As sponsors move towards a model of evolving protocols based on feedback from ongoing studies, the importance of implementing a flexible IVR/IWR system has never been more important. Those CRO teams who put clear emphasis on proactively taking actions to prepare for IVR/IWR at an early stage will reap the benefits of reduced costs and extended timelines related to rework.

IVR/IWR vendor involvement in protocol development
Historically it has been the general case that the IVR/IWR vendor has only been fully engaged at the point of commencing system design. At this stage the protocol may already be finalized and through regulatory approval. Based on their experience, the vendor may then bring out queries and considerations during the design phase, which the CRO and sponsor teams must respond to based on a fixed protocol.

CRO teams can avoid these challenges by involving the IVR/IWR vendor as soon as possible after they receive the outsource award from the sponsor. If the CRO has a strategic partnership with and IVR/WR vendor, it may even be possible to bring them in prior to award to provide consultation or participate at bid defense meetings. At this point the protocol is often still in draft status, therefore high level input from the IVR/IWR vendor can allow the clinical team to amend the protocol to support a more suitable, study specific IVR/IWR model prior to finalization.

As well as providing the IVR/IWR vendor the opportunity to provide feedback on the protocol, it also allows the vendor a place to initiate the CRO and sponsor thinking with regards to the system design. This presents a major benefit due to the fact that the combined client teams are more aware of the role and functionality of the IVR/IWR and will be able to consider this for the decisions they make regarding supplies, sites, regions and randomization.

CRO/Sponsor engagement in IVR/IWR design
Depending on the level of outsourcing the sponsor has selected with the CRO, the responsibility for clinical guidance and protocol authoring can vary. Inevitably though, the final say on clinical decisions will always fall with the sponsor’s science and medical team.

Therefore it is essential that communication channels are fully opened between the IVR/IWR vendor and the CRO and sponsor clinical teams during the IVR/IWR design phase. The IVR/IWR vendor has a small window of opportunity to work through the specification of the system; therefore it is essential that the CRO project manager works to ensure that all relevant shareholders are actively involved from the outset. With increasing degrees of data and supplies integration with IVR/IWR systems, representatives from those teams are key resources and need to be fully engaged.

IVR/IWR systems are driven by logic and therefore rely solely on the rules and calculations that are designed in at the start. As such differences in protocol interpretation can cause rework and unnecessary cost for the CRO or sponsor.

An IVR/IWR vendor will consult with the client team during the requirements phase of IVR/IWR implementation and will often raise questions of clarification and also experience based recommendations. CRO teams that proactively address these with the sponsor and provide a unified response to the IVR/IWR vendor will undoubtedly help get the system design right first time, hence reduce potential rework.

Clinical vs. operational
Clinical teams and study management teams often read protocols through two different lenses. The former is more focused on the scientific regime of the protocol, with the latter more concerned about how they can make this work at a site level.

Bringing these two worldviews together under the same umbrella in an IVR/IWR design can often be challenging. Balancing what the patient and investigator “should do” in parallel with what they “have to do” and “need to do” once a patient deviates from the protocol, can often lead to tension when designing the IVR/IWR and consumption of significant resource troubleshooting a clinical scenario that wasn’t expected, but non the less has now occurred at site. Some clinical teams can be unaware of the type or frequency of technical support issues that can occur at site and this allows the IVR/IWR vendor and CRO operational teams to share from their experience the risks identified and possible solutions.

When a CRO proactively brings their operational experts into discussion with the clinical teams early in the process, it will not only support a better IVR/IWR design, it will also provide useful feedback to the clinical team on how the draft protocol will operate in the real world. This early feedback can be vital in ensuring that when the final protocol goes for regulatory approval, it will be best placed to drive a smooth implementation to the field.

The early stage interaction of the CRO operational team also allows the IVR/IWR vendor the opportunity to gain understanding on how the sites are expected to function on a day-to-day basis. Often there are country or cultural specific issues to be considered such a demographic data collection. If these are identified early, then appropriate solutions can be created to support these. The IVR/IWR vendor also has the opportunity to understand any special training requirements that the site users may require and can include this in instruction manuals for the system.

What would you do?
While IVR/IWR design is heavily driven by protocol, clinical teams need to clearly consider how they would advise an Investigator to proceed with a patient that is deviating from the strict wording of the protocol. Often a clinical team and regulators will deem it acceptable to make small deviations from the protocol should the need arise. IVR/IWR on the other hand doesn’t have any discretion; therefore it is important that functionality is built in from the start to support the clinical decision.

A range of design methods can be employed to support this, from allowing full Investigator autonomy in functions such as dose selection, through to pre-approval functionality that allows the clinical team to review patients on a case by case basis and then open up a certain transaction route or override the main programming as required.

CRO teams, who approach all these issues with a sponsor at an early point, can greatly help to increase the flexibility of the system, which leads to less technical support queries and reduced Investigator frustration.

Final Thoughts
Once a study is live and in the recruitment and treatment phase, the IVR/IWR will be used by site on a daily basis. The best result for all is that the IVR/IWR design supports the Investigator treatment activity and does not stand in the way of any clinical discretion that the protocol affords.

By their actions, a CRO has a key opportunity to influence how this significant cost investment and operational keystone benefits their client’s trial.