Navigating a Rare Disease: A Mother’s Story

Rare Disease Day interview with Lori Leathers

Rare Disease Day®, which this year is observed on February 29 (the rarest day on the calendar) is a day to honour the millions impacted by unique and often complex conditions. While there are many who were led to Almac by their dedication to clinical development, there are some who were led to our company through very personal experiences. Today, we want to share the journey of Lori Leathers, business development manager at Almac Clinical Technologies and mother of an adult son with Fragile X syndrome.

Lori’s son, Gabe, has special needs arising from Fragile X syndrome (FXS) – a rare genetic disorder that causes various physical, intellectual, and behavioral health issues. Lori’s devotion to caring and advocating for Gabe, who was first diagnosed as a toddler, has been a central feature of her life as a mother and career woman.

Before her son’s diagnosis was even confirmed through genetic testing, Lori participated in twice-weekly occupational therapy sessions with him. Eventually, he also needed physical and speech therapy, which she could accommodate with her job in field-based sales. As Gabe grew, however, and his educational needs became more specialised and time-consuming, she felt the need to resign from her corporate position.

In a move both practical and altruistic, Lori became a self-employed consultant to help other parents in similar situations. “When children with special needs or a rare disease become 21, school districts are no longer responsible for their educational services,” Lori explained. “So, there are a number of practical supports that are needed and financial steps that families must take to ensure that their loved ones receive Supplemental Security Income (SSI) and have funding available in the future. I could share my own knowledge and experience with others, and my schedule gave me the freedom to help Gabe take part in clinical trials as they became available.”

Initially, the trials available to Gabe were non-interventional observational studies, but over time, more studies have opened for medications treating symptoms of Fragile X Syndrome. Currently, Gabe is enrolled in an open-label extension study specifically targeting Fragile X Syndrome. Gabe, now 22, is doing well. He lives independently near Lori, with round-the-clock supervision.

And Lori has once again turned her personal interest into a career focus when she joined Almac six months ago. “I’ve been able to bring my first-hand experience with being involved in clinical studies to emphasise the need for patient engagement in clinical research,” she said. “It is very helpful to be able to share my experience with Sponsors. Plus, I know that my work is helping to get much-needed therapies to patients and families much faster.”

Lori is appreciative of Almac’s work environment and culture. She notes, “Everyone has been very friendly, patient-focused, and supportive of my needs to travel with my son for research purposes. And, I have access to all the most current information about treatments in the investigational pipeline, which I can share it with other families in this space.”

Lori’s roughly 20 years of personal experience in supporting a special needs child has given her a unique perspective that is especially helpful to loved ones of those recently diagnosed with a rare disease. Her encouraging words to them are:

  • Be a strong advocate for your loved one. Don’t take “no” for an answer; find answers for yourself and question things you’re not comfortable with. Listen to your instincts.
  • Reach out to others for support. Advocacy groups are a great resource for information about potential interventions and clinical trials, and people in the rare disease and special needs communities are very helpful.
  • Don’t become discouraged. The road may be long, but there is help along the way, and hope for advances with continuing research.

Lori has been able to navigate the process of caring for Gabe through her persistence and willingness to get involved. She feels fortunate to be working at Almac where her personal and professional interests align so well. May her story shine a light on the unwavering strength and dedication of patients, their caregivers, and the continued pursuit of answers by our clinical research Sponsors and partners.  

Do I need an IRT/RTSM for my clinical trial?

While IRT/RTSM systems are not always mandatory, they offer a range of benefits that can significantly enhance the quality and efficiency of clinical trials which makes them a must-have addition to virtually any clinical trial.

What is Interactive Response Technology (IRT)?

Interactive Response Technology is a software system used in clinical trials to manage patient enrollment, randomization, and drug supply throughout the study. It supports efficient data collection and ensures that participants are assigned to the right treatments and receive the correct medications.

For more details on IRT, check out:

What is IRT and How Does it Impact Clinical Trials?

What is Randomisation and Trial Supply Management (RTSM)?

Randomization refers to the process of assigning patients to different treatments (groups, arms, etc.) in a clinical trial, while Trial Supply Management refers to the handling of investigational products used in the trial.

Can an Interactive Response Technology/Randomisation system help my clinical study?

IRT/RTSM software applications are designed to automate and streamline various aspects of clinical trial management, including patient randomization, drug and investigational product dispensing and tracking, data collection and management, and regulatory compliance.

The decision to implement these systems depends on several factors, including the complexity of the clinical trial design, trial size, and geographical distribution of the study population.

In general, systems such as these are crucial for clinical trials that are:

  • Complex: Studies with multiple treatment arms, adaptive designs, or complex randomization algorithms.
  • Large in scale: Studies with a large number of participants or sites.
  • Geographically distributed: Studies with sites located in different countries or regions.

However, even small, simple clinical trials today can benefit from these systems help to reduce the risk of human error, guarantee data quality, and streamline study management – ultimately saving time and resources.

What are the benefits of an IRT/RTSM system?

Protects patient safety: Ensure patients are assigned to the correct treatment arm and that they receive the correct corresponding investigational product.  The system also ensures that the right study drug is available on site for patients at the time of their visit, preventing any interruption of treatment. 

Ensures data integrity: Provide centralized real-time data collection and management to reduce the risk of data transcription errors and ensure that data is accurate and complete. This saves time and resources for data analysis and reporting within the clinical trial.

