Author: brendanhagan

By: Casey Doyle

Clinical Technologies PA Group Leader

What impact can IRT have on my supply chain structure?

There are many challenges and pressures within clinical trials. Some, if not most, of those challenges and pressures can be relieved through optimizing clinical supply within a validated IRT solution. From depot management to accountability and reconciliation efforts, IRT systems are designed with the flexibility to automate steps, provide continuity, and eliminate concerns for patient dosing and site stock outs.

Supply chain can be a delicate dance between managing the needs of sites, depots, vendors, etc. The more sites, depots, and kit types to manufacture and distribute, the more cumbersome it becomes to effectively manage needs across multiple countries in a variety of time zones. IRT systems can help you seamlessly integrate your different supply chain models to meet the needs of your clinical trial by providing the flexibility of multiple resupply strategies, automated drug ordering, shipping for temperature sensitivities, alerting for expiry and low stock, inventory at a glance through blinded and unblinded reporting, tracking, and return of reconciled supplies and so much more.

An IRT system can additionally incorporate capabilities such as drug pooling which can provide plasticity of inventory across a study by consolidating supply and streamlining management of depot activities. This can be particularly useful for program studies that have very high-cost materials or for those forecasting potential manufacturing delays due to resourcing of material. Drug Pooling allows supply to be shared across multiple protocols with lesser need for multiple manufacturing runs as well as reducing the carbon footprint of your trial(s) through the reduction of depot transfers.

What efficiencies in logistics can an IRT system provide?

One of the more difficult pieces of clinical trials can be ensuring that your clinical supply shows up where it is needed and when it is needed with a minimal number of disruptions. An IRT solution can help take care of both the “where” and “when” additionally providing data visibility to “how” clinical supply is being used.

IRT systems can automatically determine where clinical supplies are needed and raise shipments for clinical sites based on various factors such as static values, buffers, titrations, projected visits, damaged supply, etc. While the majority of when a shipment arrives at the site is impacted by the distributor, an IRT system can indicate to sites and clients an estimated delivery date based on calculated shipping estimates as well as provide delivery tracking capabilities through customized data integrations. This helps sites more accurately manage their subject’s visit schedule and ensure that supply will be available when the subjects are on site. Clients and sites have the ability to monitor how supply is being used through real-time reporting within an IRT. Reports allow clinical teams to monitor subject visits including completions and discontinuations, as well as, to monitor supply at sites as well as across depots.

What communication capabilities does an IRT offer for supply chain management?

With an IRT solution, there is no longer the need to play middleman with 3^rd party depots. Drug order forms can be customized to meet the needs of your distributors and are automatically sent to specified depot contacts upon order creation. With advancements in technology and expanding needs for faster delivery, depot integrations are another way in which shipment communications and inventory updates can be managed shortening the time it takes to facilitate orders from depot to site.

IRT also provides alerting which can be customized to the needs of the trial. Alerts can be transactionally triggered based on events, for example, acknowledgment of a shipment that was outside of temperature range. Additionally, alerts can be configured to trigger at various thresholds such as when depot inventory falls below a certain count, or if a depot has completely stocked out, etc. Alerts can be formed to meet a variety of scenarios and provide a different way of monitoring milestones without continuously being connected to the IRT application.

What if I have unique or highly complex trial needs?

The leaders in IRT understand the complexities of modern clinical trials and can customize your IRT to meet any unique needs. From multi-depot ordering to drug pooling to pre-enrollment drug reservation and beyond, there is an IRT solution to fit your trial’s demands.

Is it worth my budget to consider using an IRT?

Absolutely! An IRT solution is an investment in your clinical trial. Not only is it a time save at the end of the trial for reporting data pulled directly from the IRT as well as from not having to manage a paper trail, but it additionally saves time for clinical staff and patients who just want the most efficient way of participating. An IRT system allows sponsors and clinical sites to focus on what is most important, the patient. The use of an IRT system allows you to more effectively plan and adapt. Protocol changes happen and they happen frequently in some cases. IRT systems can be flexible and provide the tools to help you adapt your supply to meet the needs of the trial in addition to allowing study teams to make informed decisions in a timely, controlled manner. Knowing the industry and the ever-changing variables, there can’t be a one-size-fits-all solution. Leading IRT vendors including Almac Clinical Technologies offer multiple levels of IRT solutions to fit a variety of budget needs.

By David Pondelick
Technical Solutions Manager, Development

Entering accurate data into IRT, EDC, CTMS, eCOA, Drug Management Systems, Lab Systems, and more is hard.  Manually entering the same data accurately into many different systems is monotonous and prone to error.  Ensuring that the data is entered by hand into all relevant systems in a timely manner can be nearly impossible.  This is one of the places integrations can greatly simplify site user experience, better regulatory confidence in data gathered, and provide timely data distribution.  However, integrations done wrong can lead to headaches and low data confidence.

