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In the race to improve speed and efficiency in drug development, clinical research studies have grown dramatically in the last decade in both numbers and complexity. Adaptive design, multiple cohorts, randomization and detailed dosing instructions have been driving factors in this increase as sponsors are looking to achieve more endpoints within a single protocol.

As companies continue to collect higher volumes of data in an effort to shorten the duration and number of trials required for submission, it becomes increasingly difficult for researchers to manage this information. This means the toolsets used to conduct studies are being relied upon more heavily. At the same time, the pharmaceutical landscape continues to shift toward large molecule compounds, where a unique set of challenges is emerging. Compared to small molecule drugs, biologics are more sensitive to temperature shifts, making supply chain management increasingly difficult.

Additionally, not only are there higher costs to manage when developing a biologic, but also the submission of a Biologics License Application (BLA) is subject to higher scrutiny by regulatory agencies. Therefore, biologics inherently require an increased focus on Interactive Response Technology (IRT) processes by regulators, as the data collected in an IRT is crucial to support a regulatory submission. This is why now, more than ever, the FDA is taking a closer look at IRTs and how these systems can directly impact patient safety and clinical trial integrity. The obvious conclusion is that the partner chosen to provide the technology to assist with these challenges must be up for the task.

In today’s pharmaceutical market, nearly 20 percent of total sales are biologics. By 2020, it was expected that they will make up slightly more than half of the world’s top 100 selling drugs. As we move toward the future, the industry will look to technologies like IRT to meet the needs of the trials that will bring these drugs to market. In the competitive pool of IRT providers that have developed during the system’s evolution, how many will be able to offer the technologies, design, and experience to do this successfully?

FDA expectations of an IRT system

The IRT system captures the broader features emerging within the market, such as electronic-reported outcomes, titration/dosing calculations, shamming (blinding of patient labs or other results), supply accountability, reconciliation, and returns. It can ensure the drug is at the right place, at the right time, and in the right quantities with the ability to respond to any changes throughout the course of the trial. The information collected and generated in an IRT system is at the center of some of the most critical aspects of a clinical trial, such as:

• Integrity of randomization, implementation, and stratification of data
• Dosing calculations and/or titration rules
• Supply management aspects, such as control of expiring drugs, tracking of temperature excursions, and management of recalls

Beyond these, an IRT system improves the visibility that sponsors have into how sites are performing. For this reason, the FDA expects it to be used as a way to provide proper oversight of a clinical trial and to identify and remediate issues in a timely manner.

There are many vendors trying to use IRT in a very simplistic way and focusing solely on randomization and supply management. However, IRT saves time and money across many aspects of trial execution, and it has the potential to do even more. The use of analytics from IRT to support risk-based monitoring decisions in a controlled and objective manner is one of them. In addition, proactive identification of supply challenges or non-compliance with supply usage can save thousands or even millions of dollars. The mobile capability of IRT systems will enable even further uses, making the technology work better within a site or patient workflow than any other technology available.

There are few vendors that understand the challenges of clinical trials and the opportunity IRT has to enable these trials to run effectively. As the go-to provider for complex studies that have emerged flawlessly from the FDA’s first IRT audit, Almac has the experience, expertise, and integrity required to deliver the results necessary to bring your drug to the patients who need it.

To find out more about OVERSIGHT, click here.

In 2019, the Asia Pacific (APAC) region represented 20% of all registered trials & 22.5% of all active/ongoing trials. To keep up with this pace, APAC Study Managers, Investigators and Supply Chain Managers (who have, until today, managed manual record-keeping in clinical trials) need to automate. IRT presents an opportunity for pharmaceutical sponsors conducting clinical trials in the APAC region to significantly improve productivity and data integrity.

The following steps serve as a best-practice approach to implementing an IRT in the APAC region. When system development proceeds in this way, the resulting tool will suit the study, and development time and costs will be minimized.