Increased efficiency: Streamline study management by automating what would be otherwise manual tasks, such as patient randomization, drug dispensing, and data collection. This can free up study staff to focus on more strategic tasks, such as patient recruitment and data analysis.

Improved regulatory compliance: Provide various tools to demonstrate regulatory compliance with the execution of the clinical trial. This can ensure that sponsors are better prepared for trial audits and inspections.

Final Thoughts

If you are considering using an IRT/RTSM system for your clinical trial, it is important to carefully evaluate your needs and select a system provider that is right for your study. Sever factors to consider include trial complexity, size, geographical distribution, budget, and provider service capabilities.

Once you have selected a system, it is important to work closely with the vendor to implement the system and train your staff. With proper planning and implementation, this can be a valuable asset and a true partner to your clinical trial’s success.

What is Randomisation and Trial Supply Management (RTSM)?

Jennifer Ross

CT PA Director of Biostatistics

Kevin Venner

Group Leader, Biostatisticians

What is Randomisation and Trial Supply Management (RTSM)?

Randomisation and Trial Supply Management (RTSM) is another terminology for Interactive Response Technology (IRT).  This nomenclature is specifically calling out the main functions and utilities of IRT.  This term is becoming more popular in its use since it is industry specific for clinical trials. Almac Clinical Technologies’ RTSM / IRT platform is IXRS®3.

For more details on IRT, check out:

What is IRT and How Does it Impact Clinical Trials?

RTSM for Clinical Trials

The “R” in RTSM is randomisation (a primary utility of RTSM systems). Randomisation is the process for how patients are assigned to Treatments in a clinical trial with introducing a deliberate element of chance.

Randomisation in clinical trials:

  • Provides a sound statistical basis for evaluation of treatment effects
  • Balances treatment assignments
  • Ensures patients are similar in respect to known / unknown confounding factors
  • Protects study from selection bias

RTSM enables the global execution of randomisation across multiple sites in clinical trials.  This removes the need for site-specific code envelopes and other burdensome manual randomisation processes.

What Types of Randomisation Methodologies are included in RTSM?

The type of randomisation methodology included in an RTSM system depends on the design specified within the protocol.  Randomisation methodologies can vary from simple / standard to complex / highly customized.

For more information on:

  • Standard randomisation methodologies implemented in RTSM, click here.
  • Complex innovative designs impacting randomisation, click here.

How is Patient Randomisation implemented within the RTSM?

Determining how to implement randomisation first begins with the RTSM design team reviewing the protocol and identifying the type of randomisation methodology. The most common methodologies require a randomisation List (also referred to as Schedule or Scheme).  On occasion, the protocol’s design may require alternative algorithmic approaches (such as Minimization).

Based on the protocol review and assessment of the randomisation methodology, the RTSM experts draft the system’s specifications. This includes a document detailing the requirements for the RTSM system, as well as a separate document for the randomisation List or Algorithm. The appropriate Sponsor / Study team designees then review and confirm that these specifications meet the protocol’s expectations.

In following the finalized specifications, the RTSM development team programs the system with utilizing dummy randomisation List or Algorithm data.  The programmed functionality is thoroughly tested and validated by the RTSM testing team.  Upon test validation completion, the RTSM system goes through User Acceptance Testing (by the RTSM team and Sponsor team) and QA certification. Finally, once certified, the RTSM system is ready go live!

Who creates the Patient Randomisation List for the RTSM?

The randomisation List is created by a representative with the appropriate qualifications. This person is usually a Biostatistician who has proficiency in randomisation, RTSM randomisation functionality and statistical software coding.  Some Sponsors may have an in-house team responsible for creating randomisation Lists.  Other Sponsors may prefer to contract out to qualified vendors or third parties.

Almac’s Biostatisticians are uniquely qualified to generate randomisation Lists since they are 100% dedicated to randomisation and RTSM implementation / support.  They generate randomisation Lists with considering best RTSM implementation practices and provide recommendations (e.g., format, parameters) based on extensive experience. 

Types of randomisation lists generated for RTSM utilization may include:

  • Central / Stratified / Cohorts / Phases
  • Fixed block sizes / Variable block sizes
  • Maximum Tolerated Imbalance (MTI)
  • Replacement Randomisation / Re-Randomisation / Multi-Step Randomisation
  • Adaptive Designs / Complex Innovative Designs / Master Protocols

Almac Biostatistics group has a well-defined process for both randomisation List generation and Algorithm implementation to meet any protocol’s randomisation design needs. This includes randomisation List or Algorithm specification documentation, generation of Dummy / Live lists via SAS statistical software programming, generation of List Structure Reports (for ease of review / verification), List or Algorithm verification, and facilitation of sponsor designee approval.

Who imports the Patient Randomisation List into the RTSM?

The import of the randomisation List into the RTSM system is typically done by a representative within the RTSM organization.  This representative should encompass adept knowledge in randomisation List structure and RTSM randomisation functionality to ensure the list’s compatibility with the system and successful import.

Almac has a team of Biostatistics Data Managers who are responsible for importing randomisation List(s) in each study.  Almac’s Biostatistics group has a robust process for the data management and IXRS import of all lists which ensures high confidentiality / security and import compatibility / accuracy.  All randomisation List RTSM imports at Almac are thoroughly reviewed and documented to provide the highest quality.

