Should Cost be a Driver for Risk-Based Quality Management?

Spoiler alert – the jury is still out…but the direction of travel is clear.

Before 2020

The Regulatory Authorities cited many reasons for the introduction of RBQM, including improving quality, the modernization of clinical trials, risk aversion in the industry and of course, patient safety. Interestingly, in the EMA’s 2013 document 'Reflection paper risk-based quality management in clinical trials' top of the list was “cost of clinical development”.

As the industry worked out how to interpret the discussion papers and regulatory guidance which followed, the main focus was on data quality and patient safety. There was very little focus on RBQM as a mechanism for saving money. We did see a few early attempts to interpret the guidance as a licence to just do less monitoring overall. From an RBQM perspective, less monitoring is not something we condone. But RBQM was seen by many as an additional cost. As a result, many CROs only offered or included RBQM if a sponsor specifically asked for it.

Then 2020 happened

With the arrival of the pandemic and global lockdown, trial conduct was forced to stop, slow down, or dramatically change in monitoring approach. The industry had no choice. It had to adapt to the fact that site visits were unsafe and (during lockdown) even illegal.

As restrictions began to ease, it became very clear that trials could continue to operate without a routine site monitoring strategy if robust RBQM was deployed. That made many sponsors stop and re-think the way they conduct their trials.

Now in 2021.

Sponsors are driving RBQM adoption because they can see it can save time and money.

They are questioning the mix of central, remote, and on-site monitoring and concluding they need a more targeted approach. The traditional ‘go to site every four to six weeks, whether it needs it or not’ models of the past are now seen as inefficient use of R&D spend. They’re also seen as less effective than an approach which focuses on continual risk identification and management, which is at the core of the RBQM approach.

During the pandemic we witnessed tensions between sponsors and outsourced monitoring partners who weren't able to adapt and offer central and remote monitoring options. Sponsors are looking for CRO partners who not only “get” RBQM, but can deliver the full end-to-end RBQM process effectively and efficiently on every trial. That's creating some significant challenges for those CROs who didn’t, or still don’t, buy into RBQM because it reduces their traditional revenue streams.

What we’re seeing are the progressive CROs winning more business as a result of leading with RBQM. Those CROs are seeing an increase in revenues, not a reduction. Some of the 1Q21 earnings statements, as well as high earnings multiples on recent CRO M&A activity is testament to this.

Costs

Intuitively logic would suggest that reduced site visits will result in reduced trial costs. The industry average monitoring visit unit cost is around $2,500 USD. Site monitoring accounts for 25 to 30% of the cost of clinical trials (Branch, E. 2016, April 30). It therefore doesn’t take much of a reduction in site monitoring to have a significant positive impact on R&D spend.

But site monitoring isn’t the whole story when it comes to costs. ICH E6 (R2) allows for and encourages a reduction in on site monitoring and SDV. However, in return it expects a study specific risk management approach. That means a move to central and remote monitoring in place of site monitoring when and where appropriate. This blended, more focused approach increases the overall volume and frequency of monitoring. And that has to be good for clinical trials.

That increase in central and remote monitoring does come at a cost. Specifically, technology and resources. For these monitoring methods to be successful, technology must be selected, implemented, and licenced. Operators must be trained to effectively use the technology and execute the new processes required for RBQM, the key ones being: risk assessment: strategic monitoring planning; central monitoring; and risk management.

We’re seeing a new and relatively low bar appear

The cost of implementing central and remote monitoring must at least be offset by the savings in reduced on site monitoring. For any study with 15 or more sites, that is relatively easy to achieve. With a 50+ site study typical of a larger phase II or a phase III study, the savings can be significant.

A simple rule of thumb is that if you’re able to save 2-3 site monitoring visits per month across the whole trial, your technology costs should be covered. Beyond that, you are offsetting central and remote monitoring activity which is very efficient (with the right technology). Every monitoring strategy will be specific to the needs of the study, but the greater the shift away from on-site monitoring, the greater the saving.

Conclusion

When you combine a cost neutral or reduced monitoring budget with the inherent increase in quality, compliance, and patient safety that RBQM can deliver, the business case is incredibly strong. More and more organizations are seeing this, and the direction of travel is clear – it's towards more RBQM, not less.

COMMENTS

"Thanks for sharing this! Few thoughts-

Quality and safety is always the priority!

'Cost neutral' is tricky to understand! The transition from 100% SDR/SDV to RBM is primarily to downshift the monitoring cost. Now, shift from RBM to RBQM is another cost driver with use of integrated approach, use of technology and importantly drive through change. So, cost will always play a crucial role.

I also wonder what do you mean by 'right technology', as far as I know there isn't a definition/measure to calibrate the technology.

Lastly, if you listen to Duke CR/FDA meeting held on 2019, there was a discussion about the increasing cost associated with the use of RBM technology/implementation instead of downshifting the overall cost.

And not every RBM tool is sold at same cost, so it is not simple alternative where you can compensate reduced onsite monitoring cost with the RBM tech alone, there are other vendors patient data vendors (just not the RBQM) being used at time of pandemic which also contributes to the trial cost.

So, the bottom line is- CROs will need to consider overall trial cost and it is obvious that cost is the primary driver for RBQM adoption. "

Associate Director - Central Statistical Monitoring - CRO

Thank you for your response. By ‘right technology’, we mean technology which is designed for purpose, as opposed to re-purposed. We mean fully validated platform designed for the end to end management of the quality cycle. You are correct that there is no specific set of requirements for a RBQM platform.

The closest thing we have seen was the following, published on the Transcelerate website: Technology Considerations to Enable the Risk-Based Monitoring Methodology.

I was at the 2019 FDA event in Washington and notes that discussions on increased cost was typically associated with a lack of reciprocal adaptive monitoring to drive reduced on site time and unnecessary SDV.

You are correct that not all technology costs are the same and we can only talk about our own, which is why we gave a ‘rule of thumb’ guidance. We do know however that most commercially available, for purpose RBQM solutions fall within a reasonably narrow range of pricing from the feedback we have received during multiple competitive RFP events over the last couple of years.

Thank you for your interest, and taking the time to respond.

Duncan Hall, CEO