Effective management of clinical supplies is a bedrock of any clinical trial and it is an area in which sponsors have made great efforts to improve quality and cost-efficiency. The right configuration of systems to capture data from trial participants can have a huge impact on the management of a clinical study, and, over the years, significant investment has gone into developing interactive response technologies (IRT).
IRTs not only capture feedback from participants, they also automate key elements of a study, including randomisation and clinical supplies management (see ‘IRTs’ impact on study management’), as well as providing easily accessible reports and electronic patient diaries. These functionalities can be derived through either interactive voice response (IVR) or interactive web response (IWR).
"IRTs have been in use for 12-15 years, but have been commonplace only for seven to ten years," says Michael Moorman, senior director in Pfizer’s global clinical supply systems and support division. "They are often taken for granted, but they are very powerful systems. They enable study designs that would not otherwise be possible.
"Combined with booklet labelling, they can increase the flexibility of the clinical studies that are conducted, for example by making it possible to conduct a trial across more countries. As well as enabling us to benefit from that flexibility, they also allow us to make savings on drug supply overages. Ten years ago, when we had to package patient-specific kits for patients that might withdraw from the trial early, the overheads were four or five times greater than they are now."
Moorman is a biomedical engineer by training and he has spent his entire career working in R&D. Two thirds of his working life has been spent in the pharmaceutical sector and he now leads the team at Pfizer that specialises in optimising the systems infrastructure that supports clinical trials. As a result, IRTs fall within his remit, and he has seen first-hand how they give greater freedom to clinicians in terms of study design, particularly if IWR is deployed.
One way in which IRTs have improved the design of studies is in opening up the possibility of adaptive trials. In recent years, one of the biggest concerns for the pharmaceutical sector has been the rising cost of R&D, which has come at a time when relatively few new drugs have come to market. This has resulted in the design of adaptive clinical trials to increase efficiency – in terms of time and cost – by enabling compliant trials to be conducted across different patient populations in relatively short time frames.
In essence, adaptive trials rely on rapid response services that allow R&D processes to react to the mid-trial variation of dosing regimens.
"The systems in use now give clinicians the ability to design more complex studies," explains Moorman. "True adaptive trials are still fairly uncommon, but we are getting there. Patients can be titrated up and down in a blinded way based on an automated lab feed. We can also re-randomise a cohort of patients in the middle of a study."
From dial-up to digital interfaces
The ability to design greater flexibility into the parameters of a trial is greatly enhanced by using online interfaces rather than the once-familiar voice-response systems. In some trials, IVR is still an option, but it is used less and less because respondents tend to take the internet option.
"Everything used to be done through the telephone, but the use of voice-response systems has gone down significantly as most people choose to log on through the internet," says Moorman. "In fact, in most studies, we don’t even provide the voice capability now, as everything is done online.
"The web is a much richer interface and it means there is no need to listen to a recorded message. When you offer the choice of voice or web interaction, you find that most investigator sites choose the web option."
The dominant trend in developing IRTs is to improve usability and make the interfaces more sophisticated, which tends to favour the use of IWR rather than IVR. The use of an online interface also makes it easier to design a response system that is specifically tuned to the needs of a particular clinical study.
Whichever kind of IRT is used, the development of any interface is dependent on close contact between the system designers and the clinicians.
"Quality and patient safety are the two top priorities. IRT development follows a formal software development life-cycle process with, of course, the usual emphasis on very high standards. Then there is a process of study-specific configuration, which begins with understanding the nature and purpose of the study," remarks Moorman.
"From the systems perspective, we have to look at different protocols and talk to the clinicians to ensure that the configuration of the system meets with the specific requirements of their study. We also spend a lot of time looking at how investigator sites interact with the system, so that we make the interface as intuitive as possible. Then, of course, there is a lot of testing before implementation."
Variations, vendors and the death of voice
The development of IRT functionality continues apace and is guided by many factors. Lessons are learned incrementally from each application of an IRT in a clinical trial, as one would expect, but more significant is the creativity of clinicians who understand how IRTs can be deployed to make studies more efficient and effective.
"There are certainly opportunities to develop the capability of IRT systems further," notes Moorman. "Clinicians and statisticians are very innovative and identify new types of study design to more efficiently and effectively test medications, so IRTs need to develop in such a way as to accommodate that innovation.
"Another important factor is that IRT systems are traditionally stand-alone systems. They are not integrated with other systems used in clinical trials. For instance, supply systems, study management systems and remote data capture systems could be better integrated with IRTs. There is also growth in the use of mobile technology and there are exciting opportunities to leverage that to improve execution at investigator sites and provide better access to information."
Integration is a key focus for the pharmaceutical industry’s efforts to develop IRTs, as there is potential to improve quality and cost-efficiency by connecting these systems to logistics processes, for example. As Moorman has explained, IRTs have helped reduce drug overages already, but there is scope to increase those savings further. Plugging data flows from IRTs into supply systems is just one way to streamline the systems infrastructure that underpins the trials process.
"Integration is advancing at different speeds in different companies, but, at Pfizer, a lot of effort has already gone into integrating IRTs with supply systems, study management tools and vendor systems," says Moorman. "We pushed the concept of mobile technology, too."
Working more closely with vendors is another way in which companies are seeking to leverage the power of IRTs. Often, IRT systems are developed in-house, but vendor-supplied solutions may in some cases provide the basis on which to build more adaptable and efficient systems.
"We have an internally developed IRT system that we have used for over ten years, but we also use some vendor systems," Moorman explains. "Many vendors – over 30 – offer IRTs, some of which are technology start-ups, while others are CROs. So, there is an opportunity to develop standards across the industry. In using vendor systems, it becomes a question of choosing the right vendor, and, for that, different sponsor companies have different selection criteria.
"For us, there is an intense focus on quality, so that is always the primary criterion, but we also need to choose a vendor that has unique capabilities to suit the needs of an individual trial. The vendor market usually gives us a number of options, but it always requires investment on the part of the sponsor to ensure that a vendor meets the necessary quality requirements. Once you know a group of vendors that meets your requirements then you don’t tend to look beyond that group for each new study."
In the last decade, there has been a big swing away from voice-response systems towards web-based alternatives, but that step change only paves the way for the next one. The future will certainly see IRTs develop further in terms of the richness of their functionality and intuitiveness of their configuration, but the next big step forward will be the integration of in-house and vendor solutions with the wider systems infrastructure on which clinical trials depend.
IRTs’ impact on study management
Interactive response technologies (IRTs) can play a key role in managing vital elements of a clinical trial, including:
Subject randomisation
This is a challenging task, made increasingly so by the ever-more complex nature of study designs and treatment scenarios, and it is essential to avoid study subject bias during randomisation. IRTs can play a part in successful randomisation by:
- automatically re-randomising patients into different treatment groups between phases of a study
- rolling over qualified subjects from one study to the next when extension studies are undertaken
- randomising a study subject into a treatment group to replace participants that have left without compromising the balance of the trial.
Drug tracking, dispensing and reconciliation
IRTs can play a central role in managing complex dosing scenarios using a predictive resupply functionality that works on an analysis of actual demand. IRTs can:
- feed into drug inventory management tools to track and monitor usage
- interact with customisable inventory limit controls, shipment restrictions and threshold alert systems
- track medication through the supply chain
- minimise waste through drug pooling functionality.