Randomisation and Trial Supply Management Summary

Randomisation is an essential component of clinical trials and is considered critical to the reliability of the trial’s results.  Due to the high stakes of randomisation, the RTSM system should be developed by a RTSM company who has high level of knowledge / experience that Sponsors can entrust.  With the RTSM team, along with the Biostatistics group of Biostatisticians and Data Managers, Almac has the necessary attributes to effectively implement randomisation with the highest quality.

Are you also curious about the “TSM” in RTSM?

The “TSM” in RTSM is Trial Supply Management.  As an RTSM provider, Almac also exhibits expertise within this area. Check out the following for more information:

Elevating Study Experience in Decentralised Clinical Trials: How IRT Can Help

By Dan Ward
Product Manager

Sponsors are always seeking to make clinical trials faster and to improve the patient and physician experiences. Decentralised trials (or patient-centric trials) have become a critical tool in this pursuit.  Limiting a patient’s need to travel to a clinical site has become more common along with the advent of mail-order pharmacies and tele-health visits.

The first successful decentralised trial was completed in 2011 where there was a stronger focus on site-to-patient shipments, mostly occurring outside of the IRT.  This trend continued for the remainder of the decade.

With the onset of Covid-19 and ensuing lockdown, there was more emphasis placed on administering a trial with little to no patient in-person visits.  Allowing self-administration or with the help of a home health aide trials could continue.

Coming out of the pandemic, we’ll continue to see patients that are now accustomed to more at-home services and DCTs will continue to accelerate enrollment and improve patient satisfaction to administer a trial at home when possible.

Decentralised Trials

Will lead to accelerated enrollment and improve patient satisfaction to administer a trial at home when possible.

There are a lot of vendors in the decentralised space with features outside of the standard IRT.  With that, IRTs will need to be able to integrate, provide and utilise data to support protocol goals.

The IRT functions required to support DCT elements should be fully discussed and carefully considered as the protocol is being developed. While much is possible with a sophisticated and flexible IRT system, not everything that’s possible is advisable in each situation. It’s important to be able to distinguish functionality that’s essential from that which is only nice to have or even that which may add unnecessary complexity.

How can IRT add increased flexibility to clinical trials?

Decentralised Trials

IRTs must provide flexibility to support Direct-to-Patient (DtP) Supply Assignment and Dispensation:

  • Assign and Dispense in person at site.
  • Assign and Dispense via shipment from site to subject.
  • Assign and Dispense via shipment from depot to subject.

There are many variables that come into play with DCTs and flexibility is imperative for the IRT:

  • Patient preference – Patients may prefer to see the physician in person, face-to-face for at least some of their visits.
  • Protocol necessity – Patients may need to be seen on-site in certain instances for drug administration, assessments, or procedures that cannot be performed remotely.
  • Medical necessity – The need to see a patient at the site may change based on the patient’s medical progress.
  • The type of investigational product – Not all are good candidates for DtP shipments. Shipping drugs to patients may not be possible with controlled substances or with drugs requiring preparation or strict temperature adherence, to name a few.
  • Regulatory requirements – Varying regulations among participating countries may prohibit the use of certain DtP shipments. Depots may be required to have a pharmacist on staff to prescribe investigational product.

How do we ensure patient data remains secure?

Along with flexibility, the ability to coordinate the handling of patient data securely is equally important.  GDPR (General Data Protection Regulation) in the European Union and HIPAA (Health Insurance Portability and Accountability Act) in the USA are two of the regulations defining the protection of PII (Personally Identifiable Information).  IRTs must manage to allow access only to those entities that need it for Depot-to-Subject shipments.  Initially, the approach was to have the site provide PII to the depots directly and not involve the IRT with that data.  Moving forward, IRTs can facilitate storage and communication of PII using validated encrypted sources as well.

How can IRT help you manage drug supply?

Supply Algorithms must also be informed on what the configuration is for each subject visit.  Projections must take into account what supply will be needed for sites and what supply will be shipped directly to a patient.  If in-person visits are required, it should be included in supply projections for the site regardless of the patient’s expected dispensing location.  Site-to-patient visits will be supplied the same as an in-person visit since supply will come from site inventory.  Visits that are not in-person or site-to-patient should not be included in supply projections for the site.  However, supply algorithms may need to allow for additional buffer stock in case a patient who was expected to have supply delivered to their home has supply dispensed in person.

To support the site’s coordination of patients and visits, the IRT must provide as much guidance as possible.  IRT should clearly indicate the patient’s expected dispensing location.  Site users will need visibility of upcoming visits requiring shipments to patients to allow for supply transit time.  Visit registration should allow sites to designate the dispensing location and the expected dispensing location of the next visit. Visit details (historical) should display the dispensing location indicated at the visit.  IRT should clearly indicate the patient’s expected dispensing location in reporting and audit documents.  Site users should also have visibility to upcoming visits requiring shipments to patients to allow for supply transit time.

What are some common considerations outside of the IRT with DCTs?

  • Acknowledgment of Shipment Receipt for a Patient at Home – Site, Courier or Patient are all options for required oversight of proof of dispensing.
  • Temperature Monitoring – For patients receiving investigation product at home, viability of investigational product may require a site tele-visit, courier update or home health aide to complete the determination.
  • Post-Dispensing Chain of Custody – Accountability, Returns and Destruction of supply shipped to a patient will need to be considered.  Patients can return supply to the site to determine consumption and handle return to the depot or destruction.