1. Assemble the Project Design Team. On the sponsor side, this group typically includes the Clinical Team, the Drug Supply Team, Biostatisticians, and Data Managers. The vendor would normally involve Developers, Testers and Quality Assurance Specialists, led by a Business Analyst. To ensure efficient and clear communication, a project leader should be designated to funnel information from the stakeholders to the vendor.
2. Hold a workshop to introduce the Project Design Team to what an IRT system can do prior to kicking off the project. It is recommended to walk through the system capabilities and show team members a demo of a sample system. This ensures that all parties have the same understanding of what is possible before they embark on the challenge of determining specific needs.
3. Gather the specifications for the IRT using a systematic process. Working through a User Requirements Specification (URS) sheet helps direct the process of defining the project scope and the particulars of what will be needed. To properly configure the system, the developers will need input on a host of study elements. An experienced development team can ensure that the recommended approach is compliant with all applicable regulatory mandates from various ministries and regulatory bodies.
4. Develop the system, using templates for standard functionality and customizing only those elements that are unique to the study. The development time can be cut down significantly when standard functionality will suffice, and the system can be built using established templates.
5. Perform User Acceptance Testing (UAT) of the system. This is usually a multi-step process, with the vendor performing an initial UAT, followed by a sponsor UAT. The sponsor is provided with a test plan containing specific test cases and instructions on how to execute the UAT.
6. Launch the system. It is recommended that all site users should be invited to an investigator meeting, where they receive training appropriate to their role. Ideally, they should all be provided with a quick reference guide bearing step-by-step directions on accessing and using the system.

The ultimate performance and value of an IRT system developed and implemented for APAC clinical trials can be assured through rigorous quality checks at four stages in the start-up phase: when requirements are finalized, once the code is programmed, after testing is completed, and during the implementation process when the system is ready to go live. Companies operating in APAC can look forward to a great leap in efficiency by adopting a well-tested IRT solution.

By Richard Wagner

While there are obvious pressing logistical and operational challenges, there is also a tremendous amount of data that needs to be collected and managed during the course of a clinical trial. Not only is this data needed for the outcome of the trial itself, but it is also necessary for managing site regulatory compliance.

In a recent survey¹ by CenterWatch, the clinical trial research company found that while half of the respondents said their site was on schedule when it came to the maintenance of regulatory tasks prior to an audit or monitoring visit, 28 percent were almost a week behind and 14 percent were two weeks behind. The reason for the backlog is because data tracked on paper can often fall to the wayside as a trial is being conducted until someone has the downtime to enter it into the relevant clinical data systems. This causes sponsors and/or supply managers to lose valuable visibility into what is going on at that site. Paper records begin to accumulate, and sites are soon faced with trying to find a place to store them along with the supplies.

At the end of the study, all of this information in paper records has to somehow come together into a complete chain of custody records that regulators will need access to as questions arise. Every adverse event that is recorded during the trial needs to be investigated, in order to determine which are significant. Sponsors have an ethical and moral responsibility to protect the safety of the patient. When patients experience an adverse event, there must be absolute certainty that the right patient has been given the correct drug.

The data management burden in clinical trials is compounded by the high turnaround rate of clinical research associates and monitors. Most clinical trials can run for numerous years. If paper records and/or unanswered questions begin to pile up as a revolving door of personnel is turning, you could potentially run into a situation where you cannot provide answers to vital questions regarding your study.

A promising solution

In line with the growing awareness of the need to better record “source” data electronically, electronic systems and technology can be powerful tools in improving the fragmented nature of the current chain of custody management processes. Any proposed technology solution must meet the needs of several stakeholders, in order to be successful. Notably, the following goals are paramount:

• Reduce the supply management burden, both during the study and during study closeout, and reduce the possibility of a stock-out event at the site. The supply management team is also continually looking for ways to reduce the overall cost of producing, distributing, and tracking study medication.
• Eliminate medication dispensing errors and retain patients on the trial. Clinical Operations are also interested in optimizing the trial monitor workflow and time-on-site, as well as incorporating any available historical data into site selection processes and use ongoing site performance metrics to support risk-based monitoring programs.
• Preserve the flexibility necessary to accommodate unanticipated circumstances during patient care and to minimize the intrusiveness of the technology solution to delivering patient care. The site also wants an expedient and simple means for managing its inventory and meeting the accountability requirements of the study, while making the best use of potentially limited storage availability.

Introducing a system that can accomplish all of this and more could optimize the supply chain at every level. However, an ideal solution requires the support of both Clinical Operations and Supply Management. Both groups may have concerns about the implementation of a system such as this, and many are related to the potential disruption to established standard operating procedures. The key to designing and implementing a system that can be accepted by both teams and integrated into standard operating procedures more easily is to gain input from all stakeholders in the trial.