Who should be involved in integration design?

Communication is most accurate and efficient when it is direct.  While Sponsors should absolutely stay in the loop in integration implementation efforts, the Sponsor is responsible for the trial after all, introducing your vendor teams together to work on integrations directly will reduce misunderstandings and promote cohesion with the systems involved in your clinical trial.  Sponsors should always control what information is passed from vendor to vendor, but the details of how that happens are more valuable to the organizations integrating with one another.  This approach is valid even for integrations with Sponsor systems; there is likely an internal group, that acts as a vendor, responsible for managing and integrating those systems with clinical trial vendors.

What questions does the Sponsor need to answer?

Where should data originate, which system owns the data, and what other systems need it?

The sponsor owns the data collected in the trial and is responsible for ensuring only the systems that need access to that data have access to it.  Not every system needs every bit of collected information; in fact, some data is privileged by law (e.g. – Personal Identifiable Information) or by Sponsor policy (e.g. – trial results).  Some data may be unblinding and shouldn’t be stored in systems where blinded users could gain access to it.  Further, there generally isn’t value in storing information in systems that don’t need it for a specific purpose.

To reduce data discrepancies between systems and regulatory data reconciliation questions, one system should be designated as the “owner” (usually the originator) such that only that system can update the data it’s responsible for.  If data does need to be updated or removed, then it must be documented what is allowed to be updated as well as which other systems should receive that update.  Consider what should happen in those downstream systems when integrated data is updated.

How often does data need to be processed by other systems?

Some information is time sensitive in order to complete protocol processes appropriately (e.g. – labs taken in the morning providing information needed to dose a patient that evening).  Other information just needs to be distributed eventually (e.g. – patient demographic information for reporting).  Near real-time integrations are absolutely possible (we’ve built & maintained many for the IXRS), but they bring more complexity, potential pitfalls, and cost than scheduled/routine integrations.  Real-time integrations require nearly 100% uptime of both the sending and receiving system, a robust retry process, and real-time support; all things that are expensive for a vendor to ensure. When real-time isn’t a top priority, sponsors tend to rely on asynchronous integrations for their reliability and lower cost to implement & maintain.

Does your organization have security policies that apply to vendor integrations?

GCP (Good Clinical Practice) requires secure transmission & storage of clinical trial data.  Some sponsors have begun taking an active role in ensuring the integrations handling their data meet the latest security policies in order to get ahead of regulatory scrutiny around the protection of information.  Almac requires using modern TLS ciphers and we recommend using a strong authentication method; however, your organization may go further.  Ensure all your vendors can support your security needs.  Identifying account & password expiry rules will allow your vendors to be prepared for expiry and proactively plan password updates, preventing data from being stuck due to expiration.  Even if your organization doesn’t have specific security policies, it is best practice for vendors to have periodic security assessments of their systems in order to protect your data.

How can I make my vendor integrations easier?

If you are routinely having vendors integrate, consider requesting they standardize the process to your needs; already at Almac, we have several organizations in our Partner Network that we’ve built standard integrations with as well as with many additional organizations outside of that network.  Having the above questions answered before introducing your integrating vendors together will also significantly reduce the time it will take to design, develop, and test new integrations.  Remember that integrating vendors together takes time and letting your vendors know as soon as possible that the integration is a desire will help everyone better plan for your needs.

Ensuring your vendors have separate development/testing and production environments with separate user accounts allows for future changes to not impact production until everyone is ready for production to be updated.  Separate accounts also reduce the likelihood of non-production data from erroneously being sent/received into production systems.  Separating accounts per trial further reduces the opportunity for study data to impact other studies in unplanned ways.  Having development/testing environment(s) available for design and testing is critical for ensuring the best quality integration is designed and built.  Ensuring the production release of integrated systems are coordinated, reduces the need to backfill information later due to disparate system capabilities being live.

All vendors should have contacts identified to be informed when platform/application changes impact integrated systems.  Ensuring your integrated vendors are aware of those contacts, and proactively inform those contacts of upcoming changes or known issues, allows your vendors to be quicker in handling updates & issues without communication needing to be funneled through you.

Why trust Almac Clinical Technologies?