In Summary

  • Decentralised trials, designed and conducted properly, offer improvement of patient centricity by lessening the burden of trial participation, which in turn speeds patient recruitment and strengthens retention.
  • The IRT systems that support Decentralised Trials must be properly configured to ensure that patients are treated per the protocol requirements and that all trial processes are efficient and compliant.
  • Proper configuration will require system flexibility (the ability to adjust workflows to accommodate all variations of hybrid trials) and the ability to easily integrate with the other technologies that make up the eClinical landscape.

Beyond the audit: Taking quality and compliance to new heights with your IRT

Beyond the audit: Taking quality and compliance to new heights with your IRT

By Matt Lowrie

Quality Assurance and Regulatory Compliance Manager

The IRT in your clinical Trial

IRT lives at the center of the eClinical world.  It is often one of, if not, the first captures of subject screening, randomisation assignment, stratification, and drug dispensation.  The IRT has become far more complex and involved than it was 20-30 years ago. 

It is critical that the IRT is on the critical path for the trial, it is also critical that the IRT remains in alignment with the Clinical Trial Protocol.  It’s best to remember those two key items when building the system.  The IRT often interacts with other eClinical systems, which means the data flow should be looked at and it’s important to consider these facts and how you will maintain adherence to the various regulations not just during the trial, but during inspections and data reconciliations. 

Selection and Design of the IRT

Given the expense of a clinical trial, and the spend for an IRT, getting the wrong one could destroy the total investment.  To help you determine what and where you should be looking, there are several factors that need to be assessed.  Part of that assessment is an audit; however, you should be creating a relationship that is ongoing and not supported by an every two-year visit.

Step 1 really should be the Vendor Selection. This is a fantastic opportunity to get yourself a demo of the system.  Even if you have used it before, see what is new and what the system can offer you up front and out of the box.  This is a chance to see if you can use what already exists to decrease costs, speed up timelines, and simplify your IRT. 

Once completed I encourage everyone to open the dialogue with the IRT vendor across the stakeholders.  This should absolutely include Quality and not just for scheduling a prequalification audit.  The conversations should start around performance indicators, applicable documentation, support, and the best way to partner and maintain oversight of the IRT (or any eClinical system!).  When we work with our partners, we make it clear- they are not alone in the trial.  We are absolutely here to help and support along the way. 

It is also important to create your Subject Matter (SME) team: who will provide input and approval to the UAT strategy document and UAT test scripts? Who will help execute the scripts? What design enhancements or changes are dealbreakers to closing the UAT Phase? Who needs to give final approval to move the system Live?

All of this before the system is ready to go live. 

Support and Engagement

Once your study is live, it is imperative to maintain oversight on the trial.  This may include regular data reviews, weekly meetings, or monitoring of the overall relationship.  There are plenty of areas to consider, and luckily, you have a partner who does this across a large swath of other clients.  Utilize their expertise and experience.  I often see this made into something that is over complicated and resource heavy. It doesn’t need to be, the right people on the right topics can make this seamless and help fulfill your regulatory obligations regarding vendor/sponsor oversight. 

It’s more than just a couple of meetings.  There are aspects that should be considered such as the availability for day-to-day support, developers, and how the IRT will be supported during an inspection.  This is where having a relationship that is open, and honest really helps the overall Quality and compliance of the system.  Having a partner who is willing to share ideas and best practices is crucial for smooth and efficient trials.

At Almac, we support several inspections each month.  The most successful of those are with our partners that we have a quick strategy meeting (30 minutes) to organize, understand scope, storyboard, and ensure all the necessary documentation and data is at the ready before the inspection even begins.  Those 30 minutes save days, if not weeks, of churn, CAPAs, and updates to resolve findings. 

The key principle overall is to realize it is indeed a partnership and a relationship.  It needs to be treated as such with everyone involved utilizing their strengths and their partners’ strengths. 

Final Thoughts

There are plenty of opportunities to demonstrate oversight, however, as an industry we need to move away from the outdated method of simply performing an audit.  Audits are great as a verification, they are fantastic to help assess compliance and process, however, they cannot be used as the sole mechanism for oversight.  You have a partner for your IRT who is an expert, utilize them.  Ask them what they see as best practices, listen to their opinions on system design, ask about where they see potential risks or failures, and lean on them to identify how to best approach topics like User Acceptance Testing.  Most importantly partner together.

Entering the World of Complex Innovative Designs: What does this mean for the Randomisation?

By:

Jennifer Ross

CT PA Director of Biostatistics

Complex Innovative Designs are emerging within many clinical trial protocols. These designs often require adaptations and flexibility for the randomisation, similar to Adaptive Designs. Before entering the world of Complex Innovative Designs, it is important to understand the basic concepts of Adaptive Designs and how they may impact randomisation.

What are Adaptive Designs?

An Adaptive Design allows for a trial to adapt mid-study.  These adaptations are planned and specified in the study’s protocol.  The FDA defines adaptive designs as “a clinical trial design that allows for prospectively planned modifications to one or more aspects of the design based on accumulating data from subjects in the trial” in their 2019 guidance document Adaptive Designs for Clinical Trials of Drugs and Biologics.

What are Common Adaptations that Impact Randomisation?

Common adaptations that impact randomisation include:

  • Introducing new treatments
  • Dropping existing treatments
  • Pausing and restarting treatments
  • Adjusting treatment allocation ratios or assignment probabilities
  • Sample size readjustment

How is Randomisation different from a Traditional Design compared to an Adaptive Design?

