points including personnel roles and re­sponsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preven­tive action. With an objective to improve quality, newer inspection approaches, such as risk-based inspections, surveillance in­spections, real-time oversight, and audit of sponsor quality systems, have become a focal point.

As one example, the FDA has part­nered with Duke University to implement the Clinical Trials Transformation Initiative in order to conduct research projects on design principles, data quality and quan­tity including monitoring, study start-up, and adverse event reporting. This public-private partnership is intended to drive adoption of practices that will increase the quality and efficiency of clinical trials.

MINIMIZING THE POTENTIAL FOR HUMAN ERROR

Rejection of clinical trial data after an inspection is ineffective and even worse, wasteful in time and cost. A better approach to avoid post-inspection waste is to change the process from focusing on in­spection-based quality improvement to fo­cusing on proactively determining and finally deploying specific, automated, and documented processes for quality man­agement. When these business processes have been defined and potentially re­designed, the often error-prone human el­ement is greatly reduced.

For example, when key processes for safety document distribution require mul­tiple steps that involve constant manual in­tervention, often using systems and tools that were not designed for that purpose, undetected small errors can combine into large-scale problems. An automated process, designed for purpose, provides structure and a degree of rigidity, which means that the documents are getting to the right people at the right time, every time. Monitoring with a central dashboard means the process is transparent and con­trolled.

Globalization of clinical trials has put added pressure on quality measures. When, for example, six sites with thousands of participants are running in multi­ple geographic areas and time zones, it is almost impossible for manual intervention processes to ensure the vigilance neces­sary to meet rigid – and varying – regula­tions for delivering error-free and on-time safety information.

QUALITY IN ROLES & RESPONSIBILITIES

Quality also permeates the develop­ment of specific roles and responsibilities of the teams managing and monitoring the trial sites – and there can be various people involved – including but not limited to the principal investigator (PI), Study Manager, Site Mangers, Clinical Research Associates (CRAs), et al.

Again, globalization causes chal­lenges in maintaining clear oversight of processes when working with a variety of people often with different skill levels or ex­perience in clinical trial management. The methods and degrees of monitoring vary from one clinical trial to another depend­ing on the degree of risk involved and the size and complexity of the trial. While sponsors and CROs want to make sure the teams in charge are well-qualified, it’s not always possible to recruit the levels of ex­pertise needed to ensure the most clear and transparent outcomes. Some team participants may be contract workers/free­lancers and Site Managers may be simul­taneously working on several different trials. This can present the Study Manager with that uncomfortable question “how confident are you in the validity of data from ALL your sites?” Let’s not forget that it is the study manager who is ultimately responsible for safety document distribu­tion. Manual assembly of this information is labor intensive, costly, offers opportunity for errors, and often lacks documented audit trails.

Automating the safety document dis­tribution process clearly delivers a signifi­cant advantage. Utilizing a central “hub” into which documentation is delivered from each site can provide a clear and transparent advantage. Such automated systems to date have provided a portal into which documents are entered which, while a significant step forward, creates the issue of access and password retention for sites. However, the latest applications have solved this issue and allow secured, validated, and auditable access for all au­thorized users without the need for pass­words. The result is an easy-to-use platform for all trial sites. Depending on different roles identified at each site, there is tiered access to appropriate information. For example, a local investigator may only have access to local sites while Study Man­agers have access to all sites, no matter the geographic area. This empowers study team members and simplifies access to a real-time overview, significantly reducing the workload across the team and enhanc­ing collaborative communication. For ex­ample, in a recent case, a trial team that applied the automated interactive hub ap­proach, in just 1 month, moved from struggling to deliver 20 safety documents a day with its manual system to easily de­livering more than 50 documents daily via automation of the process.

QUALITY OF DELIVERY & OVERSIGHT

Depending on their local infrastruc­ture and regulations, sites expect to be able to receive information according to their preferred method, and the informa­tion must be blinded or unblinded de­pending on specific regulations. This means recipients expect to have courier deliveries, email with attachment, email with secure link, even fax. Any automated systems that are supporting recipients must have this flexibility, not only to ensure strong adoption, but also to deliver a uni­fied view of compliance for the sponsor. Regardless of the distribution method, the transparent oversight of the activity must remain.

With a single view, on a dashboard, the hub approach illuminates all the dis­tinct actions and rates of progress behind each specific process, which means faster and more-informed decision-making and certainty of outcome. For example, country rules that drive the safety document distri­bution are audit-proof. That means the people on the team responsible are able to see to whom a document was sent, why it was sent on a specific date, and confir­mation of receipt. Supporting this effort are automated compliance reports that can identify anomalies at a site, ie, if perhaps more training is needed to ensure better adherence to policies and proce­dures.

QUALITY IN EXECUTION

Seeking an automated approach can often seem daunting. Will a new system fit easily into the existing infrastructure, will it easily connect to an existing safety data­base and CTMS, and will it be intuitive enough not to cause interruptions in human adoption? These are all significant questions. Perhaps the simplest answer is that full automation leads to a more streamlined process that naturally en­hances the availability of critical informa­tion and provides flexibility and clarity in reporting. It also reduces manual efforts, human errors, and operational costs associated with audit trails and compliance documentation. Where solutions have been successfully implemented, they have seen significant reduction in cost and re­source requirements and seen much im­proved compliance from sites.

In short, focusing on quality in all as­pects of a clinical trial is the foundation for delivering valid and compliant outcomes. With a simple, easily implemented, auto­mated, interactive, and central database, a commitment to maintaining data in­tegrity and participant safety through qual­ity guidelines provides a systematic approach to continuous process improve­ment.

John Buchan is a Life Science Technology Specialist for pharmasol. He has spent his career in Life Sciences and Life Science technology, the latter specializing in Pharmacovigilance. Having worked in Sales & Marketing roles in major Pharma companies, he moved into working with organizations supplying technology, software, and services for Life Science and Healthcare organizations across Europe and North America. He is a passionate advocate of utilizing the best of technology to solve the challenges the pharmaceutical industry faces. He is based in the southern United Kingdom.