Using risk-based monitoring, clinical research associates (CRA) at sites, and Data Quality Scientists (DQS) remotely, are able to focus their efforts on monitoring sites, events and data points which present the greatest risk.
November 15, 2016 | by Sarah Hand, M.Sc.
Today’s clinical trials landscape is more complex than it’s ever been before. Sponsors are tasked with balancing study costs and timelines, while ensuring patient safety and regulatory compliance.
To improve the efficiency and overall operation of clinical trials, sponsors are increasingly looking to utilize updated monitoring strategies. Using risk-based monitoring, clinical research associates (CRA) at sites, and Data Quality Scientists (DQS) remotely, are able to focus their efforts on monitoring sites, events and data points which present the greatest risk.
Combined with remote monitoring, these clinical trials professionals can remotely review the data, and ensure that their site visits are spent efficiently. By capturing all of this data in an Esource format, this smart monitoring strategy can improve the quality, cost and speed of clinical trials.
For a better understanding of how these three monitoring technologies can be used in combination, I spoke with Graham Belgrave, Chief Operations Officer of Cmed. Graham has over 30 years’ experience in the pharmaceutical industry, with previous positions at companies including Pfizer, GSK and Roche.
To learn more about risk-based and remote monitoring strategies, register for Cmed’s webinar.
What are some of the biggest challenges facing the clinical trials industry today?
Apart for the often-quoted, “increasing complexity, regulatory rigor and the rising costs of conducting clinical trials,” the new challenges are the result of industry attempts to employ technology to try and address these three endemic hurdles. Pharmaceutical and technology companies both have different philosophies, attitudes to risk and operate at fundamentally different speeds.
Technology companies have sold a myriad of different solutions to pharma, which has historically resulted in piecemeal solutions where patient data are moved around between different applications and systems during the lifespan of a clinical trial. Additional challenges arise from the lack of in-depth understanding on the part of technology companies of what is required to successfully deliver clinical trials from an operational perspective.
How has 100% Source Data Verification (SDV) been applied to address these challenges in the past?
100% SDV has been the blunt instrument of study monitoring where the approach has been, “if in doubt, verify everything.” 100% SDV is neither mandated nor advocated by the regulatory agencies. It has neither the sensitivity nor specificity necessary for efficient clinical trials monitoring. Bearing in mind that on average, less than three percent of data are ever changed as a result of 100% SDV, what have we actually been looking for?
Through encapsia™ we provide a suite of programs that will allow appropriate risk-based monitoring to occur to reassure sponsors, satisfy regulators, improve quality and greatly reduce costs.
How does risk-based monitoring differ from the 100% SDV approach, and what problems does it attempt to solve?
Risk-based monitoring can mean different things to different people, but in reality it refers to factoring the management of risk into one’s monitoring planning as to where, when and which data one is either going to review, or verify. The determination of risk is now possible based on real time accessibility to data, which previously was not possible unless a site visit occurred.
In addition, the ability to determine risks regarding quality and integrity of data by looking at the behaviours surrounding how and when it is collected, also adds a new level of granularity that previously was not possible. With a combination of on-site and centralized monitoring enabled by cloud based electronic data capture (EDC), and the further addition of eSource, data is now visible in real time by all the stakeholders involved the process, hence enabling real time risk-based decision making.
Does a clinical data suite, like encapsia™, completely eliminate the need for a CRA to visit sites for monitoring purposes?
The answer, I am sure many readers will be pleased to hear, is no. It is easy to forget that CRAs do so much more than just SDV, although historically much of their time was spent doing 100% SDV because we were not able to do anything more sophisticated.
The CRA still has key activities to conduct that ensure the compliance and quality of what is going on at the site, such as checking the existence of all essential documentation, including the SIV, drug accountability, and wet ink informed consent form (ICF) for every patient. In addition, they are the sponsor’s representative at sites, responsible for helping to educate and motivate all staff involved in the study. The advent of encapsia™ does enable sponsors to reduce both the frequency and duration of routine visits, but the essential insight that CRAs provide during pre-study site selection visits (PSSVs), site initiation visits (SIVs) and the essential close out activities, still remain pivotal.
What is the stance of regulatory agencies, like the FDA and EMA, on risk-based monitoring?
Guidance recently published by the FDA has gone as far as saying that risk-based monitoring should be part of any high-quality study, and that the optimal approach to achieve the best results from the adoption of this methodology is to factor this in as early as possible in the planning and design of the study. They also stress that critical components for successful delivery, include a well-designed protocol and the adoption and leveraging of technology to monitor data quality.
According to non-profit TransCelerate, the Medicine and Healthcare Products Regulatory Agency’s (MHRA) position on the adoption of risk-based monitoring, as well as that of the FDA, is that whilst current on-site monitoring practice does provide a level of control, advances in risk-based approaches and technology provide an opportunity for a more holistic and proactive approach.
It might also be interesting to note that from a regulatory perspective, we have always been enabled to explore new and more effective ways of monitoring our studies. ICH GCP E6 states that whilst sponsors should ensure that the trials are adequately monitored, they should also determine the appropriate extent and nature of the monitoring.
This decision should be based on considerations such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial. It also says that in general, there is a need for on-site monitoring, before, during, and after the trial. However, in certain circumstances central monitoring in conjunction with on-site monitoring can assure appropriate conduct of the trial in accordance with GCP.
Are there any benefits to patients, which could improve retention, when using this smart monitoring system?
In many cases, the patient experience has not been enhanced by the use of technology employed in the capture of their data in trials, but the ease-of-use and the portability of tablets in the capture of data can only make things run more smoothly. Add to this the increasing functionality of wearable devices as a new way of capturing data, and the trial landscape really starts to take on a new shape.
The edit check functionality built into encapsia™, ensures that as patients are sitting in front of the doctor/site investigator only suitable patients are entered. The system will immediately flag entries if inclusion/exclusion criteria are violated, which facilitates a conversation with the medical monitor at that time. This significantly increases patient safety and quality of the data over what is current standard practice. In addition, the Insights™, Analytics™, Chat and Tag functions allows an immediate view and interrogation, in real time, to allow optimal decision making – something that we believe is unique to encapsia™.
What are the important features that study sponsors should be looking for when shopping for a clinical data suite?
The answer is long, but it probably starts with choosing a solution that is ideally a unified system. For example, a cloud-based system where the data only exits in one place in real time and is accessible in the appropriate format to all stakeholders, can help real time decision making.
It should be a system that supports your risk-based monitoring approach, and gives you the flexibility to evolve the roles of your monitors and data managers over time. It should have both a sophisticated, but easy to use, data entry functionality and provide a customisable dashboard to let you see what is going on.
The system should be able to evolve and grow with you, as opposed to a system that has already been crystalized and hence grows more obsolete with each day. It should be modular, and utilize app-based architecture to allow you to build a functionality that suits the way you operate. The clinical data suite should be portable, and have on-line and off-line functionality to avoid any delays in data capture.
Finally, appreciating that sometimes large organizations are not able to take leaps forward in the technology space even though they may want to, and that there are existing systems and processes embedded, the ability to integrate with other systems, where necessary, is key. As with most technological developments in the 21st Century, the user interface is integral, and whatever choices are made, the solution should be intuitive and easy to use. In the complex world of clinical trials, it has to make the lives of investigators, patients, monitors and data managers easier, not more complicated.
For more on incorporating risk-based monitoring, remote monitoring and Esource data into your clinical trial, register for Cmed’s webinar.
Keywords: Risk-Based Monitoring, Remote Monitoring, Clinical Trials
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