In a traditional randomisation design, the included treatments and allocation ratio are usually the same for the entire study. For instance, subjects are randomized to one of two treatments in an equal allocation ratio (1:1). One randomisation list is generated and used for subject randomisation across the study’s duration.

Whereas in an Adaptive Design, the randomisation design may change depending on the planned adaptations. For example, a study starts with three treatment groups assigned in a 1:1:1 ratio. Then based on the results of an interim analysis, one of those treatments could be dropped or a fourth treatment could be added. Therefore, the randomisation could change to either assigning in a 1:1 ratio or a 1:1:1:1 ratio. One randomisation list that is fixed with three treatments in a 1:1:1 ratio would not support the possible adaptations.  Additional randomisation lists or some type of flexible randomisation would be needed.

What are Complex Innovative Designs?

Complex Innovative Designs are similar to standard Adaptive Designs, but typically include additional layers of complexity.  Complex Innovative Designs have benefits such as increased flexibility and efficiency in drug development, the ability to share control arms, central electronic data capture systems and patient centricity. They are usually able to identify treatments that are effective and ineffective quicker than traditional trials.

Complex Innovative Designs include (but not limited to):

  • Master Protocols (Basket, Umbrella, Platform)
  • Biomarker-Targeted Treatments
  • Bayesian Response Adaptive Randomisation
  • Complex Dose Ranging / Dose Finding Cohorts

How do Complex Innovative Designs impact the Trial’s Randomisation?

Complex Innovative Designs that include randomisation adaptations are similar to standard Adaptive Designs, with additional dimensions of complexity.  Think of standard Adaptive Designs as one dimensional where the same adaptations are applied to the entire study.  If a treatment were dropped, it would be excluded from the study’s randomisation list. Whereas Master Protocols are studies that have multiple dimensions such as different subgroups, sub-protocols, sub-studies, etc.  In this Complex Innovative Design case, a treatment may be dropped in one subgroup’s randomisation list, and in another subgroup, a treatment may be added.  The adaptations need to be managed independently for each dimension’s (subgroup) randomisation. 

Another example is the case of biomarker-targeted treatments, where only subjects who are biomarker-positive are eligible for that biomarker-targeted treatment, and those who do not have the biomarker are ineligible.  Here, there is varying eligibility based on the included treatments that may or may not target specific biomarkers. The varying eligibility needs to be managed to allow or not allow assignment based on biomarker-targeted treatments and biomarker presence.

Due to the complexity involved, the implementation and management of randomisation for these types of designs often require a sophisticated Interactive Response Technology (IRT) system.  

What is Successful Implementation for Randomisation of Complex Innovative Designs?

Successful implementation of Randomisation is all about being able to execute the adaptations with minimal disruptions since a key characteristic of Complex Innovative Designs is efficiency in drug development.  Take the case of a study implementing a single randomisation list with the initial study parameters (e.g., included treatments / ratio) without accounting for any possible adaptations. With this set-up, if a new treatment is introduced, then a new randomisation list needs to be created and imported into the IRT system. While this approach works, it is disruptive since it incurs time and effort.  A more efficient approach would be if the IRT included a flexible randomisation scheme with user ability to enter in the adaptations in real-time without having to create a new list.

What is the Optimal Level of Flexibility for a Complex Innovative Design’s Randomisation?

Every study is different, which means that each study’s optimal level of flexibility also differs. Planned adaptations are specified within the study’s protocol. Some protocols may explicitly detail the adaptations (e.g., which treatments could be added, which treatments could be dropped), while others may not. For example, a protocol states that new treatments can be introduced throughout the study’s duration as they are discovered. Since they are yet to be discovered, they cannot be explicitly specified in the initial protocol and will be included in an amendment once identified.  If new treatments are expected, but not yet identified, the IRT randomisation could be built as flexible to allow new treatments to enter into the scheme dynamically through a user interface. If the protocol specifies that the ratio(s) can be adjusted, that should be incorporated into the IRT’s randomisation as well.

What is Recommended to Achieve the Optimal Level of Flexibility for a Complex Innovative Design’s Randomisation?

To be able to achieve the optimal level of flexibility, it is recommended to begin discussions on randomisation implementation early in the planning phase of the protocol.  These discussions should include the key stakeholders such as the study’s clinical operations leaders, program managers, biostatisticians, clinical supply managers, along with the relevant vendor partner roles such as IRT’s biostatisticians, project managers, design, and programming experts.  It is equally important to choose an IRT vendor that has the experience and expertise in implementing these complex innovative designs to be effective consultants and partners rather than simply order-takers.

Almac Clinical Technologies has the attributes necessary to successfully implement flexible randomisation for Complex Innovative Designs. Almac has a Biostatistics team that is 100% focused on IRT randomisation, and an Adaptive Design Center of Excellence comprised of cross-functional (development, testing, QA, design, project/program management) expertise to ensure every area is considered in achieving the optimal level of flexibility.

Streamlining Clinical Trial Supply Management and Reporting with Drug Pooling in the IRT World

By:

Paul Kearney

Clinical Technologies Client Design Solutions Lead

Dan Ward

Clinical Technologies PA Product Manager

What is Drug Pooling?

Effective supply management and accurate reporting are vital components of successful clinical trials. In the Interactive Response Technology (IRT) domain, drug pooling has emerged as a valuable technique for optimising logistics and enhancing data visibility. By consolidating drug supplies and providing comprehensive reporting capabilities, drug pooling streamlines supply management and facilitates monitoring of shipment and depot activities. In this blog post, we will explore the practical benefits of drug pooling in the IRT world, focusing on supply management and reporting from the perspective of supply managers.

How does Drug Pooling Help Supply Management be More Efficient?

In the context of IRT, drug pooling offers supply managers several advantages in managing clinical trial supplies. Here’s how it works:

  1. Centralised Inventory Management: Drug pooling establishes a centralised inventory where all study drugs are stored. This eliminates the need for separate inventories for each study in a programme, simplifying supply management.
  2. Comprehensive Supply Visibility: The IRT system provides supply managers with a holistic view of drug allocation and utilisation across multiple studies within the programme. This visibility allows for optimised planning and distribution of pooled supplies.
  3. Real-time Shipment Monitoring: Supply managers can monitor the movement of drug supplies in real-time, tracking shipments from the central pool of depots to individual studies and their sites. This helps ensure timely delivery and enables proactive management of any shipment issues or delays.
  4. Depot Activity Tracking: The IRT system captures and records depot activities, providing supply managers with detailed information on inventory levels, drug movements, and storage conditions. This data enables effective inventory management and ensures adherence to regulatory and quality standards.

 What are the Benefits of Drug Pooling in Supply Management?

Drug pooling in the IRT world offers notable advantages for supply managers:

  1. Streamlined Logistics: Centralising drug supplies simplifies logistics by eliminating the need for multiple inventories. Supply managers can efficiently allocate and distribute pooled supplies based on study requirements, reducing administrative burdens, and optimising the supply chain.
  2. Enhanced Resource Utilisation: By pooling drugs, supply managers can optimise procurement and inventory management, reducing costs associated with excess or underutilised supplies. This improves resource allocation and maximises the efficiency of clinical trial operations.
  3. Improved Shipment Visibility: Real-time monitoring of shipments allows supply managers to proactively address any issues that may arise during transportation. This ensures the timely delivery of study drugs to the intended sites, minimising disruptions and maintaining the continuity of trials.
  4. Accurate Depot Activity Monitoring: Tracking depot activities provides supply managers with insights into inventory levels, drug movements, and storage conditions. This enables proactive management of stock levels, identification of potential bottlenecks, and ensures compliance with regulatory requirements.

 How Does an IRT Impact Data Reporting and Insights?

In addition to supply management, the IRT system supports comprehensive data reporting for supply managers:

  1. Study-specific Allocation: Supply managers can access detailed reports that indicate which study within the programme each drug shipment is allocated to. This enables accurate tracking of drug distribution and ensures that supplies are appropriately allocated to meet the needs of individual studies.
  2. Shipment and Delivery Reports: The IRT system generates reports on shipment activities, providing information on delivery timelines, transit times, and any deviations from the expected schedule. This helps supply managers monitor and evaluate the efficiency of transportation logistics.
  3. Depot Activity Reports: Detailed reports on depot activities offer supply managers insights into inventory movements, storage conditions, and any incidents or discrepancies. This information facilitates proactive management, enabling prompt corrective actions and ensuring compliance with regulatory guidelines.

Conclusion

Drug pooling within the IRT world empowers supply managers with streamlined supply management, real-time shipment monitoring, and comprehensive reporting capabilities. By centralising drug inventory and providing detailed visibility into drug allocation, shipment activities, and depot operations, drug pooling optimises logistics and enhances data-driven decision-making. Supply managers can effectively allocate resources, monitor shipments, and ensure the smooth functioning of clinical trials within a programme of studies. Leveraging the power of drug pooling in the IRT domain accelerates research efficiency, reduces costs, and contributes to the successful execution of clinical trials.

ART™: Crafting an Automated Tool for Accountability and Reconciliation Tracking

By: Kathleen Williams, CPS Manager, Dan Ward, Product Manager

Recent updates to regulatory guidance (EU regulation 536/2014) mandate that clinical trial protocols include details regarding the tracing, storing, returning and destroying of all investigational products throughout the lifecycle of the trial. This mandate has moved accountability, reconciliation, returns and destruction from after thoughts to key considerations during the planning phase of a trial. End to end IP traceability arrangements need to be made and documented in trail protocols which in turn need IRB approval.

Almac’s ART™ feature can assist in organizing and defining these plans for trial leaders. ART™ makes planning for accountability, reconciliation and destruction seamless.  It highlights all details needing consideration in advance and ensures the end-to-end traceability of investigational products is obtained.

What is ART™?

ART™ (Accountability & Reconciliation Tracking) is an electronic chain of custody solution that incorporates all IP events—from product release through to product destruction in a single system. It’s a single solution to comply thoroughly with GCPs and GMPs. ART™ features validations and flexible, configurable workflows that streamline the accountability and reconciliation processes.

Why do Almac’s clients select ART™?

The accountability and reconciliation process is known for being time-consuming and error-prone, two characteristics that result in it adding significantly to trial costs and timelines. The task of reconciling discrepancies in supply records that have accumulated over the course of a trial often adds as much as two years to the study closeout phase.

The effort to reconcile discrepancies before the destruction of kits at depots is magnified by the sites’ lack of compliance with accountability processes and tools. ART™ helps sites maintain compliance and complete records in order to significantly reduce discrepancies at the source.