We’ve integrated the IXRS with just about every type of system imaginable (EDC, CTMS, Drug Manufacturing/Supply/Distribution/Optimization Management Systems, DCT, Central Labs, eCOA, Personalized Patient Care, Medication Compliance, and more) in just about every way possible (imports, exports, bidirectional; flat files, XML, JSON, SAS, Excel, proprietary formats; APIs, sftp, Google Drive, AWS; real-time, near real-time, hourly, daily, weekly, monthly, on demand; our capabilities are essentially endless) on hundreds of unique studies.  We have an experienced team of integration professionals made up of Solutions Leads, Developers, and Testers specifically trained in designing, developing, and testing integrations.  If a vendor is capable of being integrated with, then we can integrate with them.

By Devina Lahaie

Business Development Manager

“The days are long but the years are short.”₁ To me, this quote perfectly encapsulates the experience of being a parent with busy mornings getting your little one out the door to school and long nights when they can’t sleep with a stuffy nose. Those days were very long but looking back at photos and memories, the years went by in a flash. Parenting can be a fulfilling full-time job, however, if you’re the parent or caregiver to a child with extensive medical needs or a rare disease, the demands can be around the clock.

Having a rare disease can significantly lower the quality and length of life. With limited treatments available, parents and caregivers look to clinical trials to alleviate the effects of the disease. Participating in a clinical trial can get you access to free healthcare, compensation for your time, being the first to benefit from new medicines or therapies and most importantly, the opportunity to prolong life for those with terminal illnesses. Yet there can be hurdles to getting into and staying engaged with a clinical trial.

So, what’s in the way? A predominant rate limiting factor to participating in a trial is access to sites. The most often cited barrier to participation was “when a potential participant has no car, transportation can be difficult to access or is too costly.”₂ Only a subset of hospitals and physicians’ offices also participate in clinical trials, limiting the number of accessible site locations, hence potential participants may need to travel long distances – extending their time away from home or work. The need to transport medical supplies, a wheelchair, or other bulky medical supplies further compounds the difficulty of getting to the site.

Another factor to consider is a visit to the doctor’s office can be generally unpleasant for a child. At every visit to the doctor, my daughter asks if she has to get a shot. Just the thought of the needle causes her heart to race, and I have to bribe her with some treat or a toy to put on a brave face and halt the tears (it never works). This is both anxiety-inducing for her and frustrating for me.

There are tools available now to help young patients and their caregivers make fewer trips to the doctor’s office, while still participating in a clinical trial. Technology vendors that support clinical trials are meeting this need with decentralised clinical trial (DCT) services that enable subjects to participate in trials virtually from their homes:

Direct-to-Patient Medication Shipments

Almac Clinical Technologies along with Almac Clinical Services offers direct-to-patient shipments of clinical trial medications in studies where the IMP can be shipped. These are clinical trial medications that are not frozen, the patient lives in the same state as the site or depot shipper, and the medicine can be self-administered at home by the patient or their parent/caregiver.  Almac also integrates with other clinical data vendors that offer remote eConsent services which helps to automate enrollment into a trial, enabling patients to complete additional scheduled site visits from their home.

eConsent

In order to participate in a clinical trial, patients need to be educated about the risks of being involved and consent, or assent in the case of a minor, to participation by signing an Informed Consent Form (ICF). This process usually happens in person at a clinical site, however, trials that offer eConsent can collect signatures electronically making the process remote and eliminating a site visit for the patient.

Telehealth Site Visits

At the onset of the COVID-19 Pandemic, lockdowns delayed or completely stopped progress on many clinical trials mid-study with active patients. In response to this, clinical trial sites adopted the use of currently available tools like Zoom and other remote conference and video calling services to continue to monitor subjects. Commercial telehealth tools for clinical trials are still limited but available. Sponsors should look for vendors whose Telehealth offering is both Part 11 and HIPAA compliant.

Electronic Patient Reported Outcomes (ePRO)

Electronic tools for collecting outcomes information from patients have improved vastly since its inception. Many vendors offer a bring-your-own-device model enabling patients to use a cell phone or tablet that they are familiar with and already have in their possession. ePRO tools aid study participants’ ability to stay engaged with a trial by providing alerts when it’s time to make entries and collecting data in real-time from subjects where recall is most accurate.

Giving young patients and their parents access to remote tools for trial participation reduces the amount of time they must commit to travel and time at the site. This is time that can be much better spent on bonding or other restorative family activities that are beneficial to the child and parents. We encourage our pharma and biotech partners to engage with technology vendors that have developed DCT technologies and services for the mutual benefit of our ongoing research, giving patients more time back in their day. For more information in support of caregivers of a loved one with a rare disease, please check out: The National Organization for Rare Disorders | NORD (rarediseases.org) and the Caregiver Action Network.

1. “The Happiness Project” by Gretchen Rubin.
2. NIH: Review of the Literature: Primary Barriers and Facilitators to Participation in Clinical Research (nih.gov)

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 navigated 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.  

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.

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.