What stands in the way?

The pharmaceutical and healthcare industries are notoriously risk-averse. This is an understandable consequence of the critical nature of patient care and the potential risks associated with any errors. However, existing processes have, in many cases, evolved over a considerable period of time. Often, this may become more burdensome than desirable, while not contributing to any risk reduction or quality improvement. By implementing a more streamlined workflow with automated data entry and verification, costly and time-consuming processes, duplicate verifications and potential errors can all be reduced. Nonetheless, before you can begin the process of implementing this type of next-generation IRT system, you must first address any concerns of your stakeholders.

Find our more about OVERSIGHT here.

1 http://www.centerwatch.com/news-online/2015/04/01/ regulatory-compliance-an-increasing-burden-on-sites/

Next-Generation tool

With substantial experience in this field, Almac Clinical Technologies sought to address these pain points through the analysis of over 3,000 clinical trial protocols to identify common needs and functions that can be consolidated into a pre-validated and fully configurable clinical workflow ecosystem. The result is Simplify™, an IRT solution that allows clients to use and configure pre-validated tools and components to help sponsors and investigators focus on trial conduct.

Time savings

With the Simplify IRT system, trial workflows can be designed and implemented in days to weeks – depending upon complexity. The specific investigational products, dosing regimens, and patient inclusion/exclusion criteria are unique to each trial, but the underlying designs, randomization plan, and product distribution needs are familiar. Sponsors that don’t want—or have time—to be slowed by extensive discussions around trial requirements, documentation, and User Acceptability Testing (UAT) can pick and choose from pre-validated elements to create and implement the needed IRT system functionality in record time.

Sponsors simply select the functionality (via configuration document) needed for a particular trial, thus reducing the volume of documentation that must be reviewed and signed off in design and UAT. Without a pre-validated route, these time-consuming and laborious steps become high-overhead milestones on a slow journey toward commercialization.

Configurability

Since core functionality is already configured, tested, and validated in Simplify, sponsors can concentrate on configurations for their specific trial. This is a huge improvement over traditional e-clinical solutions where clients can expend considerable effort reviewing and testing every aspect of trial software.

The Simplify IRT system, combining fully configurable elements, is highly flexible to meet specific sponsor requirements while saving time and reducing overhead. In the current COVID-19 environment where time is of the essence, Simplify has helped sponsors move from sign-off to patient enrolment in as little as seven days. If the scope changes or evolves after the trial begins, complex and customised functionality can easily be added as needed. Few pre-validated platforms have the flexibility to expand during later-stage trials in this manner.

Streamlining the management of patients and supplies

Once a trial is launched, Simplify automates the randomisation of patients, product assignments, and tracking/order supplies. Real-time dashboards and alerts improve trial efficiency with less lag in managing cohorts and monitoring progress. Reporting mechanisms provide real-time analytics to trial monitors, sponsors, and investigators supporting efficient and timely decision making. Dosing decisions, even enrolment decisions, can be based on a complex interplay of biomarkers, laboratory values, and other factors in addition to more familiar patient demographics.

That same focus on efficiency means sponsors can create and manage dynamic supply strategies based on real-time product usage rates and today’s forecasts, not the assumptions and forecasts set before the trial was launched.

In summary, Simplify has the flexibility to accelerate rule-driven decision-making to get trials started faster and conducted more efficiently with fewer hands-on hours from managers who are already overburdened and under-resourced. Doing more with less, and doing it faster, is a strategy for success.

Best experience, best results

Sponsors, CROs, and investigators are doing more and more complex trials than ever before, and with fewer staff and resources at their disposal. The Simplify IRT system allows sponsors to implement and use the functionality they need in a manner that removes unnecessary complexities. This approach helps to reduce the time it takes to initiate a clinical trial so that much-needed therapies get to patients faster than ever before.

When time is of the essence, such as in the face of a global pandemic, IRT systems can truly be a game-changer by helping efficacious drugs show benefit as soon as possible and at a lower cost. Sponsors win, investigators win, and, most importantly, patients win.

To find out more about our IXRS^®3 IRT Platform click here.