Depots can now focus on managing their returns and destruction processes without the burden of identifying and resolving site issues. Supply managers can finally have real-time visibility into supply status and can monitor and report on compliance with Good Manufacturing Practices (GMP) without the need to construct complicated reports by collecting and assembling data from multiple sources.

What are the benefits?

ART™ helps sponsors and CROs realize time savings that come from easy setup, streamlined site operations, error reduction, and discrepancy resolution. Additionally, real-time validation checks at the time of dispensing and ongoing visibility to the condition of drug supplies throughout the supply chain improve compliance, reduce risk to patient safety, and safeguard against trial delays.

In fact, inadequate record keeping and inadequate accountability for IP are two of the most common issues cited in FDA warning letters.

Users can analyze and cross-reference patient records with supply records, all on a single screen. They can assess and report on the progress of the entire chain of custody, again in real time. And, they can perform root-cause analysis of issues relating to any IP event so they can address them as soon as possible.

What was being used before ART?

In many cases, accountability and reconciliation is still paper based, and in others it is supported by fragmented solutions that do not completely solve the problem. For example, accountability solutions that do not prevent discrepancies from creeping into data sets do little to improve reconciliation. Solutions that fail to link the drug assignment to the chain of custody records don’t provide a continuous, unbroken lineage of what was assigned, dispensed and returned, so they cannot confirm study compliance with regard to IP consumption.

In contrast, ART™ is integrated with the IXRS®3 system and provides visibility to, and an audit trail of, product conditions and movement throughout the trial. This improves patient safety, reduces trial risks, and strengthens monitoring and compliance while cutting costs and shortening timelines.

How do I fit ART to my standards?

ART™ is configurable to allow for 1 or 2 or even 3 step approval of accountability/reconciliation information. It can allow for correction of data during reconciliation or requesting for reaccounting. It can track consumption at the kit or unit (e.g. pill or other kit part) level. It can also be configured to report and alert for any discrepancies.

How can my trial achieve the best results?

Planning for accountability, reconciliation, returns and destruction of investigational product should be considered as important as planning for its release and distribution. Discussions related to this topic should be conducted as early in the lifecycle of a trial as possible. This will not only ensure compliance with EU regulation 536/2014, it will also save time and resources previously spent maintaining error-prone paper based systems.

During the design phase of your Almac IRT system, several considerations will be discussed in efforts to define and deliver an efficient vehicle to record the journey of all investigational product employed in a trial. Does IP need to be accounted for at a dosage unit level or a dispensing unit level? Will IP be returned and destroyed at sites? Or will IP need to be sent to a depot or other central location for destruction after being returned and accounted for at the site level? The Almac ART™ functionality is flexible enough to accommodate any combination of these scenarios.

ART™ guides users through steps to ensure complete collection of data and provides error-correction workflows— benefits that can only be realized when the system is used routinely. ART™ is best used as a trial progresses. It is not intended to be used sparingly or used just at study close out. Using ART™ as it is intended throughout the duration of a trial will result in accurate data collection and prevention of study close out delays.

UAT: A Custom-Built Roadmap to Kick Off Your Clinical Trial Journey

By Antoinette Walsh

Director of Technical Solutions

What is the purpose of UAT?

The purpose of a UAT is to ensure the software, in this case IRT, was built to the specifications. Sponsors have a regulatory responsibility to perform UAT as outlined in EMA GCP 600788, Section 2.2.4.

UAT is your opportunity to get your hands on your custom-built solution to ensure it will meet your end users’ needs as you envisioned. This is not the time to ”Break the System” (your vendor team has likely already performed this), but you do want to run through transactions as your end-user would typically. You will want to ensure not only are the transactions completing as expected, but the associated reporting and data exports are accurate. If you do find any issues, UAT is a more cost-efficient check point to correct them prior to production use.

What are the keys to a successful UAT?

You will have limited time to execute your UAT and so you need to make sure you have a plan of action from the beginning of your project. You will also want to ensure your other vendor’s IRT integrated systems are ready at the same time to ensure your data is integrating across systems as expected, mirroring how the system will be utilized in production end-to-end. Partnering with a vendor with expertise on the UAT script creation process can help to streamline many of the activities that happen during this time.

Plan

Create a project plan: The IRT is just one system for your clinical trial. A best practice is to ensure your integrated systems are available in a UAT environment at the same time as your IRT. This will help you validate test files as you execute IRT transactions

Create your Subject Matter (SME) team: who will provide input and approval to the UAT strategy document and UAT test scripts? Who will help execute the scripts? What design enhancements or changes are dealbreakers to closing the UAT Phase? Who needs to give final approval to move the system Live?

Prepare

Review the software specifications and prepare the UAT testing scenarios you plan to cover during the software build in a UAT strategy document. The document should be a high-level list of key scenarios that must be covered in the plan. Once you have identified your strategy, get feedback on the UAT approach from your stakeholders including internal SME’s and external vendors. When all parties have reviewed and requirements are stable, you can draft your formal scripts off this scenario document.

Your test scripts should focus on Critical/High-Risk scenarios. Leverage your vendor’s core and configurable functionality to limit your testing to the customized areas of the software. A great place to bring efficiency into your script is to re-use data created earlier in the script for later transactions. For example, you can screen a subject and carry through Randomization, Kit Assignment Visits, and End of Treatment rather than using new subjects for each feature. A step further for more advanced UAT teams to consider is using test automation tooling to speed up repetitive processes such as subject data setup.

How will you execute your scripts?

There are several ways a UAT can be executed. Here are a few we recommend and considerations you may want to think about.

  • Independently: One user executes all scripts
    • Team based: Will the team use the same script or different scripts? What methodology will be followed? Here are a few types of team-based UAT processes we have seen in our experience:

UAT Methodologies

How will the team collaborate and communicate questions/challenges/concerns?

How technology can be harnessed to bring together virtual/global teams?

Perform

The clock is ticking! Execute your scripts and add extra ones as you think of more you missed. Communicate status with key stakeholders each day in summary form. Keep a log of issues/questions and close out any showstopper issues with the vendor prior to UAT completion. Defer any non-priority changes to a later version of the software as time allows.

Approve

When all parties have completed their tests and agree that the system was built to the approved requirements, you can now give approval to the vendor declaring the acceptability of the results and request that the system or change be moved to the live environment. Congratulations! You have successfully completed the UAT Phase and meeting your regulatory obligations to ensure suitability of the system!

Final Thoughts

User Acceptance Testing is a software process that gives sponsors the opportunity to run through real-world transactions prior to system launch. UAT functions as a cost-effective checkpoint that ensures efficiency, suitability, and end-user performance as envisioned. 

Transforming Patient Data with Interactive Responsive Technology (IRT) Data Integration

What is Interactive Responsive Technology (IRT) data integration?

By definition, Interactive Responsive Technology (IRT) data integration is a mechanism to combine data from multiple source systems and add interoperability between systems. IRT is a vital trial data source and, therefore, directly responsible for sending/receiving data from one application to another.
Clinical data integrations are often required as combining data from more than one eClinical system adds the necessary context needed to transform data into valuable and actionable information. Integrations also help build a more holistic view of all data for the end user.

How is IRT data sent?

Safe data transmission can use several communication protocols, file formats, and authentication methods. While Almac Clinical Technologies’ IX®S3 IRT system can accommodate all commonly used transmission methods, selecting suitable technical parameters depends on the systems’ capabilities involved in the integration.

Almac Clinical Technologies’ standards include as much automation and self-healing capabilities for data transmission as possible. We also strive for the most secure methods possible between the two integrated systems. These standards ensure the timely delivery of adequately protected data and require no manual intervention.

Sometimes the destination system, source system, or operational process IXRS 3 is integrating with does not possess the capabilities to meet these standards. Almac Clinical Technologies can accommodate these integrations once the associated risks are identified and accepted.

What types of IRT data integrations are most used?

IRT data integrations are contracts between two systems. Therefore, the delivery team must consider both systems’ capabilities in selecting the correct interface that works well with both sides of the integration.

Common examples of the systems IRT integrates with:

  • Electronic Data Capture (EDC)
  • Clinical Trial Management System (CTMS)
  • Clinical Supplies
  • Optimization
  • Central Labs
  • Clinical Assessment

Common integrations technical interfaces used:

  • Web APIs (REST)
  • Web services (SOAP)
  • Secure file transfer (SSH, TLS)
  • Web portal posting (HTTPS)

What considerations should be made?

Key considerations should be made when determining the data integration needs of your trial.

Generating Business Value

System interoperability and data sharing are two primary high-level purposes for integrations.

System interoperability is easiest defined as sending data between systems to drive action in the destination system. These integrations often have the highest business value as they do much more than sync data between systems. A simple example of system interoperability is screening a patient in IRT and sending the relevant data to create the patient and required eCRFs in the EDC system. In this model, each system owns and maintains its data.

Data sharing is syncing data between systems, most often to support reporting use cases. The shared data may also be required for actions in the destination system to occur but does not directly initiate those actions. If these integrations are carefully specified, it is easier to understand which system owns the data and is responsible for corrections and maintenance. For example, when a human makes a mistake in one system, these data-sharing integrations propagate those errors to other systems with little warning. These scenarios often require manual data changes in one or more systems.

Information Security

As with any secure system, credentials and authorization is a component of data integrations. It is important to consider that the ‘sender’ of a data integration is an application, such as the IXRS3 application. All account credentials are stored in a secure location, and access is restricted to staff who are trained on Data Services policies and procedures. 

Providing account types for data integrations that have the same settings enforced as other individual user types is not ideal. For example, an account that is set to expire every 30 days by an end user will be managed during user log in attempts. For a data integration, an individual is not manually logging in. Accounts with these same settings will result in delays in receipt of data due to file failures, and additional support for managing password resets and account lock outs. These integrations should use service accounts that follow with the security policies for service accounts set by your organization’s information security professionals.

Data

Defining the exact data to be sent is critical to the success of the integration. Inclusion of additional data that is of no value to the specific analysis being performed will subsequently require additional processing to exclude the data.

Data may or may not be editable. When data can be edited, ensuring to account for how edits will be sent is important. Even properly working integrations will amplify human data entry errors by propagating the wrongly entered data across integrated systems. It is important to ensure that the systems have clear roles and responsibilities for correcting and editing data.

File Type Extension

Almac can submit data in all commonly required file types. Ensure to consider the file type that is required by the receiving system and/or the individual who will be receiving and analyzing the data. Receiving the data in the appropriate file type will avoid any unnecessary file type conversions.

Frequency

How often is the data needed? This may depend on the type of data, whether it be unblinded or blinded.

File Types

Data integrations will either contain:

  • Cumulative (all data)
  • Incremental (all data since latest file)
  • Transactional (one message per IRT transaction